Immunotherapy in Pancreatic Ductal Adenocarcinoma: An Emerging Entity?

Abstract

The genomic-plasticity of the immune system creates a broad immune repertoire engaged to tackle cancer cells. Promising clinical activity has been observed with several immune therapy strategies in solid tumors including melanoma, lung, kidney and bladder cancers, albeit as yet immunotherapy-based treatment approaches in pancreatic ductal adenocarcinoma (PDAC) remain to have proven value. While translational and early clinical studies have demonstrated activation of antitumor immunity, most recent late-phase clinical trials have not confirmed the early promise in PDAC except in MSI-High PDAC patients. These results may in part be explained by multiple factors, including the poorly immunogenic nature of PDAC along with immune privilege, the complex tumor microenvironment and the genetic plasticity of PDAC cells. These challenges have led to disappointments in the field, nonetheless they have also advanced our understanding that may tailor the future steps for immunotherapy for PDAC. Therefore, there is significant hope that progress is on the horizon.

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Incorporating BEAMing technology as a liquid biopsy into clinical practice for the management of colorectal cancer patients: an expert taskforce review

Abstract

The importance of mutation identification for advanced colorectal cancer treatment with anti- epidermal growth factor receptor (EGFR) agents is well established. However, due to delays in turnaround time, low-quality tissue samples, and/or lack of standardization of testing methods a significant proportion of patients are being treated without the information that KRAS and NRAS testing can provide. The detection of mutated circulating tumor DNA by BEAMing technology addresses this gap in care and allows these patients to receive international guideline-recommended expanded RAS testing with rapid turnaround times. Furthermore, the overall concordance between OncoBEAM RAS CRC testing and standard of care tissue testing is very high (93.3%). This article presents an overview of the clinical utility and potential applications of this minimally-invasive method, such as early detection of emergent resistance to anti-EGFR therapy. If appropriately implemented, BEAMing technology holds considerable promise to enhance the quality of patient care and improve clinical outcomes.

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De-escalation strategies in HER2-positive early breast cancer (EBC): Final analysis of the WSG-ADAPT HER2+/HR- phase II trial: Efficacy, safety, and predictive markers for 12-weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel

Abstract

Background: Response rates in HER2-overexpressing EBC treated with neoadjuvant chemotherapy and trastuzumab (T) have been improved by addition of pertuzumab (P). The prospective, phase II, neoadjuvant WSG-ADAPT HER2+/HR- trial assessed whether patients with strong early response to dual blockade alone might achieve pathological complete response (pCR) comparable to that of patients receiving dual blockade and chemotherapy.Patients and Methods: Female patients with HER2+/HR- EBC (M0) were randomized (5:2) to 12 weeks of T+P ± weekly paclitaxel (pac) at 80 mg/m². Early response was defined as proliferation decrease ≥30% of Ki-67 (vs. baseline) or low cellularity (<500 invasive tumor cells) in the three-week biopsy. The trial was designed to test non-inferiority for pCR in early responding patients of the T+P arm versus all chemotherapy-treated patients. Results: From 2/2014 to 12/2015, 160 patients were screened; 92 were randomized to T+P and 42 to T+P+pac. Baseline characteristics were well balanced (median age 54 vs. 51.5 years, cT2 51.1 vs. 52.4%, cN0 54.3 vs. 61.9%); 91.3% of patients completed T+P per protocol and 92.9% T+P+pac. The pCR rate in the T+P+pac arm was 90.5%, compared to 36.3% in the T+P arm as a whole. In the T+P arm, 24/92 were classified as non-responders, and their pCR rate was only 8.3% compared to 44.7% in responders (38/92) and 42.9% in patients with unclassified early response (30/92).No new safety signals were observed in the study population.Conclusion: Addition of taxane monotherapy to dual HER2 blockade in a 12-week neoadjuvant setting substantially increases pCR rates in HER2+/HR- EBC compared to dual blockade alone, even within early responders to dual blockade. Early non-response under dual blockade strongly predicts failure to achieve pCR.

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HBV related acute hepatitis due to immune checkpoint inhibitors in a patient with malignant melanoma

Immune checkpoint inhibitorHepatitis BAcute HepatitisTenofovir

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Dynamic Molecular Analysis and Clinical Correlates of Tumor Evolution Within a Phase 2 Trial of Panitumumab-Based Therapy in Metastatic Colorectal Cancer

Abstract

Background: Mutations in rat sarcoma (RAS) genes may be a mechanism of secondary resistance in EGFR inhibitor−treated patients. Tumor-tissue biopsy testing has been the standard for evaluating mutational status; however, plasma testing of cell-free DNA has been shown to be a more sensitive method for detecting clonal evolution.Materials and Methods: Archival pre- and post-treatment tumor biopsy samples from a phase 2 study of panitumumab in combination with irinotecan in patients with metastatic colorectal cancer (mCRC) that also collected plasma samples before, during, and after treatment were analyzed for emergence of mutations during/post-treatment by next-generation sequencing (NGS) and BEAMing.Results: The rate of emergence of tumor tissue RAS mutations was 9.5% by NGS (n=21) and 6.3% by BEAMing (n=16). Plasma testing of cell-free DNA by BEAMing revealed a mutant RAS emergence rate of 36.7% (n=39). Exploratory outcomes analysis of plasma samples indicated that patients who had emergent RAS mutations at progression had similar median progression-free survival to those patients who remained wild type at progression. Serial analysis of plasma samples showed that the first detected emergence of RAS mutations preceded progression by a median of 3.6 months (range, –0.3 to 7.5 months) and that there did not appear to be a mutant RAS allele frequency threshold that could predict near-term outcomes.Conclusions: This first prospective analysis in mCRC showed that serial plasma biopsies are more inclusive than tissue biopsies for evaluating global tumor heterogeneity; however, the clinical utility of plasma testing in mCRC remains to be further explored.ClinicalTrials.gov Identifier: NCT00891930

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Of Mice and Men: patient-derived xenografts in cancer medicine

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Antigen Cross-Presentation and T-Cell Cross-Priming In Cancer Immunology And Immunotherapy

Abstract

Dendritic cells are the main professional antigen-presenting cells for induction of T cell adaptive responses. Cancer cells express tumor antigens, including neoantigens generated by non-synonymous mutations, but are poor for antigen presentation and for providing costimulatory signals for T-cell priming. Mounting evidence suggests that antigen transfer to dendritic cells (DCs) and their surrogate presentation on MHC class I and II molecules together with costimulatory signals is paramount for induction of viral and cancer immunity. Of the great diversity of DCs, BATF3/IRF8-dependent conventional DCs type 1 (cDC1) excel at cross-presentation of tumor cell-associated antigens. Location of cDC1s in the tumor correlates with improved infiltration by CD8⁺ T cells and tumor-specific T cell immunity. Indeed, cDC1s are crucial for antitumor efficacy using checkpoint inhibitors and anti-CD137 agonist monoclonal antibodies in mouse models. Enhancement and exploitation of T-cell cross-priming by cDC1s offer opportunities for improved cancer immunotherapy, including in vivo targeting of tumor antigens to internalizing receptors on cDC1s and strategies to increase their numbers, activation and priming capacity within tumors and tumor-draining lymph nodes.

