Search Results (181)

Ischemic–reperfusion injury represents an extremely serious problem in the human population. It mainly affects the elderly population and currently used treatments have poor results. However, in nature there is a much more effective and relatively well-studied mechanism known as the ischemic tolerance phenomenon. If an organism is exposed to adverse conditions that do not destroy it, it responds by producing substances capable of protecting it from severe damage or death in the event of a repeated encounter with the same or a different dangerous environment. The problem with its use in the clinic is that its effectiveness decreases in the elderly and is practically lost with associated diseases and their concurrent treatment. Based on experimental animal studies and findings, it can be assumed that the activation of full tolerance—through successive exposure to two stressors in young, healthy individuals—will result in the formation of effectors of tolerance, which are spread throughout the body through the blood. Blood plasma thus activated and administered to a recipient who is unable to otherwise acquire tolerance, should be used as an immediate treatment for ischemia–reperfusion injury and a wide range of impending injuries in all individuals, since activated plasma contains effectors of ischemic tolerance. The purpose of this work is to show the possibilities of using ischemic tolerance in the clinical practice. Complete tolerance can be transferred from young, healthy, unmedicated donors to patients who have lost their ability to build tolerance in their own bodies. Full article

Background: Metabolic acidosis is a frequent and serious complication in critically ill neonates, particularly preterm infants, and is associated with an increased risk of mortality, intraventricular hemorrhage, and long-term neurodevelopmental impairment. Despite limited evidence, sodium bicarbonate (SB) is widely administered in neonatal intensive care units (NICUs) to correct acidosis, largely extrapolated from adult and pediatric practice. However, concerns have been raised about its potential adverse effects, including paradoxical intracellular acidosis, impaired cerebral autoregulation, and increased risk of neurological injury. Given the uncertainty regarding both its efficacy and safety, we conducted a systematic review and meta-analysis to evaluate the role of SB administration in the neonatal population. Methods: MEDLINE, Scopus, and the Cochrane Library were searched using specific medical subject headings and terms. We included all study published up to July 2025 that involved newborns treated with SB. The primary outcome was positive response to treatment, while secondary outcomes included mortality, morbidity, and long-term impairment. Results: We analyzed 10 studies (9 randomized and 1 unrandomized study, including 660 neonates). Pooled results from the randomized controlled studies showed no efficacy of SB in newborns. Data from one unrandomized study showed an increased risk for mortality (OR 13.1 p = 0.02), clinical seizures (OR 2.8, p = 0.01), and a combined outcome of death or neurological damage (OR 3.1 p < 0.01) for neonates treated with SB. Conclusions: Current evidence is insufficient to support the routine administration of SB in NICUs. Neonatologists have the responsibility to administer only drugs of proven efficacy, personalizing therapy on the basis of a pathology’s etiology, in order to reduce risk and optimize benefits. In the absence of robust, statistically significant data, the indiscriminate use of SB should be discouraged in current clinical practice. PROSPERO registration number: CRD420251132502. Full article

Brain damage caused by hypoxia-ischemia is a serious complication for a newborn with possible life-long sequelae. To develop targeted neuroprotective strategies, it is essential to understand the mechanisms of injury, particularly the role of microglial phagocytosis, which may contribute to neuronal loss after hypoxia-ischemia. The aim was to evaluate neuronal cell death by phagocytosis in neonatal hypoxia-ischemia by investigating key signaling molecules and the effect of gene deletion of the phagocytic receptor Myeloid-epithelial-reproductive tyrosine kinase (MerTK) in a neonatal mouse model. MerTK, growth arrest–specific 6, and genes related to phagoptosis were regulated in the brain 6–72 h after hypoxic ischemia. Brain injury was reduced in MerTK knock-out vs. wild-type mice by 48% in gray matter (p = 0.002) and by 32% in white matter (p = 0.04). There was a near 40% reduction in NeuN immunoreactivity in microglia in MerTK knock-out mice vs. wild-type (p = 0.03) indicating attenuation of neuronal phagocytosis by microglia. In summary, the reduction in microglial neuronal engulfment and brain injury in MerTK-deficient mice strongly indicates that phagoptosis contributes to neuronal loss after neonatal hypoxia-ischemia. This insight suggests that targeting MerTK-mediated phagocytosis may represent a potential therapeutic approach in neonatal hypoxia-ischemic brain injury. Full article

