δ- and β-cells are electrically coupled and regulate α-cell activity via somatostatin

Abstract

Glucagon, the body's principal hyperglycaemic hormone, is released from the α-cells of the pancreatic islet. The secretion of this hormone is dysregulated in type 2 diabetes mellitus but the mechanisms controlling secretion are not well understood. Regulation of glucagon secretion by factors secreted by neighbouring β- and δ-cells (paracrine regulation) have been proposed to be important. In this study, we explored the importance of paracrine regulation by using an optogenetic strategy. Specific light-induced activation of β-cells in mouse islets expressing the light-gated channelrhodopsin-2 resulted in stimulation of electrical activity in δ-cells but suppression of α-cell activity. The activation of the δ-cells was rapid and sensitive to the gap junction inhibitor carbenoxolone, whereas the effect on electrical activity in α-cells was blocked by CYN 154806, an antagonist of the somatostatin-2 receptor. These observations indicate that optogenetic activation of the β-cells propagates to the δ-cells via gap junctions, and the consequential stimulation of somatostatin secretion inhibits α-cell electrical activity by a paracrine mechanism. To explore whether this pathway is important for regulating α-cell activity and glucagon secretion in human islets, we constructed computational models of human islets. These models had detailed architectures based on human islets and consisted of a collection of >500 α-, β- and δ-cells. Simulations of these models revealed that this gap junctional/paracrine mechanism accounts for up to 23% of the suppression of glucagon secretion by high glucose.

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Erratum to: A multi-stage genome-wide association study of uterine fibroids in African Americans

The article "A multi-stage genome-wide association study of uterine fibroids in African Americans", written by Jacklyn N. Hellwege, was originally published Online First without open access. After publication in volume 136, issue 10, page 1363–1373 the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2017 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://ift.tt/1iwynXF), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Rapid decline in MyHC I(β) mRNA expression in rat soleus during hindlimb unloading is associated with the AMPK dephosphorylation

Abstract

One of the key events that occurs during skeletal muscle inactivation is a change in myosin phenotype, i.e. increased expression of fast isoforms and decreased expression of slow isoform of myosin heavy chain (MyHC). It is known that calcineurin/NFAT and AMP-activated protein kinase (AMPK) can regulate the expression of genes encoding MyHC slow isoform. Earlier, we found a significant decrease in phosphorylated AMPK in rat soleus after 24 h of hindlimb unloading (HU). We hypothesized that a decrease in AMPK phosphorylation and subsequent histone deacetylase (HDAC) nuclear translocation can be one of the triggering events leading to a reduced expression of slow MyHC. To test this hypothesis, Wistar rats were treated with AMPK activator (AICAR) for 6 d before HU as well as during 24-h HU. We discovered that AICAR treatment prevented a decrease in pre-mRNA and mRNA expression of MyHC I as well as MyHC IIa mRNA expression. 24-h HS resulted in HDAC4 accumulation in the nuclei of rat soleus but AICAR pretreatment prevented such an accumulation. The results of the study indicate that AMPK dephosphorylation after 24-h HU had a significant impact on the MyHC I and MyHC IIa mRNA expression in rat soleus. AMPK dephosphorylation also contributed to the HDAC4 translocation to the nuclei of soleus muscle fibres, suggesting an important role of HDAC4 as an epigenetic regulator in the process of myosin phenotype transformation.

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Sailing in a sea of disbelief: In vivo measurements of transcranial electric stimulation in human subcortical structures

Publication date: Available online 3 October 2017
Source:Brain Stimulation
Author(s): P. Ruhnau, K.S. Rufener, H.-J. Heinze, T. Zaehle




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Beyond variability: Subjective timing and the neurophysiology of motor cognition

Publication date: Available online 3 October 2017
Source:Brain Stimulation
Author(s): David Perruchoud, Mirta Fiorio, Paola Cesari, Silvio Ionta
BackgroundMovement simulation helps increasing the chances to reach goals. A cognitive task used to study the neuro-behavioral aspects of movement simulation is mental rotation: people mentally re-orient rotated pictures of hands. However, the involvement of the primary motor cortex (M1) in mental rotation is largely controversial.HypothesisSuch inconsistency could arise from potential methodological flaws in experimental procedures and data analysis. In particular, until now, the timing of M1 activity has been computed in absolute terms: from the onset of mental rotation (onset-locked), neglecting intra- and inter-subject variability.MethodsA novel phase-locked approach is introduced to synchronize the same phases of cognitive processing among different subjects and sessions. This approach was validated in the particular case of corticospinal excitability of the motor cortex during mental rotation.ResultsWe identified the relative time-windows during which the excitability of M1 is effector-specifically modulated by different features of mental rotation. These time windows correspond to the 55%–85% of the subjective timing.ConclusionsIn sum, (i) we introduce a new method to study the neurophysiology of motor cognition, and (ii) validating this method, we shed new light on the involvement of M1 in movement simulation.



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What you need to know about airway management

Sponsored by BoundTree and Ambu By Jonathan Lee for EMS1 BrandFocus Airway management in the prehospital environment is messy business. A recent study of prehospital intubation in trauma found that 44.3 percent of the patients had gross contamination of the airway at the time of intubation (most commonly blood, followed by vomit, teeth or brain). While the literature is divided on whether prehospital ...

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How linear response shaped models of neural circuits and the quest for alternatives

Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Tim Herfurth, Tatjana Tchumatchenko
In the past decades, many mathematical approaches to solve complex nonlinear systems in physics have been successfully applied to neuroscience. One of these tools is the concept of linear response functions. However, phenomena observed in the brain emerge from fundamentally nonlinear interactions and feedback loops rather than from a composition of linear filters. Here, we review the successes achieved by applying the linear response formalism to topics, such as rhythm generation and synchrony and by incorporating it into models that combine linear and nonlinear transformations. We also discuss the challenges encountered in the linear response applications and argue that new theoretical concepts are needed to tackle feedback loops and non-equilibrium dynamics which are experimentally observed in neural networks but are outside of the validity regime of the linear response formalism.



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The many worlds hypothesis of dopamine prediction error: implications of a parallel circuit architecture in the basal ganglia

Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Brian Lau, Tiago Monteiro, Joseph J Paton
Computational models of reinforcement learning (RL) strive to produce behavior that maximises reward, and thus allow software or robots to behave adaptively [1]. At the core of RL models is a learned mapping between ‘states’—situations or contexts that an agent might encounter in the world—and actions. A wealth of physiological and anatomical data suggests that the basal ganglia (BG) is important for learning these mappings [2,3]. However, the computations performed by specific circuits are unclear. In this brief review, we highlight recent work concerning the anatomy and physiology of BG circuits that suggest refinements in our understanding of computations performed by the basal ganglia. We focus on one important component of basal ganglia circuitry, midbrain dopamine neurons, drawing attention to data that has been cast as supporting or departing from the RL framework that has inspired experiments in basal ganglia research over the past two decades. We suggest that the parallel circuit architecture of the BG might be expected to produce variability in the response properties of different dopamine neurons, and that variability in response profile may not reflect variable functions, but rather different arguments that serve as inputs to a common function: the computation of prediction error.



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Common TDP1 polymorphisms in relation to survival among small cell lung cancer patients: a multicenter study from the International Lung Cancer Consortium

Purpose: DNA topoisomerase inhibitors are commonly used for treating small cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single nucleotide polymorphisms (SNPs) are associated with overall survival among SCLC patients. Experimental Design: Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan-Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months post-diagnosis, adjusting for age, sex, race, and tumor stage. Results: Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared to those carrying AA alleles, with a hazard ratio (HR) of 1.36 (95% confidence interval (CI): 1.08-1.72, p-value=0.01), but no association with survival was observed for patients carrying the AG genotype (HR=1.04, 95% CI:0.84-1.29, p-value=0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR=0.79, 95% CI: 0.61-1.02, p-value=0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190. Conclusions: We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors.

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A molecularly annotated model of patient-derived colon cancer stem-like cells to assess genetic and non-genetic mechanisms of resistance to anti-EGFR therapy

Purpose Patient-derived xenografts ("xenopatients") of colorectal cancer metastases have been essential to identify genetic determinants of resistance to the anti-EGF Receptor (EGFR) antibody cetuximab, and to explore new therapeutic strategies. From xenopatients, a genetically annotated collection of stem-like cultures ("xenospheres") was generated and characterized for response to targeted therapies. Experimental Design. Xenospheres underwent exome-sequencing analysis, gene expression profile and in vitro targeted treatments to assess genetic, biological and pharmacological correspondence with xenopatients, and to investigate non-genetic biomarkers of therapeutic resistance. The outcome of EGFR family inhibition was tested in an NRG1-expressing in vivo model. Results. Xenospheres faithfully retained the genetic make-up of their matched xenopatients over in vitro and in vivo passages. Frequent and rare genetic lesions triggering primary resistance to cetuximab through constitutive activation of the RAS signaling pathway were conserved, as well as the vulnerability to their respective targeted treatments. Xenospheres lacking such alterations (RASwt) were highly sensitive to cetuximab, but were protected by ligands activating the EGFR family, mostly NRG1. Upon reconstitution of NRG1 expression, xenospheres displayed increased tumorigenic potential in vivo, generated tumors completely resistant to cetuximab, and sensitive only to comprehensive EGFR family inhibition. Conclusions. Xenospheres are a reliable model to identify both genetic and non-genetic mechanisms of response and resistance to targeted therapies in colorectal cancer. In the absence of RAS pathway mutations, NRG1 and other EGFR ligands can play a major role in conferring primary cetuximab resistance, indicating that comprehensive inhibition of the EGFR family is required to achieve a significant therapeutic response.

