Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

When REBOA grows wings: Resuscitative endovascular balloon occlusion of the aorta to facilitate aeromedical transport.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a helpful adjunct in the control of non-compressible truncal hemorrhage. Concerns regarding ischemia time limits its applicability in transfer. We describe the first reported case of civilian transfer via aeromedical transport to a higher level of care with a zone 3 REBOA catheter deployed. CASE REPORT: We present the case of a patient in hemorrhagic shock with a complex pelvic fracture exceeding the capability of a rural level-two trauma center requiring the use of REBOA catheter to permit aeromedical transport to a level-one trauma center for definitive embolization. CONCLUSION: Deployment of REBOA catheter to facilitate aeromedical transport to an appropriate level of care may be considered if travel times can be kept brief and there is a process and training in place to empower flight medics to consider transporting with a REBOA deployed.

Racial disparities in triage of adolescent patients after bullet injury.

BACKGROUND: While pediatric trauma centers (PTCs) and adult trauma centers (ATCs) exhibit equivalent trauma mortality, the optimal care environment for traumatically injured adolescents remains controversial. Race has been shown to effect triage within emergency departments (EDs) with people of color receiving lower acuity triage scores. We hypothesized that African-American adolescents were more likely triaged to an ATC than a PTC compared with their White peers. METHODS: Institutional trauma databases from a neighboring, urban Level I PTC and ATC were queried for gunshot wounds in adolescents (15-18 years) presenting to the ED from 2015 to 2017. The PTC and ATC were compared in terms of demographics, services, and outcomes. Results were analyzed using univariate analysis and logistic regression. RESULTS: Among 316 included adolescents, 184 were treated in an ATC versus 132 in a PTC. Patients at the PTC were significantly more likely to be younger (16.1 vs. 17.5 years; p < 0.001), White (16% vs. 5%; p = 0.001), and privately insured (41% vs. 30%; p = 0.002). At each age, the proportion of Whites treated at the PTC exceeded the proportion of African-Americans. At the PTC, patients were more likely to receive inpatient and outpatient social work follow-up (89% vs. 1%, p < 0.001). Adolescents treated at the PTC were less likely to receive opioids (75% vs. 56%, p = 0.001) at discharge and to return to ED within 6 months (25% vs. 11%, p = 0.005). On multivariate logistic regression, African-American adolescents were less likely to be treated at a PTC (odds ratio, 0.30; 95% confidence interval, 0.10-0.85; p = 0.02) after controlling for age and Injury Severity Score. CONCLUSION: Disparities in triage of African-American and White adolescents after bullet injury lead to unequal care. African-Americans were more likely to be treated at the ATC, which was associated with increased opioid prescription, decreased social work support, and increased return to ED. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level IV.

Assessment of YouTube as an educational tool in teaching thyroidectomy and parathyroidectomy.

OBJECTIVE: YouTube has become the preferred resource for trainees to learn and prepare for surgical cases. This study evaluated the educational quality of YouTube videos detailing thyroidectomy and parathyroidectomy. METHOD: YouTube was systematically searched using 11 terms related to thyroidectomy and parathyroidectomy. Four independent clinical reviewers assessed the videos using Laparoscopic Surgery Video Educational Guidelines as well as modified Laparoscopic Surgery Video Educational Guidelines subgroup tools. RESULTS: Sixty-five videos were identified and evaluated. Overall Laparoscopic Surgery Video Educational Guidelines score was 8.58 ± 3.85 (mean subgroup score, 5.67 ± 2.40). Twenty-eight of 65, 25 of 65 and 12 of 65 videos were deemed medium, low and high quality, respectively. Inter-rater reliability was good for both attending surgeons and residents. Presence of audio or visual commentary had a positive correlation with total Laparoscopic Surgery Video Educational Guidelines scores (R2=0.38). Videos produced by otolaryngologists and US-based physicians scored higher on total scores compared to non-otolaryngology and non-US based physicians. CONCLUSION: Some YouTube videos on thyroidectomy and parathyroidectomy exhibit high educational value. Future efforts should increase the number of high-quality YouTube videos containing both audio and visual commentary or create an online repository of videos for medical students and residents to augment their surgical training.