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A ventral glomerular deficit in Parkinson’s disease revealed by whole olfactory bulb reconstruction

Abstract

Olfactory dysfunction is common in Parkinson's disease and is an early symptom, but its pathogenesis remains poorly understood. Hindering progress in our mechanistic understanding of olfactory dysfunction in Parkinson's disease is the paucity of literature about the human olfactory bulb, both from normal and Parkinson's disease cases. Qualitatively it is well established that the neat arrangement of the glomerular array seen in the mouse olfactory bulb is missing in humans. But rigorous quantitative approaches to describe and compare the thousands of glomeruli in the human olfactory bulb are not available. Here we report a quantitative approach to describe the glomerular component of the human olfactory bulb, and its application to draw statistical comparisons between olfactory bulbs from normal and Parkinson's disease cases. We subjected horizontal 10 µm sections of olfactory bulbs from six normal and five Parkinson's disease cases to fluorescence immunohistochemistry with antibodies against vesicular glutamate transporter-2 and neural cell adhesion molecule. We scanned the immunostained sections with a fluorescence slide scanner, segmented the glomeruli, and generated 3D reconstructions of whole olfactory bulbs. We document the occurrence of atypical glomerular morphologies and glomerular-like structures deep in the olfactory bulb, both in normal and Parkinson's disease cases. We define a novel and objective parameter: the global glomerular voxel volume, which is the total volume of all voxels that are classified immunohistochemically as glomerular. We find that the global glomerular voxel volume in Parkinson's disease cases is half that of normal cases. The distribution of glomerular voxels along the dorsal-ventral dimension of the olfactory bulb in these series of horizontal sections is significantly altered in Parkinson's disease cases: whereas most glomerular voxels reside within the ventral half of olfactory bulbs from normal cases, glomerular voxels are more evenly spread among the ventral and dorsal halves of olfactory bulbs from Parkinson's disease cases. These quantitative whole-olfactory bulb analyses indicate a predominantly ventral deficit in the glomerular component in Parkinson's disease, consistent with the olfactory vector hypothesis for the pathogenesis of this neurodegenerative disease. The distribution of serine 129-phosphorylated α-synuclein immunoreactive voxels correlates with that of glomerular voxels. The higher the serine 129-phosphorylated α-synuclein load of an olfactory bulb from a Parkinson's disease case, the lower the global glomerular voxel volume. Our rigorous quantitative approach to the whole olfactory bulb will help understand the anatomy and histology of the normal human olfactory bulb and its pathological alterations in Parkinson's disease.

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Distinct spatiotemporal patterns of neuronal functional connectivity in primary progressive aphasia variants

Abstract

Primary progressive aphasia is a syndrome characterized by progressive loss of language abilities with three main phenotypic clinical presentations, including logopenic, non-fluent/agrammatic, and semantic variants. Previous imaging studies have shown unique anatomic impacts within language networks in each variant. However, direct measures of spontaneous neuronal activity and functional integrity of these impacted neural networks in primary progressive aphasia are lacking. The aim of this study was to characterize the spatial and temporal patterns of resting state neuronal synchronizations in primary progressive aphasia syndromes. We hypothesized that resting state brain oscillations will show unique deficits within language network in each variant of primary progressive aphasia. We examined 39 patients with primary progressive aphasia including logopenic variant (n = 14, age = 61 ± 9 years), non-fluent/agrammatic variant (n = 12, age = 71 ± 8 years) and semantic variant (n = 13, age = 65 ± 7 years) using magnetoencephalographic imaging, compared to a control group that was matched in age and gender to each primary progressive aphasia subgroup (n = 20, age = 65 ± 5 years). Each patient underwent a complete clinical evaluation including a comprehensive battery of language tests. We examined the whole-brain resting state functional connectivity as measured by imaginary coherence in each patient group compared to the control cohort, in three frequency oscillation bands—delta-theta (2–8 Hz); alpha (8–12 Hz); beta (12–30 Hz). Each variant showed a distinct spatiotemporal pattern of altered functional connectivity compared to age-matched controls. Specifically, we found significant hyposynchrony of alpha and beta frequency within the left posterior temporal and occipital cortices in patients with the logopenic variant, within the left inferior frontal cortex in patients with the non-fluent/agrammatic variant, and within the left temporo-parietal junction in patients with the semantic variant. Patients with logopenic variant primary progressive aphasia also showed significant hypersynchrony of delta-theta frequency within bilateral medial frontal and posterior parietal cortices. Furthermore, region of interest-based analyses comparing the spatiotemporal patterns of variant-specific regions of interest identified in comparison to age-matched controls showed significant differences between primary progressive aphasia variants themselves. We also found distinct patterns of regional spectral power changes in each primary progressive aphasia variant, compared to age-matched controls. Our results demonstrate neurophysiological signatures of network-specific neuronal dysfunction in primary progressive aphasia variants. The unique spatiotemporal patterns of neuronal synchrony signify diverse neurophysiological disruptions and pathological underpinnings of the language network in each variant.

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Issue Cover (September 2017)

Cover image by Dr. Natalie Doig (MRC Brain Network Dynamics Unit, Department of Pharmacology, Oxford). The cover image is of a frontal section of mouse brain showing many regions of the basal ganglia. The section was triple-immunostained to reveal tyrosine hydroxylase (TH; cyan), parvalbumin (PV; green) and choline acetyltransferase (magenta).

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Tubal ligation and ovarian cancer risk in African American women

Abstract

Purpose

Tubal ligation has been associated with reduced risk of epithelial ovarian cancer (EOC) in studies of primarily white women, but less is known about the association in African American (AA) women. We sought to evaluate the associations among 597 invasive ovarian cancer cases and 742 controls of AA descent recruited from the African American Cancer Epidemiology Study, a population-based case–control study in 11 geographical areas in the US.

Methods

Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potentially confounding factors.

Results

An inverse association between tubal ligation and EOC was observed that was not statistically significant (OR 0.88, 95% CI 0.68–1.14). However, an inverse association with EOC risk was observed among women who had a tubal ligation at age 35 years or older (OR 0.64; 95% CI 0.41–0.98), but not among those who had a tubal ligation before age 35 (OR 0.98; 95% CI 0.74–1.29) (p for interaction = 0.08). The association also varied considerably by tumor subtype. A strong inverse association was observed for endometrioid tumors (OR 0.31, 95% CI 0.14–0.70), whereas associations with mucinous (OR 0.87, 95% CI 0.36–2.12) and serous (OR 0.94, 95% CI 0.71–1.24) tumors were weaker and not statistically significant. A statistically non-significant positive association for clear cell tumors (OR 1.84, 95% CI 0.58–5.82) was based on a low number of cases.

Conclusions

Our findings show that tubal ligation may confer a reduced risk for EOC among AA women that is comparable to the associations that have been previously observed in primarily white populations.

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Issue Information - Ed Board

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A novel technique for correcting the over-corrected gynaecomastia using stacked acellular dermal matrix

Abstract

The 'saucer-shaped deformity' is the undesirable outcome following over-resection of gynaecomastia. Correction can be challenging, lipomodelling may be unfavourable or unpredictable, and autologous grafts often require additional unwanted scars. We present a case of unilateral gynaecomastia over-resection where disks of acellular dermal matrix (ADM) were interwoven in the subdermal, intrapectoral, and interpectoral planes to correct the areolar cavity. A routine review at 17 months showed maintained projection of the areola, and the patient was delighted with the natural contour.

Level of Evidence: Level V, therapeutic study.

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Phase I dose escalation and pharmacokinetic study on the nanoparticle formulation of polymeric micellar paclitaxel for injection in patients with advanced solid malignancies

Summary

Background Polymeric micellar paclitaxel (PM-paclitaxel) is a novel Cremophor EL-free, nanoparticle-encapsulated paclitaxel formulation administered through intravenous injection. The primary objective of this phase I trial was to determine the first cycle dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of PM-paclitaxel. Secondary objectives included the evaluation of the safety, antitumor activity, and pharmacokinetic (PK) profile of PM-paclitaxel in patients with advanced malignancies. Methods The PM-paclitaxel dose was escalated from 175 mg/m² (level 1) to 435 mg/m² (level 5). PM-paclitaxel was intravenously administered to patients for 3 h without premedication on day 1 of a 21-day cycle. Results Eighteen patients with confirmed advanced malignancies received PM-paclitaxel. DLT included grade 4 neutropenia (four patients) and grade 3 numbness (one patient), which occurred in one of the six patients who received 300 mg/m² (level 3) PM-paclitaxel and all three patients who were treated with 435 mg/m² PM-paclitaxel. Thus, the MTD of PM-paclitaxel was determined as 390 mg/m² (level 4). Acute hypersensitive reactions were not observed. Partial response was observed in six of 18 patients (33.3%), three of whom had prior exposure to paclitaxel chemotherapy. The peak concentration and area under the curve values of paclitaxel increased with increasing dosage, indicating that PM-paclitaxel exhibits linear PKs. Conclusions PM-paclitaxel showed high MTD without additional toxicity, and exhibited desirable antitumor activity. The recommended dose of PM paclitaxel for phase II study is 300 mg/m².

