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 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.

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.

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.

Leukocyte deformability is a novel biomarker to reflect sepsis-induced disseminated intravascular coagulation.

Aim: Sepsis-induced disseminated intravascular coagulopathy is associated with a high mortality rate. The function and deformability of polymorphonuclear leukocytes change in patients with sepsis. The goal of this study was to characterize the changes in polymorphonuclear leukocyte deformability in patients with sepsis-induced disseminated intravascular coagulopathy and to evaluate the relationship between the severity of disseminated intravascular coagulopathy and the deformability of polymorphonuclear leukocytes. Methods: Thirty-five patients with sepsis-induced disseminated intravascular coagulopathy at our department were enrolled in this study. These patients were diagnosed with severe sepsis and an acute disseminated intravascular coagulopathy score ≥ 4. Blood samples were obtained from these patients on days 1, 3, and 7. Polymorphonuclear leukocyte deformability was measured with a microchannel flow analyzer, and polymorphonuclear leukocyte activity, represented as CD11b, was measured by flow cytometry. In contrast, 14 patients who fulfilled with sepsis criteria but without complicated disseminated intravascular coagulopathy were also entered in this study. Results: In patients with sepsis-induced disseminated intravascular coagulopathy, there was a significant correlation between their Japanese Association for Acute Medicine disseminated intravascular coagulopathy score and polymorphonuclear leukocyte deformability, and CD11b expression. Polymorphonuclear leukocytes became more stiffened and CD11b expression was higher in patients with sepsis-induced disseminated intravascular coagulopathy compared to patients without the condition. Conclusion: Polymorphonuclear leukocyte deformability correlated with the severity of sepsis-induced disseminated intravascular coagulopathy and the response to treatment.

Descending necrotizing mediastinitis: 5 years of published data in Japan.

Descending necrotizing mediastinitis implies infection originating from the neck, most commonly an oropharyngeal or odontogenic focus, that spreads in the cervical fascial spaces and descends into the mediastinum. Early diagnosis is essential because descending necrotizing mediastinitis can rapidly progress to septic shock and organ failure. A comprehensive review of the current data of descending necrotizing mediastinitis in Japan was carried out using PubMed and ICHUSHI from the last 5 years. The symptoms, origins, comorbid conditions, treatment modalities, complications, and survival rates were analyzed. Tonsillar and pharyngeal origin was more identified compared to odontogenic origin. More than one-third of patients were diabetic and 28% of them were not identified as having any comorbidity. Streptococcus sp. and anaerobes were most isolated, reflecting the microflora of the oral cavity. Of the broad antibiotics, carbapenem was the most used as treatment, and clindamycin was the most co-given. Mediastinal drainage approach varied widely and the optimal approach is controversial. Twenty-one patients were treated with video-assisted thoracic surgical drainage and 15 cases by percutaneous catheter drainage, whereas transcervical approach was applied in 25 patients and thoracotomy was carried out in 21 patients. The overall mortality was 5.6%. Many authors advocated that the most effective management tool is a high degree of clinical suspicion followed by prompt and adequate drainage with intensive care including hemodynamic and nutritional support and repeat computer tomographic monitoring.

Oxidative stress and heart rate variability in patients with vertigo.

Aims: Peripheral vertigo has been reported to result from oxidative stress or autonomic nervous dysfunction. Recently, heart rate variability has been used to evaluate autonomic nervous activity. Parasympathetic nervous dysfunction is associated with peripheral vertigo; however, the relationships between vertigo, oxidative stress, and autonomic nervous activity have not been investigated. The aim of this study was to elucidate the changes in oxidative stress and autonomic nervous activity in vertigo patients compared with healthy volunteers. Methods: Oxidative stress was assessed by evaluating biological antioxidant potential and reactive oxygen metabolites, and heart rate variability was measured to evaluate autonomic nervous activity. Thirty-four patients who complained of peripheral vertigo and were treated in our emergency department between January and August 2011 were enrolled in study 1. Oxidative stress and heart rate variability were measured and compared with those of healthy volunteers (n = 23). In study 2, oxidative stress in 18 vertigo patients and heart rate variability in 41 vertigo patients were measured between January and August 2012 before and after conventional treatment of vertigo to evaluate the effect of the treatment on oxidative stress and autonomic nervous activity. Results: Reactive oxygen metabolites were higher in vertigo patients than in healthy volunteers. Parasympathetic nervous activity was lower and the sympathetic/parasympathetic nervous activity ratio (autonomic nervous activity ratio) was higher in vertigo patients than in healthy volunteers. After treatment of vertigo, reactive oxygen metabolites decreased significantly and the autonomic nervous activity ratio became similar to that observed in healthy volunteers. Conclusions: Bedside monitoring of oxidative stress and heart rate variability may be useful for the diagnosis of vertigo and evaluation of the effect of treatment.