Anabolic–androgenic steroids (AAS) are synthetic derivatives of testosterone that are used therapeutically but are frequently abused by athletes and individuals seeking to increase muscle mass. Their anabolic (promoting muscle growth) and androgenic (inducing masculine characteristics) effects result from androgen receptor activation in target tissues. However, chronic supraphysiological AAS exposure is associated with serious cardiovascular consequences, ranging from hypertension and lipid disorders to cardiomyopathy, atherosclerosis, and sudden cardiac death. This review provides an updated and integrative perspective on both the molecular and clinical aspects of AAS-induced cardiovascular toxicity, highlighting recent advances in understanding endothelial injury, oxidative stress, fibrosis, and arrhythmogenesis. Importantly, it emphasizes the emerging recognition of AAS abuse as a modifiable cardiovascular risk factor and discusses potential preventive and therapeutic strategies, including early cardiovascular screening and risk stratification. Understanding these mechanisms is essential for recognizing the clinical manifestations of AAS misuse and for improving cardiovascular risk assessment in affected individuals. These insights underscore the clinical significance of AAS abuse as a cardiovascular risk factor and the need for vigilant cardiac monitoring and early intervention in this population. Full article

Road traffic accidents are a major global public health concern, ranking among the top three causes of death worldwide and constituting the leading cause of death among individuals aged 15–29. Monitoring traffic safety status and trends is a vital element of effective road safety management. This study investigates road traffic casualties involving young car drivers (aged 18–24) in the Republic of Serbia from 1997 to 2024, analyzing historical patterns and introducing a predictive model for casualty outcomes. The analytical framework employs machine learning techniques, specifically Long Short-Term Memory (LSTM) networks, to estimate the number of casualties (FSI = Fatal + Serious Injuries) based on various contributing factors. Accurate prediction of accident outcomes is essential for designing targeted road safety measures and reducing casualty numbers. Full article

Background and Objectives: Surfactant protein-D (SP-D) enters the circulation when the alveolo-capillary barrier is injured. We synthesised evidence on the diagnostic and prognostic performance of circulating SP-D in children with acute infectious lung disease. Methods: We searched MEDLINE, Embase and Scopus (inception–1 June 2025) for human studies reporting serum/plasma SP-D in patients <18 years with community-acquired pneumonia (CAP), viral pneumonitis or paediatric ARDS (PARDS). Two reviewers independently screened, extracted data and assessed risk of bias (ROBINS-I). Primary outcomes were discrimination of severe versus non-severe disease and prediction of hard outcomes (mechanical ventilation, PARDS and mortality). Heterogeneity in assays and outcome definitions precluded meta-analysis; a narrative synthesis was undertaken. Results: Five studies (n = 723) from emergency and PICU settings met inclusion criteria. Admission SP-D was consistently higher in severe versus mild CAP; reported AUCs ranged 0.699–0.802. Thresholds of 110–180 ng/mL yielded sensitivities of 67–85% and specificities of 45–70%. In influenza-associated respiratory failure, SP-D correlated with ventilator days (r ≈ 0.45) and ICU length of stay (r ≈ 0.44). In multicentre PARDS cohorts, each 10 ng/mL increase in SP-D was associated with higher odds of severe PARDS and death (adjusted OR 1.02 per 10 ng/mL). Overall risk of bias across studies was low-to-moderate, with one study rated serious due to sampling and adjustment limitations. Conclusions: Across pathogens and care settings, elevated circulating SP-D correlates with radiographic consolidation, evolving PARDS and worse short-term outcomes. Although assay standardisation and external validation are needed, current evidence supports incorporating SP-D into multiparametric, age-aware risk-stratification algorithms for childhood pneumonia and viral lung injury. Full article

Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent aminopeptidase that is found in several places and is thought to be a cytosolic enzyme that helps break down peptides. Recent studies, however, have revealed its extensive therapeutic relevance upon release into circulation, functioning not only as a biomarker for cellular injury but also as an active modulator of cardiovascular homeostasis and critical disease. High levels of circulating DPP3 (cDPP3) have been linked to the causes of cardiogenic shock, septic shock, acute coronary syndromes, heart failure, and serious viral diseases like COVID-19. Its enzymatic breakdown of angiotensin II disrupts vascular tone and myocardial contractility, leading to hemodynamic instability and multi-organ failure. In numerous cohorts, cDPP3 levels reliably correspond with disease severity, acute renal damage, and death, but dynamic trajectories yield superior predictive information relative to single assessments. In addition to risk stratification, translational studies utilizing rodent and porcine models illustrate that antibody-mediated inhibition of cDPP3 with the humanized monoclonal antibody Procizumab reinstates cardiac function, stabilizes renal perfusion, diminishes oxidative stress and inflammation, and enhances survival. First-in-human experiences in patients with refractory septic cardiomyopathy have further emphasized its therapeutic promise. DPP3 is a good example of a biomarker and a mediator in cardiovascular and critical care. Its growing clinical and translational profile makes cDPP3 a strong predictor of bad outcomes and a prospective target for treatment. Ongoing clinical trials using Procizumab will determine if neutralizing cDPP3 can lead to enhanced outcomes in individuals with cardiogenic and septic shock. This review outlines the physiological mechanisms, clinical implications, and emerging therapeutic potential of DPP3 in cardiovascular and critical care. Ongoing trials with Procizumab will clarify whether neutralizing cDPP3 can improve outcomes in patients with cardiogenic and septic shock. Full article

