Timeline to dysphagia resolution after endoscopic intervention of an interarytenoid defect based on Video Fluoroscopic Swallow Study dysphagia severity.

INTRODUCTION: We previously reported that endoscopic repair of a Type 1 Laryngeal Cleft (LC1) or Deep Interarytenoid Groove (DIG) improves swallowing function postoperatively. However, caregivers often ask about the timeline to resolution of the need for thickening. This study re-examines this cohort to answer this important caregiver-centered question. METHODS: We reassessed a 3-year retrospective, single-center dataset of children with dysphagia found to have a LC-1 or DIG on endoscopic exam. The primary outcome was rate of complete resolution of dysphagia at 2, 6, and 12 months after endoscopic intervention. A sub-group analysis was made based on severity of dysphagia prior to intervention and by type of endoscopic repair. RESULTS: Thirty-nine patients with mean age 1.35 years that had a LC-1 or DIG met criteria for inclusion. Rate of complete dysphagia resolution increased over time. Those with mild dysphagia (flow-reducing nipple and/or IDDSI consistency 1 or 2) had brisker resolution than those with moderate dysphagia (IDDSI consistency 3 or 4) at 2 months (67% vs 5%, p < 0.01) and at 6 months (80% vs 18%, p < 0.01) after endoscopic repair. There was no difference in dysphagia resolution between patients grouped by type of endoscopic repair. CONCLUSION: Addressing an interarytenoid defect in patients will not result in immediate, complete dysphagia resolution in most patients. However, patients that only require a flow-reducing nipple and/or thickening to an IDDSI consistency 1 or 2 have brisker resolution of the need for thickening than those that require an IDSSI consistency 3 or 4 prior to intervention. These results inform pre-operative discussions of the timeline to resolution based upon severity of dysphagia and help manage caregiver expectations.

Optimal timing and technique for endoscopic management of dysphagia in pediatric aerodigestive patients.

INTRODUCTION: The best strategy to manage an interarytenoid defect [Type 1 laryngeal cleft (LC-1) or deep interarytenoid groove (DIG)] in pediatric aerodigestive patients with dysphagia remains uncertain. This study compared benefit of interarytenoid augmentation (IAA) to suture repair or clinical observation alone in pediatric patients. METHODS: A 3-year retrospective, single-center analysis of children with dysphagia undergoing endoscopic airway evaluation was performed. Physician preference guided treatment plan: suture repair with CO2 laser, IAA (carboxy methylcellulose or calcium hydroxyapatite), or observation. Primary outcome was improved post-operative diet. Significance was assumed at p < 0.05. RESULTS: 449 patients underwent diagnostic endoscopy. Mean age (±SD) at procedure was 21 ± 13 months, with nearly one fourth (28 %) of children ≤ 12 months. Eighty (18 %) had either an LC-1 (n = 55) or DIG (n = 25). Of these, 35 (42 %) underwent suture repair, 22 (28 %) IAA, and 23 (30 %) observation only. Aspiration improved overall in the interventional groups compared to observational controls (58 % vs. 9 %, p < 0.05), with no change in benefit observed by age of intervention. IAA was as effective as suture repair (59 % vs 55 %, p = 0.46). In patients with only a DIG, IAA intervention alone significantly improved swallow function (66.6 % vs. 0 %, p < 0.05). CONCLUSION: In pediatric aerodigestive patients with dysphagia, 18 % of children have an addressable lesion. IAA or suture repair similarly improves dietary advancement. IAA improves swallow function in patients with DIG. These findings support a novel protocol to intervene in dysphagia patients with LC-1 or DIG via IAA at the initial operative evaluation.

Outcomes in video-assisted thoracoscopic surgery lobectomies: challenging preconceived notions.

