Recent Stanford Publications in PubMed
- Using the RE-AIM framework to evaluate physical activity public health programs in México.Jauregui E, Pacheco AM, Soltero EG, O'Connor TM, Castro CM, Estabrooks PA, McNeill LH, Lee REBMC Public Health
- Intraocular Pressure Changes in Emergent Surgical Decompression of Orbital Compartment Syndrome.Mohammadi F, Rashan A, Psaltis A, Janisewicz A, Li P, El-Sawy T, Nayak JVJAMA Otolaryngol Head Neck Surg
- Bilirubin production and hour-specific bilirubin levels.Bhutani VK, Wong RJ, Vreman HJ, Stevenson DKJ Perinatol
- Use of Laser-Assisted Indocyanine Green Angiography for Early Division of the Forehead Flap Pedicle.Surowitz JB, Most SPJAMA Facial Plast Surg
- Pharmacogenomic knowledge representation, reasoning and genome-based clinical decision support based on OWL 2 DL ontologies.Samwald M, Miñarro Giménez JA, Boyce RD, Freimuth RR, Adlassnig KP, Dumontier MBMC Med Inform Decis Mak
- Evaluating the Accuracy of Diffusion MRI Models in White Matter.Rokem A, Yeatman JD, Pestilli F, Kay KN, Mezer A, van der Walt S, Wandell BAPLoS One
- Bacterial recognition pathways that lead to inflammasome activation.Storek KM, Monack DMImmunol Rev
- A model humanitarian cleft mission: 312 cleft surgeries in 7 days.Fayyaz GQ, Gill NA, Ishaq I, Ganatra MA, Mahmood F, Kashif M, Alam I, Chen PK, Lo LJ, Laub DRPlast Reconstr Surg Glob Open
- Visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury.Zhang RP, Xu C, Liu Y, Li JD, Xie JNeural Regen Res
- Optimized protocol for simple extraction of high quality genomic DNA from Clostridium difficile for whole genome sequencing.Sim JH, Anikst V, Lohith A, Pourmand N, Banaei NJ Clin Microbiol
- Outcomes and costs of incorporating a multibiomarker disease activity test in the management of patients with rheumatoid arthritis.Michaud K, Strand V, Shadick NA, Degtiar I, Ford K, Michalopoulos SN, Hornberger JRheumatology (Oxford)
- Mouth breathing, "nasal disuse," and pediatric sleep-disordered breathing.Lee SY, Guilleminault C, Chiu HY, Sullivan SSSleep Breath
- Dissecting the Heterogeneity of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis.Minoia F, Davì S, Horne A, Bovis F, Demirkaya E, Akikusa J, Ayaz NA, Al-Mayouf SM, Barone P, Bica B, Bolt I, Breda L, De Cunto C, Enciso S, Gallizzi R, Griffin T, Hennon T, Horneff G, Jeng M, Kapovic AM, Lipton JM, Magni Manzoni S, Rumba-Rozenfelde I, Magalhaes CS, Sewairi WM, Stine KC, Vougiouka O, Weaver LK, Davidsone Z, De Inocencio J, Ioseliani M, Lattanzi B, Tezer H, Buoncompagni A, Picco P, Ruperto N, Martini A, Cron RQ, Ravelli A, Pediatric Rheumatology International Trials Organization, Childhood Arthritis and Rheumatology Research Alliance, Pediatric Rheumatology Collaborative Study Group, and the Histiocyte SocietyJ Rheumatol
- Combining immunotherapy with radiation for the treatment of glioblastoma.Chow KK, Hara W, Lim M, Li GJ Neurooncol
- Self-determination in the T cell repertoire.Birnbaum ME, Garcia KCImmunity
- Taking T cell priming down a Notch: signaling through Notch receptors enhances T cell sensitivity to antigen.Thauland TJ, Butte MJImmunity
- The role of adjuvant therapy in the management of head and neck merkel cell carcinoma: an analysis of 4815 patients.Chen MM, Roman SA, Sosa JA, Judson BLJAMA Otolaryngol Head Neck Surg
- Global discrepancies in the diagnosis, surgical management, and investigation of femoroacetabular impingement.Yeung M, Khan M, Schreiber VM, Adamich J, Letkemann S, Simunovic N, Bhandari M, Musahl V, Philippon MJ, Safran MR, Ayeni ORArthroscopy
- Human umbilical cord mesenchymal stromal cells rescue mice from acetaminophen-induced acute liver failure.Liu Z, Meng F, Li C, Zhou X, Zeng X, He Y, Mrsny RJ, Liu M, Hu X, Hu JF, Li TCytotherapy
- Functional assessment of multivessel coronary artery disease: ischemia-guided percutaneous coronary intervention.Schwartz JG, Fearon WFCoron Artery Dis
- Advances in understanding percutaneous coronary intervention pharmacology: ischemia, bleeding, the ISAR research group, and a commitment to progress.Harrington RA, Popma CJ, Gibson CMCoron Artery Dis
- A conditional system to specifically link disruption of protein-coding function with reporter expression in mice.Chiou SH, Kim-Kiselak C, Risca VI, Heimann MK, Chuang CH, Burds AA, Greenleaf WJ, Jacks TE, Feldser DM, Winslow MMCell Rep
- Role for Gr-1+ cells in the control of high-dose Mycobacterium bovis recombinant BCG.Panas MW, Letvin NLClin Vaccine Immunol
- Janus faces of amyloid proteins in neuroinflammation.Steinman L, Rothbard JB, Kurnellas MPJ Clin Immunol
- Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial.Piccini JP, Garg J, Patel MR, Lokhnygina Y, Goodman SG, Becker RC, Berkowitz SD, Breithardt G, Hacke W, Halperin JL, Hankey GJ, Nessel CC, Mahaffey KW, Singer DE, Califf RM, Fox KA, ROCKET AF InvestigatorsEur Heart J
- Different roles of cadherins in the assembly and structural integrity of the desmosome complex.Lowndes M, Rakshit S, Shafraz O, Borghi N, Harmon RM, Green KJ, Sivasankar S, Nelson WJJ Cell Sci
- Imaging features associated with disease progression after stereotactic ablative radiotherapy for stage I non-small-cell lung cancer.Shultz DB, Trakul N, Abelson JA, Murphy JD, Maxim PG, Le QT, Loo BW, Diehn MClin Lung Cancer
- Development of ProPhenol ligands for the diastereo- and enantioselective synthesis of β-hydroxy-α-amino esters.Trost BM, Miege FJ Am Chem Soc
- Outpatient endoscopic sinus surgery in cystic fibrosis patients: predictive factors for admission.Soudry E, Mohabir PK, Miglani A, Chen J, Nayak JV, Hwang PHInt Forum Allergy Rhinol
- Rhabdomyoblastic differentiation in metastatic melanoma: making sense of a rare but complex form of mimicry.Reilly DJ, Volchek M, Ting JW, Allan P, Findlay MWInt J Surg Pathol
- A novel in vivo method for isolating antibodies from a phage display library by neuronal retrograde transport selectively yields antibodies against p75(NTR.).Tani H, Osbourn JK, Walker EH, Rush RA, Ferguson IAMAbs
Using the RE-AIM framework to evaluate physical activity public health programs in México.