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Modulation of Navitoclax Sensitivity by Dihydroartemisinin-Mediated MCL-1 Repression in BCR-ABL+ B-Lineage Acute Lymphoblastic Leukemia

Purpose: BCR-ABL+ B-ALL leukemic cells are highly dependent on the expression of endogenous anti-apoptotic MCL-1 to promote viability and are resistant to BH3-mimetic agents such as navitoclax (ABT-263) that targets BCL-2, BCL-XL, and BCL-W. However, the survival of most normal blood cells and other cell types are also dependent on Mcl-1. Despite the requirement for MCL-1 in these cell types, initial reports of MCL-1-specific BH3-mimetics have not described any overt toxicities associated with single-agent use, but these agents are still early in clinical development. Therefore, we sought to identify FDA-approved drugs that could sensitize leukemic cells to ABT-263. Experimental Design: A screen identified dihydroartemisinin (DHA), a water-soluble metabolite of the anti-malarial artemisinin. Using mouse and human leukemic cell lines, and primary patient-derived xenografts, the effect of DHA on survival was tested and mechanistic studies were carried out to discover how DHA functions. We further tested in vitro and in vivo whether combining DHA with ABT-263 could enhance the response of leukemic cells to combination therapy. Results: DHA causes the down-modulation of MCL-1 expression by triggering a cellular stress response that represses translation. The repression of MCL-1 renders leukemic cells highly sensitive to synergistic cell death induced by ABT-263 in a mouse model of BCR-ABL+ B-ALL both in vitro and in vivo. Furthermore, DHA synergizes with ABT-263 in human Ph+ ALL cell lines, and primary patient derived xenografts of Ph+ ALL in culture. Conclusions: Our findings suggest that combining DHA with ABT-263 can improve therapeutic response in BCR-ABL+ B-ALL.

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The HRD decision--which PARP inhibitor to use for whom and when

Rucaparib, a polyADPribose polymerase (PARP) inhibitor, was approved recently for use in women with high grade serous ovarian cancer (HGSOC). It is now one of 3 approved PARPi for use in recurrent ovarian cancer, a family of agents that has changed the HGSOC treatment landscape and outcome.

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Selective Androgen Receptor Modulator RAD140 Inhibits the Growth of Androgen/Estrogen Receptor Positive Breast Cancer Models with a Distinct Mechanism of Action

Purpose: Steroidal androgens suppress androgen receptor and estrogen receptor positive (AR/ER+) breast cancer cells and were used to treat breast cancer eliciting favorable response. The present study evaluates the activity and efficacy of the oral selective AR modulator (SARM) RAD140 in in vivo and in vitro models of AR/ER+ breast cancer. Experimental Design: A series of in vitro assays were used to determine the affinity of RAD140 to 4 nuclear receptors and evaluate its tissue-selective AR activity. The efficacy and pharmacodynamics of RAD140 as monotherapy or in combination with palbociclib were evaluated in AR/ER+ breast cancer xenograft models. Results: RAD140 bound AR with high affinity and specificity and activated AR in breast cancer but not prostate cancer cells. Oral administration of RAD140 substantially inhibited the growth of AR/ER+ breast cancer patient-derived xenografts (PDXs). Activation of AR and suppression of ER pathway, including the ESR1 gene, were seen with RAD140-treatment. Co-administration of RAD140 and palbociclib showed improved efficacy in the AR/ER+ PDX models. In line with efficacy, a subset of AR-repressed genes associated with DNA replication were suppressed with RAD140-treatment, an effect apparently enhanced by concurrent administration of palbociclib. Conclusions: RAD140 is a potent AR agonist in breast cancer cells with a distinct mechanism of action including the AR-mediated repression of ESR1. It inhibits the growth of multiple AR/ER+ breast cancer PDX models as a single agent, and in combination with palbociclib. The preclinical data presented here supports further clinical investigation of RAD140 in AR/ER+ breast cancer patients.

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Whole-Genome Sequence Analysis of Mutations Accumulated in rad27{Delta} Yeast Strains with Defects in the Processing of Okazaki Fragments Indicates Template-Switching Events

Okazaki fragments that are formed during lagging strand DNA synthesis include an initiating primer consisting of both RNA and DNA. The RNA fragment must be removed before the fragments are joined. In Saccharomyces cerevisiae, a key player in this process is the structure-specific flap endonuclease, Rad27p (human homolog FEN1). To obtain a genomic view of the mutational consequence of loss of RAD27, a Saccharomyces cerevisiae rad27 strain was subcultured for 25 generations and sequenced using Illumina paired-end sequencing. Out of the 455 changes observed in ten colonies isolated the two most common types of events were insertions or deletions (INDELs) in simple sequence repeats (SSRs) and INDELs mediated by short direct repeats. Surprisingly, we also detected a previously neglected class of 21 template-switching events. These events were presumably generated by quasi-palindrome to palindrome correction, as well as palindrome elongation. The formation of these events is best explained by folding back of the stalled nascent strand and resumption of DNA synthesis using the same nascent strand as a template. Evidence to quasi palindrome to palindrome correction that could be generated by template switching appears also in yeast genome evolution. Out of the 455 events, 55 events appeared in multiple isolates, further analysis indicate that these loci are mutational hotspots. Since Rad27 acts on the lagging strand when the leading strand should not contain any gaps, we propose a mechanism favoring intramolecular strand switching over an intermolecular mechanism. We note that our results open new ways of understanding template switching that occur during genome instability and evolution.

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William Paske 12 June 1948 to 24 December 2016

Publication date: Available online 3 October 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Peter Bell, Giorgio M. Biasi, Jose Fernandes e Fernandes, Christos Liapis




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Immediate completion lymph node dissection in stage IIIA melanoma does not provide significant additional staging information beyond EORTC SN tumour burden criteria

Publication date: Available online 3 October 2017
Source:European Journal of Cancer
Author(s): Max F. Madu, Viola Franke, Maarten M. Bruin, Danique M.S. Berger, Carolien Bierman, Katarzyna Jóźwiak, Willem M.C. Klop, Michel W.J.M. Wouters, Alexander C.J. van Akkooi, Bart A. Van de Wiel




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Metformin and insulin impact on clinical outcome in patients with advanced hepatocellular carcinoma receiving sorafenib: Validation study and biological rationale

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Andrea Casadei Gardini, Luca Faloppi, Serena De Matteis, Francesco Giuseppe Foschi, Nicola Silvestris, Francesco Tovoli, Vincenzo Palmieri, Giorgia Marisi, Oronzo Brunetti, Umberto Vespasiani-Gentilucci, Giuseppe Perrone, Martina Valgiusti, Anna Maria Granato, Giorgio Ercolani, Giulia Negrini, Emiliano Tamburini, Giuseppe Aprile, Alessandro Passardi, Daniele Santini, Stefano Cascinu, Giovanni Luca Frassineti, Mario Scartozzi
PurposeIn 2015, we published a study on a small series of patients with hepatocellular carcinoma (HCC) treated chronically with metformin for type II diabetes mellitus (DM2) who showed a poorer response to sorafenib. The aim of the present study was to validate the prognostic significance of metformin in HCC patients treated with sorafenib, providing a biological rationale for the mechanism of resistance to sorafenib in patients on chronic metformin therapy, and to clarify the role of sirtuin-3 (SIRT-3), a protein involved in metabolic diseases and acknowledged as a tumour suppressor in HCC, in this resistance.Patients and methodsWe analysed 279 patients consecutively treated with sorafenib for the clinical analysis. Of the 86 (30%) patients with DM2, 52 (19%) were on chronic treatment with metformin and 34 (12%) with insulin. We included 43 patients with HCC for the biological study: 19 (44.1%) were diabetic and 14 (73.7%) of these received metformin for DM2. SIRT-3 expression was investigated by immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded (FFPE) samples.ResultsIn HCC patients undergoing chronic treatment with metformin, the use of sorafenib was associated with poor progression-free survival (PFS) and overall survival (OS) (1.9 and 6.6 months, respectively) compared to 3.7 months and 10.8 months, respectively, for patients without DM2 and 8.4 months and 16.6 months, respectively, for patients on insulin (P < .0001). We also observed that SIRT-3 protein expression was significantly higher in patients treated with metformin than in those not taking this medication (65% versus 25%, respectively) (P = .013).ConclusionsOur findings could be attributed to increased tumour aggressiveness and resistance to sorafenib caused by chronic treatment with metformin.



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‘Corrigendum to “Severe hepatitis under combined immunotherapy: Resolution under corticosteroids plus anti-thymocyte immunoglobulins” [Eur J Cancer 81 (August 2017) 203–205]’

Publication date: Available online 3 October 2017
Source:European Journal of Cancer
Author(s): Iris Spänkuch, Maximilian Gassenmaier, Ioanna Tampouri, Seema Noor, Andrea Forschner, Claus Garbe, Teresa Amaral




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Conservative treatment of children with chronic diffuse sclerosing osteomyelitis/tendoperiostitis of the mandible

Publication date: Available online 3 October 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Marieke M. van de Meent, Hamid Meshkini, Marta Fiocco, Miranda J.M. Wetselaar-Glas, Natasha M. Appelman-Dijkstra, J.P. Richard van Merkesteyn
Chronic diffuse sclerosing osteomyelitis (DSO) of the mandible is a rare disease of unknown etiology. It has been suggested that overuse of the masticatory muscles, tendoperiostitis (TP), is a contributing factor for DSO. Therefore, we tested this hypothesis by treating consecutive children with conservative therapy.All patients were treated with conservative therapy, comprising occlusal splint therapy, physiotherapy, and/or disease counselling. Pain intensity on a visual analogue scale (VAS) and pain frequency in number of days per 3 months were recorded before the start of treatment, and at 3, 6, and 12 months after treatment initiation.Eleven children (seven girls, four boys, mean age: 11.55 ± 1.97 years) were included in this study. Six patients showed a decrease in pain intensity and pain frequency over time and they continued with conservative therapy. For the remaining five patients, bisphosphonate administration was initiated because of persistent severe pain – one after 3 months of conservative therapy, and the other four after 1 year of conservative therapy.The pain complaints of patients with DSO/TP decreased with conservative therapy, and 55% did not require additional therapy. This suggests that DSO/TP of the mandible is precipitated by muscle overuse.