BACKGROUND: Most thoracic surgical procedures in the United States are being performed by general surgeons (GSs) without any advanced training. With the recent approval of computed tomography screening for lung malignancy in high-risk populations, the number of thoracic oncologic resections is expected to rise. Previous literature has demonstrated consistently worsened outcomes for patients undergoing thoracic surgical procedure when done by nonthoracic fellowship-trained surgeons. Using the American College of Surgeons National Surgical Quality Improvement Project database, we examined short-term outcomes in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for malignancy. MATERIALS AND METHODS: Data were obtained from the American College of Surgeons National Surgical Quality Improvement Project from 2010-2015. We identified patients who had an International Classification of Disease 9 diagnosis of lung cancer (162) who underwent VATS lobectomy (current procedural terminology 32663). We included only adults (≥18y) and elective cases. We excluded patients who had preoperative diagnosis of sepsis, contaminated wound class, or those patients with missing American Society of Anesthesiologists classification, morbid obesity, functional status, length of stay (LOS), or sex, and race information. We identified two groups by specialty: GS versus cardiothoracic (CT) surgeon. We then performed univariate analysis. We then performed propensity score analysis using a 1:3 ratio of general surgery patients to CT patients. Outcomes of interest included 30-d postoperative mortality, 30-d postoperative morbidity, and LOS. RESULTS: A total of 4105 patients were identified, 607 performed by GSs, 3508 performed by CT surgeons. The mean age for patients who underwent lobectomies by GSs was 68.6 versus 67.8 in the CT surgeon group (P < 0.05). The majority were female (58.09% GS versus 57.74% CT surgeon). There was a statistically significant difference in race between groups; patients were more likely to be African American in the CT surgeon group. Operative time was lower in the GS group as opposed to the CT surgeon group 179 min versus 196 (P < 0.01). Univariate analysis (mortality <0.1 CT surgeon and GS) and 1:3 propensity score matched analysis (0.08 GS% versus 0.08% CT surgeon) failed to demonstrate a significant difference in mortality. There was a statistically significant difference in median LOS between groups (6.2 GS versus 5.1 CT surgeon). Univariate and propensity matched analyses of pneumonia, sepsis, wound infection, deep vein thrombosis, transfusion requirement, myocardial infarction stroke, postoperative renal insufficiency, failure to wean, pulmonary embolism, reintubation, and deep organ space infection all failed to demonstrate a statistically significant difference between our groups of interest. Urinary tract infection was noted to be higher in the GS group operating room 2.29 as compared to the CT surgeon group (P value 0.02). CONCLUSIONS: In this large observational study, we found that VATS lobectomies performed by GS compared to the matched CT surgeon cohort had shorter operative time, and there was no difference in major postoperative morbidity or mortality. However, LOS was higher and there was increased risk of urinary tract infection in the GS compared to matched CT surgeon cohort.

Substantial injuries influence ranking position in young elite athletes of athletics, cross-country skiing and orienteering.

The relationship between injury and performance in young athletes is scarcely studied. The aim of this study was therefore to explore the association between injury prevalence and ranking position among adolescent elite athletes. One hundred and sixty-two male and female adolescent elite athletes (age range 15-19), competing in athletics (n = 59), cross-country skiing (n = 66), and orienteering (n = 37), were monitored weekly over 22-47 weeks using a web-based injury questionnaire. Ranking lists were collected. A significant (P = .003) difference was found in the seasonal substantial injury prevalence across the ranked athletes over the season, where the top-ranked (median 3.6%, 25-75th percentiles 0%-14.3%) and middle-ranked athletes (median 2.3%, 25-75th percentiles 0%-10.0%) had a lower substantial injury prevalence compared to the low-ranked athletes (median 11.3%, 25-75th percentiles 2.5%-27.1%), during both preseason (P = .002) and competitive season (P = .031). Athletes who improved their ranking position (51%, n = 51) reported a lower substantial injury prevalence (median 0%, 25-75th percentiles 0%-10.0%) compared to those who decreased (49%, n = 49) their ranking position (md 6.7%, 25-75th percentiles 0%-22.5%). In the top-ranked group, no athlete reported substantial injury more than 40% of all data collection time points compared to 9.6% (n = 5) in the middle-ranked, and 17.3% (n = 9) in the low-ranked group. Our results provide supporting evidence that substantial injuries, such as acute and overuse injuries leading to moderate or severe reductions in training or sports performance, influence ranking position in adolescent elite athletes. The findings are crucial to stakeholders involved in adolescent elite sports and support the value of designing effective preventive interventions for substantial injuries.