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Erratum to: comparison between inflammation-related markers in peri-implant crevicular fluid and clinical parameters during osseointegration in edentulous jaws

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A novel technique for correcting the over-corrected gynaecomastia using stacked acellular dermal matrix

Abstract

The 'saucer-shaped deformity' is the undesirable outcome following over-resection of gynaecomastia. Correction can be challenging, lipomodelling may be unfavourable or unpredictable, and autologous grafts often require additional unwanted scars. We present a case of unilateral gynaecomastia over-resection where disks of acellular dermal matrix (ADM) were interwoven in the subdermal, intrapectoral, and interpectoral planes to correct the areolar cavity. A routine review at 17 months showed maintained projection of the areola, and the patient was delighted with the natural contour.

Level of Evidence: Level V, therapeutic study.

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Erratum to: comparison between inflammation-related markers in peri-implant crevicular fluid and clinical parameters during osseointegration in edentulous jaws

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Changes in intrinsic local connectivity after reading intervention in children with autism

Publication date: December 2017
Source:Brain and Language, Volume 175
Author(s): Jose O. Maximo, Donna L. Murdaugh, Sarah O'Kelley, Rajesh K. Kana
Most of the existing behavioral and cognitive intervention programs in autism spectrum disorders (ASD) have not been tested at the neurobiological level, thus falling short of finding quantifiable neurobiological changes underlying behavioral improvement. The current study takes a translational neuroimaging approach to test the impact of a structured visual imagery-based reading intervention on improving reading comprehension and assessing its underlying local neural circuitry. Behavioral and resting state functional MRI (rs-fMRI) data were collected from children with ASD who were randomly assigned to an Experimental group (ASD-EXP; n=14) and a Wait-list control group (ASD-WLC; n=14). Participants went through an established reading intervention training program (Visualizing and Verbalizing for language comprehension and thinking or V/V; 4-h per day, 10-weeks, 200h of face-to-face instruction). Local functional connectivity was examined using a connection density approach from graph theory focusing on brain areas considered part of the Reading Network. The main results are as follows: (I) the ASD-EXP group showed significant improvement, compared to the ASD-WLC group, in their reading comprehension ability evidenced from change in comprehension scores; (II) the ASD-EXP group showed increased local brain connectivity in Reading Network regions compared to the ASD-WLC group post-intervention; (III) intervention-related changes in local brain connectivity were observed in the ASD-EXP from pre to post-intervention; and (IV) improvement in language comprehension significantly predicted changes in local connectivity. The findings of this study provide novel insights into brain plasticity in children with developmental disorders using targeted intervention programs.



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Primary Cutaneous NK/T-cell Lymphoma of Nasal Type: An Age-related Lymphoproliferative Disease?

Publication date: Available online 2 September 2017
Source:Human Pathology
Author(s): Chun-Chieh Wu, Emiko Takahashi, Naoko Asano, Tomoko Miyata-Takata, Katsuyoshi Takata, Katsuya Furukawa, Ahmed Ali Elsayed, Lei-Ming Hu, Akira Satou, Kei Kohno, Hiroshi Kosugi, Kenichi Ohashi, Tomohiro Kinoshita, Shigeo Nakamura, Seiichi Kato
Among extranodal NK/T-cell lymphoma of nasal type (NKTL), the extranasal variant (ENKTL) is known to have a worse prognosis with advanced clinical stage than the nasal variant of NKTL. However, detailed clinicopathological features of the localized extranasal disease have not been well documented in English literature. Here, we described the clinicopathological profiles of 14 patients with stage I ENKTL, including 7 in the skin, 5 in the gastrointestinal tract, and 2 in the central nervous system, highlighting the distinctiveness of the first. The 7 primary cutaneous (PCNKTL) cases were characterized by an older onset age (median, 76 vs. 53years, P=.012) and a more favorable clinical course (P=.041), compared to 17 patients with stages II-IV ENKTL that showed cutaneous involvement. The skin lesions in the PCNKTL group were distributed in the face or neck (n=4) and limbs (n=3), but not the trunk, which was most frequently affected (60%, P=.017) in the latter group. Furthermore, the stage I cutaneous disease showed a female predominance (M:F, 2:5 vs. 7:0, P=.021) and a significantly more favorable survival compared to the non-cutaneous stage I ENKTL (P=.037). These results suggested that PCNKTL constituted a distinct subgroup in the nasal type lymphoma spectrum.



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Effects of dexamethasone and nimesulide on bisphosphonate-related osteonecrosis of the jaw: An experimental study

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Camila Carvalho de Oliveira, Paulo Goberlânio de Barros Silva, Antonio Ernando Carlos Ferreira, Romélia Pinheiro Gonçalves, Fabrício Bitu de Sousa, Mário Rogério Lima Mota, Ana Paula Negreiros Nunes Alves
ObjectiveTo evaluate the effects of dexamethasone (DEX) and nimesulide (NIM) on Bisphosphonate-related Osteonecrosis of the Jaw (BRONJ) in rats.DesignBRONJ was induced by zoledronic acid (ZA) infusion (0.2mg/kg) in Wistar rats (n=8), followed by extraction of the left lower first molar (BRONJ groups). Control groups (n=40) received saline (IV). For eight weeks, DEX (0.04, 0.4, 4mg/kg) or saline (SAL) were administered by gavage 24h before each infusion of ZA or saline (IV), or NIM (10.3mg/kg) was administered 24h and 12h before each infusion of ZA or saline (IV). The haematological analyses were conducted weekly. After euthanasia (day 70), the jaws were submitted to radiographic and microscopic analysis. Kidney, liver, spleen and stomach were analysed histopathologically.ResultsThe BRONJ groups showed a higher radiolucent area compared with the control groups (p<0.05). Histomorphometric analysis revealed healing and new bone formation in the control groups, while the BRONJ groups exhibited devitalized bone with bacterial colonies and inflammatory infiltrate. The BRONJ-DEX 0.4 and 4mg/kg groups had a greater number of bacterial colonies (p<0.05) and an increased polymorphonuclear cell count compared to the saline-BRONJ group, while the BRONJ-NIM group had a lower polymorphonuclear count (p<0.05). The BRONJ groups had leucocytosis, which was reduced by DEX administration. Treatments with DEX with or without ZA caused white pulp atrophy.ConclusionThus, DEX or NIM therapy was not effective in preventing radiographic and histopathologic events associated with BRONJ. Treatment with DEX attenuated leucocytosis post-infusion with ZA.



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A pitfall in magnetic stimulation for measuring central motor conduction time

Publication date: Available online 2 September 2017
Source:Clinical Neurophysiology
Author(s): Hideyuki Matsumoto, Yoshikazu Ugawa




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Prefrontal cortical responses in children with prenatal alcohol-related neurodevelopmental impairment: A functional near-infrared spectroscopy study

Publication date: Available online 2 September 2017
Source:Clinical Neurophysiology
Author(s): Julie A. Kable, Claire D. Coles
ObjectiveDisruption in the neural activation of the prefrontal cortex (PFC) in modulating arousal was explored in children with heavy prenatal alcohol exposure (PAE), who have known neurobehavioral impairment.MethodsDuring a task that elicits frustration, functional near-infrared spectroscopy (fNIRS) was used to measure PFC activation, specifically levels of oxygenated (HBO) and deoxygenated (HBR) hemoglobin, in children with PAE (n=18) relative to typically developing Controls (n=12) and a Clinical Contrast group with other neurodevelopmental or behavioral problems (n=14).ResultsChildren with PAE had less activation during conditions with positive emotional arousal, as indicated by lower levels of HBO in the medial areas of the PFC and higher levels of HBR in all areas of the PFC sampled relative to both other groups. Children in the Control group demonstrated greater differentiation of PFC activity than did children with PAE. Children in the Clinical Contrast group demonstrated the greatest differences in PFC activity between valences of task conditions.ConclusionsSpecific patterns of PFC activation differentiated children with PAE from typically developing children and children with other clinical problems.SignificanceFNIRS assessments of PFC activity provide new insights regarding the mechanisms of commonly seen neurobehavioral dysfunction in children with PAE.



