Search Results (397)

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

Background: Emerging evidence indicates that some individuals recovering from COVID-19 develop persistent symptoms, including fatigue, pain, cognitive difficulties, and psychological distress, commonly known as Long COVID. These symptoms often overlap with those seen in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), underscoring the need for integrative, non-pharmacological interventions. This Phase II controlled trial aimed to evaluate the feasibility and preliminary efficacy of Heart Rate Variability Biofeedback (HRV-BF) in individuals with Long COVID who meet the diagnostic criteria for CFS/ME. Specific objectives included assessing feasibility indicators (drop-out rates, side effects, participant satisfaction) and changes in fatigue, depression, anxiety, pain, and health-related quality of life. Methods: Participants were assigned alternately and consecutively to the HRV-BF intervention or Treatment-as-usual (TAU), in a predefined 1:1 sequence (quasirandom assignment). The intervention consisted of 10 HRV-BF sessions, held twice weekly over 5 weeks, with each session including a 10 min respiratory preparation and 40 min of active training. Results: The overall drop-out rate was low (5.56%), and participants reported a generally high level of satisfaction. Regarding side effects, the mean total Simulator Sickness Questionnaire score was 24.31 (SD = 35.42), decreasing to 12.82 (SD = 15.24) after excluding an outlier. A significantly greater improvement in severe fatigue was observed in the experimental group (H = 4.083, p = 0.043). When considering all outcomes collectively, a tendency toward improvement was detected in the experimental group (binomial test, p < 0.0001). Conclusions: HRV-BF appears feasible and well tolerated. Findings support the need for Phase III trials to confirm its potential in mitigating fatigue in Long COVID. Full article

Opioids are among the most effective drugs for treating moderate to severe pain. Unfortunately, opioid use, even short-term, can lead to addiction, tolerance, overdose, and respiratory depression. Therefore, efforts to design and develop novel compounds that would retain analgesic activity while reducing side effects continue unabated. The present study was designed to investigate the respiratory and cardiovascular effects of the hybrid peptide LENART01, which has evidenced potent antinociceptive and antimicrobial activity. This hybrid peptide, composed of N-terminally located dermorphin and C-terminal modified ranatensin pharmacophore, was tested in vivo in anesthetized rats. The main effect of LENART01 was apnea in 70% of examined animals, sighing, and a significant increase in blood pressure. Interestingly, the hybrid induced sighs less frequently than ranatensin, and apnea dependent on vagus nerve mu opioid receptor activation much less frequently and less intensely than dermorphin itself. This shows that LENART01 is a safer opioid system-related agent as compared to dermorphin for its prospective use in the treatment of pain. Full article

Background/Objectives: Obstructive sleep apnea is a prevalent, yet often underdiagnosed, condition characterized by recurrent upper airway obstruction during sleep, leading to significant perioperative risks in surgical patients. This systematic review aims to evaluate the incidence and impact of objectively diagnosed obstructive sleep apnea on postoperative outcomes across various surgical specialties—including bariatric, orthopedic, cardiac, and otorhinolaryngologic surgeries—and to assess the effectiveness of preoperative screening and perioperative management strategies. Methods: A comprehensive literature search of PubMed was conducted for studies published between January 2013 and December 2024, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies involved adult surgical patients with OSA confirmed by polysomnography or respiratory polygraphy. Studies were assessed for methodological quality using the Oxford Centre for Evidence-Based Medicine Levels of Evidence framework. Results: The findings consistently indicated that obstructive sleep apnea significantly increases the risk of postoperative complications, such as respiratory depression, atrial fibrillation, acute kidney injury, delirium, and prolonged hospital stay. Continuous positive airway pressure therapy demonstrated a protective effect in bariatric and cardiac surgeries, though its effectiveness in orthopedic and otorhinolaryngologic contexts was inconsistent, largely due to adherence variability and limited implementation. Preoperative screening tools such as the STOP-BANG questionnaire were widely used, but their utility depended on integration with confirmatory diagnostics. Conclusions: Obstructive sleep apnea represents a significant, modifiable risk factor in surgical populations. Preoperative identification and risk-adapted perioperative management, including CPAP therapy and multimodal analgesia, may substantially reduce postoperative morbidity. However, further randomized trials and cost-effectiveness studies are needed to optimize care pathways and ensure consistent implementation across surgical disciplines. Full article

