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5 pages, 4535 KB  
Interesting Images
A Nondiagnostic 99mTc-PYP Scan with Absent Skeletal Uptake
by Hiroyuki Tokue, Azusa Tokue and Yoshito Tsushima
Diagnostics 2026, 16(12), 1829; https://doi.org/10.3390/diagnostics16121829 (registering DOI) - 12 Jun 2026
Viewed by 77
Abstract
99mTc-pyrophosphate (PYP) scintigraphy is widely used for the noninvasive evaluation of transthyretin cardiac amyloidosis. Although interpretation primarily focuses on myocardial uptake, confirmation of appropriate systemic radiotracer biodistribution is essential. We report a case in which an examination presumed to be 99mTc-PYP scintigraphy demonstrated [...] Read more.
99mTc-pyrophosphate (PYP) scintigraphy is widely used for the noninvasive evaluation of transthyretin cardiac amyloidosis. Although interpretation primarily focuses on myocardial uptake, confirmation of appropriate systemic radiotracer biodistribution is essential. We report a case in which an examination presumed to be 99mTc-PYP scintigraphy demonstrated free 99mTc-pertechnetate-like biodistribution. A 75-year-old woman with chronic kidney disease and conduction disturbance underwent 99mTc-PYP scintigraphy for suspected cardiac amyloidosis. The initial study, recorded as the administration of 740 MBq 99mTc-PYP, was imaged 3 h after injection. Planar imaging showed mild apparent activity over the cardiac region; however, SPECT/CT demonstrated no definite myocardial uptake. Instead, intense uptake was observed in the stomach and thyroid gland, with complete absence of skeletal activity. This distribution was inconsistent with correctly administered 99mTc-PYP and suggested free 99mTc-pertechnetate biodistribution, likely due to radiopharmaceutical preparation or administration error. A repeat 99mTc-PYP scan 1.5 months later showed expected skeletal uptake without gastric or thyroid activity and again demonstrated no myocardial uptake. The study was interpreted as negative for cardiac amyloidosis. Gastric and thyroid uptake with absent skeletal activity on presumed 99mTc-PYP scintigraphy should be considered nondiagnostic rather than negative. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
22 pages, 643 KB  
Review
Prehabilitation Before Cardiac Surgery and Structural Heart Interventions: An Umbrella Review of Pooled Evidence
by Elen H. Hughes, Robyn Lotto, Ellen A. Dawson, Mohamed Saber, Ethan Richards, Adrian Morris, David Mayhew, Fahmi Faraz, Reza Ashrafi and Julia D. Jones
J. Clin. Med. 2026, 15(10), 3821; https://doi.org/10.3390/jcm15103821 - 15 May 2026
Viewed by 248
Abstract
Background: Prehabilitation aims to optimise patients before cardiac procedures through interventions including exercise training, respiratory conditioning, nutritional support, psychological preparation and multimodal lifestyle programmes. Evidence from systematic reviews and meta-analyses is increasing but remains heterogeneous due to variation in intervention design, patient [...] Read more.
Background: Prehabilitation aims to optimise patients before cardiac procedures through interventions including exercise training, respiratory conditioning, nutritional support, psychological preparation and multimodal lifestyle programmes. Evidence from systematic reviews and meta-analyses is increasing but remains heterogeneous due to variation in intervention design, patient populations and overlap of primary studies. Methods: We conducted an umbrella review of 17 systematic reviews and meta-analyses evaluating prehabilitation prior to cardiac surgery and structural heart interventions in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality of included reviews was assessed using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). Outcomes of interest were postoperative pneumonia, hospital length of stay (LOS), and mortality. Results: Across pooled analyses, the most consistent finding was a reduction in postoperative pneumonia, particularly in studies incorporating inspiratory muscle training (IMT), with relative risk reductions of approximately 55–62%, corresponding to a modest absolute risk reduction. Reductions in hospital LOS were also reported, although effect sizes were smaller and more variable. In contrast, no consistent reduction in short-term mortality was demonstrated, likely reflecting low event rates. The evidence base was limited by substantial overlap between reviews and predominantly low or critically low methodological quality. Conclusions: Prehabilitation, particularly when incorporating IMT, is consistently associated with a reduction in postoperative pneumonia and may contribute to modest reductions in hospital LOS. However, the evidence base is constrained by heterogeneity, study overlap and low methodological quality. Further high-quality, adequately powered randomised trials are required to define the role of prehabilitation in contemporary cardiac surgical and structural intervention practice. Full article
(This article belongs to the Special Issue Clinical Insights and Advances in Structural Heart Disease)
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28 pages, 957 KB  
Review
Beyond Angiography: Cardiac CT for Planning Complex PCI in Calcified Coronary Lesions
by Kenji Sadamatsu, Kazumasa Kurogi, Yasuhiro Nakano and Takashi Kajiya
Tomography 2026, 12(5), 69; https://doi.org/10.3390/tomography12050069 - 12 May 2026
Viewed by 628
Abstract
Coronary artery calcification, present in 20–30% of percutaneous coronary interventions (PCI), significantly impairs procedural success. Conventional angiography detects calcification in fewer than half of affected cases, while intravascular imaging—though precise—requires lesion crossability that cannot be guaranteed in up to 20% of severely calcified [...] Read more.