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The Medial Plantar Sensory Response: A Sensitive Marker of Acute Inflammatory Demyelinating Polyneuropathy

Publication date: Available online 2 September 2017
Source:Clinical Neurophysiology
Author(s): Rechdi Ahdab, Samar Ayache, Mohammad Hassan A. Noureldine, Tarik Nordine, Jean-Pascal Lefaucheur




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Long-term effects of tDCS on fatigue, mood and cognition in multiple sclerosis

Publication date: Available online 2 September 2017
Source:Clinical Neurophysiology
Author(s): Moussa A. Chalah, Jean-Pascal Lefaucheur, Samar S. Ayache




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Electrophysiological correlates of performance monitoring in binge drinking: Impaired error-related but preserved feedback processing

Publication date: Available online 2 September 2017
Source:Clinical Neurophysiology
Author(s): Séverine Lannoy, Fabien D'Hondt, Valérie Dormal, Joël Billieux, Pierre Maurage
ObjectivePerformance monitoring, which allows efficient behavioral regulation using either internal (error processing) or external (feedback processing) cues, has not yet been explored in binge drinking despite its adaptive importance in everyday life, particularly in the regulation of alcohol consumption. Capitalizing on a theoretical model of risky behaviors, the present study aimed at determining the behavioral and electrophysiological correlates of the cognitive (inhibition) and motivational (reward sensitivity) systems during performance monitoring.MethodsEvent-related potentials were recorded from 20 binge drinkers and 20 non-binge drinkers during two experimental tasks, a speeded Go/No-Go Task [investigating internal error processing by Error-Related Negativity (ERN) and error positivity (Pe)] and a Balloon Analogue Risk Task [investigating external feedback processing by Feedback-Related Negativity (FRN) and P3].ResultsWhile no group differences were observed at the behavioral level, electrophysiological results showed that binge drinkers, despite having intact feedback-related components, presented modified error-monitoring components (i.e. larger ERN amplitude, delayed Pe latency).ConclusionsInternal performance monitoring is impaired in binge drinkers, showing an abnormal automatic processing of response errors (ERN) and a decreased processing of their motivational significance (Pe).SignificanceThese results suggest that the electrophysiological correlates of inhibitory control allow identifying the specific binge drinking consumption pattern.



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Esophagus foreign body in the thyroid gland

Publication date: Available online 2 September 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Sílvia Miguéis Picado Petrarolha, Rogério Aparecido Dedivitis, Fabíola Garcia Perruccio, Ingrid de Andrade Quirino




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DNA methylation profiles of 22 apoptosis-related genes in odontogenic keratocysts before and after marsupialization.

Related Articles

DNA methylation profiles of 22 apoptosis-related genes in odontogenic keratocysts before and after marsupialization.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Aug 03;:

Authors: Pereira KMA, Costa SFDS, Pereira NB, Diniz MG, Castro WH, Gomes CC, Gomez RS

Abstract
OBJECTIVE: Odontogenic keratocysts (OKCs) are cystic lesions of the jaw and tend to recur after treatment. Marsupialization is an effective preliminary treatment for large OKCs. This procedure induces epithelial lining changes in association with reduction of Bcl-2 protein expression, but the underlying mechanisms remain unknown. The purpose of our study was to compare the methylation profile of the apoptosis-related genes of OKCs before and after marsupialization.
STUDY DESIGN: We assessed the methylation percentages of the promoter region of 22 apoptosis-related genes in 13 OKCs, both marsupialized and nonmarsupialized lesions, by using methylation quantitative polymerase chain reaction array. We validated the expression of genes that showed the greatest differences in methylation percentages between the 2 groups.
RESULTS: LTBR and BCLAF1 showed higher DNA methylation percentages in the marsupialized OKCs, but this difference did not affect gene expression (P > .05). The other 20 genes showed similar DNA methylation in both OKC groups.
CONCLUSIONS: OKCs show a distinct methylation profile after marsupialization, but this is not followed by gene expression alterations.

PMID: 28864293 [PubMed - as supplied by publisher]

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The effect of bone mass and architecture on mandibular condyle after mandibular distraction.

Related Articles

The effect of bone mass and architecture on mandibular condyle after mandibular distraction.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 May 25;:

Authors: Suda D, Ohazama A, Maeda T, Kobayashi T

Abstract
OBJECTIVE: Mandibular distraction surgery is a critical treatment for jaw deformity. However, abnormal mandibular condylar bone resorption is often seen as complication after surgery. Our previous study using a rat mandibular distraction model suggested that overloading leads to mandibular condylar resorption. Host factors are also believed to influence the resorption. To understand the relationship between host factors and resorption, we investigated the effect of changing bone mass and architecture on the mandibular condyle using FK506.
STUDY DESIGN: FK506, an immunosuppressant, was used to compromise bone mass and architecture in this study. Animals were divided into 4 groups: distraction surgery (Dist), FK506 administration (FK), distraction surgery with FK506 administration (FK + Dist), and no surgery or FK506 administration (Cont).
RESULTS: The FK group showed reduced bone mass and impaired bone architecture. The Dist group exhibited abnormal bone resorption on the surface of the condyles, which was slightly exacerbated in the FK + Dist group. Bone defect length decreased over time as a result of bone apposition in the Dist group. However, in the FK + Dist group, the bone defect length remained the same.
CONCLUSIONS: These results suggest that bone mass and architecture strongly affect the tolerance to the overloading and adaptation with bone apposition in condylar resorption site.

PMID: 28864292 [PubMed - as supplied by publisher]

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Clinical Outcomes of Several IMRT Techniques for Patients With Head and Neck Cancer: A Propensity Score-Weighted Analysis.

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Clinical Outcomes of Several IMRT Techniques for Patients With Head and Neck Cancer: A Propensity Score-Weighted Analysis.

Int J Radiat Oncol Biol Phys. 2017 Jun 27;:

Authors: Bibault JE, Dussart S, Pommier P, Morelle M, Huguet M, Boisselier P, Coche-Dequeant B, Alfonsi M, Bardet E, Rives M, Calugaru V, Chajon E, Noel G, Mecellem H, Servagi Vernat S, Perrier L, Giraud P

Abstract
PURPOSE: The Advanced Radiotherapy Oto-Rhino-Laryngologie (ART-ORL) study (NCT02024035) was performed to prospectively evaluate the clinical and economic aspects of helical TomoTherapy and volumetric modulated arc therapy (RapidArc, Varian Medical Systems, Palo Alto, CA) for patients with head and neck cancer.
METHODS AND MATERIALS: Fourteen centers participated in this prospective comparative study. Randomization was not possible based on the availability of equipment. Patients with epidermoid or undifferentiated nasopharyngeal carcinoma or epidermoid carcinoma of the oropharynx and oral cavity (T1-T4, M0, N0-N3) were included between February 2010 and February 2012. Only the results of the clinical study are presented in this report, as the results of the economic assessment have been published previously. Inverse probability of treatment weighting using the propensity score analysis was undertaken in an effort to adjust for potential bias due to nonrandomization. Locoregional control, cancer-specific survival, and overall survival assessed 18 months after treatment, as well as long-term toxicity and salivary function, were evaluated.
RESULTS: The analysis included 166 patients. The following results are given after inverse probability of treatment weighting adjustment. The locoregional control rate at 18 months was significantly better in the TomoTherapy group: 83.3% (95% confidence interval [CI], 72.5%-90.2%) versus 72.7% (95% CI, 62.1%-80.8%) in the RapidArc group (P=.025). The cancer-specific survival rate was better in the TomoTherapy group: 97.2% (95% CI, 89.3%-99.3%) versus 85.5% (95% CI, 75.8%-91.5%) in the RapidArc group (P=.014). No significant difference was shown in progression-free or overall survival. TomoTherapy induced fewer acute salivary disorders (P=.012). Posttreatment salivary function degradation was worse in the RapidArc group (P=.012).
CONCLUSIONS: TomoTherapy provided better locoregional control and cancer-specific survival than RapidArc treatment, with fewer salivary disorders. No significant difference was shown in progression-free and overall survival. These results should be explored in a randomized trial.

PMID: 28864403 [PubMed - as supplied by publisher]

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The comparison of nasal surgery and CPAP on daytime sleepiness in patients with OSAS.

The comparison of nasal surgery and CPAP on daytime sleepiness in patients with OSAS.

