Search Results (216)

Background/Objectives: Shenfu Decoction (SFD) is a traditional Chinese herbal formula composed of Panax ginseng and Aconitum carmichaelii that can revive and counteract shock. However, how SFD can mitigate hypothermia caused by seawater immersion is poorly understood. Methods: Three commonly used ratios of SFD (Panax ginseng:Aconitum carmichaelii = 1:1, 1:2, 2:1) were prepared, and their chemical properties were analyzed with UPLC-Q-TOF-MS. A rat model of hypothermia caused by seawater immersion at 15 °C was utilized. Survival analysis was used to evaluate the prophylactic effect of single intragastric administration of SFD with different ratios and doses on the survival time of rats, and to identify the optimal intervention conditions. Network pharmacology analysis based on the absorbed constituents of SFD was performed to preliminarily predict the underlying mechanisms, which were subsequently validated using RT-PCR, Western blotting, ELISA, and H&E staining. Results: SFD contained 54 compounds, including ginsenosides and aconitine alkaloids, whose relative concentrations varied across different ratios of SFD. Animal studies showed that pretreatment of SFD (1:1) administered at a dose of 1.35 g/kg was very effective in increasing rats’ survival time in hypothermia and slowed down core body temperature decline. Based on the 28 plasma-absorbed compounds of SFD, network pharmacology identified 503 targets, enriched in cAMP and MAPK signaling pathways. SFD (1:1, 1.35 g/kg) resulted in larger lipid droplets in brown adipose tissue (BAT) and enhanced the respiratory metabolic rate in seawater-immersion-induced hypothermia rats. Furthermore, its thermogenic effect is likely associated with the upregulation of uncoupling protein 1 (UCP1) via activating p38 MAPK/PGC1α/PPARγ and NE-(β3-AR)-cAMP-PKA pathways. Conclusions: The results of this study demonstrate that a single prophylactic administration of the traditional Chinese medicine formula SFD prior to cold seawater exposure significantly prolongs the survival time of rats. This effect is associated with the upregulation of UCP1 and the subsequent enhancement of thermogenesis in BAT. These findings highlight the great potential of SFD as a promising intervention for the management of hypothermia. Full article

Introduction: This study explored how illness severity scores correspond to hypoxic-ischemic brain injury (HIBI) after cardiac arrest. Methods: This study included cardiac arrest survivors with sufficient data to calculate the Pittsburgh Cardiac Arrest Category (PCAC) and revised post-cardiac arrest syndrome for therapeutic hypothermia (rCAST) scores who underwent brain magnetic resonance imaging and cerebrospinal fluid neuron–specific enolase (CSF-NSE) measurement within 6 h after return of spontaneous circulation. The primary outcome was the association of PCAC and rCAST with quantitative brain injury markers assessed using whole brain mean apparent diffusion coefficient (mean ADC), low ADC volume fractions (PV600, 650, and 700), and CSF-NSE. Results: In total, 81 patients were included. PCAC was not significantly associated with CSF-NSE, mean ADC, or PVs. The rCAST score was significantly associated with higher CSF-NSE, lower mean ADC, and higher PV700. The neurologic sub-score of PCAC was independently associated with all evaluated brain injury markers, whereas the systemic sub-score was not. Of the individual rCAST components, anoxic time was independently associated with CSF-NSE, whereas no other single component was associated with these markers. Conclusions: rCAST was significantly associated with degree of HIBI, whereas PCAC was not. The neurologic sub-score of PCAC showed independent associations with HIBI. Full article

