bluuebunny/crossref_metadata_2025 huggingface dataset:
Subglottic stenosis: A ten‐year review of treatment outcomes
Authors: Hseu Anne F. , Benninger Michael S. , Haffey Timothy M. , Lorenz Robert
Published: October 2013

Objectives/Hypothesis

To evaluate the endoscopic surgical management of adult subglottic stenosis and describe treatment outcomes.

Study Design

Retrospective review.

Methods

Ten‐year review of adult patients with subglottic stenosis.

Results

Ninety‐two adults (23 male, 69 female) with subglottic stenosis underwent 247 endoscopic dilations between 2001 and 2010. The mean age was 48 years at time of first surgery. Etiology was GPA (granulomatosis with polyangiitis, formerly Wegener's granulomatosis) (45%), intubation (25%), or idiopathic (33%). Forty‐one patients (45%) underwent a single procedure; 51 patients (55%) required multiple surgeries. The average interval for patients requiring a subsequent procedure was 13.7 months. Variations in surgical technique did not show differences in time to next procedure, and the use of mitomycin‐C did not result in longer intervals between procedures. No significant complications were encountered after dilation.

Conclusions

Subglottic stenosis remains a treatment challenge. Although patients are often symptomatically improved after endoscopic dilation, recurrence rates remain high.

Level of Evidence

4. Laryngoscope, 124:736–741, 2014
Antisomnogenic cytokines, quality of life, and chronic rhinosinusitis: A pilot study
Authors: Alt Jeremiah A. , Sautter Nathan B. , Mace Jess C. , Detwiller Kara Y. , Smith Timothy L.
Published: October 2013

Objectives/Hypothesis

Sleep disturbance, reduced quality of life (QOL), and other components of “sickness behavior” in patients with chronic rhinosinusitis (CRS) are poorly understood. These complex changes in central behavior are due to the effects of immune mediators acting in the brain. We hypothesized that immune mediators that have been associated with CRS are also associated with sickness behavior, somnifacient complaints, and CRS disease‐specific QOL.

Study Design

Pilot study.

Methods

Twenty patients with CRS were prospectively enrolled and completed the Pittsburgh Sleep Quality Index (PSQI), disease‐specific QOL, and olfactory instruments. Ethmoid mucosa was obtained and reverse transcription‐polymerase chain reaction was performed for the cytokines interleukin (IL)−4, −13, and transforming growth factor‐β (TGF‐β). Average change in crossover threshold was calculated, and differences in gene expression were correlated with sleep quality, CRS‐specific QOL, and disease severity.

Results

Patients with CRS reported overall poor sleep quality and poor CRS‐specific QOL with significant correlations between them. Increased expression of TGF‐β (r = −0.443; P = .050) and IL‐4 (r = −0.548; P = .012) correlated with sleep dysfunction, whereas IL‐13 expression was linearly associated with worse sleep quality (PSQI scores r = −0.417; P = .075). IL‐4 and TGF‐β expression was not associated with CRS disease severity or QOL, whereas significantly higher levels of IL‐13 expression correlated with worse CRS disease severity and QOL.

Conclusions

Patients with CRS exhibited behavioral changes commonly referred to as sickness behavior, which include poor sleep quality and reduced QOL. The upregulation of IL‐4 and TGF‐β may contribute to inflammatory brain‐mediated effects on sleep quality, whereas IL‐13 may be a pleiotropic signaling molecule influencing sleep, QOL, and CRS disease severity.

Level of Evidence

2b. Laryngoscope, 124:E107–E114, 2014
A reporter assay for the next generation of biomaterials: Porous‐wall hollow glass microspheres
Authors: Cunningham Aaron , Faircloth Hunter , Jones Matthew , Johnson Christopher , Coleman Tiffany , Wicks George , Postma Gregory , Weinberger Paul
Published: October 2013

Objectives/Hypothesis

The primary objective was to design a reporter assay to measure molecular release kinetics from a new porous‐wall hollow glass microsphere biomaterial with great potential in regenerative medicine and drug delivery. Second, future avenues for research will be discussed specifically in regard to potential clinical uses in laryngology.

Study Design

Basic science data report.

Methods

We developed an assay using fluorescent nanocrystals or quantum dots (Qdot 605) as a reporter. A Nuance FX multispectral imaging system was used to detect fluorescence in aqueous phase. Spectral output of known concentrations of aqueous Qdot 605 was measured by the Nuance system to create a standard curve.

Results

These data were plotted and fit to a curve. Qdot 605 emission demonstrates excellent correlation with concentration in a log‐log relationship [R2 = 0.99649, median error = 9.9%], indicating that the Qdot 605 assay is reliable and should be explored regarding its ability to evaluate the drug‐eluting properties of this material.

Conclusions

We have derived a method to measure Qdot concentration using fluorescent microscopy, which will facilitate future research on this exciting new biomaterial. This material has great potential for use in head and neck surgery. Specific avenues within laryngology to be investigated include laryngeal and tracheal reconstruction, vocal fold healing, and nerve regeneration. Furthermore, we believe this is the first documented use of the Nuance system to determine aqueous molecular concentrations.

Level of Evidence

NA Laryngoscope, 124:1392–1397, 2014
Indications and outcomes of endoscopic CO2 laser cricopharyngeal myotomy
Authors: Bergeron Jennifer L. , Chhetri Dinesh K.
Published: October 2013

Objectives/Hypothesis

To describe indications, management, and outcomes of endoscopic CO2 laser cricopharyngeal myotomy (CPM).

Study Design

Case series with chart review.

Methods

All patients treated with endoscopic CO2 laser CPM over a 6‐year period were identified. A retrospective chart review was performed for surgical indication, history and physical examinations, and swallow evaluations. Swallowing outcomes were assessed using the Functional Outcome Swallowing Scale (FOSS); findings were compared across groups.