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Quantitative assessment of orbital fractures in Asian patients: CT measurement of orbital volume

Publication date: Available online 3 October 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Kensuke Sugiura, Harumoto Yamada, Takayuki Okumoto, Yoshikazu Inoue, Satoko Onishi
Enophthalmos is caused by an increase of orbital volume after blowout fracture and is one of the most critical complications of such fractures, but is often masked by swelling soon after injury. If surgery is performed after swelling resolves, it becomes more difficult to treat enophthalmos because of atrophy and fibrosis. Accordingly, it is important to estimate the severity of enophthalmos soon after injury. We developed a new criterion for determining whether orbital fractures are indicated for surgery in Asian patients using analysis of orbital volume.We retrospectively calculated the orbital volume of patients treated surgically or conservatively and analyzed the correlation between changes of orbital volume and the severity of enophthalmos.Regression analysis of the correlation between enophthalmos and increased orbital volume (y = 0.8x + 0.2; correlation coefficient: 0.92) showed that enophthalmos of 2.0 mm corresponded to an increase in orbital volume of 2.25 cm³. This result is similar to data reported previously for Caucasian patients — enophthalmos of 2.0 mm is a common surgical indication worldwide. Our results suggest that an increase of orbital volume of >2.25 cm³ could be a new criterion for surgical treatment of blowout fractures in Asians.



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Orthognathic surgery “again” to correct aesthetic failure of primary surgery: Report on outcomes and patient satisfaction in 70 consecutive cases

Publication date: Available online 3 October 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Mirco Raffaini, Claudia Pisani, Marco Conti
PurposeAn increasing number of patients complain about unsatisfactory aesthetic outcomes of orthognathic surgery, desiring reoperation to improve facial aesthetics. The aims of this article are to present a wide range of aesthetic reasons to justify a secondary orthognathic surgery and to report aesthetic outcomes and patient satisfaction after reoperation.Material and MethodsThis research covers 70 consecutive patients who underwent a secondary bimaxillary orthognathic surgery with simultaneous facial lipofilling procedures between January 2006 and December 2015. The screening criteria are described for patient selection, the diagnostic process, surgical procedures, and outcomes. Pre- and postoperative facial appearances are compared. Postoperatively, patients were asked to state the improvements perceived in their facial appearance and their satisfaction with the aesthetic outcomes.ResultsAfter reoperation, all patients showed a full Class I occlusion. Major complications did not occur. According to the clinicians’ evaluation, a postoperative evident aesthetic improvement was achieved in 65 patients (92.9%), and 64 patients (91.4%) were satisfied with the aesthetic outcomes achieved.ConclusionSecondary orthognathic surgery performed in conjunction with facial lipofilling procedures in most cases led to satisfactory aesthetic outcomes. A very accurate selection of patients, a meticulous three-dimensional diagnostic process and planning, and appropriate intra-operative maneuvers are required.



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Is Subcranial Le Fort III Plus Le Fort I Osteotomy Stable?

Publication date: Available online 3 October 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Fernanda Brasil Daura Jorge Boos Lima, Eduardo Hochuli Vieira, Philipp Juergens, Sergio Monteiro Lima Junior
The purpose of this study was to test whether associated subcranial Le Fort III (sLF III) and Le Fort I (LF I) osteotomies are stable after large advancements of the middle third of the face and maxilla. The authors designed a retrospective study and enrolled a sample of consecutive patients with midface hypoplasia treated with associated sLF III and LF I osteotomies in this IRB-approved study between September 2013 and February 2015. To test whether the long-term stability was satisfactory, the authors compared cephalometric changes from immediately after surgery to 18 months after surgery taken from multi-slice computed tomography using two different third-party imaging software programs. Statistical significance was set as P ≤ 0.05. The sample comprised 11 patients (mean age 23.84±4.17 yr; 54% men). The mean advancement of the upper incisor immediately after surgery was 10.03±1.6 mm. After 18 months, the position of the upper incisor did not vary significantly (10.18±2.35 mm). All other cephalometric landmarks did not present statistically significant differences between immediately after and 18 months after surgery, with horizontal and vertical variations of less than one milimeter. This study supports that sLF III and LF I osteotomies are effective in maintaining stable horizontal and vertical skeletal positioning after surgery.



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Conservative treatment of children with chronic diffuse sclerosing osteomyelitis/tendoperiostitis of the mandible

Publication date: Available online 3 October 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Marieke M. van de Meent, Hamid Meshkini, Marta Fiocco, Miranda J.M. Wetselaar-Glas, Natasha M. Appelman-Dijkstra, J.P. Richard van Merkesteyn
Chronic diffuse sclerosing osteomyelitis (DSO) of the mandible is a rare disease of unknown etiology. It has been suggested that overuse of the masticatory muscles, tendoperiostitis (TP), is a contributing factor for DSO. Therefore, we tested this hypothesis by treating consecutive children with conservative therapy.All patients were treated with conservative therapy, comprising occlusal splint therapy, physiotherapy, and/or disease counselling. Pain intensity on a visual analogue scale (VAS) and pain frequency in number of days per 3 months were recorded before the start of treatment, and at 3, 6, and 12 months after treatment initiation.Eleven children (seven girls, four boys, mean age: 11.55 ± 1.97 years) were included in this study. Six patients showed a decrease in pain intensity and pain frequency over time and they continued with conservative therapy. For the remaining five patients, bisphosphonate administration was initiated because of persistent severe pain – one after 3 months of conservative therapy, and the other four after 1 year of conservative therapy.The pain complaints of patients with DSO/TP decreased with conservative therapy, and 55% did not require additional therapy. This suggests that DSO/TP of the mandible is precipitated by muscle overuse.



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Quantitative assessment of orbital fractures in Asian patients: CT measurement of orbital volume

Publication date: Available online 3 October 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Kensuke Sugiura, Harumoto Yamada, Takayuki Okumoto, Yoshikazu Inoue, Satoko Onishi
Enophthalmos is caused by an increase of orbital volume after blowout fracture and is one of the most critical complications of such fractures, but is often masked by swelling soon after injury. If surgery is performed after swelling resolves, it becomes more difficult to treat enophthalmos because of atrophy and fibrosis. Accordingly, it is important to estimate the severity of enophthalmos soon after injury. We developed a new criterion for determining whether orbital fractures are indicated for surgery in Asian patients using analysis of orbital volume.We retrospectively calculated the orbital volume of patients treated surgically or conservatively and analyzed the correlation between changes of orbital volume and the severity of enophthalmos.Regression analysis of the correlation between enophthalmos and increased orbital volume (y = 0.8x + 0.2; correlation coefficient: 0.92) showed that enophthalmos of 2.0 mm corresponded to an increase in orbital volume of 2.25 cm³. This result is similar to data reported previously for Caucasian patients — enophthalmos of 2.0 mm is a common surgical indication worldwide. Our results suggest that an increase of orbital volume of >2.25 cm³ could be a new criterion for surgical treatment of blowout fractures in Asians.



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Orthognathic surgery “again” to correct aesthetic failure of primary surgery: Report on outcomes and patient satisfaction in 70 consecutive cases

Publication date: Available online 3 October 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Mirco Raffaini, Claudia Pisani, Marco Conti
PurposeAn increasing number of patients complain about unsatisfactory aesthetic outcomes of orthognathic surgery, desiring reoperation to improve facial aesthetics. The aims of this article are to present a wide range of aesthetic reasons to justify a secondary orthognathic surgery and to report aesthetic outcomes and patient satisfaction after reoperation.Material and MethodsThis research covers 70 consecutive patients who underwent a secondary bimaxillary orthognathic surgery with simultaneous facial lipofilling procedures between January 2006 and December 2015. The screening criteria are described for patient selection, the diagnostic process, surgical procedures, and outcomes. Pre- and postoperative facial appearances are compared. Postoperatively, patients were asked to state the improvements perceived in their facial appearance and their satisfaction with the aesthetic outcomes.ResultsAfter reoperation, all patients showed a full Class I occlusion. Major complications did not occur. According to the clinicians’ evaluation, a postoperative evident aesthetic improvement was achieved in 65 patients (92.9%), and 64 patients (91.4%) were satisfied with the aesthetic outcomes achieved.ConclusionSecondary orthognathic surgery performed in conjunction with facial lipofilling procedures in most cases led to satisfactory aesthetic outcomes. A very accurate selection of patients, a meticulous three-dimensional diagnostic process and planning, and appropriate intra-operative maneuvers are required.



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Is Subcranial Le Fort III Plus Le Fort I Osteotomy Stable?

