Search Results (572)

Background/Objectives: Evaluating noninvasive, accessible ocular and blood-based biomarkers could aid in early risk stratification and disease detection during the preclinical phase of Alzheimer’s disease. This study investigates associations between plasma biomarkers of neurodegeneration and retinal structural and microvasculature parameters in cognitively normal adults with familial or genetic risk factors for Alzheimer’s disease. Methods: Forty-one participants underwent plasma sampling for glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid-beta42 (β42), amyloid-β42/40 ratio, and phosphorylated-tau217 (p-tau217), and also underwent optical coherence tomography (OCT) and OCT angiography (OCTA) imaging. Apolipoprotein E genotyping and family history of Alzheimer’s disease were recorded. Generalized estimating equations adjusting for age, sex, race, treated hypertension, Alzheimer’s disease family history, and APOE ε4 carrier status assessed associations between plasma biomarker concentrations and OCT and OCTA measurements. Results: Higher plasma GFAP and NfL concentrations were significantly associated with reduced superficial capillary plexus perfusion density and vessel density on macular OCTA. In additional analyses restricted to participants with plasma biomarker and retinal imaging assessments obtained within 9 months, associations with GFAP remained significant, whereas NfL associations no longer remained significant after correction for multiple comparisons. Conclusions: Retinal OCTA and OCT metrics may reflect general neurovascular aging in cognitively normal individuals with familial or genetic risk factors for Alzheimer’s disease. Full article

Regional citrate anticoagulation (RCA) is the preferred anticoagulation strategy for continuous kidney replacement therapy (CKRT) because it prolongs circuit lifespan while reducing bleeding complications compared with systemic heparin. Although generally safe, systemic citrate accumulation remains the principal metabolic complication of RCA and occurs when citrate delivery exceeds the combined metabolic and extracorporeal capacity for citrate elimination. This narrative review summarizes current evidence regarding citrate metabolism, the pathophysiological mechanisms of citrate accumulation, associated risk factors, biochemical diagnosis, monitoring strategies, and therapeutic management. Citrate metabolism depends predominantly on mitochondrial oxidative capacity rather than hepatic function alone, making circulatory shock and impaired tissue perfusion the principal determinants of citrate intolerance, whereas isolated liver dysfunction is often well tolerated. Systemic citrate accumulation is characterized by a distinctive biochemical profile including ionized hypocalcemia, an increased total-to-ionized calcium ratio, escalating calcium infusion requirements, high anion-gap metabolic acidosis, and frequently hyperlactatemia, while overt clinical manifestations usually occur late. Consequently, early recognition relies on structured biochemical monitoring and interpretation of serial trends rather than isolated measurements. Management should focus on restoring the balance between citrate delivery and citrate elimination by reducing citrate exposure when appropriate, optimizing extracorporeal citrate removal, correcting metabolic abnormalities, and improving tissue perfusion. Contemporary RCA practice should therefore emphasize individualized physiological assessment and integrated biochemical monitoring to facilitate early recognition, prevent progression to overt toxicity, and preserve the well-established safety and efficacy of RCA. Full article

Background/Objectives: Femoro-femoral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is associated with limb ischemic complications. Routine near-infrared spectroscopy (NIRS) monitoring and a more standardized distal perfusion strategy were introduced at our institution in 2016. We compared ischemia-related interventions, amputations, and early mortality between the treatment eras. Methods: Consecutive patients undergoing femoro-femoral VA-ECMO from 2012 to 2024 were analyzed retrospectively and stratified by VA-ECMO initiation before 2016 or from 2016 onward. The primary endpoint was a peripheral ischemic vascular complication requiring surgical or interventional therapy; an inclusive sensitivity definition additionally incorporated four clinically plausible but less certain events. Period-specific rates were estimated using Poisson regression adjusted for baseline distal perfusion cannula (DPC) status and extracorporeal cardiopulmonary resuscitation (eCPR). Results: The analytic cohort comprised 270 patients (45 pre-2016 and 225 post-2016). The primary endpoint occurred in 50 patients (18.5%, 95% confidence interval (CI) 14.1–23.7): 3/45 (6.7%, 95% CI 1.4–18.3) before 2016 and 47/225 (20.9%, 95% CI 15.8–26.8) thereafter. Adjusted rates were 4.6% (95% CI 1.0–20.5) and 18.9% (95% CI 13.6–26.3), with an adjusted risk ratio of 4.11 (95% CI 1.06–17.93). The inclusive sensitivity analysis yielded similar estimates (adjusted risk ratio 3.31, 95% CI 1.05–11.47). Five patients underwent lower-limb amputation (1/45 pre-2016 and 4/225 post-2016). Kaplan–Meier 30-day mortality estimates were 56.8% overall (95% CI 50.8–62.9), 58.9% pre-2016 (95% CI 44.9–73.5), and 56.4% post-2016 (95% CI 49.9–63.1). Conclusions: Ischemia-related interventions were more frequently recorded after 2016, while amputations remained rare and 30-day mortality was similar. Because monitoring, DPC practice, and other aspects of care changed concurrently, and NIRS was used without a standardized trigger algorithm, the reasons for the observed era difference cannot be determined. The findings are exploratory and do not establish causal effects of NIRS or DPC use. Full article

