Search Results (189)

Background/Objectives: Mild traumatic brain injury (mTBI) is common and may result in persistent cognitive and affective disturbances driven, at least in part, by delayed secondary injury mechanisms, including oxidative stress, neuroinflammation, apoptosis-related signaling, and impaired neuroplasticity. Pharmacological strategies targeting these interconnected processes remain limited. The present study investigated leucovorin, also known as folinic acid, a clinically approved reduced folate, as a potential repurposing candidate in an experimental model of mTBI. Methods: Male Wistar rats were subjected to mild diffuse brain injury using a modified weight-drop model and received a single intraperitoneal dose of leucovorin (20 mg/kg). Behavioral performance was evaluated using the open field, elevated plus maze, forced swim, and novel object recognition tests. Oxidative stress markers, including total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), as well as inflammatory mediators tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2), caspase-3, brain-derived neurotrophic factor (BDNF), and acetylcholinesterase (AChE), were measured in hippocampal tissue and plasma. Histopathological and immunohistochemical evaluations were also performed in cortical and hippocampal regions. Results: Experimental mTBI was associated with anxiety-like and depressive-like behaviors and impaired recognition memory, whereas basal locomotor activity was not significantly altered. Trauma was also associated with increased oxidative stress, elevated inflammatory and apoptosis-related markers, reduced BDNF levels, altered AChE activity, and histopathological abnormalities. Compared with untreated mTBI animals, leucovorin-treated animals showed attenuation of biochemical and tissue alterations, accompanied by improved behavioral outcomes. Immunohistochemical findings were consistent with reduced inflammatory labeling and relative preservation of tissue architecture following leucovorin treatment. Conclusions: Leucovorin attenuated behavioral, biochemical, histopathological, and immunohistochemical alterations associated with experimental mTBI. These findings suggest that leucovorin may have neuroprotective potential in this setting; however, further studies are needed to clarify the underlying mechanisms, optimal treatment paradigms, and translational relevance. Full article

Exposure to blast waves without kinetic, penetrating, thermal, or toxic components causes a distinct form of traumatic brain injury, termed primary blast-induced TBI (pbTBI). Clinical manifestations of pbTBI span a wide spectrum, ranging from life-threatening intracranial hemorrhage, hyperemia, and delayed cerebral edema to mild and transient neurological symptoms without detectable structural abnormalities on routine imaging. At the mild end of the spectrum, symptoms after a single exposure may resolve quickly, yet repeated exposures—even at very low levels, termed “subconcussive”—can develop into post-concussive syndrome (PCS) or persistent post-concussive symptoms (PPCS) in a subset of individuals. Despite extensive studies, the molecular pathobiology linking primary blast exposure to delayed and sometimes chronic neurobehavioral deficits remains incompletely understood. A mechanistic framework connecting blast-wave physics to biomechanics to biological vulnerability may therefore help define exposure hazards, interpret clinical symptomatology, and guide diagnostic and therapeutic development. This review summarizes the physics of primary blast waves, the resulting biomechanical responses, and candidate biological substrates, emphasizing structures and interfaces with distinct acoustic impedances across anatomical, tissue, cellular, and molecular scales. We synthesize evidence supporting the hypothesis that the cerebral vasculature and endothelial cells represent critically vulnerable substrates of primary blast-wave injury, in part because the vascular tree constitutes the brain’s largest and most widely distributed interface between compartments with different acoustic impedances. Across experimental and human studies, endothelial stress, vascular injury, and downstream neuroinflammation emerge as convergent molecular responses to primary blast exposure. Temporal dynamics are central to understanding pbTBI because many blast-induced processes unfold in sequential phases. These observations support conceptualizing pbTBI as a condition characterized by prominent cerebrovascular injury of varying severity with secondary consequences for neuronal signaling, network function, and behavior. Within this framework, cerebrovascular and neurovascular unit (NVU) dysfunction provides a parsimonious bridge between primary blast-wave exposure and chronic symptom trajectories, where vascular pathology may offer more accessible therapeutic targets than neuronal injury. Key knowledge gaps include identifying which physical component(s) of the blast are most injurious, establishing biologically meaningful dose–response relationships at molecular and physiological levels, and defining windows of vulnerability during recovery that are relevant to repeated exposures. Addressing these gaps is essential for refining safety protocols, improving diagnostic specificity through mechanism-informed biomarkers, and developing evidence-based molecular and vascular therapeutic targets for pbTBI-associated conditions. Progress will require integrating waveform-aware dosimetry with longitudinal physiological and molecular monitoring across both preclinical and human cohorts. Such integration offers a practical path toward translating blast physics into actionable medical guidance for prevention, triage, and recovery management. Full article

