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  • Portuguese Heart Failure Prevalence Observational Study (PORTHOS) rationale and design – A population-based study
    Publication . Baptista, Rui; Silva Cardoso, José; Canhão, Helena; Maria Rodrigues, Ana; Kislaya, Irina; Franco, Fátima; Bernardo, Filipa; Pimenta, Joana; Mendes, Lígia; Gonçalves, Sara; Teresa Timóteo, Ana; Andrade, Aurora; Moura, Brenda; Fonseca, Cândida; Aguiar, Carlos; Brito, Dulce; Ferreira, Jorge; Filipe Azevedo, Luís; Peres, Marisa; Santos, Paulo; Moraes Sarmento, Pedro; Cernadas, Rui; Santos, Mario; Fontes-Carvalho, Ricardo; Campos Fernandes, Adalberto; Martinho, Hugo; González-Juanatey, José Ramon; Filipe Pereira, Luís; Gil, Victor; Raquel Marques, Cláudia; Almeida, Mário; Pardal, Marisa; Barbosa, Veneranda; Gavina, Cristina
    Introduction and objectives: Current epidemiological data on heart failure (HF) in Portugal derives from studies conducted two decades ago. The main aim of this study is to determine HF prevalence in the Portuguese population. Using current standards, this manuscript aims to describe the methodology and research protocol applied. Methods: The Portuguese Heart Failure Prevalence Observational Study (PORTHOS) is a large, three-stage, population-based, nationwide, cross-sectional study. Community-dwelling citizens aged 50 years and older will be randomly selected via stratified multistage sampling. Eligible participants will be invited to attend a screening visit at a mobile clinic for HF symptom assessment, anthropomorphic assessment, N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, one-lead electrocardiogram (ECG) and a sociodemographic and health-related quality of life questionnaire (EQ-5D). All subjects with NT-proBNP ≥125 pg/mL or with a prior history of HF will undergo a diagnostic confirmatory assessment at the mobile clinic composed of a 12-lead ECG, comprehensive echocardiography, HF questionnaire (KCCQ) and blood sampling. To validate the screening procedure, a control group will undergo the same diagnostic assessment. Echocardiography results will be centrally validated, and HF diagnosis will be established according to the European Society of Cardiology HF guidelines. A random subsample of patients with an equivocal HF with preserved ejection fraction diagnosis based on the application of the Heart Failure Association preserved ejection fraction diagnostic algorithm will be invited to undergo an exercise echocardiography. Conclusions: Through the application of current standards, appropriate methodologies, and a strong research protocol, the PORTHOS study will determine the prevalence of HF in mainland Portugal and enable a comprehensive characterization of HF patients, leading to a better understanding of their clinical profile and health-related quality of life.
    2023Journal article Open access Show more
  • Optimized Artificial Intelligence for Enhanced Ectasia Detection Using Scheimpflug-Based Corneal Tomography and Biomechanical Data
    Publication . Ambrósio, Renato; Machado, Aydano P.; Leão, Edileuza; Lyra, João Marcelo G.; Salomão, Marcella Q.; Esporcatte, Louise G. Pellegrino; da Fonseca Filho, João B.R.; Ferreira-Meneses, Erica; Sena, Nelson B.; Haddad, Jorge S.; Costa Neto, Alexandre; de Almeida, Gildasio Castelo; Roberts, Cynthia J.; Elsheikh, Ahmed; Vinciguerra, Riccardo; Vinciguerra, Paolo; Bühren, Jens; Kohnen, Thomas; Kezirian, Guy M.; Hafezi, Farhad; Hafezi, Nikki L.; Torres-Netto, Emilio A.; Lu, Nanji; Kang, David Sung Yong; Kermani, Omid; Koh, Shizuka; Padmanabhan, Prema; Taneri, Suphi; Trattler, William; Gualdi, Luca; Salgado-Borges, José; Faria-Correia, Fernando; Flockerzi, Elias; Seitz, Berthold; Jhanji, Vishal; Chan, Tommy C.Y.; Baptista, Pedro Manuel; Reinstein, Dan Z.; Archer, Timothy J.; Rocha, Karolinne M.; Waring, George O.; Krueger, Ronald R.; Dupps, William J.; Khoramnia, Ramin; Hashemi, Hassan; Asgari, Soheila; Momeni-Moghaddam, Hamed; Zarei-Ghanavati, Siamak; Shetty, Rohit; Khamar, Pooja; Belin, Michael W.; Lopes, Bernardo T.
