Obesity is a prevalent health issue among adolescents, characterized by chronic low-grade inflammation, which increases the risk of developing various chronic diseases in the future. The systemic immune-inflammation index (SII) serves as an indicator of inflammation and immune response. This study conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016, including 5,676 participants. A multivariate logistic regression model, Generalized Additive Models (GAM), and subgroup analysis were used to examine the relationship between obesity and SII. The multivariate logistic regression results revealed a significant positive correlation between log SII and adolescent obesity (1.254 [1.024–1.537]). Furthermore, the risk of obesity increased with higher quartiles of SII. Subgroup analysis and interaction tests showed that this positive association persisted across various factors, including female gender, race (Non-Hispanic White and Mexican American), non-hyperlipidemia, normal white blood cell count, and PIR < 1. Additionally, a U-shaped relationship between log SII and obesity was observed, with a turning point at 6.410. The findings suggest that an increase in the systemic immune-inflammation index is significantly associated with obesity in adolescents. However, further validation through large-scale prospective studies is needed.

To the Editor: We write in support of the groundbreaking research by Roberts and colleagues.1 Their study presents virtual interactive patient (VIP) videos as an innovative tool that promises to redefine medical pedagogy in the digital age, and we agree with this premise. In the current milieu, the onus put on medical educators to deliver comprehensive, practical training has never been more pronounced. The VIP videos, as meticulously detailed by Roberts and colleagues, appear poised to fill this void. The strong proficiency demonstrated by first-year students in tasks, such as formulating patient care plans and articulating problem representation statements, is a testament to the efficacy of this approach. Furthermore, the seamless alignment of the VIP videos with the biomedical curriculum offers a synergistic learning experience, harmonizing theoretical knowledge with real-world clinical simulations. However, as with any innovative venture, there are areas for improvement. The extended completion time and the perceived complexity of some videos can be addressed through iterative refinements, ensuring an optimal balance between depth and accessibility. Building on the foundational work of Roberts and colleagues, we propose that the scope of VIP videos can be expanded even further. As the methodology is fine-tuned, it could potentially serve as a template for more advanced medical training modules. Imagine a scenario where medical students, across various stages of their education, engage with a series of progressively complex clinical encounter scenarios, honing their clinical acumen in a controlled yet realistic environment. The potential benefits, both in terms of skill acquisition and patient safety, could be immense. The VIP video approach, introduced by Roberts and colleagues, represents a monumental step forward in medical education. Binding technology with traditional pedagogy opens the door to a more integrated, immersive, and pragmatic learning ecosystem. As educators and researchers, we are presented with a golden opportunity to build on this foundation, driving medical education into the future. Yu Hao, MD, PhDAttending physician, Department of Critical Care Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, and research member, Key Laboratory of Pediatric Anesthesiology of the Ministry of Education, Wenzhou, China; email: [email protected]; ORCID: https://orcid.org/0000-0002-8351-1206Suwas BhandariDoctoral student, the Second School of Medicine, Wenzhou Medical University, Wenzhou, China

Background & AimsSepsis-induced disseminated intravascular coagulation (DIC) is characterized by abnormal blood clotting resulting from severe infection, contributing to organ dysfunction in sepsis. Resolvin D1 (RvD1) is an endogenous lipid mediator, synthesized from the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) through enzymatic processes involving 15-LOX and 5-LOX. RvD1 is recognised for its protective properties against various inflammatory conditions. This study aims to investigate its potential to modulate coagulation dysfunction in sepsis and to evaluate coagulation disorders in septic patients.MethodsSepsis models were established by intraperitoneal injection LPS (20 mg/kg) or cecal ligation and puncture (CLP) followed by injection of RvD1 (10 μg/kg) or saline. The impact of RvD1 on coagulation dysfunction was assessed by clotting time and coagulation indicators such as TAT, D-dimer, PAI-1, and fibrinogen. The activity of the coagulation system in vivo was observed by evaluating dynamic microcirculation, platelets and thrombin in mice using intravital microscopy. The effect of RvD1 on pyroptosis was investigated by measuring NOD-like receptor protein 3 (NLRP3), Caspase-1, Caspase-11, and Gasdermin D (GSDMD) levels via western blot. Caspase-1 knockout mice, GSDMD knockout mice and bone marrow-derived macrophages (BMDMs) were used to elucidate the underlying mechanisms. Lastly, the concentration of RvD1 in plasma from septic patients was quantified to explore its relationship with coagulation and pyroptosis.ResultsRvD1 significantly attenuated coagulation dysfunction in septic mice induced by LPS and CLP, and inhibited Caspase-1/GSDMD-dependent pyroptosis in septic mice and bone marrow-derived macrophages. In septic patients, the plasma concentrations of RvD1 was negatively correlated with both coagulation-related indicators and markers of GSDMD activation.ConclusionThe results suggest that RvD1 can improve coagulation dysfunction in sepsis by regulating the Caspase-1/GSDMD pyroptotic pathway. Additionally, the concentration of RvD1 in septic patient plasma is related to prognosis and DIC development. RvD1 could be a potential biomarker and a promising therapeutic alternative in sepsis-induced DIC.

