Cancers, Vol. 9, Pages 111: Translocation Renal Cell Carcinoma: An Update on Clinicopathological and Molecular Features

Cancers, Vol. 9, Pages 111: Translocation Renal Cell Carcinoma: An Update on Clinicopathological and Molecular Features

Cancers doi: 10.3390/cancers9090111

Authors: Kentaro Inamura

Microphthalmia-associated transcription (MiT) family translocation renal cell carcinoma (tRCC) comprises Xp11 tRCC and t(6;11) RCC. Due to the presence of fusion genes, Xp11 tRCC and t(6;11) RCC are also known as TFE3- and TFEB-rearranged RCC, respectively. TFE3 and TFEB belong to the MiT family, which regulates melanocyte and osteoclast differentiation, and TFE3- and TFEB-rearranged RCC show characteristic clinicopathological and immunohistochemical features. Recent studies identified the fusion partner-dependent clinicopathological and immunohistochemical features in TFE3-rearranged RCC. Furthermore, RCC with chromosome 6p amplification, including TFEB, was identified as a unique subtype of RCC, along with ALK-rearranged RCC. This review summarizes these recent advancements in our tRCC-related knowledge.

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The 150 most important questions in cancer research and clinical oncology series: questions 50–56

Abstract

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, seven more questions are presented as followed. Question 50. When tumor cells spread from primary site to distant sites, are they required to be "trained" or "armed" in the bone marrow niche prior to colonizing soft tissues? Question 51. Are there tipping points during cancer progression which can be identified for manipulation? Question 52. Can we replace molecular biomarkers by network biomarkers? Question 53. Are conventional inhibitors of key cellular processes such as cell proliferation and differentiation more effective than targeted chemotherapeutics that antagonize the downstream cell signaling network via cell-surface receptors such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR) and c-Met, or intracellular receptors such as androgen receptor (AR) and estrogen receptor (ER), by drugs like erlotinib, sunitinib and cabozantinib, or enzalutamide and tomoxifen? Question 54. How can we robustly identify the candidate causal event of somatic genome alteration (SGA) by using computational approach? Question 55. How can we systematically reveal the immune evasion mechanism exploited by each tumor and utilize such information to guide targeted therapy to restore immune sensitivity? Question 56. Can the nasopharyngeal carcinoma (NPC) patients with sarcomatoid carcinoma (SC) subtype benefit from more specific targeted therapy?

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Minimal Residual Disease Eradication in CML: Does It Really Matter?

Abstract

BCR-ABL1 tyrosine kinase inhibitors (TKIs) have improved the prognosis of chronic phase chronic myeloid leukemia (CP-CML) to an extent that survival is largely determined by non-CML mortality. Monitoring for minimal residual disease by measuring BCR-ABL1 messenger RNA is a key component of CML management. CP-CML patients who achieve a stable deep molecular response may discontinue (TKIs) with an ~ 50% chance of entering treatment-free remission (TFR). So far discontinuation of TKIs has largely been limited to clinical trials, but is on the verge of becoming a part of wider clinical practice. Careful patient selection, dense molecular monitoring, and prompt reinstitution of treatment in the event of relapse are all vital to reproduce the same level of success. Much effort has been dedicated to identifying therapeutic strategies to eliminate CML stem cells and enable to TFR in more patients. Unfortunately, despite promising preclinical data, as yet, none of the various approaches have entered clinical practice.

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The 150 most important questions in cancer research and clinical oncology series: questions 50–56

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

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Synthetic lethality interaction between Aurora kinases and CHEK1 inhibitors in ovarian cancer

Ovarian cancer is characterized by frequent mutations at TP53. These tumors also harbor germline mutations at homologous recombination repair (HR) genes, so they rely on DNA-damage checkpoint proteins, like the Checkpoint kinase 1 (CHEK1) to induce G2 arrest. In our study, by using an in silico approach, we identified a synthetic lethality interaction between CHEK1 and mitotic Aurora Kinase A (AURKA) inhibitors.  Gene expression analyses were used for the identification of relevant biological functions. OVCAR3, OVCAR8, IGROV1 and SKOV3 were used for proliferation studies. Alisertib was tested as AURKA inhibitor and LY2603618 as CHEK1 inhibitor.  Analyses of cell cycle and intracellular mediators were performed by flow cytometry and Western blot. Impact on stem cell properties was evaluated by flow cytometry analysis of surface markers  and sphere formation assays. Gene expression analyses followed by functional annotation identified a series of deregulated genes which belonged to cell cycle, including AURKA/B, TTK kinase and CHEK1.  AURKA and CHEK1 were amplified in 8.7% and 3.9% of ovarian cancers, respectively. AURKA and CHEK1 inhibitors showed a synergistic interaction in different cellular models.  Combination of Alisertib and LY2603618 triggered apoptosis, reduced the stem cell population and increased the effect of taxanes and platinum compounds. Finally, expression of AURKA and CHEK1 was linked with detrimental outcome in patients. Our data describes a synthetic lethality interaction between CHEK1 and AURKA inhibitors with potential translation to the clinical setting.

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Oncolytic Reactivation of KSHV as a Therapeutic Approach for Primary Effusion Lymphoma

Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Currently treatment options for patients with PEL are limited. Oncolytic viruses have been engineered as anti-cancer agents and have recently shown increased therapeutic promise. Similarly, lytic activation of endogenous viruses from latently infected tumor cells can also be applied as a cancer therapy. In theory, such a therapeutic strategy would induce oncolysis by viral replication, while simultaneously stimulating an immune response to viral lytic cycle antigens. We examined the combination of the FDA-approved drug PEP005 (ingenol-3-angelate) with epigenetic drugs as a rational therapeutic approach for KSHV-mediated malignancies. JQ1, a bromodomain and extra terminal protein (BET) inhibitor, in combination with PEP005, not only robustly induced KSHV lytic replication, but also inhibited IL-6 production from PEL cells. Using the dosages of these agents that was found to be effective in reactivating HIV (as a means to clear latent virus with HAART therapy), we were able to inhibit PEL growth in vitro and delay tumor growth in a PEL xenograft tumor model. KSHV reactivation was mediated by activation of NF-B pathway <br />by PEP005, which led to increased occupancy of RNA polymerase II onto the KSHV genome. RNA-sequencing analysis further revealed cellular targets of PEP005, JQ1, and the synergistic effects of both. Thus, combination of PEP005 with a BET inhibitor may be considered as a rational therapeutic approach for the treatment of PEL.

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Trp53 Mutants Drive Neuroendocrine Lung Cancer through Loss-of-Function Mechanisms with Gain-of-Function Effects on Chemotherapy Response

Lung cancer is the leading cause of cancer deaths with small cell lung cancer (SCLC) as the most aggressive subtype. Preferential occurrence of TP53 missense mutations rather than loss implicates a selective advantage for TP53 mutant expression in SCLC pathogenesis. We show that lung epithelial expression of R270H and R172H (R273H and R175H in humans), common Trp53 mutations in lung cancer, combined with Rb1 loss selectively results in two subtypes of neuroendocrine carcinoma, SCLC and large cell neuroendocrine carcinoma (LCNEC). Tumor initiation and progression occur in a remarkably consistent time frame with short latency and uniform progression to lethal metastatic disease by 7 months. R270H or R172H expression and Trp53 loss result in similar phenotypes demonstrating that Trp53 mutants promote lung carcinogenesis through loss-of-function and not gain-of-function mechanisms. Tumor responses to targeted and cytotoxic therapeutics were discordant in mice and corresponding tumor cell cultures demonstrating need to assess therapeutic response at the organismal level. Rapamycin did not have therapeutic efficacy in the mouse model despite inhibiting mTOR signaling and markedly suppressing tumor cell growth in culture. In contrast, cisplatin/etoposide treatment using a patient regimen prolonged survival with development of chemoresistance recapitulating human responses. R270H, but not R172H, expression conferred gain-of-function activity in attenuating chemotherapeutic efficacy. These data demonstrate a causative role for Trp53 mutants in development of chemoresistant lung cancer, and provide tractable preclinical models to test novel therapeutics for refractory disease.

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Multiple correspondence analysis as a strategy to explore the association between categories of qualitative variables related to oral–maxillofacial trauma and violent crimes at the community level

The main objective of this study was to show the applicability of multiple correspondence analysis (MCA) in the detection and representation of underlying structures in large datasets used to investigate oral–maxillofacial lesions. A cross-sectional study was conducted involving the analysis of the medical–forensic and social records of 992 people who experienced oral–maxillofacial trauma resulting from non-fatal violent crimes that occurred in the community. Based on the MCA results, two distinct victim profiles were identified.

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Adjuvant radiation and survival following surgical resection of sinonasal melanoma

Surgery remains the mainstay of treatment for sinonasal melanoma, but it is often difficult to obtain clear, negative margins. Therefore, patients often receive adjuvant radiation therapy (RT), however its impact on overall survival (OS) is not well understood.

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Effects of surgical treatment of hypertrophic turbinates on the nasal obstruction and the quality of life

Chronic hyperplasia of the inferior nasal concha is accompanied by a nasal obstruction; however, there is no standardised surgical treatment for this condition. Here, we compared the outcome of three surgical techniques frequently used to treat the hyperplasia of inferior turbinates: turbinectomy with lateralization, submucosal electrocautery and laser cautery additional to septoplasty.

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MITF-high and MITF-low cells and a novel subpopulation expressing genes of both cell states contribute to intra and inter-tumoral heterogeneity of primary melanoma.