    Purpose: To optimize artificial intelligence (AI) algorithms to integrate Scheimpflug-based corneal tomography and biomechanics to enhance ectasia detection. Design: Multicenter cross-sectional case-control retrospective study. Methods: A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Optikgeräte GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy. Results: The area under the receiver operating characteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sensitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), developed with 18 features in 156 trees using 10-fold cross-validation, had a significantly higher AUC (0.945; DeLong, P < .0001) for detecting VAE-NT (84.4% sensitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001). Conclusions: AI optimization to integrate Scheimpflug-based corneal tomography and biomechanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning considering additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will continuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
    2023Journal article Open access Show more
  • Primary Petit Hernia: From Diagnosis to Open Surgical Approach
    Publication . Alves, Duarte Gil; Sousa, Jessica; Rodrigues, Catarina; Silva, Sara; Ribeiro, Rómulo
    Lumbar hernias are quite rare, even more so when primary or of spontaneous nature. These defects in the lumbar region demand a comprehensive knowledge of the anatomy of the lateral abdominal wall and paraspinal muscles. Given the proximity of bone structures, they can pose a surgical challenge when trying to achieve an ideal dissection and appropriate mesh overlap. The authors report the case of a primary Petit's hernia that underwent an open anterior surgical approach with the use of a preperitoneal mesh. In addition to the described surgical technique, the article also aims to detail the diagnosis and anatomic classification of this rare pathology.
    2023Journal article Open access Show more
  • Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
    Publication . Bastard, Paul; Vazquez, Sara E.; Liu, Jamin; Laurie, Matthew T.; Wang, Chung Yu; Gervais, Adrian; Le Voyer, Tom; Bizien, Lucy; Zamecnik, Colin; Philippot, Quentin; Rosain, Jérémie; Catherinot, Emilie; Willmore, Andrew; Mitchell, Anthea M.; Bair, Rebecca; Garçon, Pierre; Kenney, Heather; Fekkar, Arnaud; Salagianni, Maria; Poulakou, Garyphallia; Siouti, Eleni; Sahanic, Sabina; Tancevski, Ivan; Weiss, Günter; Nagl, Laurenz; Manry, Jérémy; Duvlis, Sotirija; Arroyo-Sánchez, Daniel; Paz Artal, Estela; Rubio, Luis; Perani, Cristiano; Bezzi, Michela; Sottini, Alessandra; Quaresima, Virginia; Roussel, Lucie; Vinh, Donald C.; Reyes, Luis Felipe; Garzaro, Margaux; Hatipoglu, Nevin; Boutboul, David; Tandjaoui-Lambiotte, Yacine; Borghesi, Alessandro; Aliberti, Anna; Cassaniti, Irene; Venet, Fabienne; Monneret, Guillaume; Halwani, Rabih; Sharif-Askari, Narjes Saheb; Danielson, Jeffrey; Burrel, Sonia; Morbieu, Caroline; Stepanovskyy, Yurii; Bondarenko, Anastasia; Volokha, Alla; Boyarchuk, Oksana; Gagro, Alenka; Neuville, Mathilde; Neven, Bénédicte; Keles, Sevgi; Hernu, Romain; Bal, Antonin; Novelli, Antonio; Novelli, Giuseppe; Saker, Kahina; Ailioaie, Oana; Antolí, Arnau; Jeziorski, Eric; Rocamora-Blanch, Gemma; Teixeira, Carla; Delaunay, Clarisse; Lhuillier, Marine; Le Turnier, Paul; Zhang, Yu; Mahevas, Matthieu; Pan-Hammarström, Qiang; Abolhassani, Hassan; Bompoil, Thierry; Dorgham, Karim; Gorochov, Guy; Laouenan, Cédric; Rodríguez-Gallego, Carlos; Ng, Lisa F. P.; Renia, Laurent; Pujol, Aurora; Belot, Alexandre; Raffi, François; Allende, Luis M.; Martinez-Picado, Javier; Ozcelik, Tayfun; Imberti, Luisa; Notarangelo, Luigi D.; Troya, Jesus; Solanich, Xavier; Zhang, Shen-Ying; Puel, Anne; Wilson, Michael R.; Trouillet-Assant, Sophie; Abel, Laurent; Jouanguy, Emmanuelle; Ye, Chun Jimmie; Cobat, Aurélie; Thompson, Leslie M.; Andreakos, Evangelos; Zhang, Qian; Anderson, Mark S.; Casanova, Jean-Laurent; DeRisi, Joseph L.
