Cardiovascular autonomic dysfunction induced by mechanical insufflation-exsufflation in Guillain-Barré syndrome.

Mechanical insufflation-exsufflation (MI-E) is an effective airway clearance device for impaired cough associated with respiratory muscle weakness caused by neuromuscular disease. Its complications on the respiratory system, such as pneumothorax, are well-recognized, but the association of the autonomic nervous system dysfunction with MI-E has never been reported. We herein describe two cases of Guillain-Barré syndrome with cardiovascular autonomic dysfunction during MI-E: a 22-year-old man who developed transient asystole and an 83-year-old man who presented with prominent fluctuation of blood pressure. These episodes occurred during the use of MI-E with abnormal cardiac autonomic testing, such as heart rate variability in both patients. While Guillain-Barré syndrome itself may cause cardiac autonomic dysfunction, MI-E possibly caused or enhanced the autonomic dysfunction by an alternation of thoracic cavity pressure. The possibility of MI-E-related cardiovascular complications should be recognized, and its appropriate monitoring and management are necessary, particularly when used for Guillain-Barré syndrome patients.

Mechanical Insufflation-exsufflation for the Prevention of Ventilator-associated Pneumonia in Intensive Care Units: A Retrospective Cohort Study.

AIM: Ventilator-associated pneumonia (VAP) is the most common intensive care unit (ICU)-acquired infection. The current study aimed to assess the efficacy of mechanical insufflation-exsufflation (MI-E) in preventing VAP in critically ill patients. MATERIALS AND METHODS: This retrospective cohort study was conducted at the ICU of Chiba University Hospital between January 2014 and September 2017. The inclusion criteria were patients who required invasive mechanical ventilation ≥48 hours and those who underwent rehabilitation, including chest physical therapy (CPT). In 2015, the study institution started the use of MI-E in patients with impaired cough reflex. From January to December 2014, patients undergoing CPT were classified under the historical control group, and those who received treatment using MI-E from January 2015 to September 2017 were included in the intervention group. The patients received treatment using MI-E via the endotracheal or tracheostomy tube, with insufflation-exsufflation pressure of 15-40 cm H2O. The treatment frequency was one to three sessions daily, and a physical therapist who is experienced in using MI-E facilitated the treatment. RESULTS: From January 2015 to September 2017, 11 patients received treatment using MI-E. Of the 169 patients screened in 2014, 19 underwent CPT. The incidence of VAP was significantly different between the CPT and MI-E groups (84.2% [16/19] vs 26.4% [3/11], p = 0.011). After adjusting for covariates, a multivariate logistic regression analysis was performed, and results showed that the covariates were not associated with the incidence of VAP. CONCLUSION: This retrospective cohort study suggests that the use of MI-E in critically ill patients is independently associated with a reduced incidence of VAP. CLINICAL SIGNIFICANCE: Assessing the efficacy of MI-E to prevent VAP. HOW TO CITE THIS ARTICLE: Kuroiwa R, Tateishi Y, Oshima T, Inagaki T, Furukawa S, Takemura R, et al. Mechanical Insufflation-exsufflation for the Prevention of Ventilator-associated Pneumonia in Intensive Care Units: A Retrospective Cohort Study. Indian J Crit Care Med 2021;25(1):62-66.

Association between serum levels of interleukin-6 on ICU admission and subsequent outcomes in critically ill patients with acute kidney injury.

