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Lack of Apparent Survival Benefit from the Use of Androgen Deprivation Therapy in Patients with High-Risk Prostate Cancer Treated with Combined External Beam Radiotherapy and Brachytherapy

Publication date: Available online 9 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): David D. Yang, Vinayak Muralidhar, Brandon A. Mahal, Paul L. Nguyen, Phillip M. Devlin, Martin T. King, Peter F. Orio
PurposeWhile level 1 evidence has demonstrated a survival benefit from the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) for patients with high-risk prostate cancer, the benefits of ADT with combined EBRT and brachytherapy for high-risk patients are unclear. We examined the association between ADT and overall survival in a national cohort of high-risk patients treated with EBRT with or without brachytherapy.Methods and MaterialsWe identified 46,325 men in the National Cancer Database diagnosed from 2004 through 2011 with high-risk prostate cancer (Gleason 8-10, clinical T3-4, or prostate-specific antigen >20 ng/mL) who were treated with EBRT with or without brachytherapy and ADT. Multivariable Cox regression adjusting for sociodemographic and clinicopathologic factors was used to identify the association between ADT and overall survival.ResultsMedian follow-ups were 48.6 and 59.2 months for patients treated with EBRT only and combined modality radiotherapy, respectively. ADT was associated with an improvement in overall survival for the 85.0% (39,361) of the study cohort managed with EBRT alone (adjusted hazard ratio 0.91, P=0.001) but not for patients treated with combined modality radiotherapy (adjusted hazard ratio 1.05, P=0.496), with a significant interaction (Pinteraction=0.036).ConclusionsAs opposed to the known survival benefit when ADT is given with EBRT, our results suggest that ADT may not improve survival for high-risk patients treated with combined EBRT and brachytherapy. Given the significant adverse effects of ADT, particularly long-term therapy, a randomized controlled trial of combined EBRT and brachytherapy with or without ADT for select high-risk patients using a non-inferiority design should be undertaken.

Teaser

The benefits of androgen deprivation therapy (ADT) with combined external beam radiotherapy and brachytherapy for patients with high-risk prostate cancer are unknown. Using a large, national cohort of high-risk patients, we found that ADT was associated with an improvement in overall survival for patients managed with EBRT alone but not for patients treated with combined modality radiotherapy, suggesting that ADT may not improve overall survival for select high-risk patients treated with combined modality radiotherapy.


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Lhermitte-Duclos disease: clinical study with long-term follow-up in a single institution

Publication date: Available online 9 September 2017
Source:Clinical Neurology and Neurosurgery
Author(s): Qiguang Wang, Si Zhang, Jian Cheng, Wenke Liu, Xuhui Hui
ObjectiveLDD is a rare lesion, controversy about diagnosis and treatment of LDD and CS still exists. We aimed to clarify clinical and radiological characteristics, the optimal treatment timing and strategies of LDD with long-term follow-up.Patients and MethodsFrom January 2004 to May 2017, 12 LDD patients were enrolled in our study. The clinical and radiological features, treatment strategies and long-term follow-up data were retrospectively analyzed.ResultsThe mean follow-up was 89.1±36.9 months (range, 31-161months). Twelve patients (7 males and 5 females, mean age 28.0±14.8 years, range 3-55 years) were included in this study. The most frequent symptoms were those related to increased intracranial pressure. Mean duration of symptoms was 15.6±9.5 months. Average tumor size was 62±9.3mm in its maximal diameter (range, 50–84mm). Tonsillar herniation and preoperative hydrocephalus was observed in 9/12 and 12/12 patients. Four of them confirmed the diagnosis of CS. Gross total resection was achieved in 3 patients, partial in 6 patients and subtotal in 3 patients. All patients experienced improvement of symptoms. Recurrence and progression were identified in only 1/12 patient.ConclusionsLDD has pathognomonic appearance on T2-weighted MRI. We recommend surgery decision should be based on symptoms appearance or progress in imaging. Total resection is difficult due to the indistinct tumor margin, favorable outcome and rare recurrence were also observed despite of partial or subtotal resection in our series. A long-term screening for Cowden's disease and tumor recurrence is essential for every patient.



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Recovery from diabetes insipidus and preservation of thyroid function after craniopharyngioma removal and pituitary stalk sectioning

Publication date: Available online 9 September 2017
Source:Clinical Neurology and Neurosurgery
Author(s): Yoshikazu Ogawa, Kuniyasu Niizuma, Teiji Tominaga
ObjectivesCraniopharyngioma is a slow-growing tumor, but long-term tumor control with maintenance of quality of life is sometimes very difficult to achieve, and hypothalamic disturbance should be strictly avoided in the treatment. However, management of the pituitary gland and/or pituitary stalk varies among surgeons and institutions.Patients and MethodsThis retrospective review identified 44 patients, 24 males and 20 females with craniopharyngiomas who were initially treated by surgery through the extended transsphenoidal approach with pituitary stalk sectioning at a single institute. If the tumor bed involved the posterior lobe of the pituitary gland, pituitary stalk, anterior and/or mid portion of the third ventricle floor, these structures were removed en-bloc together with the tumor. The closest attention was paid to preserve fine arteries running along the surface of optic chiasm and the lateral walls of the third ventricle. Surgical outcome and changes in postoperative endocrinological status were investigated.ResultsGross total removal was achieved in 40 of 44 patients (91%), and all patients could discharge without autonomic and/or thermal disturbances. Tumor remnants were identified with tight adhesion to the perforating arteries in 2 cases, tight adhesion to mammillary bodies in 1, and optic chiasm in 1. Administration of anti-diuretic hormone could be discontinued in 23 of 44 patients (52.3%) with improved diabetes insipidus (DI), although no patient could discontinue glucocorticoid administration. Preservation of thyroid function was achieved in another 23 of 44 patients (52.3%), and recovery from DI was correlated with preservation of thyroid function (p=0.016).ConclusionPituitary dysfunction is partially reversible even with pituitary stalk sectioning. Regrowth of tumor in the anterior and/or mid portion of the third ventricle floor including pituitary stalk can possibly be prevented by aggressive tumor removal, and co-achievement of long-term tumor control with maintenance of quality of life could be possible to preserve the lateral wall of the third ventricle.



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Editorial Board

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Two Scientific Awards for papers published in Sleep Medicine

Under the auspices of the World Association of Sleep Medicine (WASM), Elsevier has established two scientific awards for young basic and clinical sleep specialists in honor of Christian Guilleminault and Elio Lugaresi, respectively. The awards are a tribute to Dr. Guilleminault's and Dr. Lugaresi's contributions to establish the field of Sleep Medicine, its journal and its Society.

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Unusual Superolateral Dislocation of Bilateral Mandibular Condyles

Abstract

We describe a case of maxillofacial trauma in a paediatric patient in which the left mandibular condyle was superolaterally displaced into the temporal fossa, medial to the zygomatic arch which was intact and the right condyle was also displaced similarly but the zygomatic arch was also fractured on this side. Also, there was an associated mandibular symphyseal fracture.

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Knowledge About the Relation Between Tobacco and Disease and the Attitude Toward Advising the Cessation of Its Consumption Among a Group of Spanish Dental Students

Abstract

Tobacco is one of the leading causes of preventable death in the developed world. Smoking is associated with a large number of oral pathologies, such as cancer and periodontitis. Dental professionals can play a key role in preventing these health problems. The objectives of this study were (1) to analyze tobacco consumption habits among a group of Spanish dental students, and (2) to assess their knowledge, perceptions, and attitudes regarding procedures to help patients quit smoking. A cross-sectional descriptive study was carried out at the Faculty of Medicine and Dentistry of Santiago de Compostela (Galicia, Spain). Three validated questionnaires were distributed, and the obtained data was processed using SPSS. One hundred twenty out of 220 surveys were completed. Of the students, 18.3% were smokers and the average number of smoked cigarettes per day was 7.5. Tobacco dependence and the intention to give up the habit were low (Fagerström Test) and doubtful (Richmond test), respectively. The majority of students (94.2%) considered it appropriate to promote tobacco use cessation (TUC) activities. A great divergence of criteria regarding tobacco-associated pathologies was found among courses. This article provides positive data about the motivation of dental students to implement TUC strategies. Nevertheless, the usefulness of these interventions makes it necessary to modify the university curricula in order to improve the education on this issue to reduce the incidence of future health problems.

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Knowledge About the Relation Between Tobacco and Disease and the Attitude Toward Advising the Cessation of Its Consumption Among a Group of Spanish Dental Students

Abstract

Tobacco is one of the leading causes of preventable death in the developed world. Smoking is associated with a large number of oral pathologies, such as cancer and periodontitis. Dental professionals can play a key role in preventing these health problems. The objectives of this study were (1) to analyze tobacco consumption habits among a group of Spanish dental students, and (2) to assess their knowledge, perceptions, and attitudes regarding procedures to help patients quit smoking. A cross-sectional descriptive study was carried out at the Faculty of Medicine and Dentistry of Santiago de Compostela (Galicia, Spain). Three validated questionnaires were distributed, and the obtained data was processed using SPSS. One hundred twenty out of 220 surveys were completed. Of the students, 18.3% were smokers and the average number of smoked cigarettes per day was 7.5. Tobacco dependence and the intention to give up the habit were low (Fagerström Test) and doubtful (Richmond test), respectively. The majority of students (94.2%) considered it appropriate to promote tobacco use cessation (TUC) activities. A great divergence of criteria regarding tobacco-associated pathologies was found among courses. This article provides positive data about the motivation of dental students to implement TUC strategies. Nevertheless, the usefulness of these interventions makes it necessary to modify the university curricula in order to improve the education on this issue to reduce the incidence of future health problems.