Coronary artery calcification, present in 20–30% of percutaneous coronary interventions (PCI), significantly impairs procedural success. Conventional angiography detects calcification in fewer than half of affected cases, while intravascular imaging—though precise—requires lesion crossability that cannot be guaranteed in up to 20% of severely calcified lesions. Cardiac CT (CCT) addresses both constraints by providing comprehensive, three-dimensional calcium characterization before the procedure begins, independent of wire crossability. This review details how specific CCT-derived parameters translate into procedural decisions. Calcium arc, depth, density, and longitudinal distribution each carry distinct implications for device selection: superficial high-density calcium favors atherectomy, while deep concentric patterns are better addressed by intravascular lithotripsy. Validated scoring systems—including the ABCD score—enable objective pre-procedural risk stratification. For chronic total occlusions, bifurcation lesions, ostial stenoses, and very long calcified segments, CCT provides lesion-specific information that supports stepwise strategy selection, equipment preparation, and anticipation of combined modification approaches. Importantly, CCT also identifies anatomical configurations—such as left main bifurcations or tortuous calcified segments—where specific device-related risks warrant particular caution. CCT and intravascular imaging serve complementary roles: CCT defines the strategic framework before the procedure, while intravascular imaging guides real-time execution and optimization. Limitations include operator-dependent interpretation, the absence of standardized protocols for translating calcium morphology into device selection, and the need to validate established Hounsfield unit thresholds in emerging photon-counting CT systems. Prospective randomized evidence comparing CCT-guided and intravascular imaging-guided strategies remains limited but is anticipated from ongoing trials. Full article
(This article belongs to the Special Issue Celebrate the 10th Anniversary of Tomography)
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19 pages, 1663 KB  
Article
Aglianico Grape Pomace Extract Reduces Cardiac Pacemaker Activity by Decreasing Hyperpolarization-Activated Current Density Independently of cAMP Signaling
by Roberta De Zio, Maira Certini, Eugenia Pignataro, Daniela Russo, Simona Ida Scorza, Serena Milano, Giuseppe Procino, René Massimiliano Marsano, Maria Svelto, Isabella Maiellaro, Luigi Milella, Monica Carmosino and Andrea Gerbino
Life 2026, 16(5), 786; https://doi.org/10.3390/life16050786 - 8 May 2026
Viewed by 421
Abstract
Grape pomace extract (GPE) from Vitis vinifera L. cv. Aglianico is rich in polyphenols with recognized cardioprotective properties, yet its direct electrophysiological effects on spontaneous cardiac activity have not been previously investigated. Here, we examined the chronotropic effects of GPE using two complementary [...] Read more.
