Outcomes Associated with ICU Telemedicine and Other Risk Factors in a Multi-Hospital Critical Care System: A Retrospective, Cohort Study for 30-Day In-Hospital Mortality.

Introduction: Intensive care unit telemedicine (ICU-TM) is expanding due to increasing demands for critical care, but impact on outcomes remains controversial. This study evaluated the association of ICU-TM and other clinical factors with 30-day, in-hospital mortality. Methods: This retrospective, cohort study included 151,780 consecutive ICU patients admitted to nine hospitals in the Cleveland Clinic Health System from 2010 to 2020. Patients were identified from an institutional datamart and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) registry. Primary outcome was 30-day in-hospital mortality. Analyses included multivariate logistic regression modeling, and survival analysis. Results: Overall, unadjusted 30-day, in-hospital mortality incidence was significantly different with (5.6%) or without ICU-TM (7.2%), and risk ratio was 0.78 (95% confidence interval [CI] 0.75-0.81) (p < 0.0001). Mortality rate for ICU-TM and no ICU-TM was 2.4/1,000 versus 3.2/1,000 patient days, respectively (p < 0.0001). Multivariate logistic regression showed that ICU-TM was associated with reduced 30-day mortality (odds ratio 0.78, 95% CI 0.72-0.83). Increased risk was seen with cardiac arrest admissions, males, acute stroke, weekend admission, emergency admission, race (non-white), sepsis, APACHE IV score, ICU length of stay (LOS), and the interaction term, emergency surgical admissions. Reduced risk was associated with hospital LOS, surgical admission, and the interaction terms (weekend admissions with ICU-TM and after-hour admissions with ICU-TM). The model c-statistic was 0.77. Median ICU and hospital lengths of stay were significantly reduced with ICU-TM, with no difference in 48-h mortality or 48-h mortality rate. Conclusion: ICU telemedicine exposure appears to be one of several operational and clinical factors associated with reduced 30-day, in-hospital mortality.

Hyperinflation With Pulmonary Dysfunction in Donor Lungs With Smoking History During Lung Perfusion.

BACKGROUND: Donor lungs with smoking history are perfused in ex vivo lung perfusion (EVLP) to expand donor lung pool. However, the impact of hyperinflation of perfused lungs in EVLP remains unknown. The aim of this study was to investigate the significance of hyperinflation, using an ex vivo measurement delta VT, during EVLP in smoker's lungs. MATERIALS AND METHODS: Seventeen rejected donor lungs with smoking history of median 10 pack-years were perfused for 2 h in cellular EVLP. Hyperinflation was evaluated by measuring delta VT = inspiratory - expiratory tidal volume (VT) difference at 1 h. All lungs were divided into two groups; negative delta VT (n = 11, no air-trapping pattern) and positive delta VT (n = 6, air-trapping pattern). Transplant suitability was judged at 2 h. By using lung tissue, linear intercept analysis was performed to evaluate the degree of hyperinflation. RESULTS: The positive delta VT group had significantly lower transplant suitability than the negative delta VT group (16 versus 81%, P = 0.035). The positive delta VT group was significantly associated with lower partial pressure of oxygen/fraction of inspired oxygen ratio ratio (278 versus 356 mm Hg, P = 0.049), higher static compliance (119 versus 98 mL/cm H2O, P = 0.050), higher lung weight ratio (1.10 versus 0.96, P = 0.014), and higher linear intercept ratio (1.52 versus 0.93, P = 0.005) than the negative delta VT group. CONCLUSIONS: Positive delta VT appears as an ex vivo marker of ventilator-associated lung hyperinflation of smoker's lungs during EVLP.

Application of Unit-Level Cost Transparency, Education, Enhanced Audit, and Feedback of Anonymized Peer Ranking to Promote Judicious Use of 25% Albumin in Critical Care Units.