Background/Objectives: Endovascular thrombectomy (EVT) has transformed the treatment of acute ischaemic stroke due to large-vessel occlusion, yet peri-procedural haemodynamic instability may compromise penumbral perfusion and neurological recovery. We assessed the frequency, determinants and clinical consequences of post-procedural hypotension after EVT. Methods: We retrospectively reviewed 201 consecutive adults who underwent endovascular thrombectomy for anterior-circulation large-vessel occlusion at a single tertiary centre over a period of eight years, from 1 January 2017 to 31 January 2025. Post-procedural hypotension was defined as hypotension requiring initiation of a continuous noradrenaline infusion within 24 h of the procedure. Comorbidities, anaesthetic modality (general anaesthesia [GA] or conscious sedation [CS]), National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores, and in-hospital mortality were recorded. Logistic regression identified independent predictors of hypotension. Results: Fifty-five patients (27.4%) developed post-procedural hypotension. They presented with more severe strokes (NIHSS 16.0 ± 5.0 vs. 13.7 ± 5.0; p = 0.002), had higher NIHSS scores at day 2 (14.0 ± 6.9 vs. 9.4 ± 6.7; p < 0.001) and day 7 (p = 0.003), and displayed markedly higher in-hospital mortality (50.9% vs. 20.5%; p < 0.001). In an ordinal analysis of the day 7 modified Rankin Scale with death coded as 6, hypotension was associated with a shift towards greater disability (common OR 2.57, 95% CI 1.40–4.72; p = 0.002). In an exploratory model, each additional 10 min of door-to-groin time was independently associated with hypotension (adjusted OR 1.10, 95% CI 1.03–1.18; p = 0.003). Independent predictors of hypotension were baseline NIHSS (adjusted OR 1.11 per point, 95% CI 1.04–1.19; p = 0.003) and active malignancy (adjusted OR 2.90, 95% CI 1.04–8.09; p = 0.042). Hypotension occurred with similar frequency under GA and CS (28.6% vs. 24.6%; adjusted OR 1.12, 95% CI 0.54–2.34; p = 0.766). Conclusions: Post-EVT hypotension is common and associated with poorer early neurological recovery and a more than two-fold higher in-hospital mortality rate. Its independent predictors were baseline stroke severity and active malignancy. Patients with severe stroke or active cancer may warrant intensified haemodynamic surveillance after thrombectomy. Procedural delay emerged as the only modifiable predictor identified and warrants prospective evaluation. Full article