Purpose. Understanding tumour heterogeneity is an important challenge in current cancer research. Transcription and epigenetic profiling of cultured melanoma cells have defined at least two distinct cell phenotypes characterised by distinctive gene expression signatures associated with high or low/absent expression of Microphthalmia-associated transcription factor (MITF). Nevertheless, heterogeneity of cell populations and gene expression in primary human tumours is much less well characterised. Experimental design. We performed single cell gene expression analyses on 472 cells isolated from needle biopsies of 5 primary human melanomas, 4 superficial spreading and one acral melanoma. The expression of MITF-high and MITF-low signature genes was assessed and compared to investigate intra and inter-tumoural heterogeneity and correlated gene expression profiles. Results. Single cell gene expression analyses revealed varying degrees of intra and inter-tumour heterogeneity conferred by the variable expression of distinct sets of genes in different tumours. Expression of MITF partially correlated with that of its known target genes while SOX10 expression correlated best with PAX3 and ZEB2. Nevertheless, cells simultaneously expressing MITF-high and MITF-low signature genes were observed both by single cell analyses and RNAscope. Conclusions. Single cell analyses can be performed on limiting numbers of cells from primary human melanomas revealing their heterogeneity. While tumours comprised variable proportions of cells with the MITF-high and MITF-low gene expression signatures characteristic of melanoma cultures, primary tumours also comprised cells expressing markers of both signatures defining a novel cell state in tumours in vivo.

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Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40

Purpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.

Experimental Design: We utilized an anti-PD-1–refractory, orthotopically transplanted MMTV-PyMT mammary cancer model to investigate the antitumor effect of an agonist anti-OX40 antibody combined with anti-PD-1. As PD-1 naturally aids in immune contraction after T-cell activation, we treated mice with concurrent combination treatment versus sequentially administering anti-OX40 followed by anti-PD-1.

Results: The concurrent addition of anti-PD-1 significantly attenuated the therapeutic effect of anti-OX40 alone. Combination-treated mice had considerable increases in type I and type II serum cytokines and significantly augmented expression of inhibitory receptors or exhaustion markers CTLA-4 and TIM-3 on T cells. Combination treatment increased intratumoral CD4⁺ T-cell proliferation at day 13, but at day 19, both CD4⁺ and CD8⁺ T-cell proliferation was significantly reduced compared with untreated mice. In two tumor models, sequential combination of anti-OX40 followed by anti-PD-1 (but not the reverse order) resulted in significant increases in therapeutic efficacy. Against MMTV-PyMT tumors, sequential combination was dependent on both CD4⁺ and CD8⁺ T cells and completely regressed tumors in approximately 30% of treated animals.

Conclusions: These results highlight the importance of timing for optimized therapeutic effect with combination immunotherapies and suggest the testing of sequencing in combination immunotherapy clinical trials. Clin Cancer Res; 1–13. ©2017 AACR.

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Predictors of post-colonoscopy emergency department use

Unplanned hospital visits within 7 days of colonoscopy was recently proposed as a quality measure. It is unknown if patient, procedure, or endoscopist characteristics predict post-colonoscopy emergency department (ED) visits. Our aim was to determine the incidence and relatedness of ED visits within 7 days of colonoscopy, and to identify predictors of post-colonoscopy ED use.

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A Prospective Comparison of Live and Video-Based Assessments of Colonoscopy Performance

Colonoscopy performance is typically assessed by a supervisor in the clinical setting. There are limitations of this approach, however, as it allows for rater bias and increases supervisor workload demand during the procedure. Video-based assessment of recorded procedures has been proposed as a complementary means by which to assess colonoscopy performance. This study sought to investigate the reliability, validity and feasibility of video-based assessments of competence in performing colonoscopy, compared with live assessment.

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Success rates and complications of autologous onlay bone grafts and sinus lifts in patients with congenital hypodontia and after trauma

Autogenous bone remains the gold standard for augmentation of the alveolar ridge in congenital hypodontia and appreciable post-traumatic deformity. This generally reflects the volume of material required for such defects and the osteogenic potential of the grafts. Morbidity at the donor site and success rates may lead to autogenous grafts being superseded by xenografts or alloplastic materials in the future, but we know of little evidence to confirm this. All patients having augmentation of the alveolar ridge or sinus lift to enable subsequent placement of implants between 01 January 2009 and 31 December 2016 were identified from a prospectively-gathered database held at the Queen Elizabeth Hospital, Birmingham.

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Emergency consultation for epistaxis: A bad predictor for overall health?

To compare the mortality rate of a large epistaxis cohort with the fatalities of the general Swiss population and to evaluate significant risk factors for impending early death.

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Long-term voice outcome after thyroidectomy using energy based devices

Voice dysfunction is frequently reported after thyroidectomy even in absence of vocal fold paralysis. The energy-based devices such as Harmonic scalpel (HS) or LigaSure (LS) are commonly used in conventional thyroidectomy. The objective of this study was to investigate the long-term voice outcome after total thyroidectomy using energy based devices.

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An Algorithm for Sellar Reconstruction Following the Endoscopic Endonasal Approach: A Review of 300 Consecutive Cases

J Neurol Surg B
DOI: 10.1055/s-0037-1606293

Objectives/Hypotheses The endoscopic endonasal approach (EEA) is the workhorse endoscopic procedure for sellar and parasellar pathology. Various reconstruction techniques have been reported following EEA surgery, ranging from no reconstruction to vascularized flaps. We review our institution's experience with sellar reconstruction following EEA and propose an evidence-based algorithm. Design Retrospective review. Setting Tertiary academic medical center. Participants Patients who underwent endoscopic EEA surgery for sellar or parasellar pathology between March 1, 2013 and August 31, 2016. Main Outcome Measures Patient demographic and clinicopathologic data were collected. Outcome measures included intraoperative and postoperative cerebrospinal fluid (CSF) leak rates and extent of resection (gross or subtotal). Results Three hundred consecutive patients were included. Depending on the presence and grade of intraoperative CSF leak, cases were reconstructed using either a free mucosal graft (FMG) or nasoseptal flap (NSF). Intraoperative and postoperative CSF leak rates were 30.7% and 2.3%, respectively. Multivariable logistic regression found that intraoperative CSF leak was associated with recurrent disease (odds ratio [OR] 2.47, p = 0.004), with no apparent predictors of postoperative CSF leak. Conclusions Based on this large series, we propose the following algorithm for sellar reconstruction: FMG for no CSF leak; fat graft + FMG ± rigid fixation for low-grade leaks; and fat graft + NSF ± rigid fixation for high-grade leaks.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Esthesioneuroblastoma and Olfactory Preservation: Is it Reasonable to Attempt Smell Preservation?

J Neurol Surg B
DOI: 10.1055/s-0037-1606307

Objective Olfactory preservation after resection of esthesioneuroblastoma (ENB) has been reported, however, the ability to predict tumor involvement of the olfactory system is critical to this surgical strategy. This study aims to answer the question: Can a surgeon predict, based on preoperative imaging, whether there is unilateral involvement of the olfactory system allowing for safe attempt of olfactory preservation? Methods This is a retrospective review of post-resection ENB meeting inclusion criteria of having bilateral olfactory tracts and bulbs submitted at the time of primary resection for pathologic margins. Five board-certified skull base surgeons blinded to the pathology individually reviewed the preoperative MRI scans to predict degree of tumor involvement. Results Olfactory bulb involvement occurred in both bulbs in 35% of cases and unilateral in 39% of cases, and there was no involvement in 26% of cases sampled. When comparing physician prediction of involved tracts or bulbs, involvement was appropriate or over-called (i.e., called positive when pathology was in fact negative) in 96% of cases. Conclusion This study demonstrates unilateral or no pathologic olfactory involvement of the olfactory system in 65% of cases. Our ability to predict this involvement, which may allow for a management strategy that attempts to preserve olfactory function, was accurate at 96%. Therefore, interpretation of imaging and proceeding with smell preservation in ENB appears reasonable in this cohort.Level of Evidence: Level 2b.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Surgical Anatomy of the Orbit in Human Cadavers–An Endoscopic Pictorial Documentation

J Neurol Surg B
DOI: 10.1055/s-0037-1606294

Background The aim of our study was a pictorial documentation of the anatomical structures of the orbit. Methods We performed a transmaxillary endoscopic approach in nine formalin-fixed human heads. We identified and documented the anatomy of the inferior part of the orbit. Results The first intraorbital anatomical landmark was the inferior rectus muscle, from which important structures medially and laterally could be identified. Anatomical structures and their relation to each other were documented and presented as illustrative figures. Conclusion Knowledge of the topographic anatomy of the inferior part of the orbit could be sufficiently imparted by our illustrations. The presented transmaxillary approach allowed a wide overview of the anatomical structures located in the inferior part of the orbit. Our pictorial documentation may provide neurosurgeons more safety and the opportunity to become familiar with the endoscopic anatomy.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Very Low Prevalence of Intracranial Hypertension in Trigonocephaly

No abstract available

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Risk Factor Analysis for Capsular Contracture, Malposition, and Late Seroma in Subjects Receiving Natrelle 410 Form-Stable Silicone Breast Implants

No abstract available

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Prepectoral Breast Reconstruction: A Safe Alternative to Submuscular Prosthetic Reconstruction following Nipple-Sparing Mastectomy

Background: Nipple-sparing mastectomy with immediate prosthetic reconstruction is routinely performed because of excellent aesthetic results and safe oncologic outcomes. Typically, subpectoral expanders are placed, but in select patients, this can lead to significant postoperative pain and animation deformity, caused by pectoralis major muscle disinsertion and stretch. Prepectoral reconstruction is a technique that eliminates dissection of the pectoralis major by placing the prosthesis completely above the muscle with complete acellular dermal matrix coverage. Methods: A single surgeon's experience with immediate prosthetic reconstruction following nipple-sparing mastectomy from 2012 to 2016 was reviewed. Patient demographics, adjuvant treatment, length and characteristics of the expansion, and incidence of complications during the tissue expander stage were compared between the partial submuscular/partial acellular dermal matrix (dual-plane) cohort and the prepectoral cohort. Results: Fifty-one patients (84 breasts) underwent immediate prepectoral tissue expander placement, compared with 115 patients (186 breasts) undergoing immediate partial submuscular expander placement. The groups had similar comorbidities and postoperative radiation exposure. There was no significant difference in overall complication rate between the two groups (17.9 percent versus 18.8 percent; p = 0.49). Conclusions: Prepectoral breast reconstruction provides a safe and effective alternative to partial submuscular reconstruction, that yields comparable aesthetic results with less operative morbidity. In the authors' experience, the incidence of acute and chronic postoperative pain and animation deformity is significantly lower following prepectoral breast reconstruction. This technique is now considered for all patients who are safe oncologic candidates and are undergoing nipple-sparing mastectomy and prosthetic reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

