Clinical predictors for satisfaction with incus vibroplasty: a preliminary study

Abstract

Objective

We aimed to evaluate the subjective satisfaction after incus vibroplasty and to determine predictive factors affecting patient satisfaction in sensorineural hearing loss.

Design

A retrospective review of audiological data and an additional survey about subjective satisfaction after surgery were performed in 14 patients who underwent incus vibroplasty surgery. A numeric rating scale reflecting the degree of satisfaction after incus vibroplasty, compared with experiences using a conventional hearing aid, was used. Patients who showed median or better satisfaction were deemed the highly satisfied (HS) group, and the others were deemed the less satisfied (LS) group. To find the predictive factors correlated with satisfaction for incus vibroplasty, comparative analysis between two groups was performed.

Results

We found that the numeric rating scale for satisfaction was variable, ranged from 0 to 10, and was negatively correlated with age at operation (p < 0.01). The HS group had a younger age (27.6 ± 22.2 years) and better preoperative air conduction threshold at 250 Hz (20.7 ± 7.9 dB) than the LS group (68.0 ± 9.7 years, 32.1 ± 10.7 dB). The LS group (13.6 ± 9.9 dB) showed a larger change of air–bone gap after surgery than the HS group (5.7 ± 6.7 dB) at 250 Hz (p = 0.12).

Conclusions

Age at operation and the preoperative air conduction threshold level at 250 Hz appear to be potential predictive factors for subjective satisfaction with incus vibroplasty. Furthermore, more conservative selection of candidates and caution during surgery, considering inevitable air–bone gap development postoperatively, may be necessary to achieve higher satisfaction for incus vibroplasty.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jfmEVz

Elevated parathyroid hormone levels after successful parathyroidectomy for primary hyperparathyroidism: a clinical review

Abstract

Introduction

Surgery for primary hyperparathyroidism (PHPT) is traditionally deemed to be successful if serum calcium levels return to normal 6 months after parathyroidectomy. Regular monitoring of serum calcium and parathyroid hormone (PTH) in the follow-up of patients after parathyroidectomy for PHPT has drawn attention to the presence of a normocalcemic group of patients with elevated PTH (NCePTH) during the post-operative period. The etiological factors and mechanisms underlying this condition, its consequences, and the possibility of treatment are the object of this study.

Materials and methods

We conducted an unlimited PubMed search updated on March 31, 2017, which yielded 1628 results. We selected 37 articles, 33 of which included cases of NCePTH in their series and 23 performed statistical studies to assess factors associated with NCePTH.

Results

The maximum mean prevalence of NCePTH in the various series was 23.5%, ranging from 3 to 46%. Many factors were associated with NCePTH. The most important were higher pre-operative PTH, low pre-operative 25 (OH) D3, lower pre-operative creatinine clearance and greater adenoma weight. The origin of NCePTH may be multifactorial, since several factors were implicated in the etiology. NCePTH does not seem to be related to an increase in PHPT recurrence, although this possibility should not be dismissed. Vitamin D deficiency should be corrected. Treatment with calcium supplements seems to be clearly beneficial.

Conclusion

The prevalence of NCePTH is high. The causes of secondary hyperparathyroidism should be investigated carefully. Patients require treatment and long-term follow-up.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BBGHEp

The role of body image concern, sexual body image, and sexual self-esteem in the happiness of women seeking rhinoplasty surgery

Abstract

Background

This study aims to investigate the role of body image concern, sexual body image, and sexual self-esteem in the happiness of women seeking rhinoplasty surgery.

Methods

This study had a descriptive correlational design. Cases were defined as subjects who presented to beauty centers in Tehran. A convenience sample of 65 women participated. Each woman completed Oxford Happiness Inventory (OHI), Body Image Concern Inventory (BICI), Body Exposure during Sexual Activities Questionnaire (BESAQ), and Sexual Self-Esteem Index for Woman-Short Form (SSEI-W-SF). The data were analyzed with Pearson correlation coefficient and stepwise regression.

Results

The results showed that that there is a significant relationship between happiness with body image concern, sexual body image, and sexual self-esteem of people seeking rhinoplasty surgery (P < 0.05). Body image concern and sexual body image could predict 23% of the variance of happiness (P < 0.05).

Conclusions

A lower rate of body image concern predicts higher happiness in women seeking rhinoplasty surgery.

Level of Evidence: Level IV, risk/prognostic study.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iRGYzi

Robotic assisted gait as a tool for rehabilitation of individuals with spinal cord injury: a systematic review

Spinal cord injury (SCI) is characterized by a total or partial deficit of sensory and motor pathways. Impairments of this injury compromise muscle recruitment and motor planning, thus reducing functional capa...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zMy1un

H3.3K27M Expression Combined with Trp53 Loss Induces High-Grade Glioma [Glioma]

In utero expression of H3.3^K27M with Trp53 loss in mice recapitulates human pediatric high-grade glioma.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AvNRed

Copanlisib Produces Prolonged Responses in Lymphoma [News in Brief]

