J Immunother Cancer. 2018 Jun 6;6(1):48. doi: 10.1186/s40425-018-0368-0.
Effect of neoadjuvant chemotherapy on the immune microenvironment in non-small cell lung carcinomas as determined by multiplex immunofluorescence and image analysis approaches.
Parra ER1, Villalobos P2, Behrens C3, Jiang M2, Pataer A4, Swisher SG4, William WN Jr3, Zhang J5, Lee J6, Cascone T3, Heymach JV3, Forget MA7, Haymaker C7, Bernatchez C7, Kalhor N8, Weissferdt A8, Moran C8, Zhang J3, Vaporciyan A4, Gibbons DL3, Sepesi B9, Wistuba II10,11.
Author information
1
Department of Translational Molecular Pathology, Unit 951, The University of Texas MD Anderson Cancer Center, 2130 West Holcombe Blvd, Houston, TX, 77030, USA. erparra@mdanderson.org.
2
Department of Translational Molecular Pathology, Unit 951, The University of Texas MD Anderson Cancer Center, 2130 West Holcombe Blvd, Houston, TX, 77030, USA.
3
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
4
Department of Thoracic and Cardiovascular Surgery, Unit 1489, The University of Texas MD Anderson Cancer Center, 1400 Pressler St. Houston, Houston,, TX, 77030, USA.
5
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
6
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
7
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
8
Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
9
Department of Thoracic and Cardiovascular Surgery, Unit 1489, The University of Texas MD Anderson Cancer Center, 1400 Pressler St. Houston, Houston,, TX, 77030, USA. BSepesi@mdanderson.org.
10
Department of Translational Molecular Pathology, Unit 951, The University of Texas MD Anderson Cancer Center, 2130 West Holcombe Blvd, Houston, TX, 77030, USA. iiwistuba@mdanderson.org.
11
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. iiwistuba@mdanderson.org.
Abstract
BACKGROUND:
The clinical efficacy observed with inhibitors of programed cell death 1/programed cell death ligand 1 (PD-L1/PD-1) in cancer therapy has prompted studies to characterize the immune response in several tumor types, including lung cancer. However, the immunological profile of non-small cell lung carcinoma (NSCLC) treated with neoadjuvant chemotherapy (NCT) is not yet fully characterized, and it may be therapeutically important. The aim of this retrospective study was to characterize and quantify PD-L1/PD-1 expression and tumor-associated immune cells (TAICs) in surgically resected NSCLCs from patients who received NCT or did not receive NCT (non-NCT).

METHODS:
We analyzed immune markers in formalin-fixed, paraffin-embedded tumor tissues resected from 112 patients with stage II/III NSCLC, including 61 non-NCT (adenocarcinoma [ADC] = 33; squamous cell carcinoma [SCC] = 28) and 51 NCT (ADC = 31; SCC = 20). We used multiplex immunofluorescence to identify and quantify immune markers grouped into two 6-antibody panels: panel 1 included AE1/AE3, PD-L1, CD3, CD4, CD8, and CD68; panel 2 included AE1/AE3, PD1, granzyme B, FOXP3, CD45RO, and CD57.

RESULTS:
PD-L1 expression was higher (> overall median) in NCT cases (median, 19.53%) than in non-NCT cases (median, 1.55%; P = 0.022). Overall, density of TAICs was higher in NCT-NSCLCs than in non-NCT-NSCLCs. Densities of CD3+ cells in the tumor epithelial compartment were higher in NCT-ADCs and NCT-SCCs than in non-NCT-ADCs and non-NCT-SCCs (P = 0.043). Compared with non-NCT-SCCs, NCT-SCCs showed significantly higher densities of CD3 + CD4+ (P = 0.019) and PD-1+ (P < 0.001) cells in the tumor epithelial compartment. Density of CD68+ tumor-associated macrophages (TAMs) was higher in NCT-NSCLCs than in non-NCT-NSCLCs and was significantly higher in NCT-SCCs than in non-NCT-SCCs. In NCT-NSCLCs, higher levels of epithelial T lymphocytes (CD3 + CD4+) and epithelial and stromal TAMs (CD68+) were associated with better outcome in univariate and multivariate analyses.

CONCLUSIONS:
NCT-NSCLCs exhibited higher levels of PD-L1 expression and T-cell subset regulation than non-NCT-NSCLCs, suggesting that NCT activates specific immune response mechanisms in lung cancer. These results suggest the need for clinical trials and translational studies of combined chemotherapy and immunotherapy prior to surgical resection of locally advanced NSCLC.