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Disclosure of Financial Conflicts of Interest in Plastic and Reconstructive Surgery

Background: Recent articles in the scientific literature have expressed concerns about financial conflicts of interest in the profession of medicine in general and the specialty of plastic surgery in particular. Disclosure of financial ties to industry has been regarded as an address of a possible bias. The policies of medical journals places responsibility on authors for self-reporting of financial conflicts of interest, yet underreporting of conflicts of interest has occurred. The investigative hypothesis was that authors in the plastic surgery literature, in particular, Plastic and Reconstructive Surgery, underreported financial conflicts of interest. Methods: A review of articles published in Plastic and Reconstructive Surgery from July of 2015 through April of 2016 for author disclosures was accomplished. The disclosure statements were compared to the information available in the Open Payments database for 2015. The lack of disclosure on the part of an author, when present, was individually examined for relevance of the corporate conflicts of interest to the subject matter of the involved article. Results: A total of 302 articles authored by 1262 individuals were reviewed. One hundred thirty-nine (45.5 percent) had neither a disclosed nor an actual conflict of interest. In 61 articles (20.2 percent), one or more authors disclosed; 105 articles (34.8 percent) did not provide disclosure of a financial conflict of interest. In assessment of relevance, 10 undisclosed conflicts of interest (9.5 percent) were determined relevant, and one-third of that total were non–plastic surgeons. Conclusion: Nondisclosure of financial conflicts of interest is common, but only a small minority pose a potential for harm from bias.

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Discussion: Prepectoral Breast Reconstruction: A Safe Alternative to Submuscular Prosthetic Reconstruction following Nipple-Sparing Mastectomy

No abstract available

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Psychological Outcomes of Labiaplasty: A Prospective Study

No abstract available

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Treating Breast Conservation Therapy Defects with Brava and Fat Grafting: Technique, Outcomes, and Safety Profile

Background: Fat grafting has been demonstrated as a means of reconstructing breast conservation therapy defects. However, there is continued uncertainty regarding its clinical efficacy and oncologic safety. Furthermore, the role of external preexpansion (i.e., with the Brava device) remains unclear in this setting. The purpose of this study was to examine the safety and clinical outcomes of Brava/fat grafting following breast conservation therapy. Methods: A retrospective chart review was performed on all patients undergoing fat grafting following breast conservation therapy. Complications were defined as either a clinically palpable oil cyst/area of fat necrosis or infection. The mean time of follow-up was 2.3 years. Results: A total of 27 fat grafting sessions were performed on 20 patients, with an overall complication rate of 25 percent. The mean interval from completion of radiation therapy to fat grafting was 7 years and was not a significant predictor for complications (p = 0.46). Among those who underwent repeated grafting, there was no difference in the complication rates between their first and second encounters (p = 0.56). There was no difference in complication rates between patients with Brava preexpansion and those without preexpansion. Patients undergoing Brava preexpansion had a significantly higher initial fill volume in comparison with those who did not (219 cc versus 51 cc; p = 0.0017). There were no cases of locoregional cancer recurrence following fat grafting. Conclusion: Brava preexpansion was associated with higher initial fill volume in the setting of breast conservation therapy defects.

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Macrotextured Breast Implants with Defined Steps to Minimize Bacterial Contamination around the Device: Experience in 42,000 Implants

Background: Bacteria/biofilm on breast implant surfaces has been implicated in capsular contracture and breast implant–associated anaplastic large-cell lymphoma (ALCL). Macrotextured breast implants have been shown to harbor more bacteria than smooth or microtextured implants. Recent reports also suggest that macrotextured implants are associated with a significantly higher incidence of breast implant–associated ALCL. Using techniques to reduce the number of bacteria around implants, specifically, the 14-point plan, has successfully minimized the occurrence of capsular contracture. The authors hypothesize that a similar effect may be seen in reducing the risk of breast implant–associated ALCL. Methods: Pooled data from eight plastic surgeons assessed the use of macrotextured breast implants (Biocell and polyurethane) and known cases of breast implant–associated ALCL. Surgeon adherence to the 14-point plan was also analyzed. Results: A total of 42,035 Biocell implants were placed in 21,650 patients; mean follow-up was 11.7 years (range, 1 to 14 years). A total of 704 polyurethane implants were used, with a mean follow-up of 8.0 years (range, 1 to 20 years). The overall capsular contracture rate was 2.2 percent. There were no cases of implant–associated ALCL. All surgeons routinely performed all 13 perioperative components of the 14-point plan; two surgeons do not routinely prescribe prophylaxis for subsequent unrelated procedures. Conclusions: Mounting evidence implicates the role of a sustained T-cell response to implant bacteria/biofilm in the development of breast implant–associated ALCL. Using the principles of the 14-point plan to minimize bacterial load at the time of surgery, the development and subsequent sequelae of capsular contracture and breast implant–associated ALCL may be reduced, especially with higher-risk macrotextured implants. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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Determining the Oncologic Safety of Autologous Fat Grafting as a Reconstructive Modality: An Institutional Review of Breast Cancer Recurrence Rates and Surgical Outcomes

Background: The increasing use of autologous fat grafting in breast cancer patients has raised concerns regarding its oncologic safety. This study evaluated patient outcomes and tumor recurrence following mastectomy reconstruction and autologous fat grafting. Methods: Retrospective chart review identified patients who underwent mastectomy followed by breast reconstruction from 2010 to 2015. Eight hundred twenty-nine breasts met inclusion criteria: 248 (30.0 percent) underwent autologous fat grafting, whereas 581 (70.0 percent) breasts did not. Patient demographics, cancer characteristics, oncologic treatment, surgical treatment, surgical complications, local recurrence, and distant metastases were analyzed. Results: Autologous fat grafting patients and control patients were of similar body mass index, smoking status, and BRCA status. Patients who underwent fat grafting were significantly younger than control patients and were less likely to have diabetes, hypertension, or hyperlipidemia. The two groups represented similar distributions of BRCA status, Oncotype scores, and hormone receptor status. Patients underwent one to four grafting procedures: one procedure in 83.1 percent, two procedures in 13.7 percent, three in 2.8 percent, and four in 0.4 percent. Mean follow-up time from initial surgery was 45.6 months in the fat grafting group and 38.8 months in controls. The overall complication rate following fat grafting was 9.4 percent. Among breasts undergoing surgery for therapeutic indications, there were similar rates of local recurrence (fat grafting group, 2.5 percent; controls, 1.9 percent; p = 0.747). Interestingly, mean time to recurrence was significantly longer in the fat grafting group (52.3 months versus 22.8 months from initial surgery; p = 0.016). Conclusions: Autologous fat grafting is a powerful tool in breast reconstruction. This large, single-institution study provides valuable evidence-based support for its oncologic safety. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

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Breast Cancer Molecular Subtypes and Chemotherapy Schedules Used in Neoadjuvant or Adjuvant Setting May Show Different Effects in Nipple-Sparing Mastectomy

No abstract available

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Prophylactic Nipple-Sparing Mastectomy and Direct-to-Implant Reconstruction of the Large and Ptotic Breast: Is Preshaping of the Challenging Breast a Key to Success?

Background: Nipple-sparing mastectomy with simultaneous hammock technique direct-to-implant reconstruction is increasingly offered to patients opting for risk-reducing mastectomy. Despite this promising method, patients with macromastia and ptotic breasts remain a challenging group to treat satisfactorily and more often end up undergoing a difficult corrective procedure and experience an unacceptably high rate of failed reconstruction. The authors examined whether targeted preshaping mastopexy/reduction could prepare these patients for a successful nipple-sparing mastectomy/direct-to-implant reconstruction. Methods: Patients seeking risk-reducing nipple-sparing mastectomy/direct-to-implant reconstruction at the authors' institutions deemed unfit for a one-stage procedure based on their previous experience were offered a targeted two-stage, risk-reducing mastopexy/reduction followed by a delayed secondary nipple-sparing mastectomy and direct-to-implant reconstruction. Patients were followed up at 3 weeks and 6 or 12 months. Results: Forty-four reconstructions were performed in 22 patients aged 43 years (range, 26 to 57 years). All 44 procedures were completed successfully without any failure or nipple-areola complex losses. Patients' median body mass index was 30 kg/m2 (range, 22 to 44 kg/m2). Six patients were smokers and one had hypertension. Two patients underwent reoperation because of hematoma and fat necrosis. Conclusions: The authors' results demonstrate that a targeted preshaping mastopexy/reduction followed by nipple-sparing mastectomy/direct-to-implant reconstruction can be safely planned in women who opt for a risk-reducing mastectomy and can be performed successfully with a 3- to 4-month time span between operations. On the basis of these results and the superior cosmetic outcome, the two-stage approach has become the authors' standard of care in all such settings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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Revision Buttock Implantation: Indications, Procedures, and Recommendations

No abstract available

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Breast Cancer Genetics for Plastic Surgeons

Summary: Multidisciplinary genetic clinics offer counseling and testing to those who meet criteria for familial breast cancer, and plastic surgeons become integral to this process when risk-reducing surgery and postmastectomy reconstruction are deemed appropriate. As reconstructive surgeons, it is important that plastic surgeons are aware of the risks and issues associated with the genetic variants that cause patients to present for prophylactic or therapeutic surgery.

