Defining tetrahydrobiopterin responsiveness in phenylketonuria: Survey results from 38 countries

Background: A subset of patients with phenylketonuria benefit from treatment with tetrahydrobiopterin (BH4), although there is no consensus on the definition of BH4 responsiveness. The aim of this study therefore was to gain insight into the definitions of long-term BH4 responsiveness being used around the world. Methods: We performed a web-based survey targeting healthcare professionals involved in the treatment of PKU patients. Data were analysed according to geographical region (Europe, USA/Canada, other). Results: We analysed 166 responses. Long-term BH4 responsiveness was commonly defined using natural protein tolerance (95.6%), improvement of metabolic control (73.5%) and increase in quality of life (48.2%). When a specific value for a reduction in phenylalanine concentrations was reported (n = 89), 30% and 20% were most frequently used as cut-off values (76% and 19% of respondents, respectively). When a specific relative increase in natural protein tolerance was used to define long-term BH4 responsiveness (n = 71), respondents most commonly reported cut-off values of 30% and 100% (28% of respondents in both cases). Respondents from USA/Canada (n = 50) generally used less strict cut-off values compared to Europe (n = 96). Furthermore, respondents working within the same center answered differently. Conclusion: The results of this study suggest a very heterogeneous situation on the topic of defining long-term BH4 responsiveness, not only at a worldwide level but also within centers. Developing a strong evidence- and consensus-based definition would improve the quality of BH4 treatment.info:eu-repo/semantics/publishedVersio

The Role of a Medical Intermediate Care Unit in the Management of Budd-Chiari Syndrome: Case Series

Budd-Chiari syndrome (BCS) has a wide spectrum of presentations, from an asymptomatic status to acute liver failure (ALF). The therapeutic approach depends on disease severity and related etiology with patients with severe forms of presentation classically managed in intensive care units (ICUs). Here, we report a series of five BCS patients managed in a medical intermediate care unit (IntCU), with three of them presenting with acute liver injury. Progression to ALF was seen in three patients, two of whom died, with one being successfully submitted to liver transplantation. IntCUs allow a 24-h patient surveillance and a prompt management of BCS, with less economic impact when compared to ICUs. Mortality was related to the presence of associated comorbidities that limited therapeutic approach.info:eu-repo/semantics/publishedVersio

Crónica da mão – Uma apresentação incomum de tuberculose em idade pediátrica

Tuberculosis remains the most common cause of death from infectious diseases worldwide. Extrapulmonary tuberculosis with musculoskeletal involvement occurs in about 10-15% of cases, mainly affecting joints and bones. Of these, only 1-5% are reported as synovitis of the hand. However, prompt diagnosis and treatment are often delayed and, if left untreated, bone and tendon destruction soon ensue and may lead to chronic synovitis. A 15-year-old girl presented with recurrent pain of the hand following trauma. Imaging showed tenosynovitis and tendon rupture. Surgical treatment was performed. Pathological assessment revealed necrotic caseous granulomas. Chest radiography showed no abnormal findings, but both Tuberculin Skin Test and Interferon Gamma-Release Assay were positive. Tuberculous tenosynovitis was diagnosed, and 12-month anti-tuberculous chemotherapy was instated. Five years after surgery, the patient maintained chronic pain and functional hand limitation. Tuberculous tenosynovitis of the hand is a rare and insidious condition that should be considered in the differential diagnosis of chronic hand pain. Delayed diagnosis and treatment can lead to residual functional limitation, making disease recognition critical.info:eu-repo/semantics/publishedVersio

T790M-EGFR mutation frequency in advanced NSCLC patients on progression from a previous TKI therapy: results from a Portuguese study

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Another Twist in the Tale: Intrafamilial Phenotypic Heterogeneity in ANO3‐Related Dystonia

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Imunoterapia com veneno de himenópteros numa criança com anafilaxia