Results

Eighty‐seven patients underwent endoscopic CO2 laser CPM during the study period for cricopharyngeal dysfunction. Indications included Zenker's diverticulum (ZD) (39), DiGeorge syndrome (two), stroke (five), nerve injury (two), radiation for head and neck cancer (15), idiopathic (16), hyperfunctional tracheoesophageal speech (five) and dysphagia from cricopharyngeus stricture after laryngectomy (three). Mean, median, and mode time to feeding postoperatively were 1.4, 1, and 0 days respectively. Mean, median, and mode hospital stays were 1.8, 1, and 1 day respectively. Overall, FOSS scores improved from 2.6 to 1.6 (P < .001). Improvement was greatest for patients with ZD (2.4 to 1.0) and cricopharyngeal dysfunction from nerve injury (3.3 to 1.8) and least for those with prior radiation (3.9 to 3.2). All patients undergoing CPM for poor tracheoesophageal speech regained speech postoperatively. No patients developed mediastinitis, abscess, or fistula.

Conclusions

Endoscopic CO2 laser CPM is a safe treatment for cricopharyngeal dysfunction of various causes, though swallowing outcomes may vary depending on the surgical indication. Early feeding postoperatively after CPM is safe and facilitates early hospital discharge.

Level of Evidence

4. Laryngoscope, 124:950–954, 2014
Percutaneous injection laryngoplasty
Authors: Chhetri Dinesh K. , Jamal Nausheen
Published: October 2013

Level of Evidence

NA Laryngoscope, 124:742–745, 2014
Incidence and survival patterns of cranial chordoma in the United States
Authors: Chambers Kyle J. , Lin Derrick T. , Meier Josh , Remenschneider Aaron , Herr Marc , Gray Stacey T.
Published: October 2013

Objectives/Hypothesis

To determine trends in survival patterns for cranial chordoma in the United States.

Study Design

A cross‐sectional analysis of a national healthcare database.

Methods

All cases of microscopically confirmed cranial chordoma between 1973 and 2009 from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute were examined. Age‐adjusted incidence and survival rates were calculated and stratified by treatment. Additionally, in order to assess trends over time, comparisons in survival were conducted for 3 calendar year cohorts: 1975 to 1984, 1985 to 1994, and 1995 to 2004.

Results

A total of 594 cases of microscopically confirmed chordoma involving cranial sites were identified, which accounted for 42% of all chordomas. Age‐adjusted incidence rate (IR) of all chordomas was 0.089 per 100,000. Overall median survival time with surgery plus radiation was 9.2 years. Age and treatment modality were found to influence patient survival. Specifically, age > 50 years was associated with a significant increase in mortality rate (P < .05). Five‐year survival for the 1975 to 1984, 1985 to 1994, and 1995 to 2004 cohort was 48.5%, 73.0%, and 80.7%, respectively, with improved survival in the more recent cohorts (P < 0.01).

Conclusion

This study provides new data regarding survival patterns of cranial chordoma in the United States, with a trend toward improvement in survival in recent decades.

Level of Evidence

NA. Laryngoscope, 124:1097–1102, 2014
Cochlear implant fixation using a subperiosteal tight pocket without either suture or bone‐recess technique
Authors: Jethanamest Daniel , Channer Guyan A. , Moss William J. , Lustig Lawrence R. , Telischi Fred F.
Published: October 2013

Objectives/Hypothesis

To assess the complication and migration rates associated with the fixation of cochlear implant receiver‐stimulators using a subperiosteal tight pocket without either suture fixation or bone recession.

Study Design

Dual‐institution retrospective case review.

Methods

A retrospective case review was conducted at two tertiary referral centers. All patients who underwent cochlear implantation with device fixation using a subperiosteal tight pocket without suturing over the device or recessing of the receiver stimulator in bone were identified. There was a minimum follow‐up period of 6 months. Outcome measures included intraoperative and postoperative complications, including evidence of device migration associated with interference with external device use or the need for revision surgery. Other outcome measures included soft tissue flap complications.

Results

Sixty‐two patients were identified with a mean age of 39 years, (range 1.5–5 years). The average follow‐up period was 32.6 months (range 6–120 months). Device manufacturers included Cochlear Corporation (Denver, CO) (n = 44), MED‐EL (Durham, NC) (n = 12), and Advanced Bionics (Valencia, CA) (n = 6). There were no associated intraoperative complications related to subperiosteal pocket fixation of the receiver stimulator, and no cases of migration were identified.

Conclusion

Fixation of the cochlear implant receiver stimulator using a subperiosteal tight pocket without either suture fixation or bone recession has been demonstrated to be feasible across a range of patient demographics and cochlear implant devices. This method of fixation appears to allow for an efficient and minimally invasive approach without compromising patient safety or device performance.

Level of Evidence

4. Laryngoscope, 124:1674–1677, 2014
U. S. practice variations in the treatment of chronic laryngopharyngeal neuropathy
Authors: DePietro Joseph D. , Stein Daniel J. , Calloway Nathan , Cohen Seth M. , Noordzij Pieter J.
Published: October 2013

Objectives/Hypothesis

To evaluate differences in evaluation and workup of laryngopharyngeal neuropathy in a population of general otolaryngologists and fellowship‐trained laryngologists.

Study Design

Survey.

Methods

Members of the American Laryngological Association (ALA) and a general otolaryngologist database from the American Academy of Otolaryngology–Head and Neck Surgery (AAO‐HNS) were surveyed. A questionnaire was e‐mailed or mailed to 179 members of the ALA and 900 members from the AAO‐HNS database.