Objective: Hyperoncotic 25% albumin is widely used for fluid resuscitation in intensive care units. However, this practice remains controversial. By 2012 in our intensive care unit, annual 25% albumin expenditures had steadily increased to exceed $1 million. This prompted efforts to promote more judicious use. Design: Prospective time series cohort analysis using statistical process control charts. Setting: Seventy-six-bed quaternary level cardiovascular surgical intensive care unit (CVICU), organized into 6 adjacent units. Patients: Adult cardiac, thoracic, and vascular surgery patients admitted postoperatively to the CVICU during the study period. Interventions: Over 12 months starting March 2013, we sequentially implemented unit-level 25% albumin cost transparency, provider education, and individualized audit and feedback of anonymized peer ranking of albumin prescriptions. Measurements and Main Results: C control charts were used for analysis of monthly unit-level direct albumin costs for 20 months. Balance measures including red cell transfusions, number of diagnoses of pleural effusions, and length of stay were also tracked. Monthly average albumin expenditures had decreased 61% by December 2014, and there was no evidence of adverse changes in any of the balance measures. These reductions have been sustained. Conclusion: Sequential implementation of multimodal strategies can alter clinician practices to achieve substantial unit-level reduction in 25% albumin utilization without harm to patients.

A novel concept for evaluation of pulmonary function utilizing PaO2/FiO2 difference at the distinctive FiO2 in cellular ex vivo lung perfusion-an experimental study.

For more accurate lung evaluation in ex vivo lung perfusion (EVLP), we have devised a new parameter, PaO2 /FiO2 ratio difference (PFD); PFD1-0.4  = P/F ratio at FiO2 1.0 - P/F ratio at FiO2 0.4. The aim of this study is to compare PFD and transplant suitability, and physiological parameters utilized in cellular EVLP. Thirty-nine human donor lungs were perfused. At 2 h of EVLP, PFD1-0.4 was compared with transplant suitability and physiological parameters. In a second study, 10 pig lungs were perfused in same fashion. PFD1-0.4 was calculated by blood from upper and lower lobe pulmonary veins and compared with lobe wet/dry ratio and pathological findings. In human model, receiver operating characteristic curve analysis showed PFD1-0.4 had the highest area under curve, 0.90, sensitivity, 0.96, to detect nonsuitable lungs, and significant negative correlation with lung weight ratio (R2  = 0.26, P < 0.001). In pig model, PFD1-0.4 on lower and upper lobe pulmonary veins were significantly associated with corresponding lobe wet/dry ratios (R2  = 0.51, P = 0.019; R2  = 0.37, P = 0.060), respectively. PFD1-0.4 in EVLP demonstrated a significant correlation with lung weight ratio and allowed more precise assessment of individual lobes in detecting lung edema. Moreover, it might support decision-making in evaluation with current EVLP criteria.

Economic trends from 2003 to 2010 for perioperative myocardial infarction: a retrospective, cohort study.

BACKGROUND: Perioperative myocardial infarction (PMI) is a major surgical complication that is costly and causes much morbidity and mortality. Diagnosis and treatment of PMIs have evolved over time. Many treatments are expensive but may reduce ancillary expenses including the duration of hospital stay. The time-dependent economic impact of novel treatments for PMI remains unexplored. The authors thus evaluated absolute and incremental costs of PMI over time and discharge patterns. METHODS: Approximately 31 million inpatient discharges were analyzed between 2003 and 2010 from the California State Inpatient Database. PMI was defined using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Propensity matching generated 21,637 pairs of comparable patients. Quantile regression modeled incremental charges as the response variable and year of discharge as the main predictor. Time trends of incremental charges adjusted to 2012 dollars, mortality, and discharge destination was evaluated. RESULTS: Median incremental charges decreased annually by $1,940 (95% CI, $620 to $3,250); P < 0.001. Compared with non-PMI patients, the median length of stay of patients who experienced PMI decreased significantly over time: yearly decrease was 0.16 (0.10 to 0.23) days; P < 0.001. No mortality differences were seen; but over time, PMI patients were increasingly likely to be transferred to another facility. CONCLUSIONS: Reduced incremental cost and unchanged mortality may reflect improving efficiency in the standard management of PMI. An increasing fraction of discharges to skilled nursing facilities seems likely a result from hospitals striving to reduce readmissions. It remains unclear whether this trend represents a transfer of cost and risk or improves patient care.

The effect of the pressure-volume curve for positive end-expiratory pressure titration on clinical outcomes in acute respiratory distress syndrome: a systematic review.