Background and Objectives: Normothermic regional perfusion (NRP) is an effective technique to improve recipient outcomes. However, no valid methods for determining liver viability exist. Identifying relevant biological markers with clinical correlation to liver viability and recipient clinical outcomes is imperative to improve decision-making. Materials and Methods: Fifty-four donors undergoing NRP and their recipients were included. FMN was measured at the start, 1 h, and end of NRP. Lactate was measured at the start, 30, 60, and 90 min of NRP. Primary outcomes were early allograft function using the early allograft dysfunction (EAD) criteria and the model for early allograft function (MEAF). Secondary outcomes included the association with donor warm ischemia time (DWIT), stratified by 30 min. Spearman’s rho assessed correlations. Results: Forty (74%) livers were transplanted, with 5 (12.5%) recipients developing EAD and the mean MEAF score was 3.13 (1.49). FMN at all time points was significantly greater in the EAD group compared to the non-EAD group and was significantly correlated with the MEAF score (Peak FMN: rho = 0.507, p = 0.001). FMN during perfusion did not differ between DWIT < and ≥30 min. Lactate levels were similar across all groups and did not discriminate for adverse allograft outcomes. However, lactate levels during perfusion were higher in the DWIT ≥ 30 min group. Conclusions: These findings suggest that during NRP, elevated FMN, but not lactate, is associated with early allograft function. Full article

Background: Norepinephrine is commonly used during acute burn resuscitation to maintain adequate perfusion pressure. However, its effects, together with the burn-induced catecholamine surge, on arterial α₁-adrenergic receptors (α₁-AR) remain unclear. This study examined whether burn injury and continuous norepinephrine infusion alter arterial α₁-AR subtype expression at the transcriptional and protein levels. Methods: Sprague–Dawley rats were randomized to full-thickness scald burn involving 25% total body surface area with continuous intravenous norepinephrine or sodium chloride (NaCl) infusion, sham injury with norepinephrine infusion, or untreated controls. Mean arterial pressure (MAP) was measured at baseline and before euthanasia (six or 24 h). Aorta, carotid, and renal arteries were collected for analysis of α₁-AR subtypes (Adra1a, Adra1b, and Adra1d) using quantitative PCR (qPCR) and immunohistochemistry (IHC). Results: Norepinephrine efficiently increased MAP in sham animals. In burned animals with norepinephrine, MAP increased at six hours (+10.6 mmHg) but fell below baseline at 24 h (−6.4 mmHg). Burned animals given NaCl had persistently lower MAP than those given norepinephrine, at six hours (−19.1 mmHg) and 24 h (−21.1 mmHg). qPCR demonstrated significant downregulation of Adra1b in the renal artery across all groups compared to control (7.8–16.4-fold, p < 0.001). Overall, changes in protein expression across different vascular beds and receptor subtypes were inconsistent. Conclusions: Norepinephrine increased MAP in both sham and burned animals, confirming the drug’s efficacy. Burn injury and sustained norepinephrine exposure were associated with early, vessel-specific alterations in α₁-AR mRNA expression. The absence of consistent protein-level changes within 24 h suggests a delay in receptor expression on protein level. Full article

Thoracoabdominal aortic aneurysm (TAAA) is a complex vascular disorder involving both thoracic and abdominal segments of the aorta and remains associated with substantial morbidity and mortality. One of the most serious complications after thoracoabdominal aortic aneurysm (TAAA) repair is spinal cord ischemia (SCI), which may progress to spinal cord infarction and result in irreversible neurologic deficits including paraplegia, neurogenic bladder dysfunction, and bowel dysfunction. The incidence of SCI after TAAA repair varies with the extent of aneurysmal involvement, operative duration, and patient comorbidities. The primary pathophysiologic mechanism involves interruption of radiculomedullary arterial flow, compounded by systemic hypotension and limited collateral circulation. Because SCI profoundly affects functional recovery and long-term quality of life, prevention and early recognition are central to perioperative management. Established neuroprotective strategies emphasize maintenance of spinal cord perfusion through meticulous hemodynamic optimization, cerebrospinal fluid (CSF) drainage, and temperature modulation. Intraoperative neuromonitoring using motor and somatosensory-evoked potential facilitates early detection, while newer modalities such as near-infrared spectroscopy and CSF lactate monitoring may offer additional insight. When SCI occurs despite prophylaxis, rapid initiation of rescue measures including CSF drainage, hemodynamic augmentation, and other discussed treatments may improve neurologic outcomes. Long-term care focuses on rehabilitation, symptom management, and psychological support. Therefore, this review aims to consolidate medical evidence to improve the prevention, detection, and treatment of spinal cord infarction associated with thoracoabdominal aortic aneurysm repair. Full article