Grape pomace extract (GPE) from Vitis vinifera L. cv. Aglianico is rich in polyphenols with recognized cardioprotective properties, yet its direct electrophysiological effects on spontaneous cardiac activity have not been previously investigated. Here, we examined the chronotropic effects of GPE using two complementary models: HL-1 cardiomyocytes, assessed by whole-cell patch-clamp and intracellular Ca2+ imaging, and the Drosophila melanogaster larval heart tube, evaluated by optical recording. In HL-1 cells, chronic treatment with 25 µg/mL GPE for 48 h significantly reduced potential spontaneous action frequency and selectively prolonged the diastolic depolarization phase without altering action potential morphology, depolarization-activated currents, or cytosolic Ca2+ homeostasis. GPE reduced the hyperpolarization-activated funny current (If) density without shifting its voltage dependence. GPE-treated cells retained cAMP sensitivity, as both isoproterenol and intracellular 8-Br-cAMP significantly increased If amplitude, while ELISA quantification confirmed that global cAMP levels were unaffected by GPE. In Drosophila larvae, a cAMP-independent myogenic preparation, GPE administered in the diet significantly reduced heart rate. These findings demonstrate that Aglianico GPE exerts a negative chronotropic effect through a mechanism that reduces functional If density without altering cAMP availability or HCN channel voltage dependence, and reveal a cAMP-independent component of action conserved across phylogenetically distant species. Full article
(This article belongs to the Special Issue Channel Proteins and Transporters in Human Health and Disease)
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15 pages, 945 KB  
Article
The Role of Drug-Coated Balloons in an All-Comer Population: Outcomes from a Two-Center Real-World Registry
by Florin-Leontin Lazar, Teodor Paul Kacso, Calin Homorodean, Horea-Laurentiu Onea, Ioan-Cornel Bitea, Mihai Ober, Oana Stoia, Minodora Teodoru and Dan-Mircea Olinic
Medicina 2026, 62(4), 769; https://doi.org/10.3390/medicina62040769 - 16 Apr 2026
Viewed by 1105
Abstract
Background and Objectives: Drug-coated balloons (DCBs) represent a novel, attractive strategy for coronary revascularization; however, data supporting their use in complex real-world populations remain limited. We aimed to evaluate the safety and efficacy of a DCB-first strategy in a predominantly acute coronary syndrome [...] Read more.
Background and Objectives: Drug-coated balloons (DCBs) represent a novel, attractive strategy for coronary revascularization; however, data supporting their use in complex real-world populations remain limited. We aimed to evaluate the safety and efficacy of a DCB-first strategy in a predominantly acute coronary syndrome (ACS) and multivessel disease (MVD) population. Materials and Methods: We conducted a prospective two-center observational registry including 115 consecutive patients treated with a DCB-first strategy (DCB-only in 44 patients and a hybrid DCB–drug-eluting stent in 71 patients) for both de novo and in-stent coronary lesions. Bailout stenting was performed when required according to predefined criteria. Results: The study population was characterized by high clinical complexity, with 78.3% MVD and 67.8% presenting with ACS, including 10.5% ST-segment elevation myocardial infarctions. Bailout stenting was required in 12.2% of lesions. At 18 months, the target lesion revascularization (TLR) rate was 2.83%, while the device-oriented composite endpoint (DOCE; cardiac death, target vessel myocardial infarction or TLR) occurred in 4.7% of patients. The cumulative major adverse cardiovascular event (MACE) rate at 18 months was 14.8%, largely driven by the high-risk clinical profile of the cohort. Patients treated with a DCB-only strategy had a shorter duration of dual antiplatelet therapy compared with those treated with a hybrid strategy. Conclusions: In this two-center real-world registry including predominantly ACS and MVD patients, a DCB-first strategy was associated with low lesion-level event rates and acceptable mid-term clinical outcomes. These findings support the feasibility of a leave-nothing-behind approach in complex coronary disease when meticulous lesion preparation and provisional bailout stenting are applied. Full article
(This article belongs to the Section Cardiology)
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14 pages, 1422 KB  
Article
Preparing Nursing Students for Obstetric Emergencies: Effects of High-Fidelity Simulation on Knowledge, Confidence and Learning
by Marta Fernández Idiago, Juan Francisco Velarde-García, Oscar Arrogante, Ignacio Zaragoza-García, Beatriz Álvarez-Embarba, Victor Fernández-Alonso and Leticia López-Pedraza
Nurs. Rep. 2026, 16(4), 137; https://doi.org/10.3390/nursrep16040137 - 14 Apr 2026
Cited by 1 | Viewed by 898
Abstract
Background: Emergency obstetric situations require rapid clinical decision-making, technical competence, and emotional preparedness to ensure safe and compassionate care for both mother and newborn. However, nursing students often have limited opportunities to experience such high-risk, low-frequency events during clinical placements. Simulation-based education has [...] Read more.