Publication date: Available online 3 October 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Fernanda Brasil Daura Jorge Boos Lima, Eduardo Hochuli Vieira, Philipp Juergens, Sergio Monteiro Lima Junior
The purpose of this study was to test whether associated subcranial Le Fort III (sLF III) and Le Fort I (LF I) osteotomies are stable after large advancements of the middle third of the face and maxilla. The authors designed a retrospective study and enrolled a sample of consecutive patients with midface hypoplasia treated with associated sLF III and LF I osteotomies in this IRB-approved study between September 2013 and February 2015. To test whether the long-term stability was satisfactory, the authors compared cephalometric changes from immediately after surgery to 18 months after surgery taken from multi-slice computed tomography using two different third-party imaging software programs. Statistical significance was set as P ≤ 0.05. The sample comprised 11 patients (mean age 23.84±4.17 yr; 54% men). The mean advancement of the upper incisor immediately after surgery was 10.03±1.6 mm. After 18 months, the position of the upper incisor did not vary significantly (10.18±2.35 mm). All other cephalometric landmarks did not present statistically significant differences between immediately after and 18 months after surgery, with horizontal and vertical variations of less than one milimeter. This study supports that sLF III and LF I osteotomies are effective in maintaining stable horizontal and vertical skeletal positioning after surgery.



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TERT promoter mutation and its interaction with IDH mutations in glioma: Combined TERT promoter and IDH mutations stratifies lower-grade glioma into distinct survival subgroups—A meta-analysis of aggregate data

Publication date: Available online 3 October 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Huy Gia Vuong, Ahmed M.A. Altibi, Uyen N.P. Duong, Hanh T.T. Ngo, Thong Quang Pham, Aden Ka-Yin Chan, Chul-Kee Park, Kar-Ming Fung, Lewis Hassell
The clinical significance of telomerase reverse transcriptase (TERT) promoter mutation in glioma remains unclear. The aim of our meta-analysis is to investigate the prognostic impact TERT promoter mutation in glioma patients and its interaction with other molecular markers, particularly Isocitrate Dehydrogenase (IDH) mutation from aggregate level data. Relevant articles were searched in four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library. Pooled HRs were calculated using random effect model weighted by inverse variance method. From 1010 studies, we finally included 28 studies with 11519 patients for meta-analyses. TERT mutation is significantly associated with compromised overall survival (OS) (HR=1.38; 95% CI=1.15–1.67) and progression-free survival (PFS) (HR=1.31; 95% CI=1.06–1.63) in glioma patients. In studying its reaction with IDH, TERT promoter mutation was associated with reduced OS in both IDH-mutant (IDH-mut) and IDH-wild type (IDH-wt) glioblastomas but shown to have inverse effects on IDH-mut and IDH-wt grade II/III tumors. Our analysis categorized WHO grade II/III glioma patients into four distinct survival subgroups with descending survival as follow: TERT-mut/IDH-mut≫TERT-wt/IDH-mut≫TERT-wt/IDH-wt≫TERT-mut/IDH-wt. Prognostic value of TERT promoter mutations in gliomas is dependent on tumor grade and the IDH mutational status. With the same tumor grade in WHO grade II and III tumors and the same IDH mutation status, TERT-mut is a prognostic factor.



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Sexual function after prolapse repair

Purpose of review: The purpose of this review is to summarize available literature (from the last 18 months) assessing sexual function following pelvic reconstructive surgery for pelvic organ prolapse (POP). We include vaginal native tissue repair, abdominal/laparoscopic sacrocolpopexy, transvaginal mesh repair, and obliterative procedures. The goal is to assist providers in counseling patients and to identify areas needed for further research. Recent findings: When compared with pessary management, women who undergo POP surgical repair achieve their sexual function goals more often. In particular, vaginal native tissue repair has consistently been shown to improve sexual function. Furthermore, there does not appear to be a difference between uterosacral ligament suspension and sacrospinous ligament suspension (with or without uterine conservation) with regard to postoperative sexual function. Although less robust, literature evaluating the impact of abdominal/robotic sacrocolpopexy also supports benefit from surgical correction. However, data are conflicted with regard to transvaginal mesh repair and suggest the potential for a negative impact. Summary: POP often affects a woman's sexual function. Following surgical repair, most patients experience improvements in their sexual response. However, surgical approaches involving abdominal or transvaginal mesh may result in a decline in sexual function and worsening dyspareunia.

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Editorial introductions

No abstract available

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Evaluation and management of heavy menstrual bleeding in adolescents

Purpose of review: Heavy menstrual bleeding (HMB) is a common condition in women of reproductive age; however, adolescents with this issue present unique challenges in both diagnosis and management. Much of the research into this topic focuses on the adult population, with variable applicability to adolescents. There are currently no standard guidelines for the work up and treatment of adolescents with HMB. Recent findings: Current research into this topic has explored the utilization of standardized protocols in the evaluation of HMB in adolescents, the efficacy of various hormonal, nonhormonal, and surgical treatment modalities, and the benefits of a multidisciplinary approach. Recent literature has focused on adolescents found to have an underlying bleeding disorder, recommending more comprehensive bleeding disorder work up to identify these patients in a timely manner and initiate effective treatment plans. Summary: Providers in the primary care setting should be aware of the definitions for normal menses, and be able to recognize abnormal bleeding and HMB. Early recognition of HMB in adolescents can then lead to appropriate diagnosis of underlying disorders, and current research has proposed standard protocols to assist with the evaluation, ultimately leading to effective long-term management into adulthood. Video abstract: http://ift.tt/2hL92DC

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Restrictions and limitations after pelvic floor surgery: what's the evidence?

Purpose of review: A common concern regarding pelvic floor surgery is the relatively high risk of recurrence. In an effort to minimize this risk, many surgeons instruct their patients to avoid certain activities during the healing process so as not to damage the repair before proper healing has occurred. However, many of these restrictions have been historically based on little to no hard evidence. The purpose of this review is to present the latest evidence-based recommendations regarding restrictions and limitations after pelvic floor surgery. Recent findings: The current review covers postoperative activities that could impact proper healing of a vaginal incision and of the strength of the reconstruction itself. It also looks at safety of the patient and those around her as she heals. Topics include pelvic rest, swimming, lifting exercising, working, and driving. Observational research suggests that many unavoidable activities of daily living may have as great, if not an even greater, risk of impacting the healing process than many of the modifiable activity restrictions that are commonly imposed on patients. This may explain why recent clinical trials show no greater problem with healing in patients randomized to less strict postoperative restrictions than the standard. Summary: Although further research is necessary, it appears that patients are more satisfied with less strict postoperative limitations, and this less restrictive activity may not have any significant negative impact on the healing process.

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Anterior compartment prolapse: what's new?

Purpose of review: The purpose of this review is to summarize the treatment options for anterior compartment prolapse, describe the role that apical suspension plays in the correction of anterior vaginal wall prolapse, and assess the risks and benefits of biologic and synthetic graft use in anterior compartment repair. Recent findings: In 2016, The Cochrane Review published a review of 37 trials including 4023 participants finding that compared to native tissue repair, the use of synthetic mesh resulted in reduced symptomatic prolapse recurrence, anatomic recurrence, and repeat prolapse surgery. There was insufficient evidence regarding quality of life improvement or the use of biologic grafts. Of note the differences between native tissue and mesh kit repairs were not large. Summary: A strong consideration should be on the correction of apical prolapse when present; isolated anterior wall repairs should be pursued with caution. The surgeon may consider the use of augmenting materials in their repair of anterior vaginal wall prolapse, although the available evidence is not strongly supportive of their use given potential risks.

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Endometriosis in adolescents

Purpose of review: The current article addresses recent literature regarding the diagnosis and management of endometriosis in adolescents. Recent findings: An increasing body of literature suggests that advanced-stage endometriosis (revised scoring system of the American Society for Reproductive Medicine Stage III or IV) and deeply invasive endometriosis are relatively common in adolescents. There remains limited data on the efficacy of postoperative hormonal management of endometriosis in the adolescent population. Summary: Strong consideration should be made for surgical diagnosis of endometriosis in adolescents with pelvic pain, including noncyclic pain, with a concurrent family history of endometriosis and personal history of atopic disease. More research is needed regarding the benefits of the routine use of hypoestrogenic and other hormonal agents in the prevention of disease progression and long-term sequela in adolescents with endometriosis.

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Evaluation and management of vaginoplasty complications

Purpose of review: Indications for vaginoplasty include congenital conditions such as adrenal hyperplasia, cloacal malformations, and Müllerian agenesis, acquired conditions including stenosis from radiation or surgical resection for malignancy, and gender affirmation. All vaginoplasty techniques carry significant risk of both immediate and long-term complications. Recent findings: The purpose of this study is to provide a review of the evaluation and management of the neovagina, addressing management of human papilloma virus infections and complications including stenosis, fistula, prolapse, and neovaginal colitis. Summary: Gynecologists who care for patients who have had a vaginoplasty need to understand the importance of long-term follow up and care, including evaluation and management of complications.

