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Differential early subcortical involvement in genetic FTD within the GENFI cohort
Get PDFBackground: Studies have previously shown evidence for presymptomatic cortical atrophy in genetic FTD. Whilst initial investigations have also identified early deep grey matter volume loss, little is known about the extent of subcortical involvement, particularly within subregions, and how this differs between genetic groups.
Methods: 480 mutation carriers from the Genetic FTD Initiative (GENFI) were included (198 GRN, 202 C9orf72, 80 MAPT), together with 298 non-carrier cognitively normal controls. Cortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3 T T1-weighted MRI scans. Mutation carriers were divided into three disease stages based on their global CDR® plus NACC FTLD score: asymptomatic (0), possibly or mildly symptomatic (0.5) and fully symptomatic (1 or more).
Results: In all three groups, subcortical involvement was seen at the CDR 0.5 stage prior to phenoconversion, whereas in the C9orf72 and MAPT mutation carriers there was also involvement at the CDR 0 stage. In the C9orf72 expansion carriers the earliest volume changes were in thalamic subnuclei (particularly pulvinar and lateral geniculate, 9-10%) cerebellum (lobules VIIa-Crus II and VIIIb, 2-3%), hippocampus (particularly presubiculum and CA1, 2-3%), amygdala (all subregions, 2-6%) and hypothalamus (superior tuberal region, 1%). In MAPT mutation carriers changes were seen at CDR 0 in the hippocampus (subiculum, presubiculum and tail, 3-4%) and amygdala (accessory basal and superficial nuclei, 2-4%). GRN mutation carriers showed subcortical differences at CDR 0.5 in the presubiculum of the hippocampus (8%).
Conclusions: C9orf72 expansion carriers show the earliest and most widespread changes including the thalamus, basal ganglia and medial temporal lobe. By investigating individual subregions, changes can also be seen at CDR 0 in MAPT mutation carriers within the limbic system. Our results suggest that subcortical brain volumes may be used as markers of neurodegeneration even prior to the onset of prodromal symptoms.info:eu-repo/semantics/publishedVersio
Sarcoidosis Presenting as Cranial Multinevritis
Get PDFA 29-year-old woman presented to the emergency department with red eyes and hypoacusia since the previous weeks associated with a sudden right facial palsy. Ophthalmologic examination revealed bilateral uveitis and lumbar puncture was compatible with aseptic meningitis. Thoracic computed tomography scan showed pulmonary nodules and mediastinal and hilar lymphadenopathy. Bronchoalveolar lavage revealed a CD4/CD8 ratio of 8, and lymph node biopsy confirmed non-caseating granulomas. The diagnosis of sarcoidosis with ocular, pulmonary, and neurologic involvement was made. Due to sarcoidosis severity at presentation, the patient was started on systemic steroids and methotrexate with improvement. Sarcoidosis involvement of the central nervous system is a rare condition (5-10%) but can be the first manifestation of the disease. Its presentation can be heterogeneous; therefore, symptoms are frequently devalued by patients and physicians, leading to a late diagnosis and permanent damage. Clinicians' awareness is crucial to early diagnosis and treatment.info:eu-repo/semantics/publishedVersio
Fetal Heart Rate Fragmentation
Get PDFThis article was supported by National Funds through FCT– Fundação para a Ciência e a Tecnologia, I.P., within CINTESIS, R&D Unit (reference UIDB/4255/2020)info:eu-repo/semantics/publishedVersio
Multiple Sclerosis Patient Management During the COVID-19 Pandemic: Practical Recommendations From the Portuguese Multiple Sclerosis Study Group (GEEM)
Get PDFThe spread of the COVID-19 pandemic has imposed significant challenges on healthcare provision, requiring changes in the conventional patient management, particularly in chronic diseases like multiple sclerosis (MS). To increase patient safety and reduce the risk of infection, while ensuring an appropriate and regular follow-up, tele-medicine gained prominence as a valid alternative to face-to-face appointments. However, the urgency of the implementation and the lack of experience in most MS centers led to "ad hoc" and extremely diverse approaches, which now merit to be standardized and refined. Indeed, while tele-consultation cannot fully replace face-to-face visits, it certainly can, and will, be incorporated as part of the routine care of MS patients in the near future. Bearing this in mind, the Portuguese Multiple Sclerosis Study Group (GEEM) has developed a set of recommendations for the usage of tele-medicine in the management of MS patients, both during the pandemic and in the future. The consensus was obtained through a two-step modified Delphi methodology, resulting in 15 recommendations, which are detailed in the manuscript.The consensus and the publication of this manuscript were supported by an educational grant from Novartis Portugal to the Grupo de Estudos de Esclerose Múltipla. These funds were used to pay the work of the consultancy MOAI, which set up the online questionnaire and helped with writing the summary of the meeting and the first draft of the consensus, and the publishing fee (article processing charge). The funding source had no role in the process and did not influence, by any means, the content of the consensus or the present manuscriptinfo:eu-repo/semantics/publishedVersio
Design and Rationale of the Global Phase 3 NEURO-TTRansform Study of Antisense Oligonucleotide AKCEA-TTR-LRx (ION-682884-CS3) in Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
Get PDFTrial registration: The study is registered at ClinicalTrials.gov (NCT04136184) and EudraCT (2019-001698-10)Introduction: AKCEA-TTR-LRx is a ligand-conjugated antisense (LICA) drug in development for the treatment of hereditary transthyretin amyloidosis (hATTR), a fatal disease caused by mutations in the transthyretin (TTR) gene. AKCEA-TTR-LRx shares the same nucleotide sequence as inotersen, an antisense medicine approved for use in hATTR polyneuropathy (hATTR-PN). Unlike inotersen, AKCEA-TTR-LRx is conjugated to a triantennary N-acetylgalactosamine moiety that supports receptor-mediated uptake by hepatocytes, the primary source of circulating TTR. This advanced design increases drug potency to allow for lower and less frequent dosing. The NEURO-TTRansform study will investigate whether AKCEA-TTR-LRx is safe and efficacious, with the aim of improving neurologic function and quality of life in hATTR-PN patients.