BMC Public Health. 2015;15(1):162
Authors: Jauregui E, Pacheco AM, Soltero EG, O'Connor TM, Castro CM, Estabrooks PA, McNeill LH, Lee RE
BACKGROUND: Physical activity (PA) public health programming has been widely used in Mexico; however, few studies have documented individual and organizational factors that might be used to evaluate their public health impact. The RE-AIM framework is an evaluation tool that examines individual and organizational factors of public health programs. The purpose of this study was to use the RE-AIM framework to determine the degree to which PA programs in Mexico reported individual and organizational factors and to investigate whether reporting differed by the program's funding source.
METHODS: Public health programs promoting PA were systematically identified during 2008-2013 and had to have an active program website. Initial searches produced 23 possible programs with 12 meeting inclusion criteria. A coding sheet was developed to capture behavioral, outcome and RE-AIM indicators from program websites.
RESULTS: In addition to targeting PA, five (42%) programs also targeted dietary habits and the most commonly reported outcome was change in body composition (58%). Programs reported an average of 11.1 (±3.9) RE-AIM indicator items (out of 27 total). On average, 45% reported reach indicators, 34% reported efficacy/effectiveness indicators, 60% reported adoption indicators, 40% reported implementation indicators, and 35% reported maintenance indicators. The proportion of RE-AIM indicators reported did not differ significantly for programs that were government supported (M = 10, SD = 3.1) and programs that were partially or wholly privately or corporately supported (M = 12.0, SD = 4.4).
CONCLUSION: While reach and adoption of these programs were most commonly reported, there is a need for stronger evaluation of behavioral and health outcomes before the public health impact of these programs can be established.
PMID: 25881249 [PubMed - as supplied by publisher]
Intraocular Pressure Changes in Emergent Surgical Decompression of Orbital Compartment Syndrome.
JAMA Otolaryngol Head Neck Surg. 2015 Apr 16;
Authors: Mohammadi F, Rashan A, Psaltis A, Janisewicz A, Li P, El-Sawy T, Nayak JV
Importance: Orbital compartment syndrome is an acute rise in intraorbital volume resulting in increased intraorbital pressure and possible ischemic compromise of the optic nerve. Tonometric pressure measurement of intraocular pressure can aid surgeons in the diagnosis of this condition and in choosing the need to proceed with emergent surgical intervention. In addition, we present an unexpected cause of orbital compartment syndrome following routine frontal sinus irrigation.
Observations: An emergent lateral canthotomy and cantholysis followed by endoscopic medial wall decompression were performed, with intraocular pressure measurements performed throughout the evolution of this successful, and vision sparing, set of procedures. The techniques and continuous improvements in intraocular pressure measurements are described.
Conclusions and Relevance: There are only rare reports of the progression of intraocular pressure prior to, and concurrent with, surgical orbital decompression. While no absolute threshold for intraocular pressure exists for when surgical decompression should be performed, the decision of when and which decompression procedures to undertake should be based on clinical judgment and experience. Availability of tonometry in the operating room serves to measure response to management in these rare but challenging settings where intervention may be required to prevent irreversible visual loss.
PMID: 25880995 [PubMed - as supplied by publisher]
Bilirubin production and hour-specific bilirubin levels.
J Perinatol. 2015 Apr 16;
Authors: Bhutani VK, Wong RJ, Vreman HJ, Stevenson DK
OBJECTIVE: We assessed the relative contributions of increased bilirubin production (indexed by end-tidal carbon monoxide (CO) concentrations, corrected for ambient CO (ETCOc)) to hour-specific total bilirubin (TB) levels in healthy late preterm and term newborns.
STUDY DESIGN: Post hoc analyses of concurrent ETCOc and TB (at 30±6 h of age) and follow-up TB levels at age 96±12 h and up to 168 h after birth were performed in a cohort of 641 term and late preterm infants.
RESULTS: Increased bilirubin production (hour-specific ETCOc ⩾1.7 p.p.m. at age 30±6 h) was noted in ~80%, 42% and 32% of infants in the high-, intermediate- and low-risk TB zones, respectively. One infant with TB <40th percentile and ETCOc <1.7 p.p.m. developed TB ⩾95th percentile at age 168 h, probably due to decreased bilirubin elimination.
CONCLUSIONS: Infants in the high-risk quartile of the hour-specific bilirubin nomogram have a higher mean bilirubin production. Infants with TB levels ⩾95th percentile without increased bilirubin production have impaired bilirubin elimination.Journal of Perinatology advance online publication, 16 April 2015; doi:10.1038/jp.2015.32.
PMID: 25880796 [PubMed - as supplied by publisher]
Use of Laser-Assisted Indocyanine Green Angiography for Early Division of the Forehead Flap Pedicle.
JAMA Facial Plast Surg. 2015 Apr 16;
Authors: Surowitz JB, Most SP
Importance: The paramedian forehead flap is used to reconstruct medium to large nasal defects. The staged nature, with its vascular pedicle bridging the medial eyebrow to the nose, results in significant facial deformity. Earlier division lessens this morbidity.
Objectives: To quantify flap neovascularization 2 weeks after the initial flap transfer and to describe an algorithm for earlier division of the flap pedicle in select patient populations.
Design, Setting, and Participants: We performed a prospective and retrospective study at the Ambulatory Surgery Center, Stanford University, Palo Alto, California, from October 14, 2014, through January 21, 2015. Patients with defects appropriate for paramedian forehead flap reconstruction had partial-thickness defects, vascularized tissue in more than 50% of the recipient bed, and no nicotine use. The patients underwent reconstructive surgery by a single surgeon from August 24, 2012, through September 12, 2014. Laser-assisted indocyanine green angiography was used for imaging before and immediately after the initial flap transfer, before pedicle division with the pedicle atraumatically clamped, and immediately after pedicle division and flap inset. Analysis of data and calculation of relative perfusion were performed using a postprocessing analysis toolkit.