KEYWORDS:
Adenocarcinoma; Epithelial compartment; Squamous cell carcinoma; Stromal compartment; Survival; T cells; Tumor compartments

PMID: 29871672 PMCID: PMC5989476 DOI: 10.1186/s40425-018-0368-0
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Select item 29734476
162.
J Bone Miner Res. 2018 Sep;33(9):1657-1664. doi: 10.1002/jbmr.3461. Epub 2018 Jun 7.
Prevalence and Risk of Vertebral Fractures in Primary Hyperparathyroidism: A Nested Case-Control Study.
Ejlsmark-Svensson H1, Bislev LS1, Lajlev S1, Harsløf T1, Rolighed L2, Sikjaer T1, Rejnmark L1.
Author information
1
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
2
Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark.
Abstract
Prevalence of vertebral fractures (VFx) in primary hyperparathyroidism (PHPT) remains uncertain. We aimed to estimate the prevalence of VFx, investigate potential risk factors associated with VFx, and whether bone mineral density (BMD) differs between PHPT and osteoporotic patients with VFx. Through the Danish National Patient Register, we identified patients diagnosed with PHPT from 2005 to 2015. The diagnosis was verified by reviewing biochemical findings, and X-ray reports were reviewed by two investigators. Osteoporotic patients with VFx were identified from our outpatient clinic and matched on age and sex with PHPT patients with VFx. We identified 792 PHPT patients among whom spine X-ray was available from 588 patients. VFx were present in 122 (21%) patients and were equally frequent among sexes (77% females). Fractured patients were older (70 versus 63 years) and had lower heights (163 versus 166 cm) compared with nonfractured patients (p all < 0.02). After stratification by age groups, the prevalence of VFx differed significantly between sexes (p < 0.01). Ionized calcium and parathyroid hormone did not differ between groups. BMD at total hip and forearm were lower in fractured compared with nonfractured patients (p < 0.03 for both) after adjusting for age, sex, and body mass index (BMI). Compared with osteoporotic patients with VFx (n = 108), BMD at the lumbar spine was higher in PHPT patients with VFx (n = 108) (p < 0.01). This did not change by excluding patients with lumbar VFx (p < 0.01). The severity of PHPT assessed by biochemistry does not seem to be associated with risk of VFx. Compared with osteoporosis, VFx seems to occur at a higher BMD in PHPT.

© 2018 American Society for Bone and Mineral Research.

KEYWORDS:
BONE MINERAL DENSITY; OSTEOPOROSIS; PRIMARY HYPERPARATHYROIDISM; VERTEBRAL FRACTURE

PMID: 29734476 DOI: 10.1002/jbmr.3461
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163.
J Am Acad Audiol. 2018 May;29(5):427-442. doi: 10.3766/jaaa.17085.
Cochlear Microphonic and Summating Potential Responses from Click-Evoked Auditory Brain Stem Responses in High-Risk and Normal Infants.
Hunter LL1,2, Blankenship CM1,2, Gunter RG1, Keefe DH3, Feeney MP4,5, Brown DK6, Baroch K1.
Author information
1
Communication Sciences Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
2
Department of Otolaryngology, Head and Neck Surgery, Communication Sciences and Disorders, University of Cincinnati, Cincinnati, OH.
3
Boys Town National Research Hospital, Omaha, NE.
4
National Center for Rehabilitative Auditory Research, Portland VA Medical Center, Portland, OR.
5
Department of Otolaryngology, Head and Neck Surgery, Oregon Health and Science University, Portland, OR.
6
School of Audiology, Pacific University, Hillsboro, OR.
Abstract
BACKGROUND:
Examination of cochlear and neural potentials is necessary to assess sensory and neural status in infants, especially those cared for in neonatal intensive care units (NICU) who have high rates of hyperbilirubinemia and thus are at risk for auditory neuropathy (AN).

PURPOSE:
The purpose of this study was to determine whether recording parameters commonly used in click-evoked auditory brain stem response (ABR) are useful for recording cochlear microphonic (CM) and Wave I in infants at risk for AN. Specifically, we analyzed CM, summating potential (SP), and Waves I, III, and V. The overall aim was to compare latencies and amplitudes of evoked responses in infants cared for in NICUs with infants in a well-baby nursery (WBN), both of which passed newborn hearing screening.

RESEARCH DESIGN:
This is a prospective study in which infants who passed ABR newborn hearing screening were grouped based on their birth history (WBN and NICU). All infants had normal hearing status when tested with diagnostic ABR at about one month of age, corrected for prematurity.

STUDY SAMPLE:
Thirty infants (53 ears) from the WBN [mean corrected age at test = 5.0 weeks (wks.)] and thirty-two infants (59 ears) from the NICU (mean corrected age at test = 5.7 wks.) with normal hearing were included in this study. In addition, two infants were included as comparative case studies, one that was diagnosed with AN and another case that was diagnosed with bilateral sensorineural hearing loss (SNHL).