Results

Responses were received from 43 subjects in the ALA group (24.5%) and 96 in the AAO‐HNS database group (10.6%). Compared to the general otolaryngologists surveyed, ALA members were found to be more likely to practice in academics (79.6% vs. 6.6%) and to have been fellowship trained (79.5% vs. 16.5%). Among the general otolaryngologists, 44.6% reported being unfamiliar with laryngopharyngeal neuropathy compared to 0% from the ALA group (P < .0001). After accounting for the respondents unfamiliar with the condition, the general otolaryngologists reported being less comfortable in diagnosing laryngopharyngeal neuropathy (P < .0001) and were more concerned about the over‐diagnosis of laryngopharyngeal reflux when compared to the ALA (P = .0030).

Conclusion

General otolaryngologists and fellowship‐trained laryngologist have several differences in the knowledge, workup, and treatment of chronic laryngopharyngeal neuropathy. This may translate to unnecessary treatments and tests for effected patients and should be addressed with further education targeting general otolaryngologists.

Level of Evidence

4. Laryngoscope, 124:955–960, 2014
Transnasal endoscopic resection of symptomatic ecchordosis physaliphora
Authors: Bolzoni‐Villaret Andrea , Stefini Roberto , Fontanella Marco , Bottazzoli Marco , Turri Zanoni Mario , Pistochini Andrea , Castelnuovo Paolo , Nicolai Piero
Published: October 2013

Laryngoscope, 124:1325–1328, 2014
Association of rhinosinusitis with nasopharyngeal carcinoma: A population‐based study
Authors: Hung Shih‐Han , Chen Po‐Yueh , Lin Herng‐Ching , Ting Jonathan , Chung Shiu‐Dong
Published: October 2013

Objectives/Hypothesis

Although it is already known that the inflammation process elevates the risk of developing cancer, to date the association between rhinosinusitis and nasopharyngeal carcinoma (NPC) remains unknown. This study aimed to evaluate the association between rhinosinusitis and NPC based on a nationwide database.

Study Design

Case‐control study.

Methods

In total, the cases comprised of 2,242 subjects with NPC and 6,726 randomly selected subjects as controls. Separate conditional logistic regression analyses were used to calculate the odds ratio (OR) for having been previously diagnosed with chronic and acute rhinosinusitis between the cases and controls.

Results

Of the total sample, 607subjects (6.77%) had been diagnosed with chronic rhinosinusitis prior to the index date: 322 (14.36%) cases with NPC and 285 (4.24%) controls (P < .001). A conditional logistic regression analysis revealed that the OR of prior chronic rhinosinusitis for subjects with NPC is 3.83 (95% confidence interval [CI], 3.23‐4.53) as compared to controls after adjusting for the factors of income, urbanization, geographic location, tobacco use disorder, and alcohol abuse/dependence syndrome. Furthermore, 1,199 (53.48%) cases and 2,938 (42.19%) controls had been diagnosed with acute rhinosinusitis prior to the index date (P < .001).The adjusted OR of prior acute rhinosinusitis for subjects with NPC was 1.57 (95% CI, 1.43‐1.73) that of controls.

Conclusions

This study detected an association between NPC and rhinosinusitis. We recommend that patients who are diagnosed with rhinosinusitis, either acute or chronic, seek out aggressive management to reduce the tissue burden and lower the risk of subsequently developing NPC.

Level of Evidence

3b. Laryngoscope, 124:1515–1520, 2014
Voice quality after treatment of T1a glottic cancer
Authors: Laoufi Samia , Mirghani Haïtham , Janot François , Hartl Dana M.
Published: October 2013

Objectives/Hypothesis

To compare voice handicap and quality of life after radiotherapy (RT) versus transoral laser surgery (LS) for T1a glottic carcinoma.

Study Design

Retrospective study (1996–2011) of patients treated with RT or LS for T1a glottic squamous cell carcinoma with curative intent.

Methods

Disease‐free patients were assessed using Voice Handicap Index (VHI 30) and European Organization for Research and Treatment of Cancer Head and Neck Quality of Life (EORTC QLQ‐HN35) questionnaires.

Results

Of 147 patients, 95 (65%) completed the questionnaires: fifty‐one patients an average of 8 years after RT and 44 patients an average of 4 years after LS (no difference in age or sex ratio). The average total VHI 30 was 13.1 for RT and 29.2 for LS (P < .0001), with average emotional, physical and functional subscores significantly different. The average total EORTC QLQ‐HN35 was 37.7 for RT versus 40.7 for LS (P = .7), with a difference only in the speaking subscore (P = .04).

Conclusions

Long‐term subjective voice‐related quality of life was worse after LS, with no difference in other domains. These results should be interpreted in light of the biases inherent in retrospective studies.

Level of Evidence

4. Laryngoscope, 124:1398–1401, 2014
The Effect of a Speaking Valve on Laryngeal Aspiration and Penetration in Children With Tracheotomies
Authors: Ongkasuwan Julina , Turk Catherine L. , Rappazzo Christina A. , Lavergne Katherine A. , Smith E. O'Brian , Friedman Ellen M.
Published: October 2013

Objectives/Hypothesis

Alterations in swallowing can occur after tracheotomy and can result in varying degrees of aspiration. In tracheotomized adult patients, use of a Passy Muir Speaking Valve (PMV) has been shown to decrease laryngeal penetration and aspiration of foods and liquids. The objective of this study was to determine if the PMV has a similar effect on laryngeal penetration and aspiration in tracheotomized children.

Study Design

This is a prospective case‐control study.

Methods

Pediatric patients with tracheotomies who were able to tolerate the PMV were identified. Modified barium swallow (MBS) was performed with and without the PMV. Two consistencies, thin liquids and purées, were used. Two speech language pathologists (SLPs), who were blinded to the PMV status, reviewed the recorded MBSs. Three swallows of each consistency were graded on an 8 point Penetration‐Aspiration Scale. Residue in the vallecula, piriform sinuses, and posterior pharyngeal wall was graded.

