Trends in adoption of extravascular cardiac implantable electronic devices: the Dutch cohort.

INTRODUCTION: Conventional implantable cardioverter-defibrillators (ICDs) and pacemakers carry a risk of pocket- and lead-related complications in particular. To avoid these complications, extravascular devices (EVDs) have been developed, such as the subcutaneous ICD (S-ICD) and leadless pacemaker (LP). However, data on patient or centre characteristics related to the actual adoption of EVDs are lacking. OBJECTIVE: To assess real-world nationwide trends in EVD adoption in the Netherlands. METHODS: Using the Netherlands Heart Registration, all consecutive patients with a de novo S­ICD or conventional single-chamber ICD implantation between 2012-2020, or de novo LP or conventional single-chamber pacemaker implantation between 2014-2020 were included. Trends in adoption are described for various patient and centre characteristics. RESULT: From 2012-2020, 2190 S­ICDs and 10,683 conventional ICDs were implanted; from 2014-2020, 712 LPs and 11,103 conventional pacemakers were implanted. The general use has increased (S-ICDs 8 to 21%; LPs 1 to 8%), but this increase seems to have reached a plateau. S­ICD recipients were younger than conventional ICD recipients (p < 0.001) and more often female (p < 0.001); LP recipients were younger than conventional pacemaker recipients (p < 0.001) and more often male (p = 0.03). Both S­ICDs and LPs were mainly implanted in high-volume centres with cardiothoracic surgery on-site, although over time S­ICDs were increasingly implanted in centres without cardiothoracic surgery (p < 0.001). CONCLUSION: This nationwide study demonstrated a relatively quick adoption of innovative EVDs with a plateau after approximately 4 years. S­ICD use is especially high in younger patients. EVDs are mainly implanted in high-volume centres with cardiothoracic surgery back-up, but S­ICD use is expanding beyond those centres.

Methamphetamine and the Synthetic Cathinone 3,4-Methylenedioxypyrovalerone (MDPV) Produce Persistent Effects on Prefrontal and Striatal Microglial Morphology and Neuroimmune Signaling Following Repeated Binge-like Intake in Male and Female Rats.

Psychostimulants alter cellular morphology and activate neuroimmune signaling in a number of brain regions, yet few prior studies have investigated their persistence beyond acute abstinence or following high levels of voluntary drug intake. In this study, we examined the effects of the repeated binge-like self-administration (96 h/week for 3 weeks) of methamphetamine (METH) and 21 days of abstinence in female and male rats on changes in cell density, morphology, and cytokine levels in two addiction-related brain regions-the prefrontal cortex (PFC) and dorsal striatum (DStr). We also examined the effects of similar patterns of intake of the cocaine-like synthetic cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV) or saline as a control. Robust levels of METH and MDPV intake (~500-1000 infusions per 96 h period) were observed in both sexes. We observed no changes in astrocyte or neuron density in either region, but decreases in dendritic spine densities were observed in PFC pyramidal and DStr medium spiny neurons. The microglial cell density was decreased in the PFC of METH self-administering animals, accompanied by evidence of microglial apoptosis. Changes in microglial morphology (e.g., decreased territorial volume and ramification and increased cell soma volume) were also observed, indicative of an inflammatory-like state. Multiplex analyses of PFC and DStr cytokine content revealed elevated levels of various interleukins and chemokines only in METH self-administering animals, with region- and sex-dependent effects. Our findings suggest that voluntary binge-like METH or MDPV intake induces similar cellular perturbations in the brain, but they are divergent neuroimmune responses that persist beyond the initial abstinence phase.

Divergent cardiac and renal effects of miR-181c-5p inhibition in a rodent heart failure model.