Rhinology. 2017 Sep 02;:

Authors: Tagaya M, Otake H, Suzuki K, Yasuma F, Yamamoto H, Noda A, Nishimura Y, Sone M, Nakashima T, Nakata S

Abstract
OBJECTIVE: Residual sleepiness after continuous positive airway pressure (CPAP) is a critical problem in some patients with obstructive sleep apnea syndrome (OSAS). However, nasal surgery is likely to reduce daytime sleepiness and feelings of unrefreshed sleep. The aim of this study is to clarify the effects of nasal surgery and CPAP on daytime sleepiness.
METHODOLOGY: This is a retrospective and matched-case control study. The participants were consecutive 40 patients with OSAS who underwent nasal surgery (Surgery group) and 40 matched patients who were treated with CPAP (CPAP group).
RESULTS: In the Surgery group, although the nasal surgery did not decrease either apnea or hypopnea, it improved oxygenation, the quality of sleep. In the CPAP Group, the CPAP treatment reduced apnea and hypopnea, and improved oxygenation, quality of sleep. The degree of relief from daytime sleepiness was different between the two groups. The improvement of Epworth Sleepiness Scale was more significant in the Surgery Group than those in the CPAP Group (Surgery from 11.0 to 5.1, CPAP from 10.0 to 6.2).
DISCUSSION: These findings suggest that the results of the nasal surgery is more satisfactory for some patients with OSAS than CPAP on daytime sleepiness.

PMID: 28865140 [PubMed - as supplied by publisher]

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Paving the future of rhinosinusitis care.

Paving the future of rhinosinusitis care.

Rhinology. 2017 Sep 02;:

Authors: Hellings PW

Abstract
Novel insights into the pathophysiology of chronic rhinosinsusitis (CRS) will lead to endo-type driven treatment and reduce oral corticosteroid treatment.

PMID: 28865115 [PubMed - as supplied by publisher]

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Prospective experience of percutaneous endoscopic gastrostomy tubes placed by otorhinolaryngologist-head and neck surgeons: safe and efficacious.

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Prospective experience of percutaneous endoscopic gastrostomy tubes placed by otorhinolaryngologist-head and neck surgeons: safe and efficacious.

Eur Arch Otorhinolaryngol. 2017 Sep 01;:

Authors: Ruohoalho J, Aro K, Mäkitie AA, Atula T, Haapaniemi A, Keski-Säntti H, Kylänpää L, Takala A, Bäck LJ

Abstract
Percutaneous endoscopic gastrostomy (PEG) is often the treatment of choice in head and neck cancer (HNC) patients needing long-term nutritional support. Prospective studies on PEG tube placement in an otorhinolaryngologist service are lacking. At our hospital, otolaryngologist-head and neck (ORL-HN) surgeons-have performed PEG insertions for HNC patients since 2008. We prospectively analyzed 127 consecutive HNC patients who received their PEG tubes at the Department of Otorhinolaryngology-head and neck surgery, and evaluated the outcome of PEG tube insertions performed by ORL-HN surgeons. To compare time delays before and after, PEG placement service was transferred from gastrointestinal surgeons to ORL-HN surgeons, and we retrospectively analyzed a separate group of 110 HNC patients who had earlier received PEG tubes at the Department of Gastrointestinal Surgery. ORL-HN surgeons' success rate in PEG insertion was 97.6%, leading to a final prospective study group of 124 patients. Major complications occurred in four (3.2%): two buried bumper syndromes, one subcutaneous hemorrhage leading to an abscess in the abdominal wall, and one metastasis at the PEG site. The most common minor complication was peristomal granulomatous tissue affecting 23 (18.5%) patients. After the change in practice, median time delay before PEG insertion decreased from 13 to 10 days (P < 0.005). The proportion of early PEG placements within 0-3 days increased from 3.6 to 14.6% (P < 0.005). PEG tube insertion seems to be a safe procedure in the hands of an ORL-HN surgeon. Independence from gastrointestinal surgeons' services reduced the time delay and improved the availability of urgent PEG insertions.

PMID: 28865046 [PubMed - as supplied by publisher]

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Transoral robotic-assisted surgery for the approach to anterior cervical spine lesions.

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Transoral robotic-assisted surgery for the approach to anterior cervical spine lesions.

Eur Arch Otorhinolaryngol. 2017 Sep 01;:

Authors: Molteni G, Greco MG, Presutti L

Abstract
The Da Vinci robotic surgical system is increasingly being used by head and neck surgeons in transoral approaches for head and neck cancer. Our experience using the Da Vinci system for transoral robotic-assisted surgery (TORS) is presented. The feasibility of TORS for lesions involving the anterior portion of C1-C2 and the cranio-cervical junction has been evaluated from an anatomical viewpoint in a cadaveric laboratory. Two patients treated using the Da Vinci system to reach C1-C2 benign lesions are presented. The anatomical cadaveric study showed that this approach is safe and feasible. The first two cases which we describe confirmed the advantages of the Da Vinci system in the anterior approach to the cervical spine and allowed the limitations of this procedure to be assessed. TORS may be useful to reach anterior lesions of the cervical spine localized at the level of C1 and C2: first, for removal of small benign and well-delineated lesions; and second, for diagnostic purposes with biopsy of large lesions. Further studies and new instruments are needed to confirm the safety and results of this approach in terms of morbidity.

PMID: 28864959 [PubMed - as supplied by publisher]

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Venous Complications in One Versus Two Vein Anastomoses in Head and Neck Free Flaps.

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Venous Complications in One Versus Two Vein Anastomoses in Head and Neck Free Flaps.

Ann Otol Rhinol Laryngol. 2017 Sep 01;:3489417728089

Authors: Khaja SF, Rubin N, Bayon R

Abstract
OBJECTIVE: The purpose of this study was to compare rates of reexploration and flap failure in patients with 1- and 2-vein anastomoses in free flap reconstructions.
METHODS: Retrospective chart review of 300 patients undergoing free flap reconstruction to head and neck defects from 2010 to 2014.
RESULTS: One venous anastomosis was performed in 229 patients, and 2 venous anastomoses were performed in 71 patients. The 1-vein group had significantly more reexplorations in the operating room (36/229, 15.7%) compared with the 2-vein group (4/71, 5.6%; P = .028), even when controlling for flap type ( P = .022). This finding remained true among radial forearm flaps (17/81, 21% vs 3/53, 5.7%; P = .024). The number of venous anastomoses was not significantly associated with flap failure, though patients with flap failure did have a significantly greater proportion of venous issues ( P < .001).
CONCLUSIONS: Two-vein anastomoses do not appear to reduce rates of flap failure or postoperative venous thrombosis but are associated with a lower number of reexplorations in the operating room even after accounting for differences in flap types and surgeons.

PMID: 28863728 [PubMed - as supplied by publisher]

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Soluble Endoglin (CD105) Serum Level as a Potential Marker in the Management of Head and Neck Paragangliomas.

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Soluble Endoglin (CD105) Serum Level as a Potential Marker in the Management of Head and Neck Paragangliomas.

Ann Otol Rhinol Laryngol. 2017 Sep 01;:3489417727548

Authors: Litwiniuk M, Niemczyk K, Niderla-Bielińska J, Łukawska-Popieluch I, Grzela T

Abstract
OBJECTIVES: To assess the expression of endoglin in head and neck paragangliomas and the soluble endoglin level in serum of paraganglioma patients.
METHODS: Seven tumor samples of patients operated for cervical paraganglioma were assessed, as well as serum samples collected preoperatively, on days 4 and 28 postoperation. Serum level of endoglin in healthy controls was also determined. Tumor samples were subjected to immunofluorescent staining and examined with confocal microscope. The level of soluble endoglin in serum samples was examined using the immunoenzymatic assay (ELISA).
RESULTS: Endoglin was highly expressed in all tumor samples. The level of soluble endoglin was significantly higher in paraganglioma patients compared to healthy controls and correlated with the tumor size. The serum level of s-endoglin was reduced after surgical excision of the tumor and remained stable after 4 weeks in all patients with complete resection of the tumor.
CONCLUSION: Endoglin is an important factor in the pathophysiology of head and neck paragangliomas and may be a potential diagnostic and prognostic marker in these types of tumors.