Background: Spinal cord ischemia (SCI) is a severe complication of thoracoabdominal aortic aneurysm (TAAA) repair, associated with substantial morbidity and mortality. Despite advances in operative techniques, its pathophysiology remains incompletely understood, with no reliable biomarkers available for early detection or risk stratification. Methods: This narrative review synthesizes current evidence on the pathophysiology of SCI following aortic intervention, integrating insights from ischemic stroke and traumatic spinal cord injury to identify key mechanistic pathways and potential biomarker targets. Results: SCI results from multifactorial impairment of spinal cord perfusion pressure (SCPP) driven by extensive aortic coverage, disruption of segmental arterial inflow, hypotension, and impaired collateral circulation. While acute hypoperfusion initiates injury, secondary processes—including excitotoxicity, oxidative stress, and neuroinflammation—drive progression. Cytokine signaling and immune activation contribute to blood–spinal cord barrier disruption and vasogenic edema, with Aquaporin-4 playing a central role in delayed injury. Candidate biomarkers, including neuron-specific enolase, S100β, and glial fibrillary acidic protein, reflect neuronal damage but lack sufficient sensitivity and temporal resolution for clinical use. Emerging evidence supports a multimodal biomarker approach incorporating inflammatory, structural, and Aquaporin-4-dependent edema-related pathways. Conclusions: Spinal cord ischemia following thoracoabdominal aortic aneurysm repair is a dynamic and multifactorial process in which reduced spinal cord perfusion pressure represents a final common pathway linking diverse perioperative factors to ischemic injury. Secondary mechanisms, particularly neuroinflammation and Aquaporin-4-driven vasogenic edema, play a central role in injury propagation and represent promising targets for biomarker development. Future strategies should focus on longitudinal, multimodal biomarker approaches to improve early detection, risk stratification, and therapeutic intervention. Full article

Severe traumatic brain injury (TBI) is a leading cause of mortality and long-term disability in polytrauma (PT) patients, and its clinical outcome remains difficult to predict due to clinical heterogeneity and secondary injury mechanisms. Current diagnostic and prognostic approaches based on clinical assessment and imaging are limited, particularly in PT where neurological evaluation is often impaired. This study aimed to compare plasma- and extracellular vesicle (EV)-associated microRNA (miRNA) signatures in patients with severe TBI and healthy controls to identify their potential as minimally invasive biomarkers and to improve understanding of molecular responses. For profiling circulating miRNAs, blood samples were collected at ≤3 h and at 48 h after admission. In the screening phase, plasma samples of n = 15 patients with severe isolated TBI (Abbreviated Injury Scale [AIS]Head ≥ 4, all other AIS ≤ 1) and n = 15 age- and sex-matched healthy controls were pooled (n = 5/pool) and subjected to next-generation sequencing (NGS). In the following validation phase, n = 25 severely injured trauma patients (Injury Severity Score [ISS] ≥ 16) were enrolled and stratified into PT without TBI (PT; AISHead = 0; n = 13) and isolated TBI (n = 12). Differentially expressed candidate miRNAs identified in the screening phase were validated in individual plasma and EV samples using reverse transcription droplet digital polymerase chain reaction (RT-ddPCR). Functional enrichment and pathway analyses were performed using miRNet. NGS identified more differentially expressed miRNAs in plasma (ER: 103; 48 h: 65) than in EVs (Emergency Room [ER]: 14; 48 h: 32). Functional enrichment analysis indicated associations with pathways related to cellular stress, senescence, growth factor signaling, transcriptional regulation, and apoptosis. In validation, 12 of 16 plasma and 10 of 15 EV-miRNAs were confirmed as differentially expressed in TBI patients; among these, three plasma and four EV miRNAs differed between TBI and PT. After adjustment, most plasma miRNAs were associated with injury severity rather than group status. EV miRNA profiles showed heterogeneous patterns, with miR-1469 associated with TBI group status in adjusted analysis, while miR-1237-5p was linked to injury severity and other EV miRNAs showed no consistent group-specific effects. Plasma miRNAs mainly correlated with systemic injury markers, whereas EV miR-1469 showed a moderate association with the Glasgow Coma Scale (GCS). Overall, circulating miRNA profiles after injury appear to be predominantly influenced by systemic trauma severity rather than TBI-specific effects. Plasma miRNAs mainly reflected general injury burden, whereas EV-associated miRNAs showed more heterogeneous patterns, with miR-1469 emerging as a candidate associated with TBI after adjustment for clinical covariates. These findings suggest that EV-derived miRNAs, particularly miR-1469, may provide more targeted signals related to brain injury and warrant further investigation. Full article