Plasma ATP is required for neutrophil activation in a mouse sepsis model.

Our previous work has shown that polymorphonuclear neutrophils (PMNs) require cellular adenosine triphosphate (ATP) release and autocrine purinergic signaling for their activation. Here we studied in a mouse model of cecal ligation and puncture (CLP) whether sepsis affects this purinergic signaling process and thereby alters PMN responses after sepsis. Using high-performance liquid chromatography, we found that plasma ATP, adenosine diphosphate (ADP), and adenosine monophosphate (AMP) concentrations increased up to 6-fold during the first 8 h after CLP, reaching top levels that were significantly higher than those in sham control animals without CLP. Although leukocyte and PMN counts in sham animals increased significantly after 4 h, these blood cell counts decreased in sepsis animals. CD11b expression on the cell surface of PMNs of septic animals was significantly higher compared with sham and untreated control animals. These findings suggest increased PMN activation and sequestration of PMN from the circulation after sepsis. Plasma ATP levels correlated with CD11b expression, suggesting that increased ATP concentrations in plasma contribute to PMN activation. We found that treatment of septic mice with the ATP receptor antagonist suramin diminished CD11b expression, indicating that plasma ATP contributes to PMN activation by stimulating P2 receptors of PMNs. Increased PMN activation can protect the host from invading microorganisms. However, increased PMN activation can also be detrimental by promoting secondary organ damage. We conclude that pharmacological targeting of P2 receptors may allow modulation of PMN responses in sepsis.

A3 adenosine receptor inhibition improves the efficacy of hypertonic saline resuscitation.

We reported previously that hypertonic saline (HS) treatment can prevent or upregulate the function of polymorphonuclear neutrophils (PMNs) via A2a-type adenosine receptors or A3-type adenosine receptors (A3R), respectively. A3R translocate to the cell surface upon PMN stimulation, and thus, HS promotes PMN responses under conditions of delayed HS treatment. Here we investigated if inhibition of A3R improves the protective effects of HS resuscitation in a mouse sepsis model. We found that HS nearly triples extracellular adenosine concentrations in whole blood and that inhibition of A3R with the selective antagonist MRS-1191 dose dependently improves the inhibitory effect of HS. MRS-1191 at a concentration of 1 nM enhanced the inhibitory effect of HS and reduced stimulatory effects of delayed HS treatment. Using a mouse model of cecal ligation and puncture (CLP)-induced sepsis, we found that MRS-1191 reduces acute lung injury and PMN accumulation in lung tissue. Whereas delayed HS treatment (4 mL/kg of 7.5% NaCl) of mice 1 h after CLP aggravated PMN accumulation, lung tissue damage, and mortality 24 h after CLP, infusion of MRS-1191 (2 ng/kg body weight) combined with HS reduced these detrimental effects of delayed HS treatment. Our data thus show that A3 receptor antagonists can strengthen the beneficial effects of HS resuscitation by avoiding stimulatory adverse effects that result from delayed HS administration.

Hypertonic stress regulates T cell function via pannexin-1 hemichannels and P2X receptors.

Hypertonic saline (HS) resuscitation increases T cell function and inhibits posttraumatic T cell anergy, which can reduce immunosuppression and sepsis in trauma patients. We have previously shown that HS induces the release of cellular ATP and enhances T cell function. However, the mechanism by which HS induces ATP release and the subsequent regulation of T cell function by ATP remain poorly understood. In the present study, we show that inhibition of the gap junction hemichannel pannexin-1 (Panx1) blocks ATP release in response to HS, and HS exposure triggers significant changes in the expression of all P2X-type ATP receptors in Jurkat T cells. Blocking or silencing of Panx1 or of P2X1, P2X4, or P2X7 receptors blunts HS-induced p38 MAPK activation and the stimulatory effects of HS on TCR/CD28-induced IL-2 gene transcription. Moreover, treatment with HS or agonists of P2X receptors overcomes T cell suppression induced by the anti-inflammatory cytokine IL-10. These findings indicate that Panx1 hemichannels facilitate ATP release in response to hypertonic stress and that P2X1, P2X4, and P2X7 receptor activation enhances T cell function. We conclude that HS and P2 receptor agonists promote T cell function and thus, could be used to improve T cell function in trauma patients.