A comprehensive assessment of allograft quality is essential for predicting successful transplantation and graft survival. Elevated levels of flavin mononucleotide (FMN) in perfusate obtained during hypothermic oxygenated perfusion (HOPE) may serve as a promising predictor of early graft dysfunction and post-transplant complications. The aim of this study was to evaluate the feasibility of applying an FMN determination method to HTK-based perfusion solutions used during liver machine perfusion. The spectrofluorimetric method for FMN determination in modified HTK perfusion solution (modHTK) was evaluated for the following parameters: linearity, accuracy, repeatability, reproducibility, and stability. The study demonstrated the suitability of the quantitative FMN determination method for modHTK solution used during HOPE of liver grafts. Full article

Clinical Rationale and Objectives: Refractory out-of-hospital cardiac arrest (OHCA) is associated with very poor outcomes when treated with conventional cardiopulmonary resuscitation alone, particularly when low-flow time is prolonged. Prehospital extracorporeal cardiopulmonary resuscitation (ECPR) may shorten the interval to extracorporeal perfusion, but its implementation requires a highly standardized operational framework to ensure appropriate patient selection, procedural safety, and efficient use of specialized resources. This manuscript describes the PrehospECPR-GOKVI operational framework, a standardized prehospital ECPR protocol developed by the Gottsegen National Cardiovascular Center in cooperation with the Hungarian National Ambulance Service and the Hungarian Air Ambulance. ECPR Pathway: The programme is based on a dedicated two-person ECPR team, consisting of an experienced physician and a paramedic, deployed with mobile ECPR-specific equipment, including point-of-care ultrasound, a pre-primed VA-ECMO circuit, an ECMO console, and a mobile oxygenator/gas blender. The protocol defines strict inclusion and exclusion criteria, emphasizing witnessed OHCA, age below or apparently below 50 years, initial shockable rhythm or selected pulseless electrical activity with suspected pulmonary embolism, refractory cardiac arrest lasting at least 15 min, no-flow time below 5 min or signs of life, and the feasibility of establishing ECMO flow within 60 min from collapse or emergency call. Two mandatory sonographic STOP criteria are incorporated before cannulation: relevant pericardial effusion or suspected aortic dissection, and inability to safely visualize the femoral artery, femoral vein, and bifurcation. The operational workflow further specifies dispatch activation, ALS continuation, equipment layout, ultrasound-guided femoro-femoral cannulation, failed-access management, air-free circuit connection, post-flow stabilization, receiving-centre notification, and transport to GOKVI. A target interval of no more than 15 min from initiation of ECPR-specific steps to ECMO flow is mandated. Conclusions: The PrehospECPR-GOKVI framework describes a locally developed, standardized operational pathway intended to support early identification, safe procedural preparation, and structured delivery of prehospital ECPR for selected patients with refractory OHCA. The protocol is designed to reduce avoidable delays, standardize ALS–ECPR coordination, and incorporate predefined sonographic safety checkpoints before cannulation. As no patient-level data are reported in this manuscript, feasibility, safety, complication rates, survival, neurological outcomes, resource utilization, and transferability remain to be evaluated prospectively after programme launch. Full article

Background/Objectives: In glioma patients, acute neurologic deterioration may reflect nonconvulsive status epilepticus (NCSE), peri-ictal pseudoprogression, treatment-related change, or true progression. As these entities share imaging features, misdiagnosis can delay therapy. This review synthesizes evidence relevant to a proposed electroclinical-imaging framework for distinguishing seizure-related deterioration from treatment-related change and true progression. Methods: This narrative review synthesized English-language literature on tumor-related epilepsy, NCSE, peri-ictal imaging abnormalities, pseudoprogression, radiation necrosis, Response Assessment in Neuro-Oncology (RANO) criteria, and advanced imaging in adult diffuse glioma. Results: Seizure recurrence after glioma treatment may indicate tumor activity, but it may also reflect radiation injury, postoperative gliosis, edema, metabolic disturbance, medication effects, or transient peri-ictal change. NCSE is particularly important because it may present with aphasia, confusion, impaired consciousness, behavioral change, or deficits without convulsions, making electroencephalography central for unexplained deterioration. Seizure activity can also produce transient magnetic resonance imaging (MRI) or positron emission tomography (PET) abnormalities, including enhancement, fluid-attenuated inversion recovery (FLAIR) hyperintensity, diffusion restriction, and perfusion changes that mimic recurrence. Conclusions: This review proposes a structured electroclinical-imaging framework incorporating early EEG, seizure history, treatment timing, corticosteroid and antiseizure response, multimodal imaging, and longitudinal reassessment for prospective evaluation in treated glioma patients with new neurologic decline. Full article

