Dysregulation of Vascular Endothelial Growth Factor Receptor-2 by Multiple miRNAs in Endothelial Colony-Forming Cells of Coronary Artery Disease.

BACKGROUND/AIMS: Endothelial colony-forming cells (ECFCs) have the potential to be used in regenerative medicine. Dysfunction of ECFCs is correlated with the onset of cardiovascular disorders, especially coronary artery disease (CAD). Binding of vascular endothelial growth factor A (VEGFA) to vascular endothelial growth factor receptor-2 (VEGFR2) triggers cell motility and angiogenesis of ECFCs, which are crucial to vascular repair. METHODS: To identify the miRNA-VEGFR2-dependent regulation of ECFC functions, ECFCs isolated from peripheral blood of disease-free and CAD individuals were subjected to small RNA sequencing for identification of anti-VEGFR2 miRNAs. The angiogenic activities of the miRNAs were determined in both in vitro and in vivo mice models. RESULTS: Three miRNAs, namely miR-410-3p, miR-497-5p, and miR-2355-5p, were identified to be upregulated in CAD-ECFCs, and VEGFR2 was their common target gene. Knockdown of these miRNAs not only restored the expression of VEGFR2 and increased angiogenic activities of CAD-ECFCs in vitro, but also promoted blood flow recovery in ischemic limbs in vivo. miR-410-3p, miR-497-5p, and miR-2355-5p could serve as potential biomarkers for CAD detection as they are highly expressed in the plasma of CAD patients. CONCLUSIONS: This modulation could help develop new therapeutic modalities for cardiovascular diseases and other vascular dysregulated diseases, especially tumor angiogenesis.

Periodontal Pocket Depth, Hyperglycemia, and Progression of Chronic Kidney Disease: A Population-Based Longitudinal Study.

BACKGROUND: No large epidemiological study has been conducted to investigate the interaction and joint effects of periodontal pocket depth and hyperglycemia on progression of chronic kidney disease in patients with periodontal diseases. METHODS: Periodontal pocket depth was utilized for the grading severity of periodontal disease in 2831 patients from January 2002 to June 2013. Progression of chronic kidney disease was defined as progression of color intensity in glomerular filtration rate and albuminuria grid of updated Kidney Disease-Improving Global Outcomes guidelines. Multivariable-adjusted hazard ratios (aHR) in various models were presented across different levels of periodontal pocket depth and hemoglobin A1c (HbA1c) in forest plots and 3-dimensional histograms. RESULTS: During 7621 person-years of follow-up, periodontal pocket depth and HbA1C levels were robustly associated with incremental risks for progression of chronic kidney disease (aHR 3.1; 95% confidence interval [CI], 2.0-4.6 for periodontal pocket depth >4.5 mm, and 2.5; 95% CI, 1.1-5.4 for HbA1C >6.5%, respectively). The interaction between periodontal pocket depth and HbA1C on progression of chronic kidney disease was strong (P <.01). Patients with higher periodontal pocket depth (>4.5 mm) and higher HbA1C (>6.5%) had the greatest risk (aHR 4.2; 95% CI, 1.7-6.8) compared with the lowest aHR group (periodontal pocket depth ≤3.8 mm and HbA1C ≤6%). CONCLUSION: Our study identified combined periodontal pocket depth and HbA1C as a valuable predictor of progression of chronic kidney disease in patients with periodontal diseases. While considering the interaction between periodontal diseases and hyperglycemia, periodontal survey and optimizing glycemic control are warranted to minimize the risk of worsening renal function.

Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation.

BACKGROUND/OBJECTIVE: In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of rhGH and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers. METHODS: 72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n=63) and 12 (n=46-48) were assessed for adiponectin, C-reactive protein, homocysteine, interleukin-1, interleukin-6, tumor necrosis factor alpha, interferon gamma, fibrinogen, plasminogen activator inhibitor-1 antigen, and tissue plasminogen activator antigen. RESULTS: Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH arm alone . There were no significant changes in the other biomarkers among the different treatment groups. DISCUSSION: In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with a combination of rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT.

Does the Presence of Endometriosis Affect Prognosis of Ovarian Cancer?