PURPOSE: Methods to optimize positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) remain controversial despite decades of research. The pressure-volume curve (PVC), a graphical ventilator relationship, has been proposed for prescription of PEEP in ARDS. Whether the use of PVC's improves survival remains unclear. METHODS: In this systematic review, we assessed randomized controlled trials (RCTs) comparing PVC-guided treatment with conventional PEEP management on survival in ARDS based on the search of the National Library of Medicine from January 1, 1960, to January 1, 2010, and the Cochrane Central Register of Controlled Trials. Three RCTs were identified with a total of 185 patients, 97 with PVC-guided treatment and 88 with conventional PEEP management. RESULTS: The PVC-guided PEEP was associated with an increased probability of 28-day or hospital survival (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.5, 4.9) using a random-effects model without significant heterogeneity (I (2) test: P = .75). The PVC-guided ventilator support was associated with reduced cumulative risk of mortality (-0.24 (95% CI -0.38, -0.11). The PVC-managed patients received greater PEEP (standardized mean difference [SMD] 5.7 cm H2O, 95% CI 2.4, 9.0) and lower plateau pressures (SMD -1.2 cm H2O, 95% CI -2.2, -0.2), albeit with greater hypercapnia with increased arterial pCO2 (SMD 8 mm Hg, 95% CI 2, 14). Weight-adjusted tidal volumes were significantly lower in PVC-guided than conventional ventilator management (SMD 2.6 mL/kg, 95% CI -3.3, -2.0). CONCLUSION: This analysis supports an association that ventilator management guided by the PVC for PEEP management may augment survival in ARDS. Nonetheless, only 3 randomized trials have addressed the question, and the total number of patients remains low. Further outcomes studies appear required for the validation of this methodology.

Magnesium intake decreases Type 2 diabetes risk through the improvement of insulin resistance and inflammation: the Hisayama Study.

AIMS: Early studies have shown that magnesium intake decreases the risk of Type 2 diabetes, but the results are still inconsistent. We prospectively examined the association between magnesium intake and incidence of Type 2 diabetes in a general Japanese population. METHODS: A total of 1999 subjects without diabetes aged 40-79 years who underwent a 75-g oral glucose tolerance test were followed up prospectively for a mean of 15.6 years. RESULTS: During the follow-up, 417 subjects developed Type 2 diabetes. The age- and sex-adjusted incidence of Type 2 diabetes significantly decreased with increasing magnesium intake quartile levels (≤ 148.5, 148.6-171.5, 171.6-195.5 and ≥ 195.6 mg/day, P for trend = 0.01). In multivariate analyses, after adjusting for comprehensive risk factors and other dietary factors, the hazard ratio of Type 2 diabetes was 0.67 (95% CI 0.49-0.92; P = 0.01) in the third quartile and 0.63 (95% CI 0.44-0.90; P = 0.01) in the highest quartile compared with the first quartile. In addition, the risk of Type 2 diabetes was 14% lower (P = 0.04) for a 1-sd increment of log-transformed magnesium intake in the multivariate-adjusted model. In stratified analysis, there were statistically significant interactions between magnesium intake and levels of homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein or alcohol intake on the risk of Type 2 diabetes (all P < 0.05). CONCLUSIONS: Our findings suggest that increased magnesium intake was a significant protective factor for the incidence of Type 2 diabetes in the general Japanese population, especially among subjects with insulin resistance, low-grade inflammation and a drinking habit.

Two risk score models for predicting incident Type 2 diabetes in Japan.

AIMS: Risk scoring methods are effective for identifying persons at high risk of Type 2 diabetes mellitus, but such approaches have not yet been established in Japan. METHODS: A total of 1935 subjects of a derivation cohort were followed up for 14 years from 1988 and 1147 subjects of a validation cohort independent of the derivation cohort were followed up for 5 years from 2002. Risk scores were estimated based on the coefficients (ß) of Cox proportional hazards model in the derivation cohort and were verified in the validation cohort. RESULTS: In the derivation cohort, the non-invasive risk model was established using significant risk factors; namely, age, sex, family history of diabetes, abdominal circumference, body mass index, hypertension, regular exercise and current smoking. We also created another scoring risk model by adding fasting plasma glucose levels to the non-invasive model (plus-fasting plasma glucose model). The area under the curve of the non-invasive model was 0.700 and it increased significantly to 0.772 (P < 0.001) in the plus-fasting plasma glucose model. The ability of the non-invasive model to predict Type 2 diabetes was comparable with that of impaired glucose tolerance, and the plus-fasting plasma glucose model was superior to it. The cumulative incidence of Type 2 diabetes was significantly increased with elevating quintiles of the sum scores of both models in the validation cohort (P for trend < 0.001). CONCLUSIONS: We developed two practical risk score models for easily identifying individuals at high risk of incident Type 2 diabetes without an oral glucose tolerance test in the Japanese population.

