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BACKGROUND: Paediatric systemic lupus erythematosus is a rare autoimmune disease with a wide spectrum of clinical presentation in different populations. We present a cohort of paediatric systemic lupus erythematosus in Malaysia where the disease features and outcomes are still largely unknown. METHODS: A retrospective review of all paediatric systemic lupus erythematosus patients with at least 6 months follow-up at Selayang Hospital from 2004 to 2016. Epidemiological, clinical and outcome data were collected and analysed. RESULTS: A total of 141 paediatric systemic lupus erythematosus patients, 87.9% females, were followed up for a median 6.3 years (interquartile range 3.6-9.0). The median age at diagnosis was 10.8 years (interquartile range 9.0-12.0 years), positive family history of systemic lupus erythematosus was present in 12.1% and the majority (61.7%) were of Malay ethnicity. Common presentations included fever (87.2%), vasculitic rash (72.3%) and lethargy (69.5%). At diagnosis, leukopenia (51.1%), thrombocytopenia (41.8%) and cutaneous lupus (56%) predominate with significant renal involvement (39.7%). Renal (45.4%), liver (26%) and the central nervous system (17%) were important major organs involved during the course of the disease. At diagnosis, almost all (99.3%) patients had high disease activity (mean Systemic Lupus Erythematosus Disease Activity Index score 20.1 ± 9.6). The majority (62.4%) achieved remission or low disease activity after 6 months, maintained over the next 10 years. Damage occurred early (39.1% at 1 year) and increased with time. Ocular damage was the most common side effect (29%) and was predominantly corticosteroid related (93%). Growth retardation was significant (38.2%) with no gonadal failure or secondary malignancies. End-stage renal disease occurred in 3.1% patients whereas 53.1% had sustained renal remission. Overall mortality was 1.4%. CONCLUSION: Despite high disease activity at diagnosis, the majority had good sustained response to treatment with low overall mortality. However, there was progressive accrual of organ damage, highlighting the need for further research and refinements into therapies for paediatric systemic lupus erythematosus.
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Progressão da Doença , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Leucopenia/epidemiologia , Lúpus Eritematoso Cutâneo/epidemiologia , Malásia/epidemiologia , Masculino , Anamnese , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença , Trombocitopenia/epidemiologiaRESUMO
There has been an exponential increase in the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CA). In response, the Midlands Amyloidosis Service was launched with the aim of providing patients with a timely diagnosis, remote expertise from the National Amyloidosis Centre and access to emerging transthyretin (TTR)-directed therapies. This was a descriptive study of a pilot hub-and-spoke model of delivering specialist amyloidosis care. Patients with suspected amyloidosis were referred from the wider Midlands region, and seen in a consultant-led multidisciplinary clinic. The diagnosis of ATTR-CA was established according to either the validated non-biopsy criteria or histological confirmation of ATTR deposits with imaging evidence of amyloid. Study endpoints were the volume of service provision and the time to diagnosis from the receipt of referral. Patients (n=173, age 75±2 years; male 72 %) were referred between 2019 and 2021. Eighty patients (46 %) were found to have cardiac amyloidosis, of whom 68 (85 %) had ATTR-CA. The median time from referral to diagnosis was 43 days. By removing the need for patients to travel to London, an average of 187 patient-miles was saved. Fifteen (9 %) patients with wild-type ATTR-CA received tafamidis under the Early Access to Medicine scheme; 10 (6 %) were enrolled into phase 3 clinical trials of RNA interference or antisense oligonucleotide therapies. Our results suggest that implementing a UK amyloidosis network appears feasible and would enhance equity of access to specialised amyloidosis healthcare for the increasing numbers of older patients found to have ATTR-CA.
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Amiloidose , Pré-Albumina , Humanos , Masculino , Idoso , Estudos de Viabilidade , Instituições de Assistência Ambulatorial , LondresRESUMO
An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs.
