Sporadic minute medullary thyroid carcinoma with a double RET mutation: A case report

We describe a 74-year-old man with a nodular goiter accompanied by an incidental sporadic minute medullary thyroid carcinoma (MTC). Histopathologically, the MTC was a well-defined 1.7 mm tumor in the upper one-third right lobe, with solid cell nests (SCNs) adjacent to the MTC. C-cells were scattered mainly around the SCNs, but C-cell hyperplasia was not evident in the background thyroid. The MTC cell phenotype was immunohistochemically identical to background C-cells, but was completely different from the SCN main cells. Direct DNA analyses of isolated MTC paraffin-embedded specimens revealed two RET proto-oncogene missense point mutations in exon 11 (i.e., C630R and C634W). The non-tumor thyroid tissue did not reveal any mutations. This study reports the smallest case of sporadic MTC with a double RET somatic mutation, substantiating that RET mutations can occur during a very early stage of carcinogenesis. The combined presence of C630R and C634W represent a novel somatic mutation in sporadic MTC. The present case indicates that the sporadic MTC originated from the surrounding C-cells of the SCNs without C-cell hyperplasia and that the SCN main cells may not be able to develop into an MTC.

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Visualization of Skin Perfusion by Indocyanine Green Fluorescence Angiography-A Feasibility Study.

Summary: Plastic and reconstructive surgery relies on the knowledge of angiosomes in the raising of microsurgical flaps. Growing interest in muscle-sparing perforator flaps calls for reliable methods to assess the clinical feasibility of new donor sites in anatomical studies. Several injection techniques are known for the evaluation of vascular territories. Indocyanine green-based fluorescence angiography has found wide application in the clinical assessment of tissue perfusion. In this article, the use of indocyanine green-based fluorescence angiography for the assessment of perforasomes in anatomical studies is described for the first time. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Spontaneous Regression of Lymphangiomas in a Single Center Over 34 Years.

Background: A lymphangioma, also called a lymphatic malformation, is a congenital condition that frequently occurs in young children. It is classified into 3 groups depending on the size of the cysts (macrocystic, microcystic, and mixed). Spontaneous regression occurs in some cases; however, the characteristics of patients who show regression have not been studied previously. Furthermore, the types and the timing of the initial treatment are still controversial. Therefore, we statistically analyzed the occurrence of short-term spontaneous regression, patient age at original occurrence, cyst types, cyst sizes, and cyst locations in patients diagnosed with peripheral localized lymphangiomas in a single children center over 34 years. Methods: We retrospectively collected the data of 153 patients and reviewed the medical charts. Results: Spontaneous regression occurred only in macrocystic or mixed type; regression was most frequent in patients who, at the time of onset, were more than 2 years old. Conclusions: We concluded that elderly patients with macrocystic or mixed type lymphangioma may have to wait for treatment for over 3 months from the initial onset. Conversely, microcystic type could not be expected to show regression in a short period, and prompt initiation of the treatments may be required. The difference of the regression or not may depend on the characteristics of the lymph flow. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Autoimmune Syndrome Induced by Adjuvants (ASIA) after Silicone Breast Augmentation Surgery.

Summary: Generally, the main complications of silicone implantation are local symptoms. However, some patients develop late-onset systemic symptoms often associated with a rare form of hyperactive immune response, as part of a syndrome known as autoimmune syndrome induced by adjuvants (ASIA). Reported cases of ASIA have shown resolution with explantation, but not with immunomodulatory therapy. In this report, we described a case of a previously healthy 23-year-old woman, who has undergone silicone breast implant augmentation, for aesthetic reasons, and developed localized cutaneous impairment 3 years postsurgery. She received a diagnosis of ASIA with a new presentation: Lupus-like manifestation through localized cutaneous impairment. This patient's symptoms were managed without the need for surgical intervention, which has not been previously reported, because the patient did not want an explantation for aesthetic reasons. The patient was started on hydroxychloroquine, 400 mg per day, and remains asymptomatic after 2 years of treatment. The exact predisposition to ASIA is still unknown. Without implant explantation and with immunomodulatory treatment, this patient's condition substantially improved. Based on our current understanding of this disease, it might not be prudent to indicate breast augmentation with silicone implants in patients with documented autoimmune reaction to an adjuvant, an established autoimmune condition, or genetic predisposition. However, if a patient does develop silicone-induced ASIA, explantation is no longer the only successfully reported option, as these symptoms can be managed with immune suppression. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Comparative Effectiveness of Needle Aponeurotomy and Collagenase Injection for Dupuytren's Contracture: A Multicenter Study.

Background: Although the efficacy of collagenase clostridium histolyticum (CCH) injections has been demonstrated by randomized clinical trials, the relative effectiveness of CCH remains uncertain. Our aim was to compare the outcomes of CCH with those of percutaneous needle aponeurotomy (PNA) in daily clinical practice. Methods: We analyzed data from patients undergoing PNA or CCH between 2011 and 2014 at 7 practice sites in the Netherlands. We examined the degree of improvement in contracture and adverse effects at 6-12 weeks after surgery or the last injection. Additionally, we invited patients to complete the Michigan Hand Questionnaire before and at 6-12 months follow-up. To minimize the risk of bias, we used propensity score matching. Results: Among 130 matched patients (93% Tubiana I or II) undergoing PNA (n = 46) and CCH (n = 84), improvement in contracture was similar: 26 degrees (65% improvement from baseline) for PNA versus 31 degrees (71%) for CCH for affected metacarpophalangeal joints (P = 0.163). This was 16 degrees (50% improvement) versus 17 degrees (42%) for affected proximal interphalangeal joints (P = 0.395), respectively. No serious adverse effects occurred in either of the 2 treatment groups. Of the mild adverse effects, only skin fissures and sensory disturbances were seen in both groups. Through 1-year follow-up, patients reported similar improvements in the overall Michigan Hand Questionnaire score (PNA 5.3 points versus CCH 4.9 points; P = 0.912). Conclusions: In patients with mild contractures (Tubiana I or II), CCH was as effective as PNA in reducing contractures. Both treatments were safe and improved hand function to a similar extent in daily practice. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Hyperbaric Oxygen Inhibits Reperfusion-Induced Neutrophil Polarization and Adhesion Via Plasmin-Mediated VEGF Release.

Background: Ischemia-reperfusion (IR) injury is seen in many settings such as free flap salvage and limb replantation/revascularization. The consequences-partial/total flap loss, functional muscle loss, or amputation-can be devastating. Of the treatment options available for IR injury, hyperbaric oxygen (HBO) is the most beneficial. HBO inhibits neutrophil-endothelial adhesion through interference of CD18 neutrophil polarization in IR, a process mediated by nitric oxide. The purposes of this study were to examine the involvement of vascular endothelial growth factor (VEGF) in the beneficial HBO effect on CD18 polarization and neutrophil adhesion and investigate the effect of plasmin on VEGF expression in skeletal muscle following IR injury. Methods: A rat gracilis muscle model of IR injury was used to evaluate the effect of VEGF in IR, with and without HBO, on neutrophil CD18 polarization and adhesion in vivo and ex vivo. Furthermore, we investigated the effects that plasmin has on VEGF expression in gracilis muscle and pulmonary tissue by blocking its activation with alpha-2-antiplasmin. Results: HBO treatment following IR injury significantly decreased neutrophil polarization and adhesion ex vivo compared with the IR group. Anti-VEGF reversed the beneficial HBO effect after IR with polarization and adhesion. In vivo adhesion was also increased by anti-VEGF. HBO treatment of IR significantly increased the VEGF protein in both gracilis and pulmonary vasculature. Alpha-2-antiplasmin significantly reversed the HBO-induced increase of VEGF in gracilis muscle. Conclusions: These results suggest that HBO inhibits CD18 polarization and neutrophil adhesion in IR injury through a VEGF-mediated pathway involving the extracellular matrix plasminogen system. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Novel Double-Needle System That Can Prevent Intravascular Injection of Any Filler.

Summary: A new type of needle system combines 2 parts, an inner needle and an outer needle. The inner needle is used for filler injection and the outer needle acts as a guiding needle that can observe blood reflow when inserting into the vessel lumen during injection process. This new needle system can be used for all kinds of filler, providing real time monitoring for physician and preventing intravascular injection of any filler. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Diversity and Inclusion in Plastic Surgery Education: A National Survey by the American Council of Academic Plastic Surgeons.

Introduction: To date, there have been few studies in the field of plastic surgery examining the knowledge, attitudes, and behavior of educators and residents regarding diversity and inclusion, especially for the purposes of enhancing resident education, improving diversity efforts, and addressing health care disparities. Methods: An anonymous survey was provided electronically to a total of 462 American Council of Academic Plastic Surgeon members and 91 program coordinators (PCs), and 1,029 plastic surgery residents at 91 institutions across the United States. We analyzed the responses from PCs and program directors (PDs). Results: We collected responses from 34 institutions (37%), and 16.8% of American Council of Academic Plastic Surgeon members including 34 PCs and 44 PDs. We found that PDs were more likely to be male (86%) and above the age of 40 years (97%) compared with PCs (5% male and 61% above 40 years). Both groups were majority White. Fifty-nine percentage of PDs have a parent/guardian who attained a graduate degree versus 15% of PCs. Forty-eight percentage of PDs speak another language compared with 16% of PCs. More importantly, 95% of PDs had an opportunity to engage in diversity and inclusion-related activities in the last 6 months as compared with 43% of PCs; however, we did not find a statistical difference based on knowledge of increasing institutional capacity of diversity and inclusion between the 2 groups. PCs were more likely to witness discrimination (64%) than PDs (40%) in the health care setting, with body type/weight emerging as the most common type of discrimination. Very few respondents (10%) indicated they discriminated against others. Conclusions: Plastic surgery educators are committed to diversity and inclusion. Improvements can be made by incorporating PCs more frequently in activities related to the topic along with focused training on improving diversity on an institutional rather than individual level. Our study suggests body type/weight is the most common type of discrimination witnessed by the entire cohort and that diversity and inclusion remains a sensitive topic. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Resident Surgical Assessment.

