bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Next-Generation Sequencing and Avatar Mouse Models for Personalized Cancer Treatment
Authors: Garralda Elena , Paz Keren , López-Casas Pedro P. , Jones Siân , Katz Amanda , Kann Lisa M. , López-Rios Fernando , Sarno Francesca , Al-Shahrour Fátima , Vasquez David , Bruckheimer Elizabeth , Angiuoli Samuel V. , Calles Antonio , Diaz Luis A. , Velculescu Victor E. , Valencia Alfonso , Sidransky David , Hidalgo Manuel
Published: March 2014

Background: Current technology permits an unbiased massive analysis of somatic genetic alterations from tumor DNA as well as the generation of individualized mouse xenografts (Avatar models). This work aimed to evaluate our experience integrating these two strategies to personalize the treatment of patients with cancer.

Methods: We performed whole-exome sequencing analysis of 25 patients with advanced solid tumors to identify putatively actionable tumor-specific genomic alterations. Avatar models were used as an in vivo platform to test proposed treatment strategies.

Results: Successful exome sequencing analyses have been obtained for 23 patients. Tumor-specific mutations and copy-number variations were identified. All samples profiled contained relevant genomic alterations. Tumor was implanted to create an Avatar model from 14 patients and 10 succeeded. Occasionally, actionable alterations such as mutations in NF1, PI3KA, and DDR2 failed to provide any benefit when a targeted drug was tested in the Avatar and, accordingly, treatment of the patients with these drugs was not effective. To date, 13 patients have received a personalized treatment and 6 achieved durable partial remissions. Prior testing of candidate treatments in Avatar models correlated with clinical response and helped to select empirical treatments in some patients with no actionable mutations.

Conclusion: The use of full genomic analysis for cancer care is encouraging but presents important challenges that will need to be solved for broad clinical application. Avatar models are a promising investigational platform for therapeutic decision making. While limitations still exist, this strategy should be further tested. Clin Cancer Res; 20(9); 2476–84. ©2014 AACR.
Seeing the Forest for the Trees: Kidney Oncogenomes in Relation to Therapeutic Outcomes
Authors: Chism David D. , Rathmell W. Kimryn
Published: March 2014

Renal cell carcinoma is a heterogeneous disease, and tissue investigations provide clues that may predict treatment response. Oncogenomic analysis of five outliers, who achieved a sustained response with rapalogs, implicates alterations of the TSC1 and mTOR genes and reveals insights into the conserved evolution of tumors. Clin Cancer Res; 20(7); 1721–3. ©2014 AACR.
SETting OP449 into the PP2A-Activating Drug Family
Authors: Neviani Paolo , Perrotti Danilo
Published: March 2014

The protein phosphatase 2A (PP2A) tumor suppressor is inactivated in different leukemias through the activity of its endogenous inhibitors (e.g., SET), which are aberrantly regulated by oncogenic tyrosine kinases. Like other effective and nontoxic PP2A-activating drugs (PAD), OP449 inhibits SET and impairs leukemogenesis. This further supports the immediate use of PADs in patients with leukemia. Clin Cancer Res; 20(8); 2026–8. ©2014 AACR.
Emerging Immunologic Biomarkers: Setting the (TNM-Immune) Stage
Authors: Taube Janis M.
Published: March 2014

The cooperation of tumor-infiltrating lymphocytes and tertiary lymphoid tissue in early-stage colorectal carcinoma further corroborates the strong immune influences on tumor progression and patient outcome. Immune factors in the tumor microenvironment may warrant inclusion in pathology reports and staging systems for prognostication and prediction of therapeutic response. Clin Cancer Res; 20(8); 2023–5. ©2014 AACR.
Characterization of the Activity of the PI3K/mTOR Inhibitor XL765 (SAR245409) in Tumor Models with Diverse Genetic Alterations Affecting the PI3K Pathway
Authors: Yu Peiwen , Laird A. Douglas , Du Xiangnan , Wu Jianming , Won Kwang-Ai , Yamaguchi Kyoko , Hsu Pin Pin , Qian Fawn , Jaeger Christopher T. , Zhang Wentao , Buhr Chris A. , Shen Paula , Abulafia Wendy , Chen Jason , Young Jenny , Plonowski Arthur , Yakes F. Michael , Chu Felix , Lee Michelle , Bentzien Frauke , Lam Sanh Tan , Dale Stephanie , Matthews David J. , Lamb Peter , Foster Paul
Published: March 2014

Activation of the PI3K (phosphoinositide 3-kinase) pathway is a frequent occurrence in human tumors and is thought to promote growth, survival, and resistance to diverse therapies. Here, we report pharmacologic characterization of the pyridopyrimidinone derivative XL765 (SAR245409), a potent and highly selective pan inhibitor of class I PI3Ks (α, β, γ, and δ) with activity against mTOR. Broad kinase selectivity profiling of >130 protein kinases revealed that XL765 is highly selective for class I PI3Ks and mTOR over other kinases. In cellular assays, XL765 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 phosphorylation in multiple tumor cell lines with different genetic alterations affecting the PI3K pathway. In a panel of tumor cell lines, XL765 inhibits proliferation with a wide range of potencies, with evidence of an impact of genotype on sensitivity. In mouse xenograft models, oral administration of XL765 results in dose-dependent inhibition of phosphorylation of AKT, p70S6K, and S6 with a duration of action of approximately 24 hours. Repeat dose administration of XL765 results in significant tumor growth inhibition in multiple human xenograft models in nude mice that is associated with antiproliferative, antiangiogenic, and proapoptotic effects. Mol Cancer Ther; 13(5); 1078–91. ©2014 AACR.
Hedgehog Pathway Inhibition in Chondrosarcoma Using the Smoothened Inhibitor IPI-926 Directly Inhibits Sarcoma Cell Growth
Authors: Campbell Veronica T. , Nadesan Puviindran , Ali S. Amanda , Wang Chang Ye Yale , Whetstone Heather , Poon Raymond , Wei Qingxia , Keilty John , Proctor Jennifer , Wang Lauren W. , Apte Suneel S. , McGovern Karen , Alman Benjamin A. , Wunder Jay S.
Published: March 2014