We examined neocortical pathology and interneuron degeneration in neonatal hypoxia-ischemic encephalopathy (HIE). Piglets in two age groups (2–3 or 7–10 days old, n = 4–12/group) underwent global cerebral hypoxia–ischemia (HI) or sham treatment. Piglets (2–3 days old) had epidural electrodes for continuous electroencephalography (cEEG) and were treated with hypothermia (HT) or remained at normothermia (NT). Older piglets, all NT, had scalp EEG. Piglets at both ages had seizures and survived for 1–7 days. Cortical damage was assessed by hematoxylin & eosin staining and immunohistochemistry; calretinin (CR), parvalbumin (PV), and vasoactive intestinal peptide (VIP) interneurons (INs) were counted. Cell injury was assessed by DNA fragmentation and protein nitration. TAR DNA binding protein-43 (TDP43) and the DNA repair scaffold protein X-ray repair cross complementing-1 (XRCC1) were examined for degeneration mechanisms. Cortical layers 3 and 4 showed high vulnerability; damage emerged as isolated cells, focal and laminar, and distributed as panlaminar throughout different cortical regions that correlated with seizure burden. HT protected strongly against cortical damage. CR- and PV-INs were severely depleted in HI-NT piglets compared to sham. VIP INs appeared invulnerable. HT partially rescued the loss of INs. CR and PV formed nuclear and cytoplasmic inclusions that colocalized with TDP43 and XRCC1; co-immunoprecipitation identified interactions among these proteins, and tyrosine nitration of CR. CR and PV INs accumulated DNA single- and double-strand breaks and appeared as attritional apoptosis variants with proteinopathy. This cell death is identified as aggreosis. IN loss correlated with seizure presence. Postmortem human neonatal HIE cases had a similar loss of CR and PV INs and nuclear depletion of TDP43 in the neocortex. Thus, neonatal HIE causes the loss of neocortical inhibitory IN subtypes with vulnerabilities instructed by their intrinsic calcium-binding protein signature and by mechanisms consistent with toxic sequestration and the nuclear depletion of XRCC1 and TDP43 underlying DNA damage accumulation. Early inhibitory IN deletion could drive seizure evolution in HIE; TDP43 and XRCC1 could be therapeutic targets for neonatal HIE. Full article

Objectives: The purpose of this study was to compare the incidence of hearing loss at three months of age in a cohort of newborns with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) with that reported in the literature. We also evaluated potential risk factors associated with audiological impairment and changes in hearing threshold during follow-up. Methods: This retrospective observational cohort study was conducted at the Neonatal Intensive Care Unit of the Fondazione Policlinico Universitario A. Gemelli, IRCCS in Rome, Italy, between January 2017 and December 2023. Infants underwent audiological screening and a full diagnostic evaluation at three months of age and were followed during the first year of life. Results: A total of 149 infants were enrolled, and hearing loss was identified in six (4.0%) at three months of age. Two of these six infants showed an improvement in their hearing threshold, resulting in a prevalence of permanent bilateral sensorineural hearing loss (SNHL) of four out of 149 infants (2.7%), with no cases of late-onset hearing loss detected. Gestational age was identified as an independent protective factor against SNHL (OR 0.49; 95% CI 0.22–0.91). Conclusions: The audiological screening program demonstrates effectiveness in early intervention for diagnosing and treating hearing loss. Infants with HIE are at high risk for hearing disorders and require increased attention in neonatological and audiological management. Management should be individualized based on specific risk factors. The association between gestational age and susceptibility to cochlear damage should be confirmed by further studies. Full article

Severe accidental hypothermia represents a unique and potentially reversible cause of cardiac arrest in which prolonged resuscitation may still result in favorable neurological recovery. Unlike normothermic cardiac arrest, hypothermic cardiac arrest (HCA) is characterized by profound metabolic suppression and temperature-mediated myocardial instability, requiring a fundamentally different therapeutic paradigm. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) provides not only circulatory support but also controlled reperfusion and rewarming, positioning it as the cornerstone of modern management. Recent international guidelines have clarified indications for extracorporeal life support (ECLS) in HCA and have contributed to improved standardization of care. Building upon these recommendations, this narrative review focuses on physiological principles underlying extracorporeal rewarming and their implications for bedside management. We examine mechanisms of ischemia–reperfusion injury, rewarming-associated hemodynamic instability and myocardial stunning, discuss dynamic risk assessment beyond statistical thresholds such as the HOPE score and summarize practical considerations regarding cannulation strategies, differential hypoxia, left ventricular unloading and neurologic evaluation. By integrating current evidence with pathophysiological insight and organizational considerations, this review proposes a clinically oriented framework to support decision-making in hypothermic cardiac arrest and to optimize meaningful neurological recovery. Full article

