Factors Associated With Prolonged Ventilation in Patients Receiving Prone Positioning Protocol With Muscle Relaxants for Severe COVID-19 Pneumonia.

BACKGROUND: Prone positioning and neuromuscular blocking agents (NMBAs) are frequently used to treat severe respiratory failure from COVID-19 pneumonia. Prone positioning has shown to improve mortality, whereas NMBAs are used to prevent ventilator asynchrony and reduce patient self-inflicted lung injury. However, despite the use of lung-protective strategies, high death rates in this patient population have been reported. METHODS: We retrospectively examined the factors affecting prolonged mechanical ventilation in subjects receiving prone positioning plus muscle relaxants. The medical records of 170 patients were reviewed. Subjects were divided into 2 groups according to ventilator-free days (VFDs) at day 28. Whereas subjects with VFDs < 18 d were defined as prolonged mechanical ventilation, subjects with VFDs ≥18 d were defined as short-term mechanical ventilation. Subjects' baseline status, status at ICU admission, therapy before ICU admission, and treatment in the ICU were studied. RESULTS: Under the proning protocol for COVID-19, the mortality rate in our facility was 11.2%. The prognosis may be improved by avoiding lung injury in the early stages of mechanical ventilation. According to multifactorial logistic regression analysis, persistent SARS-CoV-2 viral shedding in blood (P = .03), higher daily corticosteroid use before ICU admission (P = .007), delayed recovery of lymphocyte count (P < .001), and higher maximal fibrinogen degradation products (P = .039) were associated with prolonged mechanical ventilation. A significant relationship was found between daily corticosteroid use before admission and VFDs by squared regression analysis (y = -0.00008522x2 + 0.01338x + 12.8; x: daily corticosteroids dosage before admission [prednisolone mg/d]; y: VFDs/28 d, R2 = 0.047, P = .02). The peak point of the regression curve was 13.4 d at 78.5 mg/d of the equivalent prednisolone dose, which corresponded to the longest VFDs. CONCLUSIONS: Persistent SARS-CoV-2 viral shedding in blood, high corticosteroid dose from the onset of symptoms to ICU admission, slow recovery of lymphocyte counts, and high levels of fibrinogen degradation products after admission were associated with prolonged mechanical ventilation in subjects with severe COVID-19 pneumonia.

Personalized ventilatory strategy based on lung recruitablity in COVID-19-associated acute respiratory distress syndrome: a prospective clinical study.

BACKGROUND: Heterogeneity is an inherent nature of ARDS. Recruitment-to-inflation ratio has been developed to identify the patients who has lung recruitablity. This technique might be useful to identify the patients that match specific interventions, such as higher positive end-expiratory pressure (PEEP) or prone position or both. We aimed to evaluate the physiological effects of PEEP and body position on lung mechanics and regional lung inflation in COVID-19-associated ARDS and to propose the optimal ventilatory strategy based on recruitment-to-inflation ratio. METHODS: Patients with COVID-19-associated ARDS were consecutively enrolled. Lung recruitablity (recruitment-to-inflation ratio) and regional lung inflation (electrical impedance tomography [EIT]) were measured with a combination of body position (supine or prone) and PEEP (low 5 cmH2O or high 15 cmH2O). The utility of recruitment-to-inflation ratio to predict responses to PEEP were examined with EIT. RESULTS: Forty-three patients were included. Recruitment-to-inflation ratio was 0.68 (IQR 0.52-0.84), separating high recruiter versus low recruiter. Oxygenation was the same between two groups. In high recruiter, a combination of high PEEP with prone position achieved the highest oxygenation and less dependent silent spaces in EIT (vs. low PEEP in both positions) without increasing non-dependent silent spaces in EIT. In low recruiter, low PEEP in prone position resulted in better oxygenation (vs. both PEEPs in supine position), less dependent silent spaces (vs. low PEEP in supine position) and less non-dependent silent spaces (vs. high PEEP in both positions). Recruitment-to-inflation ratio was positively correlated with the improvement in oxygenation and respiratory system compliance, the decrease in dependent silent spaces, and was inversely correlated with the increase in non-dependent silent spaces, when applying high PEEP. CONCLUSIONS: Recruitment-to-inflation ratio may be useful to personalize PEEP in COVID-19-associated ARDS. Higher PEEP in prone position and lower PEEP in prone position decreased the amount of dependent silent spaces (suggesting lung collapse) without increasing the amount of non-dependent silent spaces (suggesting overinflation) in high recruiter and in low recruiter, respectively.