PMID: 28863727 [PubMed - as supplied by publisher]

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Book Review: Head and Neck Ultrasonography: Essential and Extended Applications Orloff Lisa A. Head and Neck Ultrasonography: Essential and Extended Applications , 2nd ed. San Diego, CA : Plural Publishing ; 2017 . Hard cover, illustrated, 544 pages, $299.95 .

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Book Review: Head and Neck Ultrasonography: Essential and Extended Applications Orloff Lisa A. Head and Neck Ultrasonography: Essential and Extended Applications , 2nd ed. San Diego, CA : Plural Publishing ; 2017 . Hard cover, illustrated, 544 pages, $299.95 .

Ann Otol Rhinol Laryngol. 2017 Sep 01;:3489417727525

Authors: Ahmed YC

PMID: 28863716 [PubMed - as supplied by publisher]

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Mutation in the AGK gene in two siblings with unusual Sengers syndrome

Abstract

Sengers syndrome is a rare autosomal recessive metabolic disorder caused by lack of acylglycerol kinase due to mutations in the AGK gene. It is characterized by congenital cataract, hypertrophic cardiomyopathy, myopathy and lactic acidosis. Two clinical forms have been described: a severe neonatal form, and a more benign form displaying exercise intolerance. We describe two siblings with congenital cataract, cardiomyopathy, hypotonia, intellectual disability and lactic acidosis. Whole exome sequencing revealed a homozygous c.1035dup mutation in the two siblings, supporting a diagnosis of Sengers syndrome. Our patients presented an intermediate form with intellectual deficiency, an unusual feature in Sengers syndrome. This permitted a prenatal diagnosis for a following pregnancy.

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Efficacy and safety of tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel pamoate, and albendazole plus oxantel pamoate against hookworm and concomitant soil-transmitted helminth infections in Tanzania and Côte d'Ivoire: a randomised, controlled, single-blinded, non-inferiority trial.

Related Articles

Efficacy and safety of tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel pamoate, and albendazole plus oxantel pamoate against hookworm and concomitant soil-transmitted helminth infections in Tanzania and Côte d'Ivoire: a randomised, controlled, single-blinded, non-inferiority trial.

Lancet Infect Dis. 2017 Aug 29;:

Authors: Moser W, Coulibaly JT, Ali SM, Ame SM, Amour AK, Yapi RB, Albonico M, Puchkov M, Huwyler J, Hattendorf J, Keiser J

Abstract
BACKGROUND: Preventive chemotherapy is the current strategy to control soil-transmitted helminth infections (caused by Ascaris lumbricoides, hookworm, and Trichuris trichiura). But, to improve efficacy and avoid emerging resistance, new drugs are warranted. Tribendimidine has shown good anthelmintic efficacy and is therefore a frontrunner for monotherapy and combination chemotherapy.
METHODS: We did a randomised, controlled, single-blinded, non-inferiority trial on Pemba Island, Tanzania, and in Côte d'Ivoire. We recruited adolescents aged 15-18 years from four primary schools on Pemba, and school attendees and non-schoolers from two districts in Côte d'Ivoire. Only hookworm-positive participants were randomly assigned (1:1:1:1) to single, oral doses of tribendimidine 400 mg plus placebo (tribendimidine monotherapy), tribendimidine 400 mg plus ivermectin 200 μg/kg, tribendimidine 400 mg plus oxantel pamoate 25 mg/kg, or albendazole 400 mg plus oxantel pamoate 25 mg/kg. Randomisation was done via a computer-generated list in block sizes of four or eight. Participants were asked to provide two stool samples on 2 consecutive days at baseline and again 14-21 days at follow-up. The primary outcome was the difference in egg-reduction rates (ERRs; ie, the geometric mean reduction) in hookworm egg counts between treatment groups, measured by the Kato-Katz technique. Differences in coadministrated treatment groups were assessed for non-inferiority with a margin of -3% to albendazole plus oxantel pamoate based on the available-case population, analysed by intention to treat. Safety was assessed 3 h and 24 h after treatment. This study is registered with ISRCTN (number 14373201).
FINDINGS: Between July 26, and Dec 23, 2016, we treated 636 hookworm-positive participants, and outcome data were available for 601 participants (151 assigned to tribendimidine monotherapy, 154 to tribendimidine plus ivermectin, 148 to tribendimidine plus oxantel pamoate, and 148 to albendazole plus oxantel pamoate). Tribendimidine plus ivermectin was non-inferior to albendazole plus oxantel pamoate (ERRs 99·5% [95% CI 99·2-99·7] vs 96·0% [93·9-97·4]; difference 3·52 percentage points [2·05-5·65]). Likewise, tribendimidine plus oxantel pamoate was non-inferior to albendazole plus oxantel pamoate (ERRs 96·5% [95% CI 94·9 to 97·6] vs 96·0% [93·9 to 97·4]; difference 0·48 percentage points [-1·61 to 2·88]). 3 h after treatment, headache (n=50 [8%]) and vertigo (n=37 [6%]) were the most widely reported symptoms; 24 h after treatment, 50 (8%) patients reported vertigo and 41 (7%) reported headache. Mainly mild adverse events were reported with peak numbers (n=111 [18%]) at 24 h after treatment. Three participants had moderate adverse events 3 h after treatment: two (<1%) had vertigo and one (<1%) had headache, and two had moderate adverse events 24 h after treatment: one (<1%) had vomiting and one (<1%) had vomiting plus diarrhoea.
INTERPRETATION: Tribendimidine in combination with either ivermectin or oxantel pamoate had a similar, non-inferior efficacy profile as albendazole plus oxantel pamoate, hence tribendimidine will be a useful addition to the depleted anthelmintic drug armamentarium.
FUNDING: Swiss National Science Foundation.

PMID: 28864027 [PubMed - as supplied by publisher]

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Sinonasal quality of life after endoscopic resection of malignant sinonasal and skull base tumors.

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Sinonasal quality of life after endoscopic resection of malignant sinonasal and skull base tumors.

Laryngoscope. 2017 Sep 02;:

Authors: Glicksman JT, Parasher AK, Brooks SG, Workman AD, Lambert JL, Bergman JE, Palmer JN, Adappa ND

Abstract
OBJECTIVES: Improvement in sinonasal quality of life (QoL) following sinus surgery has been well-documented across the literature. To our knowledge, only one series has evaluated long-term QoL in patients undergoing tumor resection, and that study demonstrated no improvement in rhinologic QoL following malignant tumor resection at 2-year follow-up. The objective of the present study was to evaluate QoL in the 2 years following endoscopic malignant tumor resection.
METHODS: A prospective cohort study was performed, including patients with both malignant and benign sinonasal tumors in a tertiary academic medical center. Patients undergoing endoscopic tumor resection who had completed Sinonasal Outcome Test 22 (SNOT-22) questionnaires were included in the cohort. SNOT-22 questionnaires were administered preoperatively and over a 2-year follow-up period at clinic visits. Longitudinal linear mixed-effects regression was used to compare preoperative QoL to QoL over the 2 years following surgery.
RESULTS: Among 145 patients included in this study, 64 had malignant tumors. There was a statistically significant improvement in SNOT-22 score from baseline to 2 years for patients with both malignant tumors (37.0, 95% confidence Interval [CI] 32.0-42.1 at baseline; 26.5 95% CI 20.8-32.2 at 2 years; P < 0.001) and benign tumors (26.5, 95% CI 21.4-30.4 at baseline; 12.9 95% CI 7.6-18.2 at 2 years; P < 0.001).
CONCLUSION: In contrast to previously reported series, in this cohort endoscopic resection of sinonasal tumors appears to be followed by an improvement in QoL, which is sustained over a 2-year period.
LEVEL OF EVIDENCE: 2b. Laryngoscope, 2017.

PMID: 28865090 [PubMed - as supplied by publisher]

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[Cancer diagnosis disclosure and supportive care seen from the patient side. A cross sectional multicentre survey].

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[Cancer diagnosis disclosure and supportive care seen from the patient side. A cross sectional multicentre survey].