DATA COLLECTION AND ANALYSIS:
Diagnostic ABR, including click and tone-burst air- and bone-conduction stimuli were recorded. Peak Waves I, III, and V; SP; and CM latency and amplitude (peak to trough) were measured to determine if there were differences in ABR and electrocochleography (ECochG) variables between WBN and NICU infants.

RESULTS:
No significant group differences were found between WBN and NICU groups for ABR waveforms, CM, or SP, including amplitude and latency values. The majority (75%) of the NICU group had hyperbilirubinemia, but overall, they did not show evidence of effects in their ECochG or ABR responses when tested at about one-month corrected age. These data may serve as a normative sample for NICU and well infant ECochG and ABR latencies at one-month corrected age. Two infant case studies, one diagnosed with AN and another with SNHL demonstrated the complexity of using ECochG and otoacoustic emissions to assess the risk of AN in individual cases.

CONCLUSIONS:
CM and SPs can be readily measured using standard click stimuli in both well and NICU infants. Normative ranges for latency and amplitude are useful for interpreting ECochG and ABR components. Inclusion of ECochG and ABR tests in a test battery that also includes otoacoustic emission and acoustic reflex tests may provide a more refined assessment of the risks of AN and SNHL in infants.

American Academy of Audiology.

PMID: 29708492 DOI: 10.3766/jaaa.17085
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164.
Cancer Med. 2018 Jun;7(6):2405-2414. doi: 10.1002/cam4.1505. Epub 2018 Apr 19.
Major pathologic response and RAD51 predict survival in lung cancer patients receiving neoadjuvant chemotherapy.
Pataer A1, Shao R1, Correa AM1, Behrens C2, Roth JA1, Vaporciyan AA1, Wistuba II3, Swisher SG1.
Author information
1
Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Abstract
In a previous study, we determined that major pathologic response (MPR) as indicated by the percentage of residual viable tumor cells predicted overall survival (OS) in patients with non-small-cell lung cancer (NSCLC) who received neoadjuvant chemotherapy. In this study, we assessed whether two genes and five protein biomarkers could predict MPR and OS in 98 patients with NSCLC receiving neoadjuvant chemotherapy. We collected formalin-fixed, paraffin-embedded specimens of resected NSCLC tumors from 98 patients treated with neoadjuvant chemotherapy. We identified mutations in KRAS and EGFR genes using pyrosequencing and examined the expression of protein markers VEGFR2, EZH2, ERCC1, RAD51, and PKR using immunohistochemistry. We assessed whether gene mutation status or protein expression was associated with MPR or OS. We observed that KRAS mutation tended to be associated with OS (P = .06), but EGFR mutation was not associated with OS. We found that patients with high RAD51 expression levels had a poorer prognosis than did those with low RAD51 expression. We also observed that RAD51 expression was associated with MPR. MPR and RAD51 expression were associated with OS in univariate and multivariate analyses (P = .04 and P = .02, respectively). Combination of MPR with RAD51 is a significant predictor of prognosis in patients with NSCLC who received neoadjuvant chemotherapy. We demonstrated that MPR or RAD51 expression was associated with OS in patients with NSCLC receiving neoadjuvant chemotherapy. Prediction of a patient's prognosis could be improved by combined assessment of MPR and RAD51 expression.

© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

KEYWORDS:
Biomarker; RAD51; lung cancer; neoadjuvant chemotherapy

PMID: 29673125 PMCID: PMC6010873 DOI: 10.1002/cam4.1505
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Select item 29671679
165.
Logoped Phoniatr Vocol. 2018 Dec;43(4):175-180. doi: 10.1080/14015439.2018.1461925. Epub 2018 Apr 19.
The cut-off analysis using visual analogue scale and cepstral assessments on severity of voice disorder.
Lee YW1, Kim GH1, Bae IH2, Park HJ3, Wang SG4, Kwon SB5.
Author information
1
a Department of Otorhinolaryngology-Head and Neck Surgery and Biomedical Research Institute , Pusan National University Hospital , Busan , Korea.
2
b Department of Otorhinolaryngology-Head and Neck Surgery , Pusan National University Yangsan Hospital , Yangsan , South Korea.
3
c Department of Speech Rehabilitation , Choonhae College of Health Sciences , Ulsan , South Korea.
4
d Department of Otorhinolaryngology-Head and Neck Surgery , Pusan National University School of Medicine , Busan , Korea.
5
e Department of Humanities, Language and Information , Pusan National University , Busan , South Korea.
Abstract
Purpose: The aims of this study were to: (1) determine the visual analogue scale (VAS) and cepstrum peak prominence (CPP) cut-off points on the ratings of numerical scale (NS) related to the severity of voice disorder ratings and (2) verify the discriminative power of these cut-off points for distinguishing between different severities of voice disorder. Methods: Auditory-perceptual severity assessments (VAS and four-point NS) of 214 voice samples were performed by three speech-language pathologists and CPP parameters were used for the acoustic analysis. Both VAS and CPP cut-off points were obtained using receiver operating characteristic (ROC) curve analyses, based on their correspondence with NS ratings. Results: A high level of inter- and intra-rater reliability was found for the auditory-perceptual assessments of both VAS and NS. The VAS cut-off points for overall severity (OS), between normal variation and mild/moderate severity, mild/moderate and moderate severity, and moderate and severe severity were 32.7, 51.7, and 71.7 points, respectively, and CPP cut-off points were 7.050, 4.651, and 2.989 points, respectively. Areas under the ROC curves demonstrated excellent specificity and sensitivity of all cut-off points. Conclusions: The VAS and CPP cut-off points of OS of voice disorder demonstrated a high power to discriminate between different severities of voice disorder. The results of this study suggested cut-off points for clinical use.

KEYWORDS:
Auditory-perceptual evaluation; cepstrum peak prominence; dysphonia; rating scales; severity of voice disorder; vocal screening

PMID: 29671679 DOI: 10.1080/14015439.2018.1461925
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166.
Cleft Palate Craniofac J. 2018 Nov;55(10):1447-1449. doi: 10.1177/1055665618766060. Epub 2018 Apr 4.
Comparison of Pre- and Postoperative Sleep Studies in Patients Undergoing Sphincter Pharyngoplasty.
Busuito CM1, Vandjelovic N2, Flis DM1, Rozzelle A3.
Author information
1
1 Division of Plastic and Reconstructive Surgery, Detroit Medical Center/Wayne State University, Detroit, MI, USA.
2
2 Department of Otolaryngology-Head and Neck Surgery, Detroit Medical Center/Michigan State University, Detroit, MI, USA.
3
3 Plastic and Reconstructive Surgery, Children's Hospital of Michigan, Detroit, MI, USA.
Abstract
OBJECTIVE:
To determine if sphincter pharyngoplasty changes sleep study parameters on patients undergoing surgery for velopharyngeal insufficiency (VPI).

DESIGN:
Retrospective chart review on patients undergoing sphincter pharyngoplasty for VPI with pre- and postoperative polysomnography completed.

SETTING:
Institutional study at a tertiary pediatric hospital.

PATIENTS:
All patients who underwent sphincter pharyngoplasty over a 20-year period were reviewed; all patients with both pre- and postoperative sleep studies were collected for evaluation.

INTERVENTIONS:
Sphincter pharyngoplasty for patients with VPI.

MAIN OUTCOME MEASURE:
Sleep study parameters collected include apnea-hypopnea index (AHI), obstructive and central apneas, hypopneas, and mixed events. The preoperative values were compared to postoperative values.

RESULTS:
There were 98 patients collected with sleep studies for review. Of these, 32 patients had both pre- and postoperative sleep studies. The AHI increased from 1.8 preoperatively to a postoperative value of 4.8 ( P = .004). The number of obstructive events per night went from 4.6 to 17.6 postoperatively ( P = .04). The number of hypopneas increased from 4.0 to 13.6 ( P = .003). The other parameters were not statistically different, central events decreased from 4.8 to 2.1 ( P = .086), and mixed events were essentially unchanged from 0.2 to 0.5 ( P = .17) events per night.

CONCLUSIONS:
Patients undergoing sphincter pharyngoplasty for VPI may experience an increase in their postoperative AHI, obstructive events per night, and hypopneas. Sleep studies should be performed both pre- and postoperatively to assess the need for intervention or change in management.

KEYWORDS:
VPI; obstructive sleep apnea; polysomnography; sleep study; sphincter pharyngoplasty; velopharyngeal insufficiency