No abstract available

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Perceptions of Educational Value: A Survey of American Council of Academic Plastic Surgeons.

No abstract available

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Write it in the Script: A Practical Solution to Promote Gender Balance in Educational Programming.

No abstract available

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Plastic Surgery Resident Operative Performance Trends: How Soon Do Independent Residents Catch Up?.

No abstract available

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Scar Tissue Causing Saphenous Nerve Entrapment: Percutaneous Scar Release and Fat Grafting.

Summary: Painful neuropathies can be caused by nerve compression or neuromas. Nerve compressions can arise from scar adhesions causing painful posttraumatic entrapment of nerve branches via fibrosis. The classical treatment methods include neurolysis and nerve transposition. In this case, we present the treatment of recurrent scar entrapment of the saphenous nerve with percutaneous neurolysis and lipofilling in a patient who had previously undergone an open neurolysis procedure. Resolution of the condition without any complications was noted during the 2-month clinical follow-up. Percutaneous neurolysis and lipofilling are shown to be safe and reproducible methods for the treatment of neuropathic compressive scars. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Reliability of Operative Skill Evaluations: How Late Is Too Late to Give Feedback?.

No abstract available

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The Rural Plastic Surgery Residency Rotation: Rising to Meet a National Crisis.

No abstract available

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PSEN as an Educational Tool in Norway.

No abstract available

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A Novel Thermal Compression Device for Perioperative Warming

The authors tested a prototype device providing heat to the popliteal fossa and soles of the feet for prevention of inadvertent perioperative hypothermia. Is it more effective than standard methods?
BMC Anesthesiology

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Polysomnographic findings in craniopharyngioma patients

Abstract

Purpose

The purpose of this study is to evaluate whether damage to the hypothalamus due to craniopharyngioma or consequent surgery may involve the sleep-wake regulatory system, resulting in sleep disturbances and sleepiness.

Methods

Seven craniopharyngioma patients and 10 healthy controls were evaluated with sleep questionnaires including the Epworth Sleepiness Scale, polysomnography, and a multiple sleep latency test (MSLT). Five patients and eight controls had lumbar puncture performed to determine hypocretin-1 levels.

Results

Patients tended to feel sleepier than control individuals of the same age (p = 0.09). No subjects had symptoms of hypnagogic hallucinations, sleep paralyses, or cataplexies. Four patients and one control had periodic leg movements (PLMs). One patient had fragmented sleep pattern, rapid eye movement (REM) sleep without atonia, and PLMs. One patient had short sleep periods during the daytime. Four patients had fragmented sleep pattern. With the MSLT, four patients and two controls had mean sleep latency of < 8 min. One patient and three controls had sudden onset of REM sleep in 2/5 and 3/5 sleep periods, respectively. All subjects showed normal hypocretin-1 levels. Four patients had electrophysiological findings indicative of central hypersomnia including one patient meeting the criteria of narcolepsy.

Conclusion

The sleep-wake regulatory system may be involved in craniopharyngioma patients.

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Risk prediction tools for keratinocyte carcinoma after solid organ transplantation: a review of the literature

Summary

Long-term iatrogenic immunosuppression increases the risk of cutaneous malignancies in organ transplant recipients (OTRs), particularly the keratinocyte cancers basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC). cSCC is the most common malignancy in OTRs, with the risk increased to over 65-fold in transplanted patients relative to the general population. There have been very few risk prediction tools developed for accurate determination of the risk of developing keratinocyte cancers in the OTR population. This review summarizes the prediction tools developed to date, and outlines future directions for developing more accurate prediction models that are clinically useful for the transplant physician and dermatologist.

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Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part II: A Scoping Review of Continuous Methods

Journal of Neurotrauma , Vol. 0, No. 0.


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A Method of Managing Severe Traumatic Brain Injury in the Absence of Intracranial Pressure Monitoring: The Imaging and Clinical Examination Protocol

Journal of Neurotrauma , Vol. 0, No. 0.


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Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part I: A Scoping Review of Intermittent/Semi-Intermittent Methods

Journal of Neurotrauma , Vol. 0, No. 0.


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Effects of combination therapy indacaterol/glycopyrronium versus tiotropium on moderate to severe COPD: evaluation of impulse oscillometry and exacerbation rate

Small airways are considered the major site of airflow limitation in COPD. Impulse oscillometry (IOS) is a forced oscillation technique, which provides passive measurement of lung mechanics. It can differentia...

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Sphenoid Sinus Diseases: A Review of 1,442 Patients

Objective. To review and report diseases of the sphenoid sinus from the literature and from a university hospital. Methods. Inpatients' data were retrospectively gathered and reviewed from January 2006 to June 2016. Clinical data, imaging, organisms, and pathological reports were collected. Pathology was divided into infection/inflammation, tumor, and miscellaneous. A literature review was performed with the search term "isolated sphenoid disease" in PubMed. Original primary studies with 20 patients or more were reviewed. Results and Discussion. One hundred and twenty-two patients were enrolled. Seventy-two subjects were female (59%). The average age was 54.3 years (±18.0). Imaging abnormalities were found incidentally in 27 patients (22.1%). The most common symptom was headache (63.9%). Visual loss, the second most common symptom, was more frequent in the tumor group (30.6% versus 54.2%). From the literature review, 21 primary studies with 1,320 total patients were included. From all studies and the present study, infection/inflammation was the most common pathology (75%) [95% confidence interval (CI): 0.696, 0.804]. Overall, tumors were found in 18.9% and malignant tumors in 7.0% [95% CI: 0.045, 0.095]. Conclusion. A specific diagnosis of a sphenoid lesion is needed during active investigation. Infection/inflammation was the most common pathology and malignancy was found in 7%.

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Livin’ On The Edge: glia shape nervous system transition zones

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Laura Fontenas, Sarah Kucenas
The vertebrate nervous system is divided into two functional halves; the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system (PNS), which consists of nerves and ganglia. Incoming peripheral stimuli transmitted from the periphery to the CNS and subsequent motor responses created because of this information, require efficient communication between the two halves that make up this organ system. Neurons and glial cells of each half of the nervous system, which are the main actors in this communication, segregate across nervous system transition zones and never mix, allowing for efficient neurotransmission. Studies aimed at understanding the cellular and molecular mechanisms governing the development and maintenance of these transition zones have predominantly focused on mammalian models. However, zebrafish has emerged as a powerful model organism to study these structures and has allowed researchers to identify novel glial cells and mechanisms essential for nervous system assembly. This review will highlight recent advances into the important role that glial cells play in building and maintaining the nervous system and its boundaries.



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Degalactotigonin, a natural compound from Solanum nigrum L., inhibits growth and metastasis of osteosarcoma through GSK3{beta} inactivation-mediated repression of the Hedgehog/Gli1 pathway

Purpose: Agents extracted from natural sources with anti-tumor property have attracted considerable attention from researchers and clinicians because of their safety, efficacy, and immediate availability. Degalactotigonin (DGT), extracted from Solanum nigrum L., has anticancer properties without serious side effects. Here, we explored whether DGT can inhibit the growth and metastasis of osteosarcoma. Experimental Design: MTT, colony formation, and apoptosis assays were performed to analyze the effects of DGT on osteosarcoma cell viability in vitro. The migration and invasion abilities were measured using a Transwell assay. Animal models were used to assess the roles of DGT in both tumor growth and metastasis of osteosarcoma. Gli1 expression and function were measured in osteosarcoma cells and clinical samples. After DGT treatment, Gli1 activation and the phosphorylation status of multiple cellular kinases were measured with a luciferase reporter and phospho-kinase antibody array. Results: DGT inhibited proliferation, induced apoptosis, and suppressed migration and invasion in osteosarcoma cells. DGT significantly decreased the volume of osteosarcoma xenografts and dramatically diminished the occurrence of osteosarcoma xenograft metastasis to the lungs. Mechanistically, DGT inhibited osteosarcoma growth and metastasis through repression of the Hedgehog/Gli1 pathway, which maintains malignant phenotypes and is involved in the prognosis of osteosarcoma patients. DGT decreased the activity of multiple intracellular kinases that affect the survival of OS patients, including GSK3β. In addition, DGT represses the Hedgehog/Gli1 pathway mainly through GSK3β inactivation. Conclusions: DGT can suppress the growth and metastasis of human osteosarcoma through modulation of GSK3β inactivation-mediated repression of the Hedgehog/Gli1 pathway.

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Immune Activation in Early Stage Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab

Purpose: To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early stage non-small cell lung cancer (NSCLC) patients. Experimental Design: This is a single-arm chemotherapy plus phased ipilimumab Phase II study of 24 treatment-naïve patients with Stage IB-IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles. Results: Chemotherapy alone had little effect on immune parameters in PBMCs. Profound CD28 dependent activation of both CD4 and CD8 cells was observed following ipilimumab. Significant increases in the frequencies of CD4+ cells expressing activation markers ICOS, HLA-DR, CTLA-4, and PD-1 were apparent. Likewise, increased frequencies of CD8+ cells expressing the same activation markers, with the exception of PD-1, were observed. We also examined 7 resected tumors and found higher frequencies of activated TILs than those observed in PBMCs. Surprisingly, we found 4 cases of pre-existing tumor-associated antigens (TAA) responses against survivin, PRAME, or MAGE-A3 present in PBMC at baseline, but neither increased frequencies nor the appearance of newly detectable responses following ipilimumab therapy. Ipilimumab had little effect on the frequencies of circulating Tregs and MDSCs. Conclusions: This study did not meet the primary endpoint of detecting an increase in blood based tumor associated antigen T cell responses after ipilimumab. Collectively, these results highlight the immune activating properties of ipilimumab in early stage NSCLC. The immune profiling data for ipilimumab alone can contribute to the interpretation of immunological data from combined immune checkpoint blockade immunotherapies.

