Predicting Malignant Ventricular Arrhythmias Using Real-Time Remote Monitoring.

BACKGROUND: Although implantable cardioverter-defibrillator (ICD) therapies are associated with increased morbidity and mortality, the prediction of malignant ventricular arrhythmias has remained elusive. OBJECTIVES: The purpose of this study was to evaluate whether daily remote-monitoring data may predict appropriate ICD therapies for ventricular tachycardia or ventricular fibrillation. METHODS: This was a post hoc analysis of IMPACT (Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices), a multicenter, randomized, controlled trial of 2,718 patients evaluating atrial tachyarrhythmias and anticoagulation for patients with heart failure and ICD or cardiac resynchronization therapy with defibrillator devices. All device therapies were adjudicated as either appropriate (to treat ventricular tachycardia or ventricular fibrillation) or inappropriate (all others). Remote monitoring data in the 30 days before device therapy were utilized to develop separate multivariable logistic regression and neural network models to predict appropriate device therapies. RESULTS: A total of 59,807 device transmissions were available for 2,413 patients (age 64 ± 11 years, 26% women, 64% ICD). Appropriate device therapies (141 shocks, 10 antitachycardia pacing) were delivered to 151 patients. Logistic regression identified shock lead impedance and ventricular ectopy as significantly associated with increased risk of appropriate device therapy (sensitivity 39%, specificity 91%, AUC: 0.72). Neural network modeling yielded significantly better (P < 0.01 for comparison) predictive performance (sensitivity 54%, specificity 96%, AUC: 0.90), and also identified patterns of change in atrial lead impedance, mean heart rate, and patient activity as predictors of appropriate therapies. CONCLUSIONS: Daily remote monitoring data may be utilized to predict malignant ventricular arrhythmias in the 30 days before device therapies. Neural networks complement and enhance conventional approaches to risk stratification.

Ibrutinib-Associated Atrial Fibrillation.

Ibrutinib, a novel and potent Bruton tyrosine kinase inhibitor, is an effective and well-tolerated treatment for a variety of B-cell lymphomas. However, its use is associated with an increased incidence of atrial fibrillation (AF), ranging from 4% to 16%. We reviewed the original clinical trials that led to the approval of ibrutinib, as well as several other prospective and retrospective studies, to better appreciate the incidence of ibrutinib-associated AF. Based on 16 studies included in our analysis, the incidence of ibrutinib-associated AF was 5.77 per 100 person-years, which is much higher than rates previously reported with ibrutinib and compared with the general adult population. New onset AF in cancer patients is associated with a significantly higher risk of heart failure and thromboembolism, even after adjusting for known risk factors. In addition, ibrutinib poses unique challenges due to its interactions with many medications that are commonly used to manage AF. Ibrutinib also inhibits platelet activation and decisions regarding anticoagulation have to be carefully weighed against this increased risk of bleeding. Ibrutinib's interaction with calcium channel blockers, digoxin, amiodarone, and direct oral anticoagulants can result in either ibrutinib or other drug-related toxicity and careful selection and dose adjustment may be needed. Ibrutinib-associated AF can be a therapy-limiting side effect and physicians should be familiar with the special management considerations imposed by this agent. We review the potential mechanisms and incidence of ibrutinib-associated AF and propose an algorithm for its management.

Incidence and Predictors of Perioperative Complications With Transvenous Lead Extractions: Real-World Experience With National Cardiovascular Data Registry.