Ovarian cancers diagnosed between 2000 and 2013 were examined and cases with and without endometriosis compared. Among 139 epithelial ovarian, there were 49 (35%) with endometriosis and 90 (65%) without endometriosis. Endometriosis associated ovarian cancers were more likely to be confined to the pelvis (54% vs. 9%, p < 0.0001) and lower grade (51% vs. 29%, p = 0.014). Younger age and earlier stage independently predicted the presence of endometriosis (p = 0.0011 and p < 0.0001, respectively). Ovarian cancer patients with endometriosis had improved PFS and OS [(HR = 0.20; 95% CI, 0.09-0.43), (HR = 0.18; 95% CI, 0.04-0.81)], compared to patients without endometriosis; however, endometriosis had no independent prognostic significance.

MicroRNA-134 Contributes to Glucose-Induced Endothelial Cell Dysfunction and This Effect Can Be Reversed by Far-Infrared Irradiation.

Diabetes mellitus (DM) is a metabolic disease that is increasing worldwide. Furthermore, it is associated with the deregulation of vascular-related functions, which can develop into major complications among DM patients. Endothelial colony forming cells (ECFCs) have the potential to bring about medical repairs because of their post-natal angiogenic activities; however, such activities are impaired by high glucose- (HG) and the DM-associated conditions. Far-infrared radiation (FIR) transfers energy as heat that is perceived by the thermoreceptors in human skin. Several studies have revealed that FIR improves vascular endothelial functioning and boost angiogenesis. FIR has been used as anti-inflammatory therapy and as a clinical treatment for peripheral circulation improvement. In addition to vascular repair, there is increasing evidence to show that FIR can be applied to a variety of diseases, including cardiovascular disorders, hypertension and arthritis. Yet mechanism of action of FIR and the biomarkers that indicate FIR effects remain unclear. MicroRNA-134 (miR-134-5p) was identified by small RNA sequencing as being increased in high glucose (HG) treated dfECFCs (HG-dfECFCs). Highly expressed miR-134 was also validated in dmECFCs by RT-qPCR and it is associated with impaired angiogenic activities of ECFCs. The functioning of ECFCs is improved by FIR treatment and this occurs via a reduction in the level of miR-134 and an increase in the NRIP1 transcript, a direct target of miR-134. Using a mouse ischemic hindlimb model, the recovery of impaired blood flow in the presence of HG-dfECFCs was improved by FIR pretreatment and this enhanced functionality was decreased when there was miR-134 overexpression in the FIR pretreated HG-dfECFCs. In conclusion, our results reveal that the deregulation of miR-134 is involved in angiogenic defects found in DM patients. FIR treatment improves the angiogenic activity of HG-dfECFCs and dmECFCs and FIR has potential as a treatment for DM. Detection of miR-134 expression in FIR-treated ECFCs should help us to explore further the effectiveness of FIR therapy.

Health-related quality of life in midlife women in Qatar: relation to arthritis and symptoms of joint pain.

OBJECTIVE: The prevalence of osteoarthritis (OA) and rheumatoid arthritis (RA) has been poorly documented in the Middle East and North African region, including the State of Qatar. Given that musculoskeletal pain is commonly reported among midlife women, we evaluated the association between self-report of either OA or RA and health-related quality of life (HRQoL) among midlife women in Qatar. In addition, HRQoL among women in Qatar was compared with that of women in the Study of Women's Health Across the Nation (SWAN). METHODS: A cross-sectional study was conducted among 841 women 40 to 60 years recruited from primary care centers in Qatar. Face-to-face interviews were conducted and included measures of self-reported OA and RA, health-related symptom experience, and HRQoL using the SF-36 health survey. RESULTS: Most women were obese (75.5%) and reported being bothered by aches and stiffness in joints (71.6%). Prevalence of self-reported OA and RA was 4.8% and 4.3%, respectively. OA was significantly associated with reduced physical function (adjusted odds ratio [OR], 2.97; P=0.003). RA was also significantly related to reduced physical function (adjusted OR, 2.94; P = 0.01) and role physical (adjusted OR, 2.67; P = 0.01). When compared with women from the SWAN, women from the current study had significantly lower mean scores for bodily pain (53.0 vs. 68.9, P = 0.0001) and for vitality (49.9 vs. 54.8, P = 0.0001). CONCLUSIONS: Self-report of OA or RA was associated with significant disability in our sample. Because symptoms of aches and stiff joints were so frequently reported, arthritis may be under-diagnosed, especially given the high rates of obesity observed.

Hypertonic saline reduces cumulative and daily intracranial pressure burdens after severe traumatic brain injury.