Background: Emergency obstetric situations require rapid clinical decision-making, technical competence, and emotional preparedness to ensure safe and compassionate care for both mother and newborn. However, nursing students often have limited opportunities to experience such high-risk, low-frequency events during clinical placements. Simulation-based education has emerged as an effective strategy to prepare future nurses for caring in emergency contexts, allowing them to develop both technical and non-technical skills in a safe learning environment. This study aimed to evaluate the effects of a high-fidelity obstetric emergency simulation program on nursing students’ knowledge, perceived safety, and learning experience. Methods: A mixed-methods design was employed, combining a quasi-experimental pretest–posttest assessment without a control group and qualitative analysis of open-ended reflections. Eighty-two third-year nursing students participated in two simulation sessions addressing obstetric emergencies such as breech birth, shoulder dystocia, out-of-hospital delivery, eclampsia, postpartum hemorrhage, and maternal cardiac arrest. Data were collected using validated instruments measuring knowledge, perceived safety, and satisfaction and self-confidence in learning, and were analyzed using Wilcoxon signed-rank tests and thematic analysis. Results: Significant improvements were observed in specific knowledge areas related to complex obstetric maneuvers and in their perceived safety when managing emergency situations (p < 0.001, r > 0.40). Participants reported high levels of satisfaction and confidence in learning. Qualitative findings highlighted increased emotional preparedness, improved clinical reasoning, and recognition of the importance of teamwork and reflective debriefing in emergency care contexts. Conclusions: High-fidelity simulation appears to be an effective educational strategy for preparing nursing students to provide safe and confident care in obstetric emergencies. Integrating simulation into nursing curricula can strengthen both technical competence and the emotional readiness required for caring in urgent and high-pressure clinical situations. Full article
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28 pages, 1279 KB  
Review
Acute Contractile Effects of Glucagon-like-Peptide-1 Receptor Agonists in the Human Heart
by Joachim Neumann, Uwe Kirchhefer, Britt Hofmann and Ulrich Gergs
Pharmaceutics 2026, 18(4), 447; https://doi.org/10.3390/pharmaceutics18040447 - 6 Apr 2026
Viewed by 1272
Abstract
Glucagon-like-peptide-1 receptor (GLP-1R) agonists are under development as new drugs to treat type 2 diabetes, liver disease, obesity and cardiovascular diseases. Some of these drugs are solely agonists of the GLP-1R. It turned out that their benefit could be improved when they also [...] Read more.
Glucagon-like-peptide-1 receptor (GLP-1R) agonists are under development as new drugs to treat type 2 diabetes, liver disease, obesity and cardiovascular diseases. Some of these drugs are solely agonists of the GLP-1R. It turned out that their benefit could be improved when they also stimulated the glucagon receptor (GCGR) and/or the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR). Stimulation of GLP-1R in cell cultures but also in neonatal atrial and/or ventricular cardiomyocytes and adult atrial cardiomyocytes raised the activity of adenylyl cyclase and thus augmented the 3’,5’cyclic adenosine monophosphate (cAMP) levels. We discuss here the acute contractile effects of such agonists on isolated human atrial and ventricular cardiac preparations from failing and non-failing hearts. We address the receptors involved, GLP-1R expression in various cardiac regions of the human heart, single and multiple receptor agonists and the post-receptor signal transduction system of the GLP-1R in the human heart. Some of the new drugs addressed are still in the early phases of clinical development. We critically discuss the experimental and clinical data available and we also define research needs for experimental and clinical studies. Full article
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12 pages, 813 KB  
Article
Hemodynamic Effect of IgM-Enriched Immunoglobulin in the Early Stage of E. coli-Induced Experimental Sepsis
by Balázs Ujhelyi, Ádám Attila Mátrai, Mariann Berhés, Luca Panka Molnár, Ádám Deák, Zoltán Tóth, István László, Norbert Németh and Béla Fülesdi
J. Clin. Med. 2026, 15(4), 1522; https://doi.org/10.3390/jcm15041522 - 14 Feb 2026
Viewed by 581
Abstract
Background: Current sepsis guidelines recommend the best supportive treatment for severe sepsis, but they are limited on the effectiveness of immunomodulatory therapies. Recent data suggest that IgM-enriched immunoglobulin preparations may decrease mortality, but the exact pathomechanism remains unknown. The present experimental study aims [...] Read more.