BACKGROUND: Transvenous lead extraction is an integral part of management of patients with cardiovascular implantable electronic devices. Real-world incidence and predictors of perioperative complications in extractions involving implantable cardioverter-defibrillator leads have not been described in detail. METHODS AND RESULTS: Data from the National Cardiovascular Data Registry Implantable Cardioverter-Defibrillator Registry were analyzed. Lead extraction was defined as removal of leads implanted for >1 year. Predictors of major perioperative complications for all extraction procedures (11 304) and for high-voltage lead (8362, 74%), across 762 centers, were analyzed using univariate and multivariate logistic regression. Major complication occurred in 258 (2.3%) extraction procedures. Of these 258 with a complication, 41 (16%) required urgent cardiac surgery. Of these 41, 14 (34%) died during surgery. Among the total 98 (0.9%) deaths reported, 18 (0.16% of total) occurred during transvenous lead extraction. In multivariable logistic regression analysis, female sex, admission other than electively for procedure, ≥3 leads extracted, longer implant duration, dislodgement of other leads, and patient's clinical status requiring lead extraction (infection/perforation) were associated with increased risk of complications. Smaller lead diameter, flat versus round coil shape, and greater proximal surface coil area were multivariate predictors of major perioperative complications specific to high-voltage leads. CONCLUSIONS: The rate of major complications and mortality with transvenous lead extraction is similar in the real-world outcomes to that reported in recent single-center studies from high-volume centers. There is significant risk of urgent cardiac surgery, which carries a high mortality, and planning for appropriate cardiothoracic surgery backup is imperative.

The effects of cryopreserved red blood cell transfusion on tissue oxygenation in obese trauma patients.

BACKGROUND: Low tissue oxygenation (StO2) is associated with poor outcomes in obese trauma patients. A novel treatment could be the transfusion of cryopreserved packed red blood cells (CPRBCs), which the in vitro biochemical profile favors red blood cell (RBC) function. We hypothesized that CPRBC transfusion improves StO2 in obese trauma patients. METHODS: Two hundred forty-three trauma patients at five Level I trauma centers who required RBC transfusion were randomized to receive one to two units of liquid packed RBCs (LPRBCs) or CPRBCs. Demographics, injury severity, StO2, outcomes, and biomarkers of RBC function were compared in nonobese (body mass index [BMI] < 30) and obese (BMI ≥ 30) patients. StO2 was also compared between obese patients with BMI of 30 to 34.9 and BMI ≥ 35. StO2 was normalized and expressed as % change after RBC transfusion. A p value less than 0.05 indicated significance. RESULTS: Patients with BMI less than 30 (n = 141) and BMI of 30 or greater (n = 102) had similar Injury Severity Score, Glasgow Coma Scale, and baseline StO2. Plasma levels of free hemoglobin, an index of RBC lysis, were lower in obese patients after CPRBC (125 [72-259] µg/mL) versus LPRBC transfusion (230 [178-388] µg/mL; p < 0.05). StO2 was similar in nonobese patients regardless of transfusion type, but improved in obese patients who received CPRBCs (104 ± 1%) versus LPRPCs (99 ± 1%, p < 0.05; 8 hours after transfusion). Subanalysis showed improved StO2 after CPRBC transfusion was specific to BMI of 35 or greater, starting 5 hours after transfusion (p < 0.05 vs. LPRBCs). CPRBCs did not improve clinical outcomes in either group. CONCLUSION: CPRBC transfusion is associated with increased StO2 and lower free hemoglobin levels in obese trauma patients, but did not improve clinical outcomes. Future studies are needed to determine if CPRBC transfusion in obese patients attenuates hemolysis to improve StO2. LEVEL OF EVIDENCE: Therapeutic, level IV.

Attitudes on cost-effectiveness and equity: a cross-sectional study examining the viewpoints of medical professionals.

OBJECTIVE: To determine the attitudes of physicians and trainees in regard to the roles of both cost-effectiveness and equity in clinical decision making. DESIGN: In this cross-sectional study, electronic surveys containing a hypothetical decision-making scenario were sent to medical professionals to select between two colon cancer screening tests for a population. SETTING: Three Greater Boston academic medical institutions: Tufts University School of Medicine, Tufts Medical Centre and Lahey Hospital and Medical Centre. PARTICIPANTS: 819 medical students, 497 residents-in-training and 671 practising physicians were contacted electronically using institutional and organisational directories. MAIN OUTCOMES AND MEASURES: Stratified opinions of medical providers and trainee subgroups regarding cost-effectiveness and equity. RESULTS: A total of 881 respondents comprising 512 medical students, 133 medical residents-in-training and 236 practising physicians completed the survey (total response rate 44.3%). Thirty-six per cent of medical students, 44% of residents-in-training and 53% of practising physicians favoured the less effective and more equitable screening test. Residents-in-training (OR 1.49, CI 1.01 to 2.21; p=0.044) and practising physicians (OR 2.12, CI 1.54 to 2.92; p<0.001) were more likely to favour the equitable option compared with medical students. Moreover, female responders across all three cohorts favoured the more equitable screening test to a greater degree than did male responders (OR 1.70, CI 1.29 to 2.24; p<0.001). CONCLUSIONS: Cost-effectiveness analysis does not accurately reflect the importance that medical professionals place on equity. Among medical professionals, practising physicians appear to be more egalitarian than residents-in-training, while medical students appear to be most utilitarian and cost-effective. Meanwhile, female respondents in all three cohorts favoured the more equitable option to a greater degree than their male counterparts. Healthcare policies that trade off equity in favour of cost-effectiveness may be unacceptable to many medical professionals, especially practising physicians and women.