Survey of American College of Surgeons Committee on trauma members on firearm injury: Consensus and opportunities.

BACKGROUND: In the United States, there is a perceived divide regarding the benefits and risks of firearm ownership. The American College of Surgeons Committee on Trauma Injury Prevention and Control Committee designed a survey to evaluate Committee on Trauma (COT) member attitudes about firearm ownership, freedom, responsibility, physician-patient freedom and policy, with the objective of using survey results to inform firearm injury prevention policy development. METHODS: A 32-question survey was sent to 254 current U.S. COT members by email using Qualtrics. SPSS was used for χ exact tests and nonparametric tests, with statistical significance being less than 0.05. RESULTS: Our response rate was 93%, 43% of COT members have firearm(s) in their home, 88% believe that the American College of Surgeons should give the highest or a high priority to reducing firearm-related injuries, 86% believe health care professionals should be allowed to counsel patients on firearms safety, 94% support federal funding for firearms injury prevention research. The COT participants were asked to provide their opinion on the American College of Surgeons initiating advocacy efforts and there was 90% or greater agreement on 7 of 15 and 80% or greater on 10 of 15 initiatives. CONCLUSION: The COT surgeons agree on: (1) the importance of formally addressing firearm injury prevention, (2) allowing federal funds to support research on firearms injury prevention, (3) retaining the ability of health care professionals to counsel patients on firearms-related injury prevention, and (4) the majority of policy initiatives targeted to reduce interpersonal violence and firearm injury. It is incumbent on trauma and injury prevention organizations to leverage these consensus-based results to initiate prevention, advocacy, and other efforts to decrease firearms injury and death. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level I; therapeutic care, level II.

Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Metabolic Adaptation and Enables Glucose-Independent Tumor Growth.

Cancer cells adapt metabolically to proliferate under nutrient limitation. Here we used combined transcriptional-metabolomic network analysis to identify metabolic pathways that support glucose-independent tumor cell proliferation. We found that glucose deprivation stimulated re-wiring of the tricarboxylic acid (TCA) cycle and early steps of gluconeogenesis to promote glucose-independent cell proliferation. Glucose limitation promoted the production of phosphoenolpyruvate (PEP) from glutamine via the activity of mitochondrial PEP-carboxykinase (PCK2). Under these conditions, glutamine-derived PEP was used to fuel biosynthetic pathways normally sustained by glucose, including serine and purine biosynthesis. PCK2 expression was required to maintain tumor cell proliferation under limited-glucose conditions in vitro and tumor growth in vivo. Elevated PCK2 expression is observed in several human tumor types and enriched in tumor tissue from non-small-cell lung cancer (NSCLC) patients. Our results define a role for PCK2 in cancer cell metabolic reprogramming that promotes glucose-independent cell growth and metabolic stress resistance in human tumors.

Effectiveness of Minocycline and Rifampin vs Chlorhexidine and Silver Sulfadiazine-Impregnated Central Venous Catheters in Preventing Central Line-Associated Bloodstream Infection in a High-Volume Academic Intensive Care Unit: A Before and after Trial.