BACKGROUND: Exacerbated inflammatory response is considered one of the key elements of acute kidney injury (AKI). Interleukin-6 (IL-6) is an inflammatory cytokine that plays important roles in the inflammatory response and may be useful for predicting the clinical outcomes in patients with AKI. However, supporting evidence adapted to the current KDIGO criteria is lacking. METHODS: AKI patients admitted to the ICU between Jan 2011 and Dec 2015 were retrospectively screened. Patients were assigned to three groups by admission IL-6 tertiles. Associations between IL-6 on ICU admission and in-hospital 90-day mortality, short-term/long-term renal function were analyzed. RESULTS: Patients (n = 646) were divided into low (1.5-150.2 pg/mL), middle (152.0-1168 pg/mL), and high (1189-2,346,310 pg/mL) IL-6 on ICU admission groups. Patients in the high IL-6 group had higher in-hospital 90-day mortality (low vs. middle vs. high, P = 0.0050), lower urine output (low vs. middle vs. high, P < 0.0001), and an increased probability of persistent of anuria for ≥12 h (low vs. middle vs. high, P < 0.0001) within 72 h after ICU admission. In contrast, the high IL-6 group had a lower incidence of persistent AKI at 90 days after the ICU admission in survivors (low vs. middle vs. high, P = 0.013). CONCLUSIONS: Serum levels of IL-6 on ICU admission may predict short-term renal function and mortality in AKI patients and were associated with renal recovery in survivors.

Establishing extracorporeal membrane oxygenation team increased number of patients and improved data recording.

BACKGROUND: For patients treated with extracorporeal membrane oxygenation (ECMO), employing a well-coordinated, multidisciplinary team specializing in ECMO has reportedly been effective in delivering better clinical outcomes. This study aims to assess the impact of establishing such a specialized team for patients treated with ECMO. METHOD: This retrospective cohort study was performed at a tertiary-care hospital in Japan. We reviewed medical records of all consecutive patients treated with ECMO during October 2010-September 2016. The results obtained in pre-ECMO team cases (PRE group; October 2011-September 2012) and post-ECMO team cases (POST group; October 2014-September 2015) were compared. RESULTS: The results obtained in pre-ECMO team cases (PRE group; October 2011-September 2012) and post-ECMO team cases (POST group; October 2014-September 2015) were compared. During the study period, 177 patients were treated with ECMO. Before the introduction of ECMO team, an average of 22.7 patients underwent ECMO treatment per year; after establishing ECMO team, this number increased to 36.3 patients per year. ECMO was applied mainly to cardiac arrest patients 52/69 (75%). The PRE (n = 27) and POST (n = 42) groups did not differ with regard to the survival rate to hospital discharge, ECMO duration, ventilator days, and length of hospital stay. However, PaO2 and positive end-expiratory pressure were significantly higher in the POST group at 6 h after ECMO initiation than those in the PRE group [367 (186-490) vs. 239 (113-430) mmHg, p = 0.047 and 8 (5-10) vs. 7 (5-8) cmH2O, p = 0.01, respectively]. In addition, data recording the detailed time points of ECMO initiation was conducted in significantly more cases in the POST group (28/126 (22%) than in the PRE group (6/81 (7%); p = 0.01). CONCLUSIONS: Following the establishment of an ECMO team, the survival rate of patients treated with ECMO, ECMO duration, and length of hospital stay were not improved. However, the number of ECMO cases increased and the recording of clinical data was improved.

Potential role for emergency physicians with endoscopy training in the treatment of upper gastrointestinal hemorrhage: a retrospective observational study.

AIM: Urgent endoscopy is essential in gastrointestinal (GI) bleeding. Emergency physicians with endoscopy training treat patients with GI bleeding in our hospital. We compared the management and clinical outcomes of GI bleeding cases between those treated by an emergency physician (EP) and those treated by a non-emergency physician (NEP; e.g., gastroenterologist or general surgeon). METHODS: We undertook a retrospective chart review of upper GI bleeding cases treated using endoscopy in the emergency department between 2012 and 2014. We examined patients characteristics, endoscopic findings, hemostatic procedures, need for transfusion, rebleeding and adverse events, length of hospital stay, and mortality. RESULTS: The EP group included 33 patients (39%) and the NEP group included 51 (61%). Patient characteristics and diseases did not differ between the groups. The EP group underwent urgent endoscopy more often (100% versus 86%, P = 0.04). Procedure times were not statistically different between the groups. The EP group had fewer hemostatic procedures (42% versus 65%, P = 0.04). Transfusion requirements were lower in the EP group (0.5 U versus 2.1 U, P = 0.006). There were no statistical differences in rebleeding and adverse events. The length of hospital stay was shorter (8 versus 11 days, P = 0.03) and the in-hospital mortality rate was lower in the EP group (0% versus 13.7%, P = 0.04). CONCLUSION: Short-term outcomes in GI bleeding cases managed by emergency physicians with endoscopy training were comparable to those by gastroenterologists and general surgeons. However, the extent of endoscopic training and experience emergency physicians should have remains unclear.