Hedgehog (Hh) pathway inhibition in cancer has been evaluated in both the ligand-independent and ligand-dependent settings, where Hh signaling occurs either directly within the cancer cells or within the nonmalignant cells of the tumor microenvironment. Chondrosarcoma is a malignant tumor of cartilage in which there is ligand-dependent activation of Hh signaling. IPI-926 is a potent, orally delivered small molecule that inhibits Hh pathway signaling by binding to Smoothened (SMO). Here, the impact of Hh pathway inhibition on primary chondrosarcoma xenografts was assessed. Mice bearing primary human chondrosarcoma xenografts were treated with IPI-926. The expression levels of known Hh pathway genes, in both the tumor and stroma, and endpoint tumor volumes were measured. Gene expression profiling of tumors from IPI-926–treated mice was conducted to identify potential novel Hh target genes. Hh target genes were studied to determine their contribution to the chondrosarcoma neoplastic phenotype. IPI-926 administration results in downmodulation of the Hh pathway in primary chondrosarcoma xenografts, as demonstrated by evaluation of the Hh target genes GLI1 and PTCH1, as well as inhibition of tumor growth. Chondrosarcomas exhibited autocrine and paracrine Hh signaling, and both were affected by IPI-926. Decreased tumor growth is accompanied by histopathologic changes, including calcification and loss of tumor cells. Gene profiling studies identified genes differentially expressed in chondrosarcomas following IPI-926 treatment, one of which, ADAMTSL1, regulates chondrosarcoma cell proliferation. These studies provide further insight into the role of the Hh pathway in chondrosarcoma and provide a scientific rationale for targeting the Hh pathway in chondrosarcoma. Mol Cancer Ther; 13(5); 1259–69. ©2014 AACR.
Protein Kinase D as a Potential Chemotherapeutic Target for Colorectal Cancer
Authors: Wei Ning , Chu Edward , Wipf Peter , Schmitz John C.
Published: March 2014

Protein kinase D (PKD) signaling plays a critical role in the regulation of DNA synthesis, proliferation, cell survival, adhesion, invasion/migration, motility, and angiogenesis. To date, relatively little is known about the potential role of PKD in the development and/or progression of human colorectal cancer. We evaluated the expression of different PKD isoforms in colorectal cancer and investigated the antitumor activity of PKD inhibitors against human colorectal cancer. PKD2 was the dominant isoform expressed in human colon cancer cells. PKD3 expression was also observed but PKD1 expression, at both the RNA and protein levels, was not detected. Suppression of PKD using the small molecule inhibitors CRT0066101 and kb-NB142-70 resulted in low micromolar in vitro antiproliferative activity against multiple human colorectal cancer cell lines. Drug treatment was associated with dose-dependent suppression of PKD2 activation. Incubation with CRT0066101 resulted in G2–M phase arrest and induction of apoptosis in human colorectal cancer cells. Further studies showed that CRT0066101 treatment gave rise to a dose-dependent increase in expression of cleaved PARP and activated caspase-3, in addition to inhibition of AKT and ERK signaling, and suppression of NF-κB activity. Transfection of PKD2-targeted siRNAs resulted in similar effects on downstream pathways as observed with small molecule inhibitors. Daily administration of CRT0066101 resulted in significant inhibition of tumor growth in HCT116 xenograft nude mice. Taken together, our studies show that PKD plays a significant role in mediating growth signaling in colorectal cancer and may represent a novel chemotherapeutic target for the treatment of colorectal cancer. Mol Cancer Ther; 13(5); 1130–41. ©2014 AACR.
Metallothionein 1G and Zinc Sensitize Human Colorectal Cancer Cells to Chemotherapy
Authors: Arriaga Juan M. , Greco Angela , Mordoh José , Bianchini Michele
Published: March 2014

Metallothioneins (MT) are a family of low molecular weight proteins that are silenced during colorectal cancer progression, mainly through epigenetic mechanisms, and this loss is associated with poor survival. In this article, we show that overexpression of the MT1G isoform sensitizes colorectal cell lines to the chemotherapeutic agents oxaliplatin (OXA) and 5-fluorouracil (5-FU), in part through enhancing p53 and repressing NF-κB activity. Despite being silenced, MTs can be reinduced by histone deacetylase inhibitors such as trichostatin A and sodium butyrate. In fact, this induction contributes to the cytotoxicity of these agents, given that silencing of MTs by siRNAs reduces their growth-inhibitory activities. Zinc ions also potently enhance MT expression and are cytotoxic to cancer cells. We show for the first time that OXA and 5-FU induce higher levels of intracellular labile zinc, as measured using the fluorescent probe FLUOZIN-3, and that such zinc contributes to the activation of p53 and repression of NF-κB. Addition of zinc enhanced growth inhibition by OXA and 5-FU, and was also capable of resensitizing 5-FU–resistant cell lines to levels comparable with sensitive cell lines. This effect was MT independent because silencing MTs did not affect zinc cytotoxicity. In conclusion, we show that MT induction and zinc administration are novel strategies to sensitize colorectal cancer cells to presently utilized chemotherapeutic agents. Mol Cancer Ther; 13(5); 1369–81. ©2014 AACR.
Nuclear Epidermal Growth Factor Receptor Is a Functional Molecular Target in Triple-Negative Breast Cancer
Authors: Brand Toni M. , Iida Mari , Dunn Emily F. , Luthar Neha , Kostopoulos Kellie T. , Corrigan Kelsey L. , Wleklinski Matthew J. , Yang David , Wisinski Kari B. , Salgia Ravi , Wheeler Deric L.
Published: March 2014

