Centro Hospitalar do Porto
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A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis
Get PDFThe study was registered at ClinicalTrials.gov (identifier: NCT01961921 ) on October 14, 2013Background: Patisiran, an RNA interference therapeutic, has demonstrated robust reduction of wild-type and mutant transthyretin protein and was able to improve polyneuropathy and quality of life following 18 months of treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. In this 24-month Phase II open-label extension study, we evaluated the effects of patisiran treatment (0.3 mg/kg intravenously every 3 weeks) on safety, serum transthyretin levels, and clinical parameters. Efficacy assessments included modified Neuropathy Impairment Score +7 (mNIS+7) and multiple disease-relevant measures. Cardiac assessments were performed in a pre-specified cardiac subgroup.
Results: Twenty-seven patients entered this study, including 12 (44%) with ambulation difficulties due to their neuropathy and 11 (41%) who met criteria for the cardiac subgroup. During treatment, the majority of adverse events were mild/moderate in severity; there were no drug-related adverse events leading to treatment discontinuation. The most common drug-related adverse events were flushing and infusion-related reactions (22% each). Patisiran resulted in rapid, robust (~ 82%), and sustained reduction of mean transthyretin levels over 24 months. A mean 6.95-point decrease (improvement) in mNIS+7 from baseline was observed at 24 months. Patisiran's impact on mNIS+7 was irrespective of concomitant tafamidis or diflunisal use, sex, or age. Clinical assessments of motor function, autonomic symptoms, disease stage, and quality of life remained stable over 24 months. No significant changes were observed for echocardiographic measures or cardiac biomarkers in the cardiac subgroup. Exploratory analyses demonstrated improvements in nerve-fiber density with corresponding reductions in amyloid burden observed in skin biopsies over 24 months.
Conclusions: Long-term treatment with patisiran had an acceptable safety profile and was associated with halting/improvement of polyneuropathy progression in patients with hATTR amyloidosis.Alnylam Pharmaceuticals funded the study and collaborated with theauthors in the study design, collection, analysis, and interpretation of datainfo:eu-repo/semantics/publishedVersio
Assessment, Diagnosis, and Treatment of Dysphagia in Patients Infected With SARS-CoV-2: A Review of the Literature and International Guidelines
Get PDFPurpose Speech-language pathologists are playing a crucial role in the assessment and management of patients infected with severe acute respiratory syndrome coronavirus 2. Our goal was to synthesize peer-reviewed literature and association guidelines from around the world regarding dysphagia assessment and management for this specific population. Method A review of publications available in the PubMed database and official guidelines of international groups was performed on May 23, 2020. The information was synthesized and categorized into three content areas for swallowing: clinical evaluation, instrumental assessment, and rehabilitation. Results Five publications were identified in the PubMed database. Following title, abstract, and full-text review, only three publications met inclusion criteria: two reviews and one narrative report. Additionally, 19 international guidelines were reviewed. To assess swallowing, a modified clinical evaluation was recommended and only following a risk assessment. Instrumental assessments were often considered aerosol generating, especially transnasal procedures such as endoscopy and manometry. For this reason, many associations recommended that these examinations be performed only when essential and with appropriate personal protective equipment. Guidelines recommended that intervention should focus on compensatory strategies, including bolus modification, maneuvers/postural changes, and therapeutic exercises that can be conducted with physical distancing. Respiratory training devices were not recommended during rehabilitation. Conclusions International associations have provided extensive guidance regarding the level of risk related to the management of dysphagia in this population. To date, there are no scientific papers offering disease and/or recovery profiling for patients with dysphagia and coronavirus disease 2019. As a result, research in this area is urgently needed.info:eu-repo/semantics/publishedVersio
Discordance between patient and physician global assessment of disease activity in Behçet's syndrome: a multicenter study cohort
Get PDFBackground: To compare the patients' and physician's global assessment of disease activity in Behçet's syndrome (BS) and investigate the frequency, magnitude, and determinants of potential discordance.
