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Fabry disease (FD) is an X-linked rare disorder caused by mutations in the GLA gene. Women with FD have been less enrolled in studies and less treated compared with men. The aim of the present study is to describe the complete phenotype of the women cohort with FD diagnosed and evaluated in Romania and compare it to the male population. This study included all consecutive patients diagnosed with FD referred to the Expert Center for Rare Genetic Cardiovascular Diseases between 2014-2023 which included 73 consecutive Romanian FD patients: 41 women (56.2%) and 32 men (43.8%) from 33 unrelated families. Women with FD were diagnosed later and had a later symptom onset. Comparing with men, women were less often symptomatic, but with similar symptom severity. They had similar ophthalmologic and ENT involvement, but less angiokeratomas. Both women and men had similar heart failure symptoms, which were usually mild to moderate, with no difference between the age of developing of the heart failure symptoms. There were also similar rates of acroparesthesia and stroke between sexes, but women presented less renal involvement, with less requirement for renal transplant. This study demonstrates that women with Fabry disease are not just carriers of the disease, they can present symptoms as severe as men, and they have less or later access to pathogenic therapy. Further studies with more female participations are needed to better understand the burden of Fabry disease in women.
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Although whistleblowing is thought to represent an effective mechanism for detecting and uncovering doping in sport, it has yet to become a widely adopted practice. Understanding the factors that encourage or discourage whistleblowing is of vital importance for the promotion of this practice and the development of pedagogical material to enhance the likelihood of whistleblowing. The current study employed a qualitative methodology to explore the personal and organisational factors that underpin intentions to blow the whistle or that may lead to engagement in whistleblowing behaviours in sport. Thirty-three competitive athletes across a range of sports took part in a semi-structured interview which sought to explore what they would do should they encounter a doping scenario. Content analysis revealed that whistleblowing is a dynamic process characterised by the interaction of a range of personal and organisational factors in determining the intention to report PED use. These factors included moral reasoning, a desire to keep the matter "in-house", perceived personal costs, institutional attitudes to doping, and social support. Analysis revealed a number of "intervening events", including a perceived lack of organisational protection (e.g., ethical leadership) within some sporting sub-cultures, which present an important obstacle to whistleblowing. The intention to report doping was underpinned by a "fairness-loyalty trade-off" which involved athletes choosing to adhere to either fairness norms (which relate to a sense that all people and groups are treated equally) or loyalty norms (which reflect preferential treatment towards an in-group) when deciding whether they would blow the whistle. The promotion of fairness norms that emphasise a group's collective interests might encourage athletes to view whistleblowing as a means of increasing group cohesiveness and effectiveness and thereby increase the likelihood of this practice.
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Background: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory astrocytopathy. Rituximab for B-cell suppression is a common treatment for NMOSD; however, large-scale randomised controlled trials are lacking. Objective: Evaluate long-term efficacy and safety of rituximab for NMOSD. Methods: Retrospective observational study of patients with NMOSD treated with rituximab. Annualised relapse rates (ARRs) before and during rituximab treatment were evaluated; Modified Rankin Scores (mRS) were measured as a marker of disability. Results: In total, 37 patients were included: 27 aquaporin-4-IgG-seropositive and 10 seronegative NMOSD. The predominant rituximab dosing regimen was an initial 1000 mg, split over two 500 mg infusions, two weeks apart, followed by single 500 mg doses. Over a median follow-up of 54 months, ARR for the whole cohort was 0.136 (95% CI 0.088-0.201), significantly lower than the pretreatment ARR of 0.366 (95% CI 0.271-0.483, p < 0.001). There was a significant reduction in ARR for the seropositive subgroup, but not seronegative. Significant improvement in mRS was seen post-treatment. Infections were reported in 32% of patients during follow-up; most were mild. Conclusion: Rituximab, at doses lower than traditionally used, may be an efficacious therapy for NMOSD, with a favourable safety profile.