Multiple factors explain injury risk in adolescent elite athletes: Applying a biopsychosocial perspective.

Many risk factors for injury are presented in the literature, few of those are however consistent and the majority is associated with adult and not adolescent elite athletes. The aim was to identify risk factors for injury in adolescent elite athletes, by applying a biopsychosocial approach. A total of 496 adolescent elite athletes (age range 15-19), participating in 16 different sports, were monitored repeatedly over 52 weeks using a valid questionnaire about injuries, training exposure, sleep, stress, nutrition, and competence-based self-esteem. Univariate and multiple Cox regression analyses were used to calculate hazard ratios (HR) for risk factors for first reported injury. The main finding was that an increase in training load, training intensity, and at the same time decreasing the sleep volume resulted in a higher risk for injury compared to no change in these variables (HR 2.25, 95% CI, 1.46-3.45, P<.01), which was the strongest risk factor identified. In addition, an increase by one score of competence-based self-esteem increased the hazard for injury with 1.02 (HR 95% CI, 1.00-1.04, P=.01). Based on the multiple Cox regression analysis, an athlete having the identified risk factors (Risk Index, competence-based self-esteem), with an average competence-based self-esteem score, had more than a threefold increased risk for injury (HR 3.35), compared to an athlete with a low competence-based self-esteem and no change in sleep or training volume. Our findings confirm injury occurrence as a result of multiple risk factors interacting in complex ways.

Too little sleep and an unhealthy diet could increase the risk of sustaining a new injury in adolescent elite athletes.

Little is known about health variables and if these variables could increase the risk of injuries among adolescent elite athletes. The primary aim was to present overall data on self-perceived stress, nutrition intake, self-esteem, and sleep, as well as gender and age differences, on two occasions among adolescent elite athletes. A secondary aim was to study these health variables as potential risk factors on injury incidence. A questionnaire was e-mailed to 340 adolescent elite athletes on two occasions during a single school year: autumn semester and spring semester. The results show that during autumn semester, the recommended intake of fruits, vegetables, and fish was not met for 20%, 39%, and 43% of the adolescent elite athletes, respectively. The recommended amount of sleep during weekdays was not obtained by 19%. Multiple logistic regression showed that athletes sleeping more than 8 h of sleep during weekdays reduced the odds of injury with 61% (OR, 0.39; 95% CI, 0.16-0.99) and athletes reaching the recommended nutrition intake reduced the odds with 64% (OR, 0.36; 95% CI, 0.14-0.91). Our findings suggest that nutrition intake and sleep volume are of importance in understanding injury incidence.

Overestimation of N-glycoPEGylated factor IX activity in a one-stage factor IX clotting assay owing to silica-mediated premature conversion to activated factor IX.

UNLABELLED: Essentials Nonacog beta pegol (N9-GP) activity is overestimated in clot method using silica-based reagents. Mimicking contact activation phase with silica reveals N9-GP activation before recalcification. Localization of N9-GP to silica facilitates activation by factor XIa and plasma kallikrein. Silica-based reagents to be used with caution when monitoring N9-GP therapy using clot method. SUMMARY: Background Clinical laboratories routinely quantify factor IX (FIX) activity by measurement of the activated partial thromboplastin time (APTT) in a one-stage (OS) clotting assay. This assay can be performed with any of a plethora of differently composed APTT reagents, giving variable recovery when applied to nonacog beta pegol (N9-GP), an N-glycoPEGylated recombinant FIX. Objective To identify the cause of observed overestimations of N9-GP activity in an OS FIX clotting assay when most APTT reagents containing silica are used as the contact activator, and to elucidate the underlying mechanism. Methods Experiments mimicking the contact activation and clotting phases of the OS assay, combined with the use of plasmas with various deficiencies, were employed to shed light on the unique behavior of N9-GP. Confirmatory activations of N9-GP with purified enzymes and physical adsorption to silica particles were studied, and the influence of free polyethylene glycol (PEG) on these processes was investigated. Results N9-GP, but not native FIX, added to FIX-deficient plasma was prematurely converted to activated FIX (FIXa) during the contact activation phase of the clotting assay. Activated FXI (FXIa) and plasma kallikrein (PK) were responsible for the activation of N9-GP, an event that appeared to require the presence of a silica-containing APTT reagent. PEG-dependent adsorption of N9-GP to silica particles could be demonstrated. Conclusions The PEG moiety mediates colocalization of N9-GP with its activators FXIa and PK on silica surfaces, thereby facilitating premature conversion of N9-GP to FIXa during the contact activation phase, and leading to overestimation of the FIX activity in the OS clotting assay.