Results

Twelve patients were included for analysis. Laryngeal penetration and aspiration was decreased with purées over liquids (P = 0.5 and P = 0.005, respectively) with either the sham valve or the PMV. The presence of the PMV decreased piriform sinus residue (P = 0.01); however, it did not demonstrate a decrease in laryngeal aspiration or penetration.

Conclusion

Unlike in adults, the presence of PMV did not decrease laryngeal aspiration or penetration in children with tracheotomies. It did, however, improve piriform sinus residue.

Level of Evidence

3b. Laryngoscope, 124:1469–1474, 2014
A preliminary report of percutaneous craniofacial osteoplasty in a rat calvarium
Authors: Parkes William J. , Greywoode Jewel , O'Hara Brian J. , Heffelfinger Ryan N. , Krein Howard
Published: October 2013

Objectives/Hypothesis

To evaluate the potential for injectable, permanent bone augmentation by assessing the biocompatability and bioactivity of subperiosteal hydroxylapatite (Radiesse) deposition in a rat model.

Study Design

Randomized controlled animal model.

Methods

Fourteen adult Sprague Dawley rats were injected in the parietal skull with 0.2 ml of hydroxylapatite (10 animals) or 0.2 ml of a carrier gel control (4 animals), using a subperiosteal injection technique on the right and a subcutaneous injection technique on the left. At 1, 3, and 6 months, three rats (1 negative control, 2 variables) were sacrificed and the calvaria were harvested. At 12 months, the remaining five rats were sacrificed. After each harvest, the specimens were processed and then examined under both light and polarized microscopy for new bone growth at the injection sites.

Results

The inflammatory response was limited with both hydroxylapatite and carrier injections. Injectables were still present 12 months after the injection. New bone formation was only observed when the injection was located deep to a disrupted periosteum The odds of new bone formation was 48.949 times higher (95% confidence intervals CI [2.637, 3759.961]; P = 0.002) with subperiosteal hydroxylapatite injections compared to all other combinations of injection plane and injectable.

Conclusions

This preliminary report of subperiosteal hydroxylapatite (Radiesse) injection in a rat model has verified the biocompatibility of injectable hydroxylapatite at the bony interface and suggests the potential for new bone formation.

Level of Evidence

N/A. Laryngoscope, 124:1550–1553, 2014
Cricopharyngeal achalasia in children: Botulinum toxin injection as a tool for diagnosis and treatment
Authors: Scholes Melissa A. , McEvoy Timothy , Mousa Hayat , Wiet Gregory J.
Published: October 2013

Objectives/Hypothesis

Characteristics and outcomes of pediatric patients undergoing cricopharyngeus injection with botulinum toxin for the treatment of cricopharyngeal achalasia were reviewed. A parental telephone survey was performed to assess improvement and satisfaction.

Study Design

Retrospective review of patients who underwent injection of the cricopharyngeus with botulinum toxin for cricopharyngeal achalasia. A prospective survey of postoperative symptoms and parental satisfaction was also performed.

Methods

After institutional review board approval, children with cricopharyngeal achalasia who underwent injection with botulinum toxin were identified. Specific parameters were recorded for each patient. A survey of the parents' satisfaction and subjective improvement was then conducted.

Results

Six children were identified with cricopharyngeal achalasia, with an age range of 3 months to 10 years. Symptoms varied and five of the six children required some form of altered nutrition. Preoperative studies varied, and the number of injections ranged from one to three per patient. One child had transient worsening of aspiration. Two children benefited from injections and went on to myotomy, while four children did not require myotomy and their symptoms were treated with injections alone.

A parental survey was performed via telephone. All parents were satisfied with the procedure. Three children were symptom‐free, and three children still exhibit some dysphagia.

Conclusions

Botulinum toxin injection is a useful tool to help diagnose and treat pediatric cricopharyngeal achalasia. More research is needed to elucidate optimal dosing, frequency of injections, and when to move on to surgical intervention.

Level of Evidence

4. Laryngoscope, 124:1475–1480, 2014
Substance abuse treatment and its association with relapse to alcohol use after liver transplantation
Authors: Rodrigue James R. , Hanto Douglas W. , Curry Michael P.
Published: October 2013

Many liver transplantation (LT) programs require substance abuse (SA) treatment for candidates with a history of alcohol abuse. However, there are no data indicating that SA treatment prevents post-LT alcohol relapse. We examined 118 adults who underwent LT from May 2002 to February 2011 to explore the relationship between SA treatment and post-LT relapse to any alcohol use. Sixty-one patients (52%) with a history of alcohol abuse or dependence received SA treatment before LT. Relapse to any alcohol use was identified in 40 LT recipients (34%). Patients who received SA treatment before LT did not differ significantly in the rate of post-LT alcohol relapse from patients who did not receive treatment before transplantation (30% versus 39%, P = 0.20). However, patients who received SA treatment both before and after transplantation had significantly lower rates of alcohol relapse (16%) than patients who received no SA treatment (41%) or SA treatment only before LT (45%, P = 0.03). Our findings suggest that LT programs should consider placing more emphasis on the continuation of some type of SA treatment after transplantation. Future research should prospectively examine the optimal timing for SA treatment that will attenuate the risk of alcohol relapse after transplantation. Liver Transpl 19:1387–1395, 2013. © 2013 AASLD.
Identification of liver transplant candidates with hepatocellular carcinoma and a very low dropout risk: Implications for the current organ allocation policy
Authors: Mehta Neil , Dodge Jennifer L. , Goel Aparna , Roberts John Paul , Hirose Ryutaro , Yao Francis Y.
Published: October 2013