Association between tracheostomy and survival in patients with coronavirus disease 2019 who require prolonged mechanical ventilation for more than 14 days: A multicenter cohort study.

OBJECTIVE: Tracheostomy is a common procedure with potential prognostic advantages for patients who require prolonged mechanical ventilation (PMV). Early recommendations for patients with coronavirus disease 2019 (COVID-19) suggested delayed or limited tracheostomy considering the risk for viral transmission to clinicians. However, updated guidelines for tracheostomy with appropriate personal protective equipment have revised its indications. This study aimed to evaluate the association between tracheostomy and prognosis in patients with COVID-19 requiring PMV. METHODS: This was a multicenter, retrospective cohort study using data from the nationwide Japanese Intensive Care PAtient Database. We included adult patients aged ≥16 years who were admitted to the intensive care unit (ICU) due to COVID-19 and who required PMV (for >14 days or until performance of tracheostomy). The primary outcome was hospital mortality, and the association between implementation of tracheostomy and patient prognosis was assessed using weighted Cox proportional hazards regression analysis with inverse probability of treatment weighting (IPTW) using the propensity score to address confounders. RESULTS: Between January 2020 and February 2021, 453 patients with COVID-19 were observed. Data from 109 patients who required PMV were analyzed: 66 (60.6%) underwent tracheostomy and 38 (34.9%) died. After adjusting for potential confounders using IPTW, tracheostomy implementation was found to significantly reduce hospital mortality (hazard ratio [HR]: 0.316, 95% confidence interval [CI]: 0.163-0.612). Patients who underwent tracheostomy had a similarly decreased ICU and 28-day mortality (HR: 0.269, 95% CI: 0.124-0.581; HR 0.281, 95% CI: 0.094-0.839, respectively). A sensitivity analysis using different definitions of PMV duration consistently showed reduced mortality in patients who underwent tracheostomy. CONCLUSION: The implementation of tracheostomy was associated with favorable patient prognosis among patients with COVID-19 requiring PMV. Our findings support proactive tracheostomy in critically ill patients with COVID-19 requiring mechanical ventilation for >14 days.

Control of blood glucose levels by an artificial pancreas in patients with severe coronavirus disease 2019 pneumonia.

BACKGROUND: Many patients with severe coronavirus disease 2019 (COVID-19) pneumonia experience hyperglycemia. It is often difficult to control blood glucose (BG) levels in such patients using standard intravenous insulin infusion therapy. Therefore, we used an artificial pancreas. This study aimed to compare the BG status of the artificial pancreas with that of standard therapy. METHODS: Fifteen patients were included in the study. BG values and the infusion speed of insulin and glucose by the artificial pancreas were collected. Arterial BG and administration rates of insulin, parenteral sugar, and enteral sugar were recorded during the artificial pancreas and standard therapy. The target BG level was 200 mg/dl. RESULTS: Arterial BG was highly correlated with BG data from the artificial pancreas. A higher BG slightly increased the difference between the BG data from the artificial pancreas and arterial BS. No significant difference in arterial BG was observed between the artificial pancreas and standard therapy. However, the standard deviation with the artificial pancreas was smaller than that under standard therapy (p < 0.0001). More points within the target BG range were achieved with the artificial pancreas (180-220 mg/dl) than under standard therapy. The hyperglycemic index of the artificial pancreas (8.7 ± 15.6 mg/dl) was lower than that of standard therapy (16.0 ± 21.5 mg/dl) (p = 0.0387). No incidence of hypoglycemia occurred under the artificial pancreas. CONCLUSIONS: The rate of achieving target BG was higher using artificial pancreas than with standard therapy. An artificial pancreas helps to control BG in critically ill patients.