Aims: MiR-181c-5p overexpression associates with heart failure (HF) and cardiac damage, but the underlying pathophysiology remains unclear. This study investigated the effect of miR-181c-5p inhibition on cardiac function and fibrosis in a rodent model of diastolic dysfunction, and evaluated additional effects on kidney as relevant comorbid organ. Methods and results: Diastolic dysfunction was induced in male C57/BL6J mice (n = 20) by combining high-fat diet, L-NG-nitroarginine methyl ester, and angiotensin II administration, and was compared to sham controls (n = 18). Mice were randomized to subcutaneous miR-181c-5p antagomiR (INH) or scrambled antagomiR injections (40 mg/kg/week). HF mice demonstrated diastolic dysfunction and increased fibrosis, which was attenuated by INH treatment. Remarkably, HF + INH animals had a threefold higher mortality rate (60%) compared to HF controls (20%). Histological examination revealed increased glomerular damage in all INH treated mice, and signs of thrombotic microangiopathy (TMA) in mice who died prematurely. Quantitative polymerase chain reaction demonstrated a miR-181c-5p-related downregulation of cardiac but not renal Tgfbr1 in HF + INH mice, while INH treatment reduced renal but not cardiac Vegfa expression in all mice. Conclusion: This study demonstrates cardiac anti-fibrotic effects of miR-181c-5p inhibition in a rodent HF model through targeting of Tgfbr1 in the heart. Despite improved diastolic function, HF + INH mice had higher mortality due to increased predisposition for TMA, increased renal fibrosis and glomerular damage, associated with Vegfa downregulation in kidneys.

Left Atrial Appendage Occlusion in Patients With Anticoagulation Failure vs Anticoagulation Contraindication.

BACKGROUND: Left atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection for atrial fibrillation (AF) patients who cannot use oral anticoagulation therapy (OAT). Patients with a thrombotic event despite OAT are at high risk for recurrence and may also benefit from LAAO. OBJECTIVES: This study sought to investigate the efficacy of LAAO in AF patients with a thrombotic event on OAT compared to: 1) LAAO in AF patients with a contraindication for OAT; and 2) historical data. METHODS: The international LAAO after stroke despite oral anticoagulation (STR-OAC LAAO) collaboration included patients who underwent LAAO because of thrombotic events on OAT. This cohort underwent propensity score matching and was compared to the EWOLUTION (Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology) registry, which represents patients who underwent LAAO because of OAT contraindications. The primary outcome was ischemic stroke. Event rates were compared between cohorts and with historical data without OAT, yielding relative risk reductions based on risk scores. RESULTS: Analysis of 438 matched pairs revealed no significant difference in the ischemic stroke rate between the STR-OAC LAAO and EWOLUTION cohorts (2.5% vs 1.9%; HR: 1.37; 95% CI: 0.72-2.61). STR-OAC LAAO patients exhibited a higher thromboembolic risk (HR: 1.71; 95% CI: 1.04-2.83) but lower bleeding risk (HR: 0.39; 95% CI: 0.18-0.88) compared to EWOLUTION patients. The mortality rate was slightly higher in EWOLUTION (4.3% vs 6.9%; log-rank P = 0.028). Relative risk reductions for ischemic stroke were 70% and 78% in STR-OAC LAAO and EWOLUTION, respectively, compared to historical data without OAT. CONCLUSIONS: LAAO in patients with a thrombotic event on OAT demonstrated comparable stroke rates to the OAT contraindicated population in EWOLUTION. The thromboembolic event rate was higher and the bleeding rate lower, reflecting the intrinsically different risk profile of both populations. Until randomized trials are available, LAAO may be considered in patients with an ischemic event on OAT.

Pathophysiology and clinical relevance of atrial myopathy.

Atrial myopathy is a condition that consists of electrical, structural, contractile, and autonomic remodeling of the atria and is the substrate for development of atrial fibrillation, the most common arrhythmia. Pathophysiologic mechanisms driving atrial myopathy are inflammation, oxidative stress, atrial stretch, and neurohormonal signals, e.g., angiotensin-II and aldosterone. These mechanisms initiate the structural and functional remodeling of the atrial myocardium. Novel therapeutic strategies are being developed that target the pathophysiologic mechanisms of atrial myopathy. In this review, we will discuss the pathophysiology of atrial myopathy, as well as diagnostic and therapeutic strategies.

Best practices for implementing a technology-based intervention protocol: Participant and researcher considerations.

Technology-based interventions present a promising approach to support health and wellness for older adults with a range of cognitive abilities. Technology can enhance access to interventions and support scaling of programs to reach more people. However, the use of technology for intervention delivery requires particular attention to users' needs and preferences and ensuring the materials are adaptable and supportive of a diverse range of technology proficiency levels. We share best practices based on lessons learned from the deployment of a randomized controlled trial (RCT) wherein we delivered an 8-week social engagement intervention through a video technology platform called OneClick for older adults with varying cognitive abilities. We developed a set of best practices and guidelines informed by the lessons learned through this RCT implementation. Technology-based interventions require attention to the application (e.g., video calls), system requirements (e.g., system memory, broadband internet), training (e.g., adaptability based on user competency), and support (e.g., handouts, live contact). These best practices relate to user needs; training design; personnel responsibility; structuring delivery and content; and evaluating success. These research-based best practices can guide the design, development, and implementation of technology-based interventions to support older adults with varying cognitive abilities.

Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study.

BACKGROUND AND OBJECTIVES: Insomnia affects about one-third of patients with traumatic brain injury and is associated with worsened outcomes after injury. We hypothesized that higher levels of plasma neuroinflammation biomarkers at the time of TBI would be associated with worse 12-month insomnia trajectories. METHODS: Participants were prospectively enrolled from 18 level-1 trauma centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study from February 26, 2014, to August 8, 2018. Plasma glial fibrillary acidic protein (GFAP), high-sensitivity C-reactive protein (hsCRP), S100b, neuron-specific enolase (NSE), and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) were collected on days 1 (D1) and 14 (D14) after TBI. The insomnia severity index was collected at 2 weeks, 3, 6, and 12 months postinjury. Participants were classified into insomnia trajectory classes based on a latent class model. We assessed the association of biomarkers with insomnia trajectories, controlling for medical and psychological comorbidities and demographics. RESULTS: Two thousand twenty-two individuals with TBI were studied. Elevations in D1 hsCRP were associated with persistent insomnia (severe, odds ratio [OR] = 1.33 [1.11, 1.59], p = 0.002; mild, OR = 1.10 [1.02, 1.19], p = 0.011). Similarly, D14 hsCRP elevations were associated with persistent insomnia (severe, OR = 1.27 [1.02, 1.59], p = 0.03). Of interest, D1 GFAP was lower in persistent severe insomnia (median [Q1, Q3]: 154 [19, 445] pg/mL) compared with resolving mild (491 [154, 1,423], p < 0.001) and persistent mild (344 [79, 1,287], p < 0.001). D14 GFAP was similarly lower in persistent (11.8 [6.4, 19.4], p = 0.001) and resolving (13.9 [10.3, 20.7], p = 0.011) severe insomnia compared with resolving mild (20.6 [12.4, 39.6]. Accordingly, increases in D1 GFAP were associated with reduced likelihood of having persistent severe (OR = 0.76 [95% CI 0.63-0.92], p = 0.004) and persistent mild (OR = 0.88 [0.81, 0.96], p = 0.003) compared with mild resolving insomnia. No differences were found with other biomarkers. DISCUSSION: Elevated plasma hsCRP and, surprisingly, lower GFAP were associated with adverse insomnia trajectories after TBI. Results support future prospective studies to examine their utility in guiding insomnia care after TBI. Further work is needed to explore potential mechanistic connections between GFAP levels and the adverse insomnia trajectories.

Expression of the monocarboxylate transporter MCT1 is required for virus-specific mouse CD8+ T cell memory development.

Lactate-proton symporter monocarboxylate transporter 1 (MCT1) facilitates lactic acid export from T cells. Here, we report that MCT1 is mandatory for the development of virus-specific CD8+ T cell memory. MCT1-deficient T cells were exposed to acute pneumovirus (pneumonia virus of mice, PVM) or persistent γ-herpesvirus (Murid herpesvirus 4, MuHV-4) infection. MCT1 was required for the expansion of virus-specific CD8+ T cells and the control of virus replication in the acute phase of infection. This situation prevented the subsequent development of virus-specific T cell memory, a necessary step in containing virus reactivation during γ-herpesvirus latency. Instead, persistent active infection drove virus-specific CD8+ T cells toward functional exhaustion, a phenotype typically seen in chronic viral infections. Mechanistically, MCT1 deficiency sequentially impaired lactic acid efflux from activated CD8+ T cells, caused an intracellular acidification inhibiting glycolysis, disrupted nucleotide synthesis in the upstream pentose phosphate pathway, and halted cell proliferation which, ultimately, promoted functional CD8+ T cell exhaustion instead of memory development. Taken together, our data demonstrate that MCT1 expression is mandatory for inducing T cell memory and controlling viral infection by CD8+ T cells.

Toward personalized care for insomnia in the US Army: a machine learning model to predict response to cognitive behavioral therapy for insomnia.