Road traffic fatalities in low- and middle-income countries (LMICs) are continuing to rise, posing significant socio-economic and public health challenges. To prevent these road deaths and avoid the corresponding costs, the World Health Organization (WHO) has recommended implementing the vision zero approach to road safety. Vision Zero aims to eliminate road deaths and reduce serious injuries. It has been adopted by many developed countries, however LMICs have faced difficulties implementing this approach due to a lack of guidance. This study aims to develop a framework for implementing vision zero in LMICs by examining the processes in India and Sweden. A qualitative research approach with a multiple-case study design was utilized, selecting 16 participants through purposive and snowball sampling. Data was collected via semi-structured interviews and analyzed using the Grounded Theory method based on Strauss and Corbin’s approach. The study identified five core implementation steps such as agenda setting, approval, planning, monitoring and evaluation, and continuous improvement. Also, a set of influencing conditions such as preconditions, objectives, strategies, intervening factors and contextual conditions were identified. Furthermore, 38 implementation proposals were suggested in the framework to guide policymakers. The proposed framework provides a road map for LMICs that is intended to act as a guide for policymakers and road safety practitioners to enhance road safety performance in LMICs. Full article

Although significant progress has been made in the global medical level, cardiovascular diseases still pose a serious threat to human life and health. Among many cardiovascular diseases, acute myocardial infarction (AMI) is particularly severe. If not treated in a timely manner, it may lead to serious consequences such as cardiac arrest and sudden death. Early diagnosis of myocardial infarction (MI) is an important means of preventing and controlling the mortality rate of AMI. Creatine kinase isoenzyme (CK-MB) is a key biomarker of MI. It rises rapidly within 2 h after myocardial injury, reaches its peak at 24 h, and returns to normal at 72 h. Furthermore, CK-MB has a high specificity in monitoring secondary MI. Therefore, the early, real-time, and accurate detection of CK-MB is of great significance for the prevention, diagnosis, and prognosis of AMI. Conventional CK-MB detection methods have problems such as false positive elevation, large blood sampling volume, long time consumption, and complex operation, making it difficult to meet the needs of point-of-care testing (POCT). Biosensor technology, with its low cost, high sensitivity, and portability, offers a promising solution for point-of-care CK-MB testing, thereby greatly aiding AMI diagnosis. Full article

Road traffic accidents are the eighth leading cause of human deaths. In order to study two-vehicle accidents, this paper extracted data from 493 two-vehicle accidents from the CIDAS database from 2011 to 2022, used machine learning methods to analyze the accident data, and obtained the significance of two-vehicle accident parameters. Finally, five typical scenarios of two-vehicle accidents were obtained based on this. The results of the significance analysis show that vehicle parameters have a greater impact on occupant injury in the host vehicle; clustering results show that lighting, the number of lanes, the other vehicle’s type, and the speed of the host vehicle have a large impact on occupant injury (for example, the injury rate for the high-speed, nighttime Scenario II was 52.9%, compared to just 10.9% for the lower-speed Scenario IV). Factor analysis results show that precipitation has a large impact on occupant injury, as the frequency of injuries in rainy conditions was 13.4% higher, and the frequency of serious injuries was 7.9% higher, than in accidents without rain. This paper innovatively uses factor analysis to reduce the dimensionality of categorical variables, which provides research ideas for related research. At the same time, the clustering results obtained in this paper also provide references for the establishment of corresponding test scenarios for autonomous driving and the establishment of standards. Full article