A case of video-assisted thoracoscopic resection of malignant transformation of pulmonary recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a disease of the respiratory tract caused by infection with the human papillomavirus (HPV) and is characterized by multiple recurring papillomas throughout the respiratory tract. Although rare, extra laryngeal involvement carries the risk of malignant transformation in 3-7% of adults. We report the case of a patient with unmonitored juvenile onset RRP with pulmonary involvement found to have malignant transformation to squamous cell carcinoma (SCC). Incidentally found on chest radiography for mild chest wall trauma, she was found to have a large left lower lobe mass with pathology consistent with SCC. The patient underwent surgical management with thoracoscopic left lower lobectomy and mediastinal lymph node dissection followed by adjuvant chemoradiation for pathologic stage IIIA SCC. Surveillance imaging at 6 months shows no evidence of disease progression.

Perforator variability in the anterolateral thigh free flap: a systematic review.

OBJECTIVES: The use of free flaps greatly improves reconstruction options and quality of life for patients undergoing oncological resections. The anterolateral thigh (ALT) free flap is frequently used in the head and neck. The aim of this review was to provide a summary of published evidence assessing perforator anatomy of this flap. METHODS: A broad search was undertaken through the PubMed database using the terms "anterolateral thigh free flap" and "perforator". Search limits included English language and human subjects. Studies that examined more than or equal to ten patients were analysed. RESULTS: A total of 23 studies were identified, which included both clinical and cadaver studies. 1251 thighs were examined with the mean number of perforators ranging from 1.15 to 4.26. In the majority of cases, the descending branch of the lateral circumflex femoral artery was the dominant pedicle and took a musculocutaneous route. In some series, up to 5.4% of thighs were identified as having no cutaneous perforators. Venous data is limited with most studies reporting the presence of two concomitant veins of which the largest concomitant vein is selected for venous anastomoses. CONCLUSIONS AND FUTURE STUDIES: The ALT free flap is a reconstruction option in head and neck cancer. Adequate perforators for reconstruction are identified in the majority of cases. Increased anatomical perforator knowledge may lead to further uptake of ALT free flap reconstruction and improved intraoperative troubleshooting. Further studies investigating those patients with no perforators in the ALT may lead to improved clinical outcomes.

Determinants of Time in Therapeutic Range in Patients Receiving Oral Anticoagulants (A Substudy of IMPACT).