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Deterioração Clínica , Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Humanos , Emergências , Insuficiência Cardíaca/terapiaRESUMO
BACKGROUND This case illustrates the challenges in diagnosing linear scleroderma (LS) in a child who presented to a primary care setting. Diagnosis of LS is easily missed due to the lack of prominent symptoms, subtle visible skin changes, and under-recognition of this condition. CASE REPORT A 7-year-old boy presented with a linear, painless, non-itchy rash at the center of his forehead, which has been present for 6 months. The rash extends vertically from the hairline to the bridge of the nose. The color gradually evolved from reddish to purplish-grey and shiny within 3 months. He had underlying eczema, allergic rhinitis, and allergic conjunctivitis since birth. His condition remained unrecognized despite consultations with various medical specialties, including family medicine specialist, ophthalmologist, otorhinolaryngologist, and a general pediatrician. Six months after the onset of his lesion, he was subsequently referred to a pediatric dermatologist and pediatric rheumatologist, who made the diagnosis of LS. Laboratory investigations for autoimmune disease showed that negative antinuclear antibodies (ANA) and inflammatory markers, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were normal. Skin biopsy provided a tissue confirmation of the diagnosis. MRI of the lesion showed no extension into the underlying muscle or bone erosions. The patient was initially treated with intravenous (IV) methylprednisolone for 3 days, followed by oral methotrexate weekly and prednisolone. The lesion improved after 1 month of treatment, and after 15 months it was less pigmented and less noticeable. CONCLUSIONS LS is the commonest form of localized scleroderma in children. LS on the forehead can erode into the underlying tissues and is sometimes associated with extensive hemifacial atrophy. Treatment should be instituted early to prevent late irreversible fibrotic sequelae. This report aims to highlight the importance of early diagnosis and treatment of an uncommon but potentially disfiguring condition.
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Exantema , Esclerodermia Localizada , Masculino , Humanos , Criança , Esclerodermia Localizada/diagnóstico , Metilprednisolona , Metotrexato/uso terapêutico , Atenção Primária à SaúdeRESUMO
BACKGROUND: Correction of mitral regurgitation (MR) at the time of left ventricular assist device (LVAD) implantation remains controversial. There is conflicting evidence regarding the clinical impact of residual MR, and studies have not examined whether MR aetiology or right heart function impacts the likelihood of residual MR. METHODS: This is a retrospective single-centre study of 155 consecutive patients with LVAD implantation from January 2011 to March 2020. Exclusion criteria were no MR pre-LVAD (n=8), inaccessible echocardiography (n=9), duplicate records (n=10) and concomitant mitral valve repair (n=1). Statistical analysis was performed using STATA V.16 and SPSS V.24. RESULTS: Carpentier IIIb MR aetiology was associated with more severe MR pre-LVAD (severe 18/27 (67%) vs non-severe 32/91 (35%), p=0.004) and a higher likelihood of residual MR (8/11 (72%) vs 30/74 (41%), p=0.045). Of 95 patients with significant MR pre-LVAD, 15 (16%) had persistent significant MR, which was associated with higher mortality (p=0.006), post-LVAD right ventricle (RV) dilatation (10/15 (67%) vs 28/80 (35%), p=0.022) and RV dysfunction (14/15 (93%) vs 35/80 (44%), p<0.001). Aside from ischaemic aetiology, other pre-LVAD parameters that were associated with significant residual MR included left ventricular end-systolic diameter (LVESD) (6.9 cm (5.7-7.2) vs 5.9 cm (5.5-6.5), p=0.043), left atrial volume index (LAVi) (78 mL/m2 (56-88) vs 57 mL/m2 (47-77), p=0.021), posterior leaflet displacement (2.5 cm (2.3-2.9) vs 2.3 cm (1.9-2.7), p=0.042) and basal right ventricular end-diastolic diameter (RVEDD) (5.1±0.8 cm vs 4.5±0.8 cm, p=0.010). CONCLUSION: LVAD therapy improves MR and tricuspid regurgitation severity in the majority, but 14% have persistent significant residual MR, associated with right ventricular dysfunction and higher long-term mortality. This may be predicted pre-LVAD by greater LVESD, RVEDD and LAVi and by ischaemic aetiology.