STUDY OBJECTIVES: The standard of care for military personnel with insomnia is cognitive behavioral therapy for insomnia (CBT-I). However, only a minority seeking insomnia treatment receive CBT-I, and little reliable guidance exists to identify those most likely to respond. As a step toward personalized care, we present results of a machine learning (ML) model to predict CBT-I response. METHODS: Administrative data were examined for n = 1,449 nondeployed US Army soldiers treated for insomnia with CBT-I who had moderate-severe baseline Insomnia Severity Index (ISI) scores and completed 1 or more follow-up ISIs 6-12 weeks after baseline. An ensemble ML model was developed in a 70% training sample to predict clinically significant ISI improvement (reduction of at least 2 standard deviations on the baseline ISI distribution). Predictors included a wide range of military administrative and baseline clinical variables. Model accuracy was evaluated in the remaining 30% test sample. RESULTS: 19.8% of patients had clinically significant ISI improvement. Model area under the receiver operating characteristic curve (standard error) was 0.60 (0.03). The 20% of test-sample patients with the highest probabilities of improvement were twice as likely to have clinically significant improvement compared with the remaining 80% (36.5% vs 15.7%; χ21 = 9.2, P = .002). Nearly 85% of prediction accuracy was due to 10 variables, the most important of which were baseline insomnia severity and baseline suicidal ideation. CONCLUSIONS: Pending replication, the model could be used as part of a patient-centered decision-making process for insomnia treatment. Parallel models will be needed for alternative treatments before such a system is of optimal value. CITATION: Gabbay FH, Wynn GH, Georg MW, et al. Toward personalized care for insomnia in the US Army: a machine learning model to predict response to cognitive behavioral therapy for insomnia. J Clin Sleep Med. 2024;20(6):921-931.

Peripheral Microvascular Dysfunction in Children and Adults with Congenital Heart Disease: A Literature Review.

Although there is a continually growing number of patients with congenital heart disease (CHD) due to medical and surgical advances, these patients still have a poorer prognosis compared to healthy individuals of similar age. In patients with heart failure, microvascular dysfunction (MVD) has recently emerged as a crucial modulator of disease initiation and progression. Because of the substantial pathophysiological overlap between CHD and heart failure induced by other etiologies, MVD could be important in the pathophysiology of CHD as well. MVD is believed to be a systemic disease and may be manifested in several vascular beds. This review will focus on what is currently known about MVD in the peripheral vasculature in CHD. Therefore, a search on the direct assessment of the vasodilatory capacity of the peripheral microcirculation in patients with CHD was conducted in the PubMed database. Since there is little data available and the reported studies are also very heterogeneous, peripheral MVD in CHD is not sufficiently understood to date. Its exact extent and pathophysiological relevance remain to be elucidated in further research.

Knowledge, attitudes, and practices in colorectal cancer screening in the Philippines

Background and Objective@#Colorectal cancer (CRC) has the third highest incidence in the Philippines. Currently, there is a paucity in literature that is focused on the knowledge, attitudes, and perceptions of Filipinos regarding CRC screening. This is the first study in the Philippines that describes this. @*Methods@#This is a cross-sectional study that validated a 52-item Filipino questionnaire on the knowledge on colorectal cancer, willingness to undergo CRC screening, and perceived benefits and barriers to fecal occult blood test (FOBT) and colonoscopy. The study enrolled household heads more than 20 years of age residing in both urban and rural communities in the Philippines. @*Results@#The UP-PGH CRC KAP (University of the Philippines – Philippine General Hospital Colorectal Cancer Knowledge, Attitudes, and Practices) and Rawl Questionnaire’s validity and internal consistency were established in a pilot study of 30 respondents. A total of 288 respondents were then enrolled to the main study group with a median age of 54.0. Knowledge scores for prognosis and utility of CRC screening were modest (6.3/12 and 8.4/20, respectively). Perceived benefit scores to FOBT and colonoscopy were high (9.9/12 and 13.9/16, respectively).Median scores to barriers to FOBT and colonoscopy were intermediate (22.5/36 and 35.8/60, respectively). Notably, a vast majority (86.1%) were willing to participate in CRC screening programs initiated by the government, and 46.9% agreed to undergo screening tests even as out-of-pocket expense. @*Conclusion@#The UP-PGH CRC KAP Questionnaire as well as the Filipino translation of the Rawl Questionnaire are reliable and valid tools in extensively assessing the knowledge of Filipinos on CRC and willingness to undergo screening, as well as the benefits of and barriers to FOBT and colonoscopy. Knowledge scores were modest suggesting that directed educational campaigns and awareness programs can aid in increasing awareness about CRC and its screening. Household income and highest educational attainment were significantly positively correlated with knowledge scores, and perceived benefits of and barriers to CRC screening. Scores were generally comparable between urban and rural communities.