Background/Objectives: Continuous ventilation monitoring during pediatric sedation is essential, as respiratory depression may occur silently and may not be detected promptly by conventional methods such as pulse oximetry. Non-invasive capnography has been proposed to improve early detection of respiratory compromise. This prospective observational study evaluated the diagnostic accuracy of non-invasive capnography, compared to pulse oximetry, for detecting respiratory depression in pediatric patients undergoing sedation. Methods: We conducted a single-center, prospective observational study at a tertiary pediatric hospital, enrolling 101 patients (ages 1–17 years) undergoing sedation for diagnostic or therapeutic procedures. Patients were monitored using both pulse oximetry and non-invasive capnography. Episodes of respiratory depression—defined as apnea, hypopneic hypoventilation, bradypneic hypoventilation, and desaturation—were recorded. We compared the diagnostic performance and time to detection between capnography and pulse oximetry. Results: We identified 93 episodes of respiratory depression in 52 patients (51.1%). Capnography detected all apnea episodes and 76.9% of hypopneic hypoventilation episodes that were not identified by pulse oximetry. The median time advantage of capnography over pulse oximetry was 35 s (p = 0.0055). Combining capnography and pulse oximetry identified more events than pulse oximetry alone (93 vs. 53 episodes). Conclusions: Non-invasive capnography improves the early detection of respiratory depression compared to conventional monitoring with pulse oximetry in pediatric procedural sedation. While these findings support its routine use to enhance patient safety, larger multicenter studies are needed to demonstrate its diagnostic accuracy and impact on clinical outcomes. Full article

Objective: This study aims to investigate the feasibility of an online music therapy protocol for individuals previously diagnosed with COVID-19, focusing on their perceptions of their respiratory symptoms and the intervention’s impact on psychosocial measures. Methods: A within-subject experimental design was applied to examine an eight-week weekly online music therapy protocol, including singing, wind instrument playing, and music visualizations. All self-report data were collected bi-weekly throughout the 16-weeks study period, including baseline and post-tests. The measures for respiratory symptoms included the Medical Research Council’s Dyspnea Scale (MRC Dyspnea), Chronic Respiratory Questionnaire-Mastery Scores (CRQ Mastery), and Visual Analogue Scale for breathlessness. The measures for the secondary psychosocial outcomes were the Beck Depression Inventory-Short Form, the Generalized Anxiety Disorder 7-item, the Hospital Anxiety and Depression Scale, the Fatigue Severity Scale, the Epworth Sleepiness Scale, the EuroQol 5-Dimension 5-Level, and the Connor-Davidson Resilience Scale. Results: Twenty-four participants were enrolled. The participants perceived a reduction in respiratory symptoms, and shortness of breath (MRC Dyspnea). Planned comparisons showed significant decreases in MRC from baseline to post-treatment (p = 0.008). The mixed-effects model, including pre-baseline and post-treatment, was significant (p < 0.001). Significant changes in Breathing VAS were consistent with improvements in MRC Dyspnea, showing a significant baseline-to-post difference (p = 0.01). The CRQ Mastery showed significant improvements from baseline to Week 12 (p < 0.001). No significant changes were observed in other secondary measures. Conclusions: Our preliminary findings suggest that this protocol is feasible, and as a result, may help individuals previously diagnosed with COVID-19 to cope with lasting respiratory symptoms and improve their perception of shortness of breath. Live music-making, including playing accessible wind instruments and singing, may contribute to an increase sense of control over breathing. As this was a feasibility study, we conducted multiple uncorrected statistical comparisons to explore potential effects. While this approach may increase the risk of Type I error, the findings are intended to inform hypotheses for future confirmatory studies rather than to draw definitive conclusions. Full article

