Risultati per: Svelato il tallone d’Achille della malattia di Parkinson

Senza DRG, i pazienti non hanno accesso a farmaci e monitoraggio

Senza DRG, i pazienti non hanno accesso a farmaci e monitoraggio

Neurologi: ‘si apre una nuova storia per i pazienti’

Circulation, Volume 150, Issue Suppl_1, Page A4122290-A4122290, November 12, 2024. Background:Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated to reduce the risk of hospitalizations from heart failure and cardiovascular mortality. However, SGLT2i therapy’s potential effects on the risks of dementia and Parkinson’s disease are not well established, with conflicting results based on observational studies.Objective:We sought to evaluate the association between SGLT2i and the risk of dementia and Parkinson’s disease in patients with type 2 diabetes mellitus (T2DM), heart failure, or chronic kidney disease.Methods:We performed a systematic literature search on PubMed, Scopus, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until March 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model.Results:A total of 12 RCTs with 74, 442 patients (40784 in the SGLT2i group and 33658 in the control group) were included in the analysis. The mean age of patients in SGLT2i and control was 65.3 and 65.2 years respectively. The mean follow-up duration was 2.9 years. Pooled analysis showed that there is no significant association between SGLT2i and the risk of dementia (OR, 1.37 (95%CI: 0.70-2.69),P=0.36, I2=0%), dementia Alzheimer’s type (OR, 2.62 (95%CI: 0.47-14.49),P=0.27, I2=0), vascular dementia (OR, O.52 (95%CI: 0.09-2.98),P=0.46, I2=0%), and Parkinson’s disease (OR, 0.75 (95%CI: 0.25-2.25),P=0.61, I2=0%) was comparable between SGLT2i and control groups.Conclusion:Our study suggest that there is no significant association between SGLT2i and the risk of dementia, its subtypes, and Parkinson’s disease. Further large-power randomized trials are needed to strengthen the understanding of neuropsychiatric beneficial effects of SGLT2i.

Circulation, Volume 150, Issue Suppl_1, Page A4138617-A4138617, November 12, 2024. Introduction:Parkinson’s disease (PD) is a common neurodegenerative disorder, and existing evidence links it to cardiovascular (CVD) mortality.Research Question:Is the CVD-related mortality higher in PD patients compared to that in the general population?Goals:We aim to identify CVD-related mortality trends in patients with PD in the US stratified by age, sex, race, and region, and compare them to CVD-related mortality trends in the general population.Methods:Death certificates from the CDC-WONDER database were examined for adults aged ≥65 years. Crude rates (CR) and age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, and change in AAMR was estimated via annual percent change (APC) and the average annual percent change (AAPC) using Joinpoint regression.Results:From 1999 to 2020, a total of 138,151 CVD-related deaths occurred in individuals with PD. The AAMRs decreased moderately till 2002 (APC: -3.25), then sharply till 2014 (APC: -5.43), but increased thereafter till 2020 (APC: 1.77). Males had higher AAMR than females, and the AAPC for CVD-related deaths in PD differed significantly from those in the general population. NH Whites displayed the highest AAMR (16.14) while NH Blacks or African Americans displayed the lowest (9.65). Hispanics or Latinos showed an AAMR of 11.22, followed by NH Asians or Pacific Islanders (10.24) and NH American Indians or Alaska Natives (9.70). AAMRs also varied substantially by region (West: 16.64; Midwest: 16.40; Northeast: 15.59; South: 13.12). States with the highest AAMRs were Nebraska, California, and Oklahoma. Rural regions exhibited a higher AAMR (16.34) than Urban regions (14.88). The AAPC for CVD-related deaths in PD differed significantly from those in the West and in urban regions. Most deaths occurred at nursing homes or long-term care (43.85%). The adults aged ≥85 years exhibited an alarmingly high CR (53.04), and the AAPC differed significantly from the general population due to CVD.Conclusions:We observed overall decreasing trends in CVD-related deaths in adults with PD from 1999 to 2014, which increased thereafter till 2020. Highest mortality was exhibited by males and NH Whites, residents of the West and the Midwest, and adults ≥85 years.