The effect of the Elderly Development Program on the quality of life of elderly individuals / The Health Sciences Journal

Introduction @#The increasing aging population of the Philippines impacts on the socioeconomic development of the country, prompting a deeper look into their quality of life. This study sought to determine the effect of the Elderly Development Program on the quality of life of the elderly population of Los Baños.@*Methods @#A 4-month prospective cohort study of the elderly population in Los Baños, Laguna compared the quality of life scores of a group enrolled in the Elderly Development Program and an unexposed control, using the World Health Organization Quality of Life Abbreviated Version for Filipino Older Persons questionnaire.@*Results @#Quality of life scores where higher for the EDP group during the four months of observation. In Month 2, significant differences were found in all domains except for the psychological domain. Only the physical health domain score was significant in the EDP group for Month 3 (p = 0.003) and Month 4 (p = 0.029). Both the EDP and control groups had higher overall and domain scores in Month 4 compared with baseline.@*Conclusion @#The Elderly Development Program may improve the overall quality of life of elderly persons, specifically in the physical health domain. These improvements are likely due to the focus of the program on the physical aspect of the elderly.

Indication of lower neck irradiation in nasopharyngeal carcinoma without nodal metastasis: the potential impact of tumor volume / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Elective radiation of lower neck is controversial for nasopharyngeal carcinoma (NPC) without lymph node metastasis (N0 disease). Tumor volume is an important prognostic indicator. The objective of this study is to explore the potential impact of tumor volume on the indication of the lower neck irradiation for N0-NPC, by a qualitative evaluation of the relationship between tumor volume and nodal metastasis.</p><p><b>METHODS</b>Magnetic resonance (MR) images of 99 consecutive patients with NPC who underwent treatment were retrospectively reviewed. Primary tumor volumes of NPC were semi-automatically measured, nodal metastases were N-classified and neck level involvements were examined. Distributions of tumor volumes among N-category-based groups and distributions of N-categories among tumor volume-based groups were analyzed, respectively.</p><p><b>RESULTS</b>The numbers of patients with N0 to N3 disease were 12, 39, 32, and 16, respectively. The volumes of primary tumor were from 3.3 to 89.6 ml, with a median of 17.1 ml. For patients with nodal metastasis, tumor volume did not increase significantly with the advancing of N-category (P > 0.05). No significant difference was found for the distribution of N1, N2, and N3 categories among tumor volume-based groups (P > 0.05). Nevertheless patients with nodal metastasis had significantly larger tumor volumes than those without metastasis (P < 0.05). Patients with larger tumor volumes were associated with an increased incidence of nodal metastasis.</p><p><b>CONCLUSIONS</b>Certain positive correlations existed between tumor volume and the presence of nodal metastasis. The tumor volume (>10 ml) is a potential indicator for the lower neck irradiation for N0-NPC.</p>

A survey of local preclinical and clinical medical students' attitudes towards radiology

<p><b>INTRODUCTION</b>This study compares the attitudes between preclinical and clinical medical students towards radiology, following the introduction of a new radiology curriculum for 1st year students.</p><p><b>MATERIALS AND METHODS</b>Revision of the 1st year medical school curriculum for the academic year of 2008/9 with the inclusion of 13 one-hour formal radiology lectures integrated with each body system was done in an undergraduate Southeast Asian medical school. In the old curriculum, 1st and 2nd year medical students are not exposed to radiology. They received limited radiology teaching in their 3rd and 5th years with 2 one-hour lectures as part of their medicine and surgery rotations. In the 4th year, they have a one week non-examinable posting in radiology. A survey was administered to preclinical (new curriculum) and clinical (old curriculum) students. Survey responses were tabulated and attitudes between preclinical and clinical students were compared.</p><p><b>RESULTS</b>More than half of the preclinical students (155 out of 270 students, 59%) and 90 out of 720 clinical students (12.5%) responded. Students exposed to the new curriculum had attended one or two dedicated radiology lectures and were considering radiology as a clinical elective. Both groups of students did not feel familiar with radiology as with other specialties, were not considering radiology as a career, but felt that radiology was interesting and important to the overall practice of medicine.</p><p><b>CONCLUSIONS</b>Exposure of 1st year students to radiology increases their interest in the subject. Further intervention, fi ne-tuning of the curriculum and follow-up surveys will be carried out to see if this interest persists throughout their clinical years.</p>