Background: Poor mental health is prevalent among veterans who suffer from post-traumatic stress disorder (PTSD) and other psychiatric conditions. Canine-assisted interventions may improve psychological and social health in veterans. The parent study, a randomized controlled trial, revealed improvements in PTSD following both a service dog training program and an active control condition consisting of virtual dog training lessons. Thus, in the present post hoc secondary analysis, we analyzed both groups together (pooled arms) to examine gender-based differences in the effects of the altruistic service dog training programs on psychosocial outcomes. Methods: Veterans (N = 59) participated either in hands-on (with a dog and trainer) or virtual (no dog present) dog training programs over eight weeks and completed self-reported psychosocial measures before and after the program. Mixed-effect linear models were used to assess the interaction between time and gender on a series of psychosocial outcomes in the pooled sample. Results: The findings supported greater psychosocial improvements for female participants compared to male participants, including significant improvements in PTSD, perceived stress, and perceived physical health, and feeling greater closeness and lower avoidance in close relationships (ps < 0.05). The results revealed moderate to large effect sizes among female participants, suggesting meaningful clinical effects of the interventions (ds = 0.47–0.70). Conclusions: While the secondary analysis and small sample size limit causal inferences, the exploratory evidence suggests greater improvements in psychosocial health in female veterans after participating in the service dog training programs. Future research should tailor interventions to optimize the therapeutic effects for male and female veterans and identify other individual characteristics involved, such as combat exposure or post-traumatic stress symptom severity. Full article

Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic presented significant psychosocial challenges to intensive care unit health care workers (ICU HCW). Prior studies typically used single cross-sectional samples to focus on elements of burnout and psychological stress. We sought to serially assess quality of life and willingness to work before, during, and after the first peak of COVID-19. Methods: Two survey instruments were prospectively administered at regular intervals to multidisciplinary ICU HCWs, initiating at the local onset of COVID-19 and ending 6 months after the first peak ICU census of COVID-19 patients. Results: ICU HCWs reported high levels of compassion satisfaction, burnout, and secondary traumatic stress before, during and after the first peak of COVID-19. Motivation to work declined, and hesitation to work increased from study initiation to the peak ICU census of COVID-19 patients. Hesitation to work was greater in female HCWs and cardiothoracic ICU HCWs. Motivation to work was higher in those working in operating rooms compared to those in the ICU. Concerns about becoming infected, feelings of isolation, and exhaustion were associated with high hesitation to work. Feeling protected by the government and hospital was associated with decreased hesitation and increased motivation to work. Conclusions: ICU HCWs experienced high levels of stress throughout the first year of COVID-19, while satisfaction with work remained high. Willingness to work was associated with gender, work location, ICU subtype, concerns about infection risk, feelings of exhaustion, and feelings of institutional protection. Because the study methodology precludes causal inference and low survey response rates indicate that findings should be interpreted with caution, these results are best viewed as hypothesis-generating for future work aimed at improving stress mitigation in ICU HCWs. Full article