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Head and neck squamous cell carcinomas are characterized by a stable immune signature within the primary tumor over time

Purpose: Genetic and morphological heterogeneity is well-documented in solid cancers. Immune cells are also variably distributed within the tumor; this heterogeneity is difficult to assess in small biopsies, and may confound our understanding of the determinants of successful immunotherapy. We examined the transcriptomic variability of the immunological signature in head and neck squamous cell carcinoma (HNSCC) within individual tumors using transcriptomic and immunohistochemical assessments. Experimental design: Forty-four tumor biopsies from 16 HNSCC patients, taken at diagnosis and later at resection, were analyzed using RNA-sequencing. Variance filtering was used to identify the top 4000 most variable genes. Principal component analysis, hierarchical clustering and correlation analysis were performed. Gene expression of CD8A was correlated to immunohistochemical analysis. Results: Analysis of immunological gene expression was highly consistent in replicates from the same cancer. Across the cohort, samples from the same patient were most similar to each other, both spatially (at diagnosis) and notably, over time (diagnostic biopsy compared to resection); comparison of global gene expression by hierarchical clustering [p=<0.0001] and correlation analysis [median intrapatient r=0.82; median interpatient r=0.63]. CD8A gene transcript counts were highly correlated with CD8 T-cell counts by immunohistochemistry (r=0.82). Conclusion: Our data demonstrate that in HNSCC the global tumor and adaptive immune signatures are stable between discrete parts of the same tumor and also at different timepoints. This suggests that immunological heterogeneity may not be a key reason for failure of immunotherapy and underpins the use of transcriptomics for immunological evaluation of novel agents in HNSCC patients.

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Characterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes

Characterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes

British Journal of Cancer 117, 1048 (26 September 2017). doi:10.1038/bjc.2017.286

Authors: Javier Gayarre, Paloma Martín-Gimeno, Ana Osorio, Beatriz Paumard, Alicia Barroso, Victoria Fernández, Miguel de la Hoya, Alejandro Rojo, Trinidad Caldés, José Palacios, Miguel Urioste, Javier Benítez & María J García

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Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy

Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy

British Journal of Cancer 117, 921 (26 September 2017). doi:10.1038/bjc.2017.253

Authors: Rebecca Y Tay, Elizabeth Blackley, Catriona McLean, Maggie Moore, Peter Bergin, Sanjeev Gill & Andrew Haydon

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The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma

The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma

British Journal of Cancer 117, 1007 (26 September 2017). doi:10.1038/bjc.2017.249

Authors: Pirjo Åström, Krista Juurikka, Elin S Hadler-Olsen, Gunbjørg Svineng, Nilva K Cervigne, Ricardo D Coletta, Juha Risteli, Joonas H Kauppila, Sini Skarp, Samuel Kuttner, Ana Oteiza, Meeri Sutinen & Tuula Salo

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Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers

Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers

British Journal of Cancer 117, 913 (26 September 2017). doi:10.1038/bjc.2017.274

Authors: Ashley M Hopkins, Andrew Rowland, Ganessan Kichenadasse, Michael D Wiese, Howard Gurney, Ross A McKinnon, Chris S Karapetis & Michael J Sorich

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Right or left? Side selection for a totally implantable vascular access device: a randomised observational study

Right or left? Side selection for a totally implantable vascular access device: a randomised observational study

British Journal of Cancer 117, 932 (26 September 2017). doi:10.1038/bjc.2017.264

Authors: Wen-Ying Lin, Chih-Peng Lin, Chih-Hung Hsu, Ying-Hui Lee, Yi-Ting Lin, Meng-Chi Hsu & Yu-Yun Shao

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Tumour mutation status and sites of metastasis in patients with cutaneous melanoma

Tumour mutation status and sites of metastasis in patients with cutaneous melanoma

British Journal of Cancer 117, 1026 (26 September 2017). doi:10.1038/bjc.2017.254

Authors: Nikki R Adler, Rory Wolfe, John W Kelly, Andrew Haydon, Grant A McArthur, Catriona A McLean & Victoria J Mar

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SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting

SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting

British Journal of Cancer 117, 938 (26 September 2017). doi:10.1038/bjc.2017.271

Authors: Alastair Greystoke, Nicola Steele, Hendrik-Tobias Arkenau, Fiona Blackhall, Noor Md Haris, Colin R Lindsay, Raffaele Califano, Mark Voskoboynik, Yvonne Summers, Karen So, Dana Ghiorghiu, Angela W Dymond, Stuart Hossack, Ruth Plummer & Emma Dean

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Sitting, physical activity, and serum oestrogen metabolism in postmenopausal women: the Women’s Health Initiative Observational Study

Sitting, physical activity, and serum oestrogen metabolism in postmenopausal women: the Women's Health Initiative Observational Study

British Journal of Cancer 117, 1070 (26 September 2017). doi:10.1038/bjc.2017.268

Authors: Hannah Oh, Hannah Arem, Charles E Matthews, Nicolas Wentzensen, Kerryn W Reding, Louise A Brinton, Garnet L Anderson, Sally B Coburn, Jane A Cauley, Chu Chen, Deborah Goodman, Ruth M Pfeiffer, Roni T Falk, Xia Xu & Britton Trabert

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CXCL7 is a predictive marker of sunitinib efficacy in clear cell renal cell carcinomas

CXCL7 is a predictive marker of sunitinib efficacy in clear cell renal cell carcinomas

British Journal of Cancer 117, 947 (26 September 2017). doi:10.1038/bjc.2017.276

Authors: Maeva Dufies, Sandy Giuliano, Julien Viotti, Delphine Borchiellini, Linsay S Cooley, Damien Ambrosetti, Mélanie Guyot, Papa Diogop Ndiaye, Julien Parola, Audrey Claren, Renaud Schiappa, Jocelyn Gal, Antoine Frangeul, Arnaud Jacquel, Ophélie Cassuto, Renaud Grépin, Patrick Auberger, Andréas Bikfalvi, Gérard Milano, Bernard Escudier, Nathalie Rioux-Leclercq, Camillo Porta, Sylvie Negrier, Emmanuel Chamorey, Jean-Marc Ferrero & Gilles Pagès

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RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses

RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses

British Journal of Cancer 117, 954 (26 September 2017). doi:10.1038/bjc.2017.277

Authors: Saoirse O Dolly, Mark D Gurden, Konstantinos Drosopoulos, Paul Clarke, Johann de Bono, Stan Kaye, Paul Workman & Spiros Linardopoulos

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Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

British Journal of Cancer 117, 1017 (26 September 2017). doi:10.1038/bjc.2017.250

Authors: David Sefrioui, France Blanchard, Emmanuel Toure, Paul Basile, Ludivine Beaussire, Claire Dolfus, Anne Perdrix, Marianne Paresy, Michel Antonietti, Isabelle Iwanicki-Caron, Raied Alhameedi, Stephane Lecleire, Alice Gangloff, Lilian Schwarz, Florian Clatot, Jean-Jacques Tuech, Thierry Frébourg, Fabrice Jardin, Jean-Christophe Sabourin, Nasrin Sarafan-Vasseur, Pierre Michel & Frédéric Di Fiore

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miR-29a/b/c function as invasion suppressors for gliomas by targeting CDC42 and predict the prognosis of patients

miR-29a/b/c function as invasion suppressors for gliomas by targeting CDC42 and predict the prognosis of patients

British Journal of Cancer 117, 1036 (26 September 2017). doi:10.1038/bjc.2017.255

Authors: Cuijuan Shi, Linlin Ren, Cuiyun Sun, Lin Yu, Xiuwu Bian, Xuexia Zhou, Yanjun Wen, Dan Hua, Shujun Zhao, Wenjun Luo, Run Wang, Chun Rao, Qian Wang & Shizhu Yu

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Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer

Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer

British Journal of Cancer 117, 974 (26 September 2017). doi:10.1038/bjc.2017.292

Authors: Meng Li, Jingyu Yang, Wenlong Zhou, Yong Ren, Xiaoxuan Wang, Huiping Chen, Jingyuan Zhang, Junli Chen, Yuhong Sun, Lijuan Cui, Xing Liu, Lihui Wang & Chunfu Wu

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History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report

History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report

British Journal of Cancer 117, 1063 (26 September 2017). doi:10.1038/bjc.2017.267

Authors: Albina N Minlikeeva, Jo L Freudenheim, Rikki A Cannioto, Kevin H Eng, J Brian Szender, Paul Mayor, John L Etter, Daniel W Cramer, Brenda Diergaarde, Jennifer A Doherty, Thilo Dörk, Robert Edwards, Anna deFazio, Grace Friel, Marc T Goodman, Peter Hillemanns, Estrid Høgdall, Allan Jensen, Susan J Jordan, Beth Y Karlan, Susanne K Kjær, Rüdiger Klapdor, Keitaro Matsuo, Mika Mizuno, Christina M Nagle, Kunle Odunsi, Lisa Paddock, Mary Anne Rossing, Joellen M Schildkraut, Barbara Schmalfeldt, Brahm H Segal, Kristen Starbuck, Kathryn L Terry, Penelope M Webb, Emese Zsiros, Roberta B Ness, Francesmary Modugno, Elisa V Bandera, Jenny Chang-Claude & Kirsten B Moysich

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Characterisation of the cancer-associated glucocorticoid system: key role of 11β-hydroxysteroid dehydrogenase type 2