Adrenergic receptor activation involves ATP release and feedback through purinergic receptors.

Formyl peptide receptor-induced chemotaxis of neutrophils depends on the release of ATP and autocrine feedback through purinergic receptors. Here, we show that adrenergic receptor signaling requires similar purinergic feedback mechanisms. Real-time RT-PCR analysis revealed that human embryonic kidney (HEK)-293 cells express several subtypes of adrenergic (α(1)-, α(2)-, and ß-receptors), adenosine (P1), and nucleotide receptors (P2). Stimulation of G(q)-coupled α(1)-receptors caused release of cellular ATP and MAPK activation, which was blocked by inhibiting P2 receptors with suramin. Stimulation of G(i)-coupled α(2)-receptors induced weak ATP release, while G(s)-coupled ß-receptors caused accumulation of extracellular ADP and adenosine. ß-Receptors triggered intracellular cAMP signaling, which was blocked by scavenging extracellular adenosine with adenosine deaminase or by inhibiting A2a adenosine receptors with SCH58261. These findings suggest that adrenergic receptors require purinergic receptors to elicit downstream signaling responses in HEK-293 cells. We evaluated the physiological relevance of these findings using mouse aorta tissue rings. Stimulation of α(1)-receptors induced ATP release and tissue contraction, which was reduced by removing extracellular ATP with apyrase or in the absence of P2Y(2) receptors in aorta rings from P2Y(2) receptor knockout mice. We conclude that, like formyl peptide receptors, adrenergic receptors require purinergic feedback mechanisms to control complex physiological processes such as smooth muscle contraction and regulation of vascular tone.

Pannexin-1 hemichannel-mediated ATP release together with P2X1 and P2X4 receptors regulate T-cell activation at the immune synapse.

Engagement of T cells with antigen-presenting cells requires T-cell receptor (TCR) stimulation at the immune synapse. We previously reported that TCR stimulation induces the release of cellular adenosine-5'-triphosphate (ATP) that regulates T-cell activation. Here we tested the roles of pannexin-1 hemichannels, which have been implicated in ATP release, and of various P2X receptors, which serve as ATP-gated Ca(2+) channels, in events that control T-cell activation. TCR stimulation results in the translocation of P2X1 and P2X4 receptors and pannexin-1 hemichannels to the immune synapse, while P2X7 receptors remain uniformly distributed on the cell surface. Removal of extracellular ATP or inhibition, mutation, or silencing of P2X1 and P2X4 receptors inhibits Ca(2+) entry, nuclear factors of activated T cells (NFAT) activation, and induction of interleukin-2 synthesis. Inhibition of pannexin-1 hemichannels suppresses TCR-induced ATP release, Ca(2+) entry, and T-cell activation. We conclude that pannexin-1 hemichannels and P2X1 and P2X4 receptors facilitate ATP release and autocrine feedback mechanisms that control Ca(2+) entry and T-cell activation at the immune synapse.

Purinergic signaling: a fundamental mechanism in neutrophil activation.

Efficient activation of neutrophils is a key requirement for effective immune responses. We found that neutrophils released cellular adenosine triphosphate (ATP) in response to exogenous stimuli such as formylated bacterial peptides and inflammatory mediators that activated Fcgamma, interleukin-8, C5a complement, and leukotriene B(4) receptors. Stimulation of the formyl peptide receptor (FPR) led to ATP release through pannexin-1 (panx1) hemichannels, and FPRs colocalized with P2Y2 nucleotide receptors on the cell surface to form a purinergic signaling system that facilitated neutrophil activation. Disruption of this purinergic signaling system by inhibiting or silencing panx1 hemichannels or P2Y2 receptors blocked neutrophil activation and impaired innate host responses to bacterial infection. Thus, purinergic signaling is a fundamental mechanism required for neutrophil activation and immune defense.

Nonoperative catheter management for cervical necrotizing fasciitis with and without descending necrotizing mediastinitis.