Bull Cancer. 2017 Aug 29;:

Authors: Ricard C, Hamon I, Duparc A, Steffen CA

Abstract
The objective of this study was to describe patients' experience during cancer disclosure and initial carers' support phase, in three healthcare facilities in Haute-Savoie District, France.
METHODOLOGY: We conducted a multicentric, cross-sectional telephone survey. Patients registered on the multidisciplinary cancer consultation platform lists were randomised. Practitioners validated the inclusion criteria of their patients, i.e. age over 18, patient fully informed of his/her diagnosis and able to answer a telephone interview.
RESULTS: Two hundred thirty-six patients have been included. Outcome indicators reported as satisfactory were: the general setting of the disclosure consultation, the patient-doctor relationship, the coordination between the different carers and the patient carer relationship. The overall duration of the medical disclosure consultation and the time dedicated to explain the treatment and its adverse effects have been considered as insufficient.
DISCUSSION: The measured indicators, which were by essence subjective, convey useful information on the quality of care in cancer treatment in the initial disclosure phase, as experienced by patients. This study has in particular allowed carers to start exploring ways to improve the experience of care of their patients.

PMID: 28864304 [PubMed - as supplied by publisher]

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Effect of propofol combined with opioids on cough reflex suppression in gastroscopy: study protocol for a double-blind randomized controlled trial.

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Effect of propofol combined with opioids on cough reflex suppression in gastroscopy: study protocol for a double-blind randomized controlled trial.

BMJ Open. 2017 Sep 01;7(9):e014881

Authors: Yin N, Xia J, Cao YZ, Lu X, Yuan J, Xie J

Abstract
INTRODUCTION: The best methods for inducing analgesia and sedation for gastroscopy are still debated but finding an adequate regimen of sedation/analgesia is important. Stimulation of the larynx under sedation can cause reflex responses. Propofol with opioids has been recommended for gastroscopy sedation but the effects on cough reflex suppression remain unclear. This trial will evaluate the effects of propofol combined with small doses of dezocine, oxycodone, sufentanil or fentanyl for gastroscopy. We hypothesise that better performance may be obtained with a combination of propofol and oxycodone. We will observe the incidence and degree of reflex coughing and gagging under sedation when using propofol combined with one of the above drugs or propofol alone.
METHODS AND ANALYSIS: This will be a prospective, randomised, double-blind, controlled trial. ASA I-II level patients aged 18-65 years and scheduled for gastroscopy will be included. It is planned that 500 subjects will be randomised to intravenously receive 2-2.2 mg/kg propofol plus 0.5-0.8 μg/kg fentanyl (fentanyl group), 2-2.2 mg/kg propofol plus 0.05-0.08 μg/kg sufentanil (sufentanil group), 2-2.2 mg/kg propofol plus 0.04-0.05 mg/kg dezocine (dezocine group), 2-2.2 mg/kg propofol plus 0.04-0.05 mg/kg oxycodone (oxycodone group), or 2.4-3 mg/kg propofol plus 2-2.5 mL saline (control group) for sedation. The primary endpoint is the incidence and degree of reflex coughing and gagging. The secondary endpoints include the occurrence of discomfort or side effects, the use of jaw thrust, assisted ventilation or additional propofol, recovery time, duration of procedure and Steward score.
ETHICS AND DISSEMINATION: This study has been approved by the Institutional Ethics Committee for Clinical Research of Zhongda Hospital, Affiliated to Southeast University (No. 2015ZDSYLL033.0). The results of the trial will be published in an international peer-reviewed journal.
TRIAL REGISTRATION: This study has been registered with the Chinese Clinical Trial Register (No. ChiCTR-ICR-15006952).
TRIAL STATUS: At the time of manuscript submission, the study was in the recruitment phase.

PMID: 28864688 [PubMed - in process]

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Gender difference and laterality of sleep position.

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Gender difference and laterality of sleep position.

Auris Nasus Larynx. 2017 Aug 29;:

Authors: Ichijo H, Akita M

Abstract
OBJECTIVE: A higher incidence in women (approximately 7:3) and a predominant involvement of the right ear (approximately 7:5) are interesting features of BPPV (benign paroxysmal positional vertigo). It is speculated that these features are related to sleep position. The first aim of this study was to compare the frequency of position shifts during sleep between men and women. The second aim was to elucidate any differences in sleep position between men and women. The third aim was to clarify the laterality of sleep position.
METHODS: We retrospectively selected the data of 30 males (mean, 53.1 years) and 22 females (mean, 50.6 years) diagnosed as mild or moderate obstructive sleep apnea. A position sensor was attached to the patient's anterior chest. Supine position was defined as less than 45° tilt, and lateral position was defined as more than 45° tilt. A single overnight laboratory polysomnography provided the number of position shifts, total sleep time, sleep time spent in the supine position (S), sleep time spent in the right-side-down lateral position (R), and sleep time spent in the left-side-down lateral position (L).
RESULTS: The mean value and standard deviation of the number of position shifts per hour was 2.4±1.3 in males, and 2.3±1.1 in females. There was no significant difference between males and females. Twelve cases (40%) were lateral type (S<R+L), and 18 (60%) were supine type (S>R+L) in males. Ten cases (45%) were lateral type, and 12 (55%) were supine type in females. There was no significant difference between males and females. Seventeen cases (56.6%) were right-dominant type (R-L>0), and 13 (43.3%) were left-dominant type (R-L<0) in males. Thirteen cases (59%) were right-dominant type, and 9 (41%) were left-dominant type in females.
CONCLUSION: Body position and the number of position shifts during sleep differ substantially between individuals. There is no gender difference in the frequency of position shifts. Although the supine type is more common than the lateral type, there is no gender difference in sleep position. Therefore, the reason of higher incidence in women is not related to sleep. The right-dominant type occurs more than the left-dominant type in both genders. It is possible that this behavior is the reason for the predominant involvement of the right ear in BPPV.

PMID: 28863980 [PubMed - as supplied by publisher]

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A change in the study evaluation paradigm reveals that larynx preservation compromises survival in T4 laryngeal cancer patients.

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A change in the study evaluation paradigm reveals that larynx preservation compromises survival in T4 laryngeal cancer patients.

BMC Cancer. 2017 Sep 01;17(1):609

Authors: Dyckhoff G, Plinkert PK, Ramroth H

Abstract
BACKGROUND: Larynx preservation (LP) is recommended for up to low-volume T4 laryngeal cancer as an evidence-based treatment option that does not compromise survival. However, a reevaluation of the current literature raises questions regarding whether there is indeed reliable evidence to support larynx preservation for T4 tumor patients.
METHODS: In an observational cohort study of 810 laryngeal cancer patients, we evaluated the outcomes of all T4 tumor patients treated with primary chemo-radiotherapy (CRT) or primary radiotherapy alone (RT) compared with upfront total laryngectomy followed by adjuvant (chemo)radiotherapy (TL + a[C]RT). Additionally, we reevaluated the studies that form the evidence base for the recommendation of LP for patients with up to T4 tumors (Pfister et al., J Clin Oncol 24:3693-704, 2006).
RESULTS: The evaluation of all 288 stage III and IV patients together did not show a significant difference in overall survival (OS) between CRT-LP and TL + a(C)RT (hazard ratio (HR) 1.23; 95% confidence interval (CI): 0.82-1.86; p = 0.31) using a multivariate proportional hazard model. However, a subgroup analysis of T4 tumor patients alone (N = 107; 13.9%) revealed significantly worse OS after CRT compared with TL + a(C)RT (HR 2.0; 95% CI: 1.04-3.7; p = 0.0369). A reevaluation of the subgroup of T4 patients in the 5 LP studies that led to the ASCO clinical practice guidelines revealed that only 21-45 T4 patients had differential data on survival outcome. These data, however, showed a markedly worse outcome for T4 patients after LP.
CONCLUSIONS: T4 laryngeal cancer patients who reject TL as a treatment option should be informed that their chance of organ preservation with primary conservative treatment is likely to result in a significantly worse outcome in terms of OS. Significant loss of survival in T4 patients after LP is also confirmed in recent literature.

PMID: 28863776 [PubMed - in process]

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An operant-based detection method for inferring tinnitus in mice.

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An operant-based detection method for inferring tinnitus in mice.