Implanted cardiac arrhythmia devices can detect atrial tachyarrhythmias (atrial high-rate episodes [AHREs]) that are considered to correlate with atrial fibrillation and risk of stroke. In the IMPACT trial, oral anticoagulation was initiated when AHREs were detected by implanted cardioverter-defibrillators and withdrawn when they abated, according to a protocol accounting both for AHRE duration as detected by remote device monitoring and stroke risk assessment. In this analysis, we ascertained determinants of time in therapeutic range (TTR) among protocol-determined vitamin K antagonist-treated patients during the trial. We enrolled 2,718 patients with at least 1 additional stroke risk factor (CHADS2 score ≥1) at 104 arrhythmia centers. The sex, age <60, medical history, treatments interacting with VKA, tobacco use (2 points) and race (2 points for non-Caucasian) (SAMe-TT2R2) score is a simple clinical-derived score designed to aid decision-making on whether a patient is likely to achieve good anticoagulation control on vitamin K antagonist (e.g., warfarin), which was calculated and related to TTR achieved using the Rosendaal method. We analyzed 229 patients (mean age 66.7 years; mean CHADS2 score 2.85 [SD 1.1]) with mean TTR of 0.536 (SD 0.23) overall. Univariate analysis identified 5 variables associated with differences in mean TTR. Mean TTR was lower in those who were women (p = 0.031), of black race (p = 0.005) and in New York Heart Association class IV (p = 0.014), whereas hemoglobin >13.5 g/dl (p = 0.010) and New York Heart Association class I (p = 0.037) were associated with higher mean TTR. There was a significant difference in mean TTR value between US and non-US sites (Canada and Germany) (mean TTR for US: 0.513 vs non-US: 0.686; p <0.0001). Mean TTR was significantly lower (Δ = 0.1382, 95% CI 0.0382 to 0.2382) for patients with SAMe-TT2R2 scores of 4 (p = 0.007) and higher (Δ = 0.0612, 95% CI 0.0005 to 0.1219) for patients with SAMe-TT2R2 scores of 1 (p = 0.048). Linear regression confirmed a significant association between lower SAMe-TT2R2 score and improved anticoagulation control (p = 0.0021) with a 1-unit decrease in SAMe-TT2R2 score associated with an increase in TTR of 0.0404 (95% CI 0.0149 to 0.0659). In conclusion, clinical, geographical, and demographic factors were associated with the quality of anticoagulation control as reflected by TTR. Although overall TTR in this population was poor, lower SAMe-TT2R2 scores were associated with better TTR.

Implementation of a Tranexamic Acid Protocol to Reduce Blood Loss During Cranial Vault Remodeling for Craniosynostosis.

OBJECTIVE: Pediatric cranial vault remodeling for repair of craniosynostosis is associated with significant blood loss and transfusion requirements. Beginning in 2011, the authors evaluated the impact tranexamic acid (TXA) on blood loss and blood product transfusion for children less than 15 months of age undergoing primary surgical repair of nonsyndromic single suture craniosynostosis. METHODS: Following institutional review board approval, the authors performed a retrospective study of all children undergoing surgical correction of craniosynostosis at Oregon Health & Science University from 2005 to 2015. All available records were reviewed, and patient data were collected from the time of preoperative evaluation until discharge, comparing patient and clinical variables before and after the implementation of perioperative TXA. RESULTS: Of a total of 259 patients with craniosynostosis, 187 had nonsyndromic single-suture involvement; 69 of these patients (36.9%) received TXA. A single surgical team (AAK and NRS) performed all operations. Median age at the time of surgery was 8.1 months (interquartile range [IQR] of 6.0-9.8 months). The TXA group had a significant reduction in estimated intraoperative blood loss (26 mL/kg versus 36 mL/kg, P <0.001), cell saver volume transfused 6 mL/kg versus 10 mL/kg, P <0.001), red cell transfusion volume (32 mL/kg versus 42 mL/kg, P <0.001), exposure to plasma transfusion (0% versus 24% P <0.001), exposure to cryoprecipitate transfusion (0% versus 16%, P <0.001), and exposure to platelet transfusion (0% versus 7.6% P = 0.03). Despite reduced red cell transfusion, the TXA-treated patients exhibited similar postoperative hematocrits (30.4 versus 30.3 P = 0.906) to those not treated with TXA. Use of TXA was associated with reduced length of stay (4 days IQR 3-4 versus 4 days IQR 4-5, P <0.001) and reduced postoperative output from surgically placed drains (181 mL versus 311 mL P <0.001). There was no difference in postoperative complications between groups and no deaths in either group. CONCLUSIONS: The introduction of TXA for nonsyndromic single-suture synostosis repair at our institution has significantly reduced blood loss and blood product and plasma transfusion during and following primary cranial vault remodeling for single suture craniosynostosis. Postoperative hematocrit was similar in the TXA-treated and untreated groups despite reduced red cell transfusion in the treated group. In addition, TXA use in this population has eliminated the need for plasma transfusion, and is associated with a shorter hospital stay. No difference in postoperative complications was observed. Our data provide support for further investigation of TXA treatment to improve clinical outcomes in children undergoing pediatric cranial vault remodeling.

