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1.
Europace ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038231

RESUMO

AIMS : The aim of this study is to characterize recurrent syncope, including sex-specific aspects, and its impact on death and major adverse cardiovascular events (MACE). METHODS AND RESULTS: We characterized recurrent syncope in a large international multicentre study, enrolling patients ≥40 years presenting to the emergency department (ED) with a syncopal event within the last 12 h. Syncope aetiology was centrally adjudicated by two independent cardiologists using all information becoming available during syncope work-up and long-term follow-up. Overall, 1790 patients were eligible for this analysis. Incidence of recurrent syncope was 20% [95% confidence interval (CI) 18-22%] within the first 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95% CI 1.11-2.01) or syncope with an unknown aetiology even after central adjudication (HR 2.11, 95% CI 1.54-2.89) had an increased risk for syncope recurrence. Least Absolute Shrinkage and Selection Operator regression fit on all patient information available early in the ED identified >3 previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95% CI 1.64-2.75). Recurrent syncope carried an increased risk for death (HR 1.87, 95% CI 1.26-2.77) and MACE (HR 2.69, 95% CI 2.02-3.59) over 24 months of follow-up, however, with a time-dependent effect. These findings were confirmed in a sensitivity analysis excluding patients with syncope recurrence or MACE before or during ED evaluation. CONCLUSION : Recurrence rates of syncope are substantial and vary depending on syncope aetiology. Importantly, recurrent syncope carries a time-dependent increased risk for death and MACE. TRIAL REGISTRATION: BAsel Syncope EvaLuation (BASEL IX, ClinicalTrials.gov registry number NCT01548352).

2.
Swiss Med Wkly ; 150: w20346, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038262

RESUMO

AIMS OF THE STUDY: Most patients with reduced exercise capacity and acquired or congenital structural heart disease also have a reduced respiratory muscle strength. The aim of this pilot study was to investigate whether choir singing in combination with respiratory muscle training positively influences respiratory muscle strength, exercise capacity and quality of life in this population. METHODS: In this single-centre, randomised and open-label interventional study we compared respiratory muscle strength, exercise capacity and quality of life in patients with acquired or congenital structural heart disease who received either standard of care and a 12-week intervention (weekly choir rehearsal and daily breathing exercises) or standard of care alone. The primary endpoint was the difference in change in maximum inspiratory pressure (∆MIP%predicted). Secondary endpoints included the difference in change in maximum expiratory pressure (∆MEP%predicted), exercise capacity quantified as maximal oxygen uptake during exercise (∆MVO2%predicted) and quality of life quantified by the Minnesota living with heart failure questionnaire (∆MLHFQ score). RESULTS: Overall 24 patients (mean age 65, standard deviation [SD] 19 years, 46% male) were randomised after exclusion. ∆MIP%predicted was significantly higher in the intervention group (∆MIP%predicted +14, SD 21% vs −14, SD 23%; p = 0.008) and quality of life improved significantly (∆MLHFQ score −5, SD 6 vs 3, SD 5; p = 0.006) after 12 weeks. ∆MEP%predicted and ∆MVO2%predicted did not differ between both groups (∆MEP%predicted −3, SD 26% vs −3, SD 16%; p = 1.0 and ∆MVO2%predicted 18, SD 12% vs 10, SD 15%; p = 0.2). CONCLUSIONS: Choir singing in combination with respiratory muscle training improved respiratory muscle strength and quality of life in patients with structural heart disease and may therefore be valuable supplements in cardiac rehabilitation. (Clinical trial registration number: NCT03297918)  .