Background: Hypoxic–ischemic encephalopathy (HIE) remains a major cause of neonatal mortality and long-term neurodevelopmental impairment despite advances in perinatal care and the widespread use of therapeutic hypothermia. Reliable early prognostic markers are essential for risk stratification and long-term follow-up planning. This study aimed to evaluate long-term neurodevelopmental outcomes and associated prognostic factors in neonates with HIE treated in the era of therapeutic hypothermia. Methods: This retrospective cohort study was conducted in a tertiary neonatal intensive care unit between January 2020 and June 2024. Neonates with gestational age ≥ 35 weeks diagnosed with HIE were included. Clinical characteristics, laboratory parameters, neurophysiological findings, neuroimaging results, and indicators of multiorgan dysfunction were recorded. Long-term neurodevelopmental outcomes were assessed at 18 to 24 months of age. The primary outcome was death or severe neurodevelopmental impairment. Multivariable logistic regression analysis was performed to identify independent predictors of adverse outcomes. Results: A total of 99 neonates were included. Therapeutic hypothermia was administered to 86 (86.9%) infants. Severe neurodevelopmental impairment or death occurred in 18 (18.2%) patients. Cerebral palsy was diagnosed in 19 (20.9%) survivors, developmental delay in 12 (13.2%), epilepsy in 16 (17.6%), and feeding difficulties in 9 (9.9%). In multivariable analysis, higher lactate levels (adjusted OR = 1.239, 95% CI = 1.052–1.458), lower Apgar score at 5 min (adjusted OR = 0.570, 95% CI = 0.344–0.944), and renal dysfunction (adjusted OR = 7.947, 95% CI = 2.027–31.164) were independently associated with severe neurodevelopmental impairment or death. Multiorgan dysfunction and abnormal neurophysiological and neuroimaging findings were significantly associated with adverse outcomes. Conclusions: Early biochemical markers, neurological assessments, neurophysiological recordings, neuroimaging patterns, and systemic organ dysfunction are closely associated with long-term neurodevelopmental outcomes in neonates with HIE. A multidimensional approach to early prognostic evaluation may improve risk stratification and guide targeted follow-up and intervention strategies. Full article

We present a circular complementary split ring resonator (CCSRR) flexible antenna operating in the 1.4 GHz radio-astronomy quiet frequency band. The antenna is designed for microwave non-invasive brain temperature sensing of an infant’s head to aid in the therapeutic hypothermia treatment of hypoxic–ischemic encephalopathy (HIE) and traumatic brain injury (TBI). The proposed metamaterial-inspired antenna is designed on a flexible Kapton substrate with a biocompatible Polydimethylsiloxane (PDMS) protective superstrate layer. For brain temperature measurement, the flexible antenna is placed directly on the scalp to collect thermal noise power from the underlying tissue layers. The received thermal power is to be delivered to a sensitive microwave radiometer. The CCSRR antenna exhibits sharp frequency selectivity at 1.4 GHz with inherent filtering capability, strong field confinement, and excellent suppression of out-of-tissue (external) electromagnetic interference and thermal noise contributions. To closely match the realistic scenario, the CCSRR antenna, initially designed in a planar multi-layer configuration, is investigated in various bending configurations (cylindrical and spherical) with a curvature radius of 55 mm. The results indicate stable performance under bending. Good agreement between simulated and on-body measured results is observed in the desired frequency band. Full article