Main Outcomes and Measures: Perfusion was calculated using the analysis toolkit as the percentage of the area of interest relative to a predetermined reference point in normal peripheral tissue.
Results: We enrolled a total of 10 patients. The mean (SD) relative perfusion of the forehead donor site before flap transfer was 61.2% (3.4%); at initial flap transfer, 81.4% (50.2% [range, 31%-214%]) (P = .70 compared with measurement before flap transfer). The mean (SD) relative perfusion of the forehead donor site was 57.5% (21.2% [range, 32%-89%]) at the time of atraumatic pedicle clamping and 58.6% (32.4% [range, 16%-127%]) after pedicle division and flap inset (P = .85 compared with measurement before flap transfer). No flap failures or other complications were observed.
Conclusions and Relevance: In select patients (those meeting the inclusion criteria), division of the pedicle at 2 weeks after the initial flap transfer is safe. Earlier pedicle division and flap transfer reduces the duration of facial deformity for the patient.
Level of Evidence: 3.
PMID: 25880793 [PubMed - as supplied by publisher]
Pharmacogenomic knowledge representation, reasoning and genome-based clinical decision support based on OWL 2 DL ontologies.
BMC Med Inform Decis Mak. 2015;15(1):12
Authors: Samwald M, Miñarro Giménez JA, Boyce RD, Freimuth RR, Adlassnig KP, Dumontier M
BACKGROUND: Every year, hundreds of thousands of patients experience treatment failure or adverse drug reactions (ADRs), many of which could be prevented by pharmacogenomic testing. However, the primary knowledge needed for clinical pharmacogenomics is currently dispersed over disparate data structures and captured in unstructured or semi-structured formalizations. This is a source of potential ambiguity and complexity, making it difficult to create reliable information technology systems for enabling clinical pharmacogenomics.
METHODS: We developed Web Ontology Language (OWL) ontologies and automated reasoning methodologies to meet the following goals: 1) provide a simple and concise formalism for representing pharmacogenomic knowledge, 2) finde errors and insufficient definitions in pharmacogenomic knowledge bases, 3) automatically assign alleles and phenotypes to patients, 4) match patients to clinically appropriate pharmacogenomic guidelines and clinical decision support messages and 5) facilitate the detection of inconsistencies and overlaps between pharmacogenomic treatment guidelines from different sources. We evaluated different reasoning systems and test our approach with a large collection of publicly available genetic profiles.
RESULTS: Our methodology proved to be a novel and useful choice for representing, analyzing and using pharmacogenomic data. The Genomic Clinical Decision Support (Genomic CDS) ontology represents 336 SNPs with 707 variants; 665 haplotypes related to 43 genes; 22 rules related to drug-response phenotypes; and 308 clinical decision support rules. OWL reasoning identified CDS rules with overlapping target populations but differing treatment recommendations. Only a modest number of clinical decision support rules were triggered for a collection of 943 public genetic profiles. We found significant performance differences across available OWL reasoners.
CONCLUSIONS: The ontology-based framework we developed can be used to represent, organize and reason over the growing wealth of pharmacogenomic knowledge, as well as to identify errors, inconsistencies and insufficient definitions in source data sets or individual patient data. Our study highlights both advantages and potential practical issues with such an ontology-based approach.
PMID: 25880555 [PubMed - as supplied by publisher]
Evaluating the Accuracy of Diffusion MRI Models in White Matter.
PLoS One. 2015;10(4):e0123272
Authors: Rokem A, Yeatman JD, Pestilli F, Kay KN, Mezer A, van der Walt S, Wandell BA
Models of diffusion MRI within a voxel are useful for making inferences about the properties of the tissue and inferring fiber orientation distribution used by tractography algorithms. A useful model must fit the data accurately. However, evaluations of model-accuracy of commonly used models have not been published before. Here, we evaluate model-accuracy of the two main classes of diffusion MRI models. The diffusion tensor model (DTM) summarizes diffusion as a 3-dimensional Gaussian distribution. Sparse fascicle models (SFM) summarize the signal as a sum of signals originating from a collection of fascicles oriented in different directions. We use cross-validation to assess model-accuracy at different gradient amplitudes (b-values) throughout the white matter. Specifically, we fit each model to all the white matter voxels in one data set and then use the model to predict a second, independent data set. This is the first evaluation of model-accuracy of these models. In most of the white matter the DTM predicts the data more accurately than test-retest reliability; SFM model-accuracy is higher than test-retest reliability and also higher than the DTM model-accuracy, particularly for measurements with (a) a b-value above 1000 in locations containing fiber crossings, and (b) in the regions of the brain surrounding the optic radiations. The SFM also has better parameter-validity: it more accurately estimates the fiber orientation distribution function (fODF) in each voxel, which is useful for fiber tracking.
PMID: 25879933 [PubMed - as supplied by publisher]
Bacterial recognition pathways that lead to inflammasome activation.
Immunol Rev. 2015 May;265(1):112-129
Authors: Storek KM, Monack DM
Inflammasomes are multi-protein signaling platforms that upon activation trigger the maturation of the pro-inflammatory cytokines, interleukin-1β (IL-1β) and IL-18, and cell death. Inflammasome sensors detect microbial and host-derived molecules. Here, we review the mechanisms of inflammasome activation triggered by bacterial infection, primarily focusing on two model intracellular bacterial pathogens, Francisella novicida and Salmonella typhimurium. We discuss the complex relationship between bacterial recognition through direct and indirect detection by inflammasome sensors. We highlight regulation mechanisms that potentiate or limit inflammasome activation. We discuss the importance of caspase-1 and caspase-11 in host defense, and we examine the downstream consequences of inflammasome activation within the context of bacterial infections.
PMID: 25879288 [PubMed - as supplied by publisher]
A model humanitarian cleft mission: 312 cleft surgeries in 7 days.
Plast Reconstr Surg Glob Open. 2015 Mar;3(3):e313
Authors: Fayyaz GQ, Gill NA, Ishaq I, Ganatra MA, Mahmood F, Kashif M, Alam I, Chen PK, Lo LJ, Laub DR
BACKGROUND: There are many countries in the world where patients with cleft lip and palate cannot get access to specialized cleft care units. Cleft missions play an important role in providing surgical care to the areas of the world with limited resources. This article presents a model of cleft missions that can be adopted in many countries where expertise is available but resources are limited. Through proper utilization of local human resource, this type of mission can be a cost-effective and robust way of treating patients with cleft in countries with approximately 52% of the world's population.
METHODS: We present a case series of patients of one of our cleft missions carried out in Khairpur, Pakistan, in March 2014 over a period of 7 days. Specific details concerning the organization of mission, gathering of patients, preparation for surgery, and carrying out surgical procedures in a safe and swift manner are presented.