Firefighters are regularly exposed to occupational stress and potentially traumatic events. However, few evidence-based, fire service-specific interventions exist. Brief, mindfulness-based interventions may help address these challenges by improving regulation skills and reducing psychological distress. This pilot randomized controlled trial primarily evaluated the feasibility and acceptability of a one-session, group-based, virtual mindful attention training workshop developed specifically for firefighters, with secondary evaluation of preliminary efficacy. Firefighters (N = 82) were recruited from multiple fire departments across a large U.S. Southwestern metropolitan area and randomized to the mindful attention workshop (n = 45) or a waitlist control condition (n = 37). Feasibility outcomes were mixed, with strong enrollment among eligible participants (74.5%) but relatively low workshop attendance among those randomized to the intervention (53.3%). A total of 24 firefighters completed the workshop and found it to be helpful, informative, and relevant to the challenges faced in the fire service, with group processes characterized by high comfort, understanding, and low conflict. However, no significant between-group differences were observed in reductions in symptom severity or increases in mindfulness-based outcomes. Post hoc descriptive analyses revealed that most firefighters expressed strong interest in digitally delivered mental health content and the vast majority perceived online or app-based firefighter-specific mental health resources as helpful. Findings indicate mixed feasibility, strong acceptability among attendees, and a lack of preliminary efficacy, and highlight directions for refining intervention delivery of this pilot workshop and evaluating clinical impact in future trials. Full article

(1) Background: Nurses are exposed to occupational stressors that may impair their well-being and quality of life. This study examined whether burnout and secondary traumatic stress mediate the relationship between perceived stress and physical and psychological quality of life. (2) Methods: A cross-sectional study included 294 nurses employed at the Clinical Hospital Center Osijek, Croatia. Data were collected using the Perceived Stress Scale (PSS-10), the Burnout and Secondary Traumatic Stress subscales of the Professional Quality of Life Scale (ProQOL-5), and the physical and psychological domains of the WHOQOL-BREF. Pearson correlations and path analysis were used. (3) Results: Perceived stress showed significant negative effects on physical (β = −0.291; p < 0.001) and psychological quality of life (β = −0.217; p < 0.001), and positive effects on burnout (β = 0.230; p < 0.001) and secondary traumatic stress (β = 0.171; p = 0.002). Burnout significantly mediated both relationships, while secondary traumatic stress did not. The model explained 20.8% and 19.3% of variance in physical and psychological quality of life. (4) Conclusions: Burnout represents an important pathway linking perceived stress with poorer quality of life among nurses. Full article

Background: Healthcare professionals are exposed to high emotional demands, including repeated contact with suffering, death, moral distress, and organizational pressure. These factors are associated with psychological distress, burnout, and secondary traumatic stress. Expressive Writing (EW) has been proposed as a psychological intervention, but evidence of its effectiveness among healthcare professionals remains heterogeneous. Objectives: To examine the effects of EW on psychological health, psychophysical well-being, and professional satisfaction among healthcare professionals. Methods: A systematic review was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA 2020 guidelines. Searches were performed in PubMed, CINAHL, CENRAL, CENTRAL Scopus, Embase, and PsycINFO from database inception to January 2025. Quantitative studies involving healthcare professionals and evaluating structured expressive writing interventions were considered for inclusion, including randomized and non-randomized, controlled and uncontrolled designs. Studies reporting psychological, psychophysical, or work-related outcomes were eligible. Only full-text articles published in English or Italian were considered. The review protocol was registered and archived in the Open Science Framework. Methodological quality was assessed using CASP checklists, the RoB 2 tool, and the Newcastle–Ottawa Scale. Results: Seven studies published between 2017 and 2023 were included. EW interventions were associated with reductions in psychological distress, particularly perceived stress, depressive symptoms, and post-traumatic stress symptoms. Findings regarding burnout and compassion fatigue were mixed. Organizational and job-related outcomes, such as job satisfaction and organizational commitment, showed limited and heterogeneous improvements. No consistent effects were observed for resilience or social support. Overall, the methodological quality of the included studies was generally good. Conclusions: EW appears to be a promising, low-cost intervention for reducing psychological distress among healthcare professionals. However, heterogeneity in study designs, intervention protocols, and outcome measures limits the strength of the evidence. Further high-quality, controlled studies using standardized EW protocols are needed. Full article