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Current review of prepubertal vaginal bleeding

Purpose of review: Prepubertal vaginal bleeding raises many concerns and evaluation and diagnosis may prove difficult for many providers. We aim to provide a comprehensive review and recent updates for those practitioners who care for these patients. Recent findings: Prompt management in the case of prepubertal vaginal bleeding is indicated, especially to rule out malignancy or abuse. If a child is reluctant to undergo examination, or if the extent of injury or source of bleeding cannot be determined, examination under anesthesia and vaginoscopy is recommended. Use of vaginoscopy allows for clear visualization of the vagina and cervix without distorting hymenal anatomy, as well as diagnosis and removal of a foreign body and evaluation of mucosal damage caused. In the case of sexual abuse, providers specifically trained in pediatrics need to be present, and safety of the patient should always be ensured. Summary: Careful history taking and targeted examination may lead to diagnosis in the case of prepubertal vaginal bleeding. However, in more difficult cases, practitioners should not hesitate to examine a patient in the operating room using general anesthesia to elicit the cause. Although sexual abuse and malignancy are always on the differential, most causes of bleeding are benign and easily treated.

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Pelvic denervation procedures for dysmenorrhea

Purpose of review: Chronic pelvic pain and dysmenorrhea are common conditions affecting reproductive-age women. Surgical pelvic denervation procedures may be a treatment option for women with midline dysmenorrhea, in which medical management is declined by the patient, ineffective at managing symptoms, or medically contraindicated. This review describes the surgical techniques and complications associated with pelvic denervation procedures as well as the current evidence for these procedures in women with primary dysmenorrhea and dysmenorrhea secondary to endometriosis. Recent findings: Presacral neurectomy is the preferred pelvic denervation procedure in patients with primary dysmenorrhea and midline chronic pelvic pain associated with endometriosis. In patients with endometriosis presacral neurectomy is a useful adjunct to excision or ablation of all endometrial lesions to improve postoperative pain relief. There is no additional patient benefit of performing combined presacral neurectomy and uterine nerve ablation procedures. Summary: Pelvic denervation procedures can be performed safely and quickly with a low risk of complication if the surgeon is knowledgeable and skilled in operating in the presacral space. Patients should be adequately counseled on expected success rates and potential complications associated with pelvic denervation procedures.

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Editorial introductions

No abstract available

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The use of pulsed CO2 lasers for the treatment of vulvovaginal atrophy: Erratum

No abstract available

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A universal freeze all strategy: why it is not warranted

Purpose of review: There's some preclinical evidence of an adverse effect of multifollicular growth on endometrial function in assisted reproductive technology cycles. Universal elective frozen embryo transfer (eFET) in an unstimulated cycle is being promoted as a panacea, regardless of patient, and cycle characteristics. We review the clinical evidence on the effectiveness and safety of eFETs. Recent findings: Randomized controlled trials (RCTs) comparing fresh and eFET yield contradictory results in terms of live birth rates. RCTs mainly involve women with an excessive response to ovarian stimulation. Studies including women with a normal or low ovarian response are either patient/physician preference or retrospective studies, prone to bias. Yet, they yield contradictory results as well. Overall, eFET seems to have limited potential to improve effectiveness of assisted reproductive technology, which could be limited to hyper-responders. Other suggested advantages of eFET include better obstetric and perinatal outcome. However, recent studies show that frozen embryo transfers can be associated with serious complications including hypertensive disorders during pregnancy, placenta accreta, or increased perinatal mortality. Summary: The evidence behind advantages of eFET is of low quality. As such, switching to a universal eFET strategy does not seem justified. New RCTs including women from different strata of ovarian response are needed.

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Preimplantation embryonic mosaicism: origin, consequences and the reliability of comprehensive chromosome screening

Purpose of review: Embryonic mosaicism represents an ongoing challenge for contemporary comprehensive chromosome screening platforms due to the unknown reproductive potential of mosaic embryos and technical difficulties of its detection from a single embryo biopsy. Recent findings: Mosaicism in preimplantation embryos is a product of mitotic errors arising primarily from anaphase lag and chromosome nondisjunction. To date, there is high variability among estimations of prevalence of mosaicism in blastocysts, the most recent ranging from 3.3 to 83%. It has been reported that alleged mosaic embryos can develop into healthy babies, although the proper study evaluating this question remains to be completed. Technical artefacts from comprehensive chromosome screening platforms may also hinder correct classification of embryos as genuine mosaics. Summary: Although complex, embryonic mosaicism is a phenomenon that deserves further investigation. Many embryos classified as mosaic may have actual reproductive potential. The predictive value of intermediate chromosome copy number assignments for the remaining embryo and for ongoing reproductive potential needs more careful consideration. In addition, recent advancements in extended embryo culture raise the possibility of investigating whether preferential segregation, selective advantage of normal cells or surveillance of abnormal chromosome numbers occur at postimplantation stages.

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Endometrial microbiome

Purpose of review: There have been great improvements in assisted reproduction in the recent decade; however, there are still a significant number of chromosomally normal blastocysts that fail to produce live births. The human microbiome is the totality of the microbes and their genomes that exist in and on the host. The understanding of its impact on health and human disease, particularly in human reproduction, is evolving. Recent findings: New technologies have empowered metagenomic sample analysis that allows for more fully characterizing the reproductive tract microbiome. With these technologies, we have determined not only that sites previously thought to be sterile in fact have robust microbiomes, but also have better characterized the normal and abnormal vaginal and endometrial microbiome. Summary: The understanding of the microbiome in health and human disease, in particular in relation to human reproduction, is in its infancy. As the reproductive tract dysbiosis are better characterized and understood, we may be better equipped to manipulate it more expertly.

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Long-term consequences of obesity on female fertility and the health of the offspring

Purpose of review: Obesity has reached near epidemic levels among reproductive age women with a myriad of consequences. Obesity adversely affects the maternal milieu by creating conditions that decrease fertility and increase the risk of gestational diabetes, hypertensive disease in pregnancy, fetal growth abnormalities and congenital anomalies. The effects of obesity are not limited to pregnancy. Indeed, beyond the immediate postpartum period, obese women maintain a higher prevalence of insulin resistance and cardiovascular disease. In this article, we will review the pathophysiology underlying the effects of obesity on fertility, pregnancy outcome and health status of offspring. The purpose of this review is to outline proposed models responsible for the short-term and long-term consequences of obesity on fertility and offspring development, and identify knowledge gaps where additional research is needed. Recent findings: Maternal over or under nutrition adversely affect maternal reproductive capacity and pregnancy success. Separate from effects on maternal reproductive function, maternal over or under nutrition may also ‘program’ fetal pathophysiology through inheritance mechanisms that suggest epigenetic modification of DNA, differential RNA translation and protein expression, or modification of the fetal hypothalamic–pituitary axis function through programmed adverse effects on the developing hypothalamic circuitry. The concept of maternal health modifying the risk of developing noncommunicable diseases in the offspring is based on Developmental Origins of Health and Disease hypothesis. Summary: Of importance, the long-term effects of obesity are not limited to maternal health, but also programs pathophysiology in their offspring. Children of obese gravida are at increased risk for the development of cardiometabolic disease in childhood and throughout adulthood. Future studies directly interrogating mechanisms underlying the risks associated with obesity will allow us to develop interventions and therapies to decrease short-term and long-term morbidities associated with maternal obesity.

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Reduced upper obstructions in N3 and increased lower obstructions in REM sleep stage detected with manometry

Abstract

In obstructive sleep apnea (OSA), airway obstruction occurs at different anatomic levels. The frequency and location of obstructions play a crucial role in the planning of surgical treatment. The aim of this study was to evaluate the pharyngeal obstruction levels in different sleep stages with manometry in OSA patients. In addition, the manometry results were compared with drug-induced sleep endoscopy (DISE). Forty-one patients with OSA received manometry measurements during one night of sleep. All patients were simultaneously evaluated with polysomnography. The frequency of obstructions in different sleep stages was assessed. Twenty patients were additionally studied with DISE. Obstruction levels detected with manometry were compared with DISE. The frequency of upper and to a lesser extent lower obstructions decreased in sleep stage N3. In rapid eye movement (REM) sleep, lower obstructions increased. The overall proportion of upper and lower obstructions detected with manometry corresponded with DISE in 13 of 20 cases. A significant change in the obstruction levels was detected with manometry in N3 and REM sleep. The reduction of both upper and to a lesser extent lower obstructions in N3 suggests more stable airways in slow-wave sleep. Relevant lower obstructions were not detected in DISE compared to manometry in 5 out of 20 examinations. This could be a potential reason for treatment failure of site-specific surgical OSA treatment when only performing DISE preoperatively. Therefore, manometry could be a useful complementary tool in the preoperative evaluation for OSA.

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Changes in the Soleus H-reflex Test and Correlations between Its Results and Dynamic Magnetic Resonance Imaging Abnormalities in Patients with Hirayama Disease

Hirayama disease (HD) was first reported by the Japanese scholar Keizo Hirayama in 1959 (Hirayama et al., 1959). The aetiology of HD remains controversial. Currently, the main implicated mechanism is chronic cervical spinal cord ischaemia caused by microcirculatory disturbances in the territory of the anterior spinal artery during neck flexion (Hirayama, 2000; Hirayama, 2008). Because anterior horn cells are extremely vulnerable to ischaemia and a previous autopsy case of HD revealed confined necrosis in both the cervical anterior horn and ventral nerve root areas (Hirayama et al., 1987), HD is considered a neurological disease that involves only lower motor neurons (LMN) (e.g., anterior horn cells and ventral nerve roots) (Hirayama, 2008).

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Rhythmic EEG patterns in extremely preterm infants: classification and association with brain injury and outcome

In many units, neuro-monitoring with electroencephalography (EEG) during the first postnatal days has become part of standard care. Brain protection has become one of the main aims of neonatal intensive care, since the survival rate of extremely preterm infants (born <28 weeks gestational age) has increased due to major advances in perinatal care. (Costeloe et al., 2012; Zegers et al., 2016)

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Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients with prior antiangiogenic therapy

Abstract

Background

Cabozantinib is a potent, multi-target inhibitor of hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor-2 (VEGFR2). This open-label, phase II trial evaluated cabozantinib in patients with recurrent or progressive glioblastoma (GBM; NCT00704288).