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Comparison of Endothelial Differentiation Capacities of Human and Rat Adipose-Derived Stem Cells

No abstract available

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Free Diced Cartilage: A New Application of Diced Cartilage Grafts in Primary and Secondary Rhinoplasty

Background: Irregularities or deformities of the nasal dorsum after hump reduction account for a significant number of revision rhinoplasties. The authors therefore developed a technique of meticulously dicing and exactly placing free diced cartilage grafts, harvested from septum, rib, or ear cartilage. The cartilage paste is used for smoothening, augmentation, or camouflaging of the nasal dorsum in primary or revision rhinoplasties. Methods: A retrospective analysis of multisurgeon consecutive open approach rhinoplasties from January to December of 2014 was conducted at a single center. The authors compared the outcome of three different techniques to augment or cover the nasal dorsum after an observation period of 7 months. In group I, 325 patients with free diced cartilage grafts as the only onlay were included. In group II, consisting of 73 patients, the dorsal onlay was either fascia alone or in combination with free diced cartilage grafts. Forty-eight patients in group III received a dorsal augmentation with the classic diced cartilage in fascia technique. Results: Four hundred forty-six patients undergoing primary and secondary rhinoplasties in which one of the above-mentioned diced cartilage techniques was used were included in the study. The authors found revision rates for dorsal irregularities within the 7-month postoperative observation period of 5.2, 8.2, and 25 percent for groups I, II, and III, respectively. Conclusion: The authors' findings strongly support their clinical experience that the free diced cartilage graft technique presents an effective and easily reproducible method for camouflage and augmentation in aesthetic and reconstructive rhinoplasty.

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A Safe and Inexpensive Technique for Turbinate Cauterization Surgery

No abstract available

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Discussion: Free Diced Cartilage: A New Application of Diced Cartilage Grafts in Primary and Secondary Rhinoplasty

No abstract available

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Introducing the International Confederation of Plastic Surgery Societies: ICOPLAST

Summary: This article describes the formation of the International Confederation of Plastic Surgery Societies (ICOPLAST) as a novel, transparent, dynamic, and proactive confederation of national plastic surgery societies. ICOPLAST aspires to provide a voice for the entire international community of plastic surgeons. ICOPLAST has been designed to benefit the patient, plastic surgery as a profession, and each individual plastic surgeon. Its principal objective is to enhance international communication, education, and advocacy processes to ultimately improve patient outcomes for plastic surgery patients globally. The new ICOPLAST's focus is to add true value for patients. ICOPLAST's evolution, philosophy, governance, and bylaws are explained and all societies worldwide are encouraged and cordially invited to join. An open and warm invitation is provided. Additional information is found at www.ICOPLAST.org .

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Facial Assessment and Injection Guide for Botulinum Toxin and Injectable Hyaluronic Acid Fillers: Focus on the Lower Face

Summary: This third article of a three-part series addresses techniques and recommendations for aesthetic treatment of the lower face. The lower face is considered an advanced area for facial aesthetic treatment. In this region, soft-tissue fillers play a more important role than neuromodulators and should be used first to provide structure and support before neuromodulators are considered for treatment of dynamic lines. Treatment of the lip, perioral region, and chin, in addition to maintaining balance of the lower face with the face overall, is challenging. Procedures on the lip should avoid overcorrection while respecting the projection of the lips on the profile view and the ratio of lip size to chin. The chin is often neglected, but reshaping the jawline can provide dramatic improvement in facial aesthetics. Both profile and anterior views are critical in assessment and treatment of the lower face. Finally, rejuvenation of the neck region requires fillers for structural support of the chin and jawline and neuromodulators for treatment of the masseter and platysma.

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Aesthetic Facial Reconstruction after Mohs Surgery

No abstract available

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Temporal Response of Angiogenesis and Hypertrophy to Resistance Training in Young Men.

While endurance exercise training promotes angiogenesis and improves metabolic health, the effect of resistance training on this process is less well defined. We hypothesised that capillarization would increase proportionally, and concurrently, with muscle fiber hypertrophy in response to resistance training in young men. Methods: In this double blind, randomized control trial, 36 males (22 +/- 1 y) were randomized to placebo or protein supplementation, and participated in 12-wk of resistance training. Skeletal muscle biopsies were collected prior to, and following 2, 4, 8, and 12-wk of training. Immunohistochemistry assessed fiber-type specific size and capillarization. Western blot and RT-PCR assessed proteins involved in the molecular regulation of angiogenesis. Results: Resistance training effectively increased type I (15 +/- 4%; P

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Implementing Resistance Training in Secondary Schools: A Cluster RCT.

Purpose: Guidelines recommend that young people engage in muscle-strengthening activities on at least three days per week. The purpose of this study was to examine the impact of a school-based intervention focused on resistance training (RT) for adolescents. Methods: The 'Resistance Training for Teens' intervention was evaluated using a cluster randomized controlled trial with 607 adolescents (50.1% female; 14.1+/-0.5 years) from 16 secondary schools. Teachers were trained to deliver the intervention, which included: (i) an interactive student seminar; (ii) a structured physical activity program, focused on RT; (iii) lunchtime fitness sessions; and, (iv) web-based smartphone apps. The primary outcome was muscular fitness (MF) and secondary outcomes included body mass index (BMI), RT skill competency, flexibility, physical activity, self-efficacy and motivation. Assessments were conducted at baseline, 6- (post-program; primary end-point) and 12-months (follow-up). Outcomes were assessed using linear mixed models, with three potential moderators tested using interaction terms (and sub-group analyses where appropriate). Results: For the primary outcome (MF), a group-by-time effect was observed at 6-months for upper body (2.0 repetitions, 95% confidence interval [CI]: 0.8 to 3.2), but not lower body (-1.4cm, 95% CI: -4.7 to 1.9). At 6-months, there were intervention effects for RT skill competency and self-efficacy, but no other secondary outcomes. Effects for upper body MF and RT skill competency were sustained at 12-months. Despite overall no effect for BMI, there was a group-by-time effect at 12-months among students who were overweight/obese at baseline (-0.55 kg/m2, 95% CI: -1.01 to -0.08). Conclusions: The school-based RT intervention resulted in immediate and sustained improvements in upper body MF and RT skill competency, demonstrating an effective and scalable approach to delivering RT within secondary schools. (C) 2017 American College of Sports Medicine

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Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins.

Introduction: Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested physical exercise could bring beneficial effect on alleviating neuropathic pain. Yet the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NTs), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting following nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NTs expression. Methods: We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. Following TNT surgery, rats were performed swimming exercise for 5 weeks. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expression in peripheral neuroma, dorsal root ganglion (DRG) and spinal cord were measured using ELISA and western blotting. Results: TNT led to neuroma formation, induced neuroma pain and mechanical allodynia in hind paw. 5-week swimming exercise inhibited neuroma formation, relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least one week, even the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, DRG and spinal cord to different extents. Swimming also decreased the elevation of NTs expression. Conclusions: Swimming exercise not only inhibits neuroma formation induced by nerve transection, but also relieves pain behavior. These effects might be associated with the modulation of NTs. 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. (C) 2017 American College of Sports Medicine

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Feedback Leads to Better Exercise Quality in Adolescents with Patellofemoral Pain.

Purpose: Adolescents with patellofemoral pain (PFP) do not comply with their exercise prescription, performing too few and too fast repetitions, compromising recovery. We investigated if real-time feedback on contraction time would improve the ability of adolescents with PFP to perform exercises as prescribed. Methods: A randomised, controlled, participant-blinded, superiority trial with a 6-week intervention of three weekly sessions of three elastic band exercises was undertaken. Forty 15 to 19-year-old adolescents with PFP were randomised to real-time BandCizer(TM)-iPad feedback on contraction time or not by a physiotherapist. The primary outcome was the mean deviation from the prescribed contraction time of 8 seconds per repetition. Secondary outcomes included isometric hip and knee strength, Kujala Patellofemoral Scale and Global Rating of Change. Results: The mean deviation from prescribed 8 seconds per repetition contraction time was 1.5s (+/-0.5) for the feedback group, compared to 4.3s (+/-1.0) for the control group (mean difference: 2.7s (95% CI: 2.2-3.2, P

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Direct-Acting Antiviral Therapy and Improvement in Graft Survival of Hepatitis C Liver Transplant Recipients.

No abstract available

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Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia.

Background: The diagnostic yield for cytomegalovirus (CMV) PCR viral load in Bronchoalveolar Lavage (BAL) or in plasma to diagnose CMV pneumonia in lung transplant recipients remains uncertain, and was investigated in a large cohort of consecutive lung transplant recipients. Methods: Bronchoscopies within the first year of lung transplantation with CMV detectable in BAL by PCR (ie, viral load >=273 IU/mL) were included (66 recipients; 145 bronchoscopies); at each bronchoscopy episode 2 independent experts reviewed clinical and laboratory information to determine whether the patient at that time fulfilled the criteria for CMV pneumonia per current international recommendations. Corresponding plasma CMV PCR viral load determined at time of the bronchoscopy (n=126) was also studied. Optimal CMV PCR viral load cut off for CMV pneumonia diagnosis was determined using receiver operating characteristics (ROC). Results: CMV was detected in BAL with CMV PCR in 145 episodes, and 34 (23%) of these episodes fulfilled the criteria for CMV pneumonia. The AUC-ROC for CMV in BAL was 90% at the optimum cut off (4545 IU/mL) with a corresponding sensitivity of 91% and specificity of 77% (in plasma the corresponding values were 274 IU/mL, 63% and 76%, respectively). Conclusions: CMV PCR viral load in BAL had a high performance to diagnose CMV pneumonia in lung transplant recipients; plasma CMV viral load did not reliably aid as a diagnostic tool. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Improved Outcomes of Kidney Transplantation in Infants (Age < 2 years): A Single Center Experience.

