Citations

Background and Objectives: Heart failure (HF) represents a major public health challenge worldwide, with rising prevalence, high morbidity and mortality rates, and substantial healthcare costs. Non-invasive telemonitoring has emerged as a promising adjunct in HF management, yet its clinical effectiveness remains unclear. Materials and Methods: In this systematic review, we summarize randomized controlled trials (RCTs) between 2004 and 2024 examining the efficacy of non-invasive telemonitoring on mortality, readmission, and quality of life (QoL) in HF. In addition, we characterize the heterogeneity of features of different telemonitoring interventions. Results: In total, 32 RCTs were included, comprising 13,294 participants. While some individual studies reported benefits, non-invasive telemonitoring demonstrated mixed effects on mortality, readmission rates, and QoL. The most common modality for interfacing with patients was by mobile application (53%), followed by web portals (22%), and stand-alone devices (19%). Periodic feedback (63%) was more common than continuous feedback (31%) or on-demand feedback (6%). Clinician reviews of patient telemonitoring data was event-triggered (44%) more commonly than based on a prespecified timeline (38%). In most designs (90%), patients played a passive role in telemonitoring. Conclusions: Non-invasive telemonitoring interventions for HF exhibited considerable variation in duration and system design and had a low rate of patient engagement. Future work should focus on identifying telemonitoring-responsive subgroups and refining telemonitoring strategies to complement traditional HF care.

Pediatric delirium (PD) is an acute neuropsychiatric syndrome marked by fluctuating disturbances in attention and cognition, frequently observed in pediatric intensive care units (PICUs) and associated with increased morbidity, mortality, and long-term cognitive impairment. Despite its clinical significance, PD remains underdiagnosed due to challenges inherent in assessing consciousness and cognition in children at varying developmental stages. Several bedside tools have been developed and validated in recent years, including the Cornell Assessment of Pediatric Delirium (CAPD), PreSchool Confusion Assessment Method for the Intensive Care Unit (psCAM-ICU); Pediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU), and Sophia Observation Withdrawal Symptoms—Pediatric Delirium Scale (SOS-PD), enhancing early recognition and management of PD in critically ill children. This narrative review explores the historical background, epidemiology, risk factors, pathophysiology, clinical subtypes, diagnostic tools, and current prevention and treatment strategies for PD from newborns to 21 years old. The screening tools available and the integration of non-pharmacological interventions, such as environmental modifications and family-centered care, as well as cautious and selective pharmacological management, are emphasized in this review. Early identification and targeted interventions are essential to mitigate the adverse outcomes associated with PD.

Background and importance Rapid sequence intubation in emergency settings may involve opioid pretreatment to blunt hemodynamic responses during laryngoscopy and intubation; however, opioids may lead to postintubation hypotension, increasing morbidity and mortality. Global clinical practice varies significantly, reflecting uncertainty about opioids’ benefits and risks. Objective Our goal was to evaluate the association between opioid pretreatment and hemodynamic instability, focusing on postintubation hypotension in adult patients undergoing emergency intubation. Design, settings, and participants We performed a systematic review of randomized controlled trials and observational studies comparing opioid administration vs. no opioids before adult emergency intubations. Searches included Cochrane, Embase, Medline, Scopus, and Web of Science databases until November 2024. Elective intubations were excluded. Eight (6708 patients) studies met criteria. Outcomes measure and analysis The primary outcome was postintubation hypotension, variably defined across studies. Secondary outcomes included hypoxemia, first-attempt success, cardiac arrest, and vasopressor use. Independent reviewers conducted data extraction, risk-of-bias assessments, and certainty evaluation. Results were qualitatively synthesized. Main results Among 6708 (2757 opioids and 3951 controls) patients, postintubation hypotension incidence varied widely (risk differences: −12.5% favoring opioids to +13.2% favoring controls). The single low-risk randomized study reported opioids increased hypotension (risk difference: 13%, odds ratio: 2.15, 95% confidence interval: 1.22–3.78). Observational studies yielded inconsistent results. Secondary outcomes showed no consistent differences. Evidence certainty was very low because of risk of bias, inconsistency, and imprecision. Conclusions Current evidence regarding opioid pretreatment effect on postintubation hypotension risk during emergency intubation is limited and conflicting.

Ketones, which are key biomarkers of fat oxidation, are relevant for metabolic health maintenance and disease development, making continuous monitoring essential. In this study, we introduce a novel colorimetric sensor designed for potential continuous acetone detection in biological fluids. The sensor features a polydimethylsiloxane (PDMS) shell that encapsulates a sensitive and specific liquid-core acetone-sensing probe. The microsphere sensors were characterized by evaluating their size, PDMS shell thickness, colorimetric response, and sensitivity under realistic conditions, including 100% relative humidity (RH) and CO2 interference. The microsphere size and sensor sensitivity can be controlled by modifying the fabrication parameters. Critically, the sensor showed high selectivity for acetone detection, with negligible interference from CO2 concentrations up to 4%. In addition, the sensor displayed good reproducibility (CV < 5%) and stability under realistic storage conditions (over two weeks at 4 °C). Finally, the accuracy of the microsphere sensor was validated against a gold standard gas chromatography-mass spectrometry (GC-MS) method using simulated and real breath samples from healthy individuals and type 1 diabetes patients. The correlation between the microsphere sensor and GC-MS produced a linear fit with a slope of 0.948 and an adjusted R-squared value of 0.954. Therefore, the liquid-core microsphere-based sensor is a promising platform for acetone body fluid analysis.