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A randomized trial of clitoral vacuum suction versus vibratory stimulation in neurogenic female orgasmic dysfunction

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Marcalee Alexander, Khurram Bashir, Craig Alexander, Lesley Marson, Raymond Rosen
ObjectiveTo examine safety and efficacy of use of a clitoral vacuum suction device (CVSD) versus vibratory stimulation (V) to treat orgasmic dysfunction in women with MS or SCI.DesignRandomized clinical trial.SettingTwo academic medical centers.ParticipantsThirty-one women including 20 with MS and 11 with SCI.InterventionA 12-week trial of the use of a CVSD versus VMain Outcome measuresFemale Sexual Function Inventory (FSFI) and Female Sexual Distress Scale (FSDS).Results23 women (18 MS; 5 SCI) completed the study including 13/16 randomized to CVSD and 10/15 randomized to V. There was a statistically significant increase in total FSFI score (p=.011), desire (p=. 009), arousal (p=.009), lubrication (p=.008), orgasm (p=.012), and satisfaction (p=.049) and a significant decrease in distress as measured by FSDS (p=.020) in subjects using the CVSD. In subjects who used V, there was a statistically significant increase in the orgasm subscale of the FSFI (p=.028). Subjects using the CVSD maintained improvements 4 weeks after treatment.ConclusionCVSD is safe and overall efficacious to treat female neurogenic sexual dysfunction related to MS and SCI. V is also safe and efficacious to female neurogenic orgasmic dysfunction; however, results were limited to the active treatment period. Due to ease of access and cost, clinicians can consider use of V for women with MS or SCI with orgasmic dysfunction. CVSD is recommended for women with multiple sexual dysfunctions or for whom V is ineffective.



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Comparative efficacy of intra-articular steroid injection and distension in patients with frozen shoulder: a systematic review and network meta-analysis

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Meng-Ting Lin, Ming-Yen Hsiao, Yu-Kang Tu, Tyng-Guey Wang
ObjectiveTo compare the efficacy of intra-articular (IA) steroid injection and distension in patients with frozen shoulder.Data SourcesDatabases, including MEDLINE (via PubMed), EMBASE, Scopus and Cochrane Library, were searched for studies published up to November 2016.Study SelectionWe included all published randomized controlled trials (RCTs), quasi-experimental studies and observational studies investigating the effectiveness of IA steroid injection, distension and physiotherapy in patients with frozen shoulder. Sixteen RCTs and one observational study were enrolled in meta-analysis.Data ExtractionFull-texts were independently reviewed and quality of RCTs was assessed with The Cochrane Collaboration's tool. The primary outcome was functional improvement; the secondary outcomes included pain reduction and external rotation (ER) improvement.Data SynthesisIn pair-wise meta-analysis, pooled standardized mean difference (SMD) of functional improvement and pain reduction revealed equal efficacy at three follow-up time points. With respect to ER improvement, distension has a superior effect as compared to IA steroid injection at short term [2–4 weeks; SMD: −0.36; 95% confidence interval (CI): −0.68∼ −0.04] and at medium term (6–16 weeks; SMD: −0.80; 95% CI: −1.32∼ −0.29). The network meta-analysis indicated a better efficacy for distension than for IA steroid injection in ER improvement only at medium term (6–16 weeks; SMD: −0.70; 95% CI: −1.19∼ −0.21).ConclusionIA steroid injection was as effective as distension in shoulder-function improvement, pain reduction and increasing ER of shoulder. Distension yielded better ER improvement at medium term but to a minor extent in the long term. For patients with predominant ER limitation, early distension could be considered the primary choice of treatment.



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Group- and individual-level responsiveness of the 3-point Berg Balance Scale and 3-point Postural Assessment Scale for Stroke Patients

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Yi-Jing Huang, Gong-Hong Lin, Shih-Chieh Lee, Yi-Miau Chen, Sheau-Ling Huang, Ching-Lin Hsieh
ObjectiveTo examine both group- and individual-level responsiveness of the 3-point Berg Balance Scale (BBS-3P) and 3-point Postural Assessment Scale for Stroke Patients (PASS-3P) in patients with stroke, and to compare the responsiveness of both 3-point measures versus their original measures (BBS and PASS) and their short forms (SFBBS and SFPASS) and between the BBS-3P and PASS-3P.DesignThe data were retrieved from a previous study wherein 212 patients were assessed at 14 and 30 days after stroke with the BBS and PASS.SettingMedical center.ParticipantsPatients with first onset of stroke within 14 days before hospitalization.Interventions.Not applicable.Main Outcome Measures.Group-level responsiveness was examined by the standardized response mean (SRM), and individual-level responsiveness was examined by the proportion of patients whose change scores exceeded the minimal detectable change of each measure. The responsiveness was compared using bootstrap approach.ResultsThe BBS-3P and PASS-3P had good group-level (SRM=0.60 and 0.56, respectively) and individual-level (48.1% and 44.8% of the patients with significant improvement, respectively) responsiveness. Bootstrap analyses showed that the BBS-3P generally had superior responsiveness to the BBS and SFBBS, and the PASS-3P had similar responsiveness to the PASS and SFPASS. The BBS-3P and PASS-3P were equally responsive to both group and individual's change.ConclusionsThe responsiveness of the BBS-3P and PASS-3P was comparable or superior to those of the original and short-form measures. We recommend the BBS-3P and PASS-3P as responsive outcome measures of balance for individuals with stroke.



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Long-term performance and user satisfaction with implanted neuroprostheses for upright mobility after paraplegia: Two to 14-year follow-up

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ronald J. Triolo, Stephanie Nogan Bailey, Kevin M. Foglyano, Rudi Kobetic, Lisa M. Lombardo, Michael E. Miller, Gilles Pinault
ObjectiveTo quantify the long-term (LT) (>2 years) effects of lower extremity (LE) neuroprostheses (NPs) for standing, transfers, stepping and seated stability after spinal cord injury.DesignSingle-subject design case series with participants acting as their own concurrent controls, including retrospective data review.SettingHospital-based clinical biomechanics laboratory with experienced (>20 years in the field) research biomedical engineers, physical therapist and medical monitoring review.ParticipantsTwenty-two (19 male, 3 female) LT (6.2 ± 2.7 years) at-home users of implanted NPs for trunk and LE function with chronic (14.4 ± 7.1 years) spinal cord injury resulting in full or partial paralysis.InterventionsTechnical and clinical performance measurements, along with user satisfaction surveys.Main Outcome MeasuresKnee extension moment, maximum standing time, body weight supported by lower extremities, three functional standing tasks, two satisfaction surveys, NP usage, and stability of implanted components.ResultsStimulated knee extension strength and functional capabilities were maintained with 94% of implant recipients reporting being "very" or "moderately" satisfied with their system. Greater than half (60%) of the participants were still using their implanted NPs for exercise and function for more than 10 minutes per day on nearly half or more of the days monitored, although maximum standing times and percentage body weight through LEs decreased slightly over the follow-up interval. Stimulus thresholds were uniformly stable. Six-year survival rates for the first-generation implanted pulse generator (IPG) and epimysial electrodes were close to 90%, while those for the second-generation IPG along with the intramuscular and nerve cuff electrodes were greater than 98%.ConclusionsObjective and subjective measures of the technical and clinical performances of implanted LE NPs generally remained consistent for 22 participants after an average of 6 years of unsupervised use at home. These findings suggest that implanted LE NPs can provide lasting benefits that recipients value.



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Premature Growth Plate Closure in a Ballet Dancer en Pointe

Abstract: A 13-year-old ballet dancer who had been dancing en pointe (on the tips of the toes) since 10 years presented to the clinic with a shortened right second toe. She had no previous history of pain or trauma. She was diagnosed with premature growth arrest of the second metatarsal head physes resulting in a shortened metatarsal. This is the first reported case of premature growth arrest in a ballet dancer as a result of dancing en pointe.

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Radial Extracorporeal Shock Wave Therapy Is Effective and Safe in Chronic Distal Biceps Tendinopathy

Objective: To assess the efficacy and safety of radial extracorporeal shock wave therapy (rESWT) for chronic distal biceps tendinopathy (cDBT). Design: Case–control study (level of evidence, 3). Setting: SUN Orthopaedics and Sports Medicine. Patients: Patients with a diagnosis of cDBT were recruited between January 2010 and February 2015. Interventions: Patients received a single session of rESWT (2000 shock waves with energy flux density of 0.18 mJ/mm2) or other forms of nonoperative therapy. Main Outcome Measures: Patients completed the visual analog scale (VAS), the modified QuickDASH (MQD) score, and the Roles and Maudsley (RM) score over a 12-month period. Results: Forty-eight patients completed the final review at 12 months and were included in the study. Subjects ranged in age from 30 to 64 years. Mean pretreatment VAS scores for the rESWT and control groups were 8.3 and 8.5, respectively. Three and 12 months after inclusion in the study, the mean VAS scores for the rESWT and control groups were 3.4 and 5.6 (P

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Incidence of Iron Deficiency and Iron Deficient Anemia in Elite Runners and Triathletes

Objective: To assess the incidence of iron deficiency (ID), and iron deficient anemia (IDA) within a cohort of highly trained runners and triathletes, and to examine the association of oral iron supplementation history with serum ferritin (sFe) and hemoglobin (Hb) concentrations. Methods: A retrospective analysis of routine blood test data taken from 2009 to 2015 from (n = 38) elite level runners and triathletes between the ages of 21 to 36 years. Oral iron supplement intake was assessed through a questionnaire. Results: Triathletes (female, FT; male, MT) and runners (female, FR; male, MR) had higher incidence of at least 1 episode of ID (FT 60.0%, MT 37.5%, FR 55.6%, MR 31.3%) compared with values reported in the literature for endurance athletes (20%-50% females, 0%-17% males). Male triathletes and runners had a higher incidence of IDA than their female teammates (25% MT, 20% FT, 6.3% for MR, 0% FR), a finding which has previously not been reported. Hemoglobin concentrations were low, with incidence of Hb

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Effects of Femoral Rotational Taping on Dynamic Postural Stability in Female Patients With Patellofemoral Pain

Objective: To investigate the effects of femoral rotational taping on task performance, dynamic postural control, and pain during the Star Excursion Balance Test (SEBT) in patients with patellofemoral pain (PFP) compared to healthy controls. Design: Case–control study, pretest–posttest. Setting: Laboratory. Participants: Twenty-four female participants (16 with PFP, 8 controls). Interventions: Participants in both the PFP and control groups performed SEBT with no taping, sham taping, and femoral rotational taping. Main Outcome Measures: The maximum anterior excursion distance, 3-dimensional hip and knee kinematics of the stance leg, and pain score (VAS) during SEBT were recorded. The coefficients of variance (CV) of kinematic data gathered from electromagnetic sensors on pelvis and femur were calculated to represent segmental stability. Results: When performing the SEBT in the anterior direction, application of femoral rotational taping increased maximum excursion distance (65.57% vs 66.15% leg length, P = 0.027), decreased hip adduction excursion (47.6 vs 32.1 degrees, P = 0.010), and pain (3.34 vs 2.38, P = 0.040) in the PFP group. Femoral rotational taping also improved the medial-lateral (7.1 vs 4.6, P = 0.015) and proximal-distal stability (7.5 vs 4.5, P = 0.020) of the pelvis, and medial-lateral stability (7.2 vs 6.1, P = 0.009) of the femur. Conclusions: The results support the use of femoral rotational taping for improving dynamic postural control and reducing pain during SEBT. Clinical Relevance: Femoral rotational taping could be used in the management of young female patients with PFP.