Triple-negative breast cancer (TNBC) is a subclass of breast cancers (i.e., estrogen receptor–negative, progesterone receptor–negative, and HER2-negative) that have poor prognosis and very few identified molecular targets. Strikingly, a high percentage of TNBCs overexpresses the EGF receptor (EGFR), yet EGFR inhibition has yielded little clinical benefit. Over the last decade, advances in EGFR biology have established that EGFR functions in two distinct signaling pathways: (i) classical membrane-bound signaling and (ii) nuclear signaling. Previous studies have demonstrated that nuclear EGFR (nEGFR) can enhance resistance to anti-EGFR therapies and is correlated with poor overall survival in breast cancer. On the basis of these findings, we hypothesized that nEGFR may promote intrinsic resistance to cetuximab in TNBC. To examine this question, a battery of TNBC cell lines and human tumors were screened and found to express nEGFR. Knockdown of EGFR expression demonstrated that TNBC cell lines retained dependency on EGFR for proliferation, yet all cell lines were resistant to cetuximab. Furthermore, Src Family Kinases (SFKs) influenced nEGFR translocation in TNBC cell lines and in vivo tumor models, where inhibition of SFK activity led to potent reductions in nEGFR expression. Inhibition of nEGFR translocation led to a subsequent accumulation of EGFR on the plasma membrane, which greatly enhanced sensitivity of TNBC cells to cetuximab. Collectively, these data suggest that targeting both the nEGFR signaling pathway, through the inhibition of its nuclear transport, and the classical EGFR signaling pathway with cetuximab may be a viable approach for the treatment of patients with TNBC. Mol Cancer Ther; 13(5); 1356–68. ©2014 AACR.
ERBB3/HER2 Signaling Promotes Resistance to EGFR Blockade in Head and Neck and Colorectal Cancer Models
Authors: Zhang Li , Castanaro Carla , Luan Bo , Yang Katie , Fan Liangfen , Fairhurst Jeanette L. , Rafique Ashique , Potocky Terra B. , Shan Jing , Delfino Frank J. , Shi Ergang , Huang Tammy , Martin Joel H. , Chen Gang , MacDonald Douglas , Rudge John S. , Thurston Gavin , Daly Christopher
Published: March 2014

EGFR blocking antibodies are approved for the treatment of colorectal cancer and head and neck squamous cell carcinoma (HNSCC). Although ERBB3 signaling has been proposed to limit the effectiveness of EGFR inhibitors, the underlying molecular mechanisms are not fully understood. To gain insight into these mechanisms, we generated potent blocking antibodies against ERBB3 (REGN1400) and EGFR (REGN955). We show that EGFR and ERBB3 are coactivated in multiple HNSCC cell lines and that combined blockade of EGFR and ERBB3 inhibits growth of these cell lines more effectively than blockade of either receptor alone. Blockade of EGFR with REGN955 strongly inhibited activation of ERK in HNSCC cell lines, whereas blockade of ERBB3 with REGN1400 strongly inhibited activation of Akt; only the combination of the 2 antibodies blocked both of these essential downstream pathways. We used a HER2 blocking antibody to show that ERBB3 phosphorylation in HNSCC and colorectal cancer cells is strictly dependent on association with HER2, but not EGFR, and that neuregulin 1 activates ERBB3/HER2 signaling to reverse the effect of EGFR blockade on colorectal cancer cell growth. Finally, although REGN1400 and REGN955 as single agents slowed the growth of HNSCC and colorectal cancer xenografts, the combination of REGN1400 plus REGN955 caused significant tumor regression. Our results indicate that activation of the Akt survival pathway by ERBB3/HER2 limits the effectiveness of EGFR inhibition, suggesting that REGN1400, which is currently in a phase I clinical trial, could provide benefit when combined with EGFR blocking antibodies. Mol Cancer Ther; 13(5); 1345–55. ©2014 AACR.
Hospital Variation in Noninvasive Positive Pressure Ventilation for Acute Decompensated Heart Failure
Authors: Kulkarni Vivek T. , Kim Nancy , Dai Ying , Dharmarajan Kumar , Safavi Kyan C. , Bikdeli Behnood , Lindenauer Peter K. , Testani Jeffrey , Dries Daniel L. , Krumholz Harlan M.
Published: March 2014

Background—

Although noninvasive positive pressure ventilation (NIPPV) for patients with acute decompensated heart failure was introduced almost 20 years ago, the variation in its use among hospitals remains unknown. We sought to define hospital practice patterns of NIPPV use for acute decompensated heart failure and their relationship with intubation and mortality.

Methods and Results—

We conducted a cross-sectional study using a database maintained by Premier, Inc., that includes a date-stamped log of all billed items for hospitalizations at >400 hospitals. We examined hospitalizations for acute decompensated heart failure in this database from 2005 to 2010 and included hospitals with annual average volume of >25 such hospitalizations. We identified 384 hospitals that encompassed 524 430 hospitalizations (median annual average volume: 206). We used hierarchical logistic regression models to calculate hospital-level outcomes: risk-standardized NIPPV rate, risk-standardized intubation rate, and in-hospital risk-standardized mortality rate. We grouped hospitals into quartiles by risk-standardized NIPPV rate and compared risk-standardized mortality rates and risk-standardized intubation rates across quartiles. Median risk-standardized NIPPV rate was 6.2% (interquartile range, 2.8%–9.3%; 5th percentile, 0.2%; 95th percentile, 14.8%). There was no clear pattern of risk-standardized mortality rates across quartiles. The bottom quartile of hospitals had higher risk-standardized intubation rate (11.4%) than each of the other quartiles (9.0%, 9.7%, and 9.1%;
P
<0.02 for all comparisons).