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Coração Auxiliar , Insuficiência da Valva Mitral , Humanos , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Coração Auxiliar/efeitos adversos , Estudos Retrospectivos , Átrios do Coração , Ventrículos do CoraçãoRESUMO
BACKGROUND: Despite a move towards the provision of specialist training in Australia in settings that extend beyond the public hospital system, formal comparisons of case mix between public and private specialty clinics have rarely been performed. It is therefore unclear for many specialties how well training in one setting prepares trainees for practice in the other. AIMS: This study aims to compare the case mix of paediatric rheumatology patients seen in public and private settings and the referral sources of patients in each. METHODS: An audit of all new patients seen in the public and private paediatric rheumatology clinics on campus at Royal Children's Hospital between June 2009 and January 2011. Data related to demographics, primary diagnosis, referral source and location seen were abstracted and compared. RESULTS: Eight hundred and seventy-six new patients were seen during the period of interest. Of these, 429 patients (48.9%) were seen in private clinics. The commonest diagnostic categories for both type of clinics were non-inflammatory musculoskeletal pain/orthopaedic conditions (public 39.4%, private 33.6%) followed by juvenile idiopathic arthritis (public 16.6%, %, private 18.6%), other skin/soft tissue disorders (public 8.7%, private 9.6%) and pain syndromes (public 4.9%, private 11.4%). Patients with haematological and vasculitic disorders were predominantly seen in public clinics. The commonest source of referrals to both clinics was general practitioners (public 40.6%, private 53.1%). CONCLUSION: The case mix in private paediatric rheumatology clinics closely mirrors that of public clinics at our centre. Training in either setting would provide sufficient case-mix exposure to prepare trainees for practice in the other.
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Grupos Diagnósticos Relacionados/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Pediatria/educação , Doenças Reumáticas/epidemiologia , Reumatologia/educação , Adolescente , Austrália , Criança , Pré-Escolar , Hospitais Privados/estatística & dados numéricos , Hospitais Públicos/estatística & dados numéricos , Humanos , Lactente , Auditoria Médica , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Vitória/epidemiologia , Adulto JovemRESUMO
Aims: Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive and fatal cardiomyopathy. Treatment options in patients with advanced ATTR-CM are limited to cardiac transplantation (CT). Despite case series demonstrating comparable outcomes with CT between patients with ATTR-CM and non-amyloid cardiomyopathies, ATTR-CM is considered to be a contraindication to CT in some centers, partly due to a perceived risk of amyloid recurrence in the allograft. We report long-term outcomes of CT in ATTR-CM at two tertiary centers. Materials and methods and Results: We retrospectively evaluated ATTR-CM patients across two tertiary centers who underwent transplantation between 1990 and 2020. Pre-transplantation characteristics were determined and outcomes were compared with a cohort of non-transplanted ATTR-CM patients. Fourteen (12 male, 2 female) patients with ATTR-CM underwent CT including 11 with wild-type ATTR-CM and 3 with variant ATTR-CM (ATTRv). Median age at CT was 62 years and median follow up post-CT was 66 months. One, three, and five-year survival was 100, 92, and 90%, respectively and the longest surviving patient was Censored > 19 years post CT. No patients had recurrence of amyloid in the cardiac allograft. Four patients died, including one with ATTRv-CM from complications of leptomeningeal amyloidosis. Survival among the cohort of patients who underwent CT was significantly prolonged compared to UK patients with ATTR-CM generally (p < 0.001) including those diagnosed under age 65 years (p = 0.008) or with early stage cardiomyopathy (p < 0.001). Conclusion: CT is well-tolerated, restores functional capacity and improves prognosis in ATTR-CM. The risk of amyloid recurrence in the cardiac allograft appears to be low.