Methods: A total of 226 adult BS patients with a median (IQR) age of 46.9 (35.6-55.2) years were enrolled across Italy, Greece, Portugal, and Spain. Demographic, clinical, and therapeutic variables, as well as the patient reported outcomes, were collected at the recruitment visit. The physical (PCS) and mental (MCS) component summary scores of the Short Form Questionnaire 36 (SF-36) and the Behçet's syndrome Overall Damage Index (BODI) were calculated. Disease activity was assessed by the patients' (PtGA) and physician's global assessment (PGA) in a 10-cm visual analog scale, as well as the Behçet Disease Current Activity Form (BDCAF). Discordance (∆) was calculated by subtracting the PGA from the PtGA and defined as positive (PtGA>PGA) and negative (PtGA<PGA) discordance using both a more stringent (∆ = ±2) and a less stringent (∆ = ±1) cutoff. Univariate and multivariate logistic regressions were performed.
Results: Median PtGA and PGA scores were 2.0 (0.3-5.0) and 1.0 (0.0-3.0) cm, respectively. The discordance prevalence varied (from 29.6 to 55.3%) according to the cutoff applied, and the majority (> 80%) of disagreements were due to patients rating higher their disease activity. Higher values of BDCAF were associated to increased rate of positive discordance. When BDCAF = 0, the median (IQR) values of PtGA and PGA were 0.2 (0-2) and 0 (0-1), respectively. PCS (adjusted odds ratio (adjOR) 0.96 per unit, 95% CI 0.93-0.98, p = 0.006) and MCS (adjOR 0.96 per unit, 95% CI 0.93-0.99, p = 0.003) were independently associated with positive discordance using both cutoffs. Active ocular involvement emerged as a potential determinant of negative discordance (adjOR 5.88, 95% CI 1.48-23.30, p = 0.012).
Conclusions: PtGA and PGA should be considered as complementary measures in BS, as patients and physicians may be influenced by different factors when assessing active disease manifestations. Particularly, PtGA may be a useful tool in the assessment of BS disease activity, as it carries a low risk to misclassify an inactive disease, and may allow to capture aspects of the patient's health that negatively affect his well-being and the treatment.The BODI Project was partly supported by a grant from the Italian Behçet’s Syndrome Patient Association (SIMBA ONLUS).info:eu-repo/semantics/publishedVersio
The impact of the coronavirus disease 2019 pandemic on the utilisation of emergency urological services
Get PDFObjectives: To compare the number of patients attending the Urology Emergency Department (ED) of the Centro Hospitalar Universitário do Porto (CHUP), as well as their demographic characteristics, the reasons for admission, the clinical severity under the Manchester triage system (MTS), and the need for emergency surgery or hospitalisation, during the coronavirus disease 2019 (COVID-19) pandemic and the equivalent period in 2019.
Patients and methods: Data were collected from patients attending the Urology ED of the CHUP over 3 weeks, from 11 March to 1 April 2020, and from the same period in the previous year (from 11 March to 1 April 2019).
Results: During the pandemic, 46.4% fewer patients visited our urological ED (122 vs 263). There was no significant difference in the mean age or the number of old patients (aged ≥65 years) between the two periods. However, significantly fewer female patients sought emergency urological services during the COVID-19 pandemic period (32.7% vs 14.8%, P < 0.05). No significant differences were noted between different clinical severity groups under the MTS. In 2019, significantly less patients required hospitalisation. The most common reasons for admission, during both periods, were haematuria, renal colic and urinary tract infections. The authors recognise that the study has several limitations, namely, those inherent to its retrospective nature.