OBJECT: Increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI) is associated with a higher mortality rate and poor outcome. Mannitol and hypertonic saline (HTS) have both been used to treat high ICP, but it is unclear which one is more effective. Here, the authors compare the effect of mannitol versus HTS on lowering the cumulative and daily ICP burdens after severe TBI. METHODS: The Brain Trauma Foundation TBI-trac New York State database was used for this retrospective study. Patients with severe TBI and intracranial hypertension who received only 1 type of hyperosmotic agent, mannitol or HTS, were included. Patients in the 2 groups were individually matched for Glasgow Coma Scale score (GCS), pupillary reactivity, craniotomy, occurrence of hypotension on Day 1, and the day of ICP monitor insertion. Patients with missing or erroneous data were excluded. Cumulative and daily ICP burdens were used as primary outcome measures. The cumulative ICP burden was defined as the total number of days with an ICP of > 25 mm Hg, expressed as a percentage of the total number of days of ICP monitoring. The daily ICP burden was calculated as the mean daily duration of an ICP of > 25 mm Hg, expressed as the number of hours per day. The numbers of intensive care unit (ICU) days, numbers of days with ICP monitoring, and 2-week mortality rates were also compared between the groups. A 2-sample t-test or chi-square test was used to compare independent samples. The Wilcoxon signed-rank or Cochran-Mantel-Haenszel test was used for comparing matched samples. RESULTS: A total of 35 patients who received only HTS and 477 who received only mannitol after severe TBI were identified. Eight patients in the HTS group were excluded because of erroneous or missing data, and 2 other patients did not have matches in the mannitol group. The remaining 25 patients were matched 1:1. Twenty-four patients received 3% HTS, and 1 received 23.4% HTS as bolus therapy. All 25 patients in the mannitol group received 20% mannitol. The mean cumulative ICP burden (15.52% [HTS] vs 36.5% [mannitol]; p = 0.003) and the mean (± SD) daily ICP burden (0.3 ± 0.6 hours/day [HTS] vs 1.3 ± 1.3 hours/day [mannitol]; p = 0.001) were significantly lower in the HTS group. The mean (± SD) number of ICU days was significantly lower in the HTS group than in the mannitol group (8.5 ± 2.1 vs 9.8 ± 0.6, respectively; p = 0.004), whereas there was no difference in the numbers of days of ICP monitoring (p = 0.09). There were no significant differences between the cumulative median doses of HTS and mannitol (p = 0.19). The 2-week mortality rate was lower in the HTS group, but the difference was not statistically significant (p = 0.56). CONCLUSIONS: HTS given as bolus therapy was more effective than mannitol in lowering the cumulative and daily ICP burdens after severe TBI. Patients in the HTS group had significantly lower number of ICU days. The 2-week mortality rates were not statistically different between the 2 groups.

Lipid profile changes in the severely obese after laparoscopic sleeve gastrectomy (LSG), 1, 3, and 5 years after surgery.

BACKGROUND: Since there is an increasing acceptance of the laparoscopic sleeve gastrectomy (LSG) and limited information regarding its effect on cardiac risk factors, we assessed lipid profiles. METHODS: A retrospective review of patient records pre and post LSG was performed. Analysis of variance evaluated group differences and paired t tests compared variable changes. RESULTS: Eighty two patients (67 % female, age 46.4 ± 13.9) had presurgery lipid profiles and follow-up (43 at 1 year, 28 at 3 years, and 26 at 5 years). Groups were not different in gender distribution. The presurgery mean body mass index (BMI) was 55.7 kg/m(2); 65.9 % of the subjects were super obese. After surgery, percentage of excess BMI loss was 58.1 % year (yr) 1, 61.3 % yr 3, and 39.0 % yr 5. Lipids were within the normal ranges for all parameters at all times; however, at baseline 77 % had at least one abnormality. At 1 year, triglycerides decreased significantly from baseline (adjusted p value (adj-p) = 0.004) and high-density lipoprotein (HDL) increased (adj-p = 0.025). Year 3 HDL was significantly different from baseline, adj-p = 0.0001. Yr 3 cholesterol increased from baseline, (adj-p = 0.027). Negative linear correlations with weight loss were present for low-density lipoprotein (LDL) at yr 3(r = 0.46, p = 0.02) and triglyceride change at year 5 (r = 0.48, p = 0.02). The percentage of patients with dyslipidemia or medicated did not change significantly during these 5 years. CONCLUSIONS: For this population electing LSG, mean lipid profiles were within normal ranges for all parameters before surgery. However, 77 % showed at least one abnormality presurgery. Weight change correlated with some changes of triglycerides, HDL, and LDL over time, but the impact was limited.

