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The effects of nitric oxide synthase inhibition on brain acidosis, regional cortical blood flow (rCBF), and NADH redox state were examined using in vivo fluorescence imaging during four 15-min periods of moderate focal cerebral ischemia, each separated by three 5-min reperfusion periods followed by a final 3-h reperfusion period. Fasted rabbits under 1.5% halothane were divided into six groups of seven animals each: nonischemic controls, ischemic controls, and the following drug groups receiving NG-nitro-L-arginine methyl ester (L-NAME) intravenously 20 min before repetitive ischemia (as follows: 0.1 mg/kg, 1 mg/kg, 10 mg/kg, and 1 mg/kg + 5 mg/kg L-arginine). L-NAME at 0.1 and 1 mg/kg prevented the development of significant brain acidosis throughout the four ischemic insults. L-NAME at 10 mg/kg reduced preischemic rCBF by 21% (P < 0.05) and did not mitigate brain acidosis after the third and fourth ischemic insults. Brain intracellular pH returned toward baseline after the 3-h final reperfusion in all groups. NADH redox state was significantly (P < 0.05) elevated from baseline controls in all groups during the last three ischemic insults. During the final reperfusion period, NADH redox state returned toward baseline values only in the 0.1 mg/kg L-NAME and ischemic control group. In conclusion, low-dose L-NAME attenuated brain acidosis independent from rCBF changes during intermittent, moderate focal cerebral ischemia.

Purpose: Data regarding best practices for ventilator management strategies that improve outcomes in acute respiratory distress syndrome (ARDS) are readily available. However, little is known regarding processes to ensure compliance with these strategies. We developed a goal-directed mechanical ventilation order set that included physician-specified lung-protective ventilation and oxygenation goals to be implemented by respiratory therapists (RTs). We sought as a primary outcome to determine whether an RT-driven order set with predefined oxygenation and ventilation goals could be implemented and associated with improved adherence with best practice. Methods: We evaluated 1302 patients undergoing invasive mechanical ventilation (1693 separate episodes of invasive mechanical ventilation) prior to and after institution of a standardized, goal-directed mechanical ventilation order set using a controlled before-and-after study design. Patient-specific goals for oxygenation partial pressure of oxygen in arterial blood (Pao 2 ), ARDS Network [Net] positive end-expiratory pressure [PEEP]/fraction of inspired oxygen [Fio 2 ] table use) and ventilation (pH, partial pressure of carbon dioxide) were selected by prescribers and implemented by RTs. Results: Compliance with the new mechanical ventilation order set was high: 88.2% compliance versus 3.8% before implementation of the order set ( P < .001). Adherence to the PEEP/Fio 2 table after implementation of the order set was significantly greater (86.0% after vs 82.9% before, P = .02). There was no difference in duration of mechanical ventilation, intensive care unit (ICU) length of stay, and in-hospital or ICU mortality. Conclusions: A standardized best practice mechanical ventilation order set can be implemented by a multidisciplinary team and is associated with improved compliance to written orders and adherence to the ARDSNet PEEP/Fio 2 table.

OBJECTIVE Intensive treatment (INT) of type 1 diabetes reduces the incidence of cardiovascular disease (CVD) events compared with conventional treatment (CONV), but it also results in more weight gain. Our objective was to examine whether excessive weight gain from INT of type 1 diabetes is independently associated with subsequent CVD events. RESEARCH DESIGN AND METHODS Quartiles (Q) of weight gain in 1,213 participants aged 18 years and older at enrollment in the Diabetes Control and Complications Trial (DCCT) were determined within randomized treatment groups (INT vs. CONV) using change in BMI from baseline to the closeout DCCT visits. Effects of this weight gain on CVD risk factors and outcomes during an additional 20 years of observational follow-up were then determined. RESULTS The Q4 INT group experienced greater proportional weight gain (median change in BMI, 6.08 kg/m2), increases in CVD risk factors, and need for medications for hypertension and lipids compared with the Q1–3 INT and comparable CONV groups. Over a mean of 26 years of follow-up, the numbers of major and total CVD events were not statistically different in Q4 compared with Q1–3 of either the INT or CONV group. By year 14, however, the incident CVD event curve became significantly higher in the Q4 INT group than in the Q1–3 INT groups (P = 0.024) and was similar to that for the CONV group. CONCLUSIONS For the first 13 years after DCCT, INT for type 1 diabetes reduced macrovascular events compared with CONV, even when excessive weight gain occurred. After this, total CVD events significantly increased in the Q4 INT group, becoming equivalent to those in the CONV group. Longer follow-up is needed to determine whether this trend continues and results in more major CVD events.