Conclusion: COVID-19 significantly influenced people's urological care-seeking behaviour. Understanding the present situation is helpful for predicting future urological needs. Based on the results of this study, we have reason to speculate that people's requirements for urological services might grow explosively in the post-COVID-19 period. There should be further studies about the real state of long-term urological services and the consequences that this pandemic may have in terms of morbimortality not directly related to the severe acute respiratory syndrome coronavirus 2.info:eu-repo/semantics/publishedVersio
Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome
Get PDFGray platelet syndrome (GPS) is a rare recessive disorder caused by biallelic variants in NBEAL2 and characterized by bleeding symptoms, the absence of platelet α-granules, splenomegaly, and bone marrow (BM) fibrosis. Due to the rarity of GPS, it has been difficult to fully understand the pathogenic processes that lead to these clinical sequelae. To discern the spectrum of pathologic features, we performed a detailed clinical genotypic and phenotypic study of 47 patients with GPS and identified 32 new etiologic variants in NBEAL2. The GPS patient cohort exhibited known phenotypes, including macrothrombocytopenia, BM fibrosis, megakaryocyte emperipolesis of neutrophils, splenomegaly, and elevated serum vitamin B12 levels. Novel clinical phenotypes were also observed, including reduced leukocyte counts and increased presence of autoimmune disease and positive autoantibodies. There were widespread differences in the transcriptome and proteome of GPS platelets, neutrophils, monocytes, and CD4 lymphocytes. Proteins less abundant in these cells were enriched for constituents of granules, supporting a role for Nbeal2 in the function of these organelles across a wide range of blood cells. Proteomic analysis of GPS plasma showed increased levels of proteins associated with inflammation and immune response. One-quarter of plasma proteins increased in GPS are known to be synthesized outside of hematopoietic cells, predominantly in the liver. In summary, our data show that, in addition to the well-described platelet defects in GPS, there are immune defects. The abnormal immune cells may be the drivers of systemic abnormalities such as autoimmune disease.info:eu-repo/semantics/publishedVersio
Severe symptomatic hyperparathyroidism—Is it carcinoma?—Case report and literature review
Get PDFParathyroid carcinoma is a rare disease, difficult to diagnose and associated with a poor prognosis. It must be suspected preoperatively, based on clinical and imaging grounds, in order to perform the best surgical option and avoid compromising patient's prognosis.info:eu-repo/semantics/publishedVersio
Visian® ICLV4c™ and Artiflex®: Comparative Analysis with the HD Analyser™ and Integration with Subjective Performance and Anatomical Parameters
Get PDFPurpose: To analyze and compare the mid-term objective and subjective performance of two phakic intraocular lenses (PIOLs) - Visian® ICL™ V4c and Artiflex® and to correlate those results with anatomical parameters.
Patients and methods: Observational retrospective study including thirty patients (15 for each PIOL) randomly selected from those who underwent bilateral implantation of one of the PIOLs (60 eyes were analysed). Uncorrected and corrected distance visual acuities (UDVA and CDVA), anterior chamber structural parameters, and corneal endothelial cells density and morphology were evaluated. Quality of vision was assessed both subjectively with a questionnaire, and objectively using a double-pass technology optical quality analysis system.
Results: At the end of follow-up the Artiflex® group showed better UDVA (0.95±0.11 vs 0.99±0.05, p=0.027) and higher proportion of eyes reaching at least 20/20 (28/30 vs 18/30, p=0.005). Excellent and similar objective scatter index (1.79±0.9 vs 2.14±1.6, p=0.306) and modular transfer function cutoff frequency (26.91±9.2 vs 26.51±11.9, p=0.784) results were achieved in the HD Analyzer® and the questionnaire showed comparable high Satisfaction (55.7±3.5 vs 54.3±5.4, p=0.386) and low Dysphotopsia Scores (3.1±1.8 vs 2.1±2.2, p=0.213). The ICL group showed inferior anterior chamber volume (p<0.001), and angle (p<0.001) and superior pupillary diameter (p=0.007). Minimum follow-up was 24 months.
Conclusion: Both the Visian® ICLV4c™ and the Artiflex® showed excellent optical performance through the HD AnalyzerTM technology, translated in high patient satisfaction. Overall, both PIOLs showed similar safety, predictability, stability and effectiveness of for the reduction of high sphero-cylindrical refractive errors, despite better UDVA results with the Artiflex®.info:eu-repo/semantics/publishedVersio
EMQN best practice guidelines for genetic testing in dystrophinopathies
Get PDFDystrophinopathies are X-linked diseases, including Duchenne muscular dystrophy and Becker muscular dystrophy, due to DMD gene variants. In recent years, the application of new genetic technologies and the availability of new personalised drugs have influenced diagnostic genetic testing for dystrophinopathies. Therefore, these European best practice guidelines for genetic testing in dystrophinopathies have been produced to update previous guidelines published in 2010.These guidelines summarise current recommended technologies and methodologies for analysis of the DMD gene, including testing for deletions and duplications of one or more exons, small variant detection and RNA analysis. Genetic testing strategies for diagnosis, carrier testing and prenatal diagnosis (including non-invasive prenatal diagnosis) are then outlined. Guidelines for sequence variant annotation and interpretation are provided, followed by recommendations for reporting results of all categories of testing. Finally, atypical findings (such as non-contiguous deletions and dual DMD variants), implications for personalised medicine and clinical trials and incidental findings (identification of DMD gene variants in patients where a clinical diagnosis of dystrophinopathy has not been considered or suspected) are discussed.info:eu-repo/semantics/publishedVersio