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AIMS: Systemic amyloidosis represents a heterogeneous group of diseases resulting from amyloid fibre deposition. The purpose of this study is to establish a differential diagnosis algorithm targeted towards the two most frequent subtypes of CA. METHODS AND RESULTS: We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in two centres in a score derivation cohort and a different validation sample. All patients had a complete clinical, biomarker, electrocardiographic, and imaging evaluation. Confirmation of the final diagnosis with amyloid typing was performed according to the current international recommendations. The study population included 81 patients divided into two groups: ATTR (group 1, n = 32: 28 variant and 4 wild type) and AL (group 2, n = 49). ATTR patients were younger (50.7 ± 13.9 vs. 60.2 ± 7.3 years, P = 0.0001), and significantly different in terms of NT-proBNP [ATTR: 1472.5 ng/L (97-4218.5) vs. AL 8024 ng/L (3058-14 069) P = 0.001], hs-cTn I [ATTR: 10 ng/L (4-20) vs. AL 78 ng/L (32-240), P = 0.0002], GFR [ATTR 95.4 mL/min (73.8-105.3) vs. AL: 68.4 mL/min (47.8-87.4) P = 0.003]. At similar left ventricular (LV) wall thickness and ejection fraction, the ATTR group had less frequently pericardial effusion (ATTR: 15% vs. AL: 33% P = 0.0027), better LV global longitudinal strain (ATTR: -13.1% ± 3.5 vs. AL: -9.1% ± 4.3 P = 0.04), RV strain (ATTR: -21.9% ± 6.2 vs. AL: -16.8% ± 6 P = 0.03) and better reservoir function of the LA strain (ATTR: 22% ± 12 vs. AL: 13.6% ± 7.8 P = 0.02). Cut-off points were calculated based on the Youden method. We attributed to 2 points for parameters having an AUC > 0.75 (NT-proBNP AUC 0.799; hs-cTnI AUC 0.87) and 1 point for GFR (AUC 0.749) and TTE parameters (GLS AUC 0.666; RV FWS AUC 0.649, LASr AUC 0.643). A score of equal or more than 4 points has been able to differentiate between AL and ATTR (sensitivity 80%, specificity 62%, AUC = 0.798). The differential diagnosis score system was applied to the validation cohort of 52 CA patients showing a sensitivity of 81% with specificity of 77%. CONCLUSIONS: CA is a complex entity and requires extensive testing for a positive diagnosis. This study highlights a series of non-invasive checkpoints, which can be useful in guiding the decision-making process towards a more accurate and rapid differential diagnosis.
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Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder, most often caused by sarcomeric gene mutations, with a small proportion due to variants in non-sarcomeric loci. Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of cardiac contractility and relaxation. We conducted a retrospective study to determine the prevalence, phenotypical spectrum and clinical course of patients carrying the PLN p.Leu39* variant. A cohort including 11 PLN patients was identified among all patients with HCM (9/189, 4.8%) and DCM (2/62, 3.2%) who underwent genetic testing from two tertiary centers and five more were detected through cascade screening. Complete phenotyping was performed. PLN p.Leu39* variant-driven cardiomyopathy presented mostly as hypertrophic, with frequent progression to end-stage dilated HCM. We proceeded to compare these results to a similar analysis of a control cohort consisting of age-matched individuals that inherited pathogenic or likely pathogenic variants in common sarcomeric genes (MYBPC3/MYH7). Overall, the clinical characteristics and examination findings of patients carrying PLN p.Leu39* were not different from patients with cardiomyopathy related to sarcomeric mutations except for the presence of pathological Q waves and the incidence of non-sustained ventricular arrhythmias, which were higher in PLN patients than in those with MYBPC3/MYH7-related diseases.