Screening for type 2 diabetes mellitus in patients with mental illness: application of a self-assessment score for diabetes mellitus risk.

Various methods for diabetes risk assessment have been developed over a decade, but they were not evaluated in patients with mental illness. This study examined the feasibility and utility of a self-assessment score for type 2 diabetes mellitus (DM2) risk among patients with mental illness. DM2 risk was assessed by patients with mental illness as well as clinicians via a self-assessment questionnaire, and the resulting scores were compared to each other as well as with actual diagnosis. Of 100 patients, nine patients were newly revealed to have DM2 and 34 patients have pre-DM2. Patients tended to underreport risk factors - obesity and physical activity - so perceived to have lower risk. Sensitivity of the self-assessment score was different when used by patients and by clinicians despite correlation coefficient of 0.82. Based on positive predictive values, we may expect one out of two patients who have high scores actually have DM2 or pre-DM2. Also, the discrimination capability was reasonably high (AUC=0.79), comparable to its performance observed in general populations. The self-assessment score has potential as a simple and adjunct tool to identify a high risk group of DM2/pre-DM2 among persons with mental illness, especially, when used together with health care providers.

miRNome traits analysis on endothelial lineage cells discloses biomarker potential circulating microRNAs which affect progenitor activities.

BACKGROUND: Endothelial progenitor cells (EPCs) play a fundamental role in not only blood vessel development but also post-natal vascular repair. Currently EPCs are defined as early and late EPCs based on their biological properties and their time of appearance during in vitro culture. Both EPC types assist angiogenesis and have been linked to ischemia-related disorders, including coronary artery disease (CAD). RESULTS: We found late EPCs are more mobile than early EPCs and matured endothelial cells (ECs). To pinpoint the mechanism, microRNA profiles of early EPCs late EPCs, and ECs were deciphered by small RNA sequencing. Obtained signatures made up of both novel and known microRNAs, in which anti-angiogenic microRNAs such as miR-221 and miR-222 are more abundant in matured ECs than in late EPCs. Overexpression of miR-221 and miR-222 resulted in the reduction of genes involved in hypoxia response, metabolism, TGF-beta signalling, and cell motion. Not only hamper late EPC activities in vitro, both microRNAs (especially miR-222) also hindered in vivo vasculogenesis in a zebrafish model. Reporter assays showed that miR-222, but not miR-221, targets the angiogenic factor ETS1. In contrast, PIK3R1 is the target of miR-221, but not miR-222 in late EPCs. Clinically, both miR-221-PIK3R1 and miR-222-ETS1 pairs are deregulated in late EPCs of CAD patients. CONCLUSIONS: Our results illustrate EPCs and ECs exploit unique miRNA modalities to regulate angiogenic features, and explain why late EPC levels and activities are reduced in CAD patients. These data will further help to develop new plasma biomarkers and therapeutic approaches for ischemia-related diseases or tumor angiogenesis.

Research training among pediatric residency programs: a national assessment.

PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) states that "residents should participate in scholarly activity." However, there is little guidance for effectively integrating scholarly activity into residency. This study was conducted to understand how pediatric residency programs meet ACGME requirements and to identify characteristics of successful programs. METHOD: The authors conducted an online cross-sectional survey of all pediatric residency program directors in October 2012, assessing program characteristics, resident participation in scholarly activity, program infrastructure, barriers, and outcomes. Multivariate logistic regression was used to identify characteristics of programs in the top quartile for resident scholarly activity participation. RESULTS: The response rate was 52.8% (105/199 programs). Seventy-seven (78.6%) programs required scholarly activity, although definitions were variable. When including only original research, systematic reviews or meta-analyses, and case reports or series with references, resident participation averaged 56% (range 0%-100%). Characteristics associated with high-participation programs included a scholarly activity requirement (odds ratio [OR] = 5.5, 95% confidence interval [CI] = 1.03-30.0); program director belief that all residents should present work regionally or nationally (OR = 4.7, 95% CI = 1.5-15.1); and mentorship by >25% of faculty (OR = 3.6, CI = 1.2-11.4). Only 47.1% (41) of program directors were satisfied with resident participation, and only 30.7% (27) were satisfied with the quality of research training provided. CONCLUSIONS: The findings suggest that resident scholarly activity experience is highly variable and suboptimal. Identifying characteristics of successful programs can improve the resident research training experience.