Veno-venous extracorporeal membrane oxygenation bridged living-donor lung transplantation for rapid progressive respiratory failure with pleuroparenchymal fibroelastosis after allogeneic hematopoietic stem cell transplantation.

Cases of extracorporeal membrane oxygenation (ECMO) bridged lung transplantation (LTx) are rare in Japan because an allocation system to prioritize patients based on urgency remains to be established. For critically ill patients who cannot wait for a brain-dead donor LTx, ECMO bridge to living-donor LTx may be the only practical option. A 21-year-old woman with pleuroparenchymal fibroelastosis after hematopoietic stem cell transplantation was admitted to our hospital with rapidly progressive respiratory failure. She was waitlisted for 6 months before admission, but veno-venous ECMO was initiated. She was transported under ECMO support via a jet plane and underwent successful living-donor LTx.

Pharmacokinetics of Standard- and Reduced-Dose Recombinant Human Soluble Thrombomodulin in Patients with Septic Disseminated Intravascular Coagulation during Continuous Hemodiafiltration.

INTRODUCTION: Recombinant human soluble thrombomodulin (rTM) is reportedly excreted by the kidneys; therefore, the recommended dose for patients with renal impairment is one-third of the standard dose. The aim of this study was to evaluate whether this reduced dose of rTM achieves effective drug concentrations that are comparable to those of the standard dose in treating sepsis-induced disseminated intravascular coagulation (DIC) during continuous hemodiafiltration (CHDF). METHODS: Eight patients in an intensive care unit were randomized to receive either reduced-dose (0.02 mg/kg, n = 4) or standard-dose (0.06 mg/kg, n = 4) rTM. We evaluated the effect of standard dose in comparison to that of reduced dose on the pharmacokinetics (PKs) of rTM for the sepsis-induced DIC patients receiving CHDF. Patients received rTM during a 30-min infusion for six consecutive days. PK parameters of rTM were analyzed using the one-compartment model. RESULTS: The elimination half-life, clearance (T1/2), and distribution volume of sTM were similar between the reduced and standard doses. The maximum concentration (Cmax) and area under the concentration-time curve (AUC) of sTM were approximately 2.5 times higher with standard-dose daily infusions than that with reduced-dose drip infusions (p = 0.041 and 0.062, respectively). The time when the blood concentration of sTM was >500 ng/mL, i.e., the holding time, was significantly longer with standard-dose infusions than those with reduced dose (p = 0.039). CONCLUSION: rTM displayed dose-dependent PK behavior at clinically relevant doses. During CHDF, effective blood concentration of rTM was not achieved with the reduced dose, and rTM was found to not bioaccumulate. Therefore, this pilot study suggests that reducing the rTM dose is unnecessary, even in sepsis-induced DIC patients who require CHDF. However, we need to perform a definitive study to determine the dosage of rTM for the case.

Veno-arterial extracorporeal membrane oxygenation for Streptococcus pyogenes toxic shock syndrome in pregnancy.