Systemic reactions to hymenoptera venom in childhood are uncommon, comprising less than 1% of cases. The prevalence proves higher in adults, encompassing 0.3−8.9%. Anaphylaxis forms the most severe of all allergic reactions and can be fatal. Specific immunotherapy based on hymenoptera venom is the only treatment that prevents moderate-to-severe systemic reactions. Due to immunotherapy safety and effectiveness, this treatment is indicated during childhood in cases of grade II and III systemic reactions. The authors describe the clinical case of a fourteen-year-old male patient, son of a beekeeper, who was followed in the Allergy and Clinical Immunology Department due to anaphylaxis to hymenoptera venom and was under immunotherapy to Apis mellifera venom since the age of nine, besides complying with measures to evade hymenoptera.info:eu-repo/semantics/publishedVersio

Management of Psoriasis by Family Physicians: Referral Algorithm and Shared Management with Dermatology

Introduction: The implementation of models capable of improving referral quality, limiting the growth of waiting lists in hospitals, and ensuring the best possible treatment and follow-up of the psoriatic patient is of the utmost importance. Material and methods: A panel of Family Physicians and Dermatologists discussed and created a simple and effective algorithm of referral for patients with psoriasis. Results: The proposed algorithm starts when the Family Physician suspects of psoriasis. In case of diagnostic doubt, the patient should be referred to Dermatology. In case of a confirmed diagnosis, the Family Physician should assess the patient's severity and responder profile, evaluate comorbidities and assess the presence of psoriatic arthritis. If psoriasis is mild, topical treatments should be initiated, and if there is no clinical improvement or worsening of the disease, the patient should be referred to Dermatology. If psoriasis is moderate to severe, is located in high impact locations, or in pediatric age, the patient should be referred to Dermatology. In order to enable shared management in terms of follow-up and treatment of these patients, it is critical that the Family Physician has the necessary knowledge regarding the systemic treatments used in psoriasis and their side effects. Discussion and conclusion: Only a shared management of the psoriatic patient can allow for the best treatment and follow-up of these patients, a more rational use of available medical resources, thus giving the patient the best possible quality of life.Introdução: A implementação de modelos capazes de melhorar a referenciação, por forma a garantir a qualidade e precocidade do diagnóstico, o melhor tratamento e seguimento do doente psoriático é fundamental.Material e Métodos: Um painel de médicos de Medicina Geral e Familiar e Dermatologia discutiu e criou um algoritmo de referenciação simples, eficaz e célere de doentes com psoríase.Resultados: O algoritmo proposto inicia-se quando o clínico de Medicina Geral e Familiar suspeita de psoríase. Caso haja dúvidas no diagnóstico, o doente deve ser referenciado para a dermatologia. No caso de um diagnóstico confirmado, compete ao clínico de Medicina Geral e Familiar avaliar a gravidade e perfil de respondedor do doente, rastrear comorbilidades e a possibilidade de artrite psoriática. Se a psoríase for ligeira, deverão ser iniciados tratamentos tópicos, sendo que, se não houver melhoria clínica ou ocorrer agravamento da doença, o doente deverá ser referenciado para a dermatologia. Se a psoríase for considerada moderada a grave, em localizações de elevado impacto, ou em idade pediátrica, o doente deverá ser referenciado para a dermatologia. Para que o seguimento e tratamento destes doentes seja partilhado, é fundamental que o médico de Medicina Geral e Familiar tenha o conhecimento necessário sobre os tratamentos sistémicos que o doente está a fazer e os seus efeitos adversos.Discussão e Conclusão: Apenas uma gestão partilhada do doente psoriático poderá tornar possível o melhor tratamento e seguimento destes doentes, a utilização mais racional dos recursos médicos disponíveis, proporcionando ao doente a melhor qualidade devida possível.info:eu-repo/semantics/publishedVersio

Gait speed in clinical and daily living assessments in Parkinson’s disease patients: performance versus capacity