Methods

Patients were initially enrolled to a starting cabozantinib dose of 140 mg/day, but the starting dose was amended to 100 mg/day because of safety concerns. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was objective response rate, assessed by an independent radiology facility using modified Response Assessment in Neuro-Oncology (RANO) criteria. Additional endpoints included duration of response, 6-month and median progression-free survival (PFS), overall survival (OS), glucocorticoid use, and safety.

Results

Among 222 patients enrolled, 70 patients had received prior antiangiogenic therapy. Herein, we report results in this subset of 70 patients. The objective response rate was 4.3%, and the median duration of response was 4.2 months. The proportion of patients alive and progression-free at 6 months was 8.5%. Median PFS was 2.3 months, and median OS was 4.6 months. The most common adverse events (AEs) reported in all patients, regardless of dose group, included fatigue (74.3%), diarrhea (47.1%), increased alanine aminotransferase (37.1%), headache (35.7%), hypertension (35.7%), and nausea (35.7%); overall, 34 (48.6%) patients experienced AEs that resulted in dose reductions.

Conclusions

Cabozantinib treatment appeared to have modest clinical activity with a 4.3% response rate in patients who had received prior antiangiogenic therapy for GBM.

Clinical Trials Registration Number

NCT00704288 (http://ift.tt/2vWrPPz)

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Economic Hardship in Childhood: A Neglected Issue in ACE Studies?

Abstract

Objectives Adverse childhood experiences (ACEs) have been linked with ill-health in adulthood, but ACE literature has focused on family disruption or dysfunction (e.g., child abuse, parental separation), with less attention to economic adversity. We examined whether a mother's economic hardship in childhood (EHC) was associated with women's hardships and health-risk behaviors during/just before pregnancy. Methods We analyzed population-based survey data on 27,102 postpartum California women. EHC included respondents' reports that during childhood they/their families experienced hunger because of inability to afford food or moved because of problems paying rent/mortgage and the frequency of difficulty paying for basic needs. We examined six maternal hardships/behaviors during/just before pregnancy, including four hardships (poverty, food insecurity, homelessness/no regular place to sleep, intimate partner violence) and two behaviors (smoking, binge drinking). Prevalence ratios (PRs) were calculated from sequential logistic regression models estimating associations between EHC (categorized by level of hardship) and each maternal hardship/behavior, first without adjustment, then adjusting for other childhood and current maternal factors, and finally adding family disruption/dysfunction. Results Before adjustment for family disruption/dysfunction, the highest and intermediate EHC levels were associated with each maternal hardship/behavior; after full adjustment, those associations persisted except with smoking. Higher EHC levels generally appeared associated with larger PRs, although confidence intervals overlapped. Conclusions for Policy/Practice These findings link childhood economic hardship with women's hardships, binge drinking, and possibly smoking around the time of pregnancy. Without establishing causality, they support previous research indicating that childhood economic adversity should be considered an ACE.

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The Elderly Left Behind – Changes in Survival Trends of Primary Central Nervous System Lymphoma Over The Past Four Decades

Abstract

Background

There has been significant improvement in treatment outcomes of Primary Central Nervous System Lymphoma (PCNSL) at specialized centers over the past several decades; however, it is unclear if these changes have translated to benefits in the general population.

Methods

In this study, we utilized two national databases to examine survival trends over time for PCNSL (Central Brain Tumor Registry of the United States (CBTRUS, 2000 – 2013) and 18 Surveillance, Epidemiology, and End Results (SEER, 1973 – 2013) registries).

Results

The annual incidence of PCNSL in 2013 was 0.4 per 100,000 population (CBTRUS/SEER). Incidence increased from 0.1 per 100,000 in the 1970s to 0.4 per 100,000 in the 1980s, correlating with an increase in the diagnosis of patients ≥70 years (1973:0.2 vs 2013:2.1 – SEER). Incidence rates differed greatly between young and elderly patients (age 20–29 years: 0.08 vs 70–79: 4.32 – CBTRUS). Even though the median overall survival of all patients doubled from 12.5 months in the 1970s to 26 in the 2010s, this survival benefit was limited to patients age <70. Survival in the elderly population did not change in the last 40 years (6 months in the 1970s vs 7 in the 2010s, p-value = 0.1).

Conclusion

The poor outcome seen in the particularly vulnerable elderly patient population highlights the need for clinical trials targeting the elderly in hopes of improving treatment strategies and survival.

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Processing of haptic texture information over sequential exploration movements

Abstract

Where textures are defined by repetitive small spatial structures, exploration covering a greater extent will lead to signal repetition. We investigated how sensory estimates derived from these signals are integrated. In Experiment 1, participants stroked with the index finger one to eight times across two virtual gratings. Half of the participants discriminated according to ridge amplitude, the other half according to ridge spatial period. In both tasks, just noticeable differences (JNDs) decreased with an increasing number of strokes. Those gains from additional exploration were more than three times smaller than predicted for optimal observers who have access to equally reliable, and therefore equally weighted, estimates for the entire exploration. We assume that the sequential nature of the exploration leads to memory decay of sensory estimates. Thus, participants compare an overall estimate of the first stimulus, which is affected by memory decay, to stroke-specific estimates during the exploration of the second stimulus. This was tested in Experiments 2 and 3. The spatial period of one stroke across either the first or second of two sequentially presented gratings was slightly discrepant from periods in all other strokes. This allowed calculating weights of stroke-specific estimates in the overall percept. As predicted, weights were approximately equal for all strokes in the first stimulus, while weights decreased during the exploration of the second stimulus. A quantitative Kalman filter model of our assumptions was consistent with the data. Hence, our results support an optimal integration model for sequential information given that memory decay affects comparison processes.

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Contingency proportion systematically influences contingency learning

Abstract

In the color-word contingency learning paradigm, each word appears more often in one color (high contingency) than in the other colors (low contingency). Shortly after beginning the task, color identification responses become faster on the high-contingency trials than on the low-contingency trials—the contingency learning effect. Across five groups, we varied the high-contingency proportion in 10% steps, from 80% to 40%. The size of the contingency learning effect was positively related to high-contingency proportion, with the effect disappearing when high contingency was reduced to 40%. At the two highest contingency proportions, the magnitude of the effect increased over trials, the pattern suggesting that there was an increasing cost for the low-contingency trials rather than an increasing benefit for the high-contingency trials. Overall, the results fit a modified version of Schmidt’s (2013, Acta Psychologica, 142, 119–126) parallel episodic processing account in which prior trial instances are routinely retrieved from memory and influence current trial performance.

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Sound specificity effects in spoken word recognition: The effect of integrality between words and sounds

Abstract

Recent evidence has shown that nonlinguistic sounds co-occurring with spoken words may be retained in memory and affect later retrieval of the words. This sound-specificity effect shares many characteristics with the classic voice-specificity effect. In this study, we argue that the sound-specificity effect is conditional upon the context in which the word and sound coexist. Specifically, we argue that, besides co-occurrence, integrality between words and sounds is a crucial factor in the emergence of the effect. In two recognition-memory experiments, we compared the emergence of voice and sound specificity effects. In Experiment 1 , we examined two conditions where integrality is high. Namely, the classic voice-specificity effect (Exp. 1a) was compared with a condition in which the intensity envelope of a background sound was modulated along the intensity envelope of the accompanying spoken word (Exp. 1b). Results revealed a robust voice-specificity effect and, critically, a comparable sound-specificity effect: A change in the paired sound from exposure to test led to a decrease in word-recognition performance. In the second experiment, we sought to disentangle the contribution of integrality from a mere co-occurrence context effect by removing the intensity modulation. The absence of integrality led to the disappearance of the sound-specificity effect. Taken together, the results suggest that the assimilation of background sounds into memory cannot be reduced to a simple context effect. Rather, it is conditioned by the extent to which words and sounds are perceived as integral as opposed to distinct auditory objects.

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“The importance of surgical maneuvers during treatment of frontal migraines (site I): a prospective, randomized cohort study evaluating foraminotomy/fasciotomy, myectomy, and arterectomy”

The current prospective, blinded, randomized cohort study aims to delineate the relative contribution of different surgical treatments for frontal migraines.

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Antibiotic prophylaxis in breast reduction surgery: a different approach

We read with interest the manuscript entitled Antibiotic Prophylaxis in Breast Reduction Surgery: A Systematic Review and Metaanalysis published by Zapata-Copete and al. in Journal of Plastic, Reconstructive & Aesthetic Surgery in August 2017 (1).

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Preoperative fasting in children

1A012A033J03

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Paediatric airway infections

1C022D013D00

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Error and Root Cause Analysis

1I032A063I00

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Burnout and resilience in anaesthesia and intensive care medicine

1H022H013J02

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Complex pain in children and young people: part I—assessment

1H022E033J02

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Preoperative fasting in children

1A012A033J03

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Paediatric airway infections

1C022D013D00

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Error and Root Cause Analysis

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Burnout and resilience in anaesthesia and intensive care medicine

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Complex pain in children and young people: part I—assessment

1H022E033J02

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Is Subcranial Le Fort III Plus Le Fort I Osteotomy Stable?