BACKGROUND: Use of chlorhexidine and silver sulfadiazine-impregnated (CSS) central venous catheters (CVCs) has not been shown to decrease the catheter-related bloodstream infection rate in an ICU. The purpose of this study was to determine if use of minocycline and rifampin-impregnated (MR) CVCs would decrease central line-associated bloodstream infection (CLABSI) rates compared with those observed with use of CSS-impregnated CVCs. STUDY DESIGN: A total of 7,181 patients were admitted to a 24-bed university hospital surgical ICU: 2,551 between March 2004 and August 2005 (period 1) and 4,630 between April 2006 and July 2008 (period 2). All patients requiring CVC placement in period 1 had a CSS catheter inserted, and in period 2 all patients had MR CVCs placed. RESULTS: Twenty-two CLABSIs occurred during 7,732 catheter days (2.7 per 1,000 catheter days) in the 18-month period when CSS lines were used. After the introduction of MR CVCs, 21 catheter-related bloodstream infections occurred during 15,722 catheter days (1.4 per 1,000 catheter days). This represents a significant (p < 0.05) decrease in the CLABSI rate after introduction of MR CVCs. Mean length of time to infection developing after catheterization (8.6 days for CSS vs 6.1 days for MR) was also different (p = 0.04). The presence of MR did not alter the microbiologic profile of catheter-related infections, and it did not increase the incidence of resistant organisms. CONCLUSIONS: The CLABSI rate decreased more with the use of MR CVCs compared with CSS CVCs in an ICU where the CLABSI rate was already low. The types of organisms causing infection were similar. With continued use of MR-impregnated CVCs in our ICU in the subsequent 5 years, we have seen sustained low rates of CLABSIs.

Glycogen synthase kinase 3 protein kinase activity is frequently elevated in human non-small cell lung carcinoma and supports tumour cell proliferation.

BACKGROUND: Glycogen synthase kinase 3 (GSK3) is a central regulator of cellular metabolism, development and growth. GSK3 activity was thought to oppose tumourigenesis, yet recent studies indicate that it may support tumour growth in some cancer types including in non-small cell lung carcinoma (NSCLC). We examined the undefined role of GSK3 protein kinase activity in tissue from human NSCLC. METHODS: The expression and protein kinase activity of GSK3 was determined in 29 fresh frozen samples of human NSCLC and patient-matched normal lung tissue by quantitative immunoassay and western blotting for the phosphorylation of three distinct GSK3 substrates in situ (glycogen synthase, RelA and CRMP-2). The proliferation and sensitivity to the small-molecule GSK3 inhibitor; CHIR99021, of NSCLC cell lines (Hcc193, H1975, PC9 and A549) and non-neoplastic type II pneumocytes was further assessed in adherent culture. RESULTS: Expression and protein kinase activity of GSK3 was elevated in 41% of human NSCLC samples when compared to patient-matched control tissue. Phosphorylation of GSK3α/ß at the inhibitory S21/9 residue was a poor biomarker for activity in tumour samples. The GSK3 inhibitor, CHIR99021 dose-dependently reduced the proliferation of three NSCLC cell lines yet was ineffective against type II pneumocytes. CONCLUSION: NSCLC tumours with elevated GSK3 protein kinase activity may have evolved dependence on the kinase for sustained growth. Our results provide further important rationale for exploring the use of GSK3 inhibitors in treating NSCLC.

Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor.

Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R) antibody figitumumab in non-small cell lung cancer (NSCLC) patients have been discontinued owing to lack of survival benefit. We investigated whether inhibition of the highly homologous insulin receptor (IR) in addition to the IGF1R would be more effective than inhibition of the IGF1R alone at preventing the proliferation of NSCLC cells. Signalling through IGF1R and IR in the NSCLC cell lines A549 and Hcc193 was stimulated by a combination of IGF1, IGF2 and insulin. It was inhibited by antibodies that block ligand binding, αIR3 (IGF1R) and IR47-9 (IR), and by the ATP-competitive small molecule tyrosine kinase inhibitors AZ12253801 and NVPAWD742 which inhibit both IGF1R and IR tyrosine kinases. The effect of inhibitors was determined by an anchorage-independent proliferation assay and by analysis of Akt phosphorylation. In Hcc193 cells the reduction in cell proliferation and Akt phosphorylation due to anti-IGF1R antibody was enhanced by antibody-mediated inhibition of the IR whereas in A549 cells, with a relatively low IR:IGF1R expression ratio, it was not. In each cell line proliferation and Akt phosphorylation were more effectively inhibited by AZ12253801 and NVPAWD742 than by combined αIR3 and IR47-9. When the IGF1R alone is inhibited, unencumbered signalling through the IR can contribute to continued NSCLC cell proliferation. We conclude that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease.