Cut-off values of fasting and post-load plasma glucose and HbA1c for predicting Type 2 diabetes in community-dwelling Japanese subjects: the Hisayama Study.

AIMS: We examined the optimal cut-off values of fasting plasma glucose, 2-h post-load glucose and HbA(1c) for predicting Type 2 diabetes in community-dwelling Japanese subjects. METHODS: A total of 1982 subjects without diabetes aged 40-79 years who underwent a 75-g oral glucose tolerance test were followed prospectively for 14 years by annual health examination. RESULTS: During the follow-up, 295 subjects developed Type 2 diabetes. Compared with the first decile, the crude hazard ratio for incident Type 2 diabetes was significantly higher in the fifth fasting plasma glucose decile [5.4-5.4 mmol/l (97-98 mg/dl)] or higher, in the seventh 2-h post-load glucose decile [6.9-7.2 mmol/l (124-131 mg/dl)] or higher, and in the fifth HbA(1c) decile [34-36 mmol/mol (5.3-5.4%)] or higher. These associations remained substantially unchanged even after adjustment for confounding factors. The receiver operating characteristic curve analysis showed that the optimal cut-off values for predicting Type 2 diabetes were 5.6 mmol/l (101 mg/dl) for fasting plasma glucose, 6.9 mmol/l (124 mg/dl) for 2-h post-load glucose and 37 mmol/mol (5.5%) for HbA(1c). In a stratified analysis, the cut-off values were approximately 5.6 mmol/l (101 mg/dl) for fasting plasma glucose and 37 mmol/mol (5.5%) for HbA(1c), and these values were unchanged over BMI quartile levels, whereas the 2-h post-load glucose cut-off values declined with decreasing BMI levels. CONCLUSIONS: Our findings suggest that the cut-off value for predicting Type 2 diabetes in the Japanese population is 5.6 mmol/l (101 mg/dl) for fasting plasma glucose and 37 mmol/mol (5.5%) for HbA(1c), while the 2-h post-load glucose cut-off value is lower than the diagnostic criterion for impaired glucose tolerance.

The acute effectiveness and safety of the constant-flow, pressure-volume curve to improve hypoxemia in acute lung injury.

OBJECTIVE: To investigate the effectiveness of the constant-flow, pressure-volume curve (PVC) to prescribe positive end-expiratory pressure (PEEP) in acute lung injury (ALI) and risk of cardiopulmonary deterioration during the PVC process. DESIGN: A retrospective, cohort study. SETTING: A surgical intensive care unit (ICU) of a tertiary, university hospital. PATIENTS: Fifty consecutive ventilated patients diagnosed with ALI undergoing the PVC maneuver from 1999 to 2003. INTERVENTIONS: Titration of PEEP based on the lower inflection point of the constant-flow, pressure-volume curve. MEASUREMENTS AND MAIN RESULTS: Patients were divided into 2 groups based on PVC-guided PEEP changes of <3 cm H2O (PVC-NC or "no change") or ≥3 cm H2O (PVC-CHG or "change") from the initial empiric prescription. There was a greater increase in partial pressure of arterial oxygen (PaO2)/fractional concentration of inspired oxygen (FiO2) in the PVC-CHG group, with a mean change of 80 ± 50 (95% confidence interval [CI] 61, 98) versus 42 ± 54 (95% CI 17, 67) in the PVC-NC group. Eighty-two percent of patients (41/50) showed an increase in ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) by 20% within 6 to 24 hours after the PVC test-greater in the PVC-CHG group (OR 1.44, 95% CI 1.02, 2.01). Thirteen percent (4/30) within the PVC-CHG group and none within the PVC-NC group (0/20) required a 25% increase in vasoactive infusion rates (P = .089) in relation to the procedure. Univariate logistic regression showed that PVC-CHG was significantly associated with a 20% change in PaO2/FiO2 (OR 7.54, 95% CI 1.37, 41.41). Multivariate logistic modeling showed that PVC-guided PEEP changes of ≥3 cm H2O, age ≤65 years, and pre-PVC FiO2 ≥ .85 were significantly associated with a 20% increase in PaO2/FiO2 (receiver operator area under the curve = .86). CONCLUSIONS: In the setting of acute lung injury, use of the constant-flow, pressure-volume curve to prescribe PEEP appears associated with improvement in oxygenation with limited risk of acute, process-related, cardiopulmonary deterioration.

Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial.

OBJECTIVE: To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock. BACKGROUND: Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury. METHODS: Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. INCLUSION CRITERIA: injured patients, age ≥ 15 years with hypovolemic shock (systolic blood pressure ≤ 70 mm Hg or systolic blood pressure 71-90 mm Hg with heart rate ≥ 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern. RESULTS: : A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival-HSD: 74.5% (0.1; 95% confidence interval [CI], -7.5 to 7.8); HS: 73.0% (-1.4; 95% CI, -8.7-6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality-HSD: 10% (5.2; 95% CI, 0.4-10.1); HS: 12.2% (7.4; 95% CI, 2.5-12.2); and NS: 4.8%, P < 0.01]. CONCLUSION: Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov, NCT00316017.

Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa.

We have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of intestinal mucosal lymphocytes expressing functional IL-7 receptor. To clarify the mechanism by which locally produced IL-7 regulates the mucosal lymphocytes, we investigated IL-7 transgenic mice. Here we report that transgenic mice expressing murine IL-7 cDNA driver by the SRalpha promoter developed chronic colitis in concert with the expression of SRalpha/IL-7 transgene in the colonic mucosa. IL-7 transgenic but not littermate mice developed chronic colitis at 4-12 wk of age, with histopathological similarity to ulcerative colitis in humans. Southern blot hybridization and competitive PCR demonstrated that the expression of IL-7 messenger RNA was increased in the colonic mucosal lymphocytes but not in the colonic epithelial cells. IL-7 protein accumulation was decreased in the goblet cell-depleted colonic epithelium in the transgenic mice. Immunohistochemical and cytokine production analysis showed that lymphoid infiltrates in the lamina propria were dominated by T helper cell type 1 CD4+ T cells. Flow cytometric analysis demonstrated that CD4+ intraepithelial T cells were increased, but T cell receptor gamma/delta T cells and CD8alpha/alpha cells were not increased in the area of chronic inflammation. Increased IL-7 receptor expression in mucosal lymphocytes was demonstrated in the transgenic mice. These findings suggest that chronic inflammation in the colonic mucosa may be mediated by dysregulation of colonic epithelial cell-derived IL-7, and this murine model of chronic colitis may contribute to the understanding of the pathogenesis of human inflammatory bowel disease.

Trends in prevalence of Alzheimer's disease and vascular dementia in a Japanese community: the Hisayama Study.

OBJECTIVE: To examine secular trends in the prevalence of Alzheimer's disease (AD) and vascular dementia (VD) in a general Japanese population. METHOD: Four cross-sectional examinations were conducted among residents of a Japanese community aged >or=65 in 1985, 1992, 1998 and 2005. RESULTS: The age- and sex-adjusted prevalence of all-cause dementia significantly increased with time (6.0% in 1985, 4.4% in 1992, 5.3% in 1998 and 8.3% in 2005; P for trend = 0.002). A similar trend was observed for AD (1.1%, 1.3%, 2.3% and 3.8% respectively; P for trend < 0.001), while the age- and sex-adjusted prevalence of VD and other/unclassified dementia showed J-shaped patterns (for VD: 2.3%, 1.5%, 1.5% and 2.5%, respectively, P for trend = 0.82; for other/unclassified dementia: 2.6%, 1.7%, 1.5% and 2.0%, P for trend = 0.26). The prevalence of AD was likely to increase with time from 1985 to 2005 among subjects aged 75 or older. The ratio of the prevalence of VD to that of AD decreased with time (2.1 in 1985, 1.2 in 1992, 0.7 in 1998 and 0.7 in 2005). CONCLUSION: Our findings suggest that the prevalence of all-cause dementia and AD significantly increased over the past two decades in the general Japanese population.