Background: Blunt abdominal trauma in pregnancy is a medical emergency with significant maternal-fetal morbidity and mortality. Although rare, intestinal ischemia can occur as a serious abdominal complication following trauma during pregnancy. Case presentation: A 41-year-old woman at 33 weeks and 6 days of gestation was involved in a car accident, as a passenger in the front seat of a vehicle that left the road and overturned. The initial examination revealed severe chest trauma but no immediate signs of abdominal injury. However, the patient’s condition worsened, showing delayed symptoms of gastrointestinal dysfunction, clinical deterioration, and labor onset. Complementary imaging studies did not reveal conclusive findings suggesting complications related to the blunt abdominal trauma. Following a multidisciplinary team’s decision to perform an emergency cesarean section in the maternal-fetal interest, intestinal ischemia secondary to a mesenteric tear was discovered, necessitating intestinal resection and end-to-end anastomosis. Conclusions: Despite being a rare condition often associated with diagnostic delays, in cases of sudden clinical deterioration or maternal hemodynamic instability, immediate multidisciplinary intervention is essential. This approach may allow the early detection of trauma-related complications, reducing potentially preventable deaths and achieving favorable maternal and neonatal outcomes. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by providing durable responses and a favorable safety profile, ushering in a new era of tumor immunotherapy. However, immune-related adverse events (irAEs) remain a significant clinical challenge. Among these, gastrointestinal irAEs, especially immune-related colitis (ir-colitis), can lead to serious complications if not promptly recognized and managed. Here, we present a case of grade 3 ir-colitis induced by the programmed cell death protein 1 (PD-1) inhibitor sintilimab in a 68-year-old woman with endometrial cancer. The patient developed severe acute diarrhea following ICI administration, which progressed despite initial antidiarrheal and antimicrobial treatments. A multidisciplinary team (MDT) involving gastroenterologists, oncologists, a pathologist, and a clinical pharmacist confirmed the diagnosis and implemented high-dose corticosteroid therapy, yielding significant clinical improvement. Importantly, this report highlights the mechanistic link between PD-1 blockade and ir-colitis pathogenesis, focusing on the dysregulation of the mucosal immune environment and its role in triggering colonic injury. In addition to the case description, we provide a comprehensive review of the literature and clinical guidelines, discussing risk factors, diagnostic approaches, therapeutic strategies, and long-term monitoring. By integrating insights from pharmacology, immunology, and clinical practice, this work emphasizes the importance of early detection, patient education, and MDT collaboration for optimizing therapeutic outcomes and advancing the understanding of ir-colitis in the context of ICI therapy. Full article

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

Background: The management of difficult airways is one of the most critical and challenging aspects of emergency and ICU care. Despite technological advances, unanticipated airway difficulty can result in serious complications, including hypoxia, brain injury, and death. This comprehensive narrative review aims to consolidate current algorithms and evidence-based strategies to guide clinicians in the assessment and management of difficult airways. Methods: A comprehensive literature review was conducted using PubMed, Embase, and Google Scholar to identify relevant studies, clinical guidelines, and expert consensus documents related to difficult airway management. The focus was placed on both pre-intubation assessment tools and intervention strategies used in various clinical contexts. Results: Airway difficulty is best anticipated through a combination of history, physical examination, and validated tools such as the Mallampati score. Several algorithms, including those from the American Society of Anesthesiologists (ASA) and the Difficult Airway Society (DAS), provide structured approaches that emphasize preoxygenation, preparedness for failed intubation, and the use of adjuncts such as video laryngoscopy, supraglottic airway devices, and awake intubation techniques. Crisis algorithms such as the Vortex approach help simplify decision-making during emergencies. It is important to have adjuncts available in cases of anticipated difficult airways, such as fiberoptic intubation, while surgical airway access is an important component of a stepwise airway management algorithm when critical scenarios are encountered. Conclusions: Effective difficult airway management requires anticipation, a structured plan, familiarity with advanced airway tools, and adherence to validated algorithms. Training in crisis resource management and multidisciplinary rehearsal of airway scenarios are essential to improving outcomes. Full article

Background and Aims: Ornidazole, a nitroimidazole antibiotic, is widely used for protozoal and anaerobic infections and is generally considered safe. However, ornidazole-induced liver injury (OILI) is an underrecognized yet potentially severe adverse reaction. This multicenter study aims to characterize the clinical features, histopathology, and outcomes of OILI to improve the awareness and management of this rare entity worldwide. Methods: We conducted a retrospective analysis of 101 patients with OILI from eight tertiary centers between 2006 and 2023. Cases were included based on liver enzyme elevations temporally linked to ornidazole and the exclusion of other causes. Causality was assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) score. Clinical data, laboratory parameters, autoantibody profiles, histology, treatments, and outcomes were evaluated. Results: OILI was classified as highly probable in 42.6% of cases (n = 43), probable in 51.5% of cases (n = 52), and possible in 5.9% (n = 6) of cases. The predominant pattern was acute hepatocellular injury (83.2%) (n = 84). Autoimmune-like hepatitis occurred in 5% of cases (n = 5), with ANA positivity in 16.8% of cases (n = 17). Corticosteroids were used in 24.8% of cases (n = 25) and were associated with higher ANA positivity and a 20% (n = 5) relapse rate post-discontinuation. Recovery was achieved in 87.7% of cases (n = 88), while 7.9% of cases (n = 8) required liver transplantation and 4% (n = 4) died. Conclusions: Ornidazole can cause serious idiosyncratic liver injury, including autoimmune phenotypes, and should be considered in the differential diagnosis of acute hepatitis. Given the notable risk of liver failure and death, early recognition, drug discontinuation, and close monitoring are essential. In select cases, corticosteroids and plasmapheresis may be beneficial, though the evidence remains limited. Full article