No competing financial interests exist.

Background: Traumatic brain injury (TBI) is a head trauma usually associated with death and endothelial glycocalyx damage. Syndecan-1 (SDC-1)-a biomarker of glycocalyx degradation-has rarely been reported in meta-analyses to determine the clinical prognostic value in TBI patients. Methods: We looked into PubMed, EMBASE, Cochrane Library, and Web of Science databases from January 1, 1990, to May 1, 2023, to identify eligible studies. A meta-analysis was conducted using RevMan 5.4 and Stata 16.0 with the search terms "SDC-1" and "traumatic brain injury." Results: The present study included five studies with a total of 640 enrolled patients included. Syndecan-1 concentrations were higher in the isotrauma TBI group than in the non-TBI group (standardized mean difference [SMD] = 0.52; 95% CI: 0.03-1.00; P = 0.04). Subgroup analysis revealed statistical significance when comparing the SDC-1 level of multitrauma TBI (TBI + other injuries) group with the isotrauma TBI group (SMD = 0.74; 95% CI: 0.42-1.05; P < 0.001), and the SDC-1 level of the TBI coagulopathy (+) group (TBI with early coagulopathy) with the TBI coagulopathy (-) group (SMD = 1.75; 95% CI: 0.41-3.10; P = 0.01). Isotrauma TBI patients with higher SDC-1 level were at a higher risk of 30-day in-hospital mortality (odds ratio = 3.32; 95% CI: 1.67-6.60; P = 0.0006). Conclusion: This meta-analysis suggests that SDC-1 could be a biomarker of endotheliopathy and coagulopathy in TBI, as it was increased in isotrauma TBI patients and was higher in multitrauma TBI patients. There is a need for additional research into the use of SDC-1 as a prognostic biomarker in TBI, especially in isotrauma TBI patients.

The cardiopulmonary system is a physiological cornerstone in the adaptive response to hypobaric hypoxia. Portable devices make it feasible nowadays to precisely assess the response to high altitude (HA) expeditions. In this study, we investigated breathing and arterial blood pressure responses during a Himalayan trek from 665 m to 4,780 m altitude in a white European (Italian) sojourner and a native Nepali (Tamang) guide, both healthy males. Resting diurnal and nocturnal data were acquired by means of ambulatory blood pressure monitoring (ABPM) and sleep apnea monitoring. We found an increase in the mean diurnal arterial blood pressure. Nocturnal blood pressure dipping was confirmed at all altitudes. Oxygen saturation decreased at altitude, with its additional nocturnal fall. Sleep apneic episodes, present in the Italian only, increased with altitude. We conclude that the nocturnal, more than diurnal, cardiorespiratory function is affected by HA hypoxia. Further studies should address the role of ethnicity, medications, and sociodemographic factors in the cardiorespiratory responses to hypobaric hypoxia.