A phase II trial of the pan-class I PI3K inhibitor copanlisib demonstrated that it induces objective responses in 59% of patients with relapsed or refractory indolent lymphoma. The responses lasted a median of 22.6 months. Although the drugs weren't compared head to head, researchers suspect that the side effects of copanlisib may be less severe than those of idelalisib, another PI3K inhibitor.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ApDJFA

BTSA1 Activates BAX to Promote Apoptosis in Acute Myeloid Leukemia [Leukemia]

The small-molecule BAX activator BTSA1 promotes apoptosis of AML cells in vitro and in vivo.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AvKWlE

Obinutuzumab Effective in Follicular Lymphoma, but at a Cost [News in Brief]

In a phase III trial involving more than 1,200 patients with follicular lymphoma, obinutuzumab plus chemotherapy reduced the risk of disease progression, relapse, or death by 34% compared with rituximab plus chemotherapy. However, patients receiving obinutuzumab experienced more serious side effects than those receiving rituximab.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ArtmRC

A Transposon Screen Identifies Loss of Primary Cilia as a Mechanism of Resistance to SMO Inhibitors [Research Articles]

Drug resistance poses a great challenge to targeted cancer therapies. In Hedgehog pathway–dependent cancers, the scope of mechanisms enabling resistance to SMO inhibitors is not known. Here, we performed a transposon mutagenesis screen in medulloblastoma and identified multiple modes of resistance. Surprisingly, mutations in ciliogenesis genes represent a frequent cause of resistance, and patient datasets indicate that cilia loss constitutes a clinically relevant category of resistance. Conventionally, primary cilia are thought to enable oncogenic Hedgehog signaling. Paradoxically, we find that cilia loss protects tumor cells from susceptibility to SMO inhibitors and maintains a "persister" state that depends on continuous low output of the Hedgehog program. Persister cells can serve as a reservoir for further tumor evolution, as additional alterations synergize with cilia loss to generate aggressive recurrent tumors. Together, our findings reveal patterns of resistance and provide mechanistic insights for the role of cilia in tumor evolution and drug resistance.

Significance: Using a transposon screen and clinical datasets, we identified mutations in ciliogenesis genes as a new class of resistance to SMO inhibitors. Mechanistically, cilia-mutant tumors can either grow slowly in a "persister" state or evolve and progress rapidly in an "aggressive" state. Cancer Discov; 7(12); 1436–49. ©2017 AACR.

See related commentary by Goranci-Buzhala et al., p. 1374.

This article is highlighted in the In This Issue feature, p. 1355

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AwNrUK

NIH Funds Pediatric Data Resource Center [News in Brief]

Children's Hospital of Philadelphia will lead a collaborative effort—funded with $14.8 million from the NIH—to pool genomic and phenotypic data from tens of thousands of patients to study the causes of pediatric cancer and structural birth defects.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AsnRT4

Identified Selective USP7 Inhibitors Compete with Ubiquitin Binding [Ubiquitination]

Specific USP7 inhibitors stabilized p53 and exhibited toxicity in tumor cells in vitro and in vivo.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AvDqHt

Trastuzumab Deruxtecan Is Safe and Active in HER2-Expressing Tumors [Clinical Trials]

Trastuzumab deruxtecan achieved responses in patients with breast, gastric, and gastroesophageal tumors.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Ar059H

Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax [Review]

Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax. We review a number of preclinical studies that have deepened our understanding of BCL2 biology and facilitated the clinical development of venetoclax.

Significance: Basic research into the pathways governing programmed cell death have paved the way for the discovery of apoptosis-inducing agents such as venetoclax, a BCL2-selective inhibitor that was recently approved by the FDA and the European Medicines Agency. Preclinical studies aimed at identifying BCL2-dependent tumor types have translated well into the clinic thus far and will likely continue to inform the clinical development of venetoclax and other BCL2 family inhibitors. Cancer Discov; 7(12); 1376–93. ©2017 AACR.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AvNT5P

BRCA1-BARD1 Activates RAD51 for DNA Repair by Homologous Recombination [DNA Repair]

BRCA1–BARD1 binds to RAD51 to enhance its activity in the promotion of homologous DNA pairing.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AsnRCy

FDA Disperses $22 Million for Rare Diseases [News in Brief]

The FDA has awarded 15 grants totaling $22 million over 4 years through its Orphan Products Clinical Trials Grant Program. One third of the awards will support ongoing clinical trials of therapies for rare cancers for which there are few approved or effective treatment options.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Avqj96

Nivolumab Induces Tumor Evolution in Patients with Melanoma [Immunotherapy]

Nivolumab treatment results in immunoediting and loss of tumor cells expressing neoantigens.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Art90M

Breast Cancer Cells Recycle Ammonia to Generate Amino Acids [Metabolism]

Ammonia generated from glutamate metabolism enhances the proliferation of breast cancer cells.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AvKYdg

Keap1 Loss Drives Kras-Mutant Lung Cancer and Glutaminolysis Dependency [Lung Cancer]

Loss of Keap1 hyperactivates NRF2 to induce glutaminolysis-dependent Kras-driven lung cancer.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AqlD6A

Adrenergic Nerves May Promote Angiogenesis in Prostate Cancer [Prostate Cancer]