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Early Screening for Cardiovascular Abnormalities With Preparticipation Echocardiography: Feasibility Study

Objective: The traditional history and physical (H&P) is a poor screening modality to identify athletes at risk for sudden cardiac death. Although better than H&P alone, electrocardiograms (ECG) have also been found to have high false-positive rates. A limited portable echocardiogram by a frontline physician (PEFP) performed during preparticipation physical examination (PPE) allows for direct measurements of the heart to more accurately identify athletes with structural abnormalities. Therefore, it is worthwhile to assess the feasibility of incorporating limited PEFP as part of PPEs. The aim of this study was to investigate the feasibility of incorporating limited screening PEFP into routine PPEs. Methods: Thirty-five Division I male collegiate athletes were prospectively enrolled in the study after informed consent was obtained. Each athlete underwent screening with H&P, ECG, and limited PEFP. The H&P was performed based on the 2007 twelve-element preparticipation cardiovascular screening guidelines from the American Heart Association. The ECGs were interpreted using the 2013 Seattle Criteria. The limited echocardiographic (ECHO) measurements were obtained in the parasternal long axis view. End-diastolic measurements were recorded for the left ventricular diameter (LVD), left ventricular posterior wall diameter (LVPWd), interventricular septal wall diameter (IVSWd), aortic root diameter, and ascending aorta. The length of time of each screening station was recorded and reported in seconds (sec) and compared by one-way repeated-measures of analysis of variance with pairwise Bonferroni correction. A priori alpha level was set as 0.05. Results: The length of time for screening was significantly shorter with limited PEFP (137.7 ± 40.4 seconds) compared with H&P (244.2 ± 80.0 seconds) and ECG (244.9 ± 85.6 seconds, P

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Assessment of the Postural Stability of Female and Male Athletes

Objective: Postural stability is often affected by sport-related injuries and subsequently evaluated during postinjury examinations. Intrinsic factors, however, may also affect postural control. We sought to compare the postural control of female and male athletes as measured simultaneously by (1) the modified balance error scoring system (mBESS) and (2) a video-force plate system. Design: Cross-sectional study. Setting: Sports injury prevention center. Participants: Pediatric, adolescent, and young adult athletes who performed mBESS during an injury prevention evaluation. Independent Variables: We compared the postural control of female and male athletes. We also accounted for independent variables associated with postural stability, including age, body mass index, and history of ankle injury, concussion, and migraine headache. Main Outcome Measures: Total errors committed during the mBESS and measurements derived from integrated kinematic and kinetic data obtained by a video-force plate system. Differences between males and females were tested using analysis of covariance. Results: Participants (n = 409) ranged in age from 10 to 29 years (mean = 14.6 ± 2.8); 60% were female. No significant differences on mBESS were detected between females and males; however, female athletes demonstrated significantly better postural stability on the video-force plate analysis during double-leg (P = 0.03, d = 0.28), single-leg (P

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Concussion in Ice Hockey: Current Gaps and Future Directions in an Objective Diagnosis

Objective: This review provides an update on sport-related concussion (SRC) in ice hockey and makes a case for changes in clinical concussion evaluation. Standard practice should require that concussions be objectively diagnosed and provide quantitative measures of the concussion injury that will serve as a platform for future evidence-based treatment. Methods: The literature was surveyed to address several concussion-related topics: research in ice hockey-related head trauma, current subjective diagnosis, promising components of an objective diagnosis, and current and potential treatments. Main Results: Sport-related head trauma has marked physiologic, pathologic, and psychological consequences for athletes. Although animal models have been used to simulate head trauma for pharmacologic testing, the current diagnosis and subsequent treatment in athletes still rely on an athlete's motivation to report or deny symptoms. Bias-free, objective diagnostic measures are needed to guide quantification of concussion severity and assessment of treatment effects. Most of the knowledge and management guidelines of concussion in ice hockey are generalizable to other contact sports. Conclusions: There is a need for an objective diagnosis of SRC that will quantify severity, establish a prognosis, and provide effective evidence-based treatment. Potential methods to improve concussion diagnosis by health care providers include a standardized concussion survey, the King–Devick test, a quantified electroencephalogram, and blood analysis for brain cell-specific biomarkers.

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Allergies and Exercise-Induced Bronchoconstriction in a Youth Academy and Reserve Professional Soccer Team

Objectives: A high prevalence of respiratory allergies and exercise-induced bronchoconstriction (EIB) has been reported among endurance athletes. This study was designed to analyze the frequency of sensitization to respiratory allergens and EIB in young soccer players. Design: Prospective cohort design. Setting: Youth academy and reserve professional soccer team during the seasons 2012 to 2013 and 2013 to 2014. Participants: Eighty-five soccer players (mean age: 20 ± 4 years) participated. Intervention: Players underwent skin prick tests (SPTs) during the seasons 2012 to 2013 and 2013 to 2014. Spirometry and a eucapnic voluntary hyperpnea test were performed on soccer players during the first season 2012 to 2013 (n = 51) to detect EIB. Two self-administered questionnaires on respiratory history and allergic symptoms (European Community Respiratory Health Survey and Allergy Questionnaire for Athletes) were also distributed during both seasons (n = 59). Main Outcome Measures: The number of positive SPTs, exercise-induced respiratory symptoms, presence of asthma, airway obstruction, and EIB. Results: Forty-nine percent of players were sensitized to at least one respiratory allergen, 33% reported an allergic disease, 1 player presented airway obstruction at rest, and 16% presented EIB. Factors predictive of EIB were self-reported exercise-induced symptoms and sensitization to at least 5 allergens. Conclusions: Questioning players about exercise-induced respiratory symptoms and allergies as well as spirometry at the time of the inclusion medical checkup would improve management of respiratory health of soccer players and would constitute inexpensive preliminary screening to select players requiring indirect bronchial provocation test or SPTs. Clinical relevance: This study showed that despite low frequencies, EIB and allergies are underdiagnosed and undertreated in young soccer players.

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In Response to: Prediction of Maximal Heart Rate in Children and Adolescents: Prediction Study in Cross-Sectional Design, Is It True?

No abstract available

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Analysis of Central and Peripheral Vision Reaction Times in Patients With Postconcussion Visual Dysfunction

Objective: To determine whether central and peripheral vision reaction times (PVRTs) are prolonged in patients with visual dysfunction after sustaining a concussion. Design: Comparison of Dynavision D2 central and PVRTs in patients with postconcussion visual dysfunction were compared with control data from a normative patient database. Concussion patients without visual dysfunction were not included in this study. Setting: National Collegiate Athletic Association Division 1 college training room and university based, academic health center. Participants: Patients were selected for inclusion based on diagnosis of new visual dysfunction as indicated either by physical examination of the team physician or by patient self-report of symptoms. Patients included college athletes, college students, and concussion patient's presenting to a university based, academic health center. Intervention: Measurement of central and PVRTs using a Dynavision D2 reaction time program were used as the dependent variables. Evaluations were conducted from 3 days to 11 months postconcussion, depending on the temporal development of visual symptoms after the concussion. No intervention was used. Main Outcome Measures: Average central and PVRTs for patients with postconcussion visual symptoms were compared with an asymptomatic control group with no history of concussion. Results: Both central and PVRTs were significantly prolonged in patients with postconcussion visual symptoms compared with patients with no history of concussion. Conclusions: Central and PVRTs are both prolonged in patients with postconcussion visual dysfunction with PVRT being disproportionately prolonged. The percent change from central to PVRT was also increased in patients with postconcussion visual dysfunction.

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A 12-Month Prospective Cohort Study of Symptoms of Common Mental Disorders Among European Professional Footballers

Objective: To determine the 12-month incidence and comorbidity of symptoms of common mental disorders (CMD) among European professional footballers and to explore the association of potential stressors with the health conditions under study among those European professional footballers. Design: Observational prospective cohort study with a follow-up period of 12 months. Participants: Male professional footballers from 5 European countries (n = 384 at baseline). Assessment of Risk Factors: Adverse life events, conflicts with trainer/coach, and career dissatisfaction were explored by using validated questionnaires. Main Outcome Measures: Symptoms of distress, anxiety/depression, sleep disturbance, and adverse alcohol use were assessed using validated questionnaires. Results: A total of 384 players (mean age of 27 years old; mean career duration of 8 years) were enrolled, of which 262 completed the follow-up period. The incidence of symptoms of CMD were 12% for distress, 37% for anxiety/depression, 19% for sleep disturbance, and 14% for adverse alcohol use. Over the follow-up period of 12 months, approximately 13% of the participants reported 2 symptoms, 5% three symptoms, and 3% four symptoms. Professional footballers reporting recent adverse life events, a conflict with trainer/coach, or career dissatisfaction were more likely to report symptoms of CMD, but statistically significant associations were not found. Conclusions: The 12-month incidence of symptoms of CMD among European professional footballers ranged from 12% for symptoms of distress to 37% for symptoms of anxiety/depression. A professional football team typically drawn from a squad of 25 players can expect symptoms of CMD to occur among at least 3 players in one season.