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OBJECTIVE: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology. METHODS: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%. RESULTS: Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3-5). Validation of the SSR for up to 6 months post-kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6). CONCLUSION: The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials.
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Glucocorticoides/administração & dosagem , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/etiologia , Adolescente , Idade de Início , Criança , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
INTRODUCTION: The incidence, mechanisms, clinical associations, and outcomes in patients with late-onset (>3 months) atrioventricular (AV) block following heart transplantation are not well known. This study will characterize late-onset AV block following cardiac transplantation. METHODS: We retrospectively reviewed our databases to identify patients who required pacemakers for late-onset AV block postheart and heart-lung transplantation from January 1990 to December 2007. Orthotopic heart and heart-lung transplantation were separately analyzed. RESULTS: This study included 588 adults who received cardiac transplants over a 17-year period at our center (519 orthotopic, 64 heart-lung transplants, and five heterotopic heart transplants). Of the 519 patients with orthotopic heart transplant, 39 required pacing (7.5%), 17 (3.3%) within 3 months posttransplant, 11 (2.1%) for late-onset sinus node dysfunction (SND), 11 (2.1%) for late-onset AV block. Also, five patients (7.8%) out of 64 heart-lung transplants required pacemakers, two (3.1%) for late-onset SND, three (4.7%) for late-onset AV block. None of the five patients who underwent heterotopic transplant required cardiac pacing prior to or posttransplant. CONCLUSIONS: Late-onset AV block occurs in 2.4% of patients with orthotopic heart transplant or heart-lung transplant. AV block is predominantly intermittent and, often, does not progress to permanent AV block. There are no predictable factors for its onset.
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Bloqueio Atrioventricular/epidemiologia , Bloqueio Atrioventricular/prevenção & controle , Estimulação Cardíaca Artificial/estatística & dados numéricos , Transplante de Coração/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Austrália/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
A seven-year-old girl presented with pain in multiple joints and constitutional symptoms over a period of four months. There were no significant clinical findings apart from joint tenderness. Blood test results did not indicate any specific pathology and initial radiology imaging was normal. Subsequent careful examination of her X-ray images led to an MRI of her left knee, which revealed acute osteonecrotic changes. A following whole-body MRI examination demonstrated multifocal bony lesions. Bone marrow examination conclusively diagnosed acute lymphoblastic leukaemia (ALL). Acute osteonecrosis has classically been described as a complication of treatment in children with ALL and has not been recognised as a presenting feature until recently.
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Childhood onset systemic lupus erythematosus is a rare disease that is more common amongst Southeast Asian children compared to the West. It is typified by a peripubertal onset and a female preponderance, which increases with advancing age. Organs commonly involved at diagnosis include haematological, renal, and mucocutaneous. Fever, malar rash, and cutaneous vasculitis are common. Lupus nephritis is typically proliferative especially Class IV and contributes to both disease activity and damage. Antinuclear antibody and anti-dsDNA positivity are both prevalent in this region. Disease activity is higher than Western cohorts at onset but responds to therapy reducing to low disease activity by six months. However, organ damage occurs early and continues to accumulate over the time, a consequence of both active disease (neurological and renal systems) and steroid-related complications especially in the eye (cataract and glaucoma) and musculoskeletal systems (avascular necrosis). Infections remain the leading cause of death and mortality in this region is highly variable contributed by the heterogeneity in social economic status, healthcare access, and availability of paediatric rheumatology expertise in the region.
