The Wilson N. Jones Regional Medical Center (WNJ), formerly Texas Health Presbyterian Hospital–WNJ, is a hospital in Sherman, Texas. It has 237 beds, and employs 1000 staff. It was established in 1914.In 2014, Alecto Healthcare Services acquired the hospital from Texas Health Resources..
Importance:Myeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress. Objective:To determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS. Design Settings and Participants:Verdiperstat was tested as a regimen of the HEALEY ALS Platform Trial, a multicenter, double-blind, perpetual platform design, randomized clinical trial, with sharing of trial infrastructure and placebo data across multiple regimens. The study was conducted at 54 ALS referral centers across the US from July 2020 to April 2022. Adult participants with a diagnosis of clinically possible, probable, laboratory-supported probable, or definite ALS defined by the revised El Escorial criteria were randomized to verdiperstat or regimen-specific placebo. An additional group of participants concurrently randomized to placebo from other regimens was included in the analyses. Interventions:Eligible participants were randomized in a 3:1 ratio to receive oral verdiperstat, 600 mg, twice daily or matching placebo for a planned placebo-controlled duration of 24 weeks. Main Outcomes and Measures:The primary efficacy outcome was change from baseline through week 24 in disease severity, as measured by a joint model of ALS Functional Rating Scale-Revised and survival, with the treatment effect quantified by the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression of verdiperstat relative to placebo. Results:A total of 167 participants (mean [SD] age, 58.5 [11.4] years; 59 [35.3%] female; 108 [64.6%] male) were randomized to either verdiperstat (126 [75.4%]) or to placebo (41 [25.6%]). Among the participants randomized to the verdiperstat regimen, 130 (78%) completed the trial. The estimated DRR was 0.98 (95% credible interval, 0.77-1.24; posterior probability = 0.57 for slowing of disease progression [DRR <1]). Verdiperstat was estimated to slow progression by 2% vs placebo (95% credible interval, -23% to 24%; posterior probability 0.57). Verdiperstat was overall safe and well tolerated. Common adverse events in the verdiperstat group were nausea, insomnia, and elevated thyrotropin levels. Conclusions and Relevance:Results demonstrate that treatment with verdiperstat was unlikely to alter disease progression in ALS. Trial Registration:Clinical Trial Identifiers: NCT04297683 and NCT04436510.
There are limited comparative data on the use of plaque modification devices during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We compared intravascular lithotripsy (IVL) with rotational atherectomy (RA) for lesion preparation in patients who underwent CTO PCI across 50 US and non-US centers from 2019 to 2024. Of 15,690 patients who underwent CTO PCI during the study period, 436 (2.78%) underwent IVL and 381 (2.45%) RA. Patients treated with IVL had more co-morbidities and more complex CTO lesions. Antegrade wiring was the most used initial and successful crossing strategy for lesions treated with both IVL and RA, although the retrograde approach was more frequently used in IVL cases. Procedure and fluoroscopy times, and air kerma radiation doses and contrast volumes, were greater in patients treated with RA than those treated with IVL. There were no significant differences between the groups in technical success (97.2% vs 95.3%, p = 0.20), procedural success (94.7% vs 91.8%, p = 0.14), and in-hospital major adverse cardiac events (MACEs) (3.0% vs 4.2%, p = 0.47). However, coronary artery perforations were more frequent in patients who underwent RA (9.5% vs 3.2%, p <0.001). Multivariable logistic regression analysis revealed that IVL compared with RA was not independently associated with technical success, procedural success, or in-hospital MACE. In patients who undergo CTO PCI, IVL is associated with similar in-hospital MACE, technical success, and procedural success but lower incidence of coronary artery perforation compared with RA.
