Implementation and impact of the World Health Organization integrated care for older people (ICOPE) program in China: a randomised controlled trial.

BACKGROUND: Fragmentation of services increases health and social care burden as people live longer with higher prevalence of diseases, frailty and dependency. Local evidence for implementing person-centred integrated care is urgently needed to advance practice and policies to achieve healthy ageing. OBJECTIVE: To test the feasibility and impact of World Health Organization's (WHO) Integrated Care for Older People (ICOPE) approach in China. DESIGN: A randomised controlled trial examining the feasibility of implementing ICOPE approach, evaluating its impact on health outcomes and health resource utilisation. SETTING: Primary care setting in urban and suburban communities of Chaoyang District, Beijing, China. SUBJECTS: Community-dwelling older adults screened as at-risk of functional declines and randomised into intervention (537) and control (1611) groups between September 2020 and February 2021. METHODS: A 6-month intervention program following WHO's ICOPE care pathways implemented by integrated care managers compared to standard available care. RESULTS: After 1 to 1 propensity score matching, participants in intervention and control groups (totally 938) had comparable baseline characteristics, demonstrated feasibility of implementing ICOPE with satisfaction by participants (97-99%) and providers (92-93%). All outcomes showed improvements after a 6-month intervention, while statistically significant least-squares mean differences (control-intervention) in vitality (Mini-Nutritional Assessment Short Form to measure vitality, -0.21, 95% CI, -0.40-0.02), mobility (Short Physical Performance Battery to measure mobility, -0.29, 95% CI, -0.44-0.14) and psychological health (Geriatric Depression Scale five items to measure psychological health, 0.09, 95% CI, 0.03-0.14) were observed (P < 0.05). CONCLUSIONS: It is feasible to localise and implement WHO's ICOPE approach in regions with fragmented resources such as China. Preliminary evidence supports its acceptance among key stakeholders and impact on health outcomes.

WHO working definition of vitality capacity for healthy longevity monitoring.

Intrinsic capacity, a crucial concept in healthy ageing, is defined by WHO as "the composite of all the physical and mental capacities that an individual can draw on at any point in time". Vitality capacity is considered the underlying physiological determinant of intrinsic capacity. To advance the measurement and monitoring of vitality capacity, a working group of WHO staff members and twenty experts representing six WHO regions was convened to discuss and clarify the attributes of vitality capacity and to develop a clear working definition of the concept. Potential biomarkers to measure vitality capacity were identified, and the following consensual working definition was developed: vitality capacity is a physiological state (due to normal or accelerated biological ageing processes) resulting from the interaction between multiple physiological systems, reflected in (the level of) energy and metabolism, neuromuscular function, and immune and stress response functions of the body.

What long-term care interventions have been published between 2010 and 2020? Results of a WHO scoping review identifying long-term care interventions for older people around the world.

OBJECTIVE: The global population is rapidly ageing. To tackle the increasing prevalence of older adults' chronic conditions, loss of intrinsic capacity and functional ability, long-term care interventions are required. The study aim was to identify long-term care interventions reported in scientific literature from 2010 to 2020 and categorise them in relation to WHO's public health framework of healthy ageing. DESIGN: Scoping review conducted on PubMed, CINHAL, Cochrane and Google Advanced targeting studies reporting on long-term care interventions for older and frail adults. An internal validated Excel matrix was used for charting.Setting nursing homes, assisted care homes, long-term care facilities, home, residential houses for the elderly and at the community. INCLUSION CRITERIA: Studies published in peer-reviewed journals between 1 January 2010 to 1 February 2020 on implemented interventions with outcome measures provided in the settings mentioned above for subjects older than 60 years old in English, Spanish, German, Portuguese or French. RESULTS: 305 studies were included. Fifty clustered interventions were identified and organised into four WHO Healthy Ageing domains and 20 subdomains. All interventions delved from high-income settings; no interventions from low-resource settings were identified. The most frequently reported interventions were multimodal exercise (n=68 reports, person-centred assessment and care plan development (n=22), case management for continuum care (n=16), multicomponent interventions (n=15), psychoeducational interventions for caregivers (n=13) and interventions mitigating cognitive decline (n=13). CONCLUSION: The identified interventions are diverse overarching multiple settings and areas seeking to prevent, treat and improve loss of functional ability and intrinsic capacity. Interventions from low-resource settings were not identified.