Background: Marburg virus disease (MVD) is a highly lethal filoviral infection, yet its long-term health consequences remain poorly understood. We present one of the most temporally distant evaluations of MVD survivors, conducted 13 years post-outbreak in Uganda, offering novel insights into chronic physiological, biochemical, haematological, and psychosocial outcomes. Methods: A cross-sectional, community-based study compared ten MVD survivors with nineteen age- and sex-matched unexposed controls. Clinical evaluations included vital signs, anthropometry, mental health screening, and symptom reporting. Laboratory analyses covered electrolytes, inflammatory markers, renal and liver function tests, haematology, and urinalysis. Standardised psychological assessments measured anxiety, depression, perceived stigma, and social support. Findings: Survivors exhibited an elevated body mass index (BMI), higher systolic and diastolic blood pressure, and lower respiratory rates compared to controls, indicating ongoing cardiometabolic and autonomic changes. These trends may reflect persistent cardiometabolic stress and potential alterations in autonomic regulation, warranting further investigation. Biochemically, survivors exhibited disruptions in serum chloride, bilirubin, and total protein levels, suggesting subclinical hepatic and renal stress. Haematological analysis revealed persistent reticulocytosis despite normal haemoglobin levels, indicating long-term erythropoietic modulation. Despite these physiological changes, survivors reported minimal psychological morbidity, sharply contrasting with the post-recovery profiles of other viral haemorrhagic fevers. Stigma was prevalent during the outbreak; however, strong family support alleviated long-term psychosocial distress. Interpretation: Thirteen years post-infection, MVD survivors demonstrate multisystem physiological perturbations without marked psychological sequelae. These findings challenge assumptions of universal post-viral trauma and highlight the necessity for tailored survivor care models. Future longitudinal studies should investigate the mechanistic pathways underlying cardiometabolic and haematological reprogramming to inform intervention strategies in resource-limited settings. Full article

Background: Recurrent vomiting in infantile hypertrophic pyloric stenosis (IHPS) leads to metabolic alkalosis and a respiratory-driven compensatory hypercapnia. Alkalosis has been identified as the main causal factor for respiratory depression on admission. The value of contribution of hemoglobin and carbon dioxide partial pressure to this phenomenon will be evaluated. Materials and Methods: A retrospective cohort study was conducted on 105 infants with IHPS. The acid/base status, including levels of hemoglobin and lactate, were recorded. Statistical comparisons, correlation analysis, linear regression and multivariate regression analysis were applied. Results: Hypercapnia was associated with hemoconcentration. We found a positive correlation was found between pCO₂ and hemoglobin (p = 0.042). The multivariate linear regression analysis showed that pCO₂ is dependent on hemoglobin (p = 0.002). Lactate, which is used as a marker for anaerobic glycolysis, showed no systematic correlation with pCO₂. Conclusions: An increase in carbon dioxide cannot easily be attributed to a reduced transport function of carbon dioxide due to hemoglobin deficiency. Further investigation is needed to determine the extent to which low hemoglobin levels and increased pCO₂ interact with hemoconcentration to contribute to respiratory problems. Full article

Neuropeptide FF (NPFF) receptor antagonists prevent morphine-mediated antinociceptive tolerance, and compounds with dual mu opioid receptor (MOR) agonist and NPFF antagonist activity produce antinociception without tolerance. Compounds synthesized showed affinities in radioligand competition binding assays in the nM and µM range at the opioid and NPFF receptors, respectively, and displayed substitution-dependent functional profiles in the [³⁵S]GTPγS functional assay. From six compounds screened in vivo for antinociception and ability to prevent NPFF-induced hyperalgesia in mouse warm water tail withdrawal tests, compound 22b produced dose-dependent MOR-mediated antinociception with an ED₅₀ value (and 95% confidence interval) of 6.88 (4.71–9.47) nmol, i.c.v., and also prevented NPFF-induced hyperalgesia. Meanwhile, 22b did not demonstrate the respiratory depression, hyperlocomotion, or impaired intestinal transit of morphine. Moreover, repeated treatment with 22b produced a 1.6-fold rightward shift in antinociceptive dose response, significantly less acute antinociceptive tolerance than morphine. Evaluated for microsomal stability in vitro and in vivo pharmacokinetic profile, 22b showed suitable microsomal stability paired in vivo with a large apparent volume of distribution and a clearance smaller than the hepatic flow in rats, suggesting no extra-hepatic metabolism. In conclusion, the present study confirms that dual-action opioid–NPFF ligands may offer therapeutic promise as analgesics with fewer liabilities of use. Full article