Streptococcal toxic shock syndrome (STSS), an invasive Streptococcus pyogenes (Group A streptococcus) infection with hypotension and multiple organ failure, is quite rare in pregnancy but is characterized by rapid disease progression and high fatality rates. We present a case of STSS with infection-induced cardiac dysfunction in a pregnant woman who was treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A 24-year-old multiparous woman in the third trimester had early symptoms of high fever and diarrhea 1 day prior to admission to the hospital emergency department. On admission, she had multiple organ failure including circulatory failure. Due to fetal distress, emergency Cesarean section was carried out and transferred to intensive care units. She had refractory circulatory failure with depressed myocardial contractility with progressive multiple organ failure, despite receiving significant hemodynamic supports including high-dose catecholamine. Thus, VA-ECMO was initiated 18 h after intensive care unit admission. Consequently, ECMO provided extra time to recover from infection and myocardial depression. She was successfully weaned from VA-ECMO on day 7 and was discharged home on day 53. VA-ECMO can be a therapeutic option for refractory circulatory failure with significant myocardial depression in STSS.

Septic shock due to infected giant venous malformation complicated by massive bleeding.

Case: A 19-year-old man with a hemangioma that extended from the left arm to the axillary region had deteriorated due to shock, and no improvement was observed after fluid resuscitation. His status on arrival led to complications of hemorrhagic and septic shock with his left arm swollen and deep purple in color. Left arm amputation to control the source of bleeding and infection was thought to be indicated, however, the coagulation system had collapsed. Therefore, initial reduction of the blood flow to the hemangioma with angiographic endovascular treatment was carried out. Thereafter, continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter against hypercytokinemia was introduced in the intensive care unit for damage control, which resulted in success. Outcome: We completed the arm amputation, and subsequently carried out a latissimus dorsi muscle flap transfer on the amputated stump. The patient achieved an ambulatory discharge. Conclusions: We successfully treated the very rare case of massive venous malformation with shock due to hemorrhage and infection by performing damage control.

Autophagy-related IRGM polymorphism is associated with mortality of patients with severe sepsis.

OBJECTIVE: Autophagy is the regulated catabolic process for recycling damaged or unnecessary organelles, which plays crucial roles in cell survival during nutrient deficiency, and innate immune defense against pathogenic microorganisms. Autophagy has been also reported to be involved in various conditions including inflammatory diseases. IRGM (human immunity-related GTPase) has an important function in eliminating Mycobacterium tuberculosis from host cells via autophagy. We examined the association between genetic polymorphism and clinical course/outcome in severely septic patients. METHODS: The study included 125 patients with severe sepsis/septic shock (SS) and 104 non-sepsis patients who were admitted to the intensive care unit (ICU) of Chiba University Hospital between October 2001 and September 2008 (discovery cohort) and 268 SS patients and 454 non-sepsis patients who were admitted to ICUs of five Japanese institutions including Chiba University Hospital between October 2008 and September 2012 (multi-center validation cohort). Three hundred forty seven healthy volunteers who consented to this study were also included. Genotyping was performed for a single-nucleotide polymorphism (SNP) within the coding region of IRGM, IRGM(+313) (rs10065172). Lipopolysaccharide challenge of whole blood from randomly selected healthy volunteers (n = 70) was performed for comparison of IRGM mRNA expression among different genotypes. RESULTS: No significant difference in genotypic distributions (CC/CT/TT) at the IRGM(+313) locus was observed among the three subject groups (SS, non-sepsis, and healthy volunteers) in either cohort. When mortality were compared, no significant difference was observed in the non-sepsis group, while TT homozygotes exhibited a significantly higher mortality than the CC+CT genotype category in the SS group for both cohorts (P = 0.043, 0.037). Lipopolysaccharide challenge to whole blood showed a significant suppression of IRGM mRNA expression in TT compared with the CC+CT genotype category (P = 0.019). CONCLUSIONS: The data suggest that the IRGM(+313), an autophagy-related polymorphic locus, influences outcome in severely septic patients, with the possible involvement of autophagy in sepsis exacerbation.

Differential pattern of cell-surface and soluble TREM-1 between sepsis and SIRS.