Deleting Adrb2, encoding the β2-adrenergic receptor, in tumor endothelial cells suppresses angiogenesis.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AveJuC

Glucose Indirectly Fuels the TCA Cycle in Tumors via Lactate [Metabolism]

Circulating lactate derived from glucose is preferentially used as fuel for the TCA cycle over glucose.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Arshta

CNS Endothelial Cell Activation Emerges as a Driver of CAR T Cell-Associated Neurotoxicity [In the Spotlight]

Summary: Central nervous system (CNS) toxicity associated with chimeric antigen receptor–based therapeutics has emerged as a significant cause of morbidity and mortality, and insights into the pathophysiology of this syndrome have been lacking. A new study provides evidence that cytokine-induced CNS endothelial cell activation leading to disruption of the blood–brain barrier plays an early and critical role in this phenomenon. These insights provide new opportunities for targeted therapeutic interventions to modulate endothelial cell activation. Cancer Discov; 7(12); 1371–3. ©2017 AACR.

See related article by Gust et al., p. 1404.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AwJX4M

Lactate Fuels the TCA Cycle in Non-Small Cell Lung Cancer [Metabolism]

In many patients with NSCLC, lactate is a major fuel source for the tumor TCA cycle.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A5n0bZ

Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells [Research Articles]

Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor–modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19⁺ cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood–brain barrier (BBB) permeability. The permeable BBB failed to protect the cerebrospinal fluid from high concentrations of systemic cytokines, including IFN, which induced brain vascular pericyte stress and their secretion of endothelium-activating cytokines. Endothelial activation and multifocal vascular disruption were found in the brain of a patient with fatal neurotoxicity. Biomarkers of endothelial activation were higher before treatment in patients who subsequently developed grade ≥4 neurotoxicity.

Significance: We provide a detailed clinical, radiologic, and pathologic characterization of neurotoxicity after CD19 CAR-T cells, and identify risk factors for neurotoxicity. We show endothelial dysfunction and increased BBB permeability in neurotoxicity and find that patients with evidence of endothelial activation before lymphodepletion may be at increased risk of neurotoxicity. Cancer Discov; 7(12); 1404–19. ©2017 AACR.

See related commentary by Mackall and Miklos, p. 1371.

This article is highlighted in the In This Issue feature, p. 1355

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AXNyeX

SEMA3C Depletion Promotes Neuroblastoma Metastatic Dissemination [Neuroblastoma]

A neuroblastoma chick embryo xenograft model recapitulates tumor initiation and dissemination.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A6oxi0

Preservation Techniques in Fingertip Reconstruction

The authors discuss their experience using a composite tissue graft and volar V-Y advancement flap in fingertip reconstruction.
ePlasty, Open Access Journal of Plastic Surgery

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kmd72q

Is photobiomodulation (PBM) effective for the treatment of dentin hypersensitivity? A systematic review

Abstract

The present study aims to evaluate the current scientific data regarding the effectiveness of photobiomodulation (PBM) in the treatment of dentin hypersensitivity (DH) as an alternative method for pain control. A systematic review was conducted to assess the effectiveness of PBM as treatment for DH. A complete literature search was performed up to October 2016. Searches were conducted using Boolean operators and MeSH terms. References of all selected full-text articles and related reviews were scanned. A total of 280 articles were identified (241 articles were excluded by the title and abstract). Of the 39 articles selected for analysis, 36 were excluded because they presented one or more exclusion criteria. Therefore, three articles were qualified for inclusion in this systematic review. PBM may not lead to adverse effects provided that adequately controlled parameters are followed when treating DH. More consistent studies should be conducted in order to adequately observe the advantageous therapeutic effect of PBM.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AsLsme

Pharmacokinetics of recombinant asparaginase in children with acute lymphoblastic leukemia

Abstract

Purpose

The objective of this study was to assess the pharmacokinetics of recombinant asparaginase (rASNase, Spectrila^®) in children with acute lymphoblastic leukemia using a population pharmacokinetic approach in order to explore potential dosing recommendations.

Methods

Data on serum asparaginase activities of 124 children from three clinical studies were included in the analysis, covering an age range from 3 days to 17 years. Most patients received 5000 U/m² rASNase intravenously every 3 days. The non-linear mixed effects modelling software (NONMEM^®) was utilized to identify drivers of rASNase pharmacokinetics in children. Different dose adjustments were simulated for their ability to increase rASNase trough activities in children who do not reach the threshold of 100 U/L.

Results

A two-compartment model with allometric weight scaling (0.75 on clearance [CL] and inter-compartmental clearance [Q] and 1 on central [V ₁] and peripheral [V ₂] volume of distribution) was the best model to describe the pharmacokinetics of rASNase. PK parameters for the median child (19.5 kg) were: CL = 0.0592 L/h, V ₁ = 1.18 L, Q = 0.307 L/h, V ₂ = 0.316 L. Organ functions, such as liver or kidney function and laboratory values, such as fibrinogen or antithrombin III levels, showed no influence on rASNase pharmacokinetics. In simulations, changing the administration interval from 72 to 48 h was appropriate to maintain rASNase activities above the therapeutic threshold, in patients with activities below 100 U/L 72 h after the first dose.