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Normative Values of the Sport Concussion Assessment Tool 3 (SCAT3) in High School Athletes

Objective: Establish sex, age, and concussion history–specific normative baseline sport concussion assessment tool 3 (SCAT3) values in adolescent athletes. Design: Prospective cohort. Setting: Seven Wisconsin high schools. Participants: Seven hundred fifty-eight high school athletes participating in 19 sports. Independent Variables: Sex, age, and concussion history. Main Outcome Measures: Sport Concussion Assessment Tool 3 (SCAT3): total number of symptoms; symptom severity; total Standardized Assessment of Concussion (SAC); and each SAC component (orientation, immediate memory, concentration, delayed recall); Balance Error Scoring System (BESS) total errors (BESS, floor and foam pad). Results: Males reported a higher total number of symptoms [median (interquartile range): 0 (0-2) vs 0 (0-1), P = 0.001] and severity of symptoms [0 (0-3) vs 0 (0-2), P = 0.001] and a lower mean (SD) total SAC [26.0 (2.3) vs 26.4 (2.0), P = 0.026], and orientation [5 (4-5) vs 5 (5-5), P = 0.021]. There was no difference in baseline scores between sex for immediate memory, concentration, delayed recall or BESS total errors. No differences were found for any test domain based on age. Previously, concussed athletes reported a higher total number of symptoms [1 (0-4) vs 0 (0-2), P = 0.001] and symptom severity [2 (0-5) vs 0 (0-2), P = 0.001]. BESS total scores did not differ by concussion history. Conclusion: This study represents the first published normative baseline SCAT3 values in high school athletes. Results varied by sex and history of previous concussion but not by age. The normative baseline values generated from this study will help clinicians better evaluate and interpret SCAT3 results of concussed adolescent athletes.

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Epidemiology of Snow Skiing– Versus Snowboarding-Related Concussions Presenting to the Emergency Department in the United States from 2010 to 2014

Objectives: To examine the trend of concussions in skiers and snowboarders from 2010 to 2014; and to quantify and compare the incidence of concussions injuries in skiers and snowboarders who presented to emergency departments in the United States in 2014. Design: Cross-sectional study of concussions in skiers and snowboarders who were evaluated in emergency departments in the United States. Main Outcomes Measure: Incidence of concussions. Results: The trend of the annual incidence of concussions for skiers and snowboarders remained stable from 2010 to 2014. An estimated total of 5388 skiing-related concussions and 5558 snowboarding-related concussions presented to emergency departments in the United States between January 1st, 2014, and December 31st, 2014. This represented an incidence of 16.9 concussions per 1 000 000 person-years for skiers and 17.4 concussions per 1 000 000 person-years for snowboarders. The incidence of concussions in the pediatric and young adult population of skiers was significantly higher than the incidence in the adult population. Similarly, the incidence of concussions in the pediatric and young adult population of snowboarders was significantly higher than the incidence in the adult population. The incidence of concussions was significantly higher in males compared with females in both skiing and snowboarding. Conclusions: The incidence of concussions from 2010 to 2014 plateaued in both skiers and snowboarders. Pediatric and young adult skiers and snowboarders had significantly higher incidences of concussion than the adult population. In contrast to the higher incidence of concussions in females in several sports including ice hockey, soccer, and basketball, the incidence of concussions was higher in males compared with females in both skiing and snowboarding.

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Patellar Tendinopathy and Potential Risk Factors: An International Database of Cases and Controls

Objectives: Numerous risk factors have been identified for patellar tendinopathy (PT), often in small population studies. The aim was to use an international online questionnaire to generate a large database and identify significant risk factors. Design: Case–control study. Setting: Private practice and sporting teams recruited from England, Spain, and Italy with the questionnaire available in all 3 languages (equivalence between online and self-administration shown previously). All data were anonymized and password protected. Participants: Eight hundred twenty-five data sets collected between January 2012 and May 2014. Assessment of Risk Factors: A total of 23.4% of participants had clinically diagnosed PT. A comparison between these participants and participants without PT was made. Main Outcome Measure: Association between the presence of PT and risk factors. Results: Eight risk factors were included in the analysis based on a purposeful selection procedure: sex, hours of training, hamstring flexibility, previous patellar tendon rupture, previous knee injury, current/previous back pain, family history, and age. Four were found to have statistically significant odds ratios: female sex [0.70, 95% confidence interval (CI), 0.49-1.00, P = 0.05], hours of training (>20 hours 8.94, 95% CI, 4.68-17.08, P

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Abdominal Aortic Dissection and Cold-Intolerance After Whole-Body Cryotherapy: A Case Report

Abstract: Whole-body cryotherapy (WBC) involves short exposures to air temperatures below −100°C and is purported to enhance recovery after exercise and accelerate rehabilitation after injury. It is generally considered a procedure with few side effects, but there are no large studies that have established its safety profile. We present the case of a 56-year-old patient who developed an abdominal aortic dissection after receiving 15 sessions of WBC. The patient had no other strong risk factors for aortic dissection. Exposure to cold temperatures, including WBC, has multiple hemodynamic effects, including increases in blood pressure, heart rate, and an adrenergic response. We suggest that these changes could act as a trigger for the onset of aortic dissections. This could be the first reported cardiovascular complication associated with WBC.

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Trunk Muscle Function Deficit in Youth Baseball Pitchers With Excessive Contralateral Trunk Tilt During Pitching

Objective: Pitching technique is one of many factors that affect injury risk. Exhibiting excessive contralateral trunk tilt (CLT) during pitching has been linked to higher ball speed but also to increased joint loading. Deficit in trunk muscle strength has been suggested as an underlying cause of this movement pattern. The purpose of the study was to compare trunk muscle strength between youth baseball pitchers with varying degree of CLT during pitching. Design: Cross-sectional study. Setting: Baseball practice fields. Participants: Twenty-eight youth baseball pitchers. Independent Variables: Pitching technique was captured using a video camera. Based on the 2-dimensional trunk contralateral flexion angle, pitchers were categorized into low (30 degrees) CLT groups. Main Outcome Measures: Maximum isometric strength tests for trunk flexion, extension, and bilateral rotation, measured using a dynamometer. Results: The pitchers with high CLT (n = 10) had longer pitching experience (P = 0.014), produced higher ball speed (P = 0.003) compared with the pitchers with moderate (n = 10) and low (n = 8) CLT, but demonstrated greater asymmetry in trunk rotation strength (relative weakness in rotation strength toward dominant side) compared with the pitchers with low CLT (P = 0.015). Conclusions: Excessive CLT may be a strategy that young pitchers learn to achieve higher ball velocity but also may be associated with imbalance between the oblique muscles on dominant and nondominant side, which may be acquired from repetitive pitching. Strengthening and emphasizing the use of dominant side oblique muscles may keep pitchers from leaning excessively during pitching and thus decrease joint loading.

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Bilateral Anterior Knee Pain in a High School Cross-Country Runner: An Atypical Etiology

Abstract: Anterior knee pain is a common complaint found in distance runners, and can be the end result of a variety of benign processes. A 17-year-old female cross-country runner presented to a sports medicine clinic with insidious onset of bilateral patellofemoral pain (PFP). In the workup of the significant quadriceps weakness discovered on her initial examination, a principal contributing cause of her PFP, she was found to have a form of spinal muscular atrophy, an uncommon neurodegenerative disease that typically requires multidisciplinary medical care. Her case provides a good example for clinicians to consider, at times, an in-depth assessment of the root causes of benign conditions.

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Return to Sports After Multiple Trauma: Which Factors Are Responsible?—Results From a 17-Year Follow-up

Objective: We hypothesize that the majority of polytraumatised patients are unable to maintain their preinjury level of sporting activity, and that musculoskeletal injuries are a major contributing factor. We assessed the impact of such injuries on sporting prowess, with a focus on isolating, particularly debilitating musculoskeletal trauma. Methods: We conducted a cohort study of 637 patients at a level 1 trauma centre, to assess the long-term outcome of severe trauma on return to sporting activities (RTS). Data collated on the multiply injured patient included preinjury physical activity, standardized outcome scores (SF-12, GOS, HASPOC), and clinical follow-up of at least 10 years duration. The return to preinjury sports participation was defined as a primary outcome parameter. Regression analyses were performed to identify specific injuries interfering with the RTS. Study Design: Prognostic study; Level of evidence, II. Results: Mean follow-up was 17 ± 5 years. We included 465 patients, including 207 athletic and 258 nonathletic individuals. Mean age at the time of injury was 26 ± 11.5 years and injury severity was comparable between the 2 cohorts. The deleterious effects on quality of life and the total duration of the rehabilitation process were also similar in athletes and nonathletes. Athletes were more likely to be unable to return to preinjury activities, or to return to a lower level of sporting prowess posttrauma. We identified knee injuries as the type of musculoskeletal trauma most likely to be career ending for the athlete (odds ratio 3.4, 95% confidence interval, 1.4-8.3; P = 0.008). Conclusion: Our results demonstrate an enforced shift from high-impact and team sports to low-impact activities after multiple trauma. Injuries of the lower extremities, especially around the knee joint, seem to have the highest lifechanging potential, preventing individuals from returning to their previous sporting activities.

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Reply

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Response to “Re: A Systematic Review and Meta-analysis of the Association Between C-reactive Protein and Major Cardiovascular Events in Patients with Peripheral Artery Disease”

Publication date: Available online 9 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Tejas P. Singh, Dylan R. Morris, Samuel Smith, Joseph V. Moxon, Jonathan Golledge




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Pneumatosis from Esophagus to Rectum: A Comprehensive Review Focusing on Clinico-Radiological Differentiation Between Benign and Life-Threatening Causes

Pneumatosis of the alimentary tract may occur from the esophagus to rectum as a result of a wide spectrum of conditions that range from benign to life-threatening. While distinguishing between these two groups is of paramount importance for an appropriate clinical management, it still remains a challenge for the radiologist in the daily practice. In the light of the current literature we provide in the present article a comprehensive review focusing on the clinical, laboratory and radiological findings that most consistently may allow such a differentiation.