Trauma in the older adult: epidemiology and evolving geriatric trauma principles.

The older adult patient with trauma is becoming a growing part of the overall trauma population. With the world population increasing in age, the rate of the traumatically injured older adult will continue to increase. Recognizing this problem and the fact that the elderly are at higher risk for injury and its complications will be necessary if the increasing volume of patients is to be dealt with. This review discusses these issues, as well as appropriate triage and treatment of injuries and associated comorbidities. Early recognition of injury, even minor, and expedited care using specialized teams will help to improve outcomes for these patients.

Analysis and manipulation of modal ratios of cylindrical drums.

This paper uses modal analysis to investigate the effect of manipulating drumhead tension on the modal frequency ratios of a cylindrical drum with two drumheads. This analysis evaluates a drum's free vibration after excitation. It is shown that the frequency of the (01) mode of the drum is the same on both heads, whereas the frequency of each (11) mode has a decreased dependence on that of the opposite drumhead. This allows manipulation of the ratios for the (11) modes of the batter and resonant heads with respect to the overall (01) mode. This manipulation is shown to allow a range of tunings such that the (11) mode of the batter head can be tuned to a ratio of 1.5× that of the (01) mode.

Use of low-molecular-weight heparin and a deep vein thrombosis protocol to prevent DVT in elderly patients with trauma.

Thromboembolic events (TEs), including pulmonary embolisms (PEs), are life threatening. Older patients with trauma are at significantly higher risk for these complications. In March 2003, a deep vein thrombosis (DVT) prophylaxis protocol was implemented for use in all trauma patients admitted to our hospital. Here we report on the results of using this protocol for patients aged 65 years or older. A risk-stratified DVT/PE prophylaxis protocol was developed, incorporating specific injuries and history and physiologic parameters, which favored aggressive therapy and included patients at highest risk for dying from PEs. Between March 2003 and June 2005, these data were collected on all trauma patients admitted to our level I hospital. Comparisons were made with historical controls (patients admitted in 2002, before implementation of this protocol). TE rates for the study period trended lower for patients aged 65 or older (6.4% vs 2.2%, P<.1). This protocol did not increase the incidence of bleeding events in this patient population. Protocol-based, risk-adjusted DVT/TE prophylaxis is safe and efficacious in elderly trauma patients who are at increased risk for TEs.

Platelet transfusion: an unnecessary risk for mild traumatic brain injury patients on antiplatelet therapy.

INTRODUCTION: To determine whether there is a benefit to platelet transfusion in mild traumatic brain injury (MTBI) patients with intracranial hemorrhage (ICH), taking antiplatelet therapy before hospitalization. MATERIALS AND METHODS: The study design retrospectively reviewed patients admitted to a Level I trauma center during a 2-year period with an isolated MTBI (Glasgow Coma Scale score ≥13, ICH seen on a head computed tomographic scan (head computed tomography [HCT]), and taking an antiplatelet agent before hospitalization. HCT's were categorized based on the Marshall Classification, Rotterdam Score, and ICH volume. Hospital records were reviewed noting neurologic, cardiac, respiratory events, and discharge Glasgow Outcome Scale. RESULTS: There were 1,101 patients with TBI hospitalized during the 2-year study period. Three hundred twenty-one of these patients had an MTBI with ICH at the time of admission, and from this group, 113 were taking an antiplatelet agent. Only 4 (1.2%) of the 321 patients suffered a neurologic decline. All were gradual in nature, and none required emergent intervention. An analysis of the 113 patients taking antiplatelet agents, comparing patients who were not given a platelet transfusion with those who received a platelet transfusion, found no significant difference in the rate of HCT progression, neurologic decline, or Glasgow Outcome Scale at hospital discharge between the two groups. There was a trend, which was not significant, toward more medical declines in patients who received a platelet transfusion. A further review, analyzing all 321 patients with ICH showed receiving a transfusion of any type (i.e., platelets, fresh frozen plasma, or blood) was a strong predictor of medical decline (p < 0.0001). The odds ratio of having a medical decline after transfusion was 5.8 (95% confidence interval, 1.2-28.2). CONCLUSIONS: Platelet transfusion did not improve short-term outcomes after MTBI. Further randomized controlled trials need to be done to truly assess if there is no benefit in platelet transfusion in patients taking antiplatelet agents suffering an MTBI. Because the overall outcome in MTBI patients is favorable, platelet transfusion in these patients may not be indicated.