PMID: 29617152 DOI: 10.1177/1055665618766060
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167.
Sci Rep. 2018 Mar 26;8(1):5156. doi: 10.1038/s41598-018-23491-3.
Sex Genotyping of Archival Fixed and Immunolabeled Guinea Pig Cochleas.
Depreux FF1, Czech L1, Whitlon DS2,3,4.
Author information
1
Department of Otolaryngology-Head and Neck Surgery, Northwestern University, Chicago, IL, 60611, USA.
2
Department of Otolaryngology-Head and Neck Surgery, Northwestern University, Chicago, IL, 60611, USA. whitlon@northwestern.edu.
3
Interdepartmental Neurosciences Program, Northwestern University, Chicago, IL, 60611, USA. whitlon@northwestern.edu.
4
Knowles Hearing Center, Northwestern University, Evanston, IL, 60208, USA. whitlon@northwestern.edu.
Abstract
For decades, outbred guinea pigs (GP) have been used as research models. Various past research studies using guinea pigs used measures that, unknown at the time, may be sex-dependent, but from which today, archival tissues may be all that remain. We aimed to provide a protocol for sex-typing archival guinea pig tissue, whereby past experiments could be re-evaluated for sex effects. No PCR sex-genotyping protocols existed for GP. We found that published sequence of the GP Sry gene differed from that in two separate GP stocks. We used sequences from other species to deduce PCR primers for Sry. After developing a genomic DNA extraction for archival, fixed, decalcified, immunolabeled, guinea pig cochlear half-turns, we used a multiplex assay (Y-specific Sry; X-specific Dystrophin) to assign sex to tissue as old as 3 years. This procedure should allow reevaluation of prior guinea pig studies in various research areas for the effects of sex on experimental outcomes.

PMID: 29581456 PMCID: PMC5980087 DOI: 10.1038/s41598-018-23491-3
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Select item 29531195
168.
Med J Malaysia. 2018 Feb;73(1):1-6.
Quality of life and recurrence of disease in patients with eosinophilic and non-eosinophilic 1 chronic rhinosinusitis with nasal polyposis.
Khairuddin NK1, Salina H2, Gendeh BS2, Wan Hamizan AK2, Lund VJ3.
Author information
1
Universiti Kebangsaan Malaysia Medical Centre, Department of Otorhinolaryngology-Head and Neck Surgery, Kuala Lumpur, Malaysia. drsalina_h@yahoo.com.
2
Universiti Kebangsaan Malaysia Medical Centre, Department of Otorhinolaryngology-Head and Neck Surgery, Kuala Lumpur, Malaysia.
3
Royal National Throat Nose Ear Hospital, Professorial Unit, London, United Kingdom.
Abstract
OBJECTIVE:
To assess the quality of life (QoL) and recurrence of disease in patients with eosinophilic (ECRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyposis (non-ECRSwNP) post endoscopic sinus surgery (ESS).

METHODOLOGY:
A cross-sectional comparative study was carried out in the Otorhinolaryngology - HNS Department, Universiti Kebangsaan Malaysia Medical Center (UKMMC). Subjective assessments of nasal symptoms and quality of life (QoL) using SNOT-22 and Visual Analogue Scale (VAS) and objective endoscopic assessment was undertaken using a modified Hadley endoscopic examination.

RESULTS:
There was no significant statistical difference in the quality of life between the ECRSwNP and non-ECRSwNP groups as evidenced by the SNOT-22 score and the VAS comparison (p>0.05). However, there was a significant difference in terms of recurrence of disease with the presence of nasal polyps on endoscopic examination. (p = 0.016) CONCLUSION: In conclusion, we found that there is no significant difference in QoL between ECRSwNP and non- ECRSwNP. There is higher frequency of recurrence of nasal polyps amongst ECRSwNP.

PMID: 29531195
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Select item 29462449
169.
Oper Neurosurg (Hagerstown). 2018 Mar 1;14(3):243-251. doi: 10.1093/ons/opx100.
Endoscopic Transorbital Superior Eyelid Approach for the Management of Selected Spheno-orbital Meningiomas: Preliminary Experience.
Dallan I1,2, Sellari-Franceschini S1, Turri-Zanoni M2,3, de Notaris M4, Fiacchini G1, Fiorini FR1, Battaglia P2,3, Locatelli D5, Castelnuovo P2,3.
Author information
1
First ENT Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
2
Head and Neck Surgery and Forensic Dissection Research center (HNS and FDRc), Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
3
Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, University of Insubria, Ospedale di Circolo e Fondazione Macchi, Varese, Italy.
4
Division of Neurosurgery, Azienda Ospedaliera G. Rummo, Benevento, Italy.
5
Division of Neurosurgery, Department of Biotechnology and Life Sciences, University of Insubria, Ospedale di Circolo e Fondazione Macchi, Varese, Italy.
Abstract
BACKGROUND:
Feasibility and safety of spheno-orbital meningioma resection by means of endoscopic-assisted transorbital route.

OBJECTIVE:
To evaluate the feasibility and outcomes of the transorbital endoscopic management of selected spheno-orbital meningiomas. As secondary aims, symptom improvement and tumor volume removed were evaluated.