Adsorption of carboxymethyl cellulose on alumina particles.

The polyelectrolyte adsorption on colloid particles is often used for stabilization or flocculation of water suspensions. The aim of this work is to study the adsorption of carboxymethyl cellulose (CMC) on alumina (γ-Al2O3) colloid particles. The particles and polymer are chosen because of the capability of the metal-oxide ampholyte surface and the weak polyelectrolytes to alter their charge by pH. The measurements are done at pH 6.0 where the CMC carboxylic gropes are almost fully dissociated and the alumina surface is positively charged. The high linear charge density of the polyelectrolyte chain provides Na(+) counterions condensation on the COO(-) groups. The main employed method is the electric light scattering based on particle orientation in sinusoidal electric field. The electric polarizability and the relaxation time after field switching off (both depending on the particle charge and size) are used as criteria for polymer adsorption and particle aggregation. Micro-electrophoresis is applied as additional techniques indicating the sign and density of the surface charge. The results obtained give the conditions (time dependence, particle and polymer concentrations) where the CMC adsorption is complete and the suspension is stable.

Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001).

PURPOSE: Vatalanib (PTK 787/ZK22584) is an oral poly-tyrosine kinase inhibitor with strong affinity for platelet-derived growth factor and vascular endothelial growth factor (VEGF) receptors. We conducted an open-label, phase II multicenter therapeutic trial investigating the efficacy and tolerability of vatalanib in patients with metastatic or advanced pancreatic cancer who failed first-line gemcitabine-based therapy. METHODS: Vatalanib treatment consisted of a twice daily oral dosing using a "ramp-up schedule," beginning with 250 mg bid during week 1,500 mg bid during week 2, and 750 mg bid on week three and thereafter. The primary objective of this study was to evaluate the 6-month survival rate. RESULTS: Sixty-seven patients were enrolled. The median age was 64, and 66% (N = 43) had only one prior regimen. Common grade 3/4 adverse events included hypertension (20%; N = 13), fatigue (17%; N = 11), abdominal pain (17%; N = 11), and elevated alkaline phosphatase (15%; N = 10). Among the 65 evaluable patients, the 6-month survival rate was 29% (95% CI 18-41%) and the median progression-free survival was 2 months. Fifteen patients survived 6 months or more. Two patients had objective partial responses, and 28% of patients had stable disease. Changes in biomarkers including soluble VEGF and vascular endothelial growth factor receptor did not correlate with response to drug. CONCLUSION: Vatalanib was well tolerated as a second-line therapy and resulted in favorable 6-month survival rate in patients with metastatic pancreatic cancer, compared with historic controls.

Strength of shock-loaded single-crystal tantalum [100] determined using in situ broadband x-ray Laue diffraction.

The strength of shock-loaded single crystal tantalum [100] has been experimentally determined using in situ broadband x-ray Laue diffraction to measure the strain state of the compressed crystal, and elastic constants calculated from first principles. The inferred strength reaches 35 GPa at a shock pressure of 181 GPa and is in excellent agreement with a multiscale strength model [N. R. Barton et al., J. Appl. Phys. 109, 073501 (2011)], which employs a hierarchy of simulation methods over a range of length scales to calculate strength from first principles.

Effect of abiraterone acetate plus prednisone on the pharmacokinetics of dextromethorphan and theophylline in patients with metastatic castration-resistant prostate cancer.