Methods/design: Approximately 140 adults with stage 1 (independent ambulation) or 2 (requires ambulatory support) hATTR-PN are anticipated to enroll in this multicenter, open-label, randomized, phase 3 study. Patients will be assigned 6:1 to AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks or inotersen 300 mg once weekly until the prespecified week 35 interim efficacy analysis, after which patients receiving inotersen will receive AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks. All patients will then receive AKCEA-TTR-LRx through the remainder of the study treatment period. The final efficacy analysis at week 66 will compare the AKCEA-TTR-LRx arm with the historical placebo arm from the phase 3 trial of inotersen (NEURO-TTR). The primary outcome measures are between-group differences in the change from baseline in serum TTR, modified Neuropathy Impairment Score + 7, and Norfolk Quality of Life-Diabetic Neuropathy questionnaire.
Conclusion: NEURO-TTRansform is designed to determine whether targeted delivery of AKCEA-TTR-LRx to hepatocytes with lower and less frequent doses will translate into clinical and quality-of-life benefits for patients with hATTR-PN.This study and Rapid Service Publication Fee is supported by Ionis Pharmaceuticals, Inc. (Carlsbad, CA, USA) and Akcea Therapeutics (Boston, MA, USA)info:eu-repo/semantics/publishedVersio
European Registry on Helicobacter pylori management: Single‐capsule bismuth quadruple therapy is effective in real‐world clinical practice
Get PDFClinicalTrials.gov NCT02328131Background: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation.
Objective: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy.
Methods: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line.
Results: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases.
Conclusions: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile.info:eu-repo/semantics/publishedVersio
Documento de Consenso sobre a realização de ressonância magnética em doentes com dispositivos cardíacos electrónicos implantados
No full textMagnetic resonance imaging (MRI) is currently considered an essential complementary method for diagnosis in many conditions. Exponential growth in its use is expected due to the aging population and a broader spectrum of clinical indications. Growth in its use, coupled with an increasing number of pacemaker implants, implantable cardioverter-defibrillators and cardiac resynchronization therapy, has led to a frequent clinical need for this diagnostic modality in patients with cardiac implantable electronic devices (CIED). This clinical need has fueled the development of devices specifically designed and approved for use in a magnetic resonance (MR) environment under certain safety conditions (MR-conditional devices). More than a decade after the introduction of the first MR-conditional pacemaker, there are now several dozen MR-conditional devices with different safety specifications. In recent years, increasing evidence has indicated there is a low risk to MRI use in conventional (so-called non-MR-conditional) CIED patients in the right circumstances. The increasing number, as well as the greater diversity and complexity of implanted devices, justify the need to standardize procedures, by establishing institutional agreements that require close collaboration between cardiologists and radiologists. This consensus document, prepared jointly by the Portuguese Society of Cardiology and the Portuguese Society of Radiology and Nuclear Medicine, provides general guidelines for MRI in patients with CIED, ensuring the safety of patients, health professionals and equipment. In addition to briefly reviewing the potential risks of MRI in patients with CIED and major changes to MRI-conditional devices, this article provides specific recommendations on risk-benefit analysis, informed consent, scheduling, programming strategies, devices, monitoring and modification of MRI sequences. The main purpose of this document is to optimize patient safety and provide legal support to facilitate easy access by CIED patients to a potentially beneficial and irreplaceable diagnostic technique.info:eu-repo/semantics/publishedVersio
Timely and Blood-Based Multiplex Molecular Profiling of Acute Stroke
Get PDFStroke is a leading cause of death and disability in the world. To address such a problem, early diagnosis and tailored acute treatment represent one of the major priorities in acute stroke care. Since the efficacy of reperfusion treatments is highly time-dependent, there is a critical need to optimize procedures for faster and more precise diagnosis. We provide a concise review of the most relevant and well-documented blood-protein biomarkers that exhibit greater potential for translational to clinical practice in stroke differential diagnosis and to differentiate ischemic stroke from hemorrhagic stroke, followed by an overview of the most recent point-of-care technological approaches to address this problem. The integration of fluid-based biomarker profiling, using point-of-care biosensors with demographic, clinical, and neuroimaging parameters in multi-dimensional clinical decision-making algorithms, will be the next step in personalized stroke care.info:eu-repo/semantics/publishedVersio
Febre Q pediátrica. Um caso de difícil abordagem
Get PDFIntroduction: Q fever, a zoonosis caused by Coxiella burnetti, is relatively rare in the pediatric population. The disease is often asymptomatic or with mild clinical presentation in children.
Case report: A four-year-old boy with persistent fever, severe anemia, and positive IgM for Coxiella burnetti was treated with trimethoprim-sulfamethoxazole and azithromycin, with no improvement. After polymerase chain reaction confirmation, he completed 14 days of doxycycline, with good response. After eleven months, the child remains asymptomatic.
Discussion: Despite having a usually mild presentation, the severe clinical progression and lack of response to initial antibiotic therapy in this case prompt the use of doxycycline, a non-consensual drug in younger ages, with good results. New recommendations endorse the use of this drug for short periods at any age.info:eu-repo/semantics/publishedVersio