3.
Br J Anaesth ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33081973

RESUMO

BACKGROUND: Perioperative cardiovascular guidelines endorse functional capacity estimation, based on 'cut-off' daily activities for risk assessment and climbing two flights of stairs to approximate 4 metabolic equivalents. We assessed the association between self-reported functional capacity and postoperative cardiac events. METHODS: Consecutive patients at elevated cardiovascular risk undergoing in-patient noncardiac surgery were included in this predefined secondary analysis. Self-reported ability to walk up two flights of stairs was extracted from electronic charts. The primary endpoint was a composite of cardiac death and cardiac events at 30 days. Secondary endpoints included the same composite at 1 yr, all-cause mortality, and myocardial injury. RESULTS: Among the 4560 patients, mean (standard deviation) age 73 (SD 8 yr) yr, classified as American Society of Anesthesiologists physical status ≥3 in 61% (n=2786/4560), the 30-day and 1-yr incidences of major adverse cardiac events were 5.7% (258/4560) and 11.2% (509/4560), respectively. Functional capacity less than two flights of stairs was associated with the 30-day composite endpoint (adjusted hazard ratio 1.63, 95% confidence interval [CI] 1.23-2.15) and all other endpoints. The addition of functional capacity information to the revised cardiac risk index (RCRI) significantly improved risk classification (functional capacity plus RCRI vs RCRI: net reclassification improvement [NRI]Events 6.2 [95% CI 3.6-9.9], NRINonevents19.2 [95% CI 18.1-20.0]). CONCLUSIONS: In patients at high cardiovascular risk undergoing noncardiac surgery, self-reported functional capacity less than two flights of stairs was independently associated with major adverse cardiac events and all-cause mortality at 30 days and 1 yr. The addition of self-reported functional capacity to surgical and clinical risk improved risk classification. CLINICAL TRIAL REGISTRATION: INCT 02573532.

4.
Wien Klin Wochenschr ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084955

RESUMO

BACKGROUND: Olfactory dysfunction (OD) is common in the general population, affects the quality of life (QoL), and is suspected to cause depression. Long-term outcome data are lacking and there is a need to improve patient counselling regarding prognosis. We aimed to assess subjective long-term recovery rates, the QoL, and mood disturbance in a group of 65 patients, who were affected with OD. METHODS: Out of 325 patients treated for OD between 2003 and 2009 â€¯at a smell and taste clinic, 65 patients were included for a follow-up after an average of 8.6 years. A total of 28 patients answered questionnaires only and 37 patients were provided with an additional smell identification test. Among others, questionnaires included a short form of the World Health Organization quality of life questionnaire (WHOQOL-BREF) and the Beck's depression inventory. RESULTS: In the long run, subjective improvement was stated in 33.8% of all patients, with the highest rate of 42.3% in patients with postinfectious OD. The subjective rating of olfactory function on a visual analogue scale was significantly higher at study follow-up compared to first clinical contact (median 1.25 vs. 4.5; U = 469.5, p = 0.001), as were mean identification scores (6.0 ± 3.0 vs. 8.0 ± 4.0, t(18) = 2.51, p = 0.021). The QoL in general was considered reduced in 40% of all patients at follow-up. Furthermore, participants exhibited only minor, if any, depressive symptoms. CONCLUSION: Despite negative effects of OD on certain activities in daily life, such as cooking, detecting spoiled food, or personal hygiene, it seems that the patients included in this study adapted to the OD in the long-term. The current findings should aid clinicians in patient counselling.

5.
Eur J Heart Fail ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006257

RESUMO

Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33063145

RESUMO

PURPOSE: While the overall impact of chronic rhinosinusitis (CRS) on patients' health is diverse, many affected individuals have a substantially impaired quality of life (QoL). The aim of this study was to evaluate the impact of sex-associated differences specifically in the subgroups of CRS with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) by assessing QoL parameters in women and men separately. METHODS: In a retrospective single-center study, 59 patients with CRSwNP (39 males and 20 females) and 46 patients with AERD (18 males and 28 females) were included. Patient-reported outcome measures (PROM) evaluating QoL via the Sino-Nasal Outcome Test-20 German Adapted Version (SNOT-20 GAV) as well as the total polyp score (TPS) were analysed. RESULTS: There was no significant difference in TPS (p = 0.5550) and total SNOT-20 GAV scores (p = 0.0726) between male or female patients with CRSwNP or AERD. Furthermore, no significant sex differences were found within disease groups regarding the subcategories of the SNOT-20 GAV items. CONCLUSION: Thus, quality of life is severely impaired in patients suffering from various forms of CRS regardless of their sex.

8.
Eur J Heart Fail ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068051

RESUMO

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin have consistently demonstrated to be effective for the prevention of HF hospitalisation in patients with T2DM and established CV disease or at high CV risk. The specifically listed agents are recommended. Dapagliflozin or empagliflozin are recommended to reduce the combined risk of HF hospitalisation and CV death in symptomatic patients with HF and reduced ejection fraction, already receiving guideline directed medical therapy, regardless of the presence of T2DM.