It has been shown that patients with hepatocellular carcinoma (HCC) meeting the United Network for Organ Sharing T2 (Milan) criteria have an advantage in comparison with patients without HCC under the current organ allocation system for liver transplantation (LT). We hypothesized that within the T2 HCC group, there is a subgroup with a low risk of wait-list dropout that should not receive the same listing priority. This study evaluated 398 consecutive patients with T2 HCC listed for LT with a Model for End-Stage Liver Disease exception from March 2005 to January 2011 at our center. Competing risk (CR) regression was used to determine predictors of dropout. The probabilities of dropout due to tumor progression or death without LT according to the CR analysis were 9.4% at 6 months and 19.6% at 12 months. The median time from listing to LT was 8.8 months, and the median time from listing to dropout or death without LT was 7.2 months. Significant predictors of dropout or death without LT according to a multivariate CR regression included 1 tumor of 3.1 to 5 cm (versus 1 tumor of 3 cm or less), 2 or 3 tumors, a lack of a complete response to the first locoregional therapy (LRT), and a high alpha-fetoprotein (AFP) level after the first LRT. A subgroup (19.9%) that met certain criteria (1 tumor of 2 to 3 cm, a complete response after the first LRT, and an AFP level ≤ 20 ng/mL after the first LRT) had 1- and 2-year probabilities of dropout of 1.3% and 1.6%, respectively, whereas the probabilities were 21.6% and 26.5% for all other patients (P = 0.004). In conclusion, a combination of tumor characteristics and a complete response to the first LRT define a subgroup of patients with a very low risk of wait-list dropout who do not require the same listing priority. Our results may have important implications for the organ allocation policy for HCC. Liver Transpl 19:1343-1353, 2013. © 2013 AASLD.
Rituximab as therapy for the recurrence of bile salt export pump deficiency after liver transplantation
Authors: Lin Henry C. , Alvarez Luis , Laroche Greggy , Melin-Aldana Hector , Pfeifer Kim , Schwarz Kathleen , Whitington Peter F. , Alonso Estella M. , Ekong Udeme D.
Published: October 2013

Progressive familial intrahepatic cholestasis type 2 (PFIC2) results from recessive mutations in the adenosine triphosphate–binding cassette B11 gene, which encodes for bile salt export pump (BSEP). Liver transplantation (LT) is offered to PFIC2 patients with end-stage liver disease. Reports have described recurrent cholestasis in PFIC2 patients after transplantation, and this has been associated with immunoglobulin G antibodies to BSEP. High-titer anti-BSEP antibodies appear to correlate with episodes of cholestatic graft dysfunction. There is no established paradigm for treating antibody-mediated posttransplant BSEP disease. It appears to be refractory to changes in immunosuppressant medications that would typically be effective in treating allograft rejection. Taking what is known about its pathophysiology, we designed a treatment consisting of rituximab, a chimeric monoclonal anti-CD20 antibody, in combination with intravenous immunoglobulin and plasmapheresis. Using this approach, we report the successful management of 2 patients with antibody-mediated recurrence of PFIC2 after LT. Liver Transpl 19:1403-1410, 2013. © 2013 AASLD.
Improved renal function in liver transplant recipients treated for hepatitis C virus with a sustained virological response and mild chronic kidney disease
Authors: Blé Michel , Aguilera Victoria , Rubín Angel , García-Eliz María , Vinaixa Carmen , Prieto Martín , Berenguer Marina
Published: October 2013

Hepatitis C virus (HCV) is associated with renal complications. We aimed to determine whether a sustained virological response (SVR) was associated with improvements in renal function (RF) in liver transplant (LT) recipients treated for HCV. Changes in RF were compared 1, 3, and 5 years after therapy as a function of the stage of chronic kidney disease (CKD) before treatment (BT). Variables associated with renal dysfunction [RD; 4-variable Modification of Diet in Renal Disease (MDRD-4) value 60 mL/minute] at the last follow-up (LFU) were evaluated for all treated LT patients with a minimum follow-up of at least 1 year since the end of treatment (EOT; n = 175). There were 99 patients with stage 2 CKD BT (MDRD-4 value 60-89 mL/minute/1.73 m2), and an improvement in RF was observed more frequently among SVR patients versus nonresponders (NRs). The median changes in the MDRD-4 values BT to 1, 3, and 5 years after treatment were −0.5, 4.5, and 9.4 mL/minute for the SVR patients and −1, −0.3, and −1.5 mL/minute for the NRs (P = 0.61, P = 0.06, and P = 0.004, respectively). RD was present in 31% of the patients at the LFU at a median of 3.8 years after EOT (range 1-9 years). The follow-up did not differ between SVR patients and NRs. RD was present at the LFU in 19% of SVR patients versus 40% of NRs (P = 0.002). In the multivariate analysis, RD at the LFU was associated with NRs [relative risk (RR) 3.8, 95% confidence interval (CI) = 1.3-11.23, P = 0.01], EOT MDRD-4 values (RR = 1.022, 95% CI = 1.001-1.04, P = 0.04), and female sex (RR = 5.6, 95% CI = 1.84-17.5, P = 0.002). In conclusion, SVR leads to improved RF in HCV-infected LT recipients with stage 2 CKD BT. Liver Transpl 20:25–34, 2014. © 2013 AASLD.
Role of immunosuppression in post–endoscopic retrograde cholangiopancreatography pancreatitis after liver transplantation: A retrospective analysis
Authors: Law Ryan , Leal Carlos , Dayyeh Barham Abu , Leise Michael D. , Balderramo Domingo , Baron Todd H. , Cardenas Andres
Published: October 2013