A comparison of same setting versus delayed vitrectomy in the management of retained lens fragments after cataract surgery.

PURPOSE: Intravitreal retained lens fragments are a rare but potentially serious complication of phacoemulsification. The purpose of this study was to compare same setting ("no wait") vitrectomy with delayed surgery in the management of retained lens fragments in a single academic setting. METHODS: This study is a retrospective nonrandomized study of all patients undergoing pars plana vitrectomy for retained lens fragments after cataract surgery from 2007 to 2012. Outcomes included visual acuity and the development of various complications such as retinal detachment, elevated intraocular pressure >30 mmHg, and cystoid macular edema. Multivariate analysis was performed to adjust for potentially confounding variables such as age and preoperative visual acuity. RESULTS: Twenty-eight consecutive eyes (13 same setting, 15 delayed setting) were included in the analysis. Patients in the same setting group were older than in the delayed group (81.00 vs. 72.87 years, P = 0.053). No other preoperative differences existed between the groups (axial length, preoperative vision, and intraocular pressure). The mean time to pars plana vitrectomy in the delayed group was 26.6 days (range, 1-91 days). The mean follow-up time was 363 days (same setting) and 643 days (delayed). At the most recent follow-up, no significant difference existed in mean vision between the same setting (logMAR, 0.42) and the delayed group (logMAR, 0.57) (P = 0.132). Multivariate analysis showed no difference in final vision when adjusting for age and preoperative vision. Although there was a trend for eyes in the same setting group to obtain good vision (≥ 20/40) faster, a higher percentage of eyes in the delayed group obtained good vision at the most recent follow-up (66.7 vs. 23.1%, P = 0.02). More eyes in the delayed group had an intraocular pressure >30 at any point (P = 0.055). There was no significant difference between the groups in any other complications such as retinal detachment, choroidal detachment, and cystoid macular edema during the follow-up. CONCLUSION: In this cohort, same setting pars plana vitrectomy offers no significant visual acuity advantage over delayed pars plana vitrectomy in patients with retained lens fragments. Fewer eyes in the same setting group "ever" had an intraocular pressure ≥ 30 during follow-up, whereas no other complication differences were seen between the groups.

Dysregulated miR-361-5p/VEGF axis in the plasma and endothelial progenitor cells of patients with coronary artery disease.

Dysfunction and reduction of circulating endothelial progenitor cell (EPC) is correlated with the onset of cardiovascular disorders including coronary artery disease (CAD). VEGF is a known mitogen for EPC to migrate out of bone marrow to possess angiogenic activities, and the plasma levels of VEGF are inversely correlated to the progression of CAD. Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. However, how miRNAs and VEGF cooperate to regulate CAD progression is still unclear. Through the small RNA sequencing (smRNA-seq), we deciphered the miRNome patterns of EPCs with different angiogenic activities, hypothesizing that miRNAs targeting VEGF must be more abundant in EPCs with lower angiogenic activities. Candidates of anti-VEGF miRNAs, including miR-361-5p and miR-484, were enriched in not only diseased EPCs but also the plasma of CAD patients. However, we found out only miR-361-5p, but not miR-484, was able to suppress VEGF expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-361-5p to the 3'-UTR of VEGF mRNA. Knock down of miR-361-5p not only restored VEGF levels and angiogenic activities of diseased EPCs in vitro, but further promoted blood flow recovery in ischemic limbs of mice. Collectively, we discovered a miR-361-5p/VEGF-dependent regulation that could help to develop new therapeutic modalities not only for ischemia-related diseases but also for tumor angiogenesis.

SPOP mutations in prostate cancer across demographically diverse patient cohorts.

BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown. OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material. DESIGN SETTING AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features. RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P<.01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P<.01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes. CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.

The impact of sleep apnea on postoperative utilization of resources and adverse outcomes.