9.
J Am Heart Assoc ; 9(20): e017434, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33032485

RESUMO

Background Efficacy data on drug-eluting stents (DES) versus bare-metal stents (BMS) in saphenous vein grafts are controversial. We aimed to compare DES with BMS among patients undergoing saphenous vein grafts intervention regarding long-term outcome. Methods and Results In this multinational trial, patients were randomized to paclitaxel-eluting or BMS. The primary end point was major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and target-vessel revascularization at 1 year. Secondary end points included major adverse cardiac events and its individual components at 5-year follow-up. One hundred seventy-three patients were included in the trial (89 DES versus 84 BMS). One-year major adverse cardiac event rates were lower in DES compared with BMS (2.2% versus 16.0%, hazard ratio, 0.14; 95% CI, 0.03-0.64, P=0.01), which was mainly driven by a reduction of subsequent myocardial infarctions and need for target-vessel revascularization. Five-year major adverse cardiac event rates remained lower in the DES compared with the BMS arm (35.5% versus 56.1%, hazard ratio, 0.40; 95% CI, 0.23-0.68, P<0.001). A landmark-analysis from 1 to 5 years revealed a persistent benefit of DES over BMS (hazard ratio, 0.33; 95% CI, 0.13-0.74, P=0.007) in terms of target-vessel revascularization. More patients in the BMS group underwent multiple target-vessel revascularization procedures throughout the study period compared with the DES group (DES 1.1% [n=1] versus BMS 9.5% [n=8], P=0.013). Enrollment was stopped before the target sample size of 240 patients was reached. Conclusions In this randomized controlled trial with prospective long-term follow-up of up to 5 years, DES showed a better efficacy than BMS with sustained benefits over time. DES may be the preferred strategy in this patient population. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00595647.

10.
Otolaryngol Head Neck Surg ; : 194599820965242, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048605

RESUMO

OBJECTIVE: To evaluate associations between self-perceived chemosensory functions of smell, taste, and flavor perception with olfactory-specific quality of life (QoL) in patients with olfactory dysfunction (OD) and whether these associations would be influenced by other factors, such as duration or etiology of smell loss. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care, academic center. METHODS: Olfactory-specific QoL was measured with the Questionnaire of Olfactory Disorders (QOD). The QOD measures the impact of OD on QoL (QOD-negative statements) and the ability of patients to cope with smell loss (QOD-positive statements). Orthonasal olfactory function, patients' demographics, self-perceived chemosensory perception, and duration and etiology of OD were retrospectively collected in a cohort of patients with quantitative OD. Correlations and multivariable linear regression models were computed to determine possible associations with the outcome measure of QOD-negative and QOD-positive statement scores. RESULTS: A total of 133 patients with OD were included. Analysis revealed a positive correlation between self-perceived taste and flavor perception with QOD-negative statement scores, while self-perceived smell showed no significant correlation. Similarly, longer duration of smell loss and higher age were also correlated with higher QOD-positive statement scores. Multivariable regression models confirmed that self-perceived taste was independently associated with the QOD-negative statement score, while age and duration of OD were independently associated with the QOD-positive statement score. CONCLUSIONS: These findings suggest that the impact of diminished flavor perception during eating and drinking has a stronger impact on the QoL of patients with OD as compared with decreased orthonasal olfaction.