Higher cardiorespiratory fitness (CRF) is associated with less deterioration in brain microstructural white matter (WM) integrity in older adults assessed with MRI diffusion tensor imaging (DTI) and brain WM hyperintensities (WMH) volume measured with fluid-attenuated-inversion-recovery (FLAIR) imaging. This study investigated associations of CRF measured with peak oxygen consumption (V̇O2peak) with brain WM microstructural integrity and WMH in healthy individuals across the adult lifespan. We hypothesized that higher CRF is associated with less deterioration in WM microstructural integrity and WMH across the adult lifespan, which in turn is associated with better cognitive performance. A total of 177 healthy adults underwent treadmill exercise testing to measure V̇O2peak, MRI scan to measure free water (FW)–corrected DTI metrics and whole-brain WMH volume, and a comprehensive cognitive test battery. Linear regression models were used to examine the associations of DTI metrics and WMH volume with age, V̇O2peak, and age × V̇O2peak interaction. Higher CRF was associated with lower FW. Age × V̇O2peak interactions were observed in FW of the corpus callosum (CC) and WMH volume, such that the positive regression slopes of FW and WMH volume with age were lower in those with higher V̇O2peak than those with lower V̇O2peak. Lower WMH volume and FW in the CC were associated with better fluid cognition composite score. In conclusion, higher CRF is associated with less deteriorations in brain WM integrity and better cognitive function across the adult lifespan. These findings highlight the importance of maintaining and improving CRF to slow brain aging.
BACKGROUND:Prescription of obesity medications is increasing, but our understanding of their effects in patients with cardiovascular disorders, such as postural orthostatic tachycardia syndrome (POTS), is limited. CASE SUMMARY:POTS was exacerbated in a 28-year-old woman with obesity after using tirzepatide for weight reduction. Her condition was effectively treated with progressive exercise training and counseling, which reduced supine and standing heart rates to normal values, before starting tirzepatide. However, while using tirzepatide, the patient's supine and standing heart rates were markedly elevated, and she experienced recurrence of orthostatic intolerance symptoms. DISCUSSION:Although small increases in resting heart rate with glucagon-like peptide-1 receptor agonist use have been reported in adults (approximately 3 beats/min), such a large increase in both supine and standing heart rate (20-30 beats/min) with tirzepatide has not been reported to our knowledge. TAKE-HOME MESSAGE:Prescription of tirzepatide may exacerbate symptoms of orthostatic intolerance and cause marked tachycardia in patients with POTS.
Background. The impact of peripheral artery disease (PAD) on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is not well studied. Methods. We analyzed the association of PAD with CTO-PCI outcomes using data from the PROGRESS-CTO registry of procedures performed at 47 centers between 2012 and 2023. Results. The prevalence of PAD among 12 961 patients who underwent CTO PCI during the study period was 13.9% (1802). PAD patients were older, more likely to be current smokers, and had higher rates of dyslipidemia, diabetes, cerebrovascular disease, hypertension, prior myocardial infarction, PCI, and coronary artery bypass graft surgery. Their PROGRESS-CTO (1.35 vs 1.22; P < . 001) and J-CTO (2.63 vs 2.33; P < . 001) scores were higher, lesion length was longer, and angiographic characteristics were more complex. Their access site was more likely to be bifemoral (33.6% vs 30.9%; P= . 024) compared with patients with no PAD. Technical (82.9% vs 87.7%; P < . 001) and procedural (80.5% vs 86.6%; P <. 001) success rates were lower in patients with PAD, while the incidence of major adverse cardiovascular events (MACE) was higher (3.1% vs 1.8%; P < . 001), with higher incidence of death (0.8% vs 0.4%; P = . 034), acute myocardial infarction (0.9%vs 0.4%; P = . 010), and perforation (6.6% vs 4.5%; P < . 001). In multivariable analysis, PAD was associated with higher MACE (odds ratio [OR]: 1.53; 95% CI, 1.01-2.26; P = . 038) and lower technical success (OR: 0.82; 95% CI, 0.690.99; P = . 039). Conclusions. PAD patients undergoing CTO PCI have higher comorbidity burden, more complex CTOs, higher MACE, and lower technical success.