Noninvasive blood pressure measurement in patients with continuous-flow left ventricular assist devices.

Oscillatory blood pressure (OBP) with a slow cuff-deflation system has been proposed as noninvasive measurement of mean arterial pressure (MAP) in patients with continuous-flow left ventricular assist devices (LVADs). However, the challenge is that the measurement is not obtainable in certain patients. We hypothesized that the combined use of color Doppler imaging during OBP measurement (CDBP) could derive MAP accurately. We conducted a prospective observational study in critically ill patients (30 patients with continuous-flow LVADs and 30 control patients without LVADs). Triplicate OBP and CDBP measurements were performed and invasive blood pressure (IBP) was recorded. The overall success rate of OBP was 63.3% in the LVAD group and 98.9% in the control group. The CDBP was successfully obtained in 100% of all study patients. The CDBP in the LVAD group was closest to the MAP of measured IBP, while that in the control group was closest to the systolic IBP. The mean absolute differences in OBP and CDBP from the closest IBP were similar in both the control and LVAD groups. In nonpulsatile LVAD patients with a pulse pressure IBP < 10 mmHg, the success rate of OBP measurement was only 10.0%, and CDBP showed significantly reduced error in MAP measurement (mean absolute difference: OBP 23.2 ± 8.7 vs CDBP 5.2 ± 3.6 mmHg, p < 0.001). The validity of OBP measurement with a slow cuff-deflation system limited particularly in nonpulsatile LVAD patients. The concurrent use of color Doppler imaging is encouraged for more accurate measurement of MAP in patients with continuous-flow LVADs.

Timing of tracheostomy and patient outcomes in critically ill patients requiring extracorporeal membrane oxygenation: a single-center retrospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an integral method of life support in critically ill patients with severe cardiopulmonary failure; however, such patients generally require prolonged mechanical ventilation and exhibit high mortality rates. Tracheostomy is commonly performed in patients on mechanical ventilation, and its early implementation has potential advantages for favorable patient outcomes. This study aimed to investigate the association between tracheostomy timing and patient outcomes, including mortality, in patients requiring ECMO. METHODS: We conducted a single-center retrospective observational study of consecutively admitted patients who were supported by ECMO and underwent tracheostomy during intensive care unit (ICU) admission at a tertiary care center from April 2014 until December 2021. The primary outcome was hospital mortality. Using the quartiles of tracheostomy timing, the patients were classified into four groups for comparison. The association between the quartiles of tracheostomy timing and mortality was explored using multivariable logistic regression models. RESULTS: Of the 293 patients treated with ECMO, 98 eligible patients were divided into quartiles 1 (≤ 15 days), quartile 2:16-19 days, quartile 3:20-26 days, and 4 (> 26 days). All patients underwent surgical tracheostomy and 35 patients underwent tracheostomy during ECMO. The complications of tracheostomy were comparable between the groups, whereas the duration of ECMO and ICU length of stay increased significantly as the quartiles of tracheostomy timing increased. Patients in quartile 1 had the lowest hospital mortality rate (19.2%), whereas those in quartile 4 had the highest mortality rate (50.0%). Multivariate logistic regression analysis showed a significant association between the increment of the quartiles of tracheostomy timing and hospital mortality (adjusted odds ratio for quartile increment:1.55, 95% confidence interval 1.03-2.35, p for trend = 0.037). CONCLUSIONS: The timing of tracheostomy in patients requiring ECMO was significantly associated with patient outcomes in a time-dependent manner. Further investigation is warranted to determine the optimal timing of tracheostomy in terms of mortality.

Association between early tracheostomy and patient outcomes in critically ill patients on mechanical ventilation: a multicenter cohort study.