OBJECTIVE: Triggering receptor expressed on myeloid cells-1 (TREM-1) was reported to play a key roll in amplification of production of inflammatory cytokines. TREM-1 is suggested to be a specific biomarker for sepsis for this reason, but the clinical significance of TREM-1 has not been elucidated. We investigated TREM-1 expression on the cell-surface, and plasma levels of soluble TREM-1 (sTREM-1) in patients with non-infectious systemic inflammatory response syndrome (SIRS) and sepsis admitted to the ICU. METHODS: Thirty-five patients with SIRS and 21 patients with sepsis admitted to ICU were subjected to the study. TREM-1 expressions on the surfaces of monocytes and neutrophils were measured by flow cytometry. Plasma sTREM-1 level and serum interleukin (IL)-6 level were measured. RESULTS: Septic patients had decreased TREM-1 expression, clearly on neutrophils or to a lesser extent on monocyte compared to SIRS patients on ICU admission (neutrophils p<0.001, monocyte p<0.05). TREM-1 expression on neutrophils had a significant inverse correlation with serum IL-6 level (r=-0.64, p<0.0001). Plasma sTREM-1 level in septic patients was significantly higher than that in SIRS patients (p<0.05). Plasma sTREM-1 level positively correlated with severity score and non-survivors had increased plasma sTREM-1 level compared to survivors in all SIRS/sepsis patients (p<0.05). CONCLUSIONS: Patients with sepsis had increased soluble TREM-1 and decreased TREM-1 expression on neutrophil compared to SIRS patients. sTREM-1 may be useful to evaluate disease severity and outcome of patients with SIRS or sepsis.

Duration of well-controlled core temperature correlates with neurological outcome in patients with post-cardiac arrest syndrome.

PURPOSE: Detailed procedures for optimal therapeutic hypothermia (TH) have yet to be established. We examined how duration of well-controlled core temperature within the first 24 hours after cardiac arrests (CA) correlated with neurological outcomes of successfully resuscitated out-of-hospital CA (OHCA) patients. METHODS: OHCA patients who survived over 24 hours and treated with TH were included. Core temperature was measured every hour. Physicians intended to maintain temperature at 33 °C ± 1 °C for 24 hours. Cerebral performance categories (CPC) of patients at 6 months were recorded and patients were retrospectively divided into favorable (CPC1,2) and poor (CPC3-5) neurological outcome groups. Total time while the core temperature reached to 33 °C ± 1 °C within the first 24 hours after CA was measured and this duration was defined that of well-controlled temperature. receiver-operating characteristic analysis was performed on duration of well-controlled temperature to select the optimal cutoff value. Neurological outcome predictors were investigated by logistic regression analysis. RESULTS: Fifty-six patients were included. Optimal cutoff value of duration of well-controlled temperature was 18 hours. Ratio of male sex, witnessed by emergency medical service (EMS) personnel, first electrocardiogram as shockable, and duration of well-controlled core temperature ≥ 18 h of favorable neurological outcome group (n = 21) were significantly larger than that of poor neurological outcome group (n = 35). Logistic regression analysis identified "witnessed by EMS", "performed bystander CPR," and "the duration ≥ 18 h" as independent predictors of favorable neurological outcome. CONCLUSION: TH maintained at target temperature of 33 °C ± 1 °C over 18 hours independently correlated with favorable neurological outcome. Therefore, stable core temperature control may improve neurological outcome of successfully resuscitated OHCA.

Trends in and perspectives on extracorporeal membrane oxygenation for severe adult respiratory failure.

Various approaches such as ventilator management involving lung-protective ventilation, corticosteroids, prone positioning, and nitric oxide have failed to maintain sufficient lung oxygenation or appropriate ventilation competence in very severe acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) has been aggressively introduced for such patients, although in only a few institutions. The clinical usefulness of ECMO in a large-scale multicenter study (CESAR trial, 2009) and continued development/improvement of ECMO devices have facilitated performance of ECMO, with further increase in the number of institutions adopting ECMO therapy. Clinical usefulness of ECMO was documented in many cases of severe ARDS secondary to influenza A (H1N1) 2009 infection. ECMO requires establishment of an appropriate management system to minimize fatal complications (e.g., hemorrhage), which requires a multidisciplinary team. This, in combination with a new technique, interventional lung assist, will further extend the indications for ECMO. ECMO can be expected to gain importance as a respiratory support technique.