In patients with respiratory diseases, a panel of markers is often used to assess disease severity and progression. Here we test whether the serum lipid signature may surge as a reliable alternative marker to monitor systemic hypoxia, a frequent unfavourable outcome in acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary diseases (COPD). We recruited 9 healthy controls, 10 COPD patients, and 10 ARDS patients. Various markers related to inflammation, redox imbalance, and iron handling were measured alongside lipid profiles obtained through untargeted lipidomic analysis. The results show that serum lipids were moderately lower in COPD patients and significantly reduced in ARDS patients compared to the controls. Six lipid classes (cholesteryl esters, coenzyme Q, phosphatidylinositol, sterols, hexosylceramides, and phosphatidylethanolamine) exhibited significant changes (ANOVA p < 0.05) and correlated with the Horowitz index (P/F), suggesting their potential as markers of hypoxia severity. While conventional markers also correlated with P/F, the lipid signature was more specific and reliable. This study highlights that hypoxia in pulmonary diseases depresses circulating lipids, with certain lipid classes offering more precise predictions of hypoxia severity. Expanding this research to larger populations could support the lipid signature as a clinical tool. Full article

Objectives: This study explored the health-related quality of life (HRQoL), psychological health, and patient-reported outcomes (PROs) of patients with amyotrophic lateral sclerosis (ALS) in China, providing insights for enhancing clinical care. Methods: A cross-sectional study was conducted among Chinese ALS patients between February and May 2024. Demographics, clinical characteristics, and PROs were assessed. HRQoL and psychological health were evaluated via the 5-item amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-5) and the 4-item patient health questionnaire (PHQ-4), respectively. Spearman’s rank correlation, multiple linear regression, and the Kruskal–Wallis H test were used to analyze associations between clinical factors, HRQoL, and psychological health. Results: A total of 237 participants aged 46–65 years (63.3%) were included. The mean ALSAQ-5 score was 64.86±19.34, indicating an impaired HRQoL, whereas the mean PHQ-4 score (5.82 ± 4.10,) suggested varied degree of anxiety and depression. Age, disease duration, ALS severity, fatigue, stress, and pain severity, and respiratory support were significantly associated with HRQoL (p < 0.05). Age, stress severity, and pain severity were significant predictors of psychological distress (p < 0.01). Patients reported diagnostic delay, profound lifestyle changes (96.4%), fear of paralysis (84.8%), and death (49.8%). Most patients (80.6%) expressed a strong desire to stop ALS progression, prioritizing treatments that improve breathing, muscle weakness, swallowing, and mobility issues. Conclusions: ALS profoundly impacts patients’ HRQoL and psychological health. Integrating PROs into clinical care strategies is crucial for improving patient outcomes and guiding treatment priorities. Full article

Non-operating room anesthesia (NORA) is a rapidly growing domain for anesthesia professionals due to advances in procedural technology and increased emphasis on patient comfort. The majority of these procedures are conducted under monitored anesthesia care (MAC) where patients receive varying levels of sedation. Analysis of the Anesthesia Closed Claims database suggests that adverse respiratory events continue to be the main cause of morbidity and mortality in patients undergoing NORA procedures. Most NORA claims occurred under MAC, with oversedation leading to respiratory depression coupled with inadequate monitoring making up the majority of claims. The American Society of Anesthesiologists (ASA) has released standards of pre-anesthesia, intraoperative monitoring, and post-anesthesia care, which apply to all anesthetizing locations including NORA. The ASA has also made recommendations in a statement on NORA to promote patient safety. Evidence suggests that patient characteristics, monitoring tools, physical constraints, and team familiarity play a role in the risk for adverse respiratory events. Future studies are required to further understand the challenges specific to NORA locations. Full article