Background: Current sepsis guidelines recommend the best supportive treatment for severe sepsis, but they are limited on the effectiveness of immunomodulatory therapies. Recent data suggest that IgM-enriched immunoglobulin preparations may decrease mortality, but the exact pathomechanism remains unknown. The present experimental study aims to test the hypothesis that IgM-enriched immunoglobulin may improve hemodynamics in E-coli-induced severe sepsis. Subjects and methods: Sepsis was induced in the E. coli bacteriemia (n = 8), E. coli-parallel Pentaglobin treatment (PR-PG; n = 8), and E. coli-delayed Pentaglobin treatment (D-PG; n = 8). Sepsis was induced in the sepsis, PR-PG, and D-PG groups by infusing 38 mL of an E. coli suspension (2.5 × 105/mL) over 3 h. The PR-PG group received a 0.75 g/kg Pentaglobin bolus over 20 min concurrently with the start of E. coli infusion. The D-PG group was given a 0.67 g/kg Pentaglobin bolus one hour after starting E. coli, followed by a continuous infusion at 0.02 g/kg/h for 240 min. Hemodynamic parameters were monitored every 2 h using a pulse contour cardiac output monitoring technique (PiCCo™). Results: Heart rate increased in all groups to varying extents. Mean arterial pressure (MAP) remained stable in controls but declined in untreated sepsis. Both Pentaglobin-treated groups showed higher MAP than untreated septic animals. Mild cardiac index increases occurred in controls and untreated sepsis, whereas the treated groups maintained a consistently elevated CI after Pentaglobin administration. Systemic vascular resistance index (SVRI) transiently increased in controls before normalizing, while untreated septic animals experienced continuous SVRI decline. Treated animals showed an initial transient SVRI rise followed by a decline; yet, SVRI remained higher than in untreated sepsis. Conclusions: IgM-enriched immunoglobulin led to a slight stabilization of some hemodynamic parameters, probably due to the reduced extpnfiravasation of fluids into the interstitium and, hence, had an effect on preload. Full article
(This article belongs to the Special Issue Sepsis: Current Updates and Perspectives)
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14 pages, 1446 KB  
Review
Infective Endocarditis and Complications; Surgical Indications and Management: An Integrative Review
by Daniel Bishev, Michael V. DiCaro, Shudipan Chakraborty, Gregory-Thomas Stanger, Camille Ho and Tahir Tak
J. Pers. Med. 2026, 16(2), 103; https://doi.org/10.3390/jpm16020103 - 9 Feb 2026
Viewed by 2515
Abstract
Infective endocarditis (IE) is an infection of the endocardial surface of the heart involving native or prosthetic valves, endocardial structures, or intracardiac devices/leads. Unfortunately, incidence has risen in many settings over recent years. Historically, the incidence has been about 3–10 cases for every [...] Read more.
Infective endocarditis (IE) is an infection of the endocardial surface of the heart involving native or prosthetic valves, endocardial structures, or intracardiac devices/leads. Unfortunately, incidence has risen in many settings over recent years. Historically, the incidence has been about 3–10 cases for every 100,000 person-years and was elevated to about 13.8 cases per 100,000 person-years in 2019. Despite advancements in both detection and treatment, mortality remains high, seen with inpatient mortality rates of 18%, along with a 6-month mortality rate of 30%. IE can be a fatal condition if left untreated, in part due to the multiple serious complications that can arise. By anticipating certain complications, clinicians can be better prepared to treat patients with this condition. This article provides an integrative review of the potential complications of IE. These complications vary depending on whether the patient has native or prosthetic valves. There are cardiac, embolic, and immune-complex mediated complications that can occur. Ultimately, IE can lead to multiorgan dysfunction and result in septic shock and disseminated intravascular coagulopathy (DIC). While the mainstay of treatment for IE remains medical, certain cases require surgical intervention. Due to their close relationship, a review of the indications for surgery in the treatment of IE is also presented in this article. By having a general scope of the complications of IE and when to get a surgical consult, clinicians can be better equipped to care for patients with a potentially fatal condition that is becoming increasingly more frequent. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
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24 pages, 884 KB  
Review
Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction
by Mikhail Blagonravov, Anastasia Sklifasovskaya, Ruslan Karpov, Vera Ovechkina, Sofya Andrianova, Sergey Syatkin, Vsevolod Belousov and Andrey Mozhaev
Biomedicines 2026, 14(2), 344; https://doi.org/10.3390/biomedicines14020344 - 2 Feb 2026
Viewed by 1125
Abstract
Mitochondria serve as an essential component in the maintenance of cardiac function, and targeting them may represent a promising approach to handling heart failure (HF). HF in this review refers to various etiologies, including ischemic cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy, unless otherwise [...] Read more.