The purpose of this study was to test whether associated subcranial Le Fort III (sLF III) and Le Fort I (LF I) osteotomies are stable after large advancements of the middle third of the face and maxilla. The authors designed a retrospective study and enrolled a sample of consecutive patients with midface hypoplasia treated with associated sLF III and LF I osteotomies in this IRB-approved study between September 2013 and February 2015. To test whether the long-term stability was satisfactory, the authors compared cephalometric changes from immediately after surgery to 18 months after surgery taken from multi-slice computed tomography using two different third-party imaging software programs.

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Orthognathic surgery “again” to correct aesthetic failure of primary surgery: Report on outcomes and patient satisfaction in 70 consecutive cases

An increasing number of patients complain about unsatisfactory aesthetic outcomes of orthognathic surgery, desiring reoperation to improve facial aesthetics. The aims of this article are to present a wide range of aesthetic reasons to justify a secondary orthognathic surgery and to report aesthetic outcomes and patient satisfaction after reoperation.

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Conservative treatment of children with chronic diffuse sclerosing osteomyelitis/tendoperiostitis of the mandible

Chronic diffuse sclerosing osteomyelitis (DSO) of the mandible is a rare disease of unknown etiology. It has been suggested that overuse of the masticatory muscles, tendoperiostitis (TP), is a contributing factor for DSO. Therefore, we tested this hypothesis by treating consecutive children with conservative therapy.All patients were treated with conservative therapy, comprising occlusal splint therapy, physiotherapy, and/or disease counselling. Pain intensity on a visual analogue scale (VAS) and pain frequency in number of days per 3 months were recorded before the start of treatment, and at 3, 6, and 12 months after treatment initiation.

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Quantitative assessment of orbital fractures in Asian patients: CT measurement of orbital volume

Enophthalmos is caused by an increase of orbital volume after blowout fracture and is one of the most critical complications of such fractures, but is often masked by swelling soon after injury. If surgery is performed after swelling resolves, it becomes more difficult to treat enophthalmos because of atrophy and fibrosis. Accordingly, it is important to estimate the severity of enophthalmos soon after injury. We developed a new criterion for determining whether orbital fractures are indicated for surgery in Asian patients using analysis of orbital volume.

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Unraveling Pancreatic Segmentation

Abstract

Background

Limited pancreatic resections are increasingly performed, but the rate of postoperative fistula is higher than after classical resections. Pancreatic segmentation, anatomically and radiologically identifiable, may theoretically help the surgeon removing selected anatomical portions with their own segmental pancreatic duct and thus might decrease the postoperative fistula rate. We aimed at systematically and comprehensively reviewing the previously proposed pancreatic segmentations and discuss their relevance and limitations.

Methods

PubMed database was searched for articles investigating pancreatic segmentation, including human or animal anatomy, and cadaveric or surgical studies.

Results

Overall, 47/99 articles were selected and grouped into 4 main hypotheses of pancreatic segmentation methodology: anatomic, vascular, embryologic and lymphatic. The head, body and tail segments are gross description without distinct borders. The arterial territories defined vascular segments and isolate an isthmic paucivascular area. The embryological theory relied on the fusion plans of the embryological buds. The lymphatic drainage pathways defined the lymphatic segmentation. These theories had differences, but converged toward separating the head and body/tail parts, and the anterior from posterior and inferior parts of the pancreatic head. The rate of postoperative fistula was not decreased when surgical resection was performed following any of these segmentation theories; hence, none of them appeared relevant enough to guide pancreatic transections.

Conclusion

Current pancreatic segmentation theories do not enable defining anatomical–surgical pancreatic segments. Other approaches should be explored, in particular focusing on pancreatic ducts, through pancreatic ducts reconstructions and embryologic 3D modelization.

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The 150 most important questions in cancer research and clinical oncology series: questions 57–66

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and poten...

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Correction to: The 3.5-year survival rates of primary molars treated according to three treatment protocols: a controlled clinical trial

Abstract

Mw. M. Mijan will defend her PhD thesis on 15th September 2017. Whilst reviewing her work in preparation to the event, we discovered a few irregularities that prompted a recheck of the database and ditto analyses. These activities have lead to a few textual changes in the publication.

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Correction to: The 3.5-year survival rates of primary molars treated according to three treatment protocols: a controlled clinical trial

Abstract

Mw. M. Mijan will defend her PhD thesis on 15th September 2017. Whilst reviewing her work in preparation to the event, we discovered a few irregularities that prompted a recheck of the database and ditto analyses. These activities have lead to a few textual changes in the publication.

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Outcome with Primary En-bloc Esophagectomy for Submucosal Esophageal Adenocarcinoma

Abstract

Background

Intramucosal esophageal adenocarcinoma can be reliably treated endoscopically. Controversy exists about the use of endotherapy versus esophagectomy for submucosal tumors. Increasingly endotherapy is considered for submucosal tumors in part because of the presumed high mortality with esophagectomy and the perceived poor prognosis in patients with nodal disease. This study was designed to assess survival following primary en bloc esophagectomy (EBE) in patients with submucosal esophageal adenocarcinoma (EAC).

Methods

This is a retrospective review of all patients who underwent EBE for submucosal EAC between 1998 and 2015. No patient had neoadjuvant therapy.

Results

There were 32 patients (28M/4F; median age 64 years). The median tumor size was 1.5 cm (0.4–8.0), and the median number of resected nodes was 48 (23–85). There was one perioperative death. Lymph node metastases were present in 7 patients (22%). There was one involved node in four patients and 2, 3, and 31 nodes in one patient each. The one N3 patient received adjuvant therapy. The median follow-up was 87 months. Overall survival at 5 and 10 years was 84 and 70% respectively. Disease-specific survival at 10 years was 90%. Eight patients died, but only three deaths (9%) were related to EAC. Disease-specific survival at 10 years in node-positive patients was 71%.

Conclusions

Survival after primary en bloc esophagectomy for submucosal adenocarcinoma was excellent even in node-positive patients. Mortality with esophagectomy was low and far less than the 22% risk of node metastases in patients with submucosal tumor invasion. Esophagectomy should remain the preferred treatment for T1b esophageal adenocarcinoma.

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Prognostic Significance of Pre- to Postoperative Dynamics of the Prognostic Nutritional Index for Patients with Renal Cell Carcinoma Who Underwent Radical Nephrectomy

Abstract

Background

This study aimed to examine the prognostic role of Prognostic Nutritional Index (PNI) dynamics in the pre- and postoperative periods for patients with renal cell carcinoma (RCC) who undergo radical nephrectomy (RN).

Methods

The study analyzed 324 patients with RCC who underwent RN. The overall population was classified into four groups according to four types of pre- to postoperative PNI dynamics as follows: group 1 (low → low PNI), group 2 (low → high PNI), group 3 (high → low PNI), and group 4 (high → high PNI). The level of PNI was calculated using the following formula: 10 × serum albumin level (g/dL) + 0.005 × absolute lymphocyte counts in blood (/mm³). The primary end point was cancer-specific survival (CSS), and the secondary end point was overall survival (OS).

Results

The patients with higher pre- and postoperative PNI (>45) had better survival outcomes than those with lower pre- and postoperative PNI (≤45). Notably, the patients in group 4 showed the best CSS and OS rates, whereas the patients in group 1 had the worst survival outcomes. Furthermore, PNI dynamics were identified as an independent predictor of CSS and OS outcomes, in addition to pre- and postoperative PNI, tumor size, and pathologic T (pT) stage. The patients with localized RCC (≤pT2) showed significant differences in both CSS and OS estimates, whereas the patients with advanced pT stage (≥pT3) demonstrated a difference only in OS outcomes, according to PNI dynamics.

Conclusions

This study is the first to provide the independent prognostic importance of dynamics of nutritional status for patients with RCC.

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Does endogenous GLP-1 affect resting energy expenditure and fuel selection in overweight and obese adults?

Abstract

Purpose

To investigate the association between fasting glucagon-like peptide 1 (GLP-1) levels and resting energy expenditure (REE), and respiratory quotient (RQ) in overweight and obese adults.

Method

Study participants were enrolled at the Dietetic and Metabolic Unit, University of Pavia, Italy. Inclusion criteria were age ≥ 25 and ≤ 45 years, and body mass index (BMI) ≥ 25 and ≤ 35 kg/m². Diabetic subjects were excluded. Body composition was measured by dual-energy X-ray absorptiometry. REE was evaluated using indirect calorimetry, and RQ was calculated from respiratory gas exchanges. Fasting GLP-1, glucose, insulin and free fatty acid (FFA) levels, and 24-h norepinephrine urinary excretion were measured. Homeostasis model assessments of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) were calculated.

Results

Thirty-seven participants were included (age 43.4 ± 1.6 years; BMI 30.6 ± 0.5 kg/m²). REE was not associated with fasting GLP-1 levels (p = 0.98) after adjustment for age, sex, fat-free mass (FFM), and fat mass (FM). Similarly, no association was observed between RQ and GLP-1 levels (p = 0.95), after adjustment for age, sex, and body fat.

Conclusion

In adults subjects with increased adiposity fasting, GLP-1 levels do not seem to play a role in the regulation of energy metabolism and in fuel selection.

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Outcome with Primary En-bloc Esophagectomy for Submucosal Esophageal Adenocarcinoma

Abstract

Background

Intramucosal esophageal adenocarcinoma can be reliably treated endoscopically. Controversy exists about the use of endotherapy versus esophagectomy for submucosal tumors. Increasingly endotherapy is considered for submucosal tumors in part because of the presumed high mortality with esophagectomy and the perceived poor prognosis in patients with nodal disease. This study was designed to assess survival following primary en bloc esophagectomy (EBE) in patients with submucosal esophageal adenocarcinoma (EAC).