Cervical spinal clearance: A prospective Western Trauma Association Multi-institutional Trial.

BACKGROUND: For blunt trauma patients who have failed the NEXUS (National Emergency X-Radiography Utilization Study) low-risk criteria, the adequacy of computed tomography (CT) as the definitive imaging modality for clearance remains controversial. The purpose of this study was to prospectively evaluate the accuracy of CT for the detection of clinically significant cervical spine (C-spine) injury. METHODS: This was a prospective multicenter observational study (September 2013 to March 2015) at 18 North American trauma centers. All adult (≥18 years old) blunt trauma patients underwent a structured clinical examination. NEXUS failures underwent a CT of the C-spine with clinical follow-up to discharge. The primary outcome measure was sensitivity and specificity of CT for clinically significant injuries requiring surgical stabilization, halo, or cervical-thoracic orthotic placement using the criterion standard of final diagnosis at the time of discharge, incorporating all imaging and operative findings. RESULTS: Ten thousand seven hundred sixty-five patients met inclusion criteria, 489 (4.5%) were excluded (previous spinal instrumentation or outside hospital transfer); 10,276 patients (4,660 [45.3%] unevaluable/distracting injuries, 5,040 [49.0%] midline C-spine tenderness, 576 [5.6%] neurologic symptoms) were prospectively enrolled: mean age, 48.1 years (range, 18-110 years); systolic blood pressure 138 (SD, 26) mm Hg; median, Glasgow Coma Scale score, 15 (IQR, 14-15); Injury Severity Score, 9 (IQR, 4-16). Overall, 198 (1.9%) had a clinically significant C-spine injury requiring surgery (153 [1.5%]) or halo (25 [0.2%]) or cervical-thoracic orthotic placement (20 [0.2%]). The sensitivity and specificity for clinically significant injury were 98.5% and 91.0% with a negative predictive value of 99.97%. There were three (0.03%) false-negative CT scans that missed a clinically significant injury, all had a focal neurologic abnormality on their index clinical examination consistent with central cord syndrome, and two of three scans showed severe degenerative disease. CONCLUSIONS: For patients requiring acute imaging for their C-spine after blunt trauma, CT was effective for ruling out clinically significant injury with a sensitivity of 98.5%. For patients with an abnormal neurologic examination as the trigger for imaging, there is a small but clinically significant incidence of a missed injury, and further imaging with magnetic resonance imaging is warranted. LEVEL OF EVIDENCE: Diagnostic tests, level II.

Emergent reversal of vitamin K antagonists: addressing all the factors.

BACKGROUND: Reversal of warfarin-induced coagulopathy after traumatic injury may be done exclusively with prothrombin complex concentrates (PCCs). No direct comparisons between different PCC regimens exist to guide clinical decision-making. Our institution has used 2 distinct PCC strategies for warfarin reversal; a 3-Factor PCC (Profilnine) combined with activated Factor VII (3F-PCC+rVIIa), and a 4-Factor PCC (Kcentra) given without additional factor supplementation. METHODS: Retrospective review of all PCC administrations to trauma patients with acute bleeding who were taking warfarin before injury. Primary endpoints were international normalized ratio (INR) reduction, in-hospital mortality, and diagnosis of deep venous thrombosis (DVT). RESULTS: Eighty-seven patients were identified from 2011 to 2015. Fifty-three were treated with 3F-PCC+rVIIa and 34 with 4F-PCC. Patient demographics, injury severity, and presenting laboratory data were similar. The 3F-PCC+rVIIa produced a lower median (IQR) INR postreversal compared with 4F-PCC (.75 (.69, 1.00) vs 1.28 (1.13, 1.36), P<.001). Both regimens were able to obtain an INR lower than 1.5 immediately after administration (3F+rVIIA 93.9% vs 4F 97.1%, P =.51). In the 4F-PCC group, there was a significant decrease in the incidence of DVT (2.9% vs 22.6%), P < .01), and a nonsignificant reduction in mortality (2.9% vs 17.0%, P = .08). CONCLUSIONS: Use of 4F-PCC for warfarin reversal after traumatic hemorrhage is associated with a less severe decrease in INR, a significant reduction in DVT rates and a trend toward reduced mortality when compared with similar patients treated with 3F-PCC+rVIIa.