Conclusions—

Substantial variation exists among hospitals in the use of NIPPV for acute decompensated heart failure without evidence for differences in mortality. There may be a threshold effect in relation to intubation rates, with the lowest users of NIPPV having higher intubation rates.
Echocardiographic Diagnosis of Constrictive Pericarditis
Authors: Welch Terrence D. , Ling Lieng H. , Espinosa Raul E. , Anavekar Nandan S. , Wiste Heather J. , Lahr Brian D. , Schaff Hartzell V. , Oh Jae K.
Published: March 2014

Background—

Constrictive pericarditis is a potentially reversible cause of heart failure that may be difficult to differentiate from restrictive myocardial disease and severe tricuspid regurgitation. Echocardiography provides an important opportunity to evaluate for constrictive pericarditis, and definite diagnostic criteria are needed.

Methods and Results—

Patients with surgically confirmed constrictive pericarditis (n=130) at Mayo Clinic (2008–2010) were compared with patients (n=36) diagnosed with restrictive myocardial disease or severe tricuspid regurgitation after constrictive pericarditis was considered but ruled out. Comprehensive echocardiograms were reviewed in blinded fashion. Five principal echocardiographic variables were selected based on prior studies and potential for clinical use: (1) respiration-related ventricular septal shift, (2) variation in mitral inflow E velocity, (3) medial mitral annular e' velocity, (4) ratio of medial mitral annular e' to lateral e', and (5) hepatic vein expiratory diastolic reversal ratio. All 5 principal variables differed significantly between the groups. In patients with atrial fibrillation or flutter (n=29), all but mitral inflow velocity remained significantly different. Three variables were independently associated with constrictive pericarditis: (1) ventricular septal shift, (2) medial mitral e', and (3) hepatic vein expiratory diastolic reversal ratio. The presence of ventricular septal shift in combination with either medial e'≥9 cm/s or hepatic vein expiratory diastolic reversal ratio ≥0.79 corresponded to a desirable combination of sensitivity (87%) and specificity (91%). The specificity increased to 97% when all 3 factors were present, but the sensitivity decreased to 64%.

Conclusions—

Echocardiography allows differentiation of constrictive pericarditis from restrictive myocardial disease and severe tricuspid regurgitation. Respiration-related ventricular septal shift, preserved or increased medial mitral annular e' velocity, and prominent hepatic vein expiratory diastolic flow reversals are independently associated with the diagnosis of constrictive pericarditis.
Diastolic Dysfunction in Women With Signs and Symptoms of Ischemia in the Absence of Obstructive Coronary Artery Disease
Authors: Nelson Michael D. , Szczepaniak Lidia S. , Wei Janet , Haftabaradaren Afsaneh , Bharadwaj Meghan , Sharif Behzad , Mehta Puja , Zhang Xiao , Thomson Louise E. , Berman Daniel S. , Li Debiao , Bairey Merz C. Noel
Published: March 2014

Background—

Angina, in the absence of obstructive coronary artery disease, is more common in women, is associated with adverse cardiovascular morbidity and mortality, and is a major burden to the healthcare system. Although advancements have been made to understand the mechanistic underpinning of this disease, the functional consequence remains unclear.

Methods and Results—

Cardiac magnetic resonance imaging was performed to assess left ventricular function in 20 women with signs and symptoms of ischemia, but no obstructive coronary artery disease (cases), and 15 age- and body mass index–matched reference controls. Functional imaging included standard cinematic imaging to assess left ventricular morphology and global function, along with tissue tagging to assess left ventricular tissue deformation. Systolic function was preserved in both cases and controls, with no differences in ejection fraction (mean±SE: 63.1±8% versus 65±2%), circumferential strain (−20.7±0.6% versus −21.9±0.5%), or systolic circumferential strain rate (−105.9±6.1% versus −109.0±3.8% per second). In contrast, we observed significant differences between cases and controls in diastolic function, as demonstrated by reductions in both diastolic circumferential strain rate (153.8±8.9% versus 191.4±8.9% per second;
P
<0.05) and peak rate of left ventricular untwisting (−99.4±8.0° versus −129.4±12.8° per second;
P
<0.05).

Conclusions—

Diastolic function is impaired in women with signs and symptoms of ischemia in the absence of coronary artery disease, as assessed by cardiac magnetic resonance tissue tagging. These results are hypothesis-generating. Larger studies are needed to define the exact mechanism(s) responsible and to establish viable treatment strategies.
Temporal Relationship Between Subclinical Atrial Fibrillation and Embolic Events
Authors: Brambatti Michela , Connolly Stuart J. , Gold Michael R. , Morillo Carlos A. , Capucci Alessandro , Muto Carmine , Lau Chu P. , Van Gelder Isabelle C. , Hohnloser Stefan H. , Carlson Mark , Fain Eric , Nakamya Juliet , Mairesse Georges H. , Halytska Marta , Deng Wei Q. , Israel Carsten W , Healey Jeff S.
Published: March 2014

Background—

Among patients with implantable pacemakers and defibrillators, subclinical atrial fibrillation (SCAF) is associated with an increased risk of stroke; however, there is limited understanding of their temporal relationship.