RESULTS: A total of 312 patients were operated on in 7 days. There were 145 patients with cleft lip and 167 patients with cleft palate. There were 187 male and 125 female patients with mean age of 7 years. Contemporary operative techniques were utilized to repair different types of cleft lip and palate. Of 167 patients, only 16 developed fistula.
CONCLUSION: A locoregional cleft team can be more effective to care for the patients with cleft in countries where surgical and other expertise can be utilized by proper organization of cleft missions on a national level.
PMID: 25878924 [PubMed]
Visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury.
Neural Regen Res. 2015 Mar;10(3):404-11
Authors: Zhang RP, Xu C, Liu Y, Li JD, Xie J
An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T7-8. Superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cord via the subarachnoid space. An outer magnetic field was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesenchymal stem cells reached the lesion site in these rats than in those without magnetic guidance or superparamagnetic iron oxide labeling, and immunofluorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan (BBB) locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guidance. Our data confirm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic field guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively tracked in vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury.
PMID: 25878588 [PubMed]
Optimized protocol for simple extraction of high quality genomic DNA from Clostridium difficile for whole genome sequencing.
J Clin Microbiol. 2015 Apr 15;
Authors: Sim JH, Anikst V, Lohith A, Pourmand N, Banaei N
Successful sequencing of Clostridium difficile genome requires high-quality genomic DNA (gDNA) as starting material. gDNA extraction using conventional methods is laborious. We describe an optimized method for simple extraction of C. difficile gDNA using QIAamp DNA Mini Kit, which yielded high-quality sequence reads on the Illumina Miseq platform.
PMID: 25878343 [PubMed - as supplied by publisher]
Outcomes and costs of incorporating a multibiomarker disease activity test in the management of patients with rheumatoid arthritis.
Rheumatology (Oxford). 2015 Apr 15;
Authors: Michaud K, Strand V, Shadick NA, Degtiar I, Ford K, Michalopoulos SN, Hornberger J
OBJECTIVE: The multibiomarker disease activity (MBDA) blood test has been clinically validated as a measure of disease activity in patients with RA. We aimed to estimate the effect of the MBDA test on physical function for patients with RA (based on HAQ), quality-adjusted life years and costs over 10 years.
METHODS: A decision analysis was conducted to quantify the effect of using the MBDA test on RA-related outcomes and costs to private payers and employers. Results of a clinical management study reporting changes to anti-rheumatic drug recommendations after use of the MBDA test informed clinical utility. The effect of treatment changes on HAQ was derived from 5 tight-control and 13 treatment-switch trials. Baseline HAQ scores and the HAQ score relationship with medical costs and quality of life were derived from published National Data Bank for Rheumatic Diseases data.
RESULTS: Use of the MBDA test is projected to improve HAQ scores by 0.09 units in year 1, declining to 0.02 units after 10 years. Over the 10 year time horizon, quality-adjusted life years increased by 0.08 years and costs decreased by US$457 (cost savings in disability-related medical costs, US$659; in productivity costs, US$2137). The most influential variable in the analysis was the effect of the MBDA test on clinician treatment recommendations and subsequent HAQ changes.
CONCLUSION: The MBDA test aids in the assessment of disease activity in patients with RA by changing treatment decisions, improving the functional status of patients and cost savings. Further validation is ongoing and future longitudinal studies are warranted.
PMID: 25877911 [PubMed - as supplied by publisher]
Mouth breathing, "nasal disuse," and pediatric sleep-disordered breathing.
Sleep Breath. 2015 Apr 16;
Authors: Lee SY, Guilleminault C, Chiu HY, Sullivan SS
BACKGROUND: Adenotonsillectomy (T&A) may not completely eliminate sleep-disordered breathing (SDB), and residual SDB can result in progressive worsening of abnormal breathing during sleep. Persistence of mouth breathing post-T&As plays a role in progressive worsening through an increase of upper airway resistance during sleep with secondary impact on orofacial growth.
METHODS: Retrospective study on non-overweight and non-syndromic prepubertal children with SDB treated by T&A with pre- and post-surgery clinical and polysomnographic (PSG) evaluations including systematic monitoring of mouth breathing (initial cohort). All children with mouth breathing were then referred for myofunctional treatment (MFT), with clinical follow-up 6 months later and PSG 1 year post-surgery. Only a limited subgroup followed the recommendations to undergo MFT with subsequent PSG (follow-up subgroup).
RESULTS: Sixty-four prepubertal children meeting inclusion criteria for the initial cohort were investigated. There was significant symptomatic improvement in all children post-T&A, but 26 children had residual SDB with an AHI > 1.5 events/hour and 35 children (including the previous 26) had evidence of "mouth breathing" during sleep as defined [minimum of 44 % and a maximum of 100 % of total sleep time, mean 69 ± 11 % "mouth breather" subgroup and mean 4 ± 3.9 %, range 0 and 10.3 % "non-mouth breathers"]. Eighteen children (follow-up cohort), all in the "mouth breathing" group, were investigated at 1 year follow-up with only nine having undergone 6 months of MFT. The non- MFT subjects were significantly worse than the MFT-treated cohort. MFT led to normalization of clinical and PSG findings.
CONCLUSION: Assessment of mouth breathing during sleep should be systematically performed post-T&A and the persistence of mouth breathing should be treated with MFT.
PMID: 25877805 [PubMed - as supplied by publisher]
Dissecting the Heterogeneity of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis.
J Rheumatol. 2015 Apr 15;
Authors: Minoia F, Davì S, Horne A, Bovis F, Demirkaya E, Akikusa J, Ayaz NA, Al-Mayouf SM, Barone P, Bica B, Bolt I, Breda L, De Cunto C, Enciso S, Gallizzi R, Griffin T, Hennon T, Horneff G, Jeng M, Kapovic AM, Lipton JM, Magni Manzoni S, Rumba-Rozenfelde I, Magalhaes CS, Sewairi WM, Stine KC, Vougiouka O, Weaver LK, Davidsone Z, De Inocencio J, Ioseliani M, Lattanzi B, Tezer H, Buoncompagni A, Picco P, Ruperto N, Martini A, Cron RQ, Ravelli A, Pediatric Rheumatology International Trials Organization, Childhood Arthritis and Rheumatology Research Alliance, Pediatric Rheumatology Collaborative Study Group, and the Histiocyte Society
OBJECTIVE: To seek insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey.