Circulation, Volume 150, Issue Suppl_1, Page A4146019-A4146019, November 12, 2024. Background:Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, affecting more than one million persons in the United States. Cardiovascular dysautonomia is a prominent dysfunction in PD, affecting the conduction system and causing bradyarrhythmia. However, no studies have assessed the prevalence and characteristics of bradyarrhythmia in patients with PD.Research Question:Is there an increased prevalence of bradyarrhythmia and pacemaker implantation in patients with PD?Aims:The study assessed the trends, prevalence, and risk factors of bradyarrhythmia and pacemaker implantation in PD patients.Methods:The National Inpatient Sample was utilized to identify patients’ data with primary and secondary diagnoses of Parkinson’s disease (PD) in the United States from 2016 to 2020 using the International Classification of Disease, 10th Revision codes. Outcomes of interest included the trends and prevalence of bradyarrhythmia and pacemaker implantation in PD. We assessed potential predictors of bradyarrhythmia in patients with PD using a backward selection multivariable logistic regression.Results:A total of 333,242 patients with PD diagnosis were included (76.5 ± 15.2 years, 58.7% male, 80.1% white); of these, 5,092 (20.5%) had comorbid diagnoses of bradyarrhythmia, and 328,150 (79.5%) without bradyarrhythmia. The prevalence of bradyarrhythmia in patients with PD was 351.9 per 10,000 hospitalizations (3.5%). The trends of bradyarrhythmia showed a stable increase from 291.9 to 463.8 per 10,000 (AAPC 12.5%, CI: -0.2%, 26.8%). The overall prevalence of pacemaker implantation in patients with PD was 79.9 per 10,000 hospitalizations (0.8%). The overall trends of pacemaker implantation showed a stable decrease in patients with PD during 2016-2020, with an AAPC -0.9% (CI: -4.1% to 2.3%). Age≥ 65, male sex, comorbidities (atrial fibrillation, coronary artery disease, heart failure, hypertension, liver failure, obesity, peripheral vascular disease, renal failure) were associated with a higher likelihood of bradyarrhythmia in patients with PD.Conclusions:This study’s findings revealed that the prevalence of bradyarrhythmia and subsequent pacemaker implantation in patients with PD remained relatively stable over the study period. The study provides the initial prevalence of bradyarrhythmia in patients with Parkinson’s disease. Further study is necessary to provide the characteristics and outcomes of bradyarrhythmia in PD.

Circulation, Volume 150, Issue Suppl_1, Page A4134619-A4134619, November 12, 2024. Background:Ebstein anomaly (EA) is a rare congenital heart defect occurring in 1.2 to 5 in 100,000 live births, characterized by a downward displacement of the tricuspid valve, thin-walled right ventricle, and tricuspid valve regurgitation. It can present variably from asymptomatic cases to severe symptoms like arrhythmias and right-sided heart failure. EA is often associated with other anomalies such as interatrial communication and mitral valve prolapse. The condition can lead to accessory atrioventricular pathways, frequently resulting in Wolff-Parkinson-White syndrome (WPW), which involves abnormal heart electrical activity and increases the risk of sudden cardiac death. While the genetic basis of EA is not fully understood, it appears to involve multiple genes like FLNA and NKX2-5, MYH6, MYH7 suggesting a complex polygenic inheritance pattern. TNNT2 is known to be associated with Cardiomyopathy but has not been previously associated with EA and WPW.Case:In this report, we present findings from a lebanese family with EA, comprising 2 affected individuals. Whole exome sequencing in the affected individuals identified a pathogenic variant in the TNNT2 gene at coding strain position 260 (a missense mutation: C to T), resulting in the substitution of Proline with Leucine at position 87 in affected individuals (Figure 1). No variants were detected in any other candidate gene examined. Individuals I:1 and II:2 were found to be normal, with no EA findings on echocardiography.Methods:Whole exome sequencing in the patients involved collecting blood samples after obtaining consent. These samples were sent to Centogene lab, where genomic DNA is enzymatically fragmented. The regions of interest are then enriched using DNA capture probes, facilitating detailed genetic analysis.Results:The whole exome sequencing identified a heterozygous missense mutation in both the father and his daughter. This nonsynonymous variant is located on chromosome 1 (GRCh37) in the TNNT2 gene region. The specific variant, NM_001276345.1:c.260C >T p.(Pro87Leu), was found in both individuals.Conclusion:In conclusion, the genetic basis of EA is rather complex and remains poorly understood. It is established that mutations in the TNNT2 gene are linked to several cardiomyopathies, none of them overlap with the described phenotype of our patients. In this report, we therefore confirm the potential role of TNNT2 gene mutation in the genetic basis of familial EA with WPW.