Contemporary intensive care operates in an environment with high-complexity cases, large volumes of information, and vast physiological, biological, and therapeutic data, collected from laboratory results, investigations, and therapies for organ support, as well as from systems that operate in parallel. The lack of interoperability contributes to information overload, alarm fatigue, and delayed decision-making. The Smart ICU concept has been developed to address these limitations by integrating medical devices, information systems, and artificial intelligence into a unified system that allows interoperable data integration and predictive analytics. Aim: The purpose of this article is to provide a narrative review of the Smart ICU concept, with a specific focus on the cardiac intensive care unit. It summarizes Smart ICU architecture, data integration, clinical support, and applicability in monitoring perioperative inflammation in cardiac surgery. We describe the Smart ICU architecture, from data acquisition to storage and analytics, highlighting the differences between Smart ICU, artificial intelligence, and Tele-ICU, and we underline predictive analytics as a supportive tool, as well as its influence on clinical outcomes. Cardiac ICU application: Cardiac ICUs offer a data-dense, temporally well-defined model following cardiac surgery with cardiopulmonary bypass, where data concerning patients’ hemodynamics, perfusion data, and biological and inflammatory markers intertwine. Cardiac Smart ICU models could recognize early signs of hemodynamic compromise and low cardiac output states and identify early indicators of post-cardiac surgery complications. Neutrophil activation and complete blood count-derived indices may be used as dynamic biological data for Smart Cardiac ICU models. Conclusion: The Smart Cardiac ICU may support earlier risk stratification, and therefore earlier diagnostic and therapeutic interventions, but its clinical value requires prospective, multicenter validation. Cardiopulmonary bypass-induced inflammation may offer an ideal setting to integrate physiological, procedural, and immunological data into bedside predictive models. Full article

Background and Clinical Significance: Renal disease is the leading cause of secondary hypertension in children and adolescents. Among younger patients presenting with severe hypertension, renovascular and renal parenchymal disorders should be considered promptly; Case presentation: We describe the case of a 16-year-old male who presented with severe fatigue and was found to have resistant arterial hypertension (180/120 mmHg). His medical history was notable for blunt epigastric trauma sustained during football training approximately 6 months before presentation. Magnetic resonance imaging of the kidneys and retroperitoneum demonstrated a large right-sided perinephric hematoma compressing the kidney. Plasma renin activity and aldosterone levels were markedly elevated, establishing the diagnosis of Page kidney. Percutaneous drainage was performed by placement of a drainage catheter into the perinephric collection, resulting in evacuation of a substantial volume of liquefied hematoma. Following the procedure, arterial blood pressure gradually normalized, accompanied by resolution of the hormonal abnormalities; Conclusions: Page kidney is a rare but important cause of secondary hypertension resulting from activation of the renin-angiotensin-aldosterone system due to external renal compression and impaired intrarenal perfusion. Although its clinical presentation may be insidious, delayed recognition can lead to severe cardiovascular and renal complications. Management includes percutaneous drainage or surgical decortication of the affected kidney, together with antihypertensive treatment targeting the renin-angiotensin-aldosterone system. Early diagnosis and treatment are essential to optimize clinical outcomes and preserve renal function. Full article