METHODS: International pediatric rheumatologists and hemato-oncologists entered their patient data, collected retrospectively, in a Web-based database. The demographic, clinical, laboratory, histopathologic, therapeutic, and outcome data were analyzed in relation to (1) geographic location of caring hospital, (2) subspecialty of attending physician, (3) demonstration of hemophagocytosis, and (4) severity of clinical course.
RESULTS: A total of 362 patients were included by 95 investigators from 33 countries. Demographic, clinical, laboratory, and histopathologic features were comparable among patients seen in diverse geographic areas or by different pediatric specialists. Patients seen in North America were given biologics more frequently. Patients entered by pediatric hemato-oncologists were treated more commonly with biologics and etoposide, whereas patients seen by pediatric rheumatologists more frequently received cyclosporine. Patients with demonstration of hemophagocytosis had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen, and were more frequently administered cyclosporine, intravenous immunoglobulin (IVIG), and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, had more full-blown clinical picture, and were more commonly given cyclosporine, IVIG, and etoposide.
CONCLUSION: The clinical spectrum of MAS is comparable across patients seen in different geographic settings or by diverse pediatric subspecialists. There was a disparity in the therapeutic choices among physicians that underscores the need to establish uniform therapeutic protocols.
PMID: 25877504 [PubMed - as supplied by publisher]
Combining immunotherapy with radiation for the treatment of glioblastoma.
J Neurooncol. 2015 Apr 17;
Authors: Chow KK, Hara W, Lim M, Li G
Glioblastoma is a devastating cancer with universally poor outcomes in spite of current standard multimodal therapy. Immunotherapy is an attractive new treatment modality given its potential for exquisite specificity and its favorable side effect profile; however, clinical trials of immunotherapy in GBM have thus far shown modest benefit. Optimally combining radiation with immunotherapy may be the key to unlocking the potential of both therapies given the evidence that radiation can enhance anti-tumor immunity. Here we review this evidence and discuss considerations for combined therapy.
PMID: 25877468 [PubMed - as supplied by publisher]
Self-determination in the T cell repertoire.
Immunity. 2015 Jan 20;42(1):8-10
Authors: Birnbaum ME, Garcia KC
The number of T cells specific for various antigens can vary dramatically. In this issue of Immunity, Nelson et al. (2015) report that these differences might be, at least in part, set by the number of cross-reactive self peptides encountered by T cells during development.
PMID: 25607452 [PubMed - indexed for MEDLINE]
Taking T cell priming down a Notch: signaling through Notch receptors enhances T cell sensitivity to antigen.
Immunity. 2015 Jan 20;42(1):6-8
Authors: Thauland TJ, Butte MJ
Notch receptors are widely expressed and have recognized functions in thymocytes and mature T cells. In this issue, Laky et al. (2015) show that Notch interactions with Delta-like ligand 4 (DLL4) amplify priming of naive T cells.
PMID: 25607451 [PubMed - indexed for MEDLINE]
The role of adjuvant therapy in the management of head and neck merkel cell carcinoma: an analysis of 4815 patients.
JAMA Otolaryngol Head Neck Surg. 2015 Feb;141(2):137-41
Authors: Chen MM, Roman SA, Sosa JA, Judson BL
IMPORTANCE: Merkel cell carcinoma (MCC) is a rare neuroendocrine malignant neoplasm that most commonly occurs in the head and neck and is rapidly increasing in incidence. The role of adjuvant chemoradiotherapy (CRT) in the management of head and neck MCC remains controversial.
OBJECTIVE: To evaluate the association between different adjuvant therapies and survival in head and neck MCC.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of adult patients with head and neck MCC who had surgery recorded in the National Cancer Data Base from 1998 to 2011.
INTERVENTIONS: Surgical excision, adjuvant radiation therapy (RT), or adjuvant CRT.
MAIN OUTCOMES AND MEASURES: Our main outcome was overall survival (OS). Statistical analysis included χ2, t tests, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis.
RESULTS: We identified 4815 patients; 92.0% underwent standard surgical excision, and 8.0% underwent Mohs surgery. On multivariate analysis, age at least 75 years (hazard ratio [HR], 2.83 [95% CI, 1.82-4.41]), larger tumor size, positive margins (HR, 1.52 [95% CI, 1.25-1.85]), and metastatic lymph nodes (HR, 2.29 [95% CI, 1.84-2.85]) were independently associated with decreased OS. Postoperative CRT (HR, 0.62 [95% CI, 0.47-0.81]) and RT (HR, 0.80 [95% CI, 0.70-0.92]) provided a survival benefit over surgery alone. Adjuvant CRT was associated with improved OS over adjuvant RT in patients with positive margins (HR, 0.48 [95% CI, 0.25-0.93]), tumor size at least 3 cm (HR, 0.52 [95% CI, 0.30-0.90]), and male sex (HR, 0.69 [95% CI, 0.50-0.94]).
CONCLUSIONS AND RELEVANCE: To our knowledge, this the first study examining the role of adjuvant CRT in head and neck MCC. Results suggest that adjuvant CRT may help improve survival in high-risk patients, such as males and those with positive margins and larger tumors.
PMID: 25474617 [PubMed - indexed for MEDLINE]
Global discrepancies in the diagnosis, surgical management, and investigation of femoroacetabular impingement.
Arthroscopy. 2014 Dec;30(12):1625-33
Authors: Yeung M, Khan M, Schreiber VM, Adamich J, Letkemann S, Simunovic N, Bhandari M, Musahl V, Philippon MJ, Safran MR, Ayeni OR
PURPOSE: The purpose of this study was to review the global pattern of surgical management of femoroacetabular impingement (FAI), particularly in diagnosis, outcome measurement, and management.
METHODS: We performed a systematic search in duplicate for surgical studies addressing FAI published up to June 2013. Study parameters, including sample size, study location, surgical intervention technique, diagnostic imaging, outcome measures used, sex distribution, and level of evidence, were obtained. The number of trials and cumulative sample size were analyzed. The surgical interventions, sex distribution, outcome measures, and diagnostic imaging used were compared between geographic regions.
RESULTS: We identified 105 studies reporting surgical interventions for FAI. Most studies were completed in North America (52 studies, 3,629 patients) and in Europe (44 studies, 3,745 patients). Asia (3 studies, 49 patients) and Oceania (6 studies, 394 patients) had smaller contributions. There were no studies from South America or Africa. Most research performed in North America, Europe, and Oceania investigated arthroscopic FAI surgery (55% of studies) followed by surgical dislocation (33%), and miniopen (15%) and combined approaches (8%). Methods of diagnosis were consistent worldwide, with radiography being the mainstay of diagnosis (84% of studies). Case series were the most common type of study globally (75% of studies). Outcome measures varied by region; Harris hip scores were most common in North America, Oceania, and Asia, whereas Non-Arthritic Hip Scores and Western Ontario McMaster scores predominated in Europe.