Conclusions

Drug monitoring is recommended to identify patients with insufficient ASNase trough activities in serum and to modify the treatment schedule, if necessary. Shortening of the treatment interval might be preferable over increasing the rASNase dose.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jhelJ5

Clinical predictors of chronic rhinosinusitis: do the Canadian clinical practice guidelines for acute and chronic rhinosinusitis predict CT-confirmation of disease?

The diagnosis of chronic rhinosinusitis (CRS) based on clinical presentation alone remains challenging. To improve the accuracy of clinical diagnosis, the Canadian Rhinosinusitis Guidelines recommend the use o...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iORfwh

Salvage stereotactic radiosurgery for recurrent gliomas with prior radiation therapy

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zP8rFh

The effect of tumor-derived exosomes on immune regulation and cancer immunotherapy

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ntFPzB

The effect of prone and supine treatment positions for the pre-operative treatment of rectal cancer on organ-at-risk sparing and setup reproducibility using volumetric modulated arc therapy

To compare organ-at-risk doses and setup reproducibility using the prone and supine orientations in volumetric modulated arc therapy (VMAT) for rectal cancer.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jPGkyI

A 10-year clinical outcome of radiotherapy as an adjuvant or definitive treatment for primary tracheal adenoid cystic carcinoma

To evaluate the role of radiotherapy (RT) as an adjuvant or definitive treatment in primary tracheal adenoid cystic carcinoma (ACC) for local tumor control and survival.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2imuRGI

Spatially resolved and quantitative analysis of VISTA/PD-1H as a novel immunotherapy target in human non-small cell lung cancer

Purpose: Determine the localized expression pattern and clinical significance of VISTA/PD-1H in human NSCLC. Experimental Design: Using multiplex quantitative immunofluorescence (QIF), we performed localized measurements of VISTA, PD-1 and PD-L1 protein in 758 stage I-IV NSCLCs from 3 independent cohorts represented in tissue microarray format. The targets were selectively measured in cytokeratin+ tumor epithelial cells, CD3+ T-cells, CD4+ T-helper cells, CD8+ cytotoxic T-cells, CD20+ B-lymphocytes and CD68+ tumor-associated macrophages. We determined the association between the targets, clinico-pathological/molecular variables and survival. Genomic analyses of lung cancer cases from TCGA was also performed. Results: VISTA protein was detected in 99% of NSCLCs with a predominant membranous/cytoplasmic staining pattern. Expression in tumor and stromal cells was seen in 21% and 98% of cases, respectively. The levels of VISTA were positively associated with PD-L1, PD-1, CD8+ T-cells and CD68+ macrophages. VISTA expression was higher in T-lymphocytes than in macrophages; and in cytotoxic T-cells than in T-helper cells. Elevated VISTA was associated with absence of EGFR mutations and lower mutational burden in lung adenocarcinomas. Presence of VISTA in tumor compartment predicted longer 5-year survival. Conclusions: VISTA is frequently expressed in human NSCLC and shows association with increased TILs, PD-1 axis markers, specific genomic alterations and outcome. These results support the immuno-modulatory role of VISTA in human NSCLC and suggests its potential as therapeutic target.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jg1ab2

A First-in-Human Phase 1 Study of Subcutaneous Outpatient Recombinant Human IL-15 (rhIL-15) in Adults with Advanced Solid Tumors

Purpose: Preclinical data established Interleukin-15 as a homeostatic factor and powerful stimulator of NK and CD8+ T cell function, the basis for clinical testing. Experimental Design: A first-in-human outpatient phase I dose escalation trial of subcutaneous (SC) rhIL-15 was conducted in refractory solid tumor cancer patients. Therapy consisted of daily (Monday - Friday) SC injections of rhIL-15 for two consecutive weeks (10 total doses/cycle). Clinical response was assessed by RECIST. Pharmacokinetics of rhIL-15 and immune biomarkers were evaluated. Results: Nineteen patients were treated with rhIL-15 at dose levels of 0.25, 0.5, 1, 2 and 3 mcg/kg/day. Fourteen patients completed ≥ 2 cycles of therapy that was well tolerated. One serious adverse event (SAE), grade 2 pancreatitis, required overnight hospitalization. Enrollment was halted after a patient receiving 3 mcg/kg/day developed a dose limiting SAE of grade 3 cardiac chest pain associated with hypotension and increased troponin. No objective responses were observed; however, several patients had disease stabilization including a renal cell carcinoma patient who continued protocol treatment for 2 years. The treatment induced profound expansion of circulating NK cells, especially among the CD56bright subset. A proportional but less dramatic increase was found among circulating CD8+ T cells with maximal 3-fold expansion for the 2 and 3 mcg/kg patients.  Conclusions: SC rhIL-15 treatment was well tolerated, producing substantial increases in circulating NK and CD8+ T cells. This protocol establishes a safe outpatient SC rhIL-15 regimen of 2 mcg/kg/day dosing amenable to self-injection and with potential as a combination immunotherapeutic agent.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BzAGbq

NAMPT is a Potent Oncogene in Colon Cancer Progression that Modulates Cancer Stem Cell Properties and resistance to therapy through Sirt1 and PARP