Endoscopic retrograde cholangiopancreatography (ERCP) is frequently used for diagnosis and therapeutic interventions in recipients of liver transplantation (LT) who develop biliary complications. Post–endoscopic retrograde cholangiopancreatography acute pancreatitis (PEP) is the most common major adverse event after ERCP; however, the frequency of PEP in LT recipients is not well established. We aimed to determine the rate of PEP in this population and to identify its predictors, especially among immunosuppressive agents. We reviewed all ERCP procedures performed in LT recipients after duct-to-duct biliary anastomoses at 2 high-volume transplant centers. Patients who had undergone sphincterotomy or had a surgically altered pancreaticobiliary anatomy before LT were excluded. Electronic medical records and endoscopy databases were used to obtain clinical, endoscopic, and medication data. A multivariate logistic regression analysis was used to determine predictors of PEP in this cohort. In all, 730 ERCP procedures were performed in 301 patients during the study period with an observed PEP rate of 3% (22/730). A univariate analysis revealed an increased risk of PEP with index ERCP after LT [odds ratio (OR) = 4.04, 95% confidence interval (CI) = 1.40-11.65] and in cases with difficult biliary cannulation (OR = 2.89, 95% CI = 1.10-7.65), whereas prednisone use was found to have a protective effect in both univariate (OR = 0.34, 95% CI = 0.14-0.84) and multivariate analyses (OR = 0.22, 95% CI = 0.09-0.57) after adjustments for difficult biliary cannulation and post-LT index ERCP. This retrospective analysis demonstrates that corticosteroid therapy has a protective role in the development of PEP in LT recipients. Further studies are warranted to confirm our findings. Liver Transpl 19:1354-1360, 2013. © 2013 AASLD.
Low Platelet Counts After Liver Transplantation Predict Early Posttransplant Survival: The 60-5 Criterion
Authors: Lesurtel Mickaël , Raptis Dimitri A. , Melloul Emmanuel , Schlegel Andrea , Oberkofler Christian , El-Badry Ashraf Mohammad , Weber Annina , Mueller Nicolas , Dutkowski Philipp , Clavien Pierre-Alain
Published: October 2013

Platelets play a critical role in liver injury and regeneration. Thrombocytopenia is associated with increases in postoperative complications after partial hepatectomy, but it is unknown whether platelet counts could also predict outcomes after transplantation, a procedure that is often performed in thrombocytopenic patients. Therefore, the aim of this study was to evaluate whether platelet counts could be indicators of short- and long-term outcomes after liver transplantation (LT). Two hundred fifty-seven consecutive LT recipients (January 2003-December 2011) from our prospective database were analyzed. Preoperative and daily postoperative platelet counts were recorded until postoperative day 7 (POD7). Univariate and multivariate analyses were performed to assess whether low perioperative platelet counts were a risk factor for postoperative complications and graft and patient survival. The median pretransplant platelet count was 88 × 109/L [interquartile range (IQR) = 58-127 × 109/L]. The lowest platelet counts occurred on POD3: the median was 56 × 109/L (IQR = 41-86 × 109/L). Patients with low platelet counts on POD5 had higher rates of severe (grade IIIb/IV) complications [39% versus 29%, odds ratio (OR) = 1.09 (95% CI = 1.1-3.3), P = 0.02] and 90-day mortality [16% versus 8%, OR = 2.25 (95% CI = 1.0-5.0), P = 0.05]. In the multivariate analysis, POD5 platelet counts < 60 × 109/L were identified as an independent risk factor for grade IIIb/IV complications [OR = 1.96 (95% CI = 1.07-3.56), P = 0.03)], graft survival [hazard ratio (HR) = 2.0 (95% CI = 1.1-3.6), P = 0.03)], and patient survival [HR = 2.2 (95% CI = 1.1-4.6), P = 0.03)]. The predictive value of platelet counts for graft and patient survival was lost in patients who survived 90 days. In conclusion, after LT, platelet counts < 60 × 109/L on POD5 (the 60-5 criterion) are an independent factor associated with severe complications and early graft and patient survival. These findings may help us to develop protective strategies or specific interventions for high-risk patients. Liver Transpl 20:147-155, 2014. © 2013 AASLD.
Hemodynamic changes in the hepatic circulation after the modulation of the splenic circulation in an in vivo human experimental model
Authors: Akamatsu Nobuhisa , Sugawara Yasuhiko , Satou Shouichi , Mitsui Tetsuya , Ninomiya Riki , Komagome Masahiko , Ozawa Fumiaki , Beck Yoshifumi
Published: October 2013

Recent advances in liver surgery have highlighted the effects of the splenic circulation on the hepatic circulation with respect to the hepatic arterial buffer response (HABR). The aim of the present study was to investigate the actual hemodynamic effects of splenic artery embolization/ligation and splenectomy on the hepatic circulation in patients who underwent pancreaticoduodenectomy through in vivo experimental models. In vivo models of splenic artery embolization/ligation (only splenic artery clamping) and splenectomy (simultaneous clamping of both the splenic artery and the splenic vein) were created in 40 patients who underwent pancreaticoduodenectomy for various reasons. The portal venous flow velocity, the portal venous flow volume, the hepatic arterial flow velocity, and the hepatic arterial resistance index were measured with color Doppler ultrasonography. Clamping of the splenic artery induced an immediate and significant increase (16%) in the hepatic artery velocity (P < 0.001), and the portal venous flow also decreased significantly (10%, P = 0.03). Fifteen minutes after the clamping of the splenic artery, the hepatic artery velocity remained significantly increased at the level of the initial clamping, and the portal venous flow significantly decreased (16%, P < 0.001). Clamping of the splenic vein, which was performed after the clamping of the splenic artery, resulted in an immediate and significant decrease (30%) in the portal venous flow (P < 0.001), but the hepatic arterial flow was not affected. Fifteen minutes after the clamping of the splenic vein, there was no change in the portal flow, which remained significantly lower (28%) than the flow in controls, whereas the hepatic arterial flow further significantly increased (31%, P < 0.001). In conclusion, our findings indicate that both splenic artery embolization/ligation and splenectomy are effective for increasing hepatic arterial flow and decreasing portal flow, with splenectomy providing a greater advantage. The HABR underlies these hemodynamic changes. Liver Transpl 20:116–121, 2014. © 2013 AASLD.
New Insights on the Self‐Organization of PEG/α‐Cyclodextrin‐Based Polyrotaxanes in Solution: An Experimental and Theoretical Study
Authors: Peña‐Bahamonde Janire , Atencia José Joaquín , Pozuelo Javier , Tarazona María Pilar , Mendicuti Francisco
Published: October 2013