Methods and Results—

The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) enrolled 2580 pacemaker and defibrillator patients aged ≥65 years with a history of hypertension but without a history of atrial fibrillation. Pacemakers and implantable cardioverter-defibrillators precisely logged the time and duration of all episodes of SCAF and recorded electrograms that were adjudicated by experts. We examined the temporal relationship between SCAF >6 minutes in duration and stroke or systemic embolism. Of 51 patients who experienced stroke or systemic embolism during follow-up, 26 (51%) had SCAF. In 18 patients (35%), SCAF was detected before stroke or systemic embolism. However, only 4 patients (8%) had SCAF detected within 30 days before stroke or systemic embolism, and only 1 of these 4 patients was experiencing SCAF at the time of the stroke. In the 14 patients with SCAF detected >30 days before stroke or systemic embolism, the most recent episode occurred at a median interval of 339 days (25th to 75th percentile, 211–619) earlier. Eight patients (16%) had SCAF detected only after their stroke, despite continuous monitoring for a median duration of 228 days (25th to 75th percentile, 202–719) before their event.

Conclusions—

Although SCAF is associated with an increased risk of stroke and embolism, very few patients had SCAF in the month before their event.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00256152.
Four new species of Lockhartia (Orchidaceae, Oncidiinae)
Authors: Blanco Mario Alberto
Published: March 2014

Four new species of Lockhartia are described and illustrated: L. compacta from Bolivia, L. endresiana from Costa Rica, L. rugosifolia from Ecuador and Peru, and L. tenuiflora from Ecuador and Colombia. Comments are given on their phenology, distribution, conservation status, and distinction from similar species.
Notes on Early Land Plants Today. 48. Drepanolejeunea longifolia, a new synonym of Drepanolejeunea angustifolia (Marchantiophyta, Lejeuneaceae)
Authors: HE QIONG , ZHU RUI-LIANG
Published: March 2014

Drepanolejeunea (Spruce 1884: 186) Stephani (1891: 209), with about 110 currently accepted species, is the fourth largest genus of Lejeuneaceae (following Cololejeunea (Spruce 1884: 291) Stephani (1891: 208), Lejeunea Libert (1820: 373), and Cheilolejeunea (Spruce 1884: 251) Stephani (1890: 284) (He et al. 2012). Although Drepanolejeunea is a diverse pantropical genus, it is characterized and easily distinguished from other related genera by the 1) erect to widely divergent lobes of underleaves without a basal disc,  2) transverse section of stem with 7 cortical cells and 3 medullary cells, 3) presence of ocelli at least at base of leaf lobe), 4) proximal hyaline papilla, 5) pycnolejeuneoid leaf sequence of gynoecial innovation (if present), 6) inflated perianths usually with various projections near apex, and 7) asexual reproduction by means of cladia or caducous leaves (Zhu & So 2001; He et al. 2012; Pócs et al., 2013). The genus has been classified in a separate subtribe, Drepanolejeuneinae Gradstein (2013: 14), together with Vitalianthus Schuster & Giancotti (1993: 447).
Factors Affecting Outcomes of Alternating Chemoradiotherapy for Nasopharyngeal Cancer
Authors: Ueno Takayoshi , Endo Kazuhira , Kondo Satoru , Wakisaka Naohiro , Murono Shigeyuki , Ito Makoto , Yoshizaki Tomokazu
Published: March 2014

Objective:

Nasopharyngeal cancer (NPC) is radiosensitive and chemosensitive. We evaluated the efficacy of alternating chemoradiotherapy in patients with advanced NPC.

Methods:

Alternating chemoradiotherapy was initiated in 30 patients with NPC, and 27 patients with cancer stages II (n = 6), III (n = 8), IVA (n = 9), and IVB (n = 4) were retrospectively analyzed. Chemotherapy was initially administered followed by radiotherapy, and chemotherapy, radiotherapy, and chemotherapy were alternately administered. Of the 27 patients, 22 patients received cisplatin (50 mg/m2/day, days 6 and 7) and 5-fluorouracil (5-FU; 800 mg/m2/day, days 1-5), whereas 5 patients received carboplatin (AUC 4-5, day 6) and 5-FU.

Results:

Of the 27 patients, 19 (70%) received 3 chemotherapy courses. The total duration of alternating chemoradiotherapy was 81 to 101 days (median, 90 days). At a median follow-up of 53 months, the 5-year progression-free survival (PFS) was 71%. Multivariate analysis showed that weight loss and the number of chemotherapy courses had a significant effect on PFS.

Conclusion:

Alternating chemoradiotherapy led to similar or higher survival rates compared with concurrent chemoradiotherapy, which was characterized by good compliance and adaptable intensity.
Methods and Preliminary Outcomes of Pediatric Auditory Brainstem Implantation
Authors: Bayazıt Yıldırım A. , Kosaner Julie , Cicek Cınar Betul , Atac Ahmet , Tutar Hakan , Gunduz Bulent , Altinyay Senay , Gokdogan Cagıl , Ant Ayca , Ozdek Ali , Goksu Nebil
Published: March 2014

Objective:

The objective was to provide information about methods used and preliminary outcomes for pediatric ABI (auditory brainstem implant).

Study Design:

An analysis of outcome was performed in children who received an ABI.

Methods:

Twelve children received a MED-EL ABI system. Progress in audition and language was monitored through parental reports, questionnaires, profiles, and closed-set tests.

Results:

The median number of active electrodes was 9 of 12. Seven of 12 users consistently respond to sound, and 5 of 12 do not. Highest performers can recognize words in small sets and have begun to use some words.