Purpose: Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men worldwide. However, despite current progress, many patients with advanced and metastatic tumors still die from the malignancy. Refractory disease often relies on nicotinamide adenine dinucleotide(NAD)-dependent mechanisms. NAD metabolism and a stable NAD regeneration circuit are required to maintain tissue homeostasis and metabolism. However, high levels of NAD confer therapy resistance to tumors. Experimental Design: ectopic overexpression of nicotinamide phosphoribosil transferase (NAMPT) and shRNAs in CRC cell lines, Tumorigenic and stemness properties and transcription measurement in culture and in vivo. Transcriptional analisis in public databases. Therapeutic approaches.Results: NAMPT, the rate-limiting enzyme responsible for the highest source of physiological NAD biosynthesis, increases tumorigenic properties and induces cancer stem cell-like properties through pathways that control stem cell signaling, thus enriching the cancer-initiating cell (CIC) population. Furthermore, NAMPT expression correlated with high levels of CIC-like cells in colon tumors directly extracted from patients, and transcription meta-analysis revealed that NAMPT is also a key factor that induces cancer stem pathways in CRC tumors. This effect is mediated by PARP and SIRT1. Additionally, we report a novel NAMPT-driven signature that stratifies prognosis from high to low expression groups. The NAMPT signature contained SIRT1 and PARP1 levels as well as other CSC-related genes. Finally, NAMPT inhibition increased the sensitivity to apoptosis in both NAMPT-expressing cells and tumorspheres. Conclusions: NAMPT represents a novel therapeutic target in colon cancer progression and relapse, particularly the CIC subset of human colon cancers.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jhceVF

Lymph Node Metastases in Colon Cancer are Polyclonal

Purpose:  Recent studies have highlighted the existence of sub-clones in tumors. Lymph nodes are generally the first location of metastasis for most solid epithelial tumors including colorectal cancer (CRC). We sought to understand the genetic origin of lymph node metastasis in CRC by evaluating the relationship between CRC tumor sub-clones present in primary tumors and lymph nodes. Experimental Design:  A total of 33 samples from seven CRC's, including two or three spatially disparate regions from each primary tumor and one to four matched lymph nodes for each tumor, underwent next-generation whole-exome DNA sequencing, Affymetrix OncoScan SNP arrays, and targeted deep confirmatory sequencing. We performed mapping between SNPs and copy number events from the primary tumor and matched lymph node samples, allowing us to profile heterogeneity and the mutational origin of LN metastases. The computational method PyClone was used to define sub-clones within each tumor. The method Citup was subsequently used to infer phylogenetic relationships among sub-clones. Results:  We found there was substantial heterogeneity in mutations and copy number changes among all samples from any given patient. For each patient, the primary tumor regions and matched lymph node metastases were each polyclonal and the clonal populations differed from one lymph node to another. In some patients, the cancer cell populations in a given lymph node originated from multiple distinct regions of a tumor. Conclusions: Our data support a model of lymph node metastatic spread in colorectal cancer whereby metastases originate from multiple waves of seeding from the primary tumor over time.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BzgJRT

Multidisciplinary Approach to Vascular Anomalies Maximizes Outcomes

The birth of a child is a glorious and simultaneously nerve-wracking event in every family. If this is the 1 in 22 children born with a vascular lesion of the head and neck (which is visible in every picture and to every visitor), the parents' concerns multiply. Will my baby bleed? Will my baby stay deformed by this lesion? Is this the tip of the iceberg of other problems? Will my baby be forced to enter chronic medical/surgical care? These are some of the questions that race through the parents' brains, even as they marvel at the wondrousness of new life.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A50OPc

Subcutaneous granuloma annulare involving the scalp

Abstract

Subcutaneous granuloma annulare (SGA) is an uncommon subtype of granuloma annulare. There are few reports of this entity solely affecting the scalp. We report a case of biopsy-proven SGA in a 21-month-old boy with six asymptomatic, rock-hard scalp nodules.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nrbQIm

CME Accreditation Page

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AXbEqk

Psychosocial Impact of Vascular Anomalies on Children and Their Families

Vascular anomalies are divided into tumors and malformations based on their clinical and cytologic attributes. Vascular malformations are further subcategorized as low-flow lymphatic, venous, capillary, or mixed lesions and as high-flow arteriovenous malformations. Treatment is reserved for vascular anomalies that are symptomatic or cosmetically disfiguring, and surgical and nonsurgical treatment options are widely varied with variable outcomes.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A4Gld8

Forthcoming Issues

Otosclerosis and Stapes Surgery

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AXbxuU

Congenital Vascular Lesions of the Head and Neck

The number of physicians interested in the treatment of vascular anomalies has grown exponentially over the last several decades from a mere handful in the mid 1980s to several thousand today. Every year, hundreds of peer-reviewed articles are published in this field. Some of the most interesting articles have shed light on the underlying genetic and molecular bases of some of these conditions. This has led to the development of at least one group of medical therapies for some vascular lesions.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A50YpM