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BACKGROUND: Mild memory impairment, termed amnestic mild cognitive impairment (aMCI), is associated with rapid progression towards dementia in Parkinson's disease (PD). Studies have shown hyperactivation of hippocampal DG/CA3 subfields during an episodic memory task as a biomarker of aMCI related to Alzheimer's disease. This project investigates the feasibility of a trial to establish the efficacy of a repurposed antiepileptic drug, levetiracetam, in low doses as a putative treatment to target DG/CA3 hyperactivation and improve episodic memory deficits in aMCI in PD. Based on previous work, it is hypothesized that levetiracetam will normalize DG/CA3 overactivation in PD-aMCI participants and improve memory performance. METHODS: Twenty-eight PD-aMCI participants, 28 PD participants without memory impairment (PD-nMI), and 28 healthy controls will be recruited. PD-aMCI participants will undertake a 12-week randomized, placebo-controlled, double-blind cross-over trial with a 14-day treatment of 125 mg levetiracetam or placebo twice daily, separated by a 4-week washout period. After each treatment period, participants will complete an episodic memory task designed to tax hippocampal subregion-specific function during high-resolution functional magnetic resonance imaging (fMRI). PD-nMI and healthy controls will undergo the fMRI protocol only, to compare baseline DG/CA3 subfield activity. RESULTS: Episodic memory task performance and functional activation in the DG/CA3 subfield during the fMRI task will be primary outcome measures. Global cognition, PD severity, and adverse events will be measured as secondary outcomes. Recruitment, eligibility, and study completion rates will be explored as feasibility outcomes. CONCLUSIONS: This study, the first of its kind, will establish hippocampal subregion functional impairment and proof of concept of levetiracetam as an early therapeutic option to reduce dementia risk in PD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04643327 . Registered on 25 November 2020.
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BACKGROUND: For patients with nonischemic cardiomyopathy (NICM), current guidelines recommend implantable cardioverter defibrillators (ICD) when left ventricular ejection fraction (LVEF) is ≤35%, but the DANISH trial failed to confirm that ICDs reduced all-cause mortality for such patients. Circumstantial evidence suggests that scar on CMR is predictive of sudden and arrhythmic death in this population. The presence of myocardial scar identified by cardiac magnetic resonance imaging (CMR) in patients with NICM and an LVEF ≤35% might identify patients at higher risk of sudden arrhythmic death, for whom an ICD is more likely to reduce all-cause mortality. METHODS/DESIGN: The BRITISH trial is a prospective, multicenter, randomized controlled trial aiming to enrol 1,252 patients with NICM and an LVEF ≤35%. Patients with a nonischemic scar on CMR will be randomized to either: (1) ICD, with or without cardiac resynchronization (CRT-D), or (2) implantable loop recorder (ILR) or cardiac resynchronization (CRT-P). Patients who are screened for the trial but are found not to be eligible, predominantly due to an absence of scar or those who decline to be randomized will be enrolled in an observational registry. The primary endpoint is all-cause mortality, which we plan to assess at 3 years after the last participant is randomized. Secondary endpoints include clinical outcomes, appropriate and inappropriate device therapies, symptom severity and well-being, device-related complications, and analysis of the primary endpoint by subgroups with other risk markers. CONCLUSION: The BRITISH trial will assess whether the use of CMR-defined scar to direct ICD implantation in patients with NICM and an LVEF ≤35% is associated with a reduction in mortality.
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Cardiomiopatías , Desfibriladores Implantables , Insuficiencia Cardíaca Sistólica , Humanos , Volumen Sistólico , Cicatriz/complicaciones , Benchmarking , Estudios Prospectivos , Función Ventricular Izquierda , Cardiomiopatías/complicaciones , Cardiomiopatías/diagnóstico , Cardiomiopatías/terapia , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Factores de Riesgo , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND: Apathy, characterized by a quantifiable reduction in motivation or goal-directed behavior, is a multidimensional syndrome that has been observed across many neurodegenerative diseases. OBJECTIVE: To develop a novel task measuring spontaneous action initiation (ie, a nonverbal equivalent to spontaneous speech tasks) and to investigate the association between apathy and executive functions such as the voluntary initiation of speech and actions and energization (ie, ability to initiate and sustain a response). METHOD: We compared the energization and executive functioning performance of 10 individuals with neurodegenerative disease and clinically significant apathy with that of age-matched healthy controls (HC). We also investigated the association between self-reported scores on the Apathy Evaluation Scale (AES) and performance on energization tasks. RESULTS: The individuals with apathy made significantly fewer task-related actions than the HC on the novel spontaneous action task, and their scores on the AES were negatively correlated with spontaneous task-related actions, providing preliminary evidence for the task's construct validity. In addition, the individuals with apathy performed more poorly than the HC on all of the energization tasks, regardless of task type or stimulus modality, suggesting difficulty in sustaining voluntary responding over time. Most of the tasks also correlated negatively with the AES score. However, the individuals with apathy also performed more poorly on some of the executive function tasks, particularly those involving self-monitoring. CONCLUSION: Our work presents a novel experimental task for measuring spontaneous action initiation-a key symptom of apathy-and suggests a possible contribution of apathy to neuropsychological deficits such as poor energization.