Overexpression of the TXNDC5 protein in non-small cell lung carcinoma.

UNLABELLED: Thioredoxin domain containing protein 5 (TXNDC5) is a member of the thioredoxin (Trx) domain-containing family of proteins that have been implicated in cancer progression. The expression of TXNDC5 in non-small cell lung carcinoma (NSCLC) tumours compared to patient-matched normal lung tissue was determined and cell line models were used to determine if expression was regulated by hypoxia. PATIENTS AND METHODS: Samples of tumour and normal lung tissue were taken during surgery and immediately frozen. The expression of TXNDC5 was determined by Western blotting and immunohistochemistry. To analyse the effect of hypoxia on TXNDC5 expression NSCLC cell lines were used. RESULTS: Tumours from 18/29 (62%) individuals exhibited an increase in TXNDC5 expression compared to normal lung tissue (p<0.05). TXNDC5 expression was not elevated by hypoxia. CONCLUSION: TXNDC5 is up-regulated in the majority of resected human NSCLC. Cell line data indicates that the expression of TXNDC5 in tumour cells is not regulated by hypoxia.

Implementation of a mandatory checklist of protocols and objectives improves compliance with a wide range of evidence-based intensive care unit practices.

OBJECTIVE: To determine a) if a checklist covering a diverse group of intensive care unit protocols and objectives would improve clinician consideration of these domains and b) if improved consideration would change practice patterns. DESIGN: Pre- and post observational study. SETTING: A 24-bed surgical/burn/trauma intensive care unit in a teaching hospital. PATIENTS: A total of 1399 patients admitted between June 2006 and May 2007. INTERVENTIONS: The first component of the study evaluated whether mandating verbal review of a checklist covering 14 intensive care unit best practices altered verbal consideration of these domains. Evaluation was performed using real-time bedside audits on morning rounds. The second component evaluated whether the checklist altered implementation of these domains by changing practice patterns. Evaluation was performed by analyzing data from the Project IMPACT database after patients left the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Verbal consideration of evaluable domains improved from 90.9% (530/583) to 99.7% (669/671, p < .0001) after verbal review of the checklist was mandated. Bedside consideration improved on the use of deep venous thrombosis prophylaxis (p < .05), stress ulcer prophylaxis (p < .01), oral care for ventilated patients (p < 0.01), electrolyte repletion (p < .01), initiation of physical therapy (p < .05), and documentation of restraint orders (p < .0001). Mandatory verbal review of the checklist resulted in a greater than two-fold increase in transferring patients out of the intensive care unit on telemetry (16% vs. 35%, p < .0001) and initiation of physical therapy (28% vs. 42%, p < .0001) compared with baseline practice. CONCLUSIONS: A mandatory verbal review of a checklist covering a wide range of objectives and goals at each patient's bedside is an effective method to improve both consideration and implementation of intensive care unit best practices. A bedside checklist is a simple, cost-effective method to prevent errors of omission in basic domains of intensive care unit management that might otherwise be forgotten in the setting of more urgent care requirements.