Background/Objectives:This study aimed to evaluate whether early renal perfusion scintigraphy is associated with sepsis severity and short-term mortality in an experimental polymicrobial sepsis model. Methods: A total of 90 female Wistar albino rats were divided into Control, mild sepsis, and severe sepsis groups using a cecal ligation and puncture (CLP) model. Renal perfusion was evaluated 5 h after sepsis induction using technetium-99m-labeled erythrocyte scintigraphy, expressed as the kidney-to-aorta (R/A) activity ratio. Survival was monitored for 5 days. Histopathological and biochemical analyses were also performed. Results: The kidney-to-aorta (R/A) activity ratio decreased progressively with increasing sepsis severity (all p < 0.001). Kaplan–Meier analysis demonstrated significantly reduced survival in septic animals (log-rank p < 0.001). The R/A ratio showed high discrimination for 5-day mortality (AUC = 0.944, 95% CI 0.902–0.986; p < 0.001). Univariable Cox proportional hazards analysis demonstrated that a lower R/A ratio was significantly associated with an increased hazard of death (HR = 0.005, 95% CI 0.001–0.036; p < 0.001). Histopathological injury scores and biochemical markers (TNF-α, VEGF, STAT3, NGAL, BUN, creatinine, and MDA) increased significantly with sepsis severity. Conclusions: Early Tc-99m-labeled erythrocyte renal perfusion scintigraphy was associated with sepsis severity and short-term mortality in experimental polymicrobial sepsis. These findings support further investigation of this imaging approach as an experimental marker of sepsis severity and outcome; however, external validation is required before clinical translation. Full article

Oral submucous fibrosis (OSMF) is a chronic, progressive fibrotic disorder with significant malignant potential, and limited effective treatments due to an incomplete understanding of its underlying molecular mechanisms. This narrative review synthesizes current evidence on the key molecular networks involved in OSMF pathogenesis, highlighting the central role of the TGF-β1/Smad, CTGF, and COL1A1 pathways in maintaining fibroblast activation, supporting myofibroblast activity, and promoting pathological collagen accumulation. It also integrates recent findings on how profibrotic signaling interacts with important angiogenic and epithelial growth factors such as VEGF, FGF, and EGF, creating a stage-dependent fibrotic microenvironment. In early OSMF, increased angiogenic signaling, especially through the VEGF/PI3K–Akt pathway, helps maintain blood supply. However, as the disease progresses, TGF-β-induced pathways become dominant, leading to vascular rarefaction, tissue hypoxia, epithelial instability and worsening fibrosis that increases the risk of malignant transformation. By critically appraising molecular, cellular, and translational studies, this review identifies key pathways linking fibrosis, angiogenesis, and epithelial changes in OSMF. It suggests that stage-specific and combined targeting of TGF-β1, CTGF, COL1A1, along with angiogenic and epithelial pathways, may help reverse fibrosis, restore normal tissue perfusion, reduce cancer risk, and support the development of better therapies and biomarkers beyond symptom relief. Full article

Background and Objectives: Arterial hypertension is a major cause of systemic microvascular damage involving target organs such as the kidneys and retina. Because the retinal and renal microcirculations share common pathogenic mechanisms, retinal imaging may provide non-invasive biomarkers of hypertensive microvascular injury. This study investigated the association between the renal resistive index (RRI), systemic oxidative stress biomarkers, and retinal abnormalities in patients with essential hypertension. Retinal structural and microvascular parameters were evaluated using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Materials and Methods: In this cross-sectional exploratory study, 32 patients with essential hypertension (64 eyes) underwent comprehensive ophthalmic examination, OCT/OCTA imaging, renal Doppler ultrasonography for RRI assessment, and evaluation of systemic oxidative stress biomarkers. Associations between renal, ocular, and biochemical parameters were analyzed. Results: No significant differences were observed in most global OCT/OCTA parameters. However, higher RRI values were associated with localized macular thinning and reduced optic nerve head perfusion metrics. Patients with RRI values ≥ the 75th percentile showed significantly increased hydrogen peroxide levels (p = 0.004) and reduced nitric oxide bioavailability (p = 0.033), together with thinning of selected inner macular sectors. A trend toward reduced optic nerve head flow index was also observed, suggesting early microvascular impairment that may not be detected by conventional global OCT measurements. Conclusions: These exploratory findings suggest a possible association among increased renal vascular resistance, oxidative stress, and localized retinal structural alterations in patients with essential hypertension. The coexistence of systemic redox imbalance and sectorial retinal changes supports the hypothesis of an eye–kidney–redox interplay and indicates that advanced retinal imaging, particularly detailed sectorial OCT analysis, may represent a complementary non-invasive tool for the early detection of subclinical microvascular damage. Larger prospective studies are warranted to validate these findings. Full article