Background: Infants (age

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Sofosbuvir-based Regimens in HIV/HCV Coinfected Patients after Liver Transplantation: Results from the ANRS CO23 CUPILT Study.

Background: A recurrence of hepatitis C virus after liver transplantation affects survival in HIV/HCV coinfected patients. This study assessed the efficacy and safety of sofosbuvir-based regimens in HIV/HCV coinfected patients following liver transplantation. Methods: 29 HIV/HCV coinfected transplanted patients receiving tacrolimus, cyclosporine or everolimus-based immunosuppressive therapy were enrolled in the CUPILT cohort. Their antiviral treatment combined sofosbuvir, daclatasvir with or without ribavirin (n=10/n=6), or sofosbuvir, ledipasvir with or without ribavirin (n=2/n=11). Results: The median delay between liver transplantation and treatment initiation was 37.5 months (IQR 14.4-99.2). The breakdown of HCV genotypes was: G1: 22 patients (75.9%), G3: 3 patients (10.3%) and G4: 4 patients (13.8%). The treatment indications were HCV recurrence (>= F1 n=23) or fibrosing cholestatic hepatitis (n=6). Before starting sofosbuvir, the HCV viral load and CD4 count were 6.7 log10 IU/mL (IQR 5.9-7.2), and 342 cells/mm3 (IQR 172-483), respectively. At W4, the HCV viral load was

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Swine Leukocyte Antigen (SLA) Class II is a Xenoantigen.

Background: Over 130 000 patients in the United States alone need a life-saving organ transplant. Genetically modified porcine organs could resolve the donor organ shortage, but human xenoreactive antibodies destroy pig cells and are the major barrier to clinical application of xenotransplantation. The objective of this study was to determine whether waitlisted patients possess preformed antibodies to swine leukocyte antigen (SLA) class II, homologs of the class II human leukocyte antigens (HLA). Methods: Sera from people currently awaiting solid organ transplant were tested for IgG binding to class II SLA proteins when expressed on mammalian cells. Pig fibroblasts were made positive by transfection with the class II transactivator (CIITA). As a second expression system, transgenes encoding the alpha and beta chains of class II SLA were transfected into Human embryonic kidney (HEK293) cells. Results: Human sera containing IgG specific for class II HLA molecules exhibited greater binding to class II SLA positive cells than to SLA negative cells. Sera lacking antibodies against class II HLA showed no change in binding regardless of the presence of class II SLA. These antibodies could recognize either SLA-DR or SLA-DQ complexes. Conclusions: Class II SLA proteins may behave as xenoantigens for people with humoral immunity towards class II HLA molecules. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Localizing the Lost Rectus Muscle Using the Connective Tissue Framework: Revisiting the Tunnel Technique.

Purpose: To describe a technique for localizing a lost rectus muscle during strabismus or retinal surgery or following trauma. Methods: In this single center, retrospective chart review, 5 patients were identified between January 2012 and June 2016 with a lost rectus muscle; 3 during strabismus surgery and 2 post trauma. The inclusion criteria included a lost rectus muscle during strabismus surgery, or a disinserted/lacerated rectus muscle following ocular/orbital trauma. The primary outcome measure was successful reattachment of the rectus muscle. Results: The lost rectus muscle was identified in each patient and reattached to the globe by gently applying traction anteriorly at the conjunctiva/Tenon edge using double-pronged skin hooks and following the path of the rectus muscle through its Tenon capsule tunnel where it remained attached by suspensory ligaments. There was no instance where orbital fat was obscuring or blocking the view of the lost rectus muscles. There were no other complications associated with the procedure. Conclusions: The authors describe a simple and effective method in 5 patients to localize a lost rectus muscle based on knowledge of the orbital connective tissue framework. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Localizing the Lost Rectus Muscle Using the Connective Tissue Framework: Revisiting the Tunnel Technique.

No abstract available

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Durability of Protection Afforded by Fewer Doses of the HPV16/18 Vaccine: The CVT Trial

Abstract

Background: Previously, we demonstrated similar human papillomavirus (HPV)16/18 vaccine efficacy estimates and stable HPV16/18 antibody levels four years postvaccination in a nonrandomized analysis of women who received a varying number of doses of the bivalent HPV16/18 vaccine. Here we extend data to seven years following initial vaccination.Methods: We evaluated HPV16/18-vaccinated women who received one (n = 134), two (n_0/1 = 193, n_0/6 = 79), or three doses (n = 2043) to a median of 6.9 years postvaccination. Cervical HPV DNA was measured with the SPF10- DEIA-LiPA PCR system; HPV16/18-specific antibody levels were measured using enzyme-linked immunosorbent assays (n = 486). Infection and immunological measures were compared across vaccine dose groups. Prevalent HPV infection at year 7 was also compared with an unvaccinated control group (UCG). All statistical tests were two-sided.Results: Among women in the three-dose, two-dose_0/6, two-dose_0/1, and one-dose groups, cumulative incident HPV16/18 infection rates (No. of events/No. of individuals) were 4.3% (88/2036, 95% confidence interval [CI] = 3.5% to 5.3%), 3.8% (3/78, 95% CI = 1.0% to 10.1%), 3.6% (7/192, 95% CI = 1.6% to 7.1%), and 1.5% (2/133, 95% CI = 0.3% to 4.9%; P = 1.00, .85, .17 comparing the two-dose_0/6, two-dose_0/1, and one-dose groups to the three-dose group, respectively). The prevalence of other carcinogenic and noncarcinogenic HPV types, excluding HPV16/18/31/33/45, were high and not statistically different among all dose groups, indicating that the low incidence of HPV16/18 in the one- and two-dose groups was not due to lack of exposure. At seven years, 100% of participants in all dose groups remained HPV16 and HPV18 seropositive. A non–statistically significant decrease in the geometric mean of the HPV16 antibody levels between years 4 and 7 was observed among women in the three-dose group: –10.8% (95% CI = –25.3% to 6.6%); two-dose (0/6 months) group: –17.3% (95% CI = –39.3% to 12.8%), two-dose (0/1 month) group: –6.9% (95% CI = –22.1% to 11.2%), and one-dose group: –5.5% (95% CI = –29.7% to 27.0%); results were similar for HPV18.Conclusions: At an average of seven years of follow-up, we observed similar low rates of HPV16/18 infections and slight, if any, decreases in HPV16/18 antibody levels by dose group.

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Growth-induced stress enhances epithelial-mesenchymal transition induced by IL-6 in clear cell renal cell carcinoma via the Akt/GSK-3β/β-catenin signaling pathway

Growth-induced stress enhances epithelial-mesenchymal transition induced by IL-6 in clear cell renal cell carcinoma via the Akt/GSK-3β/β-catenin signaling pathway

Oncogenesis 6, e375 (August 2017). doi:10.1038/oncsis.2017.74

Authors: Q Chen, D Yang, H Zong, L Zhu, L Wang, X Wang, X Zhu, X Song & J Wang

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E6/E7 oncogenes in epithelial suprabasal layers and estradiol promote cervical growth and ear regeneration

E6/E7 oncogenes in epithelial suprabasal layers and estradiol promote cervical growth and ear regeneration

Oncogenesis 6, e374 (August 2017). doi:10.1038/oncsis.2017.73

Authors: C García, D Hernández-García, C Valencia, V Rojo-León, J-R Pérez-Estrada, M Werner & L Covarrubias

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Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers

Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers

Oncogenesis 6, e373 (August 2017). doi:10.1038/oncsis.2017.72

Authors: T Avril, E Vauléon & E Chevet

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Buccal Fat Pad: An Effective Option for Facial Reconstruction and Aesthetic Augmentation

Abstract

Introduction

Autogenous grafting with lipoaspirate and dermo-fat grafting are popular techniques employed by plastic surgeons for correcting small volume facial defects and contour deformities. These techniques however present certain disadvantages. In this article, we present the use of the buccal fat pad graft as an alternative method of correcting such facial deformities.

Patients and Methods

Free buccal fat pad grafting was carried out in 15 patients in our institution. All were harvested using an intraoral approach. The buccal fat pad graft was used to correct periorbital contour depressions, nasal tip deformities, as a camouflage graft over exposed silicon nasal implants and as a filler in the depression deformity after mass excision.

Results

All 15 patients demonstrated good contour deformity correction without a significant graft resorption up to 3 years of follow-up. There were no donor site complications. The amount used ranged from 1 to 5 cc in volume as a spacer or barrier for the moderate-sized volume defect or depression, even though more than 5 cc of fat graft could be harvested if required.

Conclusion

In conclusion, the buccal fat pad graft represents an easy, expedient and exceptional tool for the correction of contour deformities, volume replacement or for aesthetic augmentation.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

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The application of information theory for the estimation of old-age multimorbidity

Abstract

Elderly patients are commonly characterized by the presence of several chronic aging-related diseases at once, or old-age "multimorbidity," with critical implications for diagnosis and therapy. However, at the present there is no agreed or formal method to diagnose or even define "multimorbidity." There is also no formal quantitative method to evaluate the effects of individual or combined diagnostic parameters and therapeutic interventions on multimorbidity. The present work outlines a methodology to provide such a measurement and definition, using information theoretical measure of normalized mutual information. A cohort of geriatric patients, suffering from several age-related diseases (multimorbidity), including ischemic heart disease, COPD, and dementia, were evaluated by a variety of diagnostic parameters, including static as well as dynamic biochemical, functional-behavioral, immunological, and hematological parameters. Multimorbidity was formally coded and measured as a composite of several chronic age-related diseases. The normalized mutual information allowed establishing the exact informative value of particular parameters and their combinations about the multimorbidity value. With the currently intensifying attempts to reduce aging-related multimorbidity by therapeutic interventions into its underlying aging processes, the proposed method may outline a valuable direction toward the formal indication and evidence-based evaluation of effectiveness of such interventions.