Characterisation of the cancer-associated glucocorticoid system: key role of 11β-hydroxysteroid dehydrogenase type 2

British Journal of Cancer 117, 984 (26 September 2017). doi:10.1038/bjc.2017.243

Authors: Nicola Cirillo, David J Morgan, Maria Carmela Pedicillo, Antonio Celentano, Lorenzo Lo Muzio, Michael J McCullough & Stephen S Prime

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Influence of dietary insulin scores on survival in colorectal cancer patients

Influence of dietary insulin scores on survival in colorectal cancer patients

British Journal of Cancer 117, 1079 (26 September 2017). doi:10.1038/bjc.2017.272

Authors: Chen Yuan, Ying Bao, Kaori Sato, Katharina Nimptsch, Mingyang Song, Jennie C Brand-Miller, Vicente Morales-Oyarvide, Emilie S Zoltick, NaNa Keum, Brian M Wolpin, Jeffrey A Meyerhardt, Andrew T Chan, Walter C Willett, Meir J Stampfer, Kana Wu, Edward L Giovannucci, Charles S Fuchs & Kimmie Ng

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Super-enhancers promote transcriptional dysregulation in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, particularly those involving epigenetic dysregulation, remain largely elusive, hampering clinical management of this malignancy. To identify novel druggable targets, we carried out an unbiased high-throughput chemical screening and observed that NPC cells were highly sensitive to inhibitors of cyclin-dependent kinases (CDK), especially THZ1, a covalent inhibitor of CDK7. THZ1 demonstrated pronounced anti-neoplastic activities both in vitro and vivo. An integrative analysis using both whole-transcriptome sequencing (RNA-Seq) and chromatin-immunoprecipitation sequencing (ChIP-Seq) pinpointed oncogenic transcriptional amplification mediated by super-enhancers (SE) as a key mechanism underlying the vulnerability of NPC cells to THZ1 treatment. Further characterization of SE-mediated networks identified many novel SE-associated oncogenic transcripts, such as BCAR1, F3, LDLR, TBC1D2 and the long non-coding RNA TP53TG1. These transcripts were highly and specifically expressed in NPC and functionally promoted NPC malignant phenotypes. Moreover, DNA-binding motif analysis within the SE segments suggest that several transcription factors (including ETS2, MAFK and TEAD1) may help establish and maintain SE activity across the genome. Taken together, our data establish the landscape of SE-associated oncogenic transcriptional network in NPC, which can be exploited for the development of more effective therapeutic regimens for this disease.

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The Influence of Occupation on Self-perceived Vocal Problems in Patients With Voice Complaints

This study aimed to examine the relationships among patient occupation, laryngeal diagnosis, perceptual dysphonia severity, and patient-perceived voice impairment.

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Correlation between Voice and Auditory Processing

To compare and to correlate the performance of women with behavioral dysphonia and without voice disorders in auditory processing tests and in the Voice Tone Reproduction Test (VTRT).

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Effects of Voice Therapy on Laryngeal Motor Units During Phonation in Chronic Superior Laryngeal Nerve Paresis Dysphonia

Injury to the superior laryngeal nerve can result in dysphonia, and in particular, loss of vocal range. It can be an especially difficult problem to address with either voice therapy or surgical intervention. Some clinicians and scientists suggest that combining vocal exercises with adjunctive neuromuscular electrical stimulation may enhance the positive effects of voice therapy for superior laryngeal nerve paresis (SLNP). However, the effects of voice therapy without neuromuscular electrical stimulation are unknown.

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Assessment of facial asymmetry before and after the surgical repair of cleft lip in unilateral cleft lip and palate cases

This study was performed to assess facial asymmetry in patients with unilateral cleft lip and palate (UCLP) before and after primary lip repair. Three-dimensional facial images of 30 UCLP cases (mean age 3.7±0.8months) captured 1–2days before surgery and 4 months after surgery using stereophotogrammetry were analysed. A generic mesh – a mathematical facial mask consisting of thousands of points (vertices) – was conformed on the three-dimensional images. Average preoperative and postoperative conformed facial meshes were obtained and mirrored by reflecting on the lateral plane.

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Outcomes of septorhinoplasty: a new approach comparing functional and aesthetic results

The aim of this study was to compare objective and subjective functional results of septorhinoplasty with subjective aesthetic results. A prospective study was performed including global and subgroup analyses (primary versus secondary septorhinoplasty). Three instruments were used to evaluate pre- and postoperative results: rhinomanometry for the objective functional analysis, the Nasal Symptom Obstruction Evaluation (NOSE) scale for the subjective functional analysis, and the Rhinoplasty Outcome Evaluation (ROE) scale for the subjective aesthetic analysis.

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Stratifying migraine patients based on dynamic pain provocation over the upper cervical spine

Migraine patients usually report a high prevalence of neck pain preceding or during the migraine attack. A recent investigation of musculoskeletal dysfunctions in migraine patients concluded that neck pain is ...

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Facing the Future: A Call for Higher Education in Sleep Technology

The American Association of Sleep Technologists (AAST) is the national membership organization representing sleep technologists. The Board of Directors of the AAST recognizes that changes in the workforce will result in an increased need for technologists with a higher level of education. In order to meet the needs of members, the AAST has: (1) convened a summit of stakeholders to discuss the changing landscape for sleep technologists; (2) hosted an educational task force to provide ongoing communication and support; and (3) commissioned a survey of members, educators and employers to better define educational gaps and opportunities for sleep technologists.

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Manifestations of Inhalant Allergies Beyond the Nose

The upper and lower airways are linked epidemiologically and pathophysiologically. The upper and lower airways are considered a single, functional unit characterized by shared immunologic mechanisms, often referred to as the unified airway. Upper and lower airway inflammatory disease frequently coexist in the same patient. Allergic rhinitis and rhinosinusitis are associated with asthma. Treatment of both diseases impacts asthma outcomes. The otolaryngologist may be the first physician to suspect and diagnose asthma in patients with upper airway complaints. A thorough understanding of the relationship between allergic rhinitis, rhinosinusitis, and asthma will facilitate early identification of asthma and improve patient outcomes.

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Transcutaneous aponeurotic repair with small detachment of the levator aponeurosis for aponeurotic blepharoptosis in Japanese patients

To examine the surgical outcomes of a modified transcutaneous aponeurotic repair for aponeurotic blepharoptosis in a Japanese population.

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Reduction mammoplasty in adolescents and elderly a ten year case series analyzing age related outcome with focus on safety and complications

Reduction mammoplasty alleviates symptoms of macromastia in various ways. Current study results mainly identify perioperative risk factors for middle aged patients. We investigated a large series of consecutive breast reductions procedures to study whether patients' age at the time of operation is related to the postoperative outcome.

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Characterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes

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Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy

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The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma

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Comprehensive geriatric assessment in 326 older women with early breast cancer

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Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers

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Right or left? Side selection for a totally implantable vascular access device: a randomised observational study

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Tumour mutation status and sites of metastasis in patients with cutaneous melanoma

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SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting

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Sitting, physical activity, and serum oestrogen metabolism in postmenopausal women: the Women’s Health Initiative Observational Study

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CXCL7 is a predictive marker of sunitinib efficacy in clear cell renal cell carcinomas

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Non-conventional role of haemoglobin beta in breast malignancy

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RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses

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Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

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Pharmacogenetic determinants of outcomes on triplet hepatic artery infusion and intravenous cetuximab for liver metastases from colorectal cancer (European trial OPTILIV, NCT00852228)

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miR-29a/b/c function as invasion suppressors for gliomas by targeting CDC42 and predict the prognosis of patients

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Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer

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History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report

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Characterisation of the cancer-associated glucocorticoid system: key role of 11β-hydroxysteroid dehydrogenase type 2

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Abstracts from the 49th Annual Meeting of the Japanese Association for the Study of Taste and Smell (JASTS XLIX 2015), Gifu, Japan, September 24-26th, 2015 (The president of the meeting was Dr. Noritaka Sako, Asahi University)

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Articles highlighted

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Table of Contents

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Cover

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Subscriptions

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Editorial Board

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Differences in the Density of Fungiform Papillae and Composition of Saliva in Patients With Taste Disorders Compared to Healthy Controls

Abstract

This study investigated the relation of the fungiform taste papillae density and saliva composition with the taste perception of patients suffering from diagnosed taste disorders. For this purpose, 81 patients and 40 healthy subjects were included. Taste was measured by means of regional and whole mouth chemosensory tests, and electrogustometry. Olfaction was assessed using the Sniffin Sticks. Fungiform papillae were quantified using the "Denver Papillae Protocol for Objective Analysis of Fungiform Papillae". In addition, salivary parameters [flow rate, total proteins, catalase, total anti-oxidative capacity (TAC), carbonic anhydrase VI (caVI), and pH] were determined and the Beck Depression Inventory was administered. Patients showed less taste papillae compared to healthy subjects. The number of papillae correlated with total taste strip score and salivary flow rate. Regarding salivary parameters, the flow rate, protein concentration, and TAC of patients were higher compared to controls. In addition, salivary flow rate, protease, caVI, and catalase values correlated with the summed taste strip score. Regarding various taste disorders, salty-dysgeusia patients showed the lowest taste test scores compared to those with bitter or metal-dysgeusia. Olfactory function of patients was significantly worse compared to healthy controls. This difference was most pronounced for ageusia patients. Compared to controls, patients also exhibited higher depressive symptoms. The density of fungiform papillae seemed to be positively associated with taste perception. Furthermore, patients exhibited changes in saliva composition (higher salivary flow rate, increased protein concentration, proteolysis, and TAC) compared to controls indicating that assessment of saliva may be critical for the diagnostic procedure in taste disorders.