Size exclusion chromatography coupled with light scattering (SEC/MALS), dynamic light scattering (DLS), steady‐state and time‐resolved fluorescence, as well as molecular dynamics (MD) simulations are used to study the behavior of several poly(ethylene glycol) (PEG)/α‐cyclodextrins (αCDs) polyrotaxanes (PRs) in solution. The number of CD units in any of the PRs studied is always smaller than that required to saturate the PEG chains. These PRs seem to aggregate in dimethyl sulfoxide (DMSO) solution. The presence of hairpins in the non‐saturated PRs contributes to diminishing their expected large dimensions. Intra‐ and inter­molecular interactions and forces responsible for hairpins and aggregation are investigated.

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The Control of Silica Nanoparticles on the Phase Separation of Poly(methyl methacrylate)/Poly(styrene‐co‐acrylonitrile) Blends
Authors: Li Weizhen , l'Abee Roy M. A. , Goossens Johannes G. P.
Published: October 2013

The influence of silica nanoparticles on the lower critical solution temperature (LCST) phase behavior and phase‐separation kinetics of a blend consisting of poly(methyl methacrylate) (PMMA) and poly(styrene‐co‐acrylonitrile) (SAN), is studied via a high‐throughput experimentation (HTE) approach, which combines a composition (φ) and a temperature (T) gradient. The evolution of the phase‐separation process is studied by optical microscopy (OM), small‐angle light scattering (SALS), and transmission electron microscopy (TEM). Depending on the specific interaction between the silica surface and the polymers, the distribution of silica particles during phase separation can be controlled to be either in one of the polymer phases or at the PMMA/SAN interface. The hydrophilic silica nanoparticles preferentially migrate to the PMMA phase, leading to a slow down of the coarsening rate, which may be related to a reduction of the mobility of PMMA due to an increase of the silica concentration. The hydrophobic silica nanoparticles are localized at the PMMA/SAN interface, and the inhibition of coalescence corresponds to the presence of a solid barrier (the nanoparticles) between the polymers, which prevents the coarsening process.

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Poly(N‐isopropylacrylamide)‐Modified Styrene‐Butadiene Rubber as Thermoresponsive Material
Authors: Hermann Alexandra , Mruk Ralf , Roskamp Robert F. , Scherer Martin , Ma Liqing , Zentel Rudolf
Published: October 2013

Narrowly distributed (N‐isopropylacrylamide) (NIPAM) polymers are prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. After successful cleavage of the trithiocarbonate end groups (thiol generation), they can be grafted to styrene‐butadiene rubber (SBR) by a radical thiol‐ene reaction leading to various grafted SBR‐copolymers. During the grafting reaction, no crosslinking or branching of the SBR can be observed. Measurements of the contact angle of water show that the lower critical solution temperature (LCST) properties of the PNIPAM fraction affect the SBR. Films of the graft‐copolymer exhibit a distinct hydrophilicity below the LCST, while they show hydrophobic behavior above the LCST. Rheological measurements reveal a physical crosslinking of the functionalized SBR due to nanophase separation of the PNIPAM chains (hard phase) in the unpolar SBR. Compared with blends of SBR and PNIPAM, the PNIPAM‐grafted SBR possesses a much finer distribution of the PNIPAM domains (10–30 nm) within the matrix. In addition, two novel difunctional chain‐transfer agents are used, leading to difunctional PNIPAM, enabling a covalent crosslinking of SBR.

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Mechanical Performance and Transparency of Nanocellulose Reinforced Polymer Nanocomposites
Authors: Boufi Sami , Kaddami Hamid , Dufresne Alain
Published: October 2013

Cellulosic nanofibers in the form of nanofibrillated cellulose (NFC) and cellulose nanocrystals (CNCs) have been prepared from alfa and rachis of date palm tree. Nanocomposites were prepared by casting/evaporation from these materials using an acrylic polymer in the form of latex as the matrix. Dynamic mechanical properties of the nanocomposites were investigated and the rubbery modulus was found to depend mainly on the aspect ratio of the cellulosic nanoparticles. Higher aspect ratio resulted in higher reinforcing capability. However, surprisingly the transparency of the films decreased for a given nanofiller content when the diameter of the nanoparticle decreased. Percolation of the nanofiller was suggested as being responsible for these two observations.
Difference analogues of the second main theorem for meromorphic functions in several complex variables
Authors: Cao Ting‐Bin
Published: October 2013

In this paper, we obtain difference analogues of the second main theorem for meromorphic functions in several complex variables from which difference analogues of Picard‐type theorems are also obtained. Our results are improvements or extensions of some recent results of papers [Proc. Royal Soc. Edinburgh Section A Math. 137, 457–474 (2007); Comput. Meth. Funct. Theor. 12, No. 1, 343–361 (2012)]. The method we used is very different from theirs.
Revival of the R‐Group Approach: A “CTA‐shuttled” Grafting from Approach for Well‐Defined Cylindrical Polymer Brushes via RAFT Polymerization
Authors: Zheng Zhicheng , Ling Jun , Müller Axel H. E.
Published: October 2013