Endothelial glycocalyx degradation, critical for increased pulmonary vascular permeability, is thought to facilitate the development of sepsis into the multiple organ failure. Maresin conjugates in tissue regeneration 1 (MCTR1), a macrophage-derived lipid mediator, which exhibits potentially beneficial effects via the regulation of bacterial phagocytosis, promotion of inflammation resolution, and regeneration of tissue. In this study, we show that MCTR1 (100 ng/mouse) enhances the survival of mice with lipopolysaccharide (LPS)-induced (15 mg/kg) sepsis. MCTR1 alleviates LPS (10 mg/kg)-induced lung dysfunction and lung tissue inflammatory response by decreasing inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta [IL-1 beta], and IL-6) expression in serum and reducing the serum levels of heparan sulfate (HS) and syndecan-1. In human umbilical vein endothelial cells (HUVECs) experiments, MCTR1 (100 nM) was added to the culture medium with LPS for 6 hr. MCTR1 treatment markedly inhibited HS degradation by downregulating heparanase (HPA) protein expression in vivo and in vitro. Further analyses indicated that MCTR1 upregulates sirtuin 1 (SIRT1) expression and decreases NF-kappa B p65 phosphorylation. In the presence of BOC-2 or EX527, the above effects of MCTR1 were abolished. These results suggest that MCTR1 protects against LPS-induced sepsis in mice by attenuating pulmonary endothelial glycocalyx injury via the ALX/SIRT1/NF-kappa B/HPA pathway.

Maresin Conjugates in Tissue Regeneration 1 (MCTR1) is a newly identified macrophage-derived sulfido-conjugated mediator that stimulates the resolution of inflammation. This study assessed the role of MCTR1 in alveolar fluid clearance (AFC) in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Rats were intravenously injected with MCTR1 at a dose of 200 ng/rat, 8 hours after administration of 14 mg/kg LPS. The level of AFC was then determined in live rats. Primary rat ATII (Alveolar Type II) epithelial cells were also treated with MCTR1 (100 nmol/L) in a culture medium containing LPS for 8 hours. MCTR1 treatment improved AFC (18.85 +/- 2.07 vs 10.11 +/- 1.08, P < .0001) and ameliorated ALI in rats. MCTR1 also significantly promoted AFC by up-regulating epithelial sodium channel (ENaC) and Na+-K+-adenosine triphosphatase (Na, K-ATPase) expressions in vivo. MCTR1 also activated Na, K-ATPase and elevated phosphorylated-Akt (P-Akt) by up-regulating the expression of phosphorylated Nedd4-2 (P-Nedd4-2) in vivo and in vitro. However, BOC-2 (ALX inhibitor), KH7 (cAMP inhibitor) and LY294002 (PI3K inhibitor) abrogated the improved AFC induced by MCTR1. Based on the findings of this study, MCTR1 may be a novel therapeutic approach to improve reabsorption of pulmonary oedema during ALI/acute respiratory distress syndrome (ARDS).

Sepsis is life-threatening organ dysfunction caused by an imbalance in the body's response to infection and acute lung injury (ALI) related to sepsis is a common complication. The rapid morbidity and high mortality associated with sepsis is a significant clinical problem facing critical care medicine. Inflammation plays a vital role in the occurrence of sepsis. Notably, the body produces different immune cells and pro-inflammatory factors to clear pathogens. However, excessive inflammation can damage multiple tissues and organs when it fails to resolve in time. Additionally, lymphatic vessels could effectively transfer inflammatory cells and factors away from tissues and into blood circulation, thereby reducing damage, and promoting the resolution of inflammation. Therefore, any dysfunction and/or destruction of the lymphatic system may result in lymphedema followed by inflammatory storms and eventual sepsis. Consequently, the present study aimed to review and highlight the role of lymphatic vessels in related body tissues and organs during sepsis and other associated diseases.

The study aimed at exploring the mechanisms behind blood pressure and heart rate changes upon acute altitude exposure utilizing urinary excretion of biochemical factors involved in cardiovascular regulation. The study was conducted on 12 lowlander native male mountain climbers, living at sea level, exposed to altitudes ranging from 1800 to 5147 m above sea level over 4 days, during their ascent to Mount Ararat (Turkey). Blood pressure (measured by oscillometric method), heart rate, and blood oxygen saturation (SpO2) were recorded at rest (on awakening before food intake), in hypoxic conditions at 4200 m and at sea level before and after the altitude expedition. In the same study conditions (ie before‐during‐after the expedition), first‐voided urinary samples were collected and assayed for 8‐iso‐prostaglandin F2α (8‐iso‐PGF2α) and asymmetric dimethylarginine (ADMA) determination. Heart rate, and systolic and diastolic blood pressures were higher (P < .05) at high altitude than at the sea level. Furthermore, both urinary 8‐iso‐PGF2α and ADMA were significantly elevated (P < .01) at high altitude and returned to normal levels soon after returning to sea level. A 4‐day exposure to high‐altitude hypoxia induced a temporary increase in blood pressure and heart rate, confirming previous findings. Blood pressure increase at high altitude was associated with significantly enhanced production of biochemical mediators such as 8‐iso‐PGF2α, catecholamines, and ADMA, although we could not demonstrate a direct link between these parallel significant changes probably due to the forcefully limited sample size of our study, carried out in challenging environmental conditions at very high altitude.

Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The pathophysiological mechanism of sepsis is highly complex, and the mortality of in-patients suffering from sepsis is more than 10%. Severe unmanaged inflammation and inappropriate immune response characterize sepsis. Anti-inflammation therapies alone are not successful for the reason that disbalance of anti-inflammatory and pro-resolving agents. In the recent researches, the host responses during the course of self-resolving infections are found to have the involvements of specialized pro-resolution mediators (SPMs), namely, lipoxins, resolvins, protectins and maresins. These endogenous lipid metabolites are core signal molecules in the resolution of inflammation, playing a key role in regulating the inflammation and promoting return to homeostasis. Besides, heme oxygenase-1 (HO-1, a sensitive marker for oxidative stress) is also known for upregulation in inflammation profiling. Carbon monoxide, synthesized by HO-1, performs multiple stances of anti-inflammation and pro-resolution along with the SPMs. If the potentially beneficial effects of these mediators would be well evaluated in clinical trials, they present encouraging new hints in managing infectious maladies especially sepsis.

Long-term exposure to high altitude causes adaptive changes in several blood biochemical markers along with a marked body mass reduction involving both the lean and fat components. The aim of this study was to evaluate the impact of extended physical strain, due to extensive trekking at high altitude, on body composition, selected biomarkers in the blood, and the protective role of a high-protein diet in muscle dysfunction. We found that physical strain at high altitude caused a significant reduction in body mass and body fat, with a concomitant increase in the cross-sectional area of thigh muscles and an unchanged total lean body mass. Further, we found reductions in plasma leptin and homocysteine, while myoglobin, insulin, and C-reactive protein significantly increased. Creatine kinase, lactate dehydrogenase, and leptin normalized per body fat were unchanged. These findings demonstrate that high-altitude hypoxia, involving extended physical effort, has an impact on muscle function and body composition, facilitating sarcopenia and affecting body mass and fat distribution. It also activates pro-inflammatory metabolic pathways in response to muscular distress. These changes can be mitigated by a provision of a high-protein diet.

Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and alleviated mitochondrial damage. Based on a 1H NMR-based metabolomics analysis, CLP-induced septic mice had increased levels of acetate, pyruvate, and lactate in serum and decreased levels of alanine, aspartate, glutamate, and fumarate in lungs. However, these metabolic disorders, mainly involving energy and amino acid metabolism, can be recovered by MaR1 treatment. Therefore, our results suggest that the protective effects of MaR1 on sepsis could be related to the recovery of metabolic dysfunction and the alleviation of inflammation and mitochondrial damage.

Exposure to high altitude is one of the most widely used models to study the adaptive response to hypoxia in humans. However, little is known about the related effects on micturition. The present study addresses the adaptive urinary responses in four healthy adult lowlanders, comparing urodynamic indexes at Kathmandu [1,450 m above sea level (a.s.l.); K1450] and during a sojourn in Namche Bazar (3,500 m a.s.l.; NB3500). The urodynamic testing consisted of cistomanometry and bladder pressure/flow measurements. Anthropometrics, electrocardiographic, and peripheral capillary oxygen saturation data were also collected. The main findings consisted of significant reductions in bladder power at maximum urine flow by ~30%, bladder contractility index by 13%, and infused volume both at first (by 57%) and urgency sensation (by 14%) to urinate, indicating a reduced cystometric capacity, at NB3500. In addition to the urinary changes, we found that oxygen saturation, body mass index, body surface area, and median RR time were all significantly reduced at altitude. We submit that the hypoxia-related parasympathetic inhibition could be the underlying mechanism of both urodynamic and heart rate adaptive responses to high-altitude exposure. Moreover, increased diuresis and faster bladder filling at altitude may trigger the anticipation of being able to void, a common cause of urgency. We believe that the present pilot study represents an original approach to the study of urinary physiology at altitude.