Background: Neonatal hypoxic–ischemic encephalopathy remains a leading cause of neonatal mortality and long-term neurodevelopmental disability worldwide. Despite the widespread adoption of therapeutic hypothermia, a substantial proportion of affected infants experience death or significant neurological impairment. Given their metabolic vulnerability, ketogenic diet strategies and ketone bodies have emerged as potential adjunctive neuroprotective interventions. This scoping review aims to critically evaluate the mechanistic rationale, preclinical evidence, and clinical feasibility of ketogenic approaches. Methods: A scoping review of the literature was conducted, including experimental and clinical studies investigating ketogenic diets, endogenous ketosis, and exogenous ketone supplementation in neonatal hypoxia–ischemia. Evidence was synthesized across mechanistic, preclinical, nutritional, and clinical domains, with particular attention to developmental context, timing of intervention, safety considerations, and translational relevance in the contest of therapeutic hypothermia. Results: Preclinical studies consistently demonstrate that ketone bodies enhance cerebral energy metabolism, support mitochondrial function, reduce excitotoxic signaling, and attenuate oxidative stress and neuroinflammation in the immature brain. Neonatal models show preferential utilization of β-hydroxybutyrate over glucose during hypoxic–ischemic stress, suggesting intrinsic metabolic advantages. Emerging evidence also supports potential long-term effects on epigenetic regulation and white matter development, although direct causal validation in neonatal HIE remains limited. Nutritional studies indicate that carefully monitored enteral and parenteral feeding is feasible in critically ill neonates, identifying a potential window for metabolic interventions. Conclusions: Ketogenic strategies represent a plausible, multimodal approach to targeting the metabolic and inflammatory sequelae of neonatal HIE. While current evidence is insufficient to support clinical implementation, this scoping review provides a hypothesis-generating framework to guide future translational research and the design of carefully controlled clinical trials in neonatal neurocritical care. Full article

Over the past two decades, advanced airway management, early coronary angiography, and therapeutic hypothermia have shaped post-out-of-hospital cardiac arrest (OHCA) care. However, recent large randomized trials have challenged these strategies and created substantial uncertainty leading to relevant guideline changes. This review focuses on the trials that ultimately influenced current guideline recommendations by downgrading previous recommendations. We determine how structural limitations may have affected the validity and interpretation of their results. The review critically evaluates the methodological design and execution of those trials. Despite neutral findings from recent randomized trials, use of advanced airway management during resuscitation, coronary angiography in patients with a high likelihood of acute coronary occlusion, and therapeutic hypothermia for comatose OHCA survivors still play a relevant role in post-resuscitation management. Full article

Background/Objectives: Neonates with hypoxic–ischemic encephalopathy (HIE) are born in delivery facilities with different levels of neonatal care. The objective of this study was to investigate differences in the incidence of HIE and postnatal management between different levels of neonatal care in delivery facilities. Methods: This is a retrospective, multi-center cohort study of neonates with moderate-to-severe HIE receiving therapeutic hypothermia (TH) in the Canton of Zurich, Switzerland, registered in the Swiss National Asphyxia and Cooling Register between 2015 and 2023. Incidences of HIE receiving TH were calculated for all delivery facilities according to the national levels of neonatal care on site (Level I—basic; Level IIB—intermediate (no Level IIA facility in the Canton of Zurich); Level III—intensive neonatal care). Perinatal characteristics and variables on transport and outcomes were compared between neonates born in Level I and Level IIB facilities (the majority of the HIE population) and reported for neonates born in all other facilities (for completeness). Results: A total of 173 neonates (79 (45.7%) born in Level I; 80 (46.2%) in Level IIB; 9 (5.2%) in Level III; 5 (2.9%) in birthing centers) were admitted to a neonatal cooling center to receive TH. The average number of annual cases of HIE receiving TH per facility was 0.67 (0.11–1.50) in Level I and 2.22 (0.22–3.11) in Level IIB facilities (p = 0.088), respectively. There was no difference in Apgar score, worst pH (within 60 min after birth) and the severity of encephalopathy between neonates born in Level I and Level IIB facilities. Neonatal transport team requests were initiated earlier in Level I facilities (median 12 vs. 34 min of life, p < 0.001). There was no difference in age at initiation of TH (median 3 vs. 3 h, p = 0.431) and the time when target temperature was reached (median 4 vs. 4 h, p = 0.431) between neonates born in Level I and Level IIB facilities. Conclusions: The level of neonatal care available in delivery facilities influenced the management of neonates with HIE receiving TH. Full article