Contents

Sujana S. Chandrasekhar

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AXbr6w

Orthognathic Considerations of Vascular Malformations

Vascular malformations affect the craniofacial skeleton in many ways, depending on the type of the lesion and its location. The lesions may exert a mass effect and cause thinning or thickening of the bone or cause expansion from direct bony infiltration. Orthognathic surgery can be used to correct any malocclusion or open bite deformities after the soft tissues are addressed.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A50W18

Contributors

SUJANA S. CHANDRASEKHAR, MD

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AVPNjg

Copyright

Elsevier

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AXbcs8

Classification and Pathology of Congenital and Perinatal Vascular Anomalies of the Head and Neck

Accurate histopathologic description in correlation with clinical and radiological evaluation is required for treatment of vascular anomalies, both neoplastic and malformative. It is important to examine current clinical, histologic, and immunophenotypical features that distinguish the major types of congenital and perinatal vascular anomalies affecting the head and neck. General discussions of pathogenesis and molecular diagnosis must also be taken into account. This article provides an overview of the features that distinguish the major types of congenital and perinatal vascular anomalies affecting the head and neck, and summarizes the diagnostic histopathologic criteria and nomenclature currently applied to these lesions.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A50hga

Congenital Vascular Lesions of the Head and Neck

OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AVPDbE

Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) describes the presenting manifestations of a disorder that is characterized by pathologic blood vessels. HHT is inherited as an autosomal dominant trait with variable penetrance. The abnormal vascular structures (dysplasias) can affect all the organs in the human body. The link between a physical stimulus and new lesion development has been established for mucosal trauma owing to nasal airflow turbulence, for ultraviolet exposure to the fingers, and for mechanical trauma to the dominant hand. The pressing question then is whether HHT treatment constitutes a stimulus that is sufficient to trigger new lesion development.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A50C2q

Outcome Measurement for Vascular Malformations of the Head and Neck

Vascular malformations are congenital anomalies of the vascular and/or lymphatic system that affect the head and neck region. The most common treatment options are sclerotherapy, laser therapy, surgery, and embolization. Because vascular malformations are variable in type, size, extent, and location, it is a challenge to select methods for evaluation of treatment outcome. Without standardized outcome reporting, it is difficult to compare and combine scientific evidence to support therapeutic decision making. Standardized collection and reporting of outcome data are the first steps toward a fair comparison between treatments. This article describes outcome measurements for vascular malformations and initiatives to improve outcome reporting.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AUMoRu

The Surgical Management of Infantile Hemangiomas

The surgical management of facial infantile hemangiomas presents a unique challenge. The aim of the surgeon should be to remove the hemangioma and to restore normal facial features. Each of the facial zones has its own special features and challenges. The surgeon should remember that the child started out with normal anatomy and that as the hemangioma proliferated, it displaced and thinned these normal structures and in many cases, expanded adjacent tissue. Hemangiomas do not as a rule, invade adjacent tissues as they proliferate. These facts will help in planning the various surgical approaches.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A50uzY

The Management of Vascular Malformations of the Airway

Vascular malformations may affect nearly all aspects of the upper airway. Each type of malformation has a characteristic pattern of disease. These lesions may be focal or diffuse, and require directed management strategies. Physicians treating these entities should have a high level of suspicion to consider airway evaluation even in the absence of overt symptoms. However, cutaneous head and neck venous malformations or other lesions affecting the lips, oral cavity, or tongue can herald the presence of coexisting airway lesions. A multidisciplinary approach is critical in achieving comprehensive treatment.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AVHB2t

Infantile Hemangiomas in the Head and Neck Region

Infantile hemangiomas (IHs) are benign vascular tumors of infancy most common in the region of the head and neck. Infantile hemangiomas are common; but they are extremely heterogeneous and cause a range of complications depending on their morphology, size, or location. Medical interventions for high-risk patients include topical and systemic therapies, including oral propranolol, which has revolutionized the management of IHs over the past recent years. In the following article, the authors aim to provide a review of the natural history, pathology, complications, syndromes, and medical management of infantile hemangioma.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A57BZ7

Multidisciplinary Approach to the Management of Lymphatic Malformations of the Head and Neck

Lymphatic malformations (LMs) occur in 2.8 to 5 per 100,000 live births. Most involve the head and neck and they are equally common in men and women. They are developmental anomalies of unknown cause, although recent evidence suggests that an upregulation of the mammalian target of rapamycin (mTOR) pathway may be a causal factor leading to the overproduction of abnormal lymph vessels. These vessels are likely dilated lymphatic sacs sequestered from the lymphatic and venous systems. This overproduction results in the accumulation of lymph in dilated cystic spaces, which in turn results in the clinical features of an LM.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AWNlZM

The Role of Surgery in the Management of Infantile Hemangiomas

Surgery for the management of infantile hemangiomas has become commonplace. Surgical technique articles are plentiful; however, little has been written about the timing of surgery. Knowledge of the biology of the tumors, data from developmental psychology, and the utility of facial reconstruction provide guidelines for timing of surgical intervention.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A3j9fb