CONCLUSIONS: Global surgical trends for FAI show a predominance of North American and European studies, studies of lower level evidence, and inconsistent use of outcome measures. However, patterns of diagnostic imaging, sex proportions, and predominance of arthroscopic techniques are consistent worldwide. Future research should focus on development of reliable validated outcome measures and international collaboration to conduct high-quality research and improve our understanding of FAI diagnosis and management.
LEVEL OF EVIDENCE: Level IV, systematic review of Level I-IV studies.
PMID: 25150405 [PubMed - indexed for MEDLINE]
Human umbilical cord mesenchymal stromal cells rescue mice from acetaminophen-induced acute liver failure.
Cytotherapy. 2014 Sep;16(9):1207-19
Authors: Liu Z, Meng F, Li C, Zhou X, Zeng X, He Y, Mrsny RJ, Liu M, Hu X, Hu JF, Li T
BACKGROUND AIMS: Acute liver failure (ALF), a life-threatening disease characterized by the sudden loss of hepatic function, can occur after an accidental or intentional acetaminophen overdose.
METHODS: With the use of an ALF mouse model, we examined both the preventive and therapeutic potential of intravenously administered human umbilical cord-derived mesenchymal stromal cells (hUCMSCs). Primary hUCMSCs were purified from freshly collected full-term umbilical cords and intravenously transplanted into BALB/c mice either before and after ALF induced by acetaminophen intoxication. We found that hUCMSCs significantly improved survival rates and relative liver weight of mice in both pre-ALF and post-ALF animals. Correspondingly, serum levels of markers that reflect hepatic injury (ie, aspartate aminotransferase, alanine aminotransferase and total bilirubin) were significantly attenuated in the group receiving hUCMSC therapy.
RESULTS: Mechanistically, we found that the protective potential of intravenously administered hUCMSCs was mediated by paracrine pathways that involved antioxidants (glutathione, superoxide dismutase), the reduction of inflammatory agents (tumor necrosis factor-α, interleukin-6) and elevated serum levels of hepatocyte growth factor.
CONCLUSIONS: Through these paracrine effects, intravenously administered hUCMSCs reduced hepatic necrosis/apoptosis and enhanced liver regeneration. Thus, our data demonstrate that intravenously administered hUCMSCs may be useful in the prevention or treatment of acetaminophen-induced ALF.
PMID: 25108650 [PubMed - indexed for MEDLINE]
Functional assessment of multivessel coronary artery disease: ischemia-guided percutaneous coronary intervention.
Coron Artery Dis. 2014 Sep;25(6):521-8
Authors: Schwartz JG, Fearon WF
Invasive evaluation and treatment of coronary artery disease (CAD) has traditionally been based upon coronary angiography to determine the need for and the success of revascularization. However, coronary angiography augmented with fractional flow reserve (FFR) creates a paradigm shift, providing a more complete functional assessment of coronary lesions. Measuring FFR to identify ischemic lesions and guide revascularization results in fewer adverse outcomes, including persistent angina, myocardial infarction, and mortality. An ischemic lesion identified by FFR is more likely to lead to adverse events when compared with an angiographically similar lesion with nonischemic FFR when both are treated medically. Although the mechanism explaining this is unclear, it is likely multifactorial, including the impact of mechanical forces, upregulation of inflammatory mediators, and the amount of distal myocardial tissue at risk. Using both anatomic and ischemia-guided assessments (such as the Functional SYNTAX Score) aids in the therapeutic decision-making process in patients with multivessel CAD. This review focuses on the evidence for FFR-guided management of multivessel CAD.
PMID: 25072658 [PubMed - indexed for MEDLINE]
Advances in understanding percutaneous coronary intervention pharmacology: ischemia, bleeding, the ISAR research group, and a commitment to progress.
Coron Artery Dis. 2014 Sep;25(6):453-5
Authors: Harrington RA, Popma CJ, Gibson CM
PMID: 25072657 [PubMed - indexed for MEDLINE]
A conditional system to specifically link disruption of protein-coding function with reporter expression in mice.
Cell Rep. 2014 Jun 26;7(6):2078-86
Authors: Chiou SH, Kim-Kiselak C, Risca VI, Heimann MK, Chuang CH, Burds AA, Greenleaf WJ, Jacks TE, Feldser DM, Winslow MM
Conditional gene deletion in mice has contributed immensely to our understanding of many biological and biomedical processes. Despite an increasing awareness of nonprotein-coding functional elements within protein-coding transcripts, current gene-targeting approaches typically involve simultaneous ablation of noncoding elements within targeted protein-coding genes. The potential for protein-coding genes to have additional noncoding functions necessitates the development of novel genetic tools capable of precisely interrogating individual functional elements. We present a strategy that couples Cre/loxP-mediated conditional gene disruption with faithful GFP reporter expression in mice in which Cre-mediated stable inversion of a splice acceptor-GFP-splice donor cassette concurrently disrupts protein production and creates a GFP fusion product. Importantly, cassette inversion maintains physiologic transcript structure, thereby ensuring proper microRNA-mediated regulation of the GFP reporter, as well as maintaining expression of nonprotein-coding elements. To test this potentially generalizable strategy, we generated and analyzed mice with this conditional knockin reporter targeted to the Hmga2 locus.
PMID: 24931605 [PubMed - indexed for MEDLINE]
Role for Gr-1+ cells in the control of high-dose Mycobacterium bovis recombinant BCG.
Clin Vaccine Immunol. 2014 Aug;21(8):1120-7
Authors: Panas MW, Letvin NL
Mycobacterium bovis bacillus Calmette-Guérin (BCG) is an attractive target for development as a live vaccine vector delivering transgenic antigens from HIV and other pathogens. Most studies aimed at defining the clearance of BCG have been performed at doses between 10(2) and 10(4) CFU. Interestingly, however, recombinant BCG (rBCG) administered at doses of >10(6) CFU effectively generates antigen-specific T-cell responses and primes for heterologous boost responses. Thus, defining clearance at high doses might aid in the optimization of rBCG as a vector. In this study, we used bioluminescence imaging to examine the kinetics of rBCG transgene expression and clearance in mice immunized with 5 × 10(7) CFU rBCG expressing luciferase. Similar to studies using low-dose rBCG, our results demonstrate that the adaptive immune response is necessary for long-term control of rBCG beginning 9 days after immunizing mice. However, in contrast to these reports, we observed that the majority of mycobacterial antigen was eliminated prior to day 9. By examining knockout and antibody-mediated depletion mouse models, we demonstrate that the rapid clearance of rBCG occurs in the first 24 h and is mediated by Gr-1(+) cells. As Gr-1(+) granulocytes have been described as having no impact on BCG clearance at low doses, our results reveal an unappreciated role for Gr-1(+) neutrophils and inflammatory monocytes in the clearance of high-dose rBCG. This work demonstrates the potential of applying bioluminescence imaging to rBCG in order to gain an understanding of the immune response and increase the efficacy of rBCG as a vaccine vector.