Emergency medical services intervals and survival in trauma: assessment of the "golden hour" in a North American prospective cohort.

STUDY OBJECTIVE: The first hour after the onset of out-of-hospital traumatic injury is referred to as the "golden hour," yet the relationship between time and outcome remains unclear. We evaluate the association between emergency medical services (EMS) intervals and mortality among trauma patients with field-based physiologic abnormality. METHODS: This was a secondary analysis of an out-of-hospital, prospective cohort registry of adult (aged > or =15 years) trauma patients transported by 146 EMS agencies to 51 Level I and II trauma hospitals in 10 sites across North America from December 1, 2005, through March 31, 2007. Inclusion criteria were systolic blood pressure less than or equal to 90 mm Hg, respiratory rate less than 10 or greater than 29 breaths/min, Glasgow Coma Scale score less than or equal to 12, or advanced airway intervention. The outcome was in-hospital mortality. We evaluated EMS intervals (activation, response, on-scene, transport, and total time) with logistic regression and 2-step instrumental variable models, adjusted for field-based confounders. RESULTS: There were 3,656 trauma patients available for analysis, of whom 806 (22.0%) died. In multivariable analyses, there was no significant association between time and mortality for any EMS interval: activation (odds ratio [OR] 1.00; 95% confidence interval [CI] 0.95 to 1.05), response (OR 1.00; 95% CI 9.97 to 1.04), on-scene (OR 1.00; 95% CI 0.99 to 1.01), transport (OR 1.00; 95% CI 0.98 to 1.01), or total EMS time (OR 1.00; 95% CI 0.99 to 1.01). Subgroup and instrumental variable analyses did not qualitatively change these findings. CONCLUSION: In this North American sample, there was no association between EMS intervals and mortality among injured patients with physiologic abnormality in the field.

Out-of-hospital hypertonic resuscitation following severe traumatic brain injury: a randomized controlled trial.

CONTEXT: Hypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI). OBJECTIVE: To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients. INTERVENTION: A single 250-mL bolus of 7.5% saline/6% dextran 70 (hypertonic saline/dextran), 7.5% saline (hypertonic saline), or 0.9% saline (normal saline) initiated in the out-of-hospital setting. MAIN OUTCOME MEASURE: Six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4). RESULTS: The study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85%). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7% vs 51.5%; difference, 2.2% [95% CI, -4.5% to 9.0%]; hypertonic saline vs normal saline: 54.3% vs 51.5%; difference, 2.9% [95% CI, -4.0% to 9.7%]; P = .67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3% with hypertonic saline/dextran, 75.7% with hypertonic saline, and 75.1% with normal saline (P = .88). CONCLUSION: Among patients with severe TBI not in hypovolemic shock, initial resuscitation with either hypertonic saline or hypertonic saline/dextran, compared with normal saline, did not result in superior 6-month neurologic outcome or survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00316004.

Significant parameters in the evaluation of donor lungs in single-lung cellular ex vivo lung perfusion.