Abstract INTRODUCTION Neurofilament light chain (NfL) quantification aids in diagnosing and predicting neurological disorders, but clinical and laboratory practices vary across centers. Differences in result interpretation and reporting further challenge test commutability. This study aimed to review the global analytical and post‐analytical methods used for NfL measurement in routine clinical practice across different contexts. METHODS We established an international working group (WG) and distributed a survey to its members to gather information on context of use (COU), (pre) analytical methods, cutoff usage, as well as the interpretation and reporting of NfL measurements. RESULTS Among the centers, 63% measured NfL in cerebrospinal fluid (CSF), 87% in blood, and 53% in both. COU was widespread, with 50% defining pathological cutoffs based on publications and 42% considering age. Reporting was primarily done through numeric results (95%). DISCUSSION Harmonizing cutoffs, reporting, and interpretation across various clinical contexts will facilitate the incorporation of this biomarker into routine clinical practice. Highlights Unique international overview of current analytical and post‐analytical methods for neurofilament light chain (NfL) measurement in routine clinical practice. Tailored sheets for each neurological application. Strategies to harmonize cutoffs, reporting, and interpretation of NfL's measurement.

Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.

SUMMARY Tuberculosis induces diverse lesions, such as necrotic pneumonia, contributing to disease progression and transmission. Despite advances in understanding the role of ATP-gated P2RX7 ion channels in developing severe forms of tuberculosis, the regulation of this important signaling pathway remains unclear. Herein, we show that the ectonucleotidase CD39 plays an essential regulatory role in TB progression by preventing lung tissue damage, bacterial dissemination, and excessive inflammatory responses. Mechanistically, through its enzymatic activity on the cellular surface, CD39 protects infected macrophages from undergoing necrotic death mediated by P2RX7 activation. We proposed that by protecting macrophages from P2RX7-mediated cell death and bacterial dissemination, CD39 prevents the development of necrotic lesions. Altogether, these findings uncover a significant role for CD39 as an essential component of the molecular regulation underlying the development of severe tuberculosis. GRAPHICAL ABSTRACT Brief In tuberculosis, necrotic granuloma-like structures release extracellular ATP (eATP), which triggers P2RX7-mediated immune cell death. CD39 degrades eATP, preventing P2RX7 activation and promoting macrophage survival, thereby limiting inflammation, tissue damage, and bacterial dissemination.

Purpose To compare the outcomes of standard combined Phaco-Kahook Dual Blade (KDB) surgery (GI) with those of the extended technique (GII). Methods This retrospective, comparative, multicenter, case-control study enrolled patients with one-year follow-up. GI removed 90° of the trabecular meshwork (TM) extension during KDB, whereas GII removed 150°. The successful criteria were based on a modification of the AAO PPP recommendations - Reporting Clinical Endpoints in Studies of Minimally Invasive Glaucoma Surgery. Qualified success was achieved with or without medication, while absolute success was achieved without the use of any ocular hypotensive medication. Results A total of 72 eyes (36 in both groups) were included. The IOP was similar between groups preoperatively (GI: 17.0 ± 2.7 mmHg vs. GII: 17.5 ± 4.2 mmHg, p = 0.5), and at 12 months postoperatively (GI: 13.5 ± 2.8 mmHg vs. GII: 12.3 ± 2.7 mmHg, p = 0.06). The number of glaucoma medications was reduced from 1.7 ± 0.9 to 0.4 ± 0.8 in GI ( p < 0.001) and from 2.1 ± 0.8 to 0.4 ± 0.7 in GII ( p < 0.001). At 12 months, both groups reduced comparable glaucoma medications ( p = 0.9). Qualified success was achieved in 77.1% of the eyes with GI and 94.4% with GII ( p = 0.03), whereas complete success was achieved in 68.6% of the eyes with GI and 69.4% with GII ( p = 0.7). No serious complications were observed in any of the groups. Conclusion Extended combined Phaco-KDB surgery showed greater relative success than the Standard Phaco-KDB technique. Both techniques achieved similar IOP reduction at 12 months postoperatively.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Abstract INTRODUCTION Clinicians’ views on the clinical readiness of Alzheimer's disease (AD) blood biomarkers (BBMs) are not well understood. METHODS The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment Biofluid‐Based Biomarkers Professional Interest Area conducted a survey to elicit clinician opinions on AD BBM implementation, including contexts of use, assay selection, reporting, and result interpretation. RESULTS Clinician respondents ( n = 212) practiced in Europe (56%), North America (24%), the Caribbean and Central/South America (11%), and other continents (9%). Most respondents were medical doctors (80%) practicing in secondary or tertiary care (88%). For 56%, cerebrospinal fluid AD biomarkers or amyloid positron emission tomography were accessible, but 48% agreed and 52% disagreed with the implementation of AD BBMs in any clinical context. Respondents emphasized the need for data from diverse populations and educational resources to support test interpretation. DISCUSSION Surveyed clinicians generally agreed with published appropriate use recommendations but were divided on AD BBM readiness for clinical use. Highlights A survey of clinicians was conducted regarding clinical readiness of Alzheimer's disease (AD) blood biomarkers (BBMs). Views were split on AD BBM clinical readiness: 48% agreed, 52% disagreed. Most responders supported AD BBM use for treatment decisions. Most responders opposed AD BBM testing in asymptomatic individuals. Test performance data and educational materials to aid interpretation were of high importance.