J Neurosci Methods. 2017 Aug 29;:

Authors: Zuo H, Lei D, Sivaramakrishnan S, Howie B, Mulvany J, Bao J

Abstract
BACKGROUND: Subjective tinnitus is a hearing disorder in which a person perceives sound when no external sound is present. It can be acute or chronic. Because our current understanding of its pathology is incomplete, no effective cures have yet been established. Mouse models are useful for studying the pathophysiology of tinnitus as well as for developing therapeutic treatments.
NEW METHOD: We have developed a new method for determining acute and chronic tinnitus in mice, called sound-based avoidance detection (SBAD). The SBAD method utilizes one paradigm to detect tinnitus and another paradigm to monitor possible confounding factors, such as motor impairment, loss of motivation, and deficits in learning and memory.
RESULTS: The SBAD method has succeeded in monitoring both acute and chronic tinnitus in mice. Its detection ability is further validated by functional studies demonstrating an abnormal increase in neuronal activity in the inferior colliculus of mice that had previously been identified as having tinnitus by the SBAD method. COMPARISON: with Existing Methods The SBAD method provides a new means by which investigators can detect tinnitus in a single mouse accurately and with more control over potential confounding factors than existing methods.
CONCLUSION: This work establishes a new behavioral method for detecting tinnitus in mice. The detection outcome is consistent with functional validation. One key advantage of mouse models is they provide researchers the opportunity to utilize an extensive array of genetic tools. This new method could lead to a deeper understanding of the molecular pathways underlying tinnitus pathology.

PMID: 28864083 [PubMed - as supplied by publisher]

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Epiphycan is specifically expressed in cochlear supporting cells and is necessary for normal hearing.

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Epiphycan is specifically expressed in cochlear supporting cells and is necessary for normal hearing.

Biochem Biophys Res Commun. 2017 Aug 29;:

Authors: Hanada Y, Nakamura Y, Ishida Y, Takimoto Y, Taniguchi M, Ozono Y, Koyama Y, Morihana T, Imai T, Ota Y, Sato T, Inohara H, Shimada S

Abstract
The study of inner ear specific transcripts has revealed novel information about hereditary hearing loss and a mechanism of normal hearing. In this study, by analyzing a published cDNA library, we focused on Epiphycan (Epyc), a member of the small leucine-rich repeat proteoglycan family, whose transcript is enriched in the inner ear. Epyc mRNA was expressed abundantly and specifically in adult mice cochleae and was localized in supporting cells within the organ of Corti of both neonatal and adult mice. To examine the function of Epyc, we generated Epyc knockout (KO) mice using the CRISPR/Cas9 system. Epyc KO mice cochleae exhibited normal morphology. However, measurement of the auditory brain-stem response in Epyc KO mice revealed an elevated hearing threshold above 16 kHz frequency. This study suggests that Epyc is necessary for normal auditory function.

PMID: 28864419 [PubMed - as supplied by publisher]

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Corrigendum to “Advanced breast cancer rates in the epoch of service screening: The 400,000 women cohort study from Italy” [Eur J Cancer 75 (April 2017) 109–116]

Publication date: Available online 2 September 2017
Source:European Journal of Cancer
Author(s): Donella Puliti, Lauro Bucchi, Silvia Mancini, Eugenio Paci, Susanna Baracco, Cinzia Campari, Debora Canuti, Claudia Cirilli, Natalina Collina, Giovanni Maria Conti, Enza Di Felice, Fabio Falcini, Maria Michiara, Rossella Negri, Alessandra Ravaioli, Priscilla Sassoli de' Bianchi, Monica Serafini, Manuel Zorzi, Adele Caldarella, Luigi Cataliotti, Marco Zappa




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Letter to the editor regarding the paper by Loquai C et al. ‘Use of complementary and alternative medicine: a multicenter cross-sectional study in 1089 melanoma patients’

Publication date: Available online 3 September 2017
Source:European Journal of Cancer
Author(s): Elizabeth Fabre, Audrey Thomas-Schoemann, Benoit Blanchet




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A Rare Presentation of Synovial Sarcoma as Cervical Lymphadenopathy in a Pediatric Patient—a Case Report

Abstract

Synovial sarcoma is the uncommon malignant tumor of children and adolescents. It usually involves the soft tissues of the upper and lower joints and most commonly affects adults in their fourth decade of life. We report a rare case of synovial sarcoma of the head and neck region in a five-year-old child who has presented with right side cervical lymphadenopathy associated with dysphagia and hoarseness of voice. Patient was managed by modified radical neck dissection followed by chemotherapy.

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Hand eczema as a risk factor for food allergy among occupational kitchen workers

Publication date: Available online 2 September 2017
Source:Allergology International
Author(s): Takafumi Minami, Yuma Fukutomi, Kiyoshi Sekiya, Akira Akasawa, Masami Taniguchi
BackgroundAn increasing number of studies in children is highlighting the importance of transdermal routes of exposure to food allergens through damaged skin in the pathogenesis of food allergies. However, data on this in adults are limited. A few case-series studies has documented development of food allergy among kitchen workers with hand eczema after direct contact exposure to foods.MethodsTo explore the significance of hand eczema as a risk factor for food allergies in adults at the epidemiological level, we performed a cross-sectional web-based questionnaire survey on kitchen workers whose exposures were classed as occupational (cooks and food handlers, n = 1592) or non-occupational (housewives, n = 1915). Logistic regression was used to explore the association between the presence/severity of hand eczema and the risk of food allergy after adjustment for potential confounders.ResultsCurrent hand eczema and current diagnosed food allergy were more common among occupational kitchen workers (OKW) than among non-occupational kitchen workers (NOKW) (32.3%-vs-29.9% and 9.9%-vs-3.8%, respectively). Current hand eczema was significantly associated with increased risk of current diagnosed food allergy in OKW (adjusted odds ratio 2.4, 95% CI 1.6–3.7). Those with more severe hand eczema were more likely to suffer from allergic symptoms for foods, and diagnosed food allergy.ConclusionsThis study illustrates a significant public health problem in the adult population, documenting a major impact of hand eczema on the ongoing adult food allergy epidemic.



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Upregulation of Treg-Related Genes in Addition with IL6 Showed the Significant Role for the Distant Metastasis in Colorectal Cancer

Abstract

T helper 17 (Th17) and T regulatory (Treg) cytokines appear to be contributing greatly to colorectal cancer (CRC) development and progression. The aim of the current study was to investigate the expression of Foxp3; IL10; TGFB1; IL17A; IL6 and NOS2 genes in tumor tissue, regional positive lymph nodes and distant metastasis obtained from 26 patients with advanced CRC. Quantitative real-time polymerase chain reaction (qPCR) was performed for mRNA detection by TaqMan gene expression assay. In distant metastasis, IL6 was strongly expressed, over 7.5 fold, followed by Treg-related genes Foxp3; IL10 and TGFB1 in contrast to IL17A and NOS2. The similar pattern of expression was observed in positive regional lymph node in addition to significant down-regulation of NOS2 (RQ = 0.287; p = 0.011) and a trend for the elevation of IL17A. In tumor tissue, Fopx3 was significantly upregulated and Foxp3 mRNA positively correlated with TGFB1 in all investigated tissue types. In tumor tissue, expression of IL17A was correlated with NOS2 (r = 0.68; p = 0.005), while in distant metastasis IL10 was in strong relation with TGFB1 and IL6. In addition, a reverse correlation between IL6 and NOS2 (r = −0.66; p = 0.009), was observed in distant metastasis. The simultaneous expression of given Treg and Th17-related genes found both in the primary tumor and in the regional lymph nodes appears to provide suitable microenvironment sufficient for promoting metastatic growth. The upregulation of Foxp3; IL10, TGFB1 and IL6 might be a transcriptional profile hallmark for colorectal metastases.

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In human brain ornithine transcarbamylase (OTC) immunoreactivity is strongly expressed in a small number of nitrergic neurons

Abstract

There is recent evidence for ornithine transcarbamylase (OTC) expression in adult human brain. We decided to immunocytochemically map OTC throughout brain, and to further characterize OTC-immunopositive neurons. By using double immunolabeling technique for OTC and neuronal nitric oxide synthase (nNOS) OTC protein expression was revealed in a small subset of nitrergic (nNOS) neurons. Since citrulline (the reaction product of OTC) enhances the bioavailability of L-arginine, the substrate of nNOS, it is conceivable that OTC activity supports NO production in nitrergic neurons.

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