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The Influence of Sniffing on Airflow and Odorant Deposition in the Canine Nasal Cavity

Abstract

Nasal airflow plays a critical role in olfaction by transporting odorant from the environment to the olfactory epithelium, where chemical detection occurs. Most studies of olfaction neglect the unsteadiness of sniffing and assume that nasal airflow and odorant transport are "quasi-steady," wherein reality most mammals "sniff." Here, we perform computational fluid dynamics simulations of airflow and odorant deposition in an anatomically accurate model of the coyote (Canis latrans) nasal cavity during quiet breathing, a notional quasi-steady sniff, and unsteady sniffing to: quantify the influence of unsteady sniffing, assess the validity of the quasi-steady assumption, and investigate the functional advantages of sniffing compared to breathing. Our results reveal that flow unsteadiness during sniffing does not appreciably influence qualitative (gross airflow and odorant deposition patterns) or quantitative (time-averaged olfactory flow rate and odorant uptake) measures of olfactory function. A quasi-steady approximation is, therefore, justified for simulating time-averaged olfactory function in the canine nose. Simulations of sniffing versus quiet breathing demonstrate that sniffing delivers about 2.5 times more air to the olfactory recess and results in 2.5–3 times more uptake of highly- and moderately-soluble odorants in the sensory region per unit time, suggesting one reason why dogs actively sniff. Simulations also reveal significantly different deposition patterns in the olfactory region during inspiration for different odorants, and that during expiration there is little retronasal odorant deposition in the sensory region. These results significantly improve our understanding of canine olfaction, and have several practical implications regarding computer simulation of olfactory function.

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Thirst Increases Chorda Tympani Responses to Sodium Chloride

Abstract

In nature, water is present as a low-salt solution, thus we hypothesized that thirst would increase taste responses to low-salt solutions. We investigated the effect of thirst on the 2 different salt detection mechanisms present in the rat chorda tympani (CT) nerve. The first mechanism is dependent upon the epithelial sodium channel (ENaC), is blocked by benzamil, and is specific to the cation sodium. The second mechanism, while undefined, is independent of ENaC, and detects multiple cations. We expected thirst to increase benzamil-sensitive sodium responses due to mechanistically increasing the benzamil-sensitive ENaC. We recorded CT whole-nerve electrophysiological responses to lingual application of NaCl, KCl (30, 75, 150, 300, 500, and 600 mM), and imitation rainwater in both control and 24-h water-restricted male rats. NaCl solutions were presented in artificial saliva before and after lingual application of 5µM benzamil. Water restriction significantly increased the integrated CT responses to NaCl but not to KCl or imitation rainwater. Consistent with our hypothesis, only the benzamil-sensitive, and not the benzamil-insensitive, CT sodium response significantly increased. Additionally, CT responses to salt were recorded following induction of either osmotic or volemic thirst. Both thirsts significantly enhanced the integrated CT responses to NaCl and KCl, but not imitation rainwater. Interestingly, osmotic and volemic thirsts increased CT responses by increasing both the benzamil-sensitive and benzamil-insensitive CT sodium responses. We propose that thirst increases the sensitivity of the CT nerve to sodium.

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Developmental Fine-tuning of Human Olfactory Discriminability

Abstract

Unlike vision or audition, human olfaction is generally considered evolutionarily ancient and well-functioning at birth, yet there have been few empirical data on the development of olfactory acuity. The current study has assessed olfactory discriminability in children aged 3 to 6 years with 16 pairs of single-compound odorants that differ in various degrees in structure and smell. We report a significant improvement over age in young children's overall olfactory discriminability. Critically, such improvement is modulated by the degree of structural similarity between odorants independent of odor familiarity. Our findings indicate that odor representations in the olfactory system are fine-tuned during early childhood (3–6 years of age) to allow refined discrimination. Moreover, they suggest the need to take molecular similarity into consideration in the evaluation of olfactory discrimination in pediatric populations.

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Human Fear Chemosignaling: Evidence from a Meta-Analysis

Abstract

Alarm pheromones are widely used in the animal kingdom. Notably, there are 26 published studies (N = 1652) highlighting a human capacity to communicate fear, stress, and anxiety via body odor from one person (66% males) to another (69% females). The question is whether the findings of this literature reflect a true effect, and what the average effect size is. These questions were answered by combining traditional meta-analysis with novel meta-analytical tools, p-curve analysis and p-uniform—techniques that could indicate whether findings are likely to reflect a true effect based on the distribution of P-values. A traditional random-effects meta-analysis yielded a small-to-moderate effect size (Hedges' g: 0.36, 95% CI: 0.31–0.41), p-curve analysis showed evidence diagnostic of a true effect (ps < 0.0001), and there was no evidence for publication bias. This meta-analysis did not assess the internal validity of the current studies; yet, the combined results illustrate the statistical robustness of a field in human olfaction dealing with the human capacity to communicate certain emotions (fear, stress, anxiety) via body odor.

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Sodium Carbonate is Saltier Than Sodium Chloride to Sodium-Depleted Rats

Abstract

In a series of behavioral experiments in the 1960s, G.R. Morrison identified several unique features of the taste of Na₂CO₃ to rats; namely, it is 1) considerably more intense than NaCl at isomolar concentrations, 2) avoided at 10 times lower concentrations than NaCl to thirsty rats, 3) preferred at 10 times lower concentrations than NaCl in sodium-depleted rats. He also demonstrated its qualitatively similarity to NaCl. In Experiment 1, we confirmed and extended many of Morrison's observations. Rats were injected with furosemide on 3 occasions to stimulate a sodium appetite. After each depletion, rats were given a brief-access taste test in a lickometer presenting, in random order, water and 7 concentrations of salt. One test used NaCl (0.028–0.89 M, quarter log steps), another used Na₂CO₃, and the third used Na₂CO₃, but at a tenfold lower concentration range (0.0028–0.089 M). Rats licked NaCl in an inverted-U shaped concentration-response function peaking at 0.158–0.281 M. As Morrison's results predicted, rats licked Na₂CO₃ in nearly identical fashion, but at a tenfold lower concentration range (peak at 0.0158–0.028 M). In a second experiment, furosemide-treated rats were repeatedly tested with the lower Na₂CO₃ range but mixed in the epithelial sodium channel blocker amiloride at various concentrations (3–300 μM, half log steps). Amiloride reduced licking for Na₂CO₃ and shifted the peak response rightward up to about half a log unit. Thus, this "super-saltiness" of Na₂CO₃ to rats is at least partly amiloride-dependent.

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Nostril Differences in the Olfactory Performance in Health and Disease

Abstract

In the past few decades, several olfactory tests have been developed to assess olfactory performance and detect disorders. Contrary to other sensory systems, both nostrils are usually tested together; we hypothesized that monorhinal testing may reveal side differences in sensitivity which may be useful for the diagnosis of olfactory dysfunction. Using the "Sniffin' Sticks" test, we assessed olfactory function of 458 participants (278 healthy controls, 180 hyposmic patients), one nostril after the other, with 3 different tasks. For each participant and each task, we compared the scores obtained with both nostrils, and defined the best and worst nostrils. Thus we were able to establish normative data and to define cut-off values. Our results suggest that scores obtained with the worst nostril are the most efficient in detecting an olfactory disorder. This supports the importance of monorhinal testing, as it can allow an earlier and more accurate diagnosis than birhinal testing. This may be especially useful in the context of early detection of neurodegenerative diseases.

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Oral Digestion and Perception of Starch: Effects of Cooking, Tasting Time, and Salivary α-Amylase Activity

Abstract

Since starch is a significant part of human diet, its oral detection would be highly beneficial. This study was designed to determine whether starch or its degradation products can be tasted and what factors influence its perception. Subjects were asked 1) to taste 8% raw and cooked starch samples for 5, 15, and 35 s and rate perceived intensities of sweetness and "other" taste (i.e., other than sweet), 2) to donate saliva to obtain salivary flow rate (mg/s) and salivary α-amylase activity (per mg saliva), and 3) to fill out a carbohydrate consumption survey. Subsequently, in vitro hydrolysis of starch was performed; saliva was collected from 5 subjects with low and high amylase activities and reacted with 8% raw and cooked starch at 2, 15, and 30 s. Hydrolysis products were then quantified using a High performance liquid chromatography. The results showed cooking increased the digestibility of starch such that the amount of hydrolysis products increased with reaction time. However, cooking did not influence taste ratings, nor were they influenced by tasting time. Subjects' salivary amylase activities were associated with the efficacy of their saliva to degrade starch, in particular cooked starch, and thus the amount of maltooligosaccharide products generated. Effective α-amylase activity [i.e. α-amylase activity (per mg saliva) × salivary flow rate (mg/s)] and carbohydrate consumption score (i.e. consumption frequency × number of servings) were also independently associated with sensory taste ratings. Human perception of starch is undoubtedly complex as shown in this study; the data herein point to the potential roles of salivary α-amylase activity and carbohydrate consumption in the perception of cooked starch.

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Activity-Dependent Gene Expression in the Mammalian Olfactory Epithelium

Abstract

Activity-dependent processes are important to olfactory sensory neurons (OSNs) in several ways, such as cell survival and the specificity of axonal convergence. The identification of activity-dependent mRNAs has contributed to our understanding of OSN axon convergence, but has revealed surprisingly little about other processes. Published studies of activity-dependent mRNAs in olfactory mucosae overlap poorly, but by combining these agreements with meta-analysis of existing data we identify 443 mRNAs that respond to methods that alter OSN activity. Three hundred and fifty of them are expressed in mature OSNs, consistent with the expectation that activity-dependent responses are cell autonomous and driven by odor stimulation. Many of these mRNAs encode proteins that function at presynaptic terminals or support electrical activity, consistent with hypotheses linking activity dependence to synaptic plasticity and energy conservation. The lack of agreement between studies is due largely to underpowered experiments. In addition, methods used to alter OSN activity are susceptible to indirect or off-target effects. These effects deserve greater attention, not only to rigorously identify OSN mRNAs that respond to altered OSN activity, but also because these effects are of significant interest in their own right. For example, the mRNAs of some sustentacular cell enzymes believed to function in odorant clearance (Cyp2a4 and Cyp2g1) are sensitive to unilateral naris occlusion used to reduce odorant stimulation of the ipsilateral olfactory epithelium. Also problematic are odorant receptor mRNAs, which show little agreement across studies and are susceptible to differences in frequency of expression that masquerade as activity-dependent changes in mRNA abundance.