Conclusion:

Auditory brainstem implants appear to be beneficial for some pediatric patients who cannot benefit from traditional cochlear implant surgery. Benefits in the short term can be recognition of environmental sounds, recognition of some words and very commonly used phrases, and the beginning use of words. Although some of our ABI users demonstrate no response to sound, they do want to wear their sound processors all waking hours. The cause of lack of response may be related to the second intervention, which might have led to displacement of the electrode array, or presence of additional handicaps or syndromes. However, the results are less than optimal. The relatively short postoperative follow-up duration is a considered weakness of this study.
Partial Mastoid Obliteration Combined With Soft-wall Reconstruction for Middle Ear Cholesteatoma
Authors: Suzuki Hideaki , Ikezaki Shoji , Imazato Kei , Koizumi Hiroki , Ohbuchi Toyoaki , Hohchi Nobusuke , Hashida Koichi
Published: March 2014

Objectives:

The objective was to analyze the surgical outcomes of tympanoplasty with partial mastoid obliteration and soft-wall reconstruction for middle ear cholesteatoma.

Methods:

Sixty-nine patients (73 ears) with fresh middle ear cholesteatomas, 42 men and 27 women aged 6 to 89 years, were retrospectively analyzed. The cholesteatomas were the pars flaccida and tensa types in 59 and 12 ears, respectively. The patients underwent canal-wall-down tympanoplasty with partial mastoid obliteration and soft-wall reconstruction. Follow-up computed tomography was performed 6 to 12 months after surgery. Hearing outcomes were evaluated by the arithmetic mean of the hearing levels at 500, 1000, and 2000 Hz.

Results:

Residual cholesteatoma occurred in 7 ears (9.6%) and recurrent cholesteatoma in 1 ear (1.4%). No cavity problem was seen. Primary evaluation of postoperative hearing was performed 6 to 12 months after ossiculoplasy. Of the 50 ears with available audiogram in this period, the postoperative air-bone gaps were ≤15 dB and ≤20 dB in 27 (54.0%) and 37 (74.0%) ears, respectively. The postoperative hearing level was within 30 dB in 22 ears (44.0%). The hearing gain was ≥15 dB in 24 ears (48.0%).

Conclusions:

The surgical outcomes of tympanoplasty with partial mastoid obliteration and soft-wall reconstruction for middle ear cholesteatoma were satisfactory with a low incidence of cholesteatoma recidivism and tolerable postoperative hearing without cavity problems.
Spindle Cell Carcinoma of the Upper Aerodigestive Tract
Authors: Gerry Daniel , Fritsch Valerie A. , Lentsch Eric J.
Published: March 2014

Objectives:

We sought to better characterize spindle cell carcinoma (SpCC) of the upper aerodigestive tract, a rare and aggressive variant, through comparison of a large cohort of head and neck SpCCs against a cohort of conventional head and neck squamous cell carcinoma (SCC) patients.

Methods:

We compared epidemiologic and clinicopathologic characteristics of 341 SpCCs with 67 882 SCCs of the head and neck, drawing data from the SEER national database. We also compared disease-specific survivals (DSS) for SpCC and SCC based on tumor site and mode of treatment.

Results:

SpCCs were predominantly laryngeal (46.4%, P < .001) and were more likely to be high grade ( P > .001). SpCCs were also more likely than SCCs to present at an early stage ( P < .001 to P < .05). Rates of distant metastasis were similar between the tumor types. DSS was similar between SpCCs and SCCs, although site-specific survival rates were higher for SpCCs of the larynx ( P = .017) and lower for those of the oral cavity ( P = .008).

Conclusion:

SpCC of the head and neck is more likely than SCC to present at an early stage, with fewer nodal metastases. Survival rates appear to depend on anatomic site as well.
Combined Lateral Microscopic/Endoscopic Approaches to Petrous Apex Lesions
Authors: Presutti Livio , Alicandri-Ciufelli Matteo , Rubini Alessia , Gioacchini Federico Maria , Marchioni Daniele
Published: March 2014

Background:

Surgical treatment of lesions involving the temporal bone, petrous apex, or internal auditory canal is usually performed using the classical microscopic approach that necessitates wide external incisions and soft tissue dissection. At present, the main application of endoscopic surgery is in the surgical treatment of middle ear cholesteatoma, but with the natural evolution of the technique, there will be an increasing number of applications in lateral skull base surgery.

Objective:

This study aimed to describe the pilot clinical experiences of our institution with combined microscopic/endoscopic-assisted approaches to the lateral skull base.

Methods:

A retrospective chart review was performed on patients undergoing an operation between July 2005 and September 2011 for lateral skull base pathology using the endoscope-assisted technique.

Results:

Nine patients (7 female, 2 male; mean age = 57.4 years) were reviewed and included in the present study. In all cases, the petrous apex lesion of each patient was unilateral: 6 cases had cholesteatoma of the petrous bone; 2 cases had cholesterinic granuloma of the petrous apex; and 1 case had a low-grade chondrosarcoma of the petrous apex. Overall, after a mean follow-up of 30.7 months, no residual disease has been found in our series up to the present time in the cholesteatoma group. In the cholesterinic granuloma group, only a partial success was obtained in the patient who underwent the infracochlear approach, since the most medial part of the pathology was not accessed and still persisted at neuroradiologic examinations made postoperatively.

Conclusion:

In our case series, lateral combined microscopic/endoscopic procedures have proved to be effective in the treatment of petrous apex lesions, allowing less destructive approaches compared to exclusive microscopic procedures.
Regional Variation and Factors Associated With Image Guidance Utilization During Endoscopic Sinus Surgery in the Ambulatory Setting
Authors: Bhattacharyya Neil
Published: March 2014

Objective:

Determine regional variation and factors associated with the use of image guidance (IG) during endoscopic sinus surgery (ESS) in the ambulatory surgery center setting.

Methods:

All cases of ESS in 2010 were extracted from the state ambulatory surgery databases for New York, North Carolina, Florida, Iowa, and California. Current Procedural Terminology codes for individual sinusotomies and IG and International Classification of Diseases codes along with insurance and regional data were analyzed to determine factors that were associated with the use of IG during ESS.