Implementing care for healthy ageing.

The WHO concept of Healthy Ageing (ie, the process of developing and maintaining the functional ability that enables well-being in older age) has initiated a global discussion about the need for shifting paradigms to reorient health and social services towards person-centred and coordinated models of care. In particular, the integration of health and social care services is critical to provide the basis for comprehensive information sharing and service delivery to support the evolution of the older person over time. The capability to monitor and respond to an older person's changing health and social care needs will enable prompt and personalised health and social care plans to be implemented.The implementation of an integrated care approach involves all the settings where persons age, but also requires a concerted action among micro (clinical), meso (service delivery) and macro (system) level. The community is of particular relevance given the primary objective of "ageing in place". However, from the perspective of the continuum of care and services acting synergistically, all health and social care settings (including long-term care facilities and hospitals) need to evolve and embrace an integrated way of operating to support functional ability in older people, while maximising resource and information sharing efficiencies.In this paper, we explain that government actions to promote well-being in older age should be built on a seamless continuum of care starting from the assessment of the older person's intrinsic capacity and functional ability with the final aim of providing care aligned with the individual's needs and priorities.

Novel biomarkers of oxidative stress as predictive indicators of neurological outcome after out-of-hospital cardiopulmonary arrest.

AIM: Among patients of out-of-hospital cardiopulmonary arrest (OHCPA), only 6% resume their pre-OHCPA social life. The prediction of neurological outcome immediately after the return of spontaneous circulation (ROSC) is urgently needed in OHCPA patients. Novel biomarkers, biological antioxidant potential (BAP), and diacron-reactive oxygen metabolites (d-ROM) are potential predictors of neurological outcome after OHCPA. This study was conducted to evaluate the utility of BAP and d-ROM in the prediction of patient outcomes after OHCPA. METHODS: Blood samples were collected immediately after OHCPA patients were admitted to our hospital between May 2011 and June 2013. BAP and d-ROM concentrations were measured with the simple equipment FRAS4 ™ (Wismerll, Italy). Their association with favorable (cerebral performance category [CPC], 1 and 2) and unfavorable (CPC 3-5) clinical outcomes was compared. BAP and d-ROM values from 23 normal healthy volunteers (HV) were used as controls. RESULTS: Overall, 152 OHCPA patients were included, and 26 patients achieved ROSC. Eleven died during hospitalization were allocated a CPC of 5 and remaining patients were discharged or transported (CPC 1: n = 4; CPC 2: n = 6; CPC 3: n = 3; CPC 4: n = 2; CPC 5: n = 11). The receiver operating characteristics curve of d-ROM and BAP for predicting survival 28 days after OHCPA was 0.596 and 0.834, respectively. Patients without ROSC had significantly higher BAP than HV and patients with ROSC (p < 0.001). A significant correlation was evident between BAP and the time to ROSC (r = 0.641, p < 0.01). CONCLUSION: Oxidative stress, indicated by BAP on admission, strongly correlated with the neurological outcome after OHCPA.

Integrated prevention and management of non-communicable diseases, including musculoskeletal health: a systematic policy analysis among OECD countries.