METHODS:
Retrospective chart evaluation of patients with spheno-orbital meningiomas treated by means of endoscopic transorbital superior eyelid approach in 3 referral centers over the last 4 yr.

RESULTS:
Fourteen cases were included in this study. In 4 patients, the transorbital endoscopic approach was combined with an endonasal route. Mean age was 51 and male-to-female ratio was 1:6. In 8 patients (57.1%), an intraorbital involvement was observed, 3 of them (21.4%) showed significant intraconal disease. No patient presented significant cavernous sinus infiltration. Main presenting symptoms were proptosis, diplopia, and visual impairment in 14, 6, and 6 patients, respectively. Mean proptosis improvement was 2 mm (standard deviation 2.3). We observed no major postoperative complications.

CONCLUSION:
Our preliminary clinical experience seems to demonstrate that selected spheno-orbital meningiomas can be safely managed by means of an endoscopic transorbital route through a superior eyelid approach. Patients with orbital or cavernous sinus infiltration are at highest risk of persistence.

PMID: 29462449 DOI: 10.1093/ons/opx100
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Select item 29436940
170.
J Biopharm Stat. 2018;28(6):1038-1054. doi: 10.1080/10543406.2018.1434191. Epub 2018 Feb 13.
Biomarker threshold adaptive designs for survival endpoints.
Diao G1, Dong J2, Zeng D3, Ke C2, Rong A4, Ibrahim JG3.
Author information
1
a Department of Statistics , George Mason University , Fairfax , Virginia , USA.
2
b Amgen Inc ., Thousand Oaks , California , USA.
3
c Department of Biostatistics , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina , USA.
4
d Astellas Pharma US, Inc ., Los Angeles , California , USA.
Abstract
Due to the importance of precision medicine, it is essential to identify the right patients for the right treatment. Biomarkers, which have been commonly used in clinical research as well as in clinical practice, can facilitate selection of patients with a good response to the treatment. In this paper, we describe a biomarker threshold adaptive design with survival endpoints. In the first stage, we determine subgroups for one or more biomarkers such that patients in these subgroups benefit the most from the new treatment. The analysis in this stage can be based on historical or pilot studies. In the second stage, we sample subjects from the subgroups determined in the first stage and randomly allocate them to the treatment or control group. Extensive simulation studies are conducted to examine the performance of the proposed design. Application to a real data example is provided for implementation of the first-stage algorithms.

KEYWORDS:
Adaptive enrichment design; predictive biomarker; survival endpoint; two-stage design

PMID: 29436940 PMCID: PMC6342463 DOI: 10.1080/10543406.2018.1434191
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171.
Eur Heart J. 2018 Apr 1;39(13):1113. doi: 10.1093/eurheartj/ehy020.
A heart-stopping diagnosis.
Spapen J1, Michiels V1, Droogmans S1.
Author information
1
Department of Cardiology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Jette, Brussels, Belgium.
PMID: 29409052 DOI: 10.1093/eurheartj/ehy020
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Select item 29145656
172.
Oper Neurosurg (Hagerstown). 2018 Mar 1;14(3):295-302. doi: 10.1093/ons/opx093.
Refining Operative Strategies for Optic Nerve Decompression: A Morphometric Analysis of Transcranial and Endoscopic Endonasal Techniques Using Clinical Parameters.
Gogela SL1,2, Zimmer LA1,3,2, Keller JT1,2,4, Andaluz N1,2,4.
Author information
1
Departments of Neurosurgery, Unive-rsity of Cincinnati College of Medicine, Cincinnati, Ohio.
2
Brain Tumor Center at University of Cincinnati Neuroscience Institute, Cincinnati, Ohio.
3
Departments of Otola-ryngology Head and Neck Surgery, Univ-ersity of Cincinnati College of Medicine, Cincinnati, Ohio.
4
Mayfield Clinic, Cincinnati, Ohio.
Abstract
BACKGROUND:
Various approaches can be considered for decompression of the intracanalicular optic nerve. Although clinical experience has been reported, no quantitative study has yet compared the extent of decompression achieved by an endoscopic endonasal versus transcranial approach.

OBJECTIVE:
Toward this aim, our morphometric analysis compared both approaches by quantifying the circumferential degree of optic canal decompression that is possible before any meningeal violation, which would result in cerebrospinal fluid (CSF) leak.

METHODS:
From 10 cadaver heads, 20 optic canals were sequentially decompressed using an endoscopic endonasal approach and pterional craniotomy with extradural clinoidectomy. Dissections ended before violation of the sphenoid sinus during the transcranial approach, and before intracranial transgression from the endonasal corridor. Based on our study criteria, decompressions were not maximal for either approach, but were maximal before violating the other compartment. Decompression achieved from each approach was quantified using CT scans for each stage.