Results:

Among 36 646 ambulatory ESS procedures (mean age 46.0 years; 49.0% female), 6676 cases utilized IG (18.2%). Polyps were present in 27.9% of cases. North Carolina had the highest utilization rate for IG (26.0%), whereas Iowa had the lowest (12.8%). On multivariate analysis, use of IG was associated with state, insurance status, community setting, total ethmoidectomy, frontal sinusotomy, sphenoidotomy, and polyps (all P < .001), but not maxillary antrostomy ( P = .197). The highest procedural odds ratio for IG use was noted for total ethmoidectomy (2.07), followed by frontal sinusotomy (1.97) and sphenoidotomy (1.26).

Conclusion:

Although IG is utilized in a relative minority of ESS cases, there is considerable regional variation in use. Factors other than complexity of surgery influence IG utilization as well.
Extrusion of a Cochlear Implant Positioner Through the Tympanic Membrane in a Pediatric Patient
Authors: Dhillon Vaninder K. , Hoa Michael , Winter Margaret , Wilkinson Eric P.
Published: March 2014

Objective:

This study aimed to present a case of an extruded Advanced Bionics positioner, with the goal of educating a new generation of otologic surgeons on management of the delayed complications associated with this cochlear implant model.

Methods:

Retrospective case report in a pediatric patient.

Results:

We observed the extrusion of an Advanced Bionics positioner 10 years after cochlear implantation.

Conclusion:

Awareness of the Advanced Bionics positioner as a component of certain historical models of cochlear implants is important as the delayed complications associated with this model may still be encountered. Management of an extruded positioner should include precautions against infectious complications, repair of the defect, and assessment of the patient’s performance with the cochlear implant.
Safety of Concurrent Nasal and Oropharyngeal Surgery for Obstructive Sleep Apnea
Authors: Banuchi Victoria , Cohen Justin C. , Kacker Ashutosh
Published: March 2014

Objective:

This study evaluated for increased complications or risk associated with concurrent nasal and oropharyngeal surgeries to treat patients with obstructive sleep apnea (OSA).

Study Design:

Retrospective chart review.

Methods:

We performed a retrospective chart review on consecutive patients between 2006 and 2011 who underwent either simultaneous nasal and pharyngeal surgery (group 1) or pharyngeal surgery alone (group 2) to treat OSA. We compared the length of hospitalization and the rate of complications in both groups.

Results:

Group 1 consisted of 20 patients, all male, with ages ranging from 25 to 72 years (average, 35 years) and apnea-hypopnea index (AHI) from 2.6 to 119 (average, 52.2). Group 2 consisted of 20 patients, 1 female, with ages ranging from 23 to 71 years (average, 37 years) and AHI from 10 to 101 (average, 46.1). In group 1, 30% of patients were ambulatory compared to 25% of patients in group 2. In all cases, the nonambulatory patients were observed for only 1 night. The rate of complications in both groups was 10% (2 out of 20 in each group). Both complications in group 1 were post-tonsillectomy bleeds. In group 2, 1 patient had a post-tonsillectomy bleed and 1 patient was readmitted with dehydration due to poor pain control. There was no statistically significant difference in length of hospitalization or rate of complications in these 2 groups.

Conclusion:

Performing concurrent nasal and oropharyngeal surgery for OSA was safe when compared to oropharyngeal surgery alone in our cohort and, with careful selection criteria, can even be done in the ambulatory setting. Large, multi-institutional investigations are indicated.
Dysphagia Due to Inclusion Body Myositis
Authors: Ko Ellen H. , Rubin Adam D.
Published: March 2014

Objective:

This report aimed to present a case of inclusion body myositis presenting with dysphagia and to review the literature.

Methods:

Case report and literature review.

Results:

Inclusion body myositis is a chronic progressive acquired myopathy, uniquely distinguished by its selective muscle involvement, normal or moderately elevated muscle enzyme concentrations, and a progressive corticosteroid-resistant course. Compared to other inflammatory myopathies, the esophagus is the most commonly involved organ. Specifically, upper esophageal sphincter dysfunction often occurs. Dysphagia may be the only symptom at the time of presentation.

Conclusion:

Unlike other inflammatory myopathies, dysphagia in inclusion body myositis is steroid resistant. Management can be difficult. The otolaryngologist must consider underlying neuromuscular processes when evaluating the patient presenting with oropharyngeal dysphagia.
Five Days of Successful Oral Alimentation for Hospitalized Patients Based Upon Passing the Yale Swallow Protocol
Authors: Leder Steven B. , Suiter Debra M.
Published: March 2014

Objective:

This study aimed to determine the success of oral alimentation and patient retention rate 1 to 5 days after passing the Yale Swallow Protocol.

Methods:

Participants were 200 consecutive acute care inpatients referred for swallow assessment. Inclusion criteria were adequate cognitive abilities to participate safely, completing an oral mechanism examination, and passing the 3-ounce water swallow challenge. Exclusion criteria were altered mental status, failing the 3-ounce challenge, preadmission dysphagia, head-of-bed restrictions < 30°, and a tracheotomy tube. Electronic medical record monitoring post-protocol passing for 1 to 5 consecutive days determined success of oral alimentation and retention rate.

Results:

All patients who remained medically and neurologically stable drank thin liquids and ate successfully 1 to 5 days after passing the protocol. Mean (SD) volume of liquid ingested per day was 474.2 (435.5) cc. Patient retention declined steadily from day of testing (n = 200) through post-testing day 5 (n = 95).