11.
J Cardiol ; 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33054989

RESUMO

OBJECTIVE: Experts recommended that direct discharge without hospitalization (DDWH) for emergency departments (EDs) able to observe acute heart failure (AHF) patients should be >40%, and these discharged patients should fulfil the following outcome standards: 30-day all-cause mortality <2% (outcome A); 7-day ED revisit due to AHF < 10% (outcome B); and 30-day ED revisit/hospitalization due to AHF < 20% (outcome C). We investigated these outcomes in a nationwide cohort and their relationship with the ED DDWH percentage. METHODS: We analyzed the EAHFE registry (includes about 15% of Spanish EDs), calculated DDWH percentage of each ED, and A/B/C outcomes of DDWH patients, overall and in each individual ED. Relationship between ED DDWH and outcomes was assessed by linear and quadratic regression models, non-weighted and weighted by DDWH patients provided by each ED. RESULTS: Among 17,420 patients, 4488 had DDWH (25.8%, median ED stay = 0 days, IQR = 0-1). Only 12.9% EDs achieved DDWH > 40%. Considering DDWH patients altogether, outcomes A/C were above the recommended standards (4.3%/29.4%), while outcome B was nearly met (B = 10.1%). When analyzing individual EDs, 58.1% of them achieved the outcome B standard, while outcomes A/C standards were barely achieved (19.3%/9.7%). We observed clinically relevant linear/quadratic relationships between higher DDWH and worse outcomes B (weighted R2 = 0.184/0.322) and C (weighted R2 = 0.430/0.624), but not with outcome A (weighted R2 = 0.002/0.022). CONCLUSIONS: The EDs of this nationwide cohort do not fulfil the standards for AHF patients with DDWH. High DDWH rates negatively impact ED revisit or hospitalization but not mortality. This may represent an opportunity for improvement in better selecting patients for early ED discharge and in ensuring early follow-up after ED discharge.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32813170

RESUMO

PURPOSE: Testing olfaction should be an integral part of a clinical work-up in rhinosurgical procedures. Importantly, intact olfactory experience also includes retronasally perceived odors (retronasal olfaction). This study aimed at comprehensively assessing olfaction in patients undergoing rhinosurgical procedures in a comparative manner and evaluating relations to patient-reported outcome measurements (PROMs). METHODS: Each nostril odor threshold and discrimination, and birhinal identification were tested using Sniffin' Sticks in 14 subjects assigned for septoplasty (SP), 21 for septorhinoplasty (SRP), and 30 for endoscopic sinus surgery (ESS). The 27-Candy-Smell-Test was used to quantify retronasal abilities. Tests were repeated 3 months after surgery. RESULTS: Olfactory dysfunction was preoperatively present in 21% of SP, in 47.6% of SRP, and in 80% of ESS patients. Odor threshold side differences were most frequently found in SRP. Frequently, SRP and ESS patients showed severely impaired retronasal olfaction. Half of included subjects re-visited after 3 months, but olfactory function did not improve overall and rarely on an individual basis to a meaningful extent. Subjective ratings on nasal patency and PROMs were not associated with olfaction nor with changes in olfactory scores. CONCLUSION: Olfactory function can decisively be impaired a priori not only in patients awaiting sinus surgery, but also in those assigned for functional septorhinoplasty. This impairment may not improve in the short term, which has to be taken into account in patient counseling. This study adds to the current literature on olfaction in rhinosurgery with the extension of retronasal testing.

16.
Kardiol Pol ; 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32847343

RESUMO

The diagnosis of coronary artery disease (CAD), which is one of the most common causes of death and disability worldwide, still remains a significant problem for clinicians. Developing high-sensitivity cardiac troponin (hs-cTn) assays became the cornerstone in the diagnosis of acute myocardial infarction (AMI). Nowadays, they maintain the crucial position in diagnostic algorithms. However, there are still some unexplained issues in this field. This review summarizes and emphasizes the crucial role of hs-cTn in acute coronary syndromes (ACS). The 0/1-h hs-cTn algorithm was mentioned for the first time in the official European Society of Cardiology (ESC) non-ST-elevation (NSTE) ACS guidelines in 2015. It was derived, validated and implemented for all clinically-available assays since then. In this review, troponin-based strategies for rapid rule-out or rule-in of non-ST-elevation myocardial infarction (NSTEMI) are gathered and compared with the update on the official ESC 0/1-h pathway with the most recent values of hs-cTn. The document focus also on the problem of possible analytic confounders ("false-positive" and "false-negative" results) and compares the usefulness of cTn to other diagnostic techniques (e.g. magnetic resonance imaging). The review is divided into short, easy-to-read chapters emphasizing six key messages on how to use and interpret hs-cTn base algorithms in clinical practice at the emergency department.