PURPOSE: To assess the effect of abiraterone acetate plus prednisone on the pharmacokinetics of dextromethorphan HBr (CYP2D6 substrate) and theophylline (CYP1A2 substrate) in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Men with progressive metastatic mCRPC who failed gonadotropin-releasing hormone therapy and ≥1 lines of chemotherapy were enrolled. Patients received two doses of dextromethorphan HBr-30 mg (n = 18; group A) or theophylline-100 mg (n = 16; group B) under fasting conditions; one dose on cycle 1, day -8, and the other dose on cycle 1, day 8. Only patients with extensive CYP2D6 metabolizing status were assigned to group A. All patients received continuous daily oral abiraterone acetate (1,000 mg) plus prednisone (10 mg) starting on cycle 1, day 1. RESULTS: Coadministration of abiraterone acetate plus prednisone increased the systemic exposure of dextromethorphan by approximately 100%. Ratios of geometric means for maximum plasma concentration (C(max)) (275.36%) and area under plasma concentration-time curves from time 0 to 24 h (AUC(24h)) (268.14%) of dextromethorphan were outside the bioequivalence limit. The pharmacokinetics of theophylline was unaltered following coadministration of abiraterone acetate plus prednisone. Ratios of geometric means [C(max); 102.36% and AUC(24h); 108.03%] of theophylline exposure parameters were within the bioequivalence limit. The safety profile of abiraterone acetate was consistent with reported toxicities. CONCLUSION: Abiraterone acetate plus prednisone increased the exposure of dextromethorphan, suggesting a need for caution when coadministrating with known CYP2D6 substrates. The pharmacokinetics of theophylline was unaffected when coadministered with abiraterone acetate plus prednisone.

Polymer concentration dependence of kilohertz electric polarizability of alumina colloid particles with adsorbed carboxymethyl cellulose.

Polyelectrolytes are soluble polymers composed of units having charged groups. Because of the high charge density, some of the counterions are adsorbed electrostatically (ion condensation) on the polyelectrolyte chain. It was shown that in direct electric field the condensed counterions and the chain move together as one whole but it is assumed that they are mobile in alternating field and participate in the polarization. Experimental evidence is obtained by electro-optical investigations of polyelectrolytes adsorbed on colloid particles-the observed low-frequency shift of the polarizability relaxation has been interpreted as condensed counterions' mobility. The present investigation aims to verify the reports for the condensed counterions' mobility in sinusoidal electric field. By means of electric light scattering we investigated a water suspension of γ-alumina particles with adsorbed carboxymethyl cellulose. Instead of the previously used frequency approach (dispersion dependence at saturated adsorption of the polyelectrolyte) we applied an amplitude approach-determination of the polarizability at frequency 1 kHz and increasing polyelectrolyte concentration (from zero to full adsorption saturation). The results indicate the absence of polarization owing to the condensed counterions. The main evidence was obtained by comparison of the concentration dependences of the polarizability (depending on all mobile counterions) and the electrophoretic mobility (determined only by the diffuse counterions). We concluded that the condensed counterions are immobile in sinusoidal field with intensity up to 0.5  kV cm (- 1) and frequency of 1 kHz and higher.

Ischemic preconditioning phosphorylates mitogen-activated kinases and heat shock protein 27 in the diabetic rat heart.

Diabetes mellitus blocks protection by ischemic preconditioning (IPC), but the mechanism is not known. We investigated the effect of ischemic preconditioning on mitogen-activated protein kinases (extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinases, p38 mitogen-activated kinase) and heat shock protein 27 phosphorylation in diabetic and nondiabetic rat hearts in vivo. Two groups of anaesthetized nondiabetic and diabetic rats underwent a preconditioning protocol (3 cycles of 3 min coronary artery occlusion and 5 min of reperfusion). Two further groups served as untreated controls. Hearts were excised for protein measurements by Western blot. Four additional groups underwent 25 min of coronary occlusion followed by 2 h of reperfusion to induce myocardial infarction. In these animals, infarct size was measured. IPC reduced infarct size in the nondiabetic rats but not in the diabetic animals. In diabetic rats, IPC induced phosphorylation of the mitogen-activated protein kinases and of heat shock protein 27. We conclude that protection by IPC is blocked by diabetes mellitus in the rat heart in vivo without affecting phosphorylation of mitogen-activated protein kinases or heat shock protein 27. Therefore, the blockade mechanism of diabetes mellitus is downstream of mitogen-activated kinases and heat shock protein 27.