Damage-control resuscitation and emergency laparotomy: Findings from the PROPPR study.

BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial has demonstrated that damage-control resuscitation, a massive transfusion strategy targeting a balanced delivery of plasma-platelet-red blood cell in a ratio of 1:1:1, results in improved survival at 3 hours and a reduction in deaths caused by exsanguination in the first 24 hours compared with a 1:1:2 ratio. In light of these findings, we hypothesized that patients receiving 1:1:1 ratio would have improved survival after emergency laparotomy. METHODS: Severely injured patients predicted to receive a massive transfusion admitted to 12 Level I North American trauma centers were randomized to 1:1:1 versus 1:1:2 as described in the PROPPR trial. From these patients, the subset that underwent an emergency laparotomy, defined previously in the literature as laparotomy within 90 minutes of arrival, were identified. We compared rates and timing of emergency laparotomy as well as postsurgical survival at 24 hours and 30 days. RESULTS: Of the 680 enrolled patients, 613 underwent a surgical procedure, 397 underwent a laparotomy, and 346 underwent an emergency laparotomy. The percentages of patients undergoing emergency laparotomy were 51.5% (174 of 338) and 50.3% (172 of 342) for 1:1:1 and 1:1:2, respectively (p = 0.20). Median time to laparotomy was 28 minutes in both treatment groups. Among patients undergoing an emergency laparotomy, the proportions of patients surviving to 24 hours and 30 days were similar between treatment arms; 24-hour survival was 86.8% (151 of 174) for 1:1:1 and 83.1% (143 of 172) for 1:1:2 (p = 0.29), and 30-day survival was 79.3% (138 of 174) for 1:1:1 and 75.0% (129 of 172) for 1:1:2 (p = 0.30). CONCLUSION: We found no evidence that resuscitation strategy affects whether a patient requires an emergency laparotomy, time to laparotomy, or subsequent survival. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Transfusion of cryopreserved packed red blood cells is safe and effective after trauma: a prospective randomized trial.

OBJECTIVES: To determine the safety and efficacy of cryopreserved packed red blood cell (CPRBC) transfusion in trauma patients. BACKGROUND: Liquid packed red blood cells (LPRBCs) have an abbreviated shelf-life and worsening storage lesion with age. CPRBCs are frozen 2 to 6 days after donation, stored up to 10 years, and are available for 14 days after thawing and washing. CPRBCs can be utilized in diverse settings, but the effect on clinical outcomes is unknown. METHODS: We performed a prospective, randomized, double-blind study at 5 level 1 trauma centers. Stable trauma patients requiring transfusion were randomized to young LPRBCs (≤14 storage days), old LPRBCs (>14 storage days), or CPRBCs. Tissue oxygenation (StO2), biochemical and inflammatory mediators were measured, and clinical outcomes were determined. RESULTS: Two hundred fifty-six patients with well-matched injury severity and demographics (P > 0.2) were randomized (84 young, 86 old, and 86 CPRBCs). Pretransfusion and final hematocrits were similar (P > 0.68). Patients in all groups received the same number of units postrandomization (2 [1-4]; P > 0.05). There was no difference in the change in tissue oxygenation between groups. CPRBCs contained less α2-macrogobulin, haptoglobin, C-reactive protein, and serum amyloid P (P < 0.001). Organ failure, infection rate, and mortality did not differ between groups (P > 0.2). CONCLUSIONS: Transfusion of CPRBCs is as safe and effective as transfusion of young and old LPRBCs and provides a mechanism to deliver PRBCs in a wide variety of settings.

Effect of ascorbic acid concentrations on hemodynamics and inflammation following lyophilized plasma transfusion.