BACKGROUND: Despite the concern that sleep apnea (SA) is associated with increased risk for postoperative complications, a paucity of information is available regarding the effect of this disorder on postoperative complications and resource utilization in the orthopedic population. With an increasing number of surgical patients suffering from SA, this information is important to physicians, patients, policymakers, and administrators alike. METHODS: We analyzed hospital discharge data of patients who underwent total hip or knee arthroplasty in approximately 400 U.S. Hospitals between 2006 and 2010. Patient, procedure, and health care system-related demographics and outcomes such as mortality, complications, and resource utilization were compared among groups. Multivariable logistic regression models were fit to assess the association between SA and various outcomes. RESULTS: We identified 530,089 entries for patients undergoing total hip and knee arthroplasty. Of those, 8.4% had a diagnosis code for SA. In the multivariate analysis, the diagnosis of SA emerged as an independent risk factor for major postoperative complications (OR 1.47; 95% confidence interval [CI], 1.39-1.55). Pulmonary complications were 1.86 (95% CI, 1.65-2.09) times more likely and cardiac complications 1.59 (95% CI, 1.48-1.71) times more likely to occur in patients with SA. In addition, SA patients were more likely to receive ventilatory support, use more intensive care, stepdown and telemetry services, consume more economic resources, and have longer lengths of hospitalization. CONCLUSIONS: The presence of SA is a major clinical and economic challenge in the postoperative period. More research is needed to identify SA patients at risk for complications and develop evidence-based practices to aid in the allocation of clinical and economic resources.

Age-specific cerebral perfusion pressure thresholds and survival in children and adolescents with severe traumatic brain injury*.

OBJECTIVES: Evidence-based traumatic brain injury guidelines support cerebral perfusion pressure thresholds for adults at a class 2 level, but evidence is lacking in younger patients. The purpose of this study is to identify the impact of age-specific cerebral perfusion pressure thresholds on short-term survival among patients with severe traumatic brain injury. DESIGN: Institutional review board-approved, prospective, observational cohort study. SETTING: Level I or II trauma centers in New York State. PATIENTS: Data on all patients with a postresuscitation Glasgow Coma Score less than 9 were added in the Brain Trauma Foundation prospective New York State TBI-trac database. MEASUREMENTS AND MAIN RESULTS: We calculated the survival rates and relative risks of mortality for patients with severe traumatic brain injury based on predefined age-specific cerebral perfusion pressure thresholds. A higher threshold and a lower threshold were defined for each age group: 60 and 50 mm Hg for 12 years old or older, 50 and 35 mm Hg for 6-11 years, and 40 and 30 mm Hg for 0-5 years. Patients were stratified into age groups of 0-11, 12-17, and 18 years old or older. Three exclusive groups of CPP-L (events below low cerebral perfusion pressure threshold), CPP-B (events between high and low cerebral perfusion pressure thresholds), and CPP-H (events above high cerebral perfusion pressure threshold) were defined. As an internal control, we evaluated the associations between cerebral perfusion pressure events and events of hypotension and elevated intracranial pressure. Survival was significantly higher in 0-11 and 18 years old or older age groups for patients with CPP-H events compared with those with CPP-L events. There was a significant decrease in survival with prolonged exposure to CPP-B events for the 0-11 and 18 years old and older age groups when compared with the patients with CPP-H events (p = 0.0001 and p = 0.042, respectively). There was also a significant decrease in survival with prolonged exposure to CPP-L events in all age groups compared with the patients with CPP-H events (p< 0.0001 for 0- to 11-yr olds, p = 0.0240 for 12- to 17-yr olds, and p < 0.0001 for 18-yr old and older age groups). The 12- to 17-year olds had a significantly higher likelihood of survival compared with adults with prolonged exposure to CPP-L events (< 50 mm Hg). CPP-L events were significantly related to systemic hypotension for the 12- to 17-year-old group (p = 0.004) and the 18-year-old and older group (p < 0.0001). CPP-B events were significantly related to systemic hypotension in the 0- to 11-year-old group (p = 0.014). CPP-B and CPP-L events were significantly related to elevated intracranial pressure in all age groups. CONCLUSIONS: Our data provide new evidence that cerebral perfusion pressure targets should be age specific. Furthermore, cerebral perfusion pressure goals above 50 or 60 mm Hg in adults, above 50 mm Hg in 6- to 17-year olds, and above 40 mm Hg in 0- to 5-year olds seem to be appropriate targets for treatment-based studies. Systemic hypotension had an inconsistent relationship to events of low cerebral perfusion pressure, whereas elevated intracranial pressure was significantly related to all low cerebral perfusion pressure events across all age groups. This may impart a clinically important difference in care, highlighting the necessity of controlling intracranial pressure at all times, while targeting systolic blood pressure in specific instances.