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Buccal Fat Pad: An Effective Option for Facial Reconstruction and Aesthetic Augmentation

Abstract

Introduction

Autogenous grafting with lipoaspirate and dermo-fat grafting are popular techniques employed by plastic surgeons for correcting small volume facial defects and contour deformities. These techniques however present certain disadvantages. In this article, we present the use of the buccal fat pad graft as an alternative method of correcting such facial deformities.

Patients and Methods

Free buccal fat pad grafting was carried out in 15 patients in our institution. All were harvested using an intraoral approach. The buccal fat pad graft was used to correct periorbital contour depressions, nasal tip deformities, as a camouflage graft over exposed silicon nasal implants and as a filler in the depression deformity after mass excision.

Results

All 15 patients demonstrated good contour deformity correction without a significant graft resorption up to 3 years of follow-up. There were no donor site complications. The amount used ranged from 1 to 5 cc in volume as a spacer or barrier for the moderate-sized volume defect or depression, even though more than 5 cc of fat graft could be harvested if required.

Conclusion

In conclusion, the buccal fat pad graft represents an easy, expedient and exceptional tool for the correction of contour deformities, volume replacement or for aesthetic augmentation.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

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S197 Foramen ovale electrodes in epilepsy

Temporal lobe epilepsy is the most prevalent type of epileptic syndrome, and also the most frequent type of surgically treatable epilepsy. But in many cases the laterality is difficult to prove based on non-invasive investigations and scalp EEG. There is broad evidence that suggest that the seizure onset zone may be on the opposite side compared to where the seizure is seen on the scalp EEG due to rapid spread to the contralateral side.Based on these data a technique was developed first by Wieser et al., which allowed direct corticographic recordings from the medial temporal structures without performing invasive surgery.

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O207 Safety and effects on motor cortex excitability of five closely repeated cathodal transcranial direct current stimulations

To assess safety and effects of five cathodal-tDCS (charge density 342,857C/m2) delivered at increasing time intervals in 25h.

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P226 The effect of interstimulus interval between the conditioning and test stimulus on inhibition and fascilitation: A transcranial magnetic stimulation study

Transcranial magnetic stimulation (TMS) technique creates small and temporary electrical current on cerebral cortex via a strong magnetic field. Previous studies investigating the cortical excitability using paired pulse stimulation technique have implemented a suprathreshold test stimulus (TS) conditioned by subthreshold stimulus (CS). If interstimulus interval (ISI) between CS and TS is 1–6ms, motor evoked potential (MEP) amplitude will decrease and it is called short interval intracortical inhibition (SICI).

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P380 Intelligence is predicted by single-vs-double-sensory brain responses

This research investigated the association between intelligence test scores and gamma-range steady-state power-responses (SS-PR) to an auditory, a visual, and a combined audiovisual stimulation. We hypothesized, and established empirically, that the difference in SS-PR from the mono-modal to the bimodal stimulation (P) is associated with intelligence.

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P222 Diagnostic and therapeutic possibilities of transcranial magnetic stimulation in patients after traumatic brain injury

Recovery of both mental and motor functions is one of the key problems of neurorehabilitation of patients with traumatic brain injury (TBI), accompanied by posttraumatic unconsciousness state (PUS). The purpose of pilot study is to clarify the diagnostic and therapeutic potential of TMS in patients after TBI with impaired motor activity and consciousness.

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Target objects defined by a conjunction of colour and shape can be selected independently and in parallel

Abstract

It is generally assumed that during search for targets defined by a feature conjunction, attention is allocated sequentially to individual objects. We tested this hypothesis by tracking the time course of attentional processing biases with the N2pc component in tasks where observers searched for two targets defined by a colour/shape conjunction. In Experiment 1, two displays presented in rapid succession (100 ms or 10 ms SOA) each contained a target and a colour-matching or shape-matching distractor on opposite sides. Target objects in both displays elicited N2pc components of similar size that overlapped in time when the SOA was 10 ms, suggesting that attention was allocated in parallel to both targets. Analogous results were found in Experiment 2, where targets and partially matching distractors were both accompanied by an object without target-matching features. Colour-matching and shape-matching distractors also elicited N2pc components, and the target N2pc was initially identical to the sum of the two distractor N2pcs, suggesting that the initial phase of attentional object selection was guided independently by feature templates for target colour and shape. Beyond 230 ms after display onset, the target N2pc became superadditive, indicating that attentional selection processes now started to be sensitive to the presence of feature conjunctions. Results show that independent attentional selection processes can be activated in parallel by two target objects in situations where these objects are defined by a feature conjunction.

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Two kinds of bias in visual comparison illustrate the role of location and holistic/analytic processing differences

Abstract

A number of studies have shown that two stimuli appearing successively at the same spatial location are more likely to be perceived as the same, even though location is irrelevant to the task. This bias to respond "same" when stimuli are at the same location is termed spatial congruency bias. The experiments reported here demonstrate that the spatial congruency bias extends to letter strings: Participants tend to respond "same" when comparing two strings appearing successively at the same location. This bias may arise because successive stimuli at the same location are more likely to be perceived as a single object. Bias is also affected by the nature of the comparison task. We show that if letters must be compared individually (analytical comparison), there is a bias to respond "different," but if letter strings are compared as unified wholes (holistic comparison), there is no bias or a bias to respond "same." This analytical bias is apparently separate from the spatial congruency bias. It appears whether the task requires localization of differences between strings, or counting the number of differences, or ignoring differences in some parts of the stimuli while attending to others. All of these analytical comparison tasks require that letters be selected individually, and the analytical bias may reflect difficulty in preventing interference from neighboring letters in this selection process. Each type of bias reflects a different aspect of visual processing, and both can be measured to probe how processing changes across different tasks.

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Two New Therapies Approved for Acute Myeloid Leukemia

FDA has approved two new treatments for some adult patients with acute myeloid leukemia (AML): enasidenib (Idhifa®), which targets the IDH2 protein; and liposomal cytarabine-daunorubicin CPX-351 (Vyxeos®), a two-drug chemotherapy combination encapsulated in liposomes.

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Determination of Follicular Localization in Human Ovarian Cortex for Vitrification

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Atrial fibrillation and FLAIR/T2 white matter hyperintensities on MRI

Atrial fibrillation (AF) related embolism does not contribute to leukoaraiosis but AF-related perfusion changes might, by aggravating chronic microangiopathic ischemia.

White matter disease, also termed leukoaraiosis, is an established marker of cerebral small vessel disease load in older adults and it is an important predictor of incident stroke, cognitive impairment and poor outcomes after a stroke.1 First defined as periventricular hypodense regions on CT scans, research on white matter disease blossomed with frequent use of T2/fluid-attenuated inversion recovery (FLAIR) MRI sequences that are a lot more sensitive to show such chronic microangiopathic damage as hyperintense white matter regions, hence the term white matter hyperintensities (WMHs). When mapped using three-dimensional volumetric methods, the bulk of WMH is in the periventricular regions so voxel-based comparisons in different types of cerebral small vessel disease did not show significant topographic differences.1 A recent study introduced a number of visually identified WMH patterns...

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Impact of sleep-related symptoms on clinical motor subtypes and disability in Parkinsons disease: a multicentre cross-sectional study

Objectives

To investigate the impact of sleep disturbances on Parkinson's disease (PD) clinical motor subtypes and disease-related disability in a multicentre setting.

Methods

We report a cross-sectional relationship between sleep-related symptoms and clinical motor subtypes (tremor dominant (TD); intermediate; postural instability and gait disturbances (PIGDs)) identified in a multicentre study, including 436 patients with PD and 401 age-matched controls. PD-related sleep problems (PD-SP), excessive daytime sleepiness (EDS) and probable REM sleep behaviour disorder (pRBD) were evaluated using the PD sleep scale (PDSS)-2, Epworth Sleepiness Scale (ESS) and RBD screening questionnaire-Japanese version (RBDSQ-J), respectively.

Results

PD-SP (PDSS-2 ≥18; 35.1% vs 7.0%), EDS (ESS ≥10; 37.8% vs 15.5%) and pRBD (RBDSQ-J ≥5; 35.1% vs 7.7%) were more common in patients with PD than in controls. The prevalence of restless legs syndrome did not differ between patients with PD and controls (3.4% vs 2.7%). After adjusting for age, sex, disease duration and Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) part III score, the PIGD group had higher PDSS-2 and ESS scores than the TD group. The RBDSQ-J scores did not differ among the TD, intermediate and PIGD groups. A stepwise regression model predicting the MDS-UPDRS part II score identified the Hoehn and Yahr stage, followed by the number of sleep-related symptoms (PD-SP, EDS and pRBD), disease duration, MDS-UPDRS part III score, PIGD subtype, depression and MDS-UPDRS part IV score as significant predictors.

Conclusion

Our study found a significant relationship between sleep disturbances and clinical motor subtypes. An increased number of sleep-related symptoms had an impact on disease-related disability.

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Retraction

Sato Y, Manabe S, Kuno H, et al. Amelioration of osteopenia and hypovitaminosis D by 1α-hydroxyvitamin D3 in elderly patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 1999;66:64–68.

This article has been retracted. The editor received a letter from Dr Yoshihiro Sato retracting this article and two others also published in Journal of Neurology Neurosurgery and Psychiatry. Dr Sato states the reason for retraction as 'due to scientific misconduct. All co-authors did not participate study design, data collection, data analysis, interpretation of data and drafting manuscripts in these 3 articles. Thus, all co-authors are honorary.'

Despite repeated requests for further explanation, we have not received any response from Dr Sato's institution.

It was brought to our attention that several other journals have retracted articles by Dr Sato. Neurology published an article 'Systematic review and statistical analysis of the integrity of 33 randomized controlled trials' by Boland et al1 indicating that the data...