Methods

This is a retrospective review of all patients who underwent EBE for submucosal EAC between 1998 and 2015. No patient had neoadjuvant therapy.

Results

There were 32 patients (28M/4F; median age 64 years). The median tumor size was 1.5 cm (0.4–8.0), and the median number of resected nodes was 48 (23–85). There was one perioperative death. Lymph node metastases were present in 7 patients (22%). There was one involved node in four patients and 2, 3, and 31 nodes in one patient each. The one N3 patient received adjuvant therapy. The median follow-up was 87 months. Overall survival at 5 and 10 years was 84 and 70% respectively. Disease-specific survival at 10 years was 90%. Eight patients died, but only three deaths (9%) were related to EAC. Disease-specific survival at 10 years in node-positive patients was 71%.

Conclusions

Survival after primary en bloc esophagectomy for submucosal adenocarcinoma was excellent even in node-positive patients. Mortality with esophagectomy was low and far less than the 22% risk of node metastases in patients with submucosal tumor invasion. Esophagectomy should remain the preferred treatment for T1b esophageal adenocarcinoma.

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Prognostic Significance of Pre- to Postoperative Dynamics of the Prognostic Nutritional Index for Patients with Renal Cell Carcinoma Who Underwent Radical Nephrectomy

Abstract

Background

This study aimed to examine the prognostic role of Prognostic Nutritional Index (PNI) dynamics in the pre- and postoperative periods for patients with renal cell carcinoma (RCC) who undergo radical nephrectomy (RN).

Methods

The study analyzed 324 patients with RCC who underwent RN. The overall population was classified into four groups according to four types of pre- to postoperative PNI dynamics as follows: group 1 (low → low PNI), group 2 (low → high PNI), group 3 (high → low PNI), and group 4 (high → high PNI). The level of PNI was calculated using the following formula: 10 × serum albumin level (g/dL) + 0.005 × absolute lymphocyte counts in blood (/mm³). The primary end point was cancer-specific survival (CSS), and the secondary end point was overall survival (OS).

Results

The patients with higher pre- and postoperative PNI (>45) had better survival outcomes than those with lower pre- and postoperative PNI (≤45). Notably, the patients in group 4 showed the best CSS and OS rates, whereas the patients in group 1 had the worst survival outcomes. Furthermore, PNI dynamics were identified as an independent predictor of CSS and OS outcomes, in addition to pre- and postoperative PNI, tumor size, and pathologic T (pT) stage. The patients with localized RCC (≤pT2) showed significant differences in both CSS and OS estimates, whereas the patients with advanced pT stage (≥pT3) demonstrated a difference only in OS outcomes, according to PNI dynamics.

Conclusions

This study is the first to provide the independent prognostic importance of dynamics of nutritional status for patients with RCC.

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Ra-223 SPECT for semi-quantitative analysis in comparison with Tc-99m HMDP SPECT: phantom study and initial clinical experience

Abstract

Background

Image-based measurement of absorbed dose of Ra-223 dichloride may be useful in predicting therapeutic outcome in patients with castration-resistant prostate cancer (CRPC). In general, SPECT has been found to be more accurate than planar imaging in terms of lesion-based analysis. The aims of this study were to assess the feasibility and clinical usefulness of Ra-223 SPECT.

The energy spectrum of Ra-223 and SPECT images of a cylindrical phantom with a hot rod were obtained to determine the collimator candidates and energy window settings suitable for clinical Ra-223 SPECT (basic study A). Another phantom with a tube-shaped chamber and two spheres simulating bowel activity and metastatic lesions in the lumbar spine was scanned with medium-energy general-purpose (MEGP) and high-energy general-purpose (HEGP) collimators (basic study B). Ten patients with CRPC underwent SPECT imaging 2 h after Ra-223 injection successively with MEGP and HEGP collimators in random order for 30 min each. Lesion detectability and semi-quantitative analyses of bone metastasis (i.e. lesion-to-background ratio (LBR)) were performed compared to Tc-99m HMDP SPECT.

Results

Basic study A revealed that an 84-keV photopeak ± 20% using the HEGP collimator offers better SPECT image quality than the other imaging conditions. Basic study B showed that uptake in one of the spheres was overestimated by overlapped activity of the tube-shaped chamber in planar imaging whereas the spheres had similar counts and significantly higher sphere-to-background ratio in SPECT. On both planar and SPECT images, HEGP gave higher image contrast than MEGP (p < 0.01). In the clinical study, Ra-223 SPECT at 84 keV ± 20% depicted more lesions with the HEGP than with the MEGP collimator (51 vs 36, p = 0.013). There was a positive correlation between LBR in Tc-99m SPECT and in Ra-223 SPECT (r = 0.67 with the MEGP and 0.69 with the HEGP collimator, p < 0.01). LBRs were significantly higher with the HEGP than with the MEGP collimator (p < 0.01).

Conclusions

We recommended the use of the HEGP collimator at 84 keV ± 20% for Ra-223 SPECT imaging. Lesion-based semi-quantitative analysis in the human study revealed a good correlation between Ra-223 and Tc-99m HMDP SPECT in the early phase (2–3 h post injection).

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Multiple rapidly growing desmoid tumors that were difficult to distinguish from recurrence of rectal cancer

Abstract

Background

Intra-abdominal desmoid tumors are usually slow growing and solitary, but multifocal desmoid tumors develop on rare occasions. Diagnosing desmoid tumors before histological examination of a surgical biopsy is often difficult. In particular, if a patient has a prior history of malignancy, it may be difficult to differentiate between these lesions and disease recurrence or metastasis.

Case presentation

We present a rare case of multiple rapidly growing intra-abdominal desmoid tumors after surgical trauma, without familial adenomatous polyposis. A 51-year-old male underwent abdominal perineal resection with lateral lymph node dissection after neoadjuvant chemotherapy for lower rectal cancer. Follow-up computed tomography (CT), performed 6 months after primary surgery, showed a 20-mm solitary mass in the pelvic mesentery. Another CT scan, performed 3 months later, revealed that the mass had grown to 35 mm in size and that two new masses had formed. Based on imaging studies and his medical history, it was difficult to distinguish the desmoid tumors from recurrence of rectal cancer. Curative resection was chosen for therapeutic diagnosis. The pathological diagnosis was multiple mesenteric desmoid tumors.

Conclusions

Desmoid tumors should not be excluded as a differential diagnosis for intra-abdominal masses after intra-abdominal surgery, even in cases of rapidly growing multiple masses.

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Salvage re-irradiation for recurrent high-grade glioma and comparison to bevacizumab alone

Abstract

While salvage re-irradiation is often used for recurrent high-grade glioma (HGG), there have been few comparisons between various re-radiation dose/fractionation schedules or with bevacizumab alone. We analyzed patients with recurrent HGG who received re-irradiation at Dana-Farber Cancer Institute and Brigham and Women’s Hospital from 2010 to 2014 (n = 67), as well as those who received bevacizumab alone (n = 177). Cox proportional hazards modeling was used to examine factors associated with overall survival (OS). Propensity score modeling was used to compare survival after re-irradiation vs. bevacizumab alone. Median time from initial diagnosis to re-irradiation was 31.4 months. The most common re-irradiation dose/fractionations used were 6 Gy × 5 (36%), 3.5 Gy × 10 (21%), 2.67 Gy × 15 (15%), and 18–20 Gy × 1 (15%). No early or late toxicities >grade 2 were observed. Median PFS and OS after re-irradiation were 4.8 and 10.7 months, respectively. Number of progressions prior to re-irradiation (adjusted hazard ratio [AHR] 1.6; 95% CI, 1.1–2.3; p = .007), and recurrence in a new brain location (vs. local-only; AHR 7.4; 95% CI, 2.4–23.1; p < .001) were associated with OS; dose/fractionation was not. Compared with bevacizumab alone, re-irradiated patients had a non-significant increase in OS (HR 0.80; 95% CI, 0.53–1.23; P = .31). Among patients with a local-only recurrence, there was a trend towards longer median OS after re-irradiation compared to bevacizumab alone (12.4 vs. 8.0 months; p = .12). Survival after re-irradiation for recurrent HGG appears independent of dose/fractionation and compares favorably with bevacizumab alone.

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The Case of an Ugly Truth

  The great tragedy of Science — the slaying of a beautiful hypothesis by an ugly fact.                                                                             […]

EMCrit by Rory Spiegel.

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P 26 Evaluation of clinical, electrophysiological, sonographic and MRI characteristics of the CIDP spectrum disorder

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease with a wide spectrum of clinical presentation and treatment response. Electrophysiological studies constitute the gold standard used to characterise CIDP patients and contribute to treatment decisions. However, mostly at late stages electrophysiological methods show a pronounced axonal damage and are not able to distinguish CIDP subtypes. Therefore, therapeutic decisions have to be based solely on the clinical course.

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P 27 Beyond binary parcellation of the vestibular cortex

A binary approach to resting-state functional connectivity based parcellation (fCBP) provides useful insights into human brain organization, but also entails oversimplifications (Glasser, 2016). This is especially true for multisensory and higher-level associative brain areas, such as the bilateral vestibular cortical network with its multiple multisensory areas (Dieterich and Brandt, 2015). This study aimed to identify subunits of the vestibular cortex whilst accounting for a possible affiliation of voxel to different sensory systems using a multivariate fCBP within a vestibular region of interest (ROI) including known cortical areas of the vestibular network, i.e.

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