    Life-threatening "breakthrough" cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.
    2023Journal article Open access Show more
  • Olfactory Cleft Length: A Possible Risk Factor for Persistent Post-COVID-19 Olfactory Dysfunction
    Publication . Sousa, Francisco Alves De; Tarrio, João; Sousa-Machado, André; Costa, Joana Raquel; Pinto, Catarina; Nóbrega Pinto, Ana; Moreira, Bruno; Meireles, Luís
    Introduction: To date, little is known about predisposing factors for persistent COVID-19-induced olfactory dysfunction (pCIOD). The objective was to determine whether olfactory cleft (OC) measurements associate with pCIOD risk. Material and methods: Three subgroups were recruited: group A included patients with pCIOD, group B included patients without olfactory dysfunction following SARS-CoV-2 infection (ntCIOD), and group C consisted in controls without past history of SARS-CoV-2 infection (noCOVID-19). Olfactory perception threshold (OPT) and visual analog scale for olfactory impairment (VAS-olf) were obtained. OC measurements were obtained through computed tomography scans. Results were subsequently compared. Results: A total of 55 patients with a mean age of 39 ± 10 years were included. OPT was significantly lower in pCIOD patients (group A: 4.2 ± 2.1 vs. group B: 12.3 ± 1.8 and group C: 12.2 ± 1.5, p < 0.001). VAS-olf was significantly higher in pCIOD (group A: 6 ± 2.6 vs. group B: 1.7 ± 1.6 and group C: 1.6 ± 1.5, p < 0.001). OC length was significantly higher in group A (42.8 ± 4.6) compared to group B (39.7 ± 3.4, p = 0.047) and C (39.8 ± 4, p = 0.037). The odd of pCIOD occurring after COVID-19 infection increased by 21% (95% CI [0.981, 1.495]) for a one unit (mm) increase in OC length. The odd of pCIOD occurring was 6.9 times higher when OC length >40 mm. Conclusion: Longer OC may be a predisposing factor for pCIOD. This study is expected to encourage further research on OC morphology and its impact on olfactory disorders.