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Retraction

Sato Y, Iwamoto J, Honda Y. Once-weekly risedronate for prevention of hip fracture in women with Parkinson's disease: a randomised controlled trial. J Neurol Neurosurg Psychiatry 2011;82:1390–1393.

This article has been retracted. The editor received a letter from Dr Yoshihiro Sato retracting this article and two others also published in Journal of Neurology Neurosurgery and Psychiatry. Dr Sato states the reason for retraction as 'due to scientific misconduct. All co-authors did not participate study design, data collection, data analysis, interpretation of data and drafting manuscripts in these 3 articles. Thus, all co-authors are honorary.'

Despite repeated requests for further explanation, we have not received any response from Dr Sato's institution.

It was brought to our attention that several other journals have retracted articles by Dr Sato. Neurology published an article 'Systematic review and statistical analysis of the integrity of 33 randomized controlled trials' by Boland et al1 indicating that the data...

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Retraction

Sato Y, Asoh T, Metoki N, et al. Efficacy of methylprednisolone pulse therapy on neuroleptic malignant syndrome in Parkinson's disease. J Neurol Neurosurg Psychiatry 2003;74:574–576.

This article has been retracted. The editor received a letter from Dr Yoshihiro Sato retracting this article and two others also published in Journal of Neurology Neurosurgery and Psychiatry. Dr Sato states the reason for retraction as 'due to scientific misconduct. All co-authors did not participate study design, data collection, data analysis, interpretation of data and drafting manuscripts in these 3 articles. Thus, all co-authors are honorary.'

Despite repeated requests for further explanation, we have not received any response from Dr Sato's institution.

It was brought to our attention that several other journals have retracted articles by Dr Sato. Neurology published an article 'Systematic review and statistical analysis of the integrity of 33 randomized controlled trials' by Boland et al1 indicating that the data in those trials were...

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Funktionelle Genomik des Ewing‑Sarkoms

Zusammenfassung

Ewing-Sarkome sind hochaggressive Knochen- bzw. Weichgewebstumoren des Kindes- und Jugendalters und neigen zur frühen Metastasierung. Konventionelle multimodale Therapiestrategien sind mit hoher akuter und chronischer Toxizität verbunden, weshalb schonendere und effektivere Therapieoptionen dringend notwendig sind. Ewing-Sarkome sind durch spezifische EWSR1-ETS-Fusionsonkogene charakterisiert, die sich selbst aufgrund ihrer geringen Immunogenität und der ubiquitäreren Expression der Fusionspartner nur schlecht als Zielstrukturen für eine gerichtete Therapie eignen. Durch funktionelle Genomik konnten mehrere EWSR1-ETS-Zielgene, die kaum im Normalgewebe exprimiert und deshalb als mögliche Surrogatzielstrukturen für eine spezifische (Immun‑)Therapie infrage kommen, charakterisiert werden. Des Weiteren lieferten Studien aus der funktionellen Genomik erste mechanistische Erklärungsansätze für die relative hohe Inzidenz von Ewing-Sarkomen bei Europäern und sondierten das Potenzial von freier zirkulierender DNA (cfDNA) und/oder exosomaler mRNA der EWSR-ETS-Fusionsonkogene als Minimal-residual-disease-Marker. Dieser Übersichtsartikel fasst wesentliche Beiträge zu diesen Aspekten zusammen und gibt einen Ausblick auf deren medizinische Relevanz.

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How to Enjoy a Holiday Weekend

With Labor Day right around the corner, many of us may be planning some much-needed time away from the office. Are you able to truly relax and leave work behind when you are on vacation? Not everyone is able to stop thinking about work when they are not in the office. If this sounds like you, you may want to check out Art Markman's Harvard Business Review article titled "How to Forget About Work When You're Not Working."

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Therapeutic effect of cisplatin administered with a lymphatic drug delivery system on false-negative metastatic lymph nodes

Abstract

Systemic administration of drugs into the blood circulation is a standard treatment for the prevention of metastasis. However, systemic delivery cannot maintain sufficiently high concentrations of anticancer drugs in lymphatic nodes (LNs). Here, we show that administering cisplatin (CDDP) using a lymphatic drug delivery system (LDDS) has the potential to treat false-negative metastatic LNs. We found that in MXH10/Mo-lpr/lpr mice, which develop systemic swelling of LNs up to 10 mm in diameter, the accumulation of indocyanine green (ICG, which has a similar molecular weight to CDDP) in a target LN was greater for lymphatic delivery of ICG than for systemic (intravenous) administration. Furthermore, CDDP administration with a LDDS inhibited tumor growth in false-negative metastatic LNs and produced fewer adverse effects than systemically administered CDDP. We anticipate that drug delivery using a LDDS will, in time, replace systemic chemotherapy for the treatment of false-negative metastatic LNs.

This article is protected by copyright. All rights reserved.

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Mild Traumatic Brain Injury Reduces Spine Density of Projection Neurons in the Medial Prefrontal Cortex and Impairs Extinction of Contextual Fear Memory

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


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Mild Traumatic Brain Injury Reduces Spine Density of Projection Neurons in the Medial Prefrontal Cortex and Impairs Extinction of Contextual Fear Memory

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


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"Asian Pac J Cancer Prev"[jour]; +42 new citations

42 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Asian Pac J Cancer Prev"[jour]

These pubmed results were generated on 2017/08/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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The prevalence of congenital C1 arch anomalies

Abstract

Purpose

To determine the prevalence, radiographic features and reporting rate of, and the association between the congenital anterior and posterior C1 arch anomalies.

Methods

The computed tomography (CT) images of the cervical spines of all patients over 18 years who had CT examinations in our hospital during the study period were reviewed to evaluate for congenital anomalies of the anterior and posterior C1 arches. Radiology reports of the corresponding CT examinations were reviewed to determine the reporting rate of these defects.

Results

Of 3273 subjects, 185 (5.65%) had congenital atlas anomalies: 169 isolated posterior (5.16%), 15 combined anterior and posterior (bipartite, 0.46%), and one isolated anterior (0.031%) arch defects. Females had a higher prevalence than males (7.46 versus 4.72%, P = 0.0013). Eighty-three cases (44.9%) of C1 arch anomalies were not reported. The Currarino type A, B, C and E posterior arch defects accounted for 81.6, 8.1, 1.1, and 0.5% of all arch anomalies while type D was not observed. Fifteen patients (0.46%) had combined anterior and posterior arch anomalies (bipartite atlas) versus only one with an isolated anterior C1 defect, indicating a significant association between the anterior and posterior arch defects (P < 0.0001).

Conclusions

Although some types of congenital C1 arch anomalies are rare, type A defects are relatively common radiological findings that are unreported approximately 45% of the time. Based on the significant association between the anterior and posterior arch defects, we propose possible mechanisms for the formation of the bipartite atlas.

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Age-related histologic and biochemical changes in auricular and septal cartilage

Objectives/Hypothesis

To characterize the histologic and biochemical properties of auricular and septal cartilage and analyze age-related changes in middle-aged to older adults.

Study Design

Cross-sectional study of auricular and septal cartilage from 33 fresh cadavers.

Methods

Auricular and septal cartilage specimens were stained using Safranin O for glycosaminoglycans, Verhoeff's stain for elastin, and Masson's trichrome for collagen. Percentage of tissue stained, cell density and size were quantified. Relationships between donor characteristics and histologic properties were evaluated using mixed model analyses.

Results

The average donor age was 75 years (standard deviation = 11 years; range, 55–93 years). In auricular cartilage, each 1-year increase in age was associated with a 0.97% decrease in glycosaminoglycans (P < .001) and a 0.98% decrease in elastin (P < .001). In septal cartilage, glycosaminoglycans decreased 2.4% per year (P < .001). Age did not affect collagen content significantly in auricular (P = .417) or septal cartilage (P = .284). Cell density and cell size declined with age in auricular (both P < .001) and septal cartilage (P = .044, P = .032, respectively). Compared to septal cartilage in patients of all ages, auricular cartilage had more glycosaminoglycans, less collagen, higher cell density, and smaller cells.

Conclusions

In auricular and septal cartilage, glycosaminoglycans, elastin, cell density, and cell size decrease significantly with age in patients over 55 years of age. Glycosaminoglycan content declines faster with age in septal cartilage than auricular cartilage. These age-related changes may affect biomechanical properties and tissue viability, and thereby have implications for graft choice in functional, aesthetic, and reconstructive nasal surgery.

Level of Evidence

NA Laryngoscope, 2017

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A retrospective study of amrubicin monotherapy for the treatment of relapsed small cell lung cancer in elderly patients

Abstract

Purpose

Amrubicin is one of the most active chemotherapeutic drugs for small cell lung cancer (SCLC). Previous studies reported its effectiveness and severe hematological toxicity. However, the efficacy of amrubicin monotherapy in elderly patients with SCLC has not been described. The objective of this study was to investigate the feasibility of amrubicin monotherapy in elderly patients and its efficacy for relapsed SCLC.

Methods

A retrospective cohort study design was used. We retrospectively evaluated the clinical effects and adverse events of amrubicin treatment in elderly (≥70 years) SCLC patients with relapsed SCLC.

Results

Between November 2003 and September 2015, 86 patients (aged ≥70 years) received amrubicin monotherapy for relapsed SCLC at four institutions. There were 42 cases of sensitive relapse (S) and 44 of refractory relapse (R). S cases with median age of 75 years (range 70–85 years) and R cases with median age of 74 years (range 70–84 years) were included in our analysis. The median number of treatment cycles was three (range 1–9), and the response rate was 33.7% (40.5% in the S and 27.2% in the R cases). Median progression-free survival time was 4.0 months in the S and 2.7 months in the R patients (p = 0.013). Median survival time from the start of amrubicin therapy was 7.6 months in the S and 5.5 months in the R cases (p = 0.26). The frequencies of grade ≥3 hematological toxicities were as follows: leukopenia, 60.4%; neutropenia, 74.4%; anemia, 11.6%; thrombocytopenia, 16.2%; and febrile neutropenia, 17.4%. Treatment-related death was observed in one patient.