Background: An aortic disease diagnosis can be perceived by patients as a stressful and often life-altering event. In addition, an acute event, such as aortic rupture or dissection—and the surgical intervention that will be required to address it—can be viewed as potentially life-threatening and traumatic. Serious health conditions, including stroke and acute coronary syndromes, have been described in the literature to correlate with trauma-like symptoms. Post-traumatic stress disorder (PTSD) is well described in connection with external traumatic events, such as war, assault and similarly catastrophic events. A key element of this type of PTSD is that its occurrence arises secondary to an external traumatizer. However, recent work has suggested that internal events—such as a catastrophic medical event (e.g., acute cardiovascular event and/or surgery)—can trigger PTSD symptoms. An important question is whether medical event-initiated PTSD can (or should) be treated similarly to traditionally defined PTSD, when the triggering threat may persist rather than having been confined to a past event. This systematic review will summarize the literature on the occurrence of PTSD as a consequence of an acute cardiovascular event and attempt to identify effective treatments using meta-analysis, if the literature quantity and quality support it. Methods: The search strategy will include publicly available electronic databases, including MEDLINE via PubMed and OVID, EMBASE via Elsevier, Cumulative Index for Nursing and Allied Health Literature (CINAHL) via EBSCOhost, SCOPUS, PsychInfo, and the Cochrane Library, to identify publications that report the development and/or treatment of PTSD as a consequence of an acute cardiovascular event, which include cardiac arrest, acute coronary syndromes, and acute aortic syndromes. Identification of publications, article classification, methodological review/quality assessment, and data extraction will be performed by two trained experts in cardiovascular epidemiology, with the resolution of disagreements carried out by a third independent reviewer. The review conduct and meta-analysis will follow PRISMA and MOOSE guidelines. Data will be aggregated using random effects models when quantitative data are reliable and heterogeneity is reasonable. If a quantitative synthesis is not possible due to data quality, a narrative synthesis will be conducted. Statistical heterogeneity will be assessed by I² statistics. The quality of evidence will be assessed using the GRADE criteria. Ethics and Dissemination: This study did not require an institutional review board or human subjects protection committee approval given the nature of the study design. The results will be published in a peer-reviewed journal, along with recommendations for future research. Full article

Background/Objectives: Police officers are exposed to chronic occupational stress and traumatic events, placing them at increased risk for mental health problems. Previous meta-analyses have been limited by heterogeneous samples and methodological variability. This study evaluated the effectiveness of psychological interventions on mental health and posttraumatic stress disorder (PTSD) symptoms among police officers using randomized controlled trials (RCTs). Methods: A systematic search of PubMed, Embase, Web of Science, PsycINFO, and MEDLINE was conducted for studies published between January 2000 and September 2025. The search strategy utilized key terms including “police officers,” “psychological interventions,” “mental health,” and “randomized controlled trials”. Only RCTs involving police officers were included. Psychological interventions were compared with waitlist, usual-care, or active control conditions. General mental health outcomes (depression, anxiety, and stress) were analyzed as the primary outcome, and PTSD symptoms as a secondary outcome. Effect sizes were calculated as Hedges’s g using random-effects models. Subgroup, meta-regression, sensitivity, and publication bias analyses were conducted when appropriate. Results: Ten RCTs comprising 637 police officers met the inclusion criteria. Psychological interventions demonstrated moderate improvements in overall mental health (Hedges’s g = 0.516, 95% CI = 0.296–0.735, p < 0.001), albeit with substantial heterogeneity. Comparable effects were observed across waitlist and usual-care/active control comparisons. For PTSD symptoms, significant improvements were found only in comparisons with waitlist controls, whereas the overall pooled effect was not statistically significant. Meta-regression showed no dose–response relationship between total intervention hours and treatment effects. Sensitivity analyses confirmed result robustness. The certainty of evidence was rated as moderate for general mental health and low for PTSD symptoms, primarily due to substantial inconsistency and imprecision. Conclusions: These findings suggest that structured psychological programs show potential to confer added benefits for general mental health beyond routine wellness activities, although the certainty of the evidence is moderate to low. In contrast, the evidence for PTSD symptoms remains inconclusive, with effects failing to reach robust statistical significance. This underscores that preliminary individual-level intervention may be insufficient for trauma-specific symptoms, necessitating further research into specialized, trauma-focused approaches and the role of organizational determinants in enhancing intervention efficacy. Full article