    2023Journal article Open access Show more
  • Unilateral Vocal Fold Paralysis and Voice Therapy: Predictors of Long-Term Quality of Life
    Publication . Sousa, Francisco Alves de; Santos, Mariline; Azevedo, Sara; Pinto, Ana; Freitas, Susana Vaz; Coutinho, Miguel; Almeida e Sousa, Cecília; Moreira da Silva, Álvaro
    To date, little is known about the long-term predictors of quality of life (QoL) in unilateral vocal fold paralysis (UVFP). The main objective of this study was to evaluate the predictors of long-term QoL in UVFP patients submitted to voice therapy (VT) exclusively. Data from patients diagnosed with UVFP who followed a VT program between 2013 and 2019 were reviewed. Video laryngoscopy (VL) records were obtained at the beginning and at the end of VT. To assess QoL, Voice Handicap Index 30 (VHI-30) score was assessed in three temporal frames: before voice therapy (pre-VT), at the last VT session (post-VT), and in the present (cur-VHI). A longitudinal analysis was performed regarding the evolution of QoL and the factors influencing QoL through time were analyzed. Seventy-eight percent of patients had iatrogenic UVFP. The mean time of follow-up after VT was 3.942 years (range 6 months-7 years). There was a significant improvement in QoL through all time points (F (2,88)=72.179, p<0.001), with VHI-30 decrease from the baseline pre-VT to post-VT(p<0.001) and from post-VT to cur-VT (p=0.0013). In the iatrogenic UVFP population, patients starting VT earlier showed better long-term QoL (p=0.023). UVFP patients with dysphagia at presentation showed significantly worse QoL in the late follow-up (p=0.016). Hence, iatrogenic UVFP patients beginning VT rapidly may show better QoL in the future. Also, our results suggest that dysphagia at UVFP onset may predict higher morbidity later in life.
    2023-01Journal article Open access Show more
  • Evaluation of Current Antiemetic Therapy Response in Patients Undergoing MEC or HEC Regimens in Portugal
    Publication . A, Araujo; Tavares, Nuno; Faria, Ana Luísa; Gomes, Rosa; Mendonça, Joana Carvalho; Parente, Bárbara; Capela, Andreia; Barata, Fernando; Macedo, Ana
    Chemotherapy-induced nausea and vomiting (CINV) negatively impact cancer patients' quality of life and treatment outcomes. This study evaluated the achievement of complete response to CINV prophylaxis during the first five days after chemotherapy in adult outpatient cancer clinics with solid malignant tumours receiving Moderate or Highly Emetogenic Chemotherapy (MEC or HEC) in Portugal. During the study, patients completed three evaluations, and nausea severity and CINV impact on patients' daily life was assessed. A complete response (no emetic episodes, no use of rescue antiemetic medication, and no more than mild nausea) was observed in 72% of the cycles (N = 161) throughout the five days after chemotherapy. Amongst the patient population, 25% classified their CINV episodes as severe. Though more than half of the patients achieved a complete response, suggesting that a therapeutic effort is being made to minimise this side effect, the overall scenario is barely optimistic. Significantly, new CINV-control measures in MEC/HEC patients should be adopted, specifically avoiding the single use of dexamethasone and 5-HT3 and raising awareness of using NK1-RAs. Thus, it is critical to improve CINV prophylactic treatment and implement practical international antiemetic guidelines in Portuguese clinical practice, envisaging the improvement of supportive care for cancer patients.
    2023-01Journal article Open access Show more
  • Six-Year Complete Remission of Type-1 Diabetes Mellitus in an Adult Treated With Sitagliptin
    Publication . Benido Silva, Vânia; Pereira, Maria Teresa
    A "honeymoon" phase is a transient period of type 1 diabetes (T1D) remission, characterized by a significant reduction in insulin requirements and good glycemic control due to a temporary restoration of pancreatic β-cell function. This phenomenon occurs in about 60% of adults with this disease, is usually partial, and lasts for up to 1 year. We present a case of a 6-year complete remission of T1D in a 33-year-old man, the longest remission ever described in the literature to our knowledge. He was referred for presenting a 6-month history of polydipsia, polyuria, and weight loss of 5 kg. Laboratory studies confirmed the diagnosis of T1D (fasting blood glucose of 270 mg/dL; HbA1c of 10.6%, and positive antiglutamic acid decarboxylase), and the patient started intensive insulin therapy. After 3 months, a complete remission of the disease was assumed, he suspended insulin administration and since then, he has been under treatment with sitagliptin 100 mg daily, a low-carbohydrate diet, and regular aerobic physical activity. This work aims to highlight the potential role of these factors in delaying disease progression and preserving pancreatic β-cells when introduced at the time of presentation. More robust, prospective, and randomized studies will be needed to confirm its protective effect on the natural course of the disease and support its indication in adults with newly diagnosed T1D.