INTRODUCTION: Development and implementation of appropriate health policy is essential to address the rising global burden of non-communicable diseases (NCDs). The aim of this study was to evaluate existing health policies for integrated prevention/management of NCDs among Member States of the Organisation for Economic Co-operation and Development (OECD). We sought to describe policies' aims and strategies to achieve those aims, and evaluate extent of integration of musculoskeletal conditions as a leading cause of global morbidity. METHODS: Policies submitted by OECD Member States in response to a World Health Organization (WHO) NCD Capacity Survey were extracted from the WHO document clearing-house and analysed following a standard protocol. Policies were eligible for inclusion when they described an integrated approach to prevention/management of NCDs. Internal validity was evaluated using a standard instrument (sum score: 0-14; higher scores indicate better quality). Quantitative data were expressed as frequencies, while text data were content-analysed and meta-synthesised using standardised methods. RESULTS: After removal of duplicates and screening, 44 policies from 30 OECD Member States were included. Three key themes emerged to describe the general aims of included policies: system strengthening approaches; improved service delivery; and better population health. Whereas the policies of most countries covered cancer (83.3%), cardiovascular disease (76.6%), diabetes/endocrine disorders (76.6%), respiratory conditions (63.3%) and mental health conditions (63.3%), only half the countries included musculoskeletal health and pain (50.0%) as explicit foci. General strategies were outlined in 42 (95.5%) policies-all were relevant to musculoskeletal health in 12 policies, some relevant in 27 policies and none relevant in three policies. Three key themes described the strategies: general principles for people-centred NCD prevention/management; enhanced service delivery; and system strengthening approaches. Internal validity sum scores ranged from 0 to 13; mean: 7.6 (95% CI 6.5 to 8.7). CONCLUSION: Relative to other NCDs, musculoskeletal health did not feature as prominently, although many general prevention/management strategies were relevant to musculoskeletal health improvement.

Frontline Science: Escherichia coli use LPS as decoy to impair neutrophil chemotaxis and defeat antimicrobial host defense.

Bacterial infections and sepsis are leading causes of morbidity and mortality in critically ill patients. Currently, there are no effective treatments available to improve clinical outcome in sepsis. Here, we elucidated a mechanism by which Escherichia coli (E. coli) bacteria impair neutrophil (PMN) chemotaxis and we studied whether this mechanism can be therapeutically targeted to improve chemotaxis and antimicrobial host defense. PMNs detect bacteria with formyl peptide receptors (FPR). FPR stimulation triggers mitochondrial ATP production and release. Autocrine stimulation of purinergic receptors exerts excitatory and inhibitory downstream signals that induce cell polarization and cell shape changes needed for chemotaxis. Here we show that the bacterial cell wall product LPS dose-dependently impairs PMN chemotaxis. Exposure of human PMNs to LPS triggered excessive mitochondrial ATP production and disorganized intracellular trafficking of mitochondria, resulting in global ATP release that disrupted purinergic signaling, cell polarization, and chemotaxis. In mice infected i.p. with E. coli, LPS treatment increased the spread of bacteria at the infection site and throughout the systemic circulation. Removal of excessive systemic ATP with apyrase improved chemotaxis of LPS-treated human PMNs in vitro and enhanced the clearance of E. coli in infected and LPS-treated mice. We conclude that systemic ATP accumulation in response to LPS is a potential therapeutic target to restore PMN chemotaxis and to boost the antimicrobial host immune defense in sepsis.

Plasma Adenylate Levels are Elevated in Cardiopulmonary Arrest Patients and May Predict Mortality.

Cerebral and cardiac dysfunction cause morbidity and mortality in postcardiac arrest syndrome (PCAS) patients. Predicting clinical outcome is necessary to provide the optimal level of life support for these patients. In this pilot study, we examined whether plasma ATP and adenylate levels have value in predicting clinical outcome in PCAS patients. In total, 15 patients who experienced cardiac arrest outside the hospital setting and who could be reanimated were enrolled in this study. Healthy volunteers (n = 8) served as controls. Of the 15 PCAS patients, 8 died within 4 days after resuscitation. Of the 7 survivors, 2 lapsed into vegetative states, 1 survived with moderate disabilities, and 4 showed good recoveries. Arterial blood samples were drawn immediately after successful resuscitation and return of spontaneous circulation (ROSC). The concentrations of ATP and other adenylates in plasma were assessed with high-performance liquid chromatography. PCAS patients had significantly higher ATP levels than healthy controls. Plasma ATP levels correlated with lactate levels, Acute Physiology and Chronic Health Evaluation II scores, and the time it took to ROSC (time-to-ROSC). Plasma adenylate levels in patients who died after resuscitation were significantly higher than in survivors. Based on our results and receiver-operating characteristic curve analysis, we conclude that plasma adenylate levels may help predict outcome in PCAS patients.