Congenital Vascular Tumors

Vascular tumors are benign neoplasms, which result from proliferating endothelial cells. These lesions present during infancy or childhood, may affect any location, and exhibit postnatal growth. Local complications include bleeding, tissue destruction, and pain whereas systemic sequelae include thrombocytopenia, congestive heart failure, and death. Vascular tumors should be differentiated from vascular malformations, which present at birth, have a quiescent endothelium, and grow in proportion to the child. Together, vascular tumors and malformations comprise the field of vascular anomalies.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AYZhde

Muscle fiber conduction velocity and EMG amplitude of the upper trapezius muscle in healthy subjects after low-level laser irradiation: a randomized, double-blind, placebo-controlled, crossover study

Abstract

Although low-level laser therapy (LLLT) is an important resource for the treatment of non-specific neck pain patients, the dose which presents the greatest therapeutic potential for the treatment of this pathology is still unclear. The present study aimed to evaluate the immediate effect of LLLT on the muscle fiber conduction velocity (MFCV) and electromyographic activity (EMG) of the upper trapezius (UT) muscle in healthy individuals. A total of 20 healthy subjects were enrolled in a randomized, double-blind, crossover study. Active LLLT (820 nm wavelength, 30 mW, energy total 18 J) or placebo LLLT (pLLLT) was delivered on the UT muscle. Each subject was subjected to a single session of active LLLT and pLLLT. Surface electromyography (sEMG) signal of the UT muscle was recorded during five different step contractions of shoulder elevation force (10–30% maximal voluntary contraction) pre- and post-LLLT irradiation. The values of MFCV and sEMG global amplitude (RMS_G) were used to calculate the effects of LLLT. The results showed no difference in the MFCV comparing the LLLT and pLLLT groups (F = 0.72 p = 0.39, η _p² = 0.004). However, a significant difference was observed in the RMS_G between the LLLT and pLLLT (F _1,2 = 16.66; P < 0.0001, η _p² = 0.09). Individuals who received active LLLT presented a significant decrease in RMS_G after laser application (F = 61.28; p < 0.0001, η _p² = 0.43). In conclusion, the 820 nm LLLT, with energy total of 18 J, did not alter the MFCV but significantly reduced the sEMG signal amplitude of the upper trapezius muscle in healthy subjects to a level of up to 30% of maximal voluntary contraction.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kmjqmK

Usefulness of our proposed olfactory scoring system during endoscopic sinus surgery in patients with chronic rhinosinusitis

Abstract

Introduction

The primary aim of the current study was to examine the usefulness of our proposed olfactory scoring system in chronic rhinosinusitis (CRS) patients with olfactory disorders (n = 213) receiving endoscopic sinus surgery (ESS).

Materials and methods

Analyzed patients were divided into two groups: an eosinophilic CRS (ECRS) group (n = 153); and a non-ECRS group (n = 60). The T&T recognition threshold test was used to evaluate olfaction at baseline and at 3 and 12 months after ESS. Patients with mean recognition threshold < 2.0 at 3 or 12 months or with a decrease of ≥ 1.0 as compared with baseline were defined as showing clinical improvement. We scored mucosal conditions as normal (0 points), edema (1 point), and polyp (2 points) at the canopy of olfactory cleft (OC), middle and superior turbinates, superior nasal meatus, and sphenoethmoidal recess during ESS. The total score of OCs (SOCs) was calculated (range 0–20 points). We compared SOCs between ECRS and non-ECRS groups. Factors related to olfactory improvement were also investigated using uni- and multivariate analyses.

Results

SOCs in the ECRS and non-ECRS groups showed significant correlations with mean recognition thresholds at baseline and at 3 and 12 months. In the multivariate analysis for predicting improvement of mean recognition threshold, lower SOCs were significantly associated with olfactory improvement factors at 3 and 12 months postoperatively in the ECRS group.

Conclusion

SOCs appears promising for estimating olfactory prognosis after ESS in CRS patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A1k3cd

Sialendoscopy in treating pediatric salivary gland disorders: a systematic review

Abstract

Objective

The primary aim of this study is to conduct a systematic review in order to evaluate the use of sialendoscopy in treating pediatric salivary gland disorders.

Methods

Eligible articles were identified through a comprehensive search of electronic databases. Using predefined inclusion criteria, published articles on sialendoscopy in children were selected and reviewed.

Results

17 articles including 323 pediatric patients and 424 salivary glands managed by sialendoscopy were identified. The most common salivary gland disorder affected was the parotid (83% of cases), followed by the submandibular gland (16.5% of cases). Juvenile recurrent parotitis (68.9%) was the most frequent diagnosis followed by sialolithiasis (14.7%). The most common complication was ductal perforation. During a pooled mean follow-up time of 18.3 months, recurrences were reported in 14.5% of patients mostly in patients diagnosed with juvenile recurrent parotitis.

Conclusion

Sialendoscopy is a minimally invasive diagnostic and therapeutic tool for inflammatory salivary gland disorders in pediatric patients. Based on the current review, sialendoscopy can be successfully implemented in cases of pediatric salivary gland disorders.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AWvFgQ

Reply to the letter “Laryngopharyngeal reflux disease in the elderly”

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A3Cs8r

The outcome of cochlear implantation among children with genetic syndromes

Abstract

Objective

To assess the outcome and efficacy of cochlear implantation in children with genetic syndromes.

Method

Study design: case–control study.