Treatment of septic shock with continuous HDF using 2 PMMA hemofilters for enhanced intensity.

PURPOSE: Cytokines play pivotal roles in the pathophysiology of severe sepsis/septic shock, and continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) removes cytokines efficiently and continuously, mainly through adsorption to a hemofilter membrane. The aim of this study was to investigate the clinical efficacy of enhanced intensity PMMA-CHDF in treating refractory septic shock. METHODS: Seventy-two septic shock patients admitted to the intensive care unit (ICU) underwent critical care including PMMA-CHDF. We employed enhanced intensity PMMA-CHDF to improve the cytokine removal rate by increasing the hemofilter membrane area in 10 refractory septic shock patients (enhanced intensity group, EI group; 2 extracorporeal CHDF circuits using the hemofilter with a larger membrane area of 2.1 m2). Other patients undergoing conventional PMMA-CHDF and matched for severity with the EI group, comprised a matched conventional group (MC group; using a PMMA membrane hemofilter with a membrane area of 1.0 m2; n=15). The case-control comparison was performed between the 2 groups. RESULTS: Enhanced intensity PMMA-CHDF significantly increased mean arterial pressure by 23.8% in 1 hour (p=0.037), decreased the blood lactate level by 28.6% in 12 hours (p=0.006), and reduced blood IL-6 level in 24 hours (p=0.005). The ICU survival rate in the EI group was significantly better than that in the MC group (60% vs. 13.3%, p=0.028). CONCLUSION: Enhanced intensity PMMA-CHDF may improve hemodynamics and survival rate in patients with refractory septic shock.

Effects of a peripheral cholinesterase inhibitor on cytokine production and autonomic nervous activity in a rat model of sepsis.

PURPOSE: Recently, cholinergic anti-inflammatory pathway manipulation has been proposed as a new strategy to control cytokine production in sepsis. We investigated whether hypercytokinemia can be controlled via this pathway in an animal model of sepsis, with concomitant monitoring of autonomic nervous activity involving heart rate variability (HRV) analysis of electrocardiographic R-R intervals. METHODS: Sixty-eight adult male Sprague-Dawley rats were used (28 for examination of cytokine production and autonomic nervous activity; 40 for survival analysis). Each part of the study involved four animal groups, including two control groups without drug administration. Sepsis was induced by cecal ligation and puncture (CLP). Distigmine bromide, a peripheral, non-selective cholinesterase inhibitor (0.01mg/kg), was administered subcutaneously 90 min after surgery. Continuous electrocardiograms were recorded for 5 min before and after surgery (at intervals of 5h) in CLP and sham-operated animals for HRV analysis. Blood samples were collected 20 h after surgery for serum cytokine and catecholamine assay. RESULTS: On HRV analysis, distigmine inhibited reduction of total power and high-frequency components in CLP animals (P<0.05). Distigmine significantly inhibited cytokine induction (IL-6 and IL-10) (P<0.01) as well as increase in serum levels of noradrenaline and dopamine (P<0.05). Distigmine did not significantly improve CLP animal survival rate. CONCLUSIONS: The cholinesterase inhibitor distigmine inhibited induction of inflammatory cytokines and catecholamines as well as HRV suppression in a rat CLP model, suggesting that an agent modulating the cholinergic anti-inflammatory pathway can control excess cytokine production involved in the pathogenesis of severe sepsis/septic shock.

Experimental examination of anti-inflammatory effects of a 5-HT3 receptor antagonist, tropisetron, and concomitant effects on autonomic nervous function in a rat sepsis model.