Conclusion

Although hematological toxicities, particularly neutropenia, were severe, amrubicin showed favorable efficacy, not only in the S but also in the R cases, as shown in previous studies. Amrubicin could be a preferable standard treatment in elderly patients with relapsed SCLC. These results warrant further evaluation of amrubicin in elderly patients with relapsed SCLC by a prospective trial.

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Survival data for postoperative adjuvant chemotherapy comprising cisplatin plus vinorelbine after complete resection of non-small cell lung cancer

Abstract

Purpose

Despite the efficacy of postoperative adjuvant cisplatin (CDDP)-based chemotherapy for patients who have undergone surgical resection of non-small cell lung cancer (NSCLC), few reports have presented survival data for Asian patients treated with adjuvant chemotherapy involving a combination of CDDP and vinorelbine (VNR). This study was performed to evaluate the survival of patients with NSCLC who received postoperative adjuvant chemotherapy comprising CDDP + VNR.

Methods

We retrospectively evaluated patients with NSCLC who received adjuvant chemotherapy comprising CDDP + VNR at the Shizuoka Cancer Center between February 2006 and October 2011.

Results

One hundred patients who underwent surgical resection of NSCLC were included in this study. The patients' characteristics were as follows: median age 63 years (range 36–74 years), female 34%, never-smokers 20%, and non-squamous NSCLC 73%. Pathological stages IIA, IIB, and IIIA were observed in 31, 22, and 47% of patients, respectively. The 5- and 2-year overall survival rates were 73 and 93%, respectively. The 5- and 2-year relapse-free survival rates were 53 and 62%, respectively. Univariate analysis of prognostic factors showed that patient characteristics (sex, histology, and pathological stage) and CDDP dose intensity were not significantly associated with survival. In 48 patients who developed NSCLC recurrence, the 5-year survival rate after recurrence was 29%, and the median survival time after recurrence was 37 months.

Conclusions

Our results suggest that the prognosis after surgical resection of NSCLC and adjuvant chemotherapy comprising CDDP + VNR might be improving compared with previous survival data of adjuvant chemotherapy for NSCLC.

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sIL-24 peptide, a human interleukin-24 isoform, induces mitochondrial-mediated apoptosis in human cancer cells

Abstract

Purpose

Interleukin-24 (IL-24) is a unique cytokine in the IL-10 family that reveals tumor-suppressive activity against a broad range of cancers. Alternative splicing of human IL-24 generates several isoforms with different pro-apoptotic activities. In the current study, we aimed to investigate the cytotoxic properties of a recombinant smallest isoform of IL-24 (sIL-24) and the underlying molecular mechanisms in PC-3, A549, U937, and Raji cancer cells as well as normal cell line MRC-5.

Methods

Following treatment of the cells with recombinant sIL-24 peptide and full-length IL-24 protein, cytotoxicity was determined by MTT assay. Apoptosis induction was evaluated using annexin-V/PI double staining flow cytometry and Hoechst 33342 staining. The expression of Bax, Bcl-2, cytochrome c, and caspase-3 was analyzed by Western blotting.

Results

MTT assay exhibited that sIL-24 dose and time dependently inhibited the proliferation of IL-24 receptor-positive PC-3, U937, and Raji cells more effectively than full-length IL-24. In contrast, sIL-24 had little cytotoxic effect on A549 cells lacking the IL-24 receptor, or on MRC-5 normal cells. Flow cytometric analysis and morphological observation revealed an efficient apoptosis induction in the receptor-positive cells. Furthermore, Western blot assay demonstrated that cell death induced by sIL-24 was associated with upregulation of the Bax/Bcl-2 ratio, cytochrome c release, and the expression of cleaved caspase-3, suggesting that sIL-24 induced apoptosis mainly through the mitochondrial pathway. Notably, among the tested cells, induction of apoptosis was more significant in PC-3 cells.

Conclusion

Our results suggest that the sIL-24 peptide is a promising candidate for potential treatment of human cancers.

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Impact of age on intermittent hypoxia in obstructive sleep apnea: a propensity-matched analysis

Abstract

Purpose

To determine independent relationship of aging with chronic intermittent hypoxia, we compared hypoxia-related polysomnographic variables of geriatric patients (aged ≥ 65 years) with an apnea–hypopnea index (AHI)-, gender-, body mass index (BMI)-, and neck circumference-matched cohort of non-geriatric patients.

Methods

The study was conducted using clinical and polysomnographic data of 1280 consecutive patients who underwent complete polysomnographic evaluation for suspected sleep-disordered breathing (SDB) at a single sleep disorder center. A propensity score-matched analysis was performed to obtain matched cohorts of geriatric and non-geriatric patients, which resulted in successful matching of 168 patients from each group.

Results

Study groups were comparable for gender (P = 0.999), BMI (P = 0.940), neck circumference (P = 0.969), AHI (P = 0.935), and severity of SDB (P = 0.089). The oximetric variables representing the duration of chronic intermittent hypoxia such as mean (P = 0.001), the longest (P = 0.001) and total apnea durations (P = 0.003), mean (P = 0.001) and the longest hypopnea durations (P = 0.001), and total sleep time with oxygen saturation below 90% (P = 0.008) were significantly higher in the geriatric patients as compared with younger adults. Geriatric patients had significantly lower minimum (P = 0.013) and mean oxygen saturation (P = 0.001) than non-geriatric patients.

Conclusions

The study provides evidence that elderly patients exhibit more severe and deeper nocturnal intermittent hypoxia than the younger adults, independent of severity of obstructive sleep apnea, BMI, gender, and neck circumference. Hypoxia-related polysomnographic variables in geriatric patients may in fact reflect a physiological aging process rather than the severity of a SDB.

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Editorial

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Trends in restorative composites research: what is in the future?

Abstract Clinical trials have identified secondary caries and bulk fracture as the main causes for composite restoration failure. As a measure to avoid frequent reinterventions for restoration replacement, composites with some sort of defense mechanism against biofilm formation and demineralization, as well as materials with lower susceptibility to crack propagation are necessary. Also, the restorative procedure with composites are very time-consuming and technically demanding, particularly concerning the application of the adhesive system. Therefore, together with bulk-fill composites, self-adhesive restorative composites could reduce operator error and chairside time. This literature review describes the current stage of development of remineralizing, antibacterial and self-healing composites. Also, an overview of the research on fiber-reinforced composites and self-adhesive composites, both introduced for clinical use in recent years, is presented.

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Should my composite restorations last forever? Why are they failing?

Abstract Composites resins have become the first choice for direct anterior and posterior restorations. The great popularity is related to their esthetic appearance and reduced need of sound tissue removal as compared with former treatments. Several studies have demonstrated that composite restorations may last long in clinical service. In this review we discuss the factors playing a role on the long-term longevity. Composite restorations have demonstrated a good clinical performance with annual failure rates varying from 1% to 3% in posterior teeth and 1% to 5% in anterior teeth. Factors related to the patients such as caries risk and occlusal stress risk, in addition to socioeconomic factors, may affect the survival significantly. Characteristics of the clinical operators, particularly their decision making when it comes to observing or approaching an existing restoration, are decisive for longevity. Cavity features such as the number of restored walls, composite volume, and presence of endodontic treatment are of major importance and may dictate the service time of the restorative approach. The choice of restorative composite seems to have a minor effect on longevity provided that appropriate technical procedures are used. The main reasons for failure in posterior teeth are secondary caries and fracture (restoration or tooth/restoration), while in anterior teeth esthetic concerns are the main reasons leading to restoration failures. Composite resin restorations can be considered a reliable treatment as long as both the professional and the patient are aware of the factors involved in restoration failures.

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Bonding efficiency and durability: current possibilities

Abstract Bonding plays a major role in dentistry nowadays. Dental adhesives are used in association with composites to solve many restorative issues. However, the wide variety of bonding agents currently available makes it difficult for clinicians to choose the best alternative in terms of material and technique, especially when different clinical situations are considered. Moreover, although bonding agents allow for a more conservative restorative approach, achieving a durable adhesive interface remains a matter of concern, and this mainly due to degradation of the bonding complex in the challenging oral environment. This review aims to present strategies that are being used or those still in development which may help to prevent degradation. It is fundamental that professionals are aware of these strategies to counteract degradation as much as possible. None of them are efficient to completely solve this problem, but they certainly represent reasonable alternatives to increase the lifetime of adhesive restorations.

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Dental ceramics: a review of new materials and processing methods

Abstract The evolution of computerized systems for the production of dental restorations associated to the development of novel microstructures for ceramic materials has caused an important change in the clinical workflow for dentists and technicians, as well as in the treatment options offered to patients. New microstructures have also been developed by the industry in order to offer ceramic and composite materials with optimized properties, i.e., good mechanical properties, appropriate wear behavior and acceptable aesthetic characteristics. The objective of this literature review is to discuss the main advantages and disadvantages of the new ceramic systems and processing methods. The manuscript is divided in five parts: I) monolithic zirconia restorations; II) multilayered dental prostheses; III) new glass-ceramics; IV) polymer infiltrated ceramics; and V) novel processing technologies. Dental ceramics and processing technologies have evolved significantly in the past ten years, with most of the evolution being related to new microstructures and CAD-CAM methods. In addition, a trend towards the use of monolithic restorations has changed the way clinicians produce all-ceramic dental prostheses, since the more aesthetic multilayered restorations unfortunately are more prone to chipping or delamination. Composite materials processed via CAD-CAM have become an interesting option, as they have intermediate properties between ceramics and polymers and are more easily milled and polished.

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