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Relationship between neuronal network architecture and naming performance in temporal lobe epilepsy: A connectome based approach using machine learning

Publication date: Available online 9 September 2017
Source:Brain and Language
Author(s): B.C. Munsell, G. Wu, J. Fridriksson, K. Thayer, N. Mofrad, N. Desisto, D. Shen, L. Bonilha
Impaired confrontation naming is a common symptom of temporal lobe epilepsy (TLE). The neurobiological mechanisms underlying this impairment are poorly understood but may indicate a structural disorganization of broadly distributed neuronal networks that support naming ability. Importantly, naming is frequently impaired in other neurological disorders and by contrasting the neuronal structures supporting naming in TLE with other diseases, it will become possible to elucidate the common systems supporting naming. We aimed to evaluate the neuronal networks that support naming in TLE by using a machine learning algorithm intended to predict naming performance in subjects with medication refractory TLE using only the structural brain connectome reconstructed from diffusion tensor imaging. A connectome-based prediction framework was developed using network properties from anatomically defined brain regions across the entire brain, which were used in a multi-task machine learning algorithm followed by support vector regression. Nodal eigenvector centrality, a measure of regional network integration, predicted approximately 60% of the variance in naming. The nodes with the highest regression weight were bilaterally distributed among perilimbic sub-networks involving mainly the medial and lateral temporal lobe regions. In the context of emerging evidence regarding the role of large structural networks that support language processing, our results suggest intact naming relies on the integration of sub-networks, as opposed to being dependent on isolated brain areas. In the case of TLE, these sub-networks may be disproportionately indicative naming processes that are dependent semantic integration from memory and lexical retrieval, as opposed to multi-modal perception or motor speech production.



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Safe Stimulus Intensities for VEMP Testing

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Auditory Processing Testing: In the Booth versus Outside the Booth

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Listening Effort Measured in Adults with Normal Hearing and Cochlear Implants

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Tracking of Noise Tolerance to Measure Hearing Aid Benefit

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Safe Use of Acoustic Vestibular-Evoked Myogenic Potential Stimuli: Protocol and Patient-Specific Considerations

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Pediatric Hearing Aid Management: Challenges among Hispanic Families

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Hearing Aid Use and Mild Hearing Impairment: Learnings from Big Data

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Potential Audiological and MRI Markers of Tinnitus

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The Relationship between Central Auditory Processing, Language, and Cognition in Children Being Evaluated for Central Auditory Processing Disorder

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JAAA CEU Program

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Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study

Abstract

BackgroundConventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1–directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC). Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator's discretion: this analysis assessed post-progression outcomes in these patients.Patients and methodsPatients were treated with atezolizumab 1200 mg intravenously every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively.Results220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% vs 31.3%), less likely to have had baseline liver metastases (27.0% vs 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% vs 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure–adjusted adverse event frequencies were generally similar before and following progression.ConclusionIn this single-arm study, patients who continued atezolizumab beyond RECIST v1.1 progression derived prolonged clinical benefit without additional safety signals. Identification of patients most likely to benefit from atezolizumab beyond progression remains an important challenge in the management of mUC.ClinicalTrials.gov IDNCT02108652.

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P 16 The implementation of Near-Infrared-Spectroscopy (NIRS) in sports science – a verification of suitability using the compound movement squat

Near - Infrared Spectroscopy (NIRS) serves as a promising tool to examine cortical activity in a sports-scientific context. The associated feasibility of said method remains to be validated as exercise - induced confounders such as increases in extracerebral blood flow have been postulated (Tachtsidis and Scholkmann, 2016). Additionally, the relationship between force and cortical activity is yet to be investigated in compound movements. Both parameters show a linear relationship in isolated movements (Shibuya et al., 2014) yet it remains unclear whether this relationship applies to compound movements.

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P 18 Prefrontal and motor cortex transcranially evoked potentials (TEP) in children and adolescents

Potentials evoked by transcranial magnetic stimulation (TEP) differ depending on the cortical areas where TMS has been applied. Moreover, TEP underly a marked development during childhood and adolescence.

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P 15 Voice-identity processing deficits are induced by lesions in the temporal and inferior parietal lobe

Human voice recognition is an essential skill for social interactions. The mechanisms that the human brain uses for voice recognition are to-date unknown. According to studies in patients with brain lesions, voice recognition critically involves the bilateral temporal lobe and the right inferior parietal lobe. In contrast, functional magnetic resonance imaging (fMRI) studies suggest that primarily the right temporal lobe contributes to voice recognition. In order to systematically investigate brain regions required for voice recognition, we conducted a voxel-based lesion symptom mapping (VLSM) study.

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P 17 Neural signatures of post-perceptual attention and selective working memory encoding

Post-perceptual cues can enhance visual short term memory encoding even after the offset of the visual stimulus. However, both the mechanisms by which the sensory stimulus characteristics are buffered as well as the mechanisms by which post-perceptual selective attention enhances short term memory encoding remain unclear.We analyzed late post-perceptual event-related potentials (ERP) in visual change detection tasks (100ms stimulus duration) by high-resolution ERP analysis to elucidate these mechanisms.

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Immediate impact of positive airway pressure on atrial fibrillation

A 63-year old male with recently diagnosed paroxysmal atrial fibrillation (AF) was evaluated for suspected sleep-disordered breathing (SDB). Sleep history was positive for loud snoring, infrequent snort arousals and an inability to extend sleep duration beyond 6-6.5 hours. Epworth Sleepiness Scale score was 7/24. He was on diltiazem 120 mg daily. Past medical history included impaired fasting glucose, diverticulitis, gastroesophageal reflux disease and nonalcoholic fatty liver disease. He was a nonsmoker and did not endorse recreational drug or excessive caffeine/alcohol use.

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Obstructive sleep apnea and diet-controlled gestational diabetes

Obstructive sleep apnea (OSA) was shown to be associated with gestational diabetes (GDM). However, prevalence of OSA in GDM women, its relationship to metabolic control and predictive factors have not been studied.

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Short sleep duration, shift work, and actual days taken off work are predictive life-style risk factors for new-onset metabolic syndrome: a 7-year cohort study of 40,000 male workers

This longitudinal study investigated the effects of various lifestyle-related factors – including sleep duration, shift work, and actual days taken off work – on new-onset metabolic syndrome (MetS).

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Effect of a patient engagement tool on positive airway pressure adherence: analysis of a German healthcare provider database

This study investigated the addition of a real-time feedback patient engagement tool on positive airway pressure (PAP) adherence when added to a proactive telemedicine strategy.

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Sleep spindles may predict response to cognitive behavioral therapy for chronic insomnia

While cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed at determining whether sleep spindle density at pre-treatment predicts treatment response to cognitive behavioral therapy for insomnia.

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Epithelial-mesenchymal transition of tumor budding in colorectal cancer: the mystery of CD44-positive stromal cells

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Simona Gurzu, Laura Banias, Zsolt Kovacs, Ioan Jung




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Angiomyomatous Hamartoma of Lymph Nodes, Revisited: Clinico-pathologic Study of 21 Cases, Emphasizing Its Distinction from Lymphangioleiomyomatosis of Lymph Nodes

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Michelle Moh, Ankur Sangoi, Joseph T. Rabban
Angiomyomatous hamartoma of lymph nodes (AMH-LN) is an uncommon benign proliferation of smooth muscle, blood vessels, collagenous stroma and adipocytes, most commonly affecting inguinal LN. A similar constellation of cell types constitutes various members of the perivascular epithelioid cell tumor (PEComa) family, including lymphangioleiomyomatosis (LAM) which can involve LN in women. Because some LN-LAM patients have tuberous sclerosis complex (TSC) and/or other PEComa family lesions, it is clinically relevant to distinguish LN-LAM from AMH-LN. Given their similar features, however, the possibility that AMH-LN is a morphologic variant of LN-LAM merits inquiry. The dual melanocytic and myoid immunophenotype distinguishes the PEComa family from its mimics. Cathepsin K has recently emerged as a more sensitive marker for the PEComa family than HMB-45, which can be weak and focal,but cathepsin K has not been studied in AMH-LN. This study evaluated 21 AMH-LN for clinical, morphologic and immunophenotypic features of LN-LAM. None (0/21) had TSC or PEComas. Thirteen (62%) were male, unlike LN-LAM which is restricted to women. All cases exhibited intraparenchymal proliferation of variable size, thick-walled blood vessels within collagenous stroma containing a sparse to focally cellular population of haphazardly distributed smooth muscle cells. Admixed adipocytes were commonly present. None exhibited classical features of LN-LAM such as subcapsular localization, extranodal extension, intralymphatic growth, compact nests, branching lymphatic channels, plump cell shape or foamy / clear cytoplasm. None exhibited any staining for cathepsin K, HMB45, or MiTF. There is no clinical, morphologic or immunohistochemical evidence to suggest that AMH-LN is a variant of LN-LAM.



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Characterization of genome-wide copy number aberrations in colonic mixed adenoneuroendocrine carcinoma and neuroendocrine carcinoma reveals recurrent amplification of PTGER4 and MYC genes

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Namita Sinha, Daniel Gaston, Daniel Manders, Marissa Goudie, Makoto Matsuoka, Tao Xie, Weei-Yuarn Huang
Colonic Mixed adenoneuroendocrine Carcinoma (MANEC) is an aggressive neoplasm with worse prognosis compared to adenocarcinoma. To gain a better understanding of the molecular features of colonic MANEC, we characterized the genome-wide copy number aberrations (CNA) of 14 MANECs and 5 neuroendocrine carcinomas using the OncoScan FFPE assay. Compared to 269 colonic adenocarcinomas, 19 of 42 chromosomal arms of MANEC exhibited a similar frequency of major aberrant events as adenocarcinomas, and 13 chromosomal arms exhibited a higher frequency of copy number gains. Among them, the most significant chromosomal arms were 5p (77% vs. 13%, P=1.2E-05) and 8q (85% vs. 33%, P=0.0018). The genomic identification of significant targets in cancers (GISTIC) algorithm identified seven peaks that drive the tumorgenesis of MANEC. For all except 5p13.1, the peaks largely overlapped with those of adenocarcinoma. Two tumors exhibited MYC amplification localized in 8q24.21 and two tumors exhibited PTGER4 amplification localized in 5p13.1. A total of eight tumors exhibited high copy number gain of PTGER4 and/or MYC. While the frequency of MYC amplification was similar to adenocarcinoma (10.5% vs. 4%, P=0.2), the frequency of PTGER4 amplification was higher than adenocarcinoma (10.5% vs. 0.3%, P=0.01). Our study demonstrates similar, but also distinct, CNAs in MANEC compared to adenocarcinoma and suggests an important role for the MYC pathway of colonic carcinoma with neuroendocrine differentiation. The discovery of recurrent PTGER4 amplification implies a potential of exploring targeting therapy to the prostaglandin synthesis pathways in a subset of these tumors.