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Apatía , Enfermedades Neurodegenerativas , Humanos , Apatía/fisiología , Proyectos Piloto , Pruebas Neuropsicológicas , Función Ejecutiva/fisiologíaRESUMEN
A new implementation of the internally contracted multireference coupled-cluster with singles and doubles (icMRCCSD) method is presented. The new code employs an efficient tensor contraction kernel and can also avoid full four-external integral transformations, which significantly extends the scope of the applicability of icMRCCSD. The new implementation is currently restricted to the simple case of two active electrons in two orbitals and also supports the computation of spin-adapted doublet and triplet coupled-cluster wavefunctions. This contribution describes the basic approach for the automated derivation of working equations and benchmarks the current code against efficient implementations of standard methods, such as single-reference coupled-cluster singles and doubles (CCSD) and internally contracted multireference configuration interaction (icMRCI). Run times for linearized variants of icMRCCSD are only twice as long as comparable CCSD runs and similar to those of the icMRCI implementation, while non-linear terms of more complete variants of icMRCCSD lead to an order of magnitude longer computation times. Nevertheless, the new code allows for computations at larger scales than it was possible previously, with less demands on memory and disk-space resources. This is exemplified by numerical structure optimizations and harmonic force field determinations of NC2H5 isomers and the singlet and triplet states of m-benzyne. In addition, the exchange coupling of a dinuclear copper complex is determined. This work also defines a new commutator approximation for icMRCCSD, which includes all terms that are also present in the single-reference CCSD method, thus yielding a consistent pair of single-reference and multireference coupled-cluster methods.
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BACKGROUND: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation. METHODS: Across 25 hospitals in the United Kingdom, 342 patients with COVID-19 and an elevated troponin level (COVID+/troponin+) were enrolled between June 2020 and March 2021 and had a magnetic resonance imaging scan within 28 days of discharge. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin-) and 113 patients without COVID-19 or elevated troponin level matched by age and cardiovascular comorbidities (COVID-/comorbidity+). Regression modeling was performed to identify predictors of major adverse cardiovascular events at 12 months. RESULTS: Of the 519 included patients, 356 (69%) were men, with a median (interquartile range) age of 61.0 years (53.8, 68.8). The frequency of any heart abnormality, defined as left or right ventricular impairment, scar, or pericardial disease, was 2-fold greater in cases (61% [207/342]) compared with controls (36% [COVID+/troponin-] versus 31% [COVID-/comorbidity+]; P<0.001 for both). More cases than controls had ventricular impairment (17.2% versus 3.1% and 7.1%) or scar (42% versus 7% and 23%; P<0.001 for both). The myocardial injury pattern was different, with cases more likely than controls to have infarction (13% versus 2% and 7%; P<0.01) or microinfarction (9% versus 0% and 1%; P<0.001), but there was no difference in nonischemic scar (13% versus 5% and 14%; P=0.10). Using the Lake Louise magnetic resonance imaging criteria, the prevalence of probable recent myocarditis was 6.7% (23/342) in cases compared with 1.7% (2/113) in controls without COVID-19 (P=0.045). During follow-up, 4 patients died and 34 experienced a subsequent major adverse cardiovascular event (10.2%), which was similar to controls (6.1%; P=0.70). Myocardial scar, but not previous COVID-19 infection or troponin, was an independent predictor of major adverse cardiovascular events (odds ratio, 2.25 [95% CI, 1.12-4.57]; P=0.02). CONCLUSIONS: Compared with contemporary controls, patients with COVID-19 and elevated cardiac troponin level have more ventricular impairment and myocardial scar in early convalescence. However, the proportion with myocarditis was low and scar pathogenesis was diverse, including a newly described pattern of microinfarction. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: 58667920.