BACKGROUND: A 5-HT(3) receptor antagonist, tropisetron, has been reported to exhibit an anti-inflammatory effect in chronic inflammatory diseases by antagonizing a particular subtype of serotonin receptors. We investigated whether overproduction of cytokines could be controlled by intervention with tropisetron in an animal model of sepsis and also examined the effects of tropisetron on autonomic nervous activity. METHODS: Sixty-eight adult male Sprague-Dawley rats were used (28 for examination of cytokine production and autonomic nervous activity; 40 for survival analysis). Each part of the study involved 4 animal groups, including two control groups without drug administration. Sepsis was induced by cecal ligation and puncture (CLP). Tropisetron hydrochloride (1mg/kg) was administered immediately after surgery. Continuous electrocardiograms were recorded for 5 min before and 1, 2, 4, and 6h after surgery in CLP and sham-operated animals for heart rate variability (HRV) analysis. Blood samples were collected 6h after surgery for serum cytokine and catecholamine assay. RESULTS: HRV analysis demonstrated a significant increase in LF/(LF+HF) in the CLP animals compared with the sham-operated animals, regardless of tropisetron administration, indicating induction of sympathetic overstimulation. Tropisetron significantly inhibited IL-6 induction in the CLP animals (p<0.01). Although it did not significantly change HRV parameters, tropisetron significantly inhibited increase in serum level of noradrenaline (p<0.05). Tropisetron did not significantly improve CLP animal survival rate. CONCLUSIONS: Intervention with a 5-HT(3) receptor antagonist can control excess cytokine production involved in the pathogenesis of severe sepsis/septic shock.

Auditory evoked potential P50 as a predictor of neurologic outcome in resuscitated cardiac arrest patients.

In general, a prediction of neurologic outcome with respect to the resuscitated cardiac arrest patients has been performed by the auditory brainstem response and somatic evoked potential. The auditory brainstem response and somatic evoked potential are known as the predictors that correspond to neurologically poor outcome. None of the methods have been established to access neurologically good outcome. Because the hippocampal CA3 pyramidal cells have been widely used for pathophysiologic analyses concerning the hypoxic-ischemic encephalopathy and also the source of P50 components of the auditory evoked potential has been considered to be the hippocampal CA3 pyramidal cells, the authors assume that it might be possible that neurologic outcome in resuscitated cardiac arrest patients would be predicted by evaluating the P50 components. The purpose was to examine the P50 as a predictor of neurologic outcome in resuscitated cardiac arrest patients at the early stage from the onset. The P50 components of the auditory evoked potential are recorded in a conditioning-testing paradigm, that is, EEG responses to a pair of auditory stimuli with 500-millisecond interclick interval. In this study, subjects are 10 out-of-hospital cardiac arrest patients, 8 men and 2 women with a mean age of 54.8 years, who were admitted to the intensive care unit after the return of spontaneous circulation, with the presence of both the auditory brainstem response wave V and the somatic evoked potential wave N20 between the period from June 2008 to July 2009. It was found that the presence of the P50 at the early stage from the onset (days 5 ± 1.20) indicates good neurologic outcome, while the absence of the P50 implies poor prognosis. As to the auditory sensory gating of the P50, almost no reduction response to the second stimulus was observed. As a consequence, the evaluation of the P50 in resuscitated cardiac arrest patients would have a possibility to predict neurologically good outcome.

Enhanced expression of Toll-like receptor 2 in lesional tissues and peripheral blood monocytes of patients with oral lichen planus.