BACKGROUND: Tracheostomy is commonly performed in critically ill patients because of its clinical advantages over prolonged translaryngeal endotracheal intubation. Early tracheostomy has been demonstrated to reduce the duration of mechanical ventilation and length of stay. However, its association with mortality remains ambiguous. This study aimed to evaluate the association between the timing of tracheostomy and mortality in patients receiving mechanical ventilation. METHODS: We performed a retrospective cohort analysis of adult patients who underwent tracheostomy during their intensive care unit (ICU) admission between April 2015 and March 2019. Patients who underwent tracheostomy before or after 29 days of ICU admission were excluded. Data were collected from the nationwide Japanese Intensive Care Patient Database. The primary outcome was hospital mortality. The timing of tracheostomy was stratified by quartile, and the association between patient outcomes was evaluated using regression analysis. RESULTS: Among the 85558 patients admitted to 46 ICUs during the study period, 1538 patients were included in the analysis. The quartiles for tracheostomy were as follows: quartile 1, ≤ 6 days; quartile 2, 7-10 days; quartile 3, 11-14 days; and quartile 4, > 14 days. Hospital mortality was significantly higher in quartile 2 (adjusted odds ratio [aOR]: 1.52, 95% confidence interval [CI]: 1.08-2.13), quartile 3 (aOR: 1.82, 95% CI: 1.28-2.59), and quartile 4 (aOR: 2.26, 95% CI: 1.61-3.16) (p for trend < 0.001) than in quartile 1. A similar trend was observed in the subgroup analyses of patients with impaired consciousness (Glasgow Coma Scale score < 8) and respiratory failure (PaO2:FiO2 ≤ 300) at ICU admission (p for trend = 0.081 and 0.001, respectively). CONCLUSIONS: This multi-institutional observational study demonstrated that the timing of tracheostomy was significantly and independently associated with hospital mortality in a stepwise manner. Thus, early tracheostomy may be beneficial for patient outcomes, including mortality, and warrants further investigation.

Predictors of post-extubation stridor in patients on mechanical ventilation: a prospective observational study.

The cuff leak test (CLT) has been widely accepted as a simple and noninvasive method for predicting post-extubation stridor (PES). However, its accuracy and clinical impact remain uncertain. We aimed to evaluate the reliability of CLT and to assess the impact of pre-extubation variables on the incidence of PES. A prospective observational study was performed on adult critically ill patients who required mechanical ventilation for more than 24 h. Patients were extubated after the successful spontaneous breathing trial, and CLT was conducted before extubation. Of the 191 patients studied, 26 (13.6%) were deemed positive through CLT. PES developed in 19 patients (9.9%) and resulted in a higher reintubation rate (8.1% vs. 52.6%, p < 0.001) and longer intensive care unit stay (8 [4.5-14] vs. 12 [8-30.5] days, p = 0.01) than patients without PES. The incidence of PES and post-extubation outcomes were similar in patients with both positive and negative CLT results. Compared with patients without PES, patients with PES had longer durations of endotracheal intubation and required endotracheal suctioning more frequently during the 24-h period prior to extubation. After adjusting for confounding factors, frequent endotracheal suctioning more than 15 times per day was associated with an adjusted odds ratio of 2.97 (95% confidence interval, 1.01-8.77) for PES. In conclusion, frequent endotracheal suctioning before extubation was a significant PES predictor in critically ill patients. Further investigations of its impact on the incidence of PES and patient outcomes are warranted.

Perioperative Enteral Nutrition After Left Ventricular Assist Device Implantation.

OBJECTIVE: We assessed what predicts nutritional adequacy at day 14 following implantation of left ventricular assist device (LVAD). METHOD: We retrospectively reviewed the cases of 97 adult patients who underwent LVAD implantation at our institution from June 2011 to June 2016. We divided the patients into two groups based on the administered enteral nutrition (EN) calories on post-operative day (POD) 14: the EN calories of group SEN (sufficient enteral nutrition) were >80% of their total target calories, or the EN calories of group IEN (insufficient enteral nutrition) were <80% of their total target calories. We compared the two groups in terms of the perioperative factors within 1 week after surgery. RESULTS: Groups SEN and IEN consisted of 53 and 44 patients, respectively. The mean doses of adrenaline and noradrenaline, mean central venous pressure (CVP), duration of nitric oxide administration, and mean residual gastric volume during 1 week after surgery in group SEN were significantly lower than those in group IEN (P < .05). In multivariate analysis, higher CVP during 1 week after surgery was identified as an independent risk factor for delayed EN on POD14 (odds ratio, 1.40; 95% confidence interval, 1.11-1.66; P = .0037). Total bilirubin, occurrence of acute kidney injury, and mixed venous blood saturation during 1 week after surgery were not significant predictors for EN on POD14. CONCLUSIONS: Increased CVP within 1 week after LVAD implantation was an independent factor for reduced EN feeding.