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COVID-19 , Lesiones Cardíacas , Miocarditis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cicatriz , COVID-19/complicaciones , COVID-19/epidemiología , Hospitalización , Estudios Prospectivos , Factores de Riesgo , Troponina , AncianoRESUMEN
Amyloidosis is a heterogeneous group of diseases caused by the extracellular deposition of amyloid insoluble fibrils in multiple organs, resulting in various clinical manifestations. Cardiac amyloidosis (CA) occurs mainly in primary light-chain (AL) amyloidosis, hereditary transthyretin (ATTRv) amyloidosis and senile or wild-type transthyretin (ATTRwt) amyloidosis. Knowing that myocardial uptake at bone scintigraphy is an essential step in the ATTR-CA diagnostic algorithm, the level of awareness among nuclear medicine physicians (NMPs) using bone tracer scintigraphy is of great importance. The objective of the study was to evaluate NMPs' awareness of scintigraphy with bisphosphonates for the detection of CA. We conducted an online survey among NMPs from Romania to assess their current awareness and state of knowledge of nuclear techniques used in CA. Among the total 65 Romanian NMPs, 35 (53%) responded to this questionnaire. Approximately three-quarters of participants (74%) found a diffuse accumulation of bisphosphonates in the heart on scintigraphy performed for bone pathology as an incidental discovery. Detection of myocardial uptake of 99mTc-labeled bisphosphonates on scintigraphy suggests CA-AL for 3% of participants and for 9% of respondents, the appearance is of uncertain cardiac amyloidosis, while 5% of participants observed cardiac uptake but did not report it as CA. Even if more than half of those who responded to this survey (54%) found abnormal cardiac uptake and interpreted it as CA-ATTR, only 14% contacted the referring physician to draw attention to the incidental discovery to refer the patient to a specialist in rare genetic cardiomyopathy. Regarding the knowledge about the categories of bisphosphonates recommended in the diagnosis of CA-ATTR, 54% answered inadequately that methylene diphosphonate (MDP) could be used. Romanian nuclear physicians are partially familiar with CA diagnosis by scintigraphy, but its diagnostic potential and standardization, recommended radiotracers and acquisition times and interpretation algorithms are known in varying proportions. Therefore, there is a need to enhance knowledge through continuing medical education programs in order to standardize the protocols for the acquisition, processing and interpretation of bisphosphonate scintigraphy for the detection of cardiac ATTR amyloidosis.
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Background Global longitudinal shortening (GL-Shortening) and the mitral annular plane systolic excursion (MAPSE) are known markers in heart failure patients, but measurement may be subjective and less frequently reported because of the lack of automated analysis. Therefore, a validated, automated artificial intelligence (AI) solution can be of strong clinical interest. Methods and Results The model was implemented on cardiac magnetic resonance scanners with automated in-line processing. Reproducibility was evaluated in a scan-rescan data set (n=160 patients). The prognostic association with adverse events (death or hospitalization for heart failure) was evaluated in a large patient cohort (n=1572) and compared with feature tracking global longitudinal strain measured manually by experts. Automated processing took ≈1.1 seconds for a typical case. On the scan-rescan data set, the model exceeded the precision of human expert (coefficient of variation 7.2% versus 11.1% for GL-Shortening, P=0.0024; 6.5% versus 9.1% for MAPSE, P=0.0124). The minimal detectable change at 90% power was 2.53 percentage points for GL-Shortening and 1.84 mm for MAPSE. AI GL-Shortening correlated well with manual global longitudinal strain (R2=0.85). AI MAPSE had the strongest association with outcomes (χ2, 255; hazard ratio [HR], 2.5 [95% CI, 2.2-2.8]), compared with AI GL-Shortening (χ2, 197; HR, 2.1 [95% CI,1.9-2.4]), manual global longitudinal strain (χ2, 192; HR, 2.1 [95% CI, 1.9-2.3]), and left ventricular ejection fraction (χ2, 147; HR, 1.8 [95% CI, 1.6-1.9]), with P<0.001 for all. Conclusions Automated in-line AI-measured MAPSE and GL-Shortening can deliver immediate and highly reproducible results during cardiac magnetic resonance scanning. These results have strong associations with adverse outcomes that exceed those of global longitudinal strain and left ventricular ejection fraction.