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BACKGROUND: Neuropsychiatric lupus (NPSLE) serves as a marker of severe disease in children with juvenile onset systemic lupus erythematosus (JSLE). This study aims to characterise the clinical and imaging features at diagnosis; and outcomes after 12 months in Malaysian children with NPSLE. METHODS: A retrospective study of all NPSLE patients seen at the Pediatric Rheumatology Unit, Selayang Hospital from January 2004 to May 2017. RESULTS: Twenty-eight (19.8%) of 141 JSLE patients had NPSLE with a median presenting age of 10 years (IQR 9 - 12), median follow-up of 7 years (IQR 4 - 11) and female: male ratio of 3.7:1. Twenty-three patients had single episodes of NPSLE and five patients had two distinct episodes each. The mean disease activity score (SLEDAI- 2K) was 24.9±11.8 at presentation with 81.8% having high disease activity (score > 12). Majority (60.6%) present with NPSLE within the first year of SLE diagnosis whilst the remainder occurred at a median of five years (IQR 3-7) post-SLE diagnosis. Majority (75.8%) had central nervous system (CNS) involvement commonly presenting with seizures, delirium and visual complaints whilst 24.2% had peripheral nervous system (PNS) involvement. Frequent accompanying features included hypocomplementemia, acute cutaneous lupus and lupus nephritis. Autoantibodies were common; ANA (100%), anti-dsDNA (78.8%) anti-RNP (39.4%) and anti-Sm (39.4%). Abnormalities were seen in 85.7% of the magnetic resonance imaging (MRI) studies performed, predominantly supratentorial white matter hyperintensities on T2 images whilst cerebrospinal fluid examination was normal in the majority. All patients with CNS involvement received corticosteroids with immunosuppressive therapy: Cyclophosphamide (20), Rituximab (2). Treatment for PNS involvement included corticosteroids with Azathioprine (6) or Mycophenolate mofetil (2). At 12 months post-NPSLE, majority (85.7%) recovered without any neurological sequelae. CONCLUSIONS: Juvenile-onset NPSLE presents with a myriad of clinical features. It is associated with high disease activity and non-specific MRI features. With early diagnosis and treatment, the majority had good prognosis.
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Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Criança , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/terapia , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , ConvulsõesRESUMO
BACKGROUND: In response to a growing number of patients on the UK urgent heart transplant waiting list, the UK donor heart allocation scheme was revised in October 2016 with the introduction of a new super-urgent category. Patients with temporary mechanical circulatory support (tMCS) became eligible for super-urgent registration. The aim of this study was to compare activity, indications, and outcomes before and after the change. METHODS: Data on adult (aged ≥16 years) heart transplant registrations and recipients in the 2 years before (Era 1: July 1, 2014-June 30, 2016) and after (Era 2: January 2017-December 2018) the introduction of the new scheme were extracted from the UK Transplant Registry and analyzed using competing risks analysis, Kaplan-Meier analysis, and Cox proportional-hazards regression. RESULTS: There were 525 waiting-list registrations in Era 1 and 594 in Era 2, including 14% super-urgent registrations, with 90% having some form of tMCS. Median waiting time to transplant was 41 days for all urgent registrations in Era 1 compared with 17 days for super-urgent registrations and 71 days for urgent registrations in Era 2. Numbers of non-urgent transplants were not affected. Deaths on the waiting list significantly decreased from 5% to 2% at 6 months between Era 1 and Era 2 (adjusted hazard ratio = 0.29, 95% CIâ¯=â¯0.13-0.62). In addition, total number of patients with tMCS were not different between both eras, suggesting no significant change in this area of clinical decision making. Post-transplant survival at 1 year for super-urgent recipients was not significantly different from post-transplant survival at 1 year for other categories. CONCLUSIONS: The Introduction of a super-urgent heart allocation scheme in the UK reduces waiting time to transplant for the sickest patients, with comparable post-transplant survival while reducing deaths on the waiting list.