The anticoagulant treatment for sepsis induced disseminated intravascular coagulation; network meta-analysis.

INTRODUCTION: The benefits and harm caused by anticoagulant treatments for sepsis induced disseminated intravascular coagulation (DIC) remain unclear. Therefore, we performed a network meta-analysis to assess the effect of available anticoagulant treatments on patient mortality, DIC resolution and the incidence of bleeding complication in patients with septic DIC. MATERIALS AND METHODS: We considered all studies from four recent systematic reviews and searched the PubMed, MEDLINE, and Cochrane databases for other studies that investigated anticoagulant treatment for septic DIC using antithrombin, thrombomodulin, heparin, or protease inhibitors in adult critically ill patients. These four anticoagulants and placebo were compared. The primary outcome in this study was patient mortality, and the secondary outcomes were the DIC resolution rate and incidence of bleeding complications. RESULTS: The network meta-analysis included 1340 patients from nine studies. There were no significant differences in the risks of mortality and bleeding complications among all direct comparisons and the network meta-analysis. Using a placebo was associated with a significantly lower rate of DIC resolution, compared to antithrombin in the direct comparison (odds ratio [OR]: 0.20, 95% credible interval [95% CrI]: 0.046-0.81) and in the network meta-analysis (OR: 0.20, 95% CrI: 0.043-0.84). CONCLUSIONS: Our study revealed no significant differences in the risks for mortality and bleeding complications when a placebo and all four anticoagulants were compared in septic DIC patients. The results also indicated that antithrombin was associated with a five-fold higher likelihood of DIC resolution, compared to placebo.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

BACKGROUND AND PURPOSE: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] 10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. METHODS: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. RESULTS: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs. CONCLUSIONS: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

Background and Purpose: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. Methods: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (>66.6%) majority vote of each of the 19 committee members. Results: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs. Conclusions: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (JSSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within eachteam were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a twothirds (>66.6%) majority vote of each of the 19 committee members. A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in additionto ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement.We conducted meta-analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs.Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

A case of omental herniation through the esophageal hiatus successfully treated by laparoscopic surgery.

Case: We report a rare case of omental herniation through the esophageal hiatus. A 46-year-old man visited our emergency department complaining of epigastralgia. Abdominal examination revealed muscular defense and rebound tenderness in his upper abdomen. A computed tomography scan showed a fat density mass in the posterior mediastinum. A laparoscopic operation was carried out under the diagnosis of omental herniation through the esophageal hiatus. Outcome: Abdominal pain disappeared dramatically after the operation. The postoperative course was uneventful. Conclusion: Although a fat density mass in the posterior mediastinum is likely to be diagnosed as a lipomatous tumor, omental herniation through the esophageal hiatus should be taken into consideration as a possible diagnosis for acute abdominal pain in the emergency department.

Fluorescence imaging of ATP in neutrophils from patients with sepsis using organelle-localizable fluorescent chemosensors.

BACKGROUND: The activation of polymorphonuclear neutrophils (PMNs) plays an important role in sepsis. Previously, we showed that ATP release and feedback via ATP receptors are essential for PMN activation; however, the dynamics remain poorly understood. Two new fluorescent chemosensors, PMAP-1 and MitoAP-1, were developed to detect ATP in the plasma membrane and mitochondria of living cells, respectively. In this study, we aimed to evaluate ATP localization using these chemosensors in PMNs of sepsis patients. METHODS: Live PMNs isolated from 16 sepsis patients and healthy controls (HCs) were stained with these chemosensors and observed by confocal microscopy, and their mean fluorescence intensities (MFIs) were evaluated using flow cytometry. CD11b expression in PMNs was also evaluated. RESULTS: The MFIs of PMAP-1 and MitoAP-1 and CD11b expression in PMNs from sepsis patients on days 0-1 were significantly higher than those of HCs. The MFI of PMAP-1 and CD11b expression on days 3-4 decreased significantly compared to those observed at days 0-1, whereas MitoAP-1 MFI was maintained at a high level. The PMAP-1 MFI was significantly positively correlated with CD11b expression, white blood cell counts, neutrophil counts, and C-reactive protein levels in patients. CONCLUSIONS: The higher MFIs of PMAP-1 and MitoAP-1 in sepsis patients suggest a pivotal role of ATP for PMN activation. The temporal difference in ATP levels suggests that ATP plays different roles in the mitochondria and on the cell surface. These data should contribute to the understanding of the dynamics of ATP in PMNs and help to develop a novel therapy for sepsis.