BACKGROUND: Compared with lyophilized plasma (LP) buffered with other acids, LP with ascorbic acid (AA) attenuates systemic inflammation and DNA damage in a combat relevant polytrauma swine model. We hypothesize that increasing concentrations of AA in transfused LP will be safe, will be hemodynamically well tolerated, and will attenuate systemic inflammation following polytraumatic injury and hemorrhage in swine. METHODS: This prospective, randomized, blinded study involved 52 female swine. Forty animals were subjected to our validated polytrauma model and resuscitated with LP. Baseline control sham (n = 6), operative control sham (n = 6), low-AA (n = 10), medium-AA (n = 10), high-AA (n = 10) groups, and a hydrochloric acid control (HCL, n = 10) were randomized. Hemodynamics, thrombelastography, and blood chemistries were assessed. Inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], C-reactive protein, and IL-10) and DNA damage were measured at baseline, 2 hours, and 4 hours after liver injury. Significance was set at p < 0.05, with a Bonferroni correction for multiple comparisons. RESULTS: Hemodynamics, shock, and blood loss were similar between groups. All animals had robust procoagulant activity 2 hours following liver injury. Inflammation was similar between groups at baseline, and AA groups remained similar to HCL following liver injury. IL-6 and tumor necrosis factor α were increased at 2 hours and 4 hours compared with baseline within all groups (p < 0.008). DNA damage increased at 2 hours compared with baseline in all groups (p < 0.017) and further increased at 4 hours compared with baseline in HCL, low-, and high-AA groups (p < 0.005). C-reactive protein was similar between and within groups. IL-10 increased at 2 hours compared with baseline in low- and high-AA groups and remained elevated at 4 hours compared with baseline in the low-AA group (all, p < 0.017). CONCLUSION: Concentrations of AA were well tolerated and did not diminish the procoagulant activity of LP. Within our tested range of concentrations, AA can safely be used to buffer LP.

Red-luminescent europium (III) doped silica nanoshells: synthesis, characterization, and their interaction with HeLa cells.

A simple method to fabricate Eu(3+) doped silica nanoshells particles with 100 and 200 nm diameters is reported. Amino polystyrene beads were used as templates, and an 8 to 10 nm thick silica gel coating was formed by the sol-gel reaction. After removing the template by calcination, porous dehydrated silica gel nanoshells of uniform size were obtained. The Eu(3+) doped silica nanoshells exhibited a red emission at 615 nm on UV excitation. The porous structure of the silica shell wall was characterized by transmission electron microscopy measurements, while particle size and zeta potentials of the particles suspended in aqueous solution were characterized by dynamic light scattering. Two-photon microscopy was used to image the nanoshells after assimilation by HeLa cancer cells.

Quantitative comparison of surgical margin histology following excision with traditional electrosurgery and a low-thermal-injury dissection device.

BACKGROUND: This study is the first to examine in vivo the effect of thermal injury in breast conservation pathology in a direct comparison of traditional electrosurgery and an alternative low-thermal-injury device. METHODS: A prospective study of 20 consecutive subjects with biopsy-proven invasive ductal carcinoma (IDC) tumors 1 cm was conducted. Following excision, incisions were made into the tumor with the two devices. Thermal injury depth, margin distance, tissue type, and histological effect were compared on the same breast tissue cut with each excision instrument. A probability evaluation of close and positive margin cases for the true tumor margins was conducted. RESULTS: Compared to traditional electrosurgery, the low-thermal-injury instrument reduced collagen denaturation depth from 435 to 102 µm (77%), fused tissue depth from 262 to 87 µm (67%), and distortion depth from 1,132 to 774 µm (30%). CONCLUSIONS: Based on analysis of the close subset of the true margins, using the traditional electrosurgical device in place of the low-thermal-injury device would have resulted in 48% of the close margin samples being negatively converted to false-positive, and in 11% converting from close to false-negative. The methodology of this work may be readily applied to larger, more definitive studies.

Quantitative automated image analysis system with automated debris filtering for the detection of breast carcinoma cells.