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Inteligencia Artificial , Insuficiencia Cardíaca , Humanos , Válvula Mitral/diagnóstico por imagen , Pronóstico , Reproducibilidad de los Resultados , Volumen Sistólico , Sístole , Función Ventricular IzquierdaAsunto(s)
Blefaroplastia , Blefaroptosis , Lentes de Contacto , Vendajes , Blefaroptosis/cirugía , Humanos , Periodo PosoperatorioRESUMEN
BACKGROUND: Monogenic causes of isolated dystonia are heterogeneous. Assembling cohorts of affected individuals sufficiently large to establish new gene-disease relationships can be challenging. OBJECTIVE: We sought to expand the catalogue of monogenic etiologies for isolated dystonia. METHODS: After the discovery of a candidate variant in a multicenter exome-sequenced cohort of affected individuals with dystonia, we queried online platforms and genomic data repositories worldwide to identify subjects with matching genotypic profiles. RESULTS: Seven different biallelic loss-of-function variants in AOPEP were detected in five probands from four unrelated families with strongly overlapping phenotypes. In one proband, we observed a homozygous nonsense variant (c.1477C>T [p.Arg493*]). A second proband harbored compound heterozygous nonsense variants (c.763C>T [p.Arg255*]; c.777G>A [p.Trp259*]), whereas a third proband possessed a frameshift variant (c.696_697delAG [p.Ala234Serfs*5]) in trans with a splice-disrupting alteration (c.2041-1G>A). Two probands (siblings) from a fourth family shared compound heterozygous frameshift alleles (c.1215delT [p.Val406Cysfs*14]; c.1744delA [p.Met582Cysfs*6]). All variants were rare and expected to result in truncated proteins devoid of functionally important amino acid sequence. AOPEP, widely expressed in developing and adult human brain, encodes a zinc-dependent aminopeptidase, a member of a class of proteolytic enzymes implicated in synaptogenesis and neural maintenance. The probands presented with disabling progressive dystonia predominantly affecting upper and lower extremities, with variable involvement of craniocervical muscles. Dystonia was unaccompanied by any additional symptoms in three families, whereas the fourth family presented co-occurring late-onset parkinsonism. CONCLUSIONS: Our findings suggest a likely causative role of predicted inactivating biallelic AOPEP variants in cases of autosomal recessive dystonia. Additional studies are warranted to understand the pathophysiology associated with loss-of-function variation in AOPEP. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Aminopeptidasas , Distonía , Trastornos Distónicos , Mutación con Pérdida de Función , Aminopeptidasas/genética , Distonía/genética , Trastornos Distónicos/genética , Exoma , Humanos , Mutación , Linaje , FenotipoRESUMEN
Cardiac amyloidosis (CA) is a restrictive cardiomyopathy characterized by deposition of amyloid in the myocardium and recent studies revealed it is more frequently seen than we thought. Advances in diagnosis and treatment have been made over the last few years that make it desirable to diagnose CA without delay, and that may require extra education. An online survey was conducted among cardiologists from Romania, representing the first assessment of the knowledge of CA among them, with 195 cardiologists answering the questionnaire. There was a wide variation in their knowledge regarding CA. Our participants had limited experience with CA and reported a significant delay between first cardiac symptoms and diagnosis. We address the gaps in knowledge that were identified as educational opportunities in the main identified areas: prevalence and treatment of wild type transthyretin amyloidosis (ATTRwt), prevalence of variant transthyretin amyloidosis (ATTRv) in Romania, diagnosis of CA, the delay in CA diagnosis and available treatment options. Awareness among cardiologists is the most important challenge in diagnosing CA. Romanian cardiologists are partially aware of this topic, but there are still gaps in their knowledge. Educational programs can improve screening of patients with a high suspicion for this progressive condition the prognosis of which has been dramatically changed by the new treatment options.