Mitochondria serve as an essential component in the maintenance of cardiac function, and targeting them may represent a promising approach to handling heart failure (HF). HF in this review refers to various etiologies, including ischemic cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy, unless otherwise specified. Mitochondrial dysfunction, a distinctive feature of HF, leads to a progressive decrease in bioenergetic reserves due to switching of energy production from oxidation of fatty acids in mitochondria to glycolytic pathways. The main problem in developing methods to improve mitochondrial function lies in the fact that protein preparations injected through the bloodstream cannot enter cells through the plasma membrane. Modern gene therapy involving the delivery of missing genes to cells using adeno-associated virus (AAV) vectors has the potential to improve the function of cardiomyocytes (CMCs). This type of therapy aims to target proteins that have been lost, damaged, or altered due to pathological conditions in the myocardium. This review summarizes pathophysiological mechanisms associated with mitochondrial dysfunction, which is mainly caused by increased oxidative stress and impaired mitochondrial biodynamics under HF progression. It also addresses possible ways to modulate these processes using gene therapy. Special attention is paid to modern characteristics of AAVs that can be used as vectors for the efficient delivery of desired genes to CMCs. Full article
(This article belongs to the Section Gene and Cell Therapy)
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22 pages, 3191 KB  
Review
Airway Management in the ICU and Emergency Department in Resource-Limited Settings
by Sahil Kataria, Deven Juneja, Ravi Jain, Tonny Veenith and Prashant Nasa
Life 2026, 16(2), 195; https://doi.org/10.3390/life16020195 - 23 Jan 2026
Cited by 1 | Viewed by 2772
Abstract
Airway management is central to the care of critically ill patients, yet it remains one of the most challenging interventions in emergency departments and intensive care units. Patients often present with severe physiological instability, limited cardiopulmonary reserve, and high acuity, while clinicians often [...] Read more.
Airway management is central to the care of critically ill patients, yet it remains one of the most challenging interventions in emergency departments and intensive care units. Patients often present with severe physiological instability, limited cardiopulmonary reserve, and high acuity, while clinicians often work under constraints related to time for preparation, equipment availability, trained workforce, monitoring, and access to advanced rescue techniques. These challenges are particularly pronounced in low- and middle-income countries and other resource-limited or austere environments, where the margin for error is narrow and delays or repeated attempts in airway management may rapidly precipitate hypoxemia, hemodynamic collapse, or cardiac arrest. Although contemporary airway guidelines emphasize structured preparation and rescue pathways, many assume resources that are not consistently available in such settings. This narrative review discusses pragmatic, context-adapted strategies for airway management in constrained environments, with emphasis on physiology-first preparation, appropriate oxygenation and induction techniques, simplified rapid-sequence intubation, and the judicious use of basic airway adjuncts, supraglottic devices, and video laryngoscopy, where available. Adapted difficult airway algorithms, front-of-neck access in the absence of surgical backup, human factors, team training, and ethical considerations are also addressed. This review aims to support safer and effective airway management for critically ill patients in resource-limited emergency and intensive care settings. Full article
(This article belongs to the Special Issue Intensive Care Medicine: Current Concepts and Future Perspectives)
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16 pages, 2571 KB  
Article
A Nanoparticle-Based Strategy to Stabilize 5-Azacytidine and Preserve DNA Demethylation Activity in Human Cardiac Fibroblasts
by Kantaporn Kheawfu, Chuda Chittasupho, Sudarshan Singh, Siriporn Okonogi and Narainrit Karuna
Pharmaceutics 2026, 18(1), 88; https://doi.org/10.3390/pharmaceutics18010088 - 9 Jan 2026
Viewed by 1225
Abstract
Background: 5-Azacytidine (5-Aza) is a clinically important DNMT inhibitor with the potential to modulate cardiac remodeling by epigenetically reprogramming human cardiac fibroblasts (HCFs). However, its clinical utility is limited by rapid hydrolytic degradation. Nanoparticle (NP) encapsulation offers a strategy to mitigate this instability. [...] Read more.