Background/Objectives: Secondary traumatic stress (STS) affects healthcare professionals indirectly exposed to patients’ trauma, and emergency personnel may be particularly vulnerable. Evidence from Romania is limited. Methods: We conducted a cross-sectional survey (July–August 2025) among emergency medical professionals working across the integrated emergency care system in Timisoara, Romania (prehospital ambulance/SMURD services and hospital Emergency Department). Secondary Traumatic Stress (STS) symptoms were measured using the 17-item Secondary Traumatic Stress Scale (STSS; item coding 1–5). We summarized STSS total/subscale scores and reliability, classified total scores into severity categories (0–68 metric), compared scores by workplace, sex, and professional role, and examined associations with age and years of experience. Results: The analytic sample included 145 participants (49.0% women), with a median age of 44 years [33–50] and median professional experience of 10 years [5–15]. Mean total STSS was 36.4 (SD 11.9; range 17–66) and internal consistency was high (Cronbach’s alpha = 0.92). Most participants were classified as little/no STS (77.2%), followed by mild (12.4%), moderate (5.5%), high (4.1%), and severe (0.7%). STSS scores did not differ significantly between ambulance service and ED/UPU staff. Women reported higher total STSS than men (39.0 vs. 33.9; p = 0.010), with significant differences for intrusion (p = 0.035) and arousal (p = 0.004). Role differences were significant for total STSS, intrusion, and arousal (p ≤ 0.031), with nurses scoring higher than ambulance drivers/attendants in post hoc comparisons. Years of experience showed small positive correlations with total STSS (r = 0.18, p = 0.032) and intrusion (r = 0.21, p = 0.010); age was associated with intrusion only (r = 0.22, p = 0.008). Conclusions: In this Romanian emergency care cohort, most participants reported low STS severity, but a clinically relevant minority had moderate-to-severe symptoms. Higher symptom burden among women and nurses suggests groups that may benefit from targeted monitoring and support within the integrated emergency system. Full article

Mental health disorders (MHDs) and acute coronary syndromes (ACSs) demonstrate reciprocal pathophysiological connections with substantial prognostic implications. Despite robust evidence linking MHDs to adverse cardiovascular outcomes, the bidirectional relationship remains inadequately characterized in clinical practice, with limited integration of mental health screening into routine cardiac care pathways. The present narrative review comprehensively presents contemporary data on epidemiology, shared biological mechanisms, clinical consequences, and integrated management strategies across the MHD–ACS continuum. A synthesis of peer-reviewed literature, meta-analyses, observational cohorts, randomized trials, and international guideline documents was performed, focusing on depression, anxiety, post-traumatic stress disorder, bipolar disorder, schizophrenia, and suicidality in relation to ACSs. MHDs are highly prevalent in ACS populations and independently predict increased mortality, major adverse cardiac events, and poorer functional recovery. Shared mechanisms include chronic low-grade inflammation, autonomic imbalance, hypothalamic–pituitary–adrenal axis hyperactivation, platelet hyperreactivity, and endothelial dysfunction. Selective serotonin reuptake inhibitors and cognitive behavioral therapy demonstrate the strongest evidence for treating depression in cardiac populations. Collaborative, stepped-care, and integrated cardiac rehabilitation models consistently improve psychological outcomes, with variable effects on cardiovascular endpoints. MHDs and ACSs form a self-reinforcing clinical continuum. Routine mental health screening and integrated cardio-psychiatric care represent essential components of secondary prevention and long-term outcome optimization. Full article