PMID: 24920602 [PubMed - indexed for MEDLINE]
Janus faces of amyloid proteins in neuroinflammation.
J Clin Immunol. 2014 Jul;34 Suppl 1:S61-3
Authors: Steinman L, Rothbard JB, Kurnellas MP
Amyloid forming molecules are generally considered harmful. In Alzheimer's Disease two amyloid molecules Aβ A4 and tau vie for consideration as the main pathogenic culprit. But molecules obey the laws of chemistry and defy the way we categorize them as humans with our well-known proclivities to bias in our reasoning. We have been exploring the brains of multiple sclerosis patients to identify molecules that are associated with protection from inflammation and degeneration. In 2001 we noted that aB crystallin (cryab) was the most abundant transcript found in MS lesions, but not in healthy brains. Cryab can reverse paralysis and attenuate inflammation in several models of inflammation including experimental autoimmune encephalomyelitis (EAE), and various models of ischemia. Cryab is an amyloid forming molecule. We have identified a core structure common to many amyloids including amyloid protein Aβ A4, tau, amylin, prion protein, serum amyloid protein P, and cryab. The core hexapeptide structure is highly immune suppressive and can reverse paralysis in EAE when administered systemically. Administration of this amyloid forming hexapeptide quickly lowers inflammatory cytokines in plasma like IL-6 and IL-2. The hexapeptide bind a set of proinflammatory mediators in plasma, including acute phase reactants and complement components. The beneficial properties of amyloid forming hexapeptides provide a potential new therapeutic direction. These experiments indicate that amyloid forming molecules have Janus faces, providing unexpected benefit for neuroinflammatory conditions.
PMID: 24711007 [PubMed - indexed for MEDLINE]
Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial.
Eur Heart J. 2014 Jul 21;35(28):1873-80
Authors: Piccini JP, Garg J, Patel MR, Lokhnygina Y, Goodman SG, Becker RC, Berkowitz SD, Breithardt G, Hacke W, Halperin JL, Hankey GJ, Nessel CC, Mahaffey KW, Singer DE, Califf RM, Fox KA, ROCKET AF Investigators
AIMS: There are no data regarding management and outcomes of major bleeding events in patients treated with oral factor Xa inhibitors.
METHODS AND RESULTS: Using data from ROCKET AF, we analysed the management and outcomes of major bleeding overall and according to the randomized treatment. During a median follow-up of 1.9 years, 779 (5.5%) patients experienced major bleeding at a rate of 3.52 events/100 patient-years with a similar event rate in each arm (n = 395 rivaroxaban vs. n = 384 warfarin). The median number of transfused packed red blood cells (PRBC) per episode was similar in both arms [2 (25th, 75th: 2, 4) units]. Overall, few transfusions of whole blood (n = 14), platelets (n = 10), or cryoprecipitate (n = 2) were used. Transfusion of fresh frozen plasma (FFP) was significantly less in the rivaroxaban arm (n = 45 vs. n = 81 units) after adjustment for covariates [odds ratio (OR) 0.43 (95% CI 0.29-0.66); P < 0.0001]. Prothrombin complex concentrates (PCC) were administered less in the rivaroxaban arm (n = 4 vs. n = 9). Outcomes after major bleeding, including stroke or non-central nervous system embolism (4.7% rivaroxaban vs. 5.4% warfarin; HR 0.89; 95% CI 0.42-1.88) and all-cause death (20.4% rivaroxaban vs. 26.1% warfarin; HR 0.69, 95% CI 0.46-1.04) were similar in patients treated with rivaroxaban and warfarin (interaction P = 0.51 and 0.11).
CONCLUSION: Among high-risk patients with atrial fibrillation who experienced major bleeding in ROCKET AF, the use of FFP and PCC was less among those allocated rivaroxaban compared with warfarin. However, use of PRBCs and outcomes after bleeding were similar among patients randomized to rivaroxaban or to warfarin.
PMID: 24658769 [PubMed - indexed for MEDLINE]
Different roles of cadherins in the assembly and structural integrity of the desmosome complex.
J Cell Sci. 2014 May 15;127(Pt 10):2339-50
Authors: Lowndes M, Rakshit S, Shafraz O, Borghi N, Harmon RM, Green KJ, Sivasankar S, Nelson WJ
Adhesion between cells is established by the formation of specialized intercellular junctional complexes, such as desmosomes. Desmosomes contain isoforms of two members of the cadherin superfamily of cell adhesion proteins, desmocollins (Dsc) and desmogleins (Dsg), but their combinatorial roles in desmosome assembly are not understood. To uncouple desmosome assembly from other cell-cell adhesion complexes, we used micro-patterned substrates of Dsc2aFc and/or Dsg2Fc and collagen IV; we show that Dsc2aFc, but not Dsg2Fc, was necessary and sufficient to recruit desmosome-specific desmoplakin into desmosome puncta and produce strong adhesive binding. Single-molecule force spectroscopy showed that monomeric Dsc2a, but not Dsg2, formed Ca(2+)-dependent homophilic bonds, and that Dsg2 formed Ca(2+)-independent heterophilic bonds with Dsc2a. A W2A mutation in Dsc2a inhibited Ca(2+)-dependent homophilic binding, similar to classical cadherins, and Dsc2aW2A, but not Dsg2W2A, was excluded from desmosomes in MDCK cells. These results indicate that Dsc2a, but not Dsg2, is required for desmosome assembly through homophilic Ca(2+)- and W2-dependent binding, and that Dsg2 might be involved later in regulating a switch to Ca(2+)-independent adhesion in mature desmosomes.
PMID: 24610950 [PubMed - indexed for MEDLINE]
Imaging features associated with disease progression after stereotactic ablative radiotherapy for stage I non-small-cell lung cancer.
Clin Lung Cancer. 2014 Jul;15(4):294-301.e3
Authors: Shultz DB, Trakul N, Abelson JA, Murphy JD, Maxim PG, Le QT, Loo BW, Diehn M
INTRODUCTION/BACKGROUND: The aim of this study was to identify imaging-based predictors of progression in patients treated with SABR for stage I NSCLC.