Conclusion:

Passing the Yale Swallow Protocol allowed for initial determination of aspiration risk followed by successful oral alimentation for 1 to 5 days in medically and neurologically stable acute care hospitalized patients and without the need for instrumental dysphagia testing. The decline in patient retention was expected because of increasingly rapid transit through the acute care setting, which often renders longer follow-up problematic.
Screen Exposure and Body Mass Index Status in 2- to 11-Year-Old Children
Authors: Hendrix Kristin S. , Carroll Aaron E. , Downs Stephen M.
Published: March 2014

Objective. To measure the relationship between screen exposure and obesity in a large, urban sample of children and to examine whether the relationship is moderated by sociodemographics. Methods. We asked parents of 11 141 children visiting general pediatrics clinics if the child had a television (TV) in the bedroom and/or watched more than 2 hours of TV/computer daily. We measured children’s height and weight, then used logistic regression to determine whether screen exposure indicators predicted obesity (body mass index ≥85th percentile) and interacted with race/ethnicity, sex, age, and health care payer. Results. Having a TV in the bedroom predicted obesity risk ( P = .01); however, watching TV/computer for more than 2 hours a day did not ( P = 0.54). There were no interactions. Conclusions. Asking whether a child has a TV in the bedroom may be more important than asking about duration of screen exposure to predict risk for obesity.
Learning to Deliver Care in a Medical Home
Authors: Kind Terry , Goldman Ellen , Fratantoni Karen , Wiedermann Bernhard L. , Agrawal Dewesh , Coddington Dale
Published: March 2014

Objective. We used online structured reflection to improve residents’ understanding of care delivery in the medical home. Methods. Third-year pediatric residents participated in an online curriculum on delivering effective, patient-centered primary care in the medical home to children with special health care needs. Residents were prompted to respond to questions designed to stimulate reflection. We qualitatively assessed their responses, graded their depth of reflection, and provided structured feedback. Results. Residents identified aspects of their practice consistent with medical home principles. Depth of reflection increased over time. Residents realized they needed to better understand families’ financial, emotional, and social needs and increase families’ involvement in care planning. Residents identified systems issues and practice changes to improve care delivery. Conclusions. Online reflective writing with feedback is a powerful strategy to improve residents’ learning. Residents identified and began to make practice changes to provide patient-centered care in a medical home.
A Randomized Controlled Trial of Clinician-Led Tactile Stimulation to Reduce Pain During Vaccination in Infants
Authors: Taddio Anna , Ho Tommy , Vyas Charmy , Thivakaran Suganthan , Jamal Ali , Ilersich Andrew F. , Hogan Mary-Ellen , Shah Vibhuti
Published: March 2014

Background. Clinician-led tactile stimulation (rubbing the skin adjacent to the injection site or applying pressure) has been demonstrated to reduce pain in children and adults undergoing vaccination. Objective. To evaluate the analgesic effectiveness of clinician-led tactile stimulation in infants undergoing vaccination. Methods. This was a partially blinded randomized controlled trial that included infants undergoing vaccination in a private clinic in Toronto. Infants were randomly allocated to tactile stimulation or no tactile stimulation immediately prior to, during, and after vaccination. The primary outcome was infant pain, assessed using a validated observational measure, the Modified Behavioral Pain Scale (MBPS; range = 0-10). Results. Altogether, 121 infants participated (n = 62 tactile stimulation; n = 59 control); demographics did not differ ( P > .05) between groups. MBPS scores did not differ between groups: mean = 7.2 (standard deviation = 2.4) versus 7.6 (1.9); P = .245. Conclusion. Tactile stimulation cannot be recommended as a strategy to reduce vaccination pain in infants because of insufficient evidence of a benefit.
Serious Impact of Handlebar Injuries
Authors: Cherniawsky Hannah , Bratu Ioana , Rankin Tara , Sevcik William (Bill)
Published: March 2014

Background. Injuries from bicycles is a leading cause of trauma in children. We sought to investigate the epidemiology of bicycle handlebar injuries. Methods. A retrospective analysis of bicycle trauma treated at our institution was preformed. Results. A total of 462 children younger than 17 years had bicycle trauma. Abdominal handlebar injuries, representing 9% of bicycle injuries, contributed to 19% of all internal organ injuries, and 45.4% of solid, 87.5% of hollow, 66.6% of vascular or lymphatic, and 100% of pancreatic injuries. Handlebar injuries were 10 times more likely to cause severe injury, yet more than half of the children were misdiagnosed at their initial presentation. Delayed diagnosis and longer hospital stays were observed in handlebar injuries to the abdomen. Conclusion. Physicians should be aware of the serious impact of bicycle handlebar injury to the abdomen. The mechanism alone should raise the suspicion of internal organ injury, and timely imaging and surgical consultation.
Overweight Among Children Younger Than 3 Years in a Low-Income Patient Population
Authors: Robbins Jessica M. , Nguyen John V. , Houck Kevin L. , Inman Katelyn A. , Nobis Elizabeth A. , Robbins Susan W.
Published: March 2014

Objectives. To examine the prevalence and correlates of overweight and obesity among patients aged 0 to 2 years, and to compare 3 measures of early childhood weight status, weight-for-age, weight-for-length, and body mass index–for-age. Setting. Well-child visits in the Philadelphia Health Centers, public community health centers providing primary health care to predominantly low-income residents. Study design. Cross-sectional. Results. Using the 3 measures, 13% to 16% of boys and 10% to 13% of girls seen during 2010 were classified as high in weight. No consistent associations with feeding method were identified. “Other/unknown” race was consistently associated with higher rates of overweight than the African American reference group. Hispanic girls had higher rates of high weight-for-age and weight-for-length than African American girls. Conclusion. Elevated weight status emerges in a significant proportion of very young children, by all of the commonly used weight measures. There is an urgent need for appropriate clinical strategies to prevent and respond to overweight in this age group.