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Resveratrol inhibits Extranodal NK/T cell lymphoma through activation of DNA damage response pathway

Extranodal NK/T cell lymphoma (NKTCL) is a highly aggressive non-Hodgkin lymphoma with poor prognosis. Resveratrol (RSV, 3,5,4′-trihydroxystilbene), a natural nontoxic phenolic compound found in the skin of gr...

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Endocrine Society Updates Guidelines on Transgender Medical Care

The Endocrine Society has updated guidelines on transgender medical care, opening the door for earlier treatment and fertility preservation in transgender teens.
Medscape Medical News

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CT-guided minimally invasive treatment for an extensive spinal epidural abscess: a case report and literature review

Abstract

Purpose

We present a case involving an extensive epidural abscess that was successfully treated with computed tomography (CT)-guided percutaneous needle drainage and systemic antibiotic therapy.

Methods

A 44-year-old woman with a history of spine injection procedures complained of severe backache and progressive radiating pain in her right lower extremity followed by sensory deficits in her right lower limb. A laboratory examination revealed leukocytosis and hyperglycemia. Magnetic resonance imaging of the lumbar region revealed an extremely large posterior spinal epidural abscess (SEA) extending from L2 to S2. Because the patient did not respond to intravenous antibiotics alone, she underwent CT-guided percutaneous needle drainage and irrigation.

Results

Staphylococcus aureus was detected in the purulent material from this abscess. Her clinical symptoms were dramatically and immediately relieved after this procedure. She achieved complete neurological recovery after 2 months of antibiotic therapy.

Conclusion

CT-guided percutaneous needle drainage and irrigation may be a rational treatment choice for patients with SEA with the exception of patients with a chronic abscess, an anterior abscess or discitis.

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Therapeutic Approaches for Zika Virus Infection of the Nervous System

Abstract

Zika virus has spread rapidly in the Americas and has caused devastation of human populations affected in these regions. The virus causes teratogenic effects involving the nervous system, and in adults and children can cause a neuropathy similar to Guillain-Barré syndrome, an anterior myelitis, or, rarely, an encephalitis. While major efforts have been undertaken to control mosquito populations that spread the virus and to develop a vaccine, drug development that directly targets the virus in an infected individual to prevent or treat the neurological manifestations is necessary. Rational and targeted drug development is possible since the viral life cycle and the structure of the key viral proteins are now well understood. While several groups have identified therapeutic candidates, their approaches differ in the types of screening processes and viral assays used. Animal studies are available for only a few compounds. Here we provide an exhaustive review and compare each of the classes of drugs discovered, the methods used for drug discovery, and their potential use in humans for the prevention or treatment of neurological complications of Zika virus infection.

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A genomic screen for angiosuppressor genes in the tumor endothelium identifies a multifaceted angiostatic role for bromodomain containing 7 (BRD7)

Abstract

Tumor angiogenesis is characterized by deregulated gene expression in endothelial cells (EC). While studies until now have mainly focused on overexpressed genes in tumor endothelium, we here describe the identification of transcripts that are repressed in tumor endothelium and thus have potential suppressive effects on angiogenesis. We identified nineteen putative angiosuppressor genes, one of them being bromodomain containing 7 (BRD7), a gene that has been assigned tumor suppressor properties. BRD7 was studied in more detail, and we demonstrate that BRD7 expression is inversely related to EC activation. Ectopic expression of BRD7 resulted in a dramatic reduction of EC proliferation and viability. Furthermore, overexpression of BRD7 resulted in a bromodomain-dependent induction of NFκB-activity and NFκB-dependent gene expression, including ICAM1, enabling leukocyte–endothelial interactions. In silico functional annotation analysis of genome-wide expression data on BRD7 knockdown and overexpression revealed that the transcriptional signature of low BRD7 expressing cells is associated with increased angiogenesis (a.o. upregulation of angiopoietin-2, VEGF receptor-1 and neuropilin-1), cytokine activity (a.o. upregulation of CXCL1 and CXCL6), and a reduction of immune surveillance (TNF-α, NFκB, ICAM1). Thus, combining in silico and in vitro data reveals multiple pathways of angiosuppressor and anti-tumor activities of BRD7.

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Stroke mimics add to the phenotypic spectrum of GLUT1 deficiency syndrome

Introduction

Glucose transporter protein 1 (GLUT1) is the principal glucose transporter of the blood–brain barrier. In GLUT1 deficiency syndrome (GLUT1DS), glucose transport into the brain is disturbed, which leads to the clinical symptomatology as well as characteristic (and diagnostic) abnormalities in cerebrospinal fluid.1 In approximately 90% of patients with GLUT1DS, heterozygous mutations in the SLC2A1 gene, encoding the GLUT1 protein, can be demonstrated.1 So far, this is the only gene known to be associated with this condition. The classic phenotype of GLUT1DS includes microcephaly, mild to severe developmental delay, infantile-onset drug-resistant epilepsy, and movement disorders, including spasticity, ataxia and dystonia.1 Recognising GLUT1DS is crucial because it can be treated with the ketogenic diet, as ketone bodies serve as alternative energy source for the brain.1

In the past decade, the range of clinical syndromes associated with GLUT1DS has expanded tremendously. Various paroxysmal or episodic disorders...

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Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients

Objective

To report the clinical and immunological characteristics of 22 new patients with glial fibrillar acidic protein (GFAP) autoantibodies.

Methods

From January 2012 to March 2017, we recruited 451 patients with suspected neurological autoimmune disease at the Catholic University of Rome. Patients' serum and cerebrospinal fluid (CSF) samples were tested for neural autoantibodies by immunohistochemistry on mouse and rat brain sections, by cell-based assays (CBA) and immunoblot. GFAP autoantibodies were detected by immunohistochemistry and their specificity confirmed by CBA using cells expressing human GFAPα and GFAP proteins, by immunoblot and immunohistochemistry on GFAP-/- mouse brain sections.

Results

Serum and/or CSF IgG of 22/451 (5%) patients bound to human GFAP, of which 22/22 bound to GFAPα, 14/22 to both GFAPα and GFAP and none to the GFAP isoform only. The neurological presentation was: meningoencephalomyelitis or encephalitis in 10, movement disorder (choreoathetosis or myoclonus) in 3, anti-epileptic drugs (AED)-resistant epilepsy in 3, cerebellar ataxia in 3, myelitis in 2, optic neuritis in 1 patient. Coexisting neural autoantibodies were detected in five patients. Six patients had other autoimmune diseases. Tumours were found in 3/22 patients (breast carcinoma, 1; ovarian carcinoma, 1; thymoma, 1). Nineteen patients were treated with immunotherapy and 16 patients (84%) improved. Histopathology analysis of the leptomeningeal biopsy specimen from one patient revealed a mononuclear infiltrate with macrophages and CD8+ T cells.

Conclusions

GFAP autoimmunity is not rare. The clinical spectrum encompasses meningoencephalitis, myelitis, movement disorders, epilepsy and cerebellar ataxia. Coexisting neurological and systemic autoimmunity are relatively common. Immunotherapy is beneficial in most cases.

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Effects of dopaminergic depletion and brain atrophy on neuropsychiatric symptoms in de novo Parkinsons disease

Background

Neuropsychiatric symptoms impact the patients' quality of life and caregivers' burdens in Parkinson's disease (PD). We aimed to investigate the effects of striatal dopaminergic depletion and brain atrophy on the neuropsychiatric symptoms of patients with PD.

Methods

Two hundred and seven patients with de novo drug-naïve PD underwent dopamine transporter (DAT) positron emission tomography and brain MRI scanning. In addition, the patients were assessed with caregiver-administered neuropsychiatric inventory (NPI) questionnaires. To evaluate the effects of DAT uptake, subcortical volume and cortical thinning on the patients' neuropsychiatric symptoms, we performed logistic regression and negative binomial regression analyses on the NPI data after controlling for possible confounders.

Results

Frontal cortical thinning was associated with the presence of nighttime behaviour and irritability, and the thinning correlated with the severity of the nighttime behaviour. Temporal cortical thinning was associated with the presence of aggression/agitation, and it correlated with the severity of the aggression/agitation. Subcortical atrophy in the accumbens was associated with the presence of disinhibition and correlated with the severity of the disinhibition. Putamen atrophy and insular thinning were independently associated with the presence of apathy, but only insular thinning correlated with the severity of the apathy. Of the predictors, only frontal cortical thinning correlated with the total NPI score.

Conclusions

The results of this study suggested that accumbens atrophy and frontotemporal cortical thinning, especially frontal cortical thinning, independently contributed to neuropsychiatric symptoms in patients with PD, while DAT uptake did not affect the neuropsychiatric symptoms.

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Increased methylation of the oxytocin receptor gene in motor functional neurological disorder: a preliminary study

Background

Functional neurological disorder (FND) represents a paradigmatic neuropsychiatric disorder; patients present neurological physical symptoms but associated psychosocial stressors play a role as predisposing and precipitating factors.1 Recent neuroscience research has shed light on how the physical symptoms arise in terms of aberrant brain mechanisms2 but little is known in terms of why certain individual develop the disorder. Childhood abuse and life adversities have been linked to FND but cannot be viewed solely/exclusively as causal,3 as this association is partially non-specific. A multifactorial causal model has to be considered and a gene–environment interaction is plausible, as it could theoretically integrate life stressors as precipitating factors in a subset of susceptible individuals. There is to date no evidence for genetic risks of FND with only one study reporting familial cases suggesting disease modelling in families rather than genetic transmission.4 Twin studies in other...