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Transplante de Coração/métodos , Sistema de Registros , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Adulto , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Reino Unido , Listas de EsperaRESUMO
OBJECTIVES: Left ventricular assist devices are funded in the UK exclusively as a bridge to transplant (BTT). However, patients who potentially could receive a transplant may develop reversible contraindications to transplant. Bridge to candidacy (BTC) has sometimes been controversial, given the uncertain clinical efficacy of BTC and the risk that reimbursement could be denied. We analysed the UK ventricular assist device database to understand how common BTC was and to assess patient survival rates and incidences of transplants. METHODS: We identified BTC implants in patients with pulmonary hypertension, chronic kidney disease and obesity using the UK guidelines for heart transplants. RESULTS: A total of 306 of 540 patients had complete data and 157 were identified as BTC (51%). Overall, there was no difference in survival rates between patients designated as BTC and those designated at BTT (71.9 vs 72.9% at 1 year, respectively; P = 0.82). However, the survival rate was lower at all time points in those with an estimated glomerular filtration rate (eGFR) <40 and in patients with a body mass index (BMI) >32 up to 1-year postimplant. There were no significant differences in the incidence of transplant between patients who were BTC and BTT or for any subgroup up to 5 years. However, we noted a diverging trend towards a lower cumulative incidence of transplant for patients with a BMI >32. CONCLUSIONS: BTC is common in the UK and appears clinically effective, given that the survival rates and the incidence of transplants were comparable with those for BTT. Patients with a high BMI have a worse survival rate through to 1 year and a trend for a lower incidence of a transplant. Patients with a low eGFR also have a worse survival rate, but a similar proportion received transplants.
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Insuficiência Cardíaca/cirurgia , Transplante de Coração , Coração Auxiliar , Transplantados , Adulto , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências , Resultado do Tratamento , Reino Unido/epidemiologiaRESUMO
Biventricular pacing has been shown to improve the overall clinical outcomes in patients with systolic heart failure and ventricular conduction delay on electrocardiogram. As correction of ventricular dyssynchrony is the putative mechanism of benefit, biventricular pacing is also termed as cardiac resynchronization therapy. The development of separate programmability of right and left ventricular output has led to a growing number of reports on the potential benefit of optimization of cardiac resynchronization by sequential biventricular pacing with different techniques and endpoints. This systematic review summarizes the current data for the optimization of sequential (V-V delay) compared with (default) simultaneous biventricular pacing in heart failure.
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Estimulação Cardíaca Artificial/métodos , Sistema de Condução Cardíaco/fisiopatologia , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controle , Disfunção Ventricular Esquerda/fisiopatologia , HumanosRESUMO
OBJECTIVE: Blau syndrome is characterized by noncaseating granulomatous arthritis, dermatitis, and uveitis, and results from gain-of-function NOD2 mutations. This study was undertaken to identify the genetic cause of the disease in a family with 3 members with Blau syndrome. METHODS: We studied a family with 3 affected members across 2 consecutive generations. The children's symptoms started early (at 6 and 7 months of age) and included polyarthritis, dermatitis, uveitis, and fever. In contrast, the father's symptoms started later (at 22 years of age) and included noncaseating granulomatous dermatitis and uveitis. We analyzed the NOD2 gene in all patients by both the Sanger method of DNA sequencing and amplicon-based deep sequencing using an Ion Torrent PGM platform. RESULTS: Sanger chromatograms revealed the heterozygous c.1001G>A transition in both children, which resulted in the p.Arg334Gln mutation that causes Blau syndrome. In contrast, the father's chromatograms revealed a small peak of adenine at the c.1001 position, suggesting the presence of a somatic NOD2 mutation. To evaluate this hypothesis, we performed amplicon-based deep sequencing using DNA from different tissues, which confirmed a variable degree (0.9-12.9%) of somatic NOD2 mosaicism. The previous detection of the NOD2 mutation in his daughters strongly suggests the presence of gonosomal (somatic plus gonadal) NOD2 mosaicism in the father. Comparative analyses with Blau syndrome patients carrying the germline p.Arg334Gln NOD2 mutation revealed late onset of the disease, a mild inflammatory phenotype, and an absence of complications in patients with NOD2 mosaicism. CONCLUSION: This is the first description of gonosomal NOD2 mosaicism as the cause of intrafamilial recurrence of Blau syndrome. Our findings also indicate that Blau syndrome includes more diverse and milder phenotypes than previously described.