Impact of Cognitive Impairment on Long-Term Outcomes After Transcatheter Aortic Valve Implantation.

Background: Cognitive impairment assessed using the Mini-Mental Status Examination (MMSE) is associated with short-term mortality after transcatheter aortic valve implantation (TAVI). We assessed the long-term prognostic impact of cognitive impairment in patients with severe aortic stenosis post-TAVI. Methods and Results: We enrolled 1,057 consecutive patients who underwent TAVI at the Kokura Memorial Hospital and prospectively assessed them using the MMSE. Results showed that 319 (30%) patients had cognitive impairment. Compared with normal cognition, cognitive impairment was associated with an increased risk for 5-year all-cause mortality (55% vs. 39%; P<0.001), cardiovascular mortality (23% vs. 14%; P=0.007), and non-cardiovascular mortality (42% vs. 29%; P<0.001). Multivariable analysis showed that cognitive impairment was independently associated with all-cause mortality (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI] 1.10-1.70; P=0.005), and this result was consistent regardless of stratification based on age, sex, body mass index, left ventricular ejection fraction and clinical frailty scale without significant interaction. Patients with MMSE scores <16 had a significantly higher mortality rate compared with patients with MMSE scores >25, 21-25, and 16-20, respectively. Conclusions: Cognitive impairment assessed using MMSE scores is independently associated with an increased risk for 5-year all-cause mortality in patients undergoing TAVI.

Impact of the clinical frailty scale on long-term outcomes after transcatheter aortic valve implantation.

BACKGROUND: The semiquantitative Clinical Frailty Scale (CFS) is reportedly a useful marker for predicting short- and mid-term mortality after transcatheter aortic valve implantation (TAVI). We assessed the long-term prognostic impact of CFS in patients with severe aortic stenosis undergoing TAVI. METHODS: We prospectively assessed patients undergoing TAVI in Kokura Memorial Hospital using a 9-level CFS and enrolled 1594 patients after excluding patients with CFS 8-9. The patients were divided into the low (CFS level, 1-3; N = 842), intermediate (4; N = 469), and high (5-7; N = 283) groups according to their CFS levels. RESULTS: In the low, intermediate, and high groups, 3-year all-cause mortality rates were 17.4%, 29.4%, and 41.7% (P < .001) and composite rates of cardiovascular mortality and heart failure hospitalization were 12.1%, 19.1%, and 23.9% (P < .001), respectively. Multivariable analysis showed that higher frailty was independently associated with all-cause mortality (intermediate group: adjusted hazard ratio [HR], 1.63, 95% confidence interval [CI], 1.24-2.15, P < .001; high group: adjusted HR, 2.18, 95% CI, 1.59-2.99, P < .001) and composite of cardiovascular mortality and heart failure hospitalization (intermediate group: adjusted HR, 1.47, 95% CI, 1.04-2.08, P = .030; high group: adjusted HR, 1.66, 95% CI, 1.09-2.51, P = .018) and this result was consistent, irrespective of stratification based on age, sex, body mass index, left ventricular ejection fraction, Society of Thoracic Surgeons score, and New York Heart Association functional class without significant interaction. CONCLUSIONS: The simple CFS tool predicts the long-term adverse outcomes post-TAVI.

Using Buddhist Meditation-informed Hypnotic Techniques to Manage Rumination: Two Case Illustrations.

Rumination is a clinical phenomenon that causes significant distress in clients who suffer from various psychological and physical disorders. It also has a deleterious impact on both therapeutic process and outcome. One approach that holds promise to manage rumination is mindfulness meditation in combination with clinical hypnosis. This article: (1) reviews the concept of and techniques to manage rumination in the Buddhist psychological framework, (2) introduces 2 simple mindfulness-based techniques to deal with rumination, i.e., mindful thought detachment and mindful dereflection, and (3) describes 2 case studies in which these strategies were applied successfully. Hypnosis-informed clinicians are encouraged to integrate these approaches in their practices.

Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling.

Although inflammation plays critical roles in the development of atherosclerosis, its regulatory mechanisms remain incompletely understood. Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, we show that vascular injury induces the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response and thus vascular remodeling as a protective mechanism. In a mouse model of endovascular injury, macrophages accumulate in PVAT, causing beiging phenotype change. Inhibition of PVAT beiging by genetically silencing PRDM16, a key regulator to beiging, exacerbates inflammation and vascular remodeling following injury. Conversely, activation of PVAT beiging attenuates inflammation and pathological vascular remodeling. Single-cell RNA sequencing reveals that beige adipocytes abundantly express neuregulin 4 (Nrg4) which critically regulate alternative macrophage activation. Importantly, significant beiging is observed in the diseased aortic PVAT in patients with acute aortic dissection. Taken together, vascular injury induces the beiging of adjacent PVAT with macrophage accumulation, where NRG4 secreted from the beige PVAT facilitates alternative activation of macrophages, leading to the resolution of vascular inflammation. Our study demonstrates the pivotal roles of PVAT in vascular inflammation and remodeling and will open a new avenue for treating atherosclerosis.

Sex Differences and Regulatory Actions of Estrogen in Cardiovascular System.

Great progress has been made in the understanding of the pathophysiology of cardiovascular diseases (CVDs), and this has improved the prevention and prognosis of CVDs. However, while sex differences in CVDs have been well documented and studied for decades, their full extent remains unclear. Results of the latest clinical studies provide strong evidence of sex differences in the efficacy of drug treatment for heart failure, thereby possibly providing new mechanistic insights into sex differences in CVDs. In this review, we discuss the significance of sex differences, as rediscovered by recent studies, in the pathogenesis of CVDs. First, we provide an overview of the results of clinical trials to date regarding sex differences and hormone replacement therapy. Then, we discuss the role of sex differences in the maintenance and disruption of cardiovascular tissue homeostasis.