101 Background: Socioeconomic status (SES) influences healthcare outcomes, but the influence of SES on cancer cachexia is unknown. We identify components of SES associated with pre-treatment cachexia in patients with non-small cell lung cancer (NSCLC) and assess their prognostic significance on survival. Methods: A prospectively maintained institutional tumor registry identified 1,365 patients with NSCLC consecutively treated at a tertiary care health system from 1/1/06 to 12/31/13. Insurance status was abstracted from the registry. Educational attainment and household income were estimated from census data using location of primary residence. Cancer cachexia was defined retrospectively using the international consensus definition. Multivariable regression analysis was used to identify prognostic factors of pre-treatment cancer cachexia and survival. Results: Cachexia was present at the time of NSCLC diagnosis in 30% of all patients including 17% of patients with stage I disease. Patients with Medicaid or no insurance were more likely to have pre-treatment cachexia compared to those with private insurance (Odds Ratio [OR] 1.9, 95% Confidence Interval [CI] 1.2-3.1; OR 2.1, 95% CI 1.2-3.4, respectively). Attainment of a high school diploma was inversely associated with pre-treatment cachexia (OR: 0.1, 95% CI 0.02-0.2). On multivariable analysis, comorbidity, histology, tumor grade, and disease stage were prognostic of survival among cachectic patients; however, insurance status, educational attainment, and household income were not. Conclusions: Lower SES is associated with pre-treatment cachexia in patients with NSCLC, but pre-treatment cachexia is detrimental to survival regardless of SES. Together, these findings suggest early intervention for patients with cancer cachexia may improve outcomes.

Abstract BACKGROUND When clinical presentation, laboratory studies, or imaging cannot diagnose cavernous sinus (CS) and/or Meckel's cave (MC) lesions, biopsy may be necessary. OBJECTIVE To review our institutional series of biopsies of indeterminate CS and MC lesions. METHODS Records from January 1994 to June 2016 were searched for biopsied indeterminate CS and MC lesions. We defined indeterminate as having an atypical imaging appearance or a broad differential and the need for tissue for definitive diagnosis. We defined primary tumors as originating from cells inherent or near the CS and MC. RESULTS Eighty-five patients were included (median age 59 [2-85] yr); 22 (28%) had a cancer history. Approaches included frontotemporal craniotomy (n = 48, 56%), endoscopic endonasal (n = 20, 24%), percutaneous transforamen ovale (n = 12, 14%), or retrosigmoid craniotomy (n = 5, 6%). Final diagnosis was metastatic in 27 (32%), primary in 21 (25%), inflammatory in 13 (15%), hematologic in 11 (13%), fungal in 5 (5%), and nondefinitive or nondiagnostic in 8 (10%) patients. Thirteen (59%) patients with a cancer history (n = 22) had a diagnosis consistent with their prior cancer; the remaining had a second pathology (n = 6, 27%) or nondiagnostic biopsy (n = 3, 14%). Two patients had surgical complications resulting in death. CONCLUSION In this patient cohort, metastatic tumors were the most likely pathology. The biopsy threshold should be lower in patients with a cancer history if clinical or radiographic diagnosis is uncertain as 27% had a second disease. However, we consider biopsy as a last resort because the risk of major morbidity/mortality, while low, is not zero.

Objectives: The purpose of this study is to investigate the ability of competitive athletes to remain at a high level of competition following osteochondral allograft transplantation (OCA) of the knee. Methods: A retrospective review was performed to identify all competitive athletes (high school, collegiate, professional) who underwent an isolated femoral condyle OCA between 2004 and 2012. Patient reported outcome (PRO) questionnaires (Lysholm, International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMasters Universities Arthritis Index (WOMAC), Short Form-12 (SF-12), Tegner, and Marx) and custom return-to-sport surveys were administered. All subsequent reoperations were documented. Results: A total of 13 (7 male, 6 female) athletes were identified with an average follow-up of 5.9 ± 2.5 years. Four athletes competed at an intercollegiate level, while 9 played high-level high-school sports. Seven athletes returned to competitive sport (54%) at an average of 7.9 ± 3.5 months, five of whom were returned to pre-injury levels of play. Of the eight athletes who either did not return to sport or failed to sustain their high level of play, the most common reasons cited were a change in life circumstances, such as graduation, or a fear of re-injury (Figure 1). At final follow-up, regardless of return-to-play, all athletes had significant improvements in all PRO scores except for KOOS-Sport, WOMAC-Stiffness, and SF-12 Mental subscales. Tegner Activity scores dropped significantly from pre-injury to final follow-up (8.2 ± 2.4, 4.5 ± 2.1, p < 0.01). There were three reoperations and zero instances of graft failure. Conclusion: OCAs provide acceptable rates of return-to-play and excellent long-term outcomes for high-level athletes with large osteochondral defects. Social factors are three times more likely than persistent pain to prevent return to sport.

Insertion of tympanostomy tubes is a common elective pediatric surgical procedure and is typically performed under general anesthesia. The potential to reduce general anesthetic requirements for young children has led to increased interest in alternatives for tympanostomy tube placement. A tympanostomy tube system, developed to enable tympanostomy tube placement in a single pass on conscious patients under moderate sedation, was evaluated. A prospective study on 128 children and 253 tympanostomy tube placements conducted at 4 centers in the United States demonstrated an 88.3% success rate in performing the procedure under moderate sedation with adverse events within normal rates reported in the literature. The feasibility of completing tympanostomy tube placement under moderate sedation enables avoidance of general anesthesia and provides additional choices to physicians and parents.