The impact of a simple, low-cost oral care protocol on ventilator-associated pneumonia rates in a surgical intensive care unit.

OBJECTIVE: The purpose of this study was to determine the effects of a simple low-cost oral care protocol on ventilator-associated pneumonia rates in a surgical intensive care unit. DESIGN: Preintervention and postintervention observational study. SETTING: Twenty-four bed surgical/trauma/burn intensive care units in an urban university hospital. PATIENTS: All mechanically ventilated patients that were admitted to the intensive care unit between June 1, 2004 and May 31, 2005. INTERVENTIONS: An oral care protocol to assist in prevention of bacterial growth of plaque by cleaning the patients' teeth with sodium monoflurophosphate 0.7% paste and brush, rinsing with tap water, and subsequent application of a 0.12% chlorhexidine gluconate chemical solution done twice daily at 12-hour intervals. MEASUREMENTS AND MAIN RESULTS: During the preintervention period from June 1, 2003 to May 31, 2004, there were 24 infections in 4606 ventilator days (rate = 5.2 infections per 1000 ventilator days). After the institution of the oral care protocol, there were 10 infections in 4158 ventilator days, resulting in a lower rate of 2.4 infections per 1000 ventilator days. This 46% reduction in ventilator-associated pneumonia was statistically significant (P = .04). Staff compliance with the oral care protocol during the 12-month period was also monitored biweekly and averaged 81%. The total cost of the oral care protocol was US$2187.49. There were 14 fewer cases of ventilator-associated pneumonia, which led to a decrease in cost of US$140 000 to US$560 000 based on the estimated cost per ventilator-associated pneumonia infection of US$10 000 to US$40 000. There was an overall reduction in ventilator-associated pneumonia without a change to the gram-negative or gram-positive microorganism profile. CONCLUSIONS: The implementation of a simple, low-cost oral care protocol in the surgical intensive care unit led to a significantly decreased risk of acquiring ventilator-associated pneumonia.

Trauma rehabilitation outcome scoring.

PURPOSE OF REVIEW: Appropriate measurements of success in trauma systems are evolving. We review the rationale behind prior trauma and rehabilitation outcomes measures, and how they have led to the current rehabilitation tools in use today. In addition, we review the difficulties with current methods and future improvements that need to occur. RECENT FINDINGS: As medicine marches toward improved used of clinical evidence, trauma practitioners have worked for improved outcomes research. A major part of this is that outcomes such as functional status and quality of life are as important as mortality statistics. Trauma rehabilitation outcomes are thus more important, yet in the past all such tools have had major impediments to implementation across a heterogeneous trauma population. Newly recognized major domains such as quality of life, preinjury status, patient perceptions, and actual function at work have not been adequately addressed with current rehabilitation measures. At this time, no clinically applicable trauma rehabilitation score exists. SUMMARY: Trauma rehabilitation outcomes are an important measurement of trauma system effectiveness. A more effective, easily applied rehabilitation score is needed to adequately assess all appropriate domains of clinical improvement in the injured patient.

Extracorporeal membrane oxygenation: current clinical practice, coding, and reimbursement.

Extracorporeal membrane oxygenation (ECMO) is a technique for providing life support for patients experiencing both pulmonary and cardiac failure by maintaining oxygenation and perfusion until native organ function is restored. ECMO is used routinely at many specialized hospitals for infants and less commonly for children with respiratory or cardiac failure from a variety of causes. Its usage is more controversial in adults, but select medical centers have reported favorable findings in patients with ARDS and other causes of severe pulmonary failure. ECMO is also rarely used as a rescue therapy in a small subset of adult patients with cardiac failure. This article will review the current uses and techniques of ECMO in the critical care setting as well as the evidence supporting its usage. In addition, current practice management related to coding and reimbursement for this intensive therapy will be discussed.