OBJECTIVE: To develop an intraoperative method for margin status evaluation during breast conservation therapy (BCT) using an automated analysis of imprint cytology specimens. STUDY DESIGN: Imprint cytology samples were prospectively taken from 47 patients undergoing either BCT or breast reduction surgery. Touch preparations from BCT patients were taken on cut sections through the tumor to generate positive margin controls. For breast reduction patients, slide imprints were taken at cuts through the center of excised tissue. Analysis results from the presented technique were compared against standard pathologic diagnosis. Slides were stained with cytokeratin and Hoechst, imaged with an automated fluorescent microscope, and analyzed with a fast algorithm to automate discrimination between epithelial cells and noncellular debris. RESULTS: The accuracy of the automated analysis was 95% for identifying invasive cancers compared against final pathologic diagnosis. The overall sensitivity was 87% while specificity was 100% (no false positives). This is comparable to the best reported results from manual examination of intraoperative imprint cytology slides while reducing the need for direct input from a cytopathologist. CONCLUSION: This work demonstrates a proof of concept for developing a highly accurate and automated system for the intraoperative evaluation of margin status to guide surgical decisions and lower positive margin rates.

Single-leg cycle training is superior to double-leg cycling in improving the oxidative potential and metabolic profile of trained skeletal muscle.

Single-leg cycling may enhance the peripheral adaptations of skeletal muscle to a greater extent than double-leg cycling. The purpose of the current study was to determine the influence of 3 wk of high-intensity single- and double-leg cycle training on markers of oxidative potential and muscle metabolism and exercise performance. In a crossover design, nine trained cyclists (78 ± 7 kg body wt, 59 ± 5 ml·kg(-1)·min(-1) maximal O(2) consumption) performed an incremental cycling test and a 16-km cycling time trial before and after 3 wk of double-leg and counterweighted single-leg cycle training (2 training sessions per week). Training involved three (double) or six (single) maximal 4-min intervals with 6 min of recovery. Mean power output during the single-leg intervals was more than half that during the double-leg intervals (198 ± 29 vs. 344 ± 38 W, P < 0.05). Skeletal muscle biopsy samples from the vastus lateralis revealed a training-induced increase in Thr(172)-phosphorylated 5'-AMP-activated protein kinase α-subunit for both groups (P < 0.05). However, the increase in cytochrome c oxidase subunits II and IV and GLUT-4 protein concentration was greater following single- than double-leg cycling (P < 0.05). Training-induced improvements in maximal O(2) consumption (3.9 ± 6.2% vs. 0.6 ± 3.6%) and time-trial performance (1.3 ± 0.5% vs. 2.3 ± 4.2%) were similar following both interventions. We conclude that short-term high-intensity single-leg cycle training can elicit greater enhancement in the metabolic and oxidative potential of skeletal muscle than traditional double-leg cycling. Single-leg cycling may therefore provide a valuable training stimulus for trained and clinical populations.

Changes in markers of muscle damage, inflammation and HSP70 after an Ironman Triathlon race.

We investigated the effects of an Ironman triathlon race on markers of muscle damage, inflammation and heat shock protein 70 (HSP70). Nine well-trained male triathletes (mean +/- SD age 34 +/- 5 years; VO(2peak) 66.4 ml kg(-1) min(-1)) participated in the 2004 Western Australia Ironman triathlon race (3.8 km swim, 180 km cycle, 42.2 km run). We assessed jump height, muscle strength and soreness, and collected venous blood samples 2 days before the race, within 30 min and 14-20 h after the race. Plasma samples were analysed for muscle proteins, acute phase proteins, cytokines, heat shock protein 70 (HSP70), and clinical biochemical variables related to dehydration, haemolysis, liver and renal functions. Muscular strength and jump height decreased significantly (P < 0.05) after the race, whereas muscle soreness and the plasma concentrations of muscle proteins increased. The cytokines interleukin (IL)-1 receptor antagonist, IL-6 and IL-10, and HSP70 increased markedly after the race, while IL-12p40 and granulocyte colony-stimulating factor (G-CSF) were also elevated. IL-4, IL-1beta and tumour necrosis factor-alpha did not change significantly, despite elevated C-reactive protein and serum amyloid protein A on the day after the race. Plasma creatinine, uric acid and total bilirubin concentrations and gamma-glutamyl transferase activity also changed after the race. In conclusion, despite evidence of muscle damage and an acute phase response after the race, the pro-inflammatory cytokine response was minimal and anti-inflammatory cytokines were induced. HSP70 is released into the circulation as a function of exercise duration.