    2023-01Journal article Open access Show more
  • Iatrogenic Cushing’s Syndrome: The Result of Cobicistat and Glucocorticoid Interaction in an HIV Patient After Bariatric Surgery
    Publication . Benido Silva, Vânia; Cardoso, Joana; Esteves Brandão, Maria; Mesquita, Isabel; Pereira, Maria Teresa
    Cobicistat, used as a pharmacokinetic booster in therapeutic combination with human immunodeficiency virus (HIV) protease inhibitors and integrase inhibitors, is a strong inhibitor of cytochrome P450 3A4 (CYP3A4). Since most glucocorticoids are metabolized by the isoenzyme of the cytochrome P450 pathway, their plasma concentrations can be highly increased in the presence of cobicistat-boosted darunavir, with subsequent risk of iatrogenic Cushing's syndrome (ICS) and secondary adrenal insufficiency. We report a case of a 45-year-old man with HIV-hepatitis C virus co-infection treated with raltegravir and darunavir/cobicistat since 2019. In May 2021, he underwent a sleeve gastrectomy due to morbid obesity (BMI: 50.9 kg/m2) with multiple comorbidities. Four months after surgery, he was diagnosed with asthma and was started on inhaled budesonide, which was later changed to fluticasone propionate. At the 12-month postoperative visit, the patient referred proximal muscle weakness and asthenia, and suboptimal weight loss (excess weight loss of 39%) and high blood pressure were documented. Moon facies, buffalo hump, and abdominal large vinous striae were evident on physical examination. Laboratory studies showed impaired glucose metabolism and hypokalemia. Cushing's syndrome was suspected and further investigation confirmed its iatrogenic origin. The diagnosis of ICS and consequent secondary adrenal insufficiency due to an interaction between the darunavir/cobicistat combination and budesonide/fluticasone was established. Darunavir/cobicistat therapy was replaced by dolutegravir/doravirine dual therapy, inhaled corticoid was switched to beclomethasone, and glucocorticoid substitutive therapy was introduced. This is a particular case of overt ICS due to cobicistat-inhaled corticosteroid interaction in a superobese patient, developed after he underwent bariatric surgery. The presence of morbid obesity, combined with the rarity of this pharmacological complication in individuals taking cobicistat, made the correct diagnosis even more challenging. A meticulous review of pharmacologic habits and potential interactions is essential to avoid serious harm to patients.
    2023-01Journal article Open access Show more
  • Domiciliary High-Flow Nasal Therapy in Primary Ciliary Dyskinesia
    Publication . Gomes, Rita; Queirós, Joana; Borges, Joana; Cardoso, Ana Lúcia; Barbosa, Telma
    We report the case of an adolescent with severe primary ciliary dyskinesia (PCD) phenotype associated with a rare genotype. His clinical condition deteriorated, with daily cough and breathlessness, hypoxemia, and lung function decline. Despite being started on home noninvasive ventilation (NIV), the symptoms progressed to dyspnea at rest and thoracic pain. High-flow nasal cannula (HFNC) was started during the daytime as an adjuvant to NIV, and he was started on regular oral opioids for pain and dyspnea control. There was a clear improvement in comfort and dyspnea and breathing work relief. Additionally, better exercise tolerance was also noted. He is currently on the lung transplant waiting list. We aim to emphasize the benefits of HFNC as an add-on therapy for the management of chronic breathlessness since our patient experienced an improvement in breathing and exercise tolerance. However, there is a paucity of studies regarding domiciliary HFNC, particularly in pediatric age. Therefore, further studies are needed to achieve optimal and personalized care. Close monitoring and frequent reassessment in a specialized center are key to adequate management.
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