RESULTS:
Greater circumferential bony optic canal decompression was obtained from transcranial (245.2°) than endonasal (114.8°) routes (P < .001). By endonasal perspective, the anatomical point where the optic nerve traverses intracranially was approximated by the medial border of the anterior ascending cavernous internal carotid artery.

CONCLUSION:
Our morphometric analysis comparing optic canal decompression for endonasal and transcranial corridors provides important guidance for this location. Ample visualization and wide exposure can be achieved via a transcranial approach with limited risk of CSF leak. A landmark, where the intracanalicular segment ends and optic nerve traverses intracranially, can mark the extent of decompression safely obtained before risking CSF leak.

Copyright © 2017 by the Congress of Neurological Surgeons

PMID: 29145656 DOI: 10.1093/ons/opx093
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Select item 29133225
173.
J Allergy Clin Immunol Pract. 2018 Jul - Aug;6(4):1327-1335.e3. doi: 10.1016/j.jaip.2017.10.012. Epub 2017 Nov 10.
Longitudinal Evaluation of Chronic Rhinosinusitis Symptoms in a Population-Based Sample.
Sundaresan AS1, Hirsch AG2, Young AJ2, Pollak J3, Tan BK4, Schleimer RP4, Kern RC4, Kennedy TL5, Greene JS5, Stewart WF6, Bandeen-Roche K7, Schwartz BS8.
Author information
1
Department of Epidemiology and Health Services Research, Geisinger Health System, Danville, Pa. Electronic address: ashsundaresan@geisinger.edu.
2
Department of Epidemiology and Health Services Research, Geisinger Health System, Danville, Pa.
3
Department of Environmental Health and Engineering, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Md.
4
Department of Otolaryngology Head and Neck Surgery and the Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
5
Department of Otolaryngology/Head and Neck/Facial Plastic Surgery, Geisinger Health System, Danville, Pa.
6
Sutter Health, Walnut Creek, Calif.
7
Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Md.
8
Department of Epidemiology and Health Services Research, Geisinger Health System, Danville, Pa; Department of Environmental Health and Engineering, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Md.
Abstract
BACKGROUND:
Chronic rhinosinusitis (CRS) is a prevalent and disabling condition of the nose and sinuses. The natural history of CRS symptoms in a general population sample has not been previously studied.

OBJECTIVE:
In a general population-based sample from Pennsylvania, we used 2 questionnaires mailed 6 months apart to estimate the prevalence of, and identify predictors for, stability or change in symptoms over time.

METHODS:
We mailed the baseline and 6-month follow-up questionnaires to 23,700 primary care patients and 7,801 baseline responders, respectively. We categorized nasal and sinus symptoms using European Position Paper on Rhinosinusitis (EPOS) epidemiologic criteria. We defined 6 symptom groups over time on the basis of the presence of CRS symptoms at baseline and follow-up. We performed multivariable survey logistic regression controlling for confounding variables comparing persistent versus nonpersistent, recurrent versus stable past, and incident versus never.

RESULTS:
There were 4,966 responders at follow-up: 558 had persistent symptoms, 190 recurrent symptoms, and 83 new symptoms meeting EPOS criteria for CRS. The prevalence of persistent symptoms was 4.8% (95% CI, 3.8-5.8), whereas the annual cumulative incidence of new symptoms was 1.9% and of recurrent symptoms was 3.2%. More severe symptoms at baseline were associated with persistence, whereas minor symptoms, allergies, and multiple treatments were associated with the development of new symptoms.

CONCLUSIONS:
Less than half with nasal and sinus symptoms meeting CRS EPOS criteria in our general, regional population had symptom persistence over time, with symptom profiles at baseline and age of onset being strongly associated with stability of symptoms.

Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

KEYWORDS:
Chronic rhinosinusitis; Incidence; Longitudinal; Persistence; Recurrence