Gait speed often referred as the sixth vital sign is the most powerful biomarker of mobility. While a clinical setting allows the estimation of gait speed under controlled conditions that present functional capacity, gait speed in real-life conditions provides the actual performance of the patient. The goal of this study was to investigate objectively under what conditions during daily activities, patients perform as well as or better than in the clinic. To this end, we recruited 27 Parkinson's disease (PD) patients and measured their gait speed by inertial measurement units through several walking tests in the clinic as well as their daily activities at home. By fitting a bimodal Gaussian model to their gait speed distribution, we found that on average, patients had similar modes in the clinic and during daily activities. Furthermore, we observed that the number of medication doses taken throughout the day had a moderate correlation with the difference between clinic and home. Performing a cycle-by-cycle analysis on gait speed during the home assessment, overall only about 3% of the strides had equal or greater gait speeds than the patients' capacity in the clinic. These strides were during long walking bouts (>1 min) and happened before noon, around 26 min after medication intake, reaching their maximum occurrence probability 3 h after Levodopa intake. These results open the possibility of better control of medication intake in PD by considering both functional capacity and continuous monitoring of gait speed during real-life conditions.info:eu-repo/semantics/publishedVersio

International multicentre observational study to evaluate the association between perioperative red blood cell transfusions and 1-year mortality after major cancer surgery (ARCA-1): study design, statistical analysis plan and study protocol

Introduction: Blood transfusion is still common in patients undergoing major cancer surgery. Blood transfusion can be associated with poor prognosis in patients with cancer. Perioperative Care in the Cancer Patient -1 (ARCA-1) aims to assess in a large cohort of patients the current incidence, pattern of practice and associations between perioperative blood transfusions and 1-year survival in patients undergoing major cancer surgery. Methods and analysis: ARCA-1 is a prospective international multicentre observational study that will include adult patients scheduled to have major cancer surgical procedures with the intention to cure, and an overnight planned hospital admission. The study will be opened for 1 year for enrolment (7 January 2020-7 February 2021). Each centre will enrol patients for 30 days. The primary endpoint of this study is all-cause mortality 1 year after major cancer surgery. Secondary endpoints are rate of perioperative blood product use, cancer-specific mortality at 1 year and PFSs and 30-day morbidity and mortality. Ethics and dissemination: This study was approved by the Institutional Review Board at The University of Texas-MD Anderson Cancer Center. The study results will be published in peer-reviewed journals and disseminated at international conferences. Trial registration number: NCT04491409.info:eu-repo/semantics/publishedVersio

Female preponderance in genetic generalized epilepsies

Introduction: Epilepsy is more prevalent in men but Genetic Generalized Epilepsies (GGE) seem to be more common in women. A predominant maternal inheritance has been previously described in GGE. Our objective was to determine sex and inheritance patterns in a GGE population compared to mesial temporal lobe epilepsy with hippocampal sclerosis (MTLEHS). Methods: We performed a prospective observational study including adult GGE and MTLEHS patients followed up at a tertiary epilepsy center from January 2016 to December 2019. Patients' familial history was obtained by a detailed questionnaire. Clinical and demographic data was retrieved from clinical notes. Results: A cohort of 641 patients, 403 with GGE and 238 with MTLEHS, was analyzed. GGE was more common in women than MTLEHS (58.8% vs 44.5%, OR=1.63, p = 0.004). Compared to MTLEHS patients, more GGE patients had familial history of epilepsy (45.4% vs 25.2%; p<0.001). The GGE group had a higher percentage of female relatives with epilepsy (55% vs 37%; p = 0.006). The prevalence of maternal inheritance was not different between GGE and MTLEHS groups (62.9% vs 57.7%; p = 0.596). Photosensitivity was more common in females than in males (44.7% vs 34.3%, p = 0.036). Conclusion: There is a female preponderance in GGE when compared to MTLEHS, as both GGE patients and their affected relatives are more frequently women. The prevalence of maternal inheritance was not higher in GGE than in MTLEHS.info:eu-repo/semantics/publishedVersio