Innate-like function of memory Th17 cells for enhancing endotoxin-induced acute lung inflammation through IL-22.

Lipopolysaccharide (LPS)-induced acute lung injury (ALI) is known as a mouse model of acute respiratory distress syndrome; however, the function of T-cell-derived cytokines in ALI has not yet been established. We found that LPS challenge in one lung resulted in a rapid induction of innate-type pro-inflammatory cytokines such as IL-6 and TNF-α, followed by the expression of T-cell-type cytokines, including IL-17, IL-22 and IFN-γ. We discovered that IL-23 is important for ALI, since blockage of IL-23 by gene disruption or anti-IL-12/23p40 antibody treatment reduced neutrophil infiltration and inflammatory cytokine secretion into the bronchoalveolar lavage fluid (BALF). IL-23 was mostly produced from F4/80(+)CD11c(+) alveolar macrophages, and IL-23 expression was markedly reduced by the pre-treatment of mice with antibiotics, suggesting that the development of IL-23-producing macrophages required commensal bacteria. Unexpectedly, among T-cell-derived cytokines, IL-22 rather than IL-17 or IFN-γ played a major role in LPS-induced ALI. IL-22 protein levels were higher than IL-17 in the BALF after LPS instillation, and the major source of IL-22 was memory Th17 cells. Lung memory CD4(+) T cells had a potential to produce IL-22 at higher levels than IL-17 in response to IL-1ß plus IL-23 without TCR stimulation. Our study revealed an innate-like function of the lung memory Th17 cells that produce IL-22 in response to IL-23 and are involved in exaggeration of ALI.

[Anesthetic management of a patient with moyamoya disease undergoing mitral valve repair].

Moyamoya disease is the result of progressive steno-occlusive changes in the internal carotid arteries followed by formation of bilateral abnormal vascular networks. The disease may present with cerebral ischemia causing cerebral hemorrhage in the perioperative period. There are few reports of cardiac surgeries in patients with moyamoya disease, and the management during cardiopulmonary bypass for moyamoya disease has not been established. We gave general anesthesia for mitral valve plasty in patient with the moyamoya disease. A 52-year-old woman underwent mitral valve plasty. She had been diagnosed with moyamoya disease and during the cardiopulmonary bypass, we used alpha-stat blood gas management with mild hypothermia, and maintained PaCO2 around 40 mmHg. We maintained the perfusion flow of CPB above 3.0 l x min(-1) x m(-2) and the mean perfusion pressure above 70 mmHg. In addition, we used the pulsatile perfusion assist with intraaortic balloon pumping to maintain cerebral circulation. Postoperative course was uneventful without apparent neurologic deficit, and she was discharged from hospital on 10th postoperative day.

Aryl hydrocarbon receptor plays protective roles in ConA-induced hepatic injury by both suppressing IFN-γ expression and inducing IL-22.

The aryl hydrocarbon receptor (AhR), a ligand-activated nuclear transcription factor, is known to mediate the toxic and carcinogenic effects of various environmental pollutants, while AhR has been shown to protect animals from various types of tissue injury. ConA-induced hepatitis is known as a mouse model of acute liver injury. Here, we found a protective role of AhR in ConA-induced hepatitis. AhR is induced in the liver during ConA-induced hepatitis, and Ahr (-/-) mice were highly sensitive to this model. Bone marrow chimera experiments indicate that Ahr (-/-) hematopoietic cells are responsible for hypersensitivity to ConA-induced hepatitis. We found that IFN-γ from invariant NKT cells was up-regulated and IL-22 from innate lymphoid cells (ILCs) was abolished in Ahr (-/-) mice. In addition, IL-22 production was still observed in Rag2 (-/-) mice but it was severely reduced in Ahr (-/-) Rag2 (-/-) mice. ConA-induced IL-22 production was also dependent on retinoic acid-related orphan receptor γt. These results show that AhR has crucial protective roles in ConA-induced liver injury via promoting IL-22 production from ILCs and suppressing IFN-γ expression from NKT cells.