Background: 5-Azacytidine (5-Aza) is a clinically important DNMT inhibitor with the potential to modulate cardiac remodeling by epigenetically reprogramming human cardiac fibroblasts (HCFs). However, its clinical utility is limited by rapid hydrolytic degradation. Nanoparticle (NP) encapsulation offers a strategy to mitigate this instability. This study evaluated the physical and chemical stability of free 5-Aza and 5-Aza-loaded lipid nanoparticles (5-Aza-NP) under different storage temperatures and examined their effects on DNA methylation-related gene expression in HCFs. Methods: Hyaluronic acid-stabilized lipid NPs were prepared using a solvent displacement method. Particle size, polydispersity index (PDI), and zeta potential were monitored over four days at −20 °C, 4 °C, and 30 °C. Chemical stability was assessed using HPLC and first-order kinetic modeling. Functional activity was evaluated by treating HCFs with free 5-Aza or 5-Aza-NP stored for 96 h and measuring DNMT1, DNMT3A, and DNMT3B expression by RT-qPCR. Results: 5-Aza-NP remained physically stable at 4 °C, while −20 °C induced aggregation and 30 °C caused thermal variability. Free 5-Aza degraded rapidly at 30 °C (6.56% remaining at 72 h), whereas 5-Aza-NP preserved 11.54%. Kinetic modeling confirmed first-order degradation, with consistently longer half-lives for the NP formulation. Functionally, 5-Aza–NP preserved its ability to suppress DNMT1 expression following 96 h of storage at 4 °C, whereas free 5-Aza showed reduced activity. In contrast, DNMT3A and DNMT3B levels remained low and unchanged across all treatments. Conclusions: NP encapsulation enhances the physicochemical stability of 5-Aza and preserves its DNMT1-inhibitory activity, while DNMT3A/B remain unaffected. These findings support NP-based delivery as a promising strategy to stabilize labile epigenetic drugs such as 5-Aza. Full article
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18 pages, 3675 KB  
Article
Highly Sensitive Biosensor for the Detection of Cardiac Troponin I in Serum via Surface Plasmon Resonance on Polymeric Optical Fiber Functionalized with Castor Oil-Derived Molecularly Imprinted Nanoparticles
by Alice Marinangeli, Pinar Cakir Hatir, Mustafa Baris Yagci and Alessandra Maria Bossi
Biosensors 2026, 16(1), 12; https://doi.org/10.3390/bios16010012 - 23 Dec 2025
Cited by 3 | Viewed by 1390
Abstract
In this work, we report the development of a highly sensitive optical sensor for the detection of cardiac troponin I (cTnI), a key biomarker for early-stage myocardial infarction diagnosis. The sensor combines castor oil-derived biomimetic receptors, called GreenNanoMIPs and prepared via the molecular [...] Read more.
In this work, we report the development of a highly sensitive optical sensor for the detection of cardiac troponin I (cTnI), a key biomarker for early-stage myocardial infarction diagnosis. The sensor combines castor oil-derived biomimetic receptors, called GreenNanoMIPs and prepared via the molecular imprinting technology using as a template an epitope of cTnI (i.e., the NR10 peptide), with a portable multimode plastic optical fiber surface plasmon resonance (POF-SPR) transducer. For sensing, gold SPR chips were functionalized with GreenNanoMIPs as proven by refractive index changes and confirmed by means of XPS. Binding experiments demonstrated the cTnI_nanoMIP-SPR sensor’s ability to detect both the NR10 peptide epitope and the full-length cTnI protein within minutes (t = 10 min), with high sensitivity and selectivity in buffer and serum matrices. The cTnI_nanoMIP-SPR showed an LOD of 3.53 × 10−15 M, with a linearity range of 1 pM–100 pM, outperforming previously reported sensor platforms and making it a promising tool for early-stage myocardial infarction detection. Full article
(This article belongs to the Section Optical and Photonic Biosensors)
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27 pages, 4806 KB  
Article
Contractile Effects of Glucagon in Mouse Cardiac Preparations
by Joachim Neumann, Franziska Schmidt, Pauline Braekow, Uwe Kirchhefer, Jan Klimas, Katarina Hadova and Ulrich Gergs
Int. J. Mol. Sci. 2026, 27(1), 126; https://doi.org/10.3390/ijms27010126 - 22 Dec 2025
Viewed by 740
Abstract
Glucagon is an endogenous peptide that is produced in the pancreas. Via glucagon receptors, glucagon increases the beating rate in cultured rat neonatal cardiomyocytes and also in isolated right atrial preparations from adult rats. Moreover, in living adult mice, injections of glucagon can [...] Read more.