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Histone 3.3 Mutations in Giant Cell Tumor and Giant Cell-Rich Sarcomas of Bone

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Alberto Righi, Irene Mancini, Marco Gambarotti, Piero Picci, Gabriella Gamberi, Cristina Marraccini, Angelo Paolo Dei Tos, Lisa Simi, Pamela Pinzani, Alessandro Franchi
Mutually exclusive histone 3.3 gene mutations have been recognized in chondroblastoma and giant cell tumor of bone (GCTB), which may be useful for differential diagnostic purposes in morphologically ambiguous cases. While over 90% of GCTB presents histone 3.3 variants exclusively in the H3F3A gene, chondroblastoma is mutated mainly in H3F3B. In this study we examined a series of giant cell rich primary bone tumors, aiming to evaluate the possible diagnostic role of histone 3.3 mutations in the differential diagnosis between GCTB and giant cell rich sarcomas. Sixteen cases of non-metastatic GCTB, 9 GCTB with lung metastases, and 35 giant cell-rich sarcomas were selected from our institutional archives. Eight chondroblastomas were used as controls. Direct sequencing for the presence of H3F3A and H3F3B variants in coding region between codons 1 and 42, including the hot spot codons (28, 35 and 37) was performed on DNA extracted from formalin-fixed paraffin-embedded tissue using conventional polymerase chain reaction (PCR) and fast COamplification at Lower Denaturation temperature-PCR (COLD-PCR). Overall, 24 GCTB (96%) presented a mutation in the H3F3A gene (15 of 16 non metastatic and 9 of 9 metastatic). Five sarcomas harbored a H3F3A mutation (3 p.G35 W, 1 p.G35 L and 1 p.G35E), and these were all secondary malignant GCTB. In conclusion, we confirm that H3F3A mutational testing may be a useful adjunct to differentiate GCTB from giant cell rich sarcomas. Although the presence of H3F3A mutations does not exclude with certainty a diagnosis of sarcoma, the possibility of a malignant evolution of GCTB should also be considered.



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Expression of YES-associated protein (YAP) and its clinical significance in breast cancer tissues

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Lanqing Cao, Ping-Li Sun, Min Yao, Meng Jia, Hongwen Gao
The transcriptional co-activator YES-associated protein (YAP) has been reported to act as both an oncogene and tumor suppressor in breast cancers. In this study, we evaluated YAP expression immunohistochemically in 324 breast cancer tissues and correlated the expression with clinicopathological findings and patient survival data. Additionally, we reviewed the literature to clarify the role of YAP in breast cancer. We detected YAP, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth receptor-2 (HER2) expression and a Ki67 labeling index >20% in 53.4%, 49.0%, 45.0%, 28.3%, and 57.4% of invasive ductal carcinoma (IDC) tissues, respectively. YAP is mainly localized within the tumor cell nuclei, and its expression was associated with the PR status and Luminal A subtype. YAP expression also inversely correlated with the HER2 and Ki67 levels and lymph node metastasis. Kaplan–Meier curves revealed associations of YAP expression with favorable disease-free survival (DFS) and overall survival (OS) in patients with Luminal A subtype breast cancer and with favorable DFS association among patients with IDC, Luminal B (HER2-) and Luminal B (HER2+) subtype breast cancers. A multivariate Cox analysis revealed that YAP expression and PR status were independent favorable predictors of DFS and OS, respectively, among patients with breast cancer, whereas TNM stage and an old age were independent predictors of a poor DFS. Our results, together with the literature review findings, suggest that YAP could be a prognostic marker in patients with breast cancer.



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Small bowel stenosis: a manifestation of chronic graft-versus-host disease in children?

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Mickael Tordjman, Marie Ouachee, Arnaud Bonnard, Bogdana Tilea, Karima Yakouben, Jerome Viala, Michel Peuchmaur, Dominique Berrebi
Digestive graft versus host disease (GVHD) is a frequent complication after bone marrow transplantation (BMT), but small bowel obstruction is an extremely rare event. We present herein the first pediatric series of 4 cases of small bowel obstruction after BMT with detailed gross, histological data and their genetic status of the NOD2 gene. All patients had a history of severe acute GVHD treated by immunosuppressive agents and/or infliximab (in 3 cases). Acute or progressively worsening abdominal pain accompanied by small bowel occlusion occurred 5–16months after graft and CT-scan revealed multiple small intestinal stenosis. Failure of intensive medical treatment led to surgical resection of affected loops. Stigmata of acute (apoptosis of crypts and satellitosis) and chronic GVHD features (submucosal fibrosis and serosae sclerolipomatosis), as well as extensive ulcerations, were observed in all ileal specimens. NOD2 mutation was found in only one patient. The follow up showed successful outcome after surgery.



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The preliminary radiogenomics association between MR perfusion imaging parameters and genomic biomarkers, and their predictive performance of overall survival in patients with glioblastoma

Abstract

The radiogenomics association of neovascularization is important for overall survival (OS) in glioblastoma patients and remains unclear. The purpose of this study is to assess the association between MR perfusion imaging derived parameters and genomic biomarkers of glioblastoma, and to evaluate their prognostic value. This retrospective study enrolled 41 patients with newly diagnosed glioblastoma. The mean and maximal relative cerebral blood volume (rCBV) ratio (rCBV_mean and rCBV_max), derived from MR perfusion weighted imaging, of the enhancing tumor, as well as maximal rCBV ratio of peri-enhancing tumor area (rCBV_peri-tumor) were measured. The ki-67 labeling index, mammalian target of rapamycin (mTOR) activation, epidermal growth factor receptor (EGFR) amplification, isocitrate dehydrogenase (IDH) mutation and TP53 were assessed. There was a significant correlation between rCBV_max and mTOR based on Pearson's correlations with Benjamini–Hochberg adjustment for controlling false discovery rate, p = 0.047. The rCBV_peri-tumor showed significant correlation with mTOR (p = 0.0183) after adjustment of gender and EGFR status. The mean rCBV_peri-tumor value of the patients with OS shorter than 14 months was significantly higher than patients with OS longer than 14 months, p = 0.002. The rCBV_peri-tumor and age were the two strongest predictors of OS (hazard ratio = 1.29 and 1.063 respectively) by Cox regression analysis. This study showed that hemodynamic abnormalities of glioblastoma were associated with genomics activation status of mTOR-EGFR pathway, however, the radiogenomics associations are different in enhancing and peri-enhancing area of glioblastoma. The rCBV_peri-tumor has better prognostic value than genomic biomarkers alone.

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Bone Density Development of the Temporal Bone Assessed by Computed Tomography.

Hypothesis: The temporal bone shows regional differences in bone development. Background: The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis. Methods: Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions. Results: The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively. Conclusion: To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Vertigo in Vestibular Schwannoma Patients Due to Other Pathologies.

Objective: To report findings from a cohort of vestibular schwannoma (VS) patients presenting with vertigo from a secondary comorbid vestibular disorder; and to discuss management strategies for this subset of patients presenting with both episodic vertigo and VS. Patients: All VS patients who presented with vertigo as the primary symptom from 2012 to 2015 and endorsing no other major complaints were examined. Intervention: Treatment with migraine lifestyle and prophylactic therapy, or Epley maneuver. Main Outcome Measure: Resolution of vertigo following medical treatment alone. Results: Of the nine patients studied, seven (78%) suffered from vestibular migraine, and two (22%) experienced benign positional vertigo. All patients experienced complete resolution of symptoms after treatment. As a result of symptomatic improvement, seven patients (78%) avoided surgery in favor of observation, while two patients (22%) underwent radiosurgery due to continued tumor growth and other nonvertigo symptoms. Conclusion: VS patients can sometimes present with a history of recurrent episodic vertigo. The etiology of the vertigo could be due to the tumor itself or may be due to an underlying comorbidity such as vestibular migraine or benign positional vertigo. VS patients presenting with vertigo should undergo a standard vertigo history and examination to identify other potential causes of vertigo. Most VS patients in our cohort avoided intervention and had resolution of their vertigo. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Hearing Outcome With the Use of Glass Ionomer Cement as an Alternative to Crimping in Stapedotomy.

Objective: To evaluate early hearing outcomes using glass ionomer cement to fix the Teflon piston prosthesis onto the long process of incus to minimize residual conductive hearing loss after stapedotomy. Study Design: Original report of prospective randomized control study. Setting: Tertiary referral center. Patients: A total of 80 consecutive patients with otosclerosis were randomized into two groups. Group A is a control group in which 40 patients underwent small fenestra stapedotomy using the classic technique. Group B included 40 patients who were subjected to small fenestra stapedotomy with fixation of the incus-prosthesis junction with glass ionomer bone cement. Interventions: Stapedotomy with the classical technique in group A and the alternative technique in group B. Primary Outcome Measure: The audiometric results before and after surgery. Results: Analysis of the results was performed using the paired t test to compare between pre and postoperative results. [chi]2 test was used to compare the results of the two groups. A p value less than 0.05 was considered significant from the statistical standpoint. Significant postoperative improvement of both pure-tone air conduction thresholds and air-bone gaps were reported in the two studied groups. The postoperative average residual air-bone gap and hearing gain were statistically significant in group B (p

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REPLY TO LETTER TO THE EDITOR: PAGET'S DISEASE OF THE TEMPORAL BONE, A SINGLE-INSTITUTION CONTEMPORARY REVIEW OF 27 PATIENTS.