[Perioperative management of a patient with anomalous origin of the left coronary artery from the pulmonary artery].

Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital disease, also known as Bland-White-Garland (BWG) syndrome. Mitral valve regurgitation secondary to papillary muscle dysfunction due to myocardial ischemia and progressive left ventricular dysfunction are major clinical manifestations of BWG syndrome. We report perioperative management of a five-year-old patient with BWG syndrome who underwent the Takeuchi procedure making an intrapulmonary baffle using anterior pulmonary artery wall. General anesthesia was maintained with inhalation of sevoflurane in 25-40% oxygen and continuous infusion of remifentanil. Since a decrease in pulmonary artery pressure could induce coronary steal phenomenon, we ventilated the patient with minimally required FI(O2) to maintain Sp(O2) 98-100%, and maintained Pa(CO2) between 40 and 50 mmHg to avoid myocardial ischemia before the induction of cardiopulmonary bypass (CPB). We started continuous infusions of nitroglycerin and milrinone after the initiation of CPB, which were continued through the post-CPB period. The patient was transferred to the ICU and the postoperative course was uneventful. There are two key points in the management of BWG syndrome : the balance between systemic and pulmonary artery pressure in pre-CPB period, and left ventricular support including both inotropes and vasodilators in post-CPB period.

Post-ischemic inflammation in the brain.

Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. In this review, we focus on the post-ischemic inflammation triggered by infiltrating immune cells, macrophages, and T lymphocytes. Brain ischemia is a sterile organ, but injury-induced inflammation is mostly dependent on Toll-like receptor (TLR) 2 and TLR4. Some endogenous TLR ligands, high mobility group box 1 (HMGB1) and peroxiredoxin family proteins, in particular, are implicated in the activation and inflammatory cytokine expression in infiltrating macrophages. Following macrophage activation, T lymphocytes infiltrate the ischemic brain and regulate the delayed phase inflammation. IL-17-producing γδT lymphocytes induced by IL-23 from macrophages promote ischemic brain injury, whereas regulatory T lymphocytes suppress the function of inflammatory mediators. A deeper understanding of the inflammatory mechanisms of infiltrating immune cells may lead to the development of novel neuroprotective therapies.

Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo.

Intracellular cyclic adenosine monophosphate (cAMP) suppresses innate immunity by inhibiting proinflammatory cytokine production by monocytic cells. We have shown that the transcription factor c-Fos is responsible for cAMP-mediated suppression of inflammatory cytokine production, and that c-Fos protein is stabilized by IKKß-mediated phosphorylation. We found that S308 is one of the major phosphorylation sites, and that the S308D mutation prolongs c-Fos halflife. To investigate the role of stabilized c-Fos protein in dendritic cells (DCs) in vivo, we generated CD11c-promoter-deriven c-FosS308D transgenic mice. As expected, bone marrow-derived DCs (BMDCs) from these Tg mice produced smaller amounts of inflammatory cytokines, including TNF-α, IL-12, and IL-23, but higher levels of IL-10, in response to LPS, than those from wild-type (Wt) mice. When T cells were co-cultured with BMDCs from Tg mice, production of Th1 and Th17 cytokines was reduced, although T cell proliferation was not affected. Tg mice demonstrated more resistance to experimental autoimmune encephalomyelitis (EAE) than did Wt mice. These data suggest that c-Fos in DCs plays a suppressive role in certain innate and adaptive immune responses.

Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain.

Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. However, the mechanism that activates infiltrating macrophages in the ischemic brain remains to be clarified. Here we demonstrate that peroxiredoxin (Prx) family proteins released extracellularly from necrotic brain cells induce expression of inflammatory cytokines including interleukin-23 in macrophages through activation of Toll-like receptor 2 (TLR2) and TLR4, thereby promoting neural cell death, even though intracellular Prxs have been shown to be neuroprotective. The extracellular release of Prxs in the ischemic core occurred 12 h after stroke onset, and neutralization of extracellular Prxs with antibodies suppressed inflammatory cytokine expression and infarct volume growth. In contrast, high mobility group box 1 (HMGB1), a well-known damage-associated molecular pattern molecule, was released before Prx and had a limited role in post-ischemic macrophage activation. We thus propose that extracellular Prxs are previously unknown danger signals in the ischemic brain and that its blocking agents are potent neuroprotective tools.

Preferential induction of Th17 cells in vitro and in vivo by Fucogalactan from Ganoderma lucidum (Reishi).

The mushroom known as Reishi (Ganoderma lucidum) has been used as an herbal medicine for tumor treatment and immune system activation. Because its effects on the differentiation of effector T helper cells have not yet been fully understood, we investigated the effects of Reishi and those of its principal ingredient, ß-glucan, on the activation of dendritic cells and the differentiation of Th17 cells. Reishi extracts as well as purified ß-glucan (Curdran) activated DCs and caused them to produce large amounts of IL-23. ß-glucan also enhanced and sustained the transcription of IL-23p19. The MEK-ERK signaling pathway positively regulates IL-23p19 transcription in ß-glucan-stimulated DCs. In a mixed leukocyte reaction, Reishi-stimulated DCs preferentially induced Th17 cells. Furthermore, orally-administrated Reishi increased the percentages of Th17 cells and the transcription levels of antimicrobial peptides. Our results show that Reishi and ß-glucan activate DCs to produce large amounts of IL-23, which induces Th17 differentiation both in vitro and in vivo.

SOCS, Inflammation, and Autoimmunity.

Cytokines play essential roles in innate and adaptive immunity. However, excess cytokines or dysregulation of cytokine signaling will cause a variety of diseases, including allergies, autoimmune diseases, inflammation, and cancer. Most cytokines utilize the so-called Janus kinase-signal transducers and activators of transcription pathway. This pathway is negatively regulated by various mechanisms including suppressors of cytokine signaling (SOCS) proteins. SOCS proteins bind to JAK or cytokine receptors, thereby suppressing further signaling events. Especially, suppressor of cytokine signaling-1 (SOCS1) and SOCS3 are strong inhibitors of JAKs, because these two contain kinase inhibitory region at the N-terminus. Studies using conditional knockout mice have shown that SOCS proteins are key physiological as well as pathological regulators of immune homeostasis. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of helper T cell differentiation and functions. This review focuses on the roles of SOCS1 and SOCS3 in T cell mediated inflammatory diseases.

[Evaluation of perioperative management of seven patients with pulmonary artery sling in recent seven years].

BACKGROUND: Pulmonary artery sling (PA sling) is a rare vascular anomaly in which the left pulmonary artery arises from the right pulmonary artery. It can cause compression of trachea. Due to its rarity, risk factors influencing postsurgical outcome are still unclear. The purpose of our study is to investigate past cases of PA sling to clarify risk factors. METHODS: We investigated 7 patients who had undergone one-stage operation of PA sling from 2001 to 2007. Hospital stay, ICU stay and length of artificial ventilation are set as primary outcome. Patients' weight, range of tracheal stenosis, operation time, cardiopulmonary bypass time, presence of tracheal stenosis, bronchial anomaly, preoperative intubation, intracardiac anomaly and postoperative re-intubation were compared. RESULTS: In-hospital mortality was none. Two cases in patients with tracheomalacia were re-intubated. Concomitant tracheoplasty was performed in six patients. Two patients with intracardiac anomaly underwent cardiac operation. No factor except tracheomalacia affected primary outcome. CONCLUSIONS: We need more cases to clarify factors affecting outcome of patients with PA sling. However, existence of tracheomalacia is found to be a risk factor of longer artificial ventilation.