PATIENTS AND METHODS: Between March 2003 and December 2012, 117 patients with stage I NSCLC meeting our study criteria were treated with SABR at Stanford University. Median follow-up was 17 months (range, 3-74 months) for all patients and 19 months for living patients (range, 3-74 months). Tumors were classified according to whether or not they contacted the pleura adjacent to the chest wall or mediastinum (MP), according to their maximum dimension based on computed tomography scans, and, for 102 patients who had archived pretreatment fluorine-18 fluorodeoxyglucose positron-emission tomography scans, according to SUVmax.
RESULTS: Ten patients (9%) developed local progression, 17 (15%) developed regional progression, and 19 (16%) developed distant metastasis. Two-year freedom from local progression, freedom from regional progression, and freedom from distant metastasis (FFDM) were 88%, 83%, and 83%, respectively. Overall survival was 70% at 2 years. FFDM was significantly associated with MP contact, maximum tumor dimension, and SUVmax, and these variables could be combined into an exploratory prognostic index that identified patients at highest risk for developing metastases.
CONCLUSION: In our cohort, noninvasive, imaging-based features were associated with distant progression after SABR for early stage NSCLC. If validated, our prognostic index could allow identification of patients who might benefit from systemic therapy after SABR.
PMID: 24594400 [PubMed - indexed for MEDLINE]
Development of ProPhenol ligands for the diastereo- and enantioselective synthesis of β-hydroxy-α-amino esters.
J Am Chem Soc. 2014 Feb 26;136(8):3016-9
Authors: Trost BM, Miege F
A zinc-ProPhenol-catalyzed direct asymmetric aldol reaction between glycine Schiff bases and aldehydes is reported. The design and synthesis of new ProPhenol ligands bearing 2,5-trans-disubstituted pyrrolidines was essential for the success of this process. The transformation operates at room temperature and affords syn β-hydroxy-α-amino esters in high yields with good to excellent levels of diastereo- and enantioselectivity.
PMID: 24502188 [PubMed - indexed for MEDLINE]
Outpatient endoscopic sinus surgery in cystic fibrosis patients: predictive factors for admission.
Int Forum Allergy Rhinol. 2014 May;4(5):416-21
Authors: Soudry E, Mohabir PK, Miglani A, Chen J, Nayak JV, Hwang PH
BACKGROUND: An increasing number of adult patients with cystic fibrosis (CF) are becoming candidates for elective endoscopic sinus surgery (ESS). We sought to identify perioperative factors in this patient population that were predictive of postoperative admission.
METHODS: Retrospective chart review of CF patients who underwent ESS during the years 2005 through 2012. Multiple preoperative, intraoperative, and immediate postoperative variables were analyzed.
RESULTS: Thirty-three patients who underwent 37 outpatient ESSs were identified. Successful same-day discharge was observed in 54%. In 46% of cases, postoperative admission was necessary, with a mean postoperative stay of 1.4 days. Pulmonary function, CF-related comorbidities, and history of lung transplant were not predictors of postoperative admission. Univariate analysis demonstrated that patients were more likely to be admitted if they had 1 of the following conditions: history of ≥4 prior ESS; procedure duration >2.5 hours; intraoperative blood loss greater than 150 mL; increased immediate postoperative pain scores; or larger narcotic requirements for pain control. On logistic regression analysis, a maximum pain score ≥ 7 out of 10 in the postanesthesia recovery unit was the only significant predisposing factor for postoperative admission.
CONCLUSION: Although over 50% of adult CF patients can successfully undergo ESS on a same-day discharge basis, it is prudent to have contingent plans for potential inpatient observation postoperatively. Multivariate analysis suggests that preoperative demographics and pulmonary status cannot predict the need for postoperative admission, whereas higher pain scores in the postanesthesia care unit are predictive of the necessity for inpatient observation.
PMID: 24431198 [PubMed - indexed for MEDLINE]
Rhabdomyoblastic differentiation in metastatic melanoma: making sense of a rare but complex form of mimicry.
Int J Surg Pathol. 2014 Sep;22(6):520-4
Authors: Reilly DJ, Volchek M, Ting JW, Allan P, Findlay MW
A case of melanoma with rhabdomyoblastic differentiation is presented in the context of the previously reported cases. The emerging literature seeking to identify the molecular basis of rhabdoid and rhabdomyoblastic differentiation, as well as their poor prognosis, is reviewed. The combination of a diverse range of morphology and the potential for spontaneous primary tumor regression, despite metastasis, makes the accurate diagnosis of melanoma challenging. Histopathology review is often recommended in these cases, as is referral to a specialized cancer center for discussion in a multidisciplinary meeting. Improved recognition of this rare pattern of melanoma morphology may provide the means for omics-based techniques to identify novel therapeutic targets to improve the prognostic outlook for these patients.
PMID: 24275885 [PubMed - indexed for MEDLINE]
A novel in vivo method for isolating antibodies from a phage display library by neuronal retrograde transport selectively yields antibodies against p75(NTR.).
MAbs. 2013 May-Jun;5(3):471-8
Authors: Tani H, Osbourn JK, Walker EH, Rush RA, Ferguson IA
The neurotrophin receptor p75(NTR) is utilized by a variety of pathogens to gain entry into the central nervous system (CNS). We tested if this entry portal might be exploited using a phage display library to isolate internalizing antibodies that target the CNS in vivo. By applying a phage library that expressed human single chain variable fragment (scFv) antibodies on their surface to a transected sciatic nerve, we showed that (1) phage conjugated to anti-p75(NTR) antibody or phage scFv library pre-panned against p75(NTR) are internalized by neurons expressing p75(NTR); (2) subsequent retrograde axonal transport separates internalized phage from the applied phage; and, (3) internalized phage can be recovered from a proximal ligature made on a nerve. This approach resulted in 13-fold increase in the number of phage isolated from the injured nerve compared with the starting population, and isolation of 18 unique internalizing p75(NTR) antibodies that were transported from the peripheral nerve into the spinal cord, through the blood-brain barrier. In addition, antibodies recognizing other potentially internalized antigens were identified through in vivo selection using a fully diverse library. Because p75(NTR) expression is upregulated in motor neurons in response to injury and in disease, the p75(NTR) antibodies may have substantial potential for cell-targeted drug/gene delivery. In addition, this novel selection method provides the potential to generate panels of antibodies that could be used to identify further internalization targets, which could aid drug delivery across the blood-brain barrier.
PMID: 23549155 [PubMed - indexed for MEDLINE]
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