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Predictive AI and Voice Recognition Shift Clinical Practice

Medicine is being transformed by machines that extrapolate valuable information from several data streams, systems that render typing obsolete, and medical schools where cadavers are no longer used.
Medscape Medical News

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Diagnosis and management of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma (NHL) that is confined to the brain, eyes, spinal cord, or leptomeninges without systemic involvement. The overall prognosis, diagnosis, and management of PCNSL differ from those for other types of NHL. Prompt diagnosis and initiation of treatment are vital for improving clinical outcomes. PCNSL is responsive to radiation therapy; however, whole-brain radiotherapy (WBRT) inadequately controls the disease when it is used alone, and its delayed neurotoxicity causes neurocognitive impairment, especially in elderly patients. High-dose methotrexate (HD-MTX)–based induction chemotherapy with or without autologous stem cell transplantation (ASCT) or reduced-dose WBRT leads to durable disease control and less neurotoxicity. The optimal treatment has yet to be defined; however, HD-MTX–based induction chemotherapy is considered standard for newly diagnosed PCNSL. Ongoing randomized trials are addressing the roles of rituximab and consolidative treatment with ASCT or reduced-dose WBRT. Despite high tumor response rates with the initial treatment, many patients relapse with a very poor prognosis. The optimal treatment for refractory or relapsed PCNSL is poorly defined. The choice of salvage treatment depends on a patient's age, previous treatment and response, performance status, and comorbidities at the time of relapse. This review provides an overview of the clinical features, diagnosis, pathology, and management of PCNSL in immunocompetent patients, and it focuses on recent advances in treatment. Cancer 2017. © 2017 American Cancer Society.

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Human papillomavirus 16 E6 antibodies are sensitive for human papillomavirus–driven oropharyngeal cancer and are associated with recurrence

BACKGROUND

Human papillomavirus 16 (HPV16) E6 antibodies may be an early marker of the diagnosis and recurrence of human papillomavirus–driven oropharyngeal cancer (HPV-OPC).

METHODS

This study identified 161 incident oropharyngeal cancer (OPC) cases diagnosed at the University of Pittsburgh (2003-2013) with pretreatment serum. One hundred twelve had preexisting clinical HPV testing with p16 immunohistochemistry and HPV in situ hybridization (87 were dual-positive [HPV-OPC], and 25 were dual-negative [HPV-negative]); 62 had at least 1 posttreatment serum sample. Eighty-six of the 161 tumors were available for additional HPV16 DNA/RNA testing (45 were dual-positive [HPV16–OPC], and 19 were dual-negative [HPV16–negative). HPV16 E6 antibody testing was conducted with multiplex serology. The following were evaluated: 1) the sensitivity and specificity of HPV16 E6 serology for distinguishing HPV-OPC and HPV16–OPC from HPV-negative OPC, 2) HPV16 E6 antibody decay after treatment with linear models accommodating correlations in variance estimates, and 3) pre- and posttreatment HPV16 E6 levels and the risk of recurrence with Cox proportional hazards models.

RESULTS

Seventy-eight of 87 HPV-OPCs were HPV16 E6–seropositive (sensitivity, 89.7%; 95% confidence interval [CI], 81.3%-95.2%), and 24 of 25 HPV-negative OPCs were HPV16 E6–seronegative (specificity, 96.0%; 95% CI, 79.6%-99.9%). Forty-two of 45 HPV16–OPCs were HPV16 E6–seropositive (sensitivity, 93.3%; 95% CI, 81.7%-98.6%), and 18 of 19 HPV16–negative OPCs were HPV16 E6–seronegative (specificity, 94.7%; 95% CI, 74.0%-99.9%). Posttreatment HPV16 E6 antibody levels did not decrease significantly from the baseline (P = .575; median follow-up, 307 days) and were not associated with the risk of recurrence. However, pretreatment HPV16 E6 seropositivity was associated with an 86% reduced risk of local/regional recurrence (hazard ratio, 0.14; 95% CI, 0.03-0.68; P = .015).

CONCLUSIONS

HPV16 E6 antibodies may have potential clinical utility for the diagnosis and/or prognosis of HPV-OPC. Cancer 2017. © 2017 American Cancer Society.

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Serum antibodies open the door to prediction and prognostication in human papillomavirus–related head and neck cancer

In human papillomavirus–related head and neck cancer, who can be de-escalated, and who requires more intensive therapy to achieve similar oncologic efficacy? The answers may very well be circulating in saliva and serum. See also pages 000-000.

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Prognostic impact of pretreatment neutrophil-to-lymphocyte ratio (NLR) in nasopharyngeal carcinoma – a retrospective study of 180 Taiwanese patients

Abstract

Objectives

Nasopharyngeal cancer (NPC) is an endemic disease in Taiwan. Prognostic factors the anatomical TNM stage are important for its prognostic stratification. An elevated neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor prognosis in various solid tumors. In this study, we analyzed the prognostic impact of the NLR in NPC in Taiwan.

Design

Single institution retrospective study.

Setting

Medical Center.

Participants

One hundred and eighty patients with NPC treated at the Far Eastern Memorial Hospital, Taiwan, from January 2007 to December 2013.

Main outcome measures

The association between the clinical or hematological presentations and the prognosis.

Results

The majority of the 180 patients included in this study were men (80%) and were <65 years old (91.7%). A neck mass (55.6%) was the most common clinical presentation, followed by nasal (39.4%) and aural (30.6%) symptoms. In addition, the majority (75.4%) of patients had advanced stage (III and IV) disease. Patients with a high NLR (≧3.6) had significantly lower progression-free survival, overall survival, and disease-specific survival rates. The association between high NLR and poor prognosis was more pronounced in patients with advanced disease than in those with early stage NPC. The results of a multivariate analysis revealed that advanced age, clinical symptoms including headache, diplopia and facial numbness, advanced disease stage, and high NLR were independent prognostic factors.

Conclusion

A high NLR is an independent poor prognostic factor of NPC in Taiwan.

This article is protected by copyright. All rights reserved.

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Age specific incidence and treatment patterns of head and neck cancer in the Netherlands – a cohort study

Abstract

Objectives

To explore the incidence and treatment pattern of head and neck cancer in different age groups.

Design

cohort study.

Setting

Netherlands Cancer Registry.

Participants

All new primary head and neck cancer cases diagnosed between 2010 and 2014 were included and categorized in different age groups.

Main outcome measures

Tumour site, stage, treatment modality, location of diagnosis and treatment.

Results

The study population was composed of 11,558 tumours. Oral cancer was the most common primary site (31%), followed by laryngeal (25%) and oropharyngeal cancer (22%). Ninety-six percent of the entire study population was diagnosed and/or treated in a certified head and neck oncology centre which was lower in the 80+ population (92%). Multimodality treatment was less frequently applied with increasing age (e.g. oral cavity: 17% in 80+ vs. 34% in 60-; p<0.001). The percentage of patients not receiving tumour directed treatment increased with age (e.g. oropharyngeal cancer: 25% in 80+ vs. 6% in 80-; p<0.001).

Conclusions

This study confirms that less multimodal and tumour directed treatment is applied with the increasing age of head and neck cancer patients.

This article is protected by copyright. All rights reserved.

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On the Evaluation of a SuperPower Sound Processor for Bone-Anchored Hearing

Abstract

Objectives

Performance of a superpower bone-anchored hearing aid (Baha), the Baha Cordelle from Cochlear Bone-Anchored Solutions (BCD1), was compared to its successor, the Baha 5 SuperPower (BCD2)

Design

a comparative study in which each patient served as its own control.

Setting

tertiary clinic.

Participants

Ten experienced BCD1 users with profound mixed hearing loss. For comparison, data from another study with ten experienced users with a severe mixed hearing loss using a Cochlear Baha 5 power sound processor (BCD-P) were included.

Main outcome measures

speech reception thresholds in noise and APHAB and SSQ questionnaires.

Results

Speech reception thresholds for the digits-in-noise test were significantly lower (p<5%), i.e. more favourable, for BCD2 in the speech and noise frontal condition and in the speech frontal and noise contralateral condition than for BCD1. For the group with severe mixed loss fitted with BCD-P the SRTs were not significantly different (p>5%) from the BCD2 values.

With the APHAB questionnaire scores were significantly lower, i.e. more favourable, for the ease-of-communication (p<5%) and the background noise (p<1%) domains for BCD2 than for BCD1. APHAB scores for the aversiveness of loud sounds domain were not significantly different for both devices (p>5%). Scores for the speech and quality domains of the SSQ questionnaire were significantly higher, i.e. more favourable, for BCD2 than for BCD1. APHAB and SSQ scores for BCD-P were not significantly different from those for BCD2 (p>5%).

Conclusions

Data for BCD2 in profound mixed loss are similar to those for BCD-P and a severe mixed loss. Out of ten patients two expressed a strong preference for BCD2 over BCD1 and seven patients had a preference for BCD2 over BCD1. One patient preferred BCD1 because of its built-in telecoil facility.

This article is protected by copyright. All rights reserved.

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Intravenous Opioid Drug Abuse as an Independent Risk Factor for Supraglottic Squamous Cell Carcinoma – A Case Control Study

Abstract

Objectives

Intravenous opioid drug abuse (IVDA) was previously correlated with laryngeal cancer. However, discrimination of this correlation by anatomical subsites has not yet been described. In this study we aim to further establish the association between IVDA and laryngeal squamous cell carcinoma (SCC) and to indicate the laryngeal subsites that are predisposed for this correlation.