Background: Red cell distribution width (RDW) and the RDW-to-platelet ratio (RPR) have emerged as readily available hematologic markers reflecting systemic inflammation in neonates with hypoxic–ischemic encephalopathy (HIE); however, their early postnatal trajectories across the clinical spectrum of HIE remain insufficiently characterized. Methods: This retrospective cohort study included 229 term or near-term infants diagnosed with HIE. Among them, 166 infants received therapeutic hypothermia, whereas 63 infants who did not undergo cooling served as the reference group. RDW and RPR values were measured at birth and at 72 h of life (after completion of cooling in the hypothermia group). Results: In the reference group, RDW values significantly decreased at 72 h, reflecting normal postnatal hematologic adaptation. In contrast, the hypothermia group demonstrated a blunted decline, with RDW levels remaining relatively stable over the first 72 h, consistent with a blunted early postnatal RDW decline. RPR values showed a mild, non-significant upward trend during the first 72 h of life; however, exploratory analyses suggested an association between higher RPR levels and increasing HIE severity. Conclusions: Across the spectrum of hypoxic–ischemic encephalopathy, RDW demonstrated a blunted postnatal decline, whereas RPR showed a mild, non-significant increase during the early neonatal period. These readily available hematologic markers may provide complementary insights into early systemic inflammatory and hematologic responses in HIE. Prospective multicenter studies are needed to determine their prognostic value and relationship with clinical and neurodevelopmental outcomes. Full article

Fishing is a widely practiced recreational activity that offers psychological, physical, and social benefits, but it also poses risks such as acute trauma and chronic overuse injuries. This narrative review aims to (1) synthesize current evidence on the musculoskeletal disorders, psychological outcomes, and environmental factors associated with recreational and sport fishing; (2) identify the physical, mental, and social health benefits reported across different angling disciplines; (3) characterize acute and chronic injury risks, including overuse syndromes and environment-related hazards; and (4) highlight gaps in the literature to guide future research directions in public health, rehabilitation, and preventive medicine. Materials and Methods: A narrative review was conducted in accordance with SANRA guidelines. A structured search of PubMed, Scopus, Web of Science and Google Scholar identified studies published between 2000 and 2025. Eligible sources included population surveys, clinical studies, therapeutic angling programs, epidemiological reports, and case studies addressing physical, psychological, or injury-related outcomes in recreational or sport fishing. Studies on commercial or occupational fishing were excluded. Evidence was synthesized thematically across benefit and risk domains. A total of 565 records were identified across four databases (PubMed, Scopus, Web of Science, Google Scholar). After screening, duplication, and full-text assessment, 41 studies met the eligibility criteria and were included in the narrative synthesis. The evidence indicates significant psychological benefits of fishing, including reductions in stress, improved mood, and clinically meaningful decreases in Post-Traumatic Stress Disorder (PTSD) symptoms reported in therapeutic fly-fishing programs. Musculoskeletal outcomes were more heterogeneous: chronic conditions such as low back pain and repetitive strain injuries of the shoulder, elbow, and wrist were commonly reported among regular anglers, particularly in physically demanding disciplines. Ice and sea fishing were associated with distinct environmental risks, including hypothermia, frostbite, and rare but documented fatal incidents. The results of this narrative review highlight the therapeutic potential of both recreational and sport fishing. However, they also point to the need for greater awareness of the risk of injury and environmental hazards associated with this type of fishing. Full article