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Cardiac amyloidosis is a restrictive cardiomyopathy determined by the accumulation of amyloid, which is represented by misfolded protein fragments in the cardiac extracellular space. The main classification of systemic amyloidosis is determined by the amyloid precursor proteins causing a very heterogeneous disease spectrum, but the main types of amyloidosis involving the heart are light chain (AL) and transthyretin amyloidosis (ATTR). AL, in which the amyloid precursor is represented by misfolded immunoglobulin light chains, can involve almost any system carrying the worst prognosis among amyloidosis patients. This has however dramatically improved in the last few years with the increased usage of the novel therapies such as proteasome inhibitors and haematopoietic cell transplantation, in the case of timely diagnosis and initiation of treatment. The treatment for AL is directed by the haematologist working closely with the cardiologist when there is a significant cardiac involvement. Transthyretin (TTR) is a protein that is produced by the liver and is involved in the transportation of thyroid hormones, especially thyroxine and retinol binding protein. ATTR results from the accumulation of transthyretin amyloid in the extracellular space of different organs and systems, especially the heart and the nervous system. Specific therapies for ATTR act at various levels of TTR, from synthesis to deposition: TTR tetramer stabilization, oligomer aggregation inhibition, genetic therapy, amyloid fibre degradation, antiserum amyloid P antibodies, and antiserum TTR antibodies. Treatment of systemic amyloidosis has dramatically evolved over the last few years in both AL and ATTR, improving disease prognosis. Moreover, recent studies revealed that timely treatment can lead to an improvement in clinical status and in a regression of amyloid myocardial infiltration showed by imaging, especially by cardiac magnetic resonance, in both AL and ATTR. However, treating cardiac amyloidosis is a complex task due to the frequent association between systemic congestion and low blood pressure, thrombo-embolic and haemorrhagic risk balance, patient frailty, and generally poor prognosis. The aim of this review is to describe the current state of knowledge regarding cardiac amyloidosis therapy in this constantly evolving field, classified as treatment of the cardiac complications of amyloidosis (heart failure, rhythm and conduction disturbances, and thrombo-embolic risk) and the disease-modifying therapy.
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Neuropatías Amiloides Familiares , Cardiomiopatías , Cardiomiopatía Restrictiva , Cardiopatías , Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/terapia , Cardiomiopatías/diagnóstico , Cardiomiopatías/terapia , Humanos , PrealbúminaRESUMEN
OBJECTIVES: The purpose of this study was to detect cardiovascular changes after mild severe acute respiratory syndrome-coronavirus-2 infection. BACKGROUND: Concern exists that mild coronavirus disease 2019 may cause myocardial and vascular disease. METHODS: Participants were recruited from COVIDsortium, a 3-hospital prospective study of 731 health care workers who underwent first-wave weekly symptom, polymerase chain reaction, and serology assessment over 4 months, with seroconversion in 21.5% (n = 157). At 6 months post-infection, 74 seropositive and 75 age-, sex-, and ethnicity-matched seronegative control subjects were recruited for cardiovascular phenotyping (comprehensive phantom-calibrated cardiovascular magnetic resonance and blood biomarkers). Analysis was blinded, using objective artificial intelligence analytics where available. RESULTS: A total of 149 subjects (mean age 37 years, range 18 to 63 years, 58% women) were recruited. Seropositive infections had been mild with case definition, noncase definition, and asymptomatic disease in 45 (61%), 18 (24%), and 11 (15%), respectively, with 1 person hospitalized (for 2 days). Between seropositive and seronegative groups, there were no differences in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T1, T2, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro-B-type natriuretic peptide). With abnormal defined by the 75 seronegatives (2 SDs from mean, e.g., ejection fraction <54%, septal T1 >1,072 ms, septal T2 >52.4 ms), individuals had abnormalities including reduced ejection fraction (n = 2, minimum 50%), T1 elevation (n = 6), T2 elevation (n = 9), late gadolinium enhancement (n = 13, median 1%, max 5% of myocardium), biomarker elevation (borderline troponin elevation in 4; all N-terminal pro-B-type natriuretic peptide normal). These were distributed equally between seropositive and seronegative individuals. CONCLUSIONS: Cardiovascular abnormalities are no more common in seropositive versus seronegative otherwise healthy, workforce representative individuals 6 months post-mild severe acute respiratory syndrome-coronavirus-2 infection.