Design

A retrospective matched case control study.

Setting and Participants

Patients diagnosed with supraglottic SCC (SG-SCC) between 1996 and 2016 treated in a tertiary academic referral center were enrolled to the case group. The control group comprised of matched patients diagnosed with glottis SCC (G-SCC). Matching was based on gender, age and socioeconomic rank.

Main outcome measures

Variables studies as risk factors included: smoking, alcohol consumption, history of IVDA and infectious diseases. The variables were tested for association with the two groups and with each other.

Results

Forty eight patients with SG-SCC were matched with 48 G-SCC patients. IVDA rates significantly increased among SG-SCC patients. Of the SG-SCC group, 18.8% had a positive history for IVDA compared with 2.1% of the G-SCC (p-value=0.008). A history of IVDA was found to be a risk factor for SG-SCC, independent of smoking, excessive alcohol, and socioeconomic status. The odds ratio for patients with an IVDA history to have SG-SCC relatively to G-SCC was 10.846 (95% CI:1.3-89.4).

Conclusions

IVDA represent an independent risk factor for SG-SCC. The pathogenesis should be investigated not just as a risk factor, since opioids are commonly used for pain management in oncologic patients.

This article is protected by copyright. All rights reserved.

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Low-Tech Outreach Methods Improve Colorectal Cancer Screening

Proactive, low-tech outreach approaches can help increase the number of people who get screened for colorectal cancer with a colonoscopy or home stool test and complete the appropriate follow-up.

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Management of precancerous anal intraepithelial lesions in human immunodeficiency virus–positive men who have sex with men: Clinical effectiveness and cost-effectiveness

BACKGROUND

Human immunodeficiency virus (HIV)–positive men who have sex with men (MSM) are at disproportionately high risk for anal cancer. There is no definitive approach to the management of high-grade squamous intraepithelial lesions (HSIL), which are precursors of anal cancer, and evidence suggests that posttreatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves HSIL treatment effectiveness. The objectives of this study were to evaluate the optimal HSIL management strategy with respect to clinical effectiveness and cost-effectiveness and to identify the optimal age for initiating HSIL management.

METHODS

A decision analytic model of the natural history of anal carcinoma and HSIL management strategies was constructed for HIV-positive MSM who were 27 years old or older. The model was informed by the Surveillance, Epidemiology, and End Results–Medicare database and published studies. Outcomes included the lifetime cost, life expectancy, quality-adjusted life expectancy, cumulative risk of cancer and cancer-related deaths, and cost-effectiveness from a societal perspective.

RESULTS

Active monitoring was the most effective approach in patients 29 years or younger; thereafter, HSIL treatment plus adjuvant qHPV vaccination became most effective. When cost-effectiveness was considered (ie, an incremental cost-effectiveness ratio [ICER] < $100,000/quality-adjusted life-year), do nothing was cost-effective until the age of 38 years, and HSIL treatment plus adjuvant qHPV vaccination was cost-effective beyond the age of 38 years (95% confidence interval, 34-43 years). The ICER decreased as the age at HSIL management increased. Outcomes were sensitive to the rate of HSIL regression or progression and the cost of high-resolution anoscopy and biopsy.

CONCLUSIONS

The management of HSIL in HIV-positive MSM who are 38 years old or older with treatment plus adjuvant qHPV vaccination is likely to be cost-effective. The conservative approach of no treatment is likely to be cost-effective in younger patients. Cancer 2017. © 2017 American Cancer Society.

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CUX1 Stimulates APE1 Enzymatic Activity and Increases the Resistance of Glioblastoma Cells to the Mono-Alkylating Agent, Temozolomide

Abstract

Background

CUX1, which encodes an auxiliary factor in base excision repair, resides on 7q22.1, the most frequently and highly amplified chromosomal region in glioblastomas. The resistance of glioblastoma cells to the mono-alkylating agent temozolomide is determined to some extent by the activity of the apurinic/apyrimidinic endonuclease 1, APE1.

Methods

To monitor the effect of CUX1 and its CUT domains on APE1 activity, DNA repair assays were performed with purified proteins and cell extracts. CUX1 protein expression was analyzed by immunohistochemistry using a tumor microarray of 150 glioblastoma samples. The effect of CUX1 knockdown and overexpression on the resistance of glioblastoma cell lines to temozolomide was investigated.

Results

We show that CUT domains stimulate APE1 activity. In agreement with these findings, CUX1 knockdown causes an increase in the number of abasic sites in genomic DNA and a decrease in APE1 activity as measured in cell extracts. Conversely, ectopic CUX1 expression increases APE1 activity and lowers the number of abasic sites. Having established that CUX1 is expressed at high levels in most glioblastomas, we next show that the resistance of glioblastoma cells to temozolomide and to a combined treatment with temozolomide and ionizing radiation is reduced following CUX1 knockdown, but increased by overexpression of CUX1 or a short protein containing only two CUT domains, which is active in DNA repair but devoid of transcriptional activity.

Conclusion

These findings indicate that CUX1 expression level impacts on the response of glioblastoma cells to treatment and identify the CUT domains as potential therapeutic targets.

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Assessing outcome following levatorplasty: when east meets west editorial on paper “transcutaneous aponeurotic repair with small detachment of the levator aponeurosis for aponeurotic blepharoptosis in japanese patients”

Publication date: Available online 25 September 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Jan J. van Wingerden




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Debunking the myth of e-cigarettes: a case of free flap compromise due to e-cigarette use within the first 24 hours

Publication date: Available online 25 September 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Nneamaka Agochukwu, James Y. Liau




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Evaluation of the effect of an innovative automated text messaging service on patient experience in day-case hand trauma surgery

Publication date: Available online 25 September 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): O.J. Smith, C.J. Stewart, N. Rastogi, A. Abdaal, N. Hachach-Haram, R. Kerstein, A. Mosahebi




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Comparing sensation of common donor site regions for autologous breast reconstruction to a healthy breast.

Publication date: Available online 25 September 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Anouk J.M. Cornelissen, Jop Beugels, Arno Lataster, Esther M. Heuts, Shai M. Rozen, Aldona J. Spiegel, René R.W.J. van der Hulst, Stefania M.H. Tuinder
IntroductionAutologous breast reconstruction has become standard care for breast cancer patients. Although excellent cosmetic results can be achieved, most reconstructed breasts fail to regain normal sensation. Nerve coaptation of the flap has been suggested to improve sensation, the effect of the donor flap native sensory threshold, on the degree of sensory restoration has yet to be determined. The aim of this study is to evaluate the differences in sensation between various potential donor site regions in comparison to sensation of the healthy breast.Patients and methodsIn the Maastricht University Medical Centre a cross-sectional study in healthy women was performed. Monofilaments were used to measure sensation in the breast and at different flap donor sites: Deep Inferior Epigastric Perforator (DIEP), Lateral Thigh Perforator (LTP), Profunda Artery Perforator (PAP), Superior Gluteal Artery Perforator (SGAP) and Transverse Musculocutaneous Gracilis (TMG) flap. The Wilcoxon Signed Rank Test was used to analyse statistical significance in sensation.ResultsFifty women with a mean age of 49±2.72 years and mean BMI of 26.14±0.89 kg/m² were included in the study. The median monofilament value of the normal breasts was 2.97(2.56-3.55). The median monofilament value of each donor site and p value when compared to the healthy breast were: DIEP-flap 2.62(2.36-3.22) p <0.01, LTP-flap 3.61(2.83-4.08) p<0.01, PAP-flap 3.09(2.67-3.5) p=0.97, SGAP-flap 3.22(2.64-3.87) p=0.01 and TMG-flap 3.03(2.6-3.47) p=0.69.ConclusionsThere is a significant difference in sensation between the various donor site regions for breast reconstruction and the healthy breast. This might be taken into consideration for donor site selection.



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A new all-purpose bilateral cleft lip repair: bilateral cheiloplasty suitable for most conditions

Publication date: Available online 25 September 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Rong-Min Baek, Yujin Myung, Iehyon Park, Chang-Sik Pak, Baek-kyu Kim, Vũ Ngọc Lâm, Jae Hoon Jeong
BackgroundOnly experienced surgeons are able to produce satisfactory results with most of the current surgical methods for bilateral cleft lip repair. The existing methods require not only preoperative orthodontic maneuvers but also accurate measurements for surgical design. We describe an easy-to-design and simple-to-execute general purpose surgical technique to repair most bilateral cleft lips.MethodsA retrospective review was performed for the patients who underwent bilateral cleft lip repair using our novel method between 2003 and 2016. The authors collected data from medical records and the aesthetic results were judged using the aesthetic result categories by three independent surgeons; indirect anthropometry was applied to patients over 9 years of age. In addition, we investigated the complications, the reoperation rate, and the reasons for reoperation.ResultsBilateral cleft lip surgery was performed in 146 cases between 2003 and 2016. Seventy-eight patients had bilateral complete cleft lips, 47 patients had bilateral incomplete cleft lips, and 21 patients had bilateral complete and incomplete cleft lips (asymmetric patients). There were no acute complications requiring re-surgery, such as wound dehiscence, hematoma, and infection. According to aesthetic classification, 74 patients (51%) were classified into category I, and 72 (49%) into category II; no patients were classified into categories III and IV. Seventy patients (48%) underwent secondary lip operations. In anthropometry, the measurements were observed to be symmetrical; left and right measurement data were not significantly different. The main purposes of the revision were excision of widened philtral scars (42 cases) and correction of lateral vermilion bulging (28 cases).ConclusionsWe have found our novel technique to be simple and capable of providing consistent, reproducible, and reliable results.



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