Some members of the Toll-like receptor (TLR) family, which plays key roles in both innate and adaptive immune responses, are involved in the pathogenesis of autoimmune, chronic inflammatory and infectious diseases. However, the role of TLR in the pathogenesis of oral lichen planus (OLP) has not been investigated. The aim of this study was to understand the roles of TLR in OLP. The expression of TLR genes in OLP tissues was analyzed by cDNA microarray and reverse transcription polymerase chain reaction, and TLR protein expression in OLP tissues and peripheral blood monocytes was examined by immunohistochemical analysis and flow cytometry, respectively. Furthermore, TLR ligand-induced cytokine production from peripheral blood monocytes was measured by enzyme-linked immunosorbent assay. Among 10 TLR genes, the average expression ratio of the genes for TLR1, 2, 3, 5, 6 and 10 in OLP tissues compared to that in the normal buccal mucosae was more than 1.0. In contrast, the average ratio of the genes for TLR7, 8 and 9 was less than 1.0. TLR2 but not TLR4 was highly expressed in the cells of the spinous layer and infiltrating monocytes in OLP tissues, and the mean fluorescence intensity of TLR2 on peripheral blood monocytes was significantly higher in OLP patients than in healthy controls. Furthermore, the peripheral blood monocytes from OLP patients produced considerably higher amounts of interleukin (IL)-12 and lower amounts of IL-10 than those from healthy controls. In OLP, the T-helper cell (Th)1/Th2 balance appears to shift toward Th1 dominance, probably depending on the upregulation of TLR2 expression and these alterations in TLR2-mediated immunity may be involved in the pathogenesis and maintenance of OLP.

Outcome prediction in sepsis combined use of genetic polymorphisms - A study in Japanese population.

Genetic polymorphisms have recently been found to be related to clinical outcome in septic patients. The present study investigated to evaluate the influence of genetic polymorphisms in Japanese septic patients on clinical outcome and whether use of genetic polymorphisms as predictors would enable more accurate prediction of outcome. Effects of 16 genetic polymorphisms related to pro-inflammatory mediators and conventional demographic/clinical parameters (age, sex, past medical history, and APACHE II score) on ICU mortality as well as disease severity during ICU stay were examined in the septic patients (n=123) admitted to the ICU between October 2001 and November 2007 by multivariable logistic regression analysis. ICU mortality was significantly associated with TNF -308GA, IL1ß -31CT/TT, and APACHE II score. Receiver-operating characteristics (ROC) analysis demonstrated that, compared with APACHE II score alone (ROC-AUC=0.68), use of APACHE II score and two genetic parameters (TNF -308 and IL1ß -31) enabled more accurate prediction of ICU mortality (ROC-AUC=0.80). Significant association of two genetic polymorphisms, TNF -308 and IL1ß -31, with ICU mortality was observed in septic patients. In addition, combined use of these genetic parameters with APACHE II score may enable more accurate prediction of outcome in septic patients.

Blood ammonia and lactate levels on hospital arrival as a predictive biomarker in patients with out-of-hospital cardiac arrest.

INTRODUCTION: No reliable predictor for the prognosis of out-of-hospital cardiac arrest (OHCA) on arrival at hospital has been identified so far. We speculate that ammonia and lactate may predict patient outcome. METHODS: This is a prospective observational study. Non-traumatic OHCA patients who gained sustained return of spontaneous circulation and were admitted to acute care unit were included. Blood ammonia and lactate levels were measured on arrival at hospital. The patients were classified into two groups: 'favourable outcome' group (Cerebral Performance Category CPC1-2 at 6-months' follow-up) and 'poor outcome' group (CPC3-5). Basal characteristics obtained from the Utstein template and biomarker levels were compared between these two outcome groups. Independent predictors were selected from all candidates using logistic regression analysis. RESULTS: A total of 98 patients were included. Ammonia and lactate levels in the favourable outcome group (n=10) were significantly lower than those in poor outcome group (n=88) (p<0.05, respectively). On receiver operating characteristic analysis, the optimal cut-off value for predicting favourable outcome was determined as 170 µg dl(-1) of ammonia and 12.0 mmol l(-1) of lactate (area under the curve; 0.714 and 0.735, respectively). Logistic regression analysis identified ammonia (≤170 µg dl(-1)), therapeutic hypothermia and witnessed by emergency medical service personnel as independent predictors of favourable outcome. When both these biomarker levels were over threshold, positive predictive value (PPV) for poor outcome was calculated as 100%. CONCLUSIONS: Blood ammonia and lactate levels on arrival are independent prognostic factors for OHCA. PPV with the combination of these biomarkers predicting poor outcome is high enough to be useful in clinical settings.