Circulation, Volume 150, Issue Suppl_1, Page A4125701-A4125701, November 12, 2024. Background:Racial and ethnic disparities have been reported in catheter ablation in adults. There are limited data on the impact of race/ethnicity on the diagnosis and management of children with Wolff-Parkinson-White pattern (WPW).Hypothesis:Diagnosis of WPW by electrocardiogram (ECG) and risk stratification by exercise stress test (EST) and electrophysiology study (EPS) will differ by race/ethnicity in children.Methods:We performed a retrospective cohort study of patients 0-21 years old, excluding those with congenital heart disease, at a children’s hospital from 1991-2021. The primary exposure was race/ethnicity. Outcomes were 1) diagnosis of WPW on ECG, 2) undergoing EST, and 3) undergoing EPS. Likelihood and time to outcome were assessed with multivariable logistic regression adjusted for birth year and Cox regression, respectively.Results:The cohort consisted of 1,638,746 patients (White 53.0%, Black 21.0%, Hispanic 6.8%, Asian 4.2%, Multi-racial 2.0%, Other 11.0%, and Missing 1.7%). WPW was diagnosed in 898 patients (0.05%). After adjusting for birth year, Asian, Black, and Other race were associated with lower odds of WPW diagnosis compared to White patients (OR 0.57, 0.66, 0.70; p≤0.01). There was no association between race and age at first diagnosis (p=0.2). A total of 616 WPW patients (69%) underwent EST. Compared with White patients, Asian, Hispanic, and Other race were less likely to undergo EST (OR 0.39, 0.59, 0.62; p≤0.04), and those who did had their EST at later ages (HR 0.59, 0.65, 0.46; p≤0.04). A total of 739 WPW patients (82%) underwent EPS. Compared with White patients, Black, Hispanic, and Other race were less likely to undergo EPS (OR 0.44, 0.53, 0.59; p≤0.02), and those who did had their EPS at later ages (HR 0.60, 0.63, 0.66; p≤0.004).Conclusion:This analysis found that non-White racial and ethnic groups are less likely to be diagnosed with WPW. This may reflect differences in WPW prevalence by race/ethnicity, but differential access to ECG cannot be ruled out. Among WPW patients, however, Asian and Hispanic patients are approximately half as likely to undergo EST, while Black and Hispanic patients are approximately half as likely to undergo EPS, compared to White patients.

Circulation, Volume 150, Issue Suppl_1, Page A4143917-A4143917, November 12, 2024. Background:PRKAG2 syndrome is an inherited disease caused by mutations in thePRKAG2gene, which encodes the γ2 regulatory subunit of AMP-activated protein kinase (AMPK). These mutations result in increased AMPK activity leading to aberrant myocardial glycogen deposition. Patients with PRKAG2 syndrome can develop cardiac hypertrophy, ventricular pre-excitation, supraventricular arrhythmias and conduction system disease, all of which increase the risk of sudden cardiac death. Some patients develop progressive heart failure necessitating heart transplantation. Current treatments include standard medications for heart failure and pacemaker/ICD implantation for arrhythmias. However, there is a significant need to treat the underlying causes of PRKAG2 syndrome. Small interfering RNA (siRNA) oligonucleotides present a promising therapeutic approach by reducing mutantPRKAG2mRNA levels, thereby lowering AMPK activity.Hypothesis:Antibody oligonucleotide conjugates (AOCs) can be designed to targetPRKAG2mRNA to treat PRKAG2 syndrome.Aims:To investigate the tolerability and efficacy of an AOC targetingPRKAG2mRNA in mice and non-human primates (NHPs).Methods:iPSC-derived cardiomyocytes were used to screen and identify a potent siRNA againstPRKAG2. The lead siRNA was conjugated to an anti-TfR1 monoclonal antibody to create AOC 1072 for targeted cardiac delivery and was subsequently administered to mice and NHPs.Results:In vitroscreening identified an siRNA with an EC50 90%. A single, IV injection of the mouse surrogate of AOC 1072 at 1 mg/kg (siRNA component) resulted in a potent and durable myocardialPrkag2mRNA reduction in mice, with about 75% and 50% reduction observed at 2 and 6 months, respectively. AOC treatment reduced glycogen accumulation in the skeletal muscle of mice expressing thePrkag2-R528G disease variant. A single IV administration of AOC 1072 at 3 mg/kg (siRNA component) resulted in about 85% reduction of cardiacPRKAG2mRNA in NHPs at 28 days, with no adverse effects (ECG or heart weight).Conclusions:Our data suggests AOC technology can be used efficiently to deliver siRNA to the heart. This precision cardiology treatment can significantly reducePRKAG2mRNA expression, offering a promising therapeutic approach for PRKAG2 syndrome, a currently incurable genetic condition with very limited treatment options.

Colpito almeno il 7% italiani, solo il 10% dei pazienti lo sa

Iss, “servono di bimbi sani o con sindrome di Rett fino a 6 mesi”