PMID: 29133225 PMCID: PMC5945347 DOI: 10.1016/j.jaip.2017.10.012
[Indexed for MEDLINE] Free PMC Article
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Select item 28801828
174.
Clin Neuroradiol. 2018 Dec;28(4):523-528. doi: 10.1007/s00062-017-0617-5. Epub 2017 Aug 11.
A New Classification System is Helpful in Diagnosing Intracranial Complications of Acute Mastoiditis in CT.
Saat R1,2, Kurdo G3, Brandstack N3, Laulajainen-Hongisto A4, Jero J4,5, Markkola A3.
Author information
1
Dept. of Radiology, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 4, HUS 00029, POB 340, Helsinki, Finland. riste.saat@hus.fi.
2
Dept. of Radiology, East Tallinn Central Hospital, Ravi tn.18, 10138, Tallinn, Estonia. riste.saat@hus.fi.
3
Dept. of Radiology, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 4, HUS 00029, POB 340, Helsinki, Finland.
4
Dept. of Otorhinolaryngology and Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Kasarmikatu 11-13, HUS 00029, Helsinki, Finland.
5
Dept. of Otorhinolaryngology and Head and Neck Surgery, Turku University Hospital and University of Turku, Kiinamyllynkatu 4-8, P.O.BOX 52, 20521, Turku, Finland.
Abstract
PURPOSE:
To assess the usefulness of the new computed tomography (CT) classification criteria proposed by Horowitz et al. and their effect on inter-observer agreement when estimating intracranial complications of acute mastoiditis.

METHODS:
In this study 53 contrast-enhanced CT scans of patients with acute mastoiditis were each retrospectively reviewed by two radiologists, using two different assessment criteria for intracranial complications. According to the new criteria, intracranial CT findings in the perisinuous area were graded into four classes (I normal, II linear halo, III nodular halo ≤4 mm thick and IV nodular halo >4 mm thick), where classes III and IV indicate a high risk for epidural abscesses. Inter-reader agreement was estimated by weighted kappa analysis for both methods.

RESULTS:
With the old method, epidural abscesses were suspected in six and venous sinus thrombosis in five patients. With the new method, high-risk perisinuous lesions (classes III or IV) were detected in 11 patients, and sinus thrombosis outside the perisinuous area in 3 patients. All epidural abscesses were in the perisinuous area. Of the patients four, in whom intracranial pathology was not suspected with the old method, fell into the high-risk group (class III) according to the new method. All class IV lesions were also determined to be pathological with the old method. The inter-observer agreement (weighted kappa) rose from 0.21 (old method) to 0.80 (new method) when assessing epidural abscesses and from 0.44 (old method) to 0.85 (new method) when assessing sinus thrombosis.

CONCLUSION:
The new assessment method raised the inter-observer agreement for detection of intracranial acute mastoiditis complications, namely epidural abscesses and venous sinus thrombosis.

KEYWORDS:
Acute mastoiditis; Computed tomography (CT); Imaging; Infection; Otitis media complications; Temporal bone

PMID: 28801828 DOI: 10.1007/s00062-017-0617-5
[Indexed for MEDLINE]
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Select item 28541487
175.
Oper Neurosurg (Hagerstown). 2018 Mar 1;14(3):215-223. doi: 10.1093/ons/opx098.
Tumor Progression Following Petroclival Meningioma Subtotal Resection: A Volumetric Study.
Hunter JB1, O'Connell BP1, Carlson ML2, Chambless LC3, Yawn RJ1, Wang R1, Mistry A3, Thompson RC1,3, Weaver KD3, Wanna GB1,3.
Author information
1
Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
2
Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic School of Medicine, Roch-ester, Minnesota.
3
Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
Abstract
BACKGROUND:
One study has investigated postoperative growth rates following subtotal resection of petroclival meningiomas utilizing linear measurements, which are insensitive to the multidimensional complex growth of meningiomas, to estimate tumor volume.

OBJECTIVE:
To describe petroclival meningioma growth patterns following less-than-complete resection utilizing volumetric analysis and to identify variables associated with tumor progression.

METHODS:
Patients with surgically resected WHO grade I petroclival meningiomas were retrospectively reviewed (1999-2015). Image analysis software was utilized to perform volumetric analyses of tumor size and growth on serial MRI studies. The impact of preoperative and postoperative variables on tumor growth after subtotal resection was analyzed. An increase in tumor volume of at least 20% was defined as "tumor growth."

RESULTS:
Twenty-three patients had immediate preoperative and serial postoperative MRI studies available for review. The mean preoperative tumor volume was 20.9 cm3 (range 0.4-54.6). The mean extent of resection was 75.5% (range 31.5%-100.0%). At a mean follow-up of 24.8 mo, 12 tumors (66.7%) exhibited radiological tumor growth, while 6 tumors did not change in size. The median annual volumetric growth rate was 2.82 cm3/yr (range -0.34 to 10.1). Extent of resection and immediate postoperative tumor volume were significantly correlated with the annual volumetric growth rate following resection. At last follow-up, 3 (13%) patients required further intervention.

CONCLUSION:
The majority of petroclival meningiomas exhibit growth following subtotal resection. Extent of resection is strongly associated with risk for disease progression following surgery.

Copyright © 2017 by the Congress of Neurological Surgeons

PMID: 28541487 DOI: 10.1093/ons/opx098