Utility of blood lactate level in triage.

Aim: Simple Triage and Rapid Treatment (START) is commonly used at disaster scenes. The Canadian Emergency Department Triage and Acuity Scale (CTAS) is used in urban and rural emergency departments (ED). However, triage is not always accurate or appropriate. The blood lactate level (BLL) is a major biomarker of physical status. We measured BLL using the Lactate Pro-1710 Test Meter in all patients transported to our ED and assessed their correlation with the triage level determined using START and the CTAS. Methods: This retrospective study included 510 patients admitted to our ED between January 2011 and July 2012 whose BLL was measured. The patients were classified into triage divisions (green, yellow, red, and black) according to vital signs and chief complaints, and correlations among BLL, triage level, and prognosis were assessed in all groups. Results: Of the total, 62 patients had cardiopulmonary arrest (CPA), 262 had internal pathologies, and 186 had external pathologies. Significant correlations were observed between BLL and both START and CTAS triage. Also BLL was significantly higher in severe patients categorized with START and CTAS (P < 0.0001), especially in the death group when the patients were divided into two groups according to prognosis (P < 0.0001). Two patients categorized yellow with START died during the hospitalization, however BLL of these two patients were high on admission at the ED. Conclusion: BLL could be used to correct the triage level, and decide the priority of treatment and transportation even within the same triage level, thereby avoiding under-triage.

Inhibition of Neutrophils by Hypertonic Saline Involves Pannexin-1, CD39, CD73, and Other Ectonucleotidases.

Hypertonic saline (HS) resuscitation has been studied as a possible strategy to reduce polymorphonuclear neutrophil (PMN) activation and tissue damage in trauma patients. Hypertonic saline blocks PMNs by adenosine triphosphate (ATP) release and stimulation of A2a adenosine receptors. Here, we studied the underlying mechanisms in search of possible reasons for the inconsistent results of recent clinical trials with HS resuscitation. Purified human PMNs or PMNs in whole blood were treated with HS to simulate hypertonicity levels found after HS resuscitation (40 mmol/L beyond isotonic levels). Adenosine triphosphate release was measured with a luciferase assay. Polymorphonuclear neutrophil activation was assessed by measuring oxidative burst. The pannexin-1 (panx1) inhibitor panx1 and the gap junction inhibitor carbenoxolone (CBX) blocked ATP release from PMNs in purified and whole blood preparations, indicating that HS releases ATP via panx1 and gap junction channels. Hypertonic saline blocked N-formyl-Met-Leu-Phe-induced PMN activation by 40% in purified PMN preparations and by 60% in whole blood. These inhibitory effects were abolished by panx1 but only partially reduced by CBX, which indicates that panx1 has a central role in the immunomodulatory effects of HS. Inhibition of the ectonucleotidases CD39 and CD73 abolished the suppressive effect of HS on purified PMN cultures but only partially reduced the effect of HS in whole blood. These findings suggest redundant mechanisms in whole blood that may strengthen the immunomodulatory effect of HS in vivo. We conclude that HS resuscitation exerts anti-inflammatory effects that involve panx1, CD39, CD73, and other ectonucleotidases, which produce the adenosine that blocks PMNs by stimulating their A2a receptors. Our findings shed new light on the immunomodulatory mechanisms of HS and suggest possible new strategies to improve the clinical efficacy of hypertonic resuscitation.