No abstract available

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LETTER TO THE EDITOR: REGARDING DEEP N, BESCH-STOKES J, LANE J, DRISCOLL C, CARLSON M, "PAGET'S DISEASE OF THE TEMPORAL BONE: A SINGLE-INSTITUTION CONTEMPORARY REVIEW OF 27 PATIENTS".

No abstract available

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Prognostic role of progesterone receptor expression in a population-based analysis

Abstract

Purpose

The role of progesterone (PR) expression in the management of breast cancer is controversial. The aim of this study is to evaluate the characteristics and prognosis of progesterone status among breast cancers patients in a population-based analysis.

Materials and methods

Through the Tuscan Cancer Registry data on all the invasive breast cancer cases diagnosed during the period 2004–2005 in the provinces of Florence and Prato, central Italy, were retrieved. Histological reports were re-examined to obtain information on the percentage of positive tumor cells for estrogen (ER), progesterone (PR) receptors, Ki67 marker and human epidermal growth factor 2 (HER2). Information on age, stage, differentiation grade were also obtained.

Results

Out of 1487 patients, 28% had PR− breast cancer. These patients were older (p 0.006) than PR+ cancer patients, with more frequently high Ki67 (p < 0.0001), HER2 + (p < 0.0001), ER− (p < 0.0001) tumoral expression. The ER+/PR+ subtype was the most represented (n.1053), while ER−/PR+ was the most rare (n.23); 210 cases (14.1%) ER+ PR− and 201 (13.5%) ER−/PR− cases were found. Analysis of survival by the Cox proportional hazards model showed an independent prognostic value of PR expression (p < 0.0001), also when estrogen, Ki67, HER2 status and age were included. The 5-year cancer-specific survival was 82.1, 86.5, 100, 92% for ER−/PR−, ER+/PR−, ER−/PR+, ER+/PR+ subtype, respectively.

Conclusions

Our study revealed significant differences in clinicopathological characteristics among breast cancer according to PR expression and confirmed its prognostic independent role, suggesting a role of PR in the improvement of breast cancer prognostic characterization.

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The preliminary radiogenomics association between MR perfusion imaging parameters and genomic biomarkers, and their predictive performance of overall survival in patients with glioblastoma

Abstract

The radiogenomics association of neovascularization is important for overall survival (OS) in glioblastoma patients and remains unclear. The purpose of this study is to assess the association between MR perfusion imaging derived parameters and genomic biomarkers of glioblastoma, and to evaluate their prognostic value. This retrospective study enrolled 41 patients with newly diagnosed glioblastoma. The mean and maximal relative cerebral blood volume (rCBV) ratio (rCBV_mean and rCBV_max), derived from MR perfusion weighted imaging, of the enhancing tumor, as well as maximal rCBV ratio of peri-enhancing tumor area (rCBV_peri-tumor) were measured. The ki-67 labeling index, mammalian target of rapamycin (mTOR) activation, epidermal growth factor receptor (EGFR) amplification, isocitrate dehydrogenase (IDH) mutation and TP53 were assessed. There was a significant correlation between rCBV_max and mTOR based on Pearson's correlations with Benjamini–Hochberg adjustment for controlling false discovery rate, p = 0.047. The rCBV_peri-tumor showed significant correlation with mTOR (p = 0.0183) after adjustment of gender and EGFR status. The mean rCBV_peri-tumor value of the patients with OS shorter than 14 months was significantly higher than patients with OS longer than 14 months, p = 0.002. The rCBV_peri-tumor and age were the two strongest predictors of OS (hazard ratio = 1.29 and 1.063 respectively) by Cox regression analysis. This study showed that hemodynamic abnormalities of glioblastoma were associated with genomics activation status of mTOR-EGFR pathway, however, the radiogenomics associations are different in enhancing and peri-enhancing area of glioblastoma. The rCBV_peri-tumor has better prognostic value than genomic biomarkers alone.

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Analysis of known amyotrophic lateral sclerosis and frontotemporal dementia genes reveals a substantial genetic burden in patients manifesting both diseases not carrying the C9orf72 expansion mutation

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of a clinical, pathological and genetic continuum.

Objectives

The purpose of the present study was to assess the mutation burden that is present in patients with concurrent ALS and FTD (ALS/FTD) not carrying the chromosome 9 open reading frame 72 (C9orf72) hexanucleotide repeat expansion, the most important genetic cause in both diseases.

Methods

From an initial group of 973 patients with ALS, we retrospectively selected those patients fulfilling diagnostic criteria of concomitant ALS and FTD lacking the repeat expansion mutation in C9orf72. Our final study group consisted of 54 patients clinically diagnosed with ALS/FTD (16 with available postmortem neuropathological diagnosis). Data from whole exome sequencing were used to screen for mutations in known ALS and/or FTD genes.

Results

We identified 11 patients carrying a probable pathogenic mutation, representing an overall mutation frequency of 20.4%. TBK1 was the most important genetic cause of ALS/FTD (n=5; 9.3%). The second most common mutated gene was SQSTM1, with three mutation carriers (one of them also harboured a TBK1 mutation). We also detected probable pathogenic genetic alterations in TAF15, VCP and TARDBP and possible pathogenic mutations in FIG4 and ERBB4.

Conclusion

Our results indicate a high genetic burden underlying the co-occurrence of ALS and FTD and expand the phenotype associated with TAF15, FIG4 and ERBB4 to FTD. A systematic screening of ALS and FTD genes could be indicated in patients manifesting both diseases without the C9orf72 expansion mutation, regardless of family history of disease.

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Striatal molecular alterations in HD gene carriers: a systematic review and meta-analysis of PET studies

Background

Over the past years, positron emission tomography (PET) imaging studies have investigated striatal molecular changes in premanifest and manifest Huntington's disease (HD) gene expansion carriers (HDGECs), but they have yielded inconsistent results.

Objective

To systematically examine the evidence of striatal molecular alterations in manifest and premanifest HDGECs as measured by PET imaging studies.

Methods

MEDLINE, ISI Web of Science, Cochrane Library and Scopus databases were searched for articles published until 7 June 2017 that included PET studies in manifest and premanifest HDGECs. Meta-analyses were conducted with random effect models, and heterogeneity was addressed with I² index, controlling for publication bias and quality of study. The primary outcome was the standardised mean difference (SMD) of PET uptakes in the whole striatum, caudate and putamen in manifest and premanifest HDGECs compared with healthy controls (HCs).

Results

Twenty-four out of 63 PET studies in premanifest (n=158) and manifest (n=191) HDGECs and HCs (n=333) were included in the meta-analysis. Premanifest and manifest HDGECs showed significant decreases in dopamine D₂ receptors in caudate (SMD=–1.233, 95% CI –1.753 to –0.713, p<0.0001; SMD=–5.792, 95% CI –7.695 to –3.890, p<0.0001) and putamen (SMD=–1.479, 95% CI –1.965 to –0.992, p<0.0001; SMD=–5.053, 95% CI –6.558 to –3.549, p<0.0001), in glucose metabolism in caudate (SMD=–0.758, 95% CI –1.139 to –0.376, p<0.0001; SMD=–3.738, 95% CI –4.880 to –2.597, p<0.0001) and putamen (SMD=–2.462, 95% CI –4.208 to –0.717, p=0.006; SMD=–1.650, 95% CI –2.842 to –0.458, p<0.001) and in striatal PDE10A binding (SMD=–1.663, 95% CI –2.603 to –0.723, p=0.001; SMD=–2.445, 95% CI –3.371 to –1.519, p<0.001).

Conclusions

PET imaging has the potential to detect striatal molecular changes even at the early premanifest stage of HD, which are relevant to the neuropathological mechanisms underlying the development of the disease.

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Quantitative MR spectroscopic imaging in metachromatic leukodystrophy: value for prognosis and treatment

Objective

To determine whether proton magnetic resonance spectroscopic imaging is useful in predicting clinical course of patients with metachromatic leukodystrophy (MLD), an inherited white matter disorder treatable with haematopoietic cell transplantation (HCT).

Methods

21 patients with juvenile or adult MLD (12 HCT-treated) were compared with 16 controls in the same age range. Clinical outcome was determined as good, moderate or poor. Metabolites were quantified in white matter, and significance of metabolite concentrations at baseline for outcome prediction was assessed using logistic regression analysis. Evolution of metabolic changes was assessed for patients with follow-up examinations.

Results

In this retrospective study, 16 patients with baseline scans were included, 5 with good, 3 with moderate and 8 with poor outcome, and 16 controls. We observed significant group differences for all metabolite concentrations in white matter (p<0.001). Compared with controls, patients had decreased N-acetylaspartate and glutamate, and increased myo-inositol and lactate, most pronounced in patients with poor outcome (post hoc, all p<0.05). Logistic regression showed complete separation of data. Creatine could distinguish poor from moderate and good outcome, the sum of glutamate and glutamine could distinguish good from moderate and poor outcome, and N-acetylaspartate could distinguish all outcome groups. For 13 patients (8 with baseline scans), one or more follow-up examinations were evaluated, revealing stabilisation or even partial normalisation of metabolites in patients with moderate and good outcome, clearly visible in the ratio of choline/N-acetylaspartate.

Conclusion

In MLD, quantitative spectroscopic imaging at baseline is predictive for outcome and aids in determining eligibility for HCT.

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MRI in sarcoglycanopathies: a large international cohort study

Objectives

To characterise the pattern and spectrum of involvement on muscle MRI in a large cohort of patients with sarcoglycanopathies, which are limb-girdle muscular dystrophies (LGMD2C–2F) caused by mutations in one of the four genes coding for muscle sarcoglycans.

Methods

Lower limb MRI scans of patients with LGMD2C–2F, ranging from severe childhood variants to milder adult-onset forms, were collected in 17 neuromuscular referral centres in Europe and USA. Muscle involvement was evaluated semiquantitatively on T1-weighted images according to a visual score, and the global pattern was assessed as well.