Background and Objectives: Traumatic brain injury (TBI) triggers oxidative stress, mitochondrial dysfunction, and sterile inflammation. Amantadine (ATD), a weak NMDA receptor antagonist, has shown neuroprotective potential, but its mechanistic basis remains unclear. This study examined whether ATD treatment is associated with changes in molecular and histological markers related to the HIF-1α/BNIP3L/HMGB1-mediated hypoxia–mitophagy–inflammation response in a rat TBI model. Materials and Methods: Thirty-two Wistar rats were assigned to four groups: sham, trauma, trauma + ATD (1 day), and trauma + ATD (7 days). TBI was induced using the impact-acceleration model, and ATD (45 mg/kg, i.p.) was administered post-injury. Oxidative stress indices (TOS, TAS, OSI), histopathology, inflammatory/apoptotic markers (CRP, TNF-α, Caspase-3), and gene expression (HIF-1α, BNIP3L, HMGB1) were evaluated. Results: ATD improved oxidative balance and histopathological integrity while reducing TNF-α, CRP, and Caspase-3 immunoreactivity. qPCR analysis showed lower HIF-1α, BNIP3L, and HMGB1 expression in ATD-treated groups, which is consistent with attenuation of hypoxia-related, mitochondrial stress-associated, and damage-associated molecular pattern-associated signaling after injury. Conclusions: In this experimental model, amantadine ameliorated oxidative, inflammatory, and apoptotic markers and was associated with reduced expression of HIF-1α, BNIP3L, and HMGB1. These findings support a mechanistic correlation between ATD treatment and suppression of secondary injury signatures; however, causal pathway relationships and functional neurological outcomes were not assessed. Full article

Background and Objectives: The COVID-19 pandemic has led to an unprecedented mental health crisis among workers in the healthcare field, with average burnout rates increasing from about 32% before the pandemic to 46–52% during peak times and post-traumatic stress disorder (PTSD) affecting 24–34% of frontline staff. The primary objective of this article is to synthesize evidence on the prevalence of burnout and PTSD among healthcare workers before and during the COVID-19 pandemic. The secondary objectives are: (a) to examine the mechanisms and empirical evidence linking clinician mental health to medical errors and patient safety outcomes and (b) to analyze the medico-legal implications of this relationship, including malpractice liability, institutional responsibility, and opportunities for policy reform. Materials and Methods: We conducted a narrative review searching PubMed (November 2025–January 2026) using predefined keyword combinations. Inclusion criteria comprised original research, systematic reviews, and meta-analyses examining mental health outcomes or patient safety among clinical staff. Data were synthesized narratively across five thematic domains. Results: Burnout prevalence increased from approximately 32% pre-pandemic to 46–52% during peak periods, with emotional exhaustion reaching 67.5% in some settings. PTSD rates rose to 24–34% among frontline staff, exceeding pre-pandemic levels of 15–20%, with ICU staff particularly affected (27–40%). Substantial overlap exists between conditions (86–98% comorbidity). Physician burnout is associated with 2.72 times higher odds of self-reported errors (95% CI: 2.19–3.37), with each point increase in emotional exhaustion raising the error risk by 5–11%. Mechanisms include cognitive impairment (reduced executive function, g = −0.39; impaired working memory, g = −0.36) and sleep disturbance. Malpractice litigation compounds psychological harm, increasing depression and suicidal ideation. Conclusions: This review, synthesizing data from over 500,000 healthcare workers, demonstrates bidirectional relationships among burnout, PTSD, and medical errors with significant medico-legal ramifications. Addressing this crisis requires systemic interventions including workload management, psychological support, blame-free reporting cultures, and policy reforms balancing accountability with recognition of system-level contributors to error. Full article