The Mindfulness-Based Phase-Oriented Trauma Therapy (MB-POTT): Hypnosis-informed mindfulness approach to trauma.

Hypnosis has long been successfully used in the treatment of trauma and related disorders. In this paper, I describe a hypnosis-informed approach to PTSD using mindfulness. The Mindfulness-Based Phase-Oriented Traumatic Therapy (MB-POTT) follows the phase-oriented tradition that was originally proposed by Pierre Janet, later expanded by Daniel Brown and Erika Fromm using clinical hypnosis. MB-POTT comprises four distinct, yet recursive, stages: (1) therapeutic alliance building and symptom stabilization, (2) formation of a narrative about the trauma, (3) re-creation of meaning of life after trauma, and (4) future symptom management. In explaining these categories, I delineate the nature of mindfulness, both similarities and dissimilarities to hypnosis, with an emphasis on techniques that resemble hypnotic approaches (e.g., ego state therapy, ego-strengthening). Finally, I provide a case study in which MB-POTT was implemented with a client who suffered from PTSD after a near-fatal industrial accident.

Development of a 1,3a,6a-triazapentalene derivative as a compact and thiol-specific fluorescent labeling reagent.

For the fluorescence imaging of biologically active small compounds, the development of compact fluorophores that do not perturb bioactivity is required. Here we report a compact derivative of fluorescent 1,3a,6a-triazapentalenes, 2-isobutenylcarbonyl-1,3a,6a-triazapentalene (TAP-VK1), as a fluorescent labeling reagent. The reaction of TAP-VK1 with various aliphatic thiols proceeds smoothly to afford the corresponding 1,4-adducts in high yields, and nucleophiles other than thiols do not react. After the addition of thiol groups in dichloromethane, the emission maximum of TAP-VK1 shifts to a shorter wavelength and the fluorescence intensity is substantially increased. The utility of TAP-VK1 as a compact fluorescent labeling reagent is clearly demonstrated by the labeling of Captopril, which is a small molecular drug for hypertension. The successful imaging of Captopril, one of the most compact drugs, in this study demonstrates the usefulness of compact fluorophores for mechanistic studies.

Comparison of mid-term clinical outcomes after acute myocardial infarction in diabetic men between living alone and living together.

Because living alone is associated with an increased risk of type 2 diabetes mellitus in men but not women, living alone may be a risk factor of cardiovascular events after acute myocardial infarction (AMI) in diabetic men. The aim of the present study was to investigate the association between living alone and mid-term clinical outcomes after AMI in diabetic men. We conducted a single center, retrospecitve study. The primary endpoint was the major adverse cardiovascular events (MACE) defined as the composite of all cause death, AMI, and target vessel revascularization. A total of 253 AMI men with diabetes mellitus were included from our hospital records, and divided into the living together group (n = 203) and the living alone group (n = 50). Median follow-up duration was 239 days (Q1: 94 days, Q3: 451 days). A total of 66 MACE was observed during the study period, and Kaplan-Meier curves were constructed to compare the MACE. The MACE was more frequently observed in the living alone group than the living together group (P = 0.041). Multivariate Cox regression analysis revealed that the living alone group was significantly associated with the MACE (Odds ratio: 1.770, 95% confidence interval 1.018-3.077, P = 0.043) after known clinical risk factors. In conclusion, living alone was significantly associated with the mid-term MACE after AMI in diabetic men. It may be important to provide multiple interventions including lifestyle guidance as well as sufficient acute medical care for such high-risk patients.

Substituent Effect at the C4-Position of 1,3a,6a-Triazapentalene.

Various 2,4-disubstituted-1,3a,6a-triazapentalenes possessing methyl and phenyl groups at the C4-position were synthesized. Fluorescence observation of the synthetic 4-methyl- and 4-phenyl-1,3a,6a-triazapentalenes revealed that the introduction of a substituent at the C4-position allowed a long-wavelength shift of the fluorescence maximum. Furthermore, the phenyl group at the C4-position was found to induce a substantial increase in the extinction coefficient value.

Hypnosis and Mindfulness: The Twain Finally Meet.

Mindfulness meditation (or simply mindfulness) is an ancient method of attention training. Arguably, developed originally by the Buddha, it has been practiced by Buddhists over 2,500 years as part of their spiritual training. The popularity in mindfulness has soared recently following its adaptation as Mindfulness-Based Stress Management by Jon Kabat-Zinn (1995). Mindfulness is often compared to hypnosis but not all assertions are accurate. This article, as a primer, delineates similarities and dissimilarities between mindfulness and hypnosis in terms of 12 specific facets, including putative neuroscientific findings. It also provides a case example that illustrates clinical integration of the two methods.

Eastern meditative techniques and hypnosis: a new synthesis.

In this article major ancient Buddhist meditation techniques, samatha, vipassana, Zen, and ton-len, will be described in reference to contemporary clinical hypnosis. In so doing, the Eastern healing framework out of which these techniques emerged is examined in comparison with and in contrast to its Western counterpart. A growing body of empirical literature shows that meditation and hypnosis have many resemblances despite the distinct differences in underlying philosophy and technical methodologies. Although not all meditation techniques "fit" the Western culture, each has much to offer to clinicians who are familiar with hypnosis.