Results

Scans from 69 patients were examined (38 LGMD2D, 18 LGMD2C, 12 LGMD2E and 1 LGMD2F). A common pattern of involvement was found in all the analysed scans irrespective of the mutated gene. The most and earliest affected muscles were the thigh adductors, glutei and posterior thigh groups, while lower leg muscles were relatively spared even in advanced disease. A proximodistal gradient of involvement of vasti muscles was a consistent finding in these patients, including the most severe ones.

Conclusions

Muscle involvement on MRI is consistent in patients with LGMD2C–F and can be helpful in distinguishing sarcoglycanopathies from other LGMDs or dystrophinopathies, which represent the most common differential diagnoses. Our data provide evidence about selective susceptibility or resistance to degeneration of specific muscles when one of the sarcoglycans is deficient, as well as preliminary information about progressive involvement of the different muscles over time.

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Statistical approach to quality assessment in liver transplantation

Abstract

Purpose

This study investigated the utility of retrospective two one-sided cumulative sum (CUSUM) charts combined with multivariable regression analysis in liver transplantation for transplant center benchmarking.

Methods

One thousand seven hundred and forty-nine consecutive adult primary liver transplants (January 1, 1983 to December 31, 2012) were analyzed retrospectively with two one-sided CUSUM chart analysis of 90-day mortality.

Results

Three eras and two subseries in latest era 3 were identified due to graphically delineated relevant shifts in mean 90-day mortality. Delineation of eras 1, 2, and 3 coincided with relevant changes in allocation policies. CUSUM analysis detected a resurgence of higher mean 90-day mortality in era 3 after results had improved continuously over 25 years. In era 3, two subseries were identified with improving mean 90-day mortality rates from 15.4% in subseries 1 to 8.9% in the following subseries 2. The quantitative influence of independent risk factors on 90-day mortality differed markedly between all identified eras and subseries as assessed with multivariable regression analysis deployed on era-specific subcohorts.

Conclusion

The assessed methodology is able to identify meaningful center-specific eras and subseries of liver transplantation with striking alterations of the significance and weight of outcome drivers for post-transplant 90-day mortality over time. This warrants the introduction of prospective risk-adjusted two one-sided CUSUM chart analysis into quality management in liver transplantation in Germany with the goal to obtain alarm signals as early as possible.

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Bone Density Development of the Temporal Bone Assessed by Computed Tomography.

Hypothesis: The temporal bone shows regional differences in bone development. Background: The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis. Methods: Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions. Results: The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively. Conclusion: To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Vertigo in Vestibular Schwannoma Patients Due to Other Pathologies.

Objective: To report findings from a cohort of vestibular schwannoma (VS) patients presenting with vertigo from a secondary comorbid vestibular disorder; and to discuss management strategies for this subset of patients presenting with both episodic vertigo and VS. Patients: All VS patients who presented with vertigo as the primary symptom from 2012 to 2015 and endorsing no other major complaints were examined. Intervention: Treatment with migraine lifestyle and prophylactic therapy, or Epley maneuver. Main Outcome Measure: Resolution of vertigo following medical treatment alone. Results: Of the nine patients studied, seven (78%) suffered from vestibular migraine, and two (22%) experienced benign positional vertigo. All patients experienced complete resolution of symptoms after treatment. As a result of symptomatic improvement, seven patients (78%) avoided surgery in favor of observation, while two patients (22%) underwent radiosurgery due to continued tumor growth and other nonvertigo symptoms. Conclusion: VS patients can sometimes present with a history of recurrent episodic vertigo. The etiology of the vertigo could be due to the tumor itself or may be due to an underlying comorbidity such as vestibular migraine or benign positional vertigo. VS patients presenting with vertigo should undergo a standard vertigo history and examination to identify other potential causes of vertigo. Most VS patients in our cohort avoided intervention and had resolution of their vertigo. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Hearing Outcome With the Use of Glass Ionomer Cement as an Alternative to Crimping in Stapedotomy.

Objective: To evaluate early hearing outcomes using glass ionomer cement to fix the Teflon piston prosthesis onto the long process of incus to minimize residual conductive hearing loss after stapedotomy. Study Design: Original report of prospective randomized control study. Setting: Tertiary referral center. Patients: A total of 80 consecutive patients with otosclerosis were randomized into two groups. Group A is a control group in which 40 patients underwent small fenestra stapedotomy using the classic technique. Group B included 40 patients who were subjected to small fenestra stapedotomy with fixation of the incus-prosthesis junction with glass ionomer bone cement. Interventions: Stapedotomy with the classical technique in group A and the alternative technique in group B. Primary Outcome Measure: The audiometric results before and after surgery. Results: Analysis of the results was performed using the paired t test to compare between pre and postoperative results. [chi]2 test was used to compare the results of the two groups. A p value less than 0.05 was considered significant from the statistical standpoint. Significant postoperative improvement of both pure-tone air conduction thresholds and air-bone gaps were reported in the two studied groups. The postoperative average residual air-bone gap and hearing gain were statistically significant in group B (p

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REPLY TO LETTER TO THE EDITOR: PAGET'S DISEASE OF THE TEMPORAL BONE, A SINGLE-INSTITUTION CONTEMPORARY REVIEW OF 27 PATIENTS.

No abstract available

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LETTER TO THE EDITOR: REGARDING DEEP N, BESCH-STOKES J, LANE J, DRISCOLL C, CARLSON M, "PAGET'S DISEASE OF THE TEMPORAL BONE: A SINGLE-INSTITUTION CONTEMPORARY REVIEW OF 27 PATIENTS".

No abstract available

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Significance of perivascular tumour cells defined by CD109 expression in progression of glioma

Abstract

In the progression of glioma, tumour cells often exploit the perivascular microenvironment to promote their survival and resistance to conventional therapies. Some of these cells are considered to be brain tumour stem cells (BTSCs); however, the molecular nature of perivascular tumour cells has not been specifically clarified because of the complexity of glioma. Here, we identified CD109, a glycosylphosphatidylinositol- anchored protein and regulator of multiple signalling pathways, as a critical regulator of the progression of lower-grade glioma (World Health Organization grade II/III) by clinicopathological and whole genome sequencing analysis of tissues from human glioma. The importance of CD109-positive perivascular tumour cells was confirmed not only in human lower-grade glioma tissues, but also in a mouse model that recapitulated human glioma. Intriguingly, BTSCs isolated from mouse glioma expressed high levels of CD109. CD109-positive BTSCs exerted a proliferative effect on differentiated glioma cells treated with temozolomide. These data reveal the significance of tumour cells that populate perivascular regions during glioma progression, and indicate that CD109 is a potential therapeutic target for the disease.

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MYC drives overexpression of telomerase RNA (hTR/TERC) in prostate cancer

Abstract

Telomerase consists of at least two essential elements, an RNA component hTR or TERC that contains the template for telomere DNA addition, and a catalytic reverse transcriptase (TERT). While expression of TERT has been considered the key rate limiting component for telomerase activity, increasing evidence suggests an important role for the regulation of TERC in telomere maintenance and perhaps other functions in human cancer. By using three orthogonal methods including RNAseq, RT-qPCR, and an analytically validated chromogenic RNA in situ hybridization assay, we report consistent overexpression of TERC in prostate cancer. This overexpression occurs at the precursor stage (e.g. high grade prostatic intraepithelial neoplasia or PIN), and persists throughout all stages of disease progression. Levels of TERC correlate with levels of MYC (a known driver of prostate cancer) in clinical samples and we also show the following: forced reductions of MYC result in decreased TERC levels in 8 cancer cell lines (prostate, lung, breast, and colorectal); forced overexpression of MYC in PCa cell lines, and in the mouse prostate, results in increased TERC levels; human TERC promoter activity is decreased after MYC silencing; and MYC occupies the TERC locus as assessed by chromatin immunoprecipitation (ChIP). Finally, we show that knockdown of TERC by siRNA results in reduced proliferation of prostate cancer cell lines. These studies indicate that TERC is consistently overexpressed in all stages of prostatic adenocarcinoma, and its expression is regulated by MYC. These findings nominate TERC as a novel prostate cancer biomarker and therapeutic target.

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Visual and semiquantitative 11 C-methionine PET: An independent prognostic factor for survival of newly diagnosed and treatment naive gliomas

Abstract

Background

Few data exist regarding the prognostic value of L-[S-methyl- ¹¹C]methionine (MET) PET for treatment-naive gliomas.

Methods

A total of 160 glioma patients (89 men, 71 women, mean age: 45, range 18 - 84 yrs) underwent a MET PET prior to any therapy. The PET scans were evaluated visually and semiquantitatively by tumor to background (T/N) ratio thresholds chosen by ROC-Analysis. Additionally, isocitrate dehydrogenase 1-R132H (IDH1-R132H) immunohistochemistry was performed. Survival analysis was done using Kaplan-Meier estimate and Cox proportional hazard model.

Results

Significantly shorter mean survival times (7.2 vs. 8.6 yrs; p=0,024) were seen in patients with amino-acid avid gliomas (n=137) compared to visually negative tumors (n=33) in MET PET. T/N ratio thresholds of 2.1 and 3.5 were significantly associated with survival (10.3 vs. 7 vs. 4.3 yrs; p < 0.001). Mean survival differed significantly using the median T/N ratio of 2.4 as cut-off, independent of histopathology (p<0.01; mean survival: 10.2 ± 0.8 yrs versus 5.5 ± 0.6 yrs). In the subgroup of 142 glioma patients characterized by the IDH1-R132H status MET T/N ratio demonstrated a significant prognostic impact in IDH1-R132H wildtype astrocytomas and glioblastoma (p = 0.001). Additionally, multivariate testing revealed semiquantitative MET PET as an independent prognostic parameter for treatment-naive glioma patients without (p=0.031) and with IDH1-R132H characterization of gliomas (p=0.024; OR 1.57).

Conclusion

This retrospective analysis demonstrates the value of MET PET as a prognostic parameter on survival in treatment-naive glioma patients.

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