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COVID-19 , Anomalías Cardiovasculares , Adolescente , Adulto , Inteligencia Artificial , Estudios de Casos y Controles , Medios de Contraste , Femenino , Gadolinio , Personal de Salud , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Miocardio , Valor Predictivo de las Pruebas , Estudios Prospectivos , SARS-CoV-2 , Función Ventricular Izquierda , Adulto JovenRESUMEN
Introduction: Autoimmune encephalitis is a disorder associated with antibodies directed against central nervous system proteins with variable clinical features. This study aims to add to knowledge of the disease by reporting the details of a cohort of patients with autoimmune encephalitis in Queensland, Australia. Methodology: We surveyed patients with autoimmune encephalitis diagnosed and managed through public hospitals in Queensland, Australia between 2010 and the end of 2019. Cases were identified via case detection through a centralized diagnostic neuroimmunology laboratory (Division of Immunology, HSQ Pathology Queensland Central Laboratory, Brisbane, Queensland, Australia) and a survey of neurologists. Data including demographic details, clinical presentation, investigation results, treatments including immune therapy and outcomes was collected. Results: Sixty cases of antibody positive autoimmune encephalitis were identified. Twenty-eight were of anti-NMDA-receptor encephalitis with other cases associated with antibodies against LGi1, Caspr2, glycine receptor, DPPX, GABAB receptor, IgLON5, GFAP, and SOX1. The number of diagnosed cases, especially of anti-NMDA-receptor encephalitis has markedly increased over the period 2017 to 2019. Clinical presentations were marked by heterogeneous symptom complexes and prolonged hospital admissions. Imaging studies were largely normal or non-specific. There was a response to immune therapy and a low mortality rate. Most cases affected by this disorder were left with ongoing symptoms associated with mild disability. Conclusion: Autoimmune encephalitis in Queensland, Australia is an increasingly common but complex clinical entity marked by heterogeneous presentations, response to immune therapy and outcome results marked by low mortality and incomplete recovery.
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PURPOSE: To determine whether a bandage contact lens (BCL) improves patient comfort in the postoperative period in patients undergoing ptosis repair using the Fasanella-Servat technique, compared with no BCL. METHODS: In this prospective, randomized, double-masked, comparison study, all patients had bilateral Fasanella-Servat surgery. A total of 30 patients were randomized to receive a BCL in one eye and no BCL in the other eye. Patient discomfort was measured as the primary outcome using the Eye Sensation Scale. Blurred vision was measured as a secondary outcome using selected questions from the Ocular Surface Disease Index. The surgeries were performed by 2 surgeons (J.T.H and R.S.A). Outcomes were measured one week following the procedure. RESULTS: Patients reported significantly less discomfort in the eye receiving a BCL, with only 13.3% ranking discomfort as "moderate" or "severe," compared with the eye not receiving BCL, where 63.3% of patients rated discomfort as "moderate" or "severe" (p < 0.001). There was no significant difference in patient-reported blurred vision between the 2 groups (p = 0.520). CONCLUSIONS: The use of a bandage contact lens after Fasanella-Servat procedure for ptosis repair is recommended as it improves patient comfort. In addition, it has no detrimental effect on patient-reported blurring of vision.