17.
Eur Heart J ; 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32820320

RESUMO

AIMS: Statins reduce cardiovascular risk in patients with acute coronary syndrome (ACS) and normal-to-moderately impaired renal function. It is not known whether proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide similar benefit across a range of renal function. We determined whether effects of the PCSK9 inhibitor alirocumab to reduce cardiovascular events and death after ACS are influenced by renal function. METHODS AND RESULTS: ODYSSEY OUTCOMES compared alirocumab with placebo in patients with recent ACS and dyslipidaemia despite intensive statin treatment. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 was exclusionary. In 18 918 patients, baseline eGFR was 82.8 ± 17.6 mL/min/1.73 m2, and low-density lipoprotein cholesterol (LDL-C) was 92 ± 31 mg/dL. At 36 months, alirocumab decreased LDL-C by 48.5% vs. placebo but did not affect eGFR (P = 0.65). Overall, alirocumab reduced risk of the primary outcome (coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization) with fewer deaths. There was no interaction between continuous eGFR and treatment on the primary outcome or death (P = 0.14 and 0.59, respectively). Alirocumab reduced primary outcomes in patients with eGFR ≥90 mL/min/1.73 m2 (n = 7470; hazard ratio 0.784, 95% confidence interval 0.670-0.919; P = 0.003) and 60 to <90 (n = 9326; 0.833, 0.731-0.949; P = 0.006), but not in those with eGFR < 60 (n = 2122; 0.974, 0.805-1.178; P = 0.784). Adverse events other than local injection-site reactions were similar in both groups across all categories of eGFR. CONCLUSIONS: In patients with recent ACS, alirocumab was associated with fewer cardiovascular events and deaths across the range of renal function studied, with larger relative risk reductions in those with eGFR > 60 mL/min/1.73 m2.

18.
Swiss Med Wkly ; 150: w20320, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32835386

RESUMO

Acute heart failure (AHF) is a complex and heterogeneous syndrome not only associated with a concerning rise in incidence, but also with still unacceptably high rates of mortality and morbidity. As this dismal outcome is at least in part due to a mismatch between the severity of AHF and the intensity of its management, both in-hospital and immediately after discharge, early and accurate risk prediction could contribute to more effective, risk-adjusted management. Biomarkers are noninvasive and highly reproducible quantitative tools that have improved the understanding of AHF pathophysiology. They can help guide the intensity of AHF management. In addition, using a statistical model to estimate risk from a combination of several predictor variables such as vital signs or demographics has gained more and more attention over recent years. In this context, the aim of a statistical model, which gives a so-called risk score, is to help clinicians to make more standardised decisions. This review highlights recent advances and remaining uncertainties regarding risk stratification in AHF by characterising and comparing the potential of biomarkers and risk scores.  .

19.
Circulation ; 142(16): 1532-1544, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32820656

RESUMO

BACKGROUND: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. METHODS: Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. RESULTS: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P=0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI. CONCLUSIONS: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.

20.
N Engl J Med ; 383(2): 151-158, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32640133

RESUMO

Two patients with familial amyotrophic lateral sclerosis (ALS) and mutations in the gene encoding superoxide dismutase 1 (SOD1) were treated with a single intrathecal infusion of adeno-associated virus encoding a microRNA targeting SOD1. In Patient 1, SOD1 levels in spinal cord tissue as analyzed on autopsy were lower than corresponding levels in untreated patients with SOD1-mediated ALS and in healthy controls. Levels of SOD1 in cerebrospinal fluid were transiently and only slightly lower in Patient 1 but were not affected in Patient 2. In Patient 1, meningoradiculitis developed after the infusion; Patient 2 was pretreated with immunosuppressive drugs and did not have this complication. Patient 1 had transient improvement in the strength of his right leg, a measure that had been relatively stable throughout his disease course, but there was no change in his vital capacity. Patient 2 had stable scores on a composite measure of ALS function and a stable vital capacity during a 12-month period. This study showed that intrathecal microRNA can be used as a potential treatment for SOD1-mediated ALS.


Assuntos
Esclerose Amiotrófica Lateral/terapia , MicroRNAs/uso terapêutico , Superóxido Dismutase-1/líquido cefalorraquidiano , Esclerose Amiotrófica Lateral/líquido cefalorraquidiano , Esclerose Amiotrófica Lateral/genética , Dependovirus , Evolução Fatal , Inativação Gênica , Terapia Genética , Vetores Genéticos , Humanos , Injeções Espinhais , Masculino , Meningoencefalite , Pessoa de Meia-Idade , Mutação , Estudo de Prova de Conceito , Medula Espinal/química , Medula Espinal/patologia , Superóxido Dismutase-1/análise , Superóxido Dismutase-1/genética , Capacidade Vital , Adulto Jovem
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