OBJECTIVE: To evaluate the clinical utility of catheter drainage for cervical necrotizing fasciitis (CNF) with and without descending necrotizing mediastinitis (DNM). DESIGN: Retrospective analysis. SETTING: Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine. PATIENTS: Thirty-two patients with clinically and radiographically diagnosed CNF with and without DNM were included. INTERVENTIONS: Catheters were introduced into the infected space through the patients' necks under sonographic and x-ray fluoroscopic guidance. MAIN OUTCOME MEASURES: Treatments, clinical course, complications, and mortality were evaluated. RESULTS: Catheter drainage was successfully performed in all patients. The CNF was due to pharyngeal infection in 14 patients (44%) and dental infection in 14 other patients (44%). Mediastinal extension occurred in 14 patients (44%). Overall mortality was 3.1%; only 1 patient with DNM died due to Clostridium sepsis. Both pharyngeal origin and diabetes mellitus were significantly associated with the development of DNM. More intensive treatment is necessary for patients with CNF with DNM than for patients with CNF without DNM. CONCLUSION: Percutaneous catheter drainage may be used as an effective treatment for CNF with and without DNM.

Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes from patients with severe systemic inflammatory response syndrome.

BACKGROUND: Monocyte deactivation is an important contributor to infectious susceptibility in critically ill patients. However, the mechanism of monocyte deactivation has not been fully elucidated. Recently, intracellular heme oxygenese-1 (HO-1), an anti-inflammatory heat-shock protein, was reported to be activated by Toll-like receptors (TLRs), and to inhibit inflammatory cytokine production such as that of TNF-alpha. In the present study, we evaluated the expression of intracellular HO-1 and TLRs in monocytes from patients with severe systemic inflammatory response syndrome (SIRS) and examined the role of HO-1 in monocyte deactivation. PATIENTS: Twenty-seven patients who fulfilled the criteria for severe SIRS and had a serum C-reactive protein (CRP) level >10 mg/dL were included in this study. The cause of SIRS was sepsis in 16 patients, trauma in 7, and other in 4. Expression of intracellular HO-1, surface TLR2 and TLR4, and intracellular cytokines (TNF-alpha, Interleukin-6) stimulated via TLR activation were measured in circulating monocytes by flow cytometry. Intracellular HO-1 expression was evaluated in normal monocytes stimulated with patient serum. Serum cytokine levels were also measured. Patient data were compared with data from healthy volunteers (n = 16). RESULTS: Cytoplasmic HO-1 was clearly detected by fluorescence microscopy. Expression of HO-1, TLR2, and TLR4 in monocytes was significantly enhanced in patients with severe SIRS compared with that in healthy volunteers, whereas intracellular TNF-alpha expression with peptidoglycan was significantly decreased (p < 0.05) in patients compared with that in healthy volunteers. HO-1 expression was significantly enhanced in normal monocytes stimulated with patient serum. Intracellular HO-1 levels were positively related to serum TNF-alpha levels in patients (r = 0.46). CONCLUSIONS: Expression of intracellular HO-1 and of TLRs was enhanced in deactivated monocytes from patients with SIRS. Increased production of intracellular HO-1 in response to serum factors may play a role in monocyte deactivation after systemic inflammation.

[Smoke inhalation injury: diagnosis and respiratory management].

Smoke inhalation is a significant comorbid factor following major thermal injury. Smoke exposure is only a trigger for the sequence of events responsible for the development of inhalation injury. Noxious chemicals generated by incomplete combustion injure the exposed bronchoepithelium and stimulate the release of chemical mediators that cause a progressive inflammatory process. Airway inflammation and pulmonary edema impair gas exchange and increase the susceptibility to pulmonary infection. Earlier diagnosis and treatment of inhalation injury is an important element to improve the clinical course of severe burn patients. The American Burn Association, however, recently concluded that there are insufficient data to support a treatment standard for the diagnosis of inhalation injury. At present, the diagnosis of inhalation injury is supported by the combination of history, physical examination, bronchoscopy, and laboratory findings For accurate diagnosis of inhalation injury, helical CT scanning and examination to detect activated leukocytes in bronchoalveolar lavage fluid may be warranted. In the respiratory management of inhalation injury, repeated removal of pseudomembrane by fiberoptic bronchoscopy and the use of adequate PEEP to avoid airway obstruction are essential. High-frequency percussive ventilation can be a suitable mode of ventilation for inhalation injury.