Background and Clinical Significance: Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, is increasingly prescribed for autoimmune and inflammatory diseases. Although its therapeutic safety profile is well established, fatal intoxications have not been reported to date. Case Presentation: We describe the first fatal case of upadacitinib overdose in a 13-year-old girl. Following ingestion of approximately 600 mg (40 × 15 mg tablets Rinvoq^®), the patient presented with deep coma, profound bradycardia (~40 bpm) with third-degree atrioventricular block, conduction delay, hypotension, hypothermia, and metabolic acidosis. Laboratory tests showed hyperglycemia (17.8 mmol/L) and only minimal elevations in cardiac biomarkers (CK 57.03 U/L, CK-MB 30.64 U/L, troponin 0.003 ng/mL). Despite advanced resuscitation, the patient succumbed within a few hours. Forensic toxicology revealed extremely high concentrations of upadacitinib, 1.84 µg/mL (~1840 ng/mL) in blood and 70.3 µg/mL in gastric contents, far exceeding reported therapeutic plasma levels (Cmax 36.0 ± 8.8 ng/mL). This case establishes the first reported value for a lethal upadacitinib concentration in humans. The combination of conduction abnormalities, refractory shock, and minimal biomarker changes is consistent with an acute electrophysiological and hemodynamic collapse rather than myocardial infarction. Conclusions: The toxicity of upadacitinib in this case is characterized by profound central nervous system depression, severe cardiovascular (electrophysiological and hemodynamic) disturbances, and metabolic abnormalities (acidosis and hyperglycemia). These findings provide essential reference data for clinical and forensic toxicology, highlight the fatal potential of upadacitinib in overdose, and underscore the importance of secure medication storage and pharmacovigilance in households with adolescents. Full article

Hypoxic–ischemic encephalopathy remains a major cause of neonatal mortality and long-term neurological disability. Therapeutic hypothermia is currently the only available treatment in hospitals, but its efficacy is limited, making the search for alternative neuroprotective strategies essential. Melatonin has shown promising results in other models of hypoxia–ischemia, acting as a potent antioxidant and anti-inflammatory molecule. Here, we studied the effects of hypoxia–ischemia and melatonin treatment in two brain regions that are particularly vulnerable to hypoxic–ischemic injury. Neonatal rat organotypic slice cultures from the corticostriatal and hippocampal regions were subjected to oxygen–glucose deprivation and reperfusion (OGDR) and treated with melatonin (50 μM). Cell death (propidium iodide staining), redox state (GSH/GSSG ratio) and the inflammatory profile (Proteome Profiler) were analyzed. OGDR markedly increased cell death in both regions and melatonin treatment significantly reduced it. The GSH/GSSG ratio decreased only in the hippocampus after OGDR, but melatonin treatment elevated this ratio in both regions. In contrast, the inflammatory profile was more pronounced in the corticostriatal region, where the treatment strongly reduced proinflammatory mediators. These findings reveal region-specific mechanisms involved in the response to hypoxic–ischemic damage and support the potential of melatonin as a promising therapy for neonatal brain injury. Full article

Hypoxic–ischaemic encephalopathy (HIE) is a major cause of neonatal brain injury and is associated with a high rate of death and lifelong disability. Its pathogenesis is still poorly understood, and there is no proven treatment for preterm infants. Therapeutic hypothermia for term and near-term infants partially improves outcomes, highlighting the need to target additional mechanisms. This review evaluates evidence that necrosis and necroptosis contribute materially to evolving brain injury in both term and preterm brains. Serial imaging studies suggest that lesions typically develop over many days after birth for term infants and over many weeks after birth for preterm infants. Growing evidence from animal studies shows that severe white matter injury can be mediated by programmed necroptosis. In particular, lesions that evolve late after acute HI are characterised by necrosis in association with agglomerations of microglia, with little apoptotic cell death. Critically, preclinical studies in large and small animals show that outcomes can be dramatically improved by very delayed intervention after HI including with cell therapy, anti-inflammatory agents, and endogenous neurotrophins. These findings strongly support the hypothesis that there may be a window of therapeutic opportunity for days or even weeks after birth to prevent delayed necrotic lesions. Full article