Background and Objectives: Percutaneous liver radiofrequency ablation (RFA) under monitored anesthesia care (MAC) carries a risk of hypoxia due to respiratory depression. Ensuring adequate oxygenation during such procedures is essential for patient safety. This study aimed to evaluate whether a high-flow nasal cannula (HFNC) improves oxygenation compared to a simple facemask during RFA. Materials and Methods: In this prospective, randomized controlled trial, 51 patients undergoing ultrasound-guided RFA under MAC were allocated to receive oxygen via an HFNC (30 L/min) or a facemask (6 L/min). Arterial blood gases were collected at the baseline and 5 min after oxygenation. The primary outcome was the arterial partial pressure of oxygen (PaO₂). Secondary outcomes included hypoxia incidence (SpO₂ < 95%), the difference in the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen concentration (ΔP/F ratio), the difference in the arterial partial pressure of carbon dioxide (ΔPaCO₂), respiratory rate (RR) changes, and patient satisfaction. Results: After adjustment for the baseline PaO₂, the HFNC group showed significantly higher intra-procedural PaO₂ compared to the facemask group (299 ± 18.6 vs. 194 ± 19.0 mmHg, p < 0.001). No significant differences were found in the ΔP/F ratio, ΔPaCO₂, or patient satisfaction. Among the secondary outcomes, RR was more stable in the HFNC group throughout the procedure (Group × Time interaction, p = 0.003). Conclusions: The HFNC significantly improved intra-procedural PaO₂ during RFA under MAC but did not reduce hypoxia incidence or improve other clinical outcomes compared to facemask oxygenation. The stability of RR observed with the HFNC may reflect a physiological advantage, though further studies are needed to determine its clinical relevance. Full article

Background/Objectives: The use of opioid drugs in the elderly population is characterized by an increased risk of sedation and respiratory depression, and in the immediate postoperative period, it is associated with a higher incidence of postoperative delirium. The dilemma of opioid use as an element of acute postoperative pain therapy is crucial in elderly patients. Methods: This study was conducted in 80 patients qualified for laparoscopic cholecystectomy under general combined anesthesia. Two methods of analgesia were performed—Low-Opioid Analgesia (LOA) and Opioid-Based Analgesia (OBA)—and pain intensity based on the Numerical Rating Scale (NRS) was assessed at 0–2, 2–6, 6–12, and 12–24 h after surgery. The mean NRS in LOA and OBA was compared in age categories. Pain trajectory in patients over 60 years old was compared between LOA and OBA. Results: The trajectory of analgesia presented a negative slope in LOA for patients over 60 years of age, with reductions in pain intensity of 33%, 25%, and 66%. In OBA, a positive slope trajectory was noted, and pain intensity was higher within 12–24 h after surgery than within 0–2 and 2–6 h. Conclusions: Opioid analgesia in patients over 60 years of age presented a better effect in the immediate postoperative period. Non-opioid analgesia is indicated for patients over 60 years old in the later postoperative period. The model of combined minimal opioid anesthesia and non-opioid postoperative analgesia presents a favorable therapeutic effect for patients over 60 years old. Full article

Background: Late-life depression is a critical public health concern, particularly among older adults with chronic multimorbidity. Existing studies often focus on single-disease associations, neglecting the complex interplay of coexisting conditions. Understanding how multimorbidity patterns contribute to depression risk and identifying high-risk subgroups through integrated statistical and machine learning approaches remain underexplored, limiting targeted prevention strategies. Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS), latent class analysis (LCA) was employed to cluster multimorbidity patterns. Associations between these patterns and depression were analyzed using multivariable logistic regression, while predictive performance and interaction effects were evaluated via an XGBoost machine learning model. Results: Four distinct multimorbidity patterns were identified: cardio-metabolic, digestive–joint, respiratory, and cardiovascular–digestive pattern. All clusters showed significant independent associations with depression, with the cardiovascular–digestive pattern exhibiting the strongest association (OR = 4.56). However, the digestive–joint pattern demonstrated the highest predictive effects for depression. Sociodemographic factors—low income, limited education, female gender, and rural residence—emerged as robust predictors, amplifying depression risk in older adults with multimorbidity. Conclusions: This study bridges epidemiological insights with predictive analytics to inform depression risk stratification. We recommend routine depression screening for all individuals with cardiovascular–digestive diseases and prioritize screening for women with digestive–joint diseases. Additionally, low-income and rural-dwelling older adults with chronic conditions warrant heightened clinical vigilance. These findings provide a framework for integrating multimorbidity profiling into depression prevention protocols, addressing both biological and socioeconomic determinants. Full article