Glucagon is an endogenous peptide that is produced in the pancreas. Via glucagon receptors, glucagon increases the beating rate in cultured rat neonatal cardiomyocytes and also in isolated right atrial preparations from adult rats. Moreover, in living adult mice, injections of glucagon can elevate the heart rate. It is unknown whether these effects of glucagon in living adult mice are mediated via central glucagon receptors or via a direct effect on cardiac glucagon receptors. Thus, we tested the hypothesis that glucagon can exert a direct positive chronotropic effect in the adult mouse heart. We measured the contractile effects of cumulatively increasing concentrations of glucagon (0.1–100 nM) in isolated paced (1 Hz) left atrial preparations, in isolated spontaneously beating right atrial preparations and in isolated spontaneously beating retrogradely perfused whole hearts. We detected in isolated right atrial preparations time- and concentration-dependent positive chronotropic effects of glucagon that were reversed by the glucagon receptor antagonists SC203972 and desglucagon. The positive chronotropic effects of glucagon were also attenuated by 1 µM of ivabradine, an inhibitor of the hyperpolarization-activated cation channels (HCN), but not by 100 nM rolipram, a phosphodiesterase 4 inhibitor, nor by 10 µM of propranolol, a β-adrenoceptor antagonist. Moreover, the positive chronotropic effects of glucagon were also attenuated by stimulation of the A1-adenosine receptor or muscarinic receptors. Glucagon decreased the force of contraction in right atrial preparations. In left atrial preparations, glucagon failed to alter the force of contraction. In isolated adult mouse hearts perfused in the Langendorff mode, 10 nM of glucagon increased the beating rate and reduced left ventricular force of contraction. The gene expression of the glucagon receptors was lowest in the left atrium, higher in the ventricle and highest in the right atrium of adult mice. In summary, glucagon exerted a positive chronotropic effect in the mouse heart via glucagon receptors, mediated, at least in part, via HCN channels in the sinus node. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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14 pages, 398 KB  
Article
Improving Accuracy in Cardiopulmonary Resuscitation Training: Results on Undergraduate Nursing School Students’ with OMNI2 Simulator
by Fani Alevrogianni, Anna Korompeli, Christos Triantafyllou, Theodoros Katsoulas, Panagiotis Koulouvaris and Pavlos Myrianthefs
Int. Med. Educ. 2025, 4(4), 51; https://doi.org/10.3390/ime4040051 - 25 Nov 2025
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Abstract
Cardiopulmonary resuscitation (CPR) is a vital skill for healthcare professionals, crucial in life-saving situations. More than 80% of cardiac arrest cases occur out of hospital. As the demand for competent CPR practitioners grows, the effectiveness of training methods becomes increasingly important, especially for [...] Read more.
Cardiopulmonary resuscitation (CPR) is a vital skill for healthcare professionals, crucial in life-saving situations. More than 80% of cardiac arrest cases occur out of hospital. As the demand for competent CPR practitioners grows, the effectiveness of training methods becomes increasingly important, especially for undergraduate students preparing to enter the healthcare field. The primary objective of our study is to investigate the effectiveness of simulation-based teaching methods and by integrating innovative technologies, such as the OMNI2 simulator, to enhance practitioners’ performance and to improve the precision and objectivity of CPR instruction. A cohort of 144 undergraduate students from the Nursing School Department of the National Kapodistrian University of Athens participated in an 8 h Basic Life Support Seminar. It consisted of a 5 h theoretical instruction followed by 3 h of practical training using the OMNI2 simulator. Each student was tasked to identify cardiac arrest and to perform two cycles of CPR according to the 2021 guidelines. Metrics, including total session time, cycles performed, compression-to-ventilation ratio, compression depth, compressions and ventilations per minute, full recoil, peak inspiratory pressure, and ventilation duration, were measured and compared against the simulator’s preset targets. Statistically significant differences (p < 0.05) were observed for all outcomes. In conclusion, while simulation-based teaching has conventionally been proven effective for CPR proficiency, real-time data collected in this study reveal a disparity between anticipated and actual performance. Our research underscores the necessity of refining instructional methods to enhance skill acquisition, potentially leading to improved patient outcomes in the future. Full article
(This article belongs to the Special Issue New Advancements in Medical Education)
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