The synthesis of well‐defined cylindrical polymer brushes (CPBs) from a linear polymer backbone with a high density of RAFT functionalities (“grafting from” approach) is challenging when the chain transfer agent (CTA) is attached to the backbone via its R‐group. It is proposed that the difficulties of the R‐group approach in controlling the grafting polymerization are induced by the “entrapment” of active free radicals within individual growing CPBs. A facile “CTA‐shuttled” R‐group approach overcoming this entrapment effect is developed, and used to synthesize well‐defined CPBs with polystyrene or poly(tert‐butyl acrylate) branches and core–shell CPBs with polystyrene‐block‐poly(N‐isopropylacrylamide) branches. The polydispersity index (PDI = 1.23) of the obtained CPBs with polystyrene branches is much lower than that from the conventional R‐group approach (PDI = 2.18). Monte Carlo simulations confirm that the advantage of the “CTA‐shuttled” R‐group approach consists in the release of the active radicals from the trapping CPB systems.

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Single‐Chain Self‐Folding of Synthetic Polymers Induced by Metal–Ligand Complexation
Authors: Willenbacher Johannes , Altintas Ozcan , Roesky Peter W. , Barner‐Kowollik Christopher
Published: October 2013

The controlled folding of a single polymer chain is for the first time realized by metal‐ complexation. α,ω‐Bromine functional linear polymers are prepared via activators regenerated by electron transfer (ARGET) ATRP (,SEC = 5900 g mol−1, Đ = 1.07 and 12 000 g mol−1, Đ = 1.06) and the end groups of the polymers are subsequently converted to azide functionalities. A copper‐catalyzed azide–alkyne cycloaddition (CuAAC) reaction is carried out in the presence of a novel triphenylphosphine ligand and the polymers to afford homotelechelic bis‐triphenylphosphine polymeric‐macroligands (MLs) (,SEC = 6600 g mol−1, Đ = 1.07, and 12 800 g mol−1, Đ = 1.06). Single‐chain metal complexes (SCMCs) are formed in the presence of Pd(II) ions in highly diluted solution at ambient temperature. The results derived via 1H and 31P{1H} NMR experiments, SEC, and DLS unambiguously evidence the efficient formation of SCMCs via metal ligand complexation.

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Unexpected Cononsolvency Behavior of Poly (N‐isopropylacrylamide)‐Based Microgels
Authors: Heppner Ian N. , Islam Molla R. , Serpe Michael J.
Published: October 2013

Poly (N‐isopropylacrylamide) (pNIPAm)‐based microgels undergo a transition from fully water swollen (solvated) to deswollen (desolvated) as the temperature of the water they are dissolved in is increased >32 °C. In this submission, we examine how the temperature of this transition, i.e., the volume phase transition temperature (VPTT), depends on the concentration of methanol (MeOH) in water the microgels are dissolved in. To accomplish this, pNIPAm‐based etalons are utilized, and it is shown that the VPTT for the microgels is much less than that previously observed for linear pNIPAm and pNIPAm‐based microgels. Furthermore, and most interestingly, it is determined that the microgels can collapse in solutions containing high MeOH (>∼65% MeOH) concentration. This is in contrast to previous studies, which show that no VPTT is observed for pNIPAm in aqueous solutions containing >∼65% MeOH.

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Hollow Polydimethylsiloxane Beads with a Porous Structure for Cell Encapsulation
Authors: Oh Myeong‐Jin , Ryu Tae‐Kyoung , Choi S.‐W.
Published: October 2013

Based on a water‐in‐oil‐in‐water emulsion system, porous and hollow polydimethylsiloxane (PDMS) beads containing cells using a simple fluidic device with three flow channels are fabricated. Poly(ethylene glycol) (PEG) in the PDMS oil phase is served as a porogen for pore development. The feasibility of the porous PDMS beads prepared with different PEG concentrations (10, 20, and 30 wt%) for cell encapsulation in terms of pore size, protein diffusion, and cell proliferation inside the PDMS beads is evaluated. The PDMS beads prepared with PEG 30 wt% are exhibited a highly porous structure and facilitated fast diffusion of protein from the core domain to the outer phase, eventually leading to enhanced cell proliferation. The results clearly indicate that hollow PDMS beads with a porous structure could provide a favorable microenvironment for cell survival due to the large porous structure.

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No evidence that associations of incident, sporadic colorectal adenoma with its major modifiable risk factors differ by chromosome 8q24 region rs6983267 genotype
Authors: Yang Baiyu , Thyagarajan Bharat , Gross Myron D. , Fedirko Veronika , Goodman Michael , Bostick Roberd M.
Published: October 2013

A single nucleotide polymorphism (SNP), rs6983267, in the chromosome 8q24 region, has been associated with higher risk for colorectal neoplasms, but its relation to carcinogenic mechanisms is unclear. To investigate whether associations of colorectal adenoma with its major modifiable risk factors differ according to rs6983267 genotype, we performed a pooled analysis of the White participants (n = 401 cases, 518 controls) from three colonoscopy‐based, case–control studies of incident, sporadic colorectal adenoma conducted between 1991 and 2002. There was a statistically significant direct association of rs6983267 with colorectal adenoma that was consistent with those in previous reports. We found no clear indications that rs6983267 impacts the association of colorectal adenomas with the following risk factors: physical activity, body mass index (BMI), nonsteroidal anti‐inflammatory drug (NSAID) use, tobacco or alcohol use, hormone replacement therapy among women, blood 25‐OH‐vitamin D3 levels, oxidative balance, or total energy, calcium, red meat, vegetable and fruit, and folate intakes. These findings, together with previously reported null results on 8q24–environment interactions for colorectal cancer, suggest that associations of colorectal adenoma with its major modifiable risk factors may not differ according to chromosome 8q24 region rs6983267 genotype. © 2013 Wiley Periodicals, Inc.