OBJECTIVES: Typically, single-lung ex vivo lung perfusion (SL-EVLP) is preferred when there is concern of contamination from the opposite lung. However, a comprehensive assessment of the SL-EVLP has not been completed. The purpose of this study is to compare the physiological parameters of SL-EVLP and double-lung EVLP (DL-EVLP) in the assessment of transplant suitability. METHODS: Seven pairs of rejected donor lungs were perfused in cellular EVLP, with a tidal volume of 6 ml/kg ideal body weight and a perfusion flow of 70 ml/kg/min. The transplant suitability of each side was judged in the DL-EVLP. Subsequently, the tidal volume and flow were reduced by half. The right SL-EVLP was maintained for 10 min by clamping the left main pulmonary artery and the bronchus. Similarly, left SL-EVLP was performed. The physiological parameters were compared between SL-EVLP and DL-EVLP. RESULTS: PO2/FiO2 ratio was significantly lower in SL-EVLP than in DL-EVLP [182.5 (127.5-309.5) vs 311.5 (257.5-377.0) mmHg, P < 0.001]. There was a significant correlation with a higher shunt fraction and PCO2 in the pulmonary vein in SL-EVLP when compared to DL-EVLP. There was no difference in peak inspiratory and plateau pressures between SL-EVLP and DL-EVLP. Suitable lungs (n = 6) were associated with better PO2/FiO2 ratios and lower airway pressures than non-suitable lungs (n = 8). CONCLUSIONS: In SL-EVLP, peak inspiratory and plateau pressures have clinical utility in the assessment of the transplant suitability. It is important that PO2/FiO2 ratio in SL-EVLP is appreciably lower than that in DL-EVLP. This discrepancy should be considered in the evaluation of the transplant suitability in SL-EVLP.

Periodontitis Is Associated with Chronic Obstructive Pulmonary Disease.

Although they are known to share pathophysiological processes, the relationship between periodontitis and chronic obstructive pulmonary disease (COPD) is not fully understood. The aim of the present study was to test the hypothesis that periodontitis is associated with a greater risk of development of COPD, when smoking is taken into account. The analysis in a 5-y follow-up population-based cohort study was based on 900 community-dwelling Japanese adults (age: 68.8 ± 6.3 [mean ± SD], 46.0% male) without COPD aged 60 or older with at least 1 tooth. Participants were classified into 3 categories according to baseline periodontitis severity (no/mild, moderate, and severe). COPD was spirometrically determined by a fixed ratio of <0.7 for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and by FEV1/FVC below the lower limit of normal. Poisson regression was used to calculate the relative risk (RR) of developing COPD according to the severity of periodontitis. The population attributable fraction (PAF) was also calculated. During follow-up, 22 (2.4%) subjects developed COPD. Compared with no/mild periodontitis subjects, a significantly increased risk of COPD occurred among severe periodontitis subjects (RR = 3.55; 95% confidence interval [CI], 1.18 to 10.67), but no significant differences were observed between the no/mild and moderate categories (RR = 1.48; 95% CI, 0.56 to 3.90). After adjustment for potential confounders, including smoking intensity, the relationship between severe periodontitis and risk of COPD remained significant (RR = 3.51; 95% CI, 1.15 to 10.74). Likewise, there was a positive association of periodontitis severity with risk of COPD ( P for trend = 0.043). The PAF for COPD due to periodontitis was 22.6%. These data highlight the potential importance of periodontitis as a risk factor for COPD.

Polymorphism in the sorbin and SH3-domain-containing-1 (SORBS1) gene and the risk of brain infarction in the Japanese population: the Fukuoka Stroke Registry and the Hisayama study.

BACKGROUND AND PURPOSE: Sorbin and SH3-domain-containing-1 (SORBS1) is an important adaptor protein in insulin-signalling pathway, and its genetic polymorphism may regulate the activity of insulin resistance. We investigated the association between the SORBS1 T228A polymorphism and ischaemic stroke. METHODS: Genotyping was achieved by a rapid-cycle PCR and melting curve analysis using fluorescent probes in 1049 incident cases of ischaemic stroke and 1049 age- and sex-matched control subjects recruited from the Hisayama study. RESULTS: The allele distributions of the SORBS1 T228A polymorphism were similar amongst cases and controls. The multivariate-adjusted odds ratio (OR) of the AA genotype for ischaemic stroke was 2.897 (95% CI, 0.907-8.018) compared with the TT genotype. In terms of stroke subtype, there was a trend toward a difference in the AA genotypes for lacunar infarction, compared with the TT genotype (OR = 8.740, P = 0.0510), and combined TT and TA genotypes (OR = 8.768, P = 0.0505). The other polymorphisms genotyped were not associated with any subtypes of ischaemic stroke. T228A polymorphism of SORBS1 was not associated with the prevalence of diabetes. CONCLUSIONS: The AA genotype of SORBS1 T228A polymorphism may play a role in lacunar infarction in the Japanese population.