Setting

A cochlear implantation tertiary referral center.

Patients

All pediatric cochlear implantation recipients with Waardenburg syndrome, Usher syndrome, Dandy–Walker syndrome, or albinism. A control group was appropriately matched to the syndromic group with regard to age at implantation and duration of device use.

Intervention

Cochlear implantation.

Main outcome measures

Subjects' auditory abilities, speech intelligibility, and pure tone thresholds were compared between the syndromic and non-syndromic group.

Results

A total of 25 subjects (13 syndromic and 12 non-syndromic) participated in the study. Neither auditory ability nor speech intelligibility scores differed significantly by group. The final PTA of both the groups showed normal-to-mild hearing loss: 26 dB HL in the syndromic group and 23 dB HL for the control group.

Conclusions

Cochlear implant recipients with genetic syndromes achieved similar levels auditory perception and speech intelligibility as their peers with a genetic syndrome. The presence of any of the genetic syndromes described herein should not be a contraindication to cochlear implant provision, as it would have a positive impact on the patients' sensory perception and lifestyle.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AWnwJp

Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status

Abstract

Objective

Lymph node ratio (LNR) was shown to be a prognostic factor in laryngeal and oral cavity primaries. The purpose of this study was to investigate the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR was evaluated as an additional predictive parameter to the 8th edition of AJCC TNM staging system.

Methods

From December 2009 to August 2015, patients diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively enrolled. After tumor resection with uni- or bilateral neck dissection, patients with ≥ 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis.

Results

137 patients underwent tumor resection with uni- or bilateral neck dissection. The proportion of HPV-associated disease was 42%. Most patients (n = 96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of pN + cases was significantly increased compared to p16-negative OPSCC (86% vs. 58%, p = 0.007). Patients with LNR ≤ 10% had a significant better overall survival (OS) and disease-specific survival (DSS). However, when stratified for p16-status, LNR ≤ 10% had a significant impact on OS only for HPV-associated tumors (p = 0.027), whereas LNR of ≤ 10% was not a significant predictor for better OS in p16-negative OPSCC (p = 0.143).

Conclusion

The LNR with a cut-off value of 10% serves as an additional prognostic parameter in HPV-related OPSCC and may help to improve risk stratification in combination with the revised AJCC 8th edition TNM classification.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A3DLUQ

Reply to the Letter to the Editor concerning “Combined microscopic/endoscopic management of petrous apex lesions”

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AWnmSj

Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the rat

Abstract

Cirrhosis represents the end-stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited. More specifically, detailed anatomical data on the vascular adaptations during disease development is lacking. To address this need, we studied the 3D architecture of the hepatic vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was chemically induced with thioacetamide (TAA). At predefined time points, the hepatic vasculature was fixed and visualized using a combination of vascular corrosion casting and deep tissue microscopy. Three-dimensional reconstruction and data-fitting enabled cirrhogenic features to extracted at multiple scales, portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel, we noticed that regenerative nodules severely compressed pliant venous vessels from 12 weeks of TAA intoxication onwards. Especially hepatic veins were highly affected by this compression, with collapsed vessel segments severely reducing perfusion capabilities. At the microlevel, we discovered zone-specific sinusoidal degeneration, with sinusoids located near the surface being more affected than those in the middle of a liver lobe. Our data shed light on and quantify the evolving angioarchitecture during cirrhogenesis. These findings may prove helpful for future targeted invasive interventions.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nsE71o

Melanomacrophage functions in the liver of the caecilian Siphonops annulatus

Abstract

Melanomacrophages are phagocytes that synthesize melanin. They are found in the liver and spleen of ectothermic vertebrates, and in the kidney of fish. In agnathan and elasmobranch fish, melanomacrophages are seen as isolated cells, and forming clusters in all the other vertebrates. The natural phagocytic activity of melanomacrophages is poorly characterized, as most of the research works have focused on induced phagocytic activity only. Furthermore, little is known about amphibian melanomacrophages, mainly about those in caecilians – wormlike amphibians in the order of Gymnophiona, which is the least known group of terrestrial vertebrates. The present research work aimed at the structure and function of hepatic melanomacrophages of Siphonops annulatus, a species largely found in South America. We identified the role of these cells in the control of circulating basophils (pro-melanogenic cells), in the turnover of liver collagen stroma and in the hemocatheresis, interrelated physiological mechanisms.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zMqBaG

Normothermia after decompressive surgery for space-occupying middle cerebral artery infarction: a protocol-based approach

Moderate hypothermia after decompressive surgery might not be beneficial for stroke patients. However, normothermia may prove to be an effective method of enhancing neurological outcomes. The study aims were t...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AWhJU6

Atrial fibrillation is not uncommon among patients with ischemic stroke and transient ischemic stroke in China

Atrial fibrillation (AF) is reported to be a less frequent cause of ischemic stroke in China than in Europe and North America, but it is not clear whether this is due to underestimation. Our aim was to define ...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A3pszE

Selection bias in clinical stroke trials depending on ability to consent

Clinical trials are the hallmark of evidence-based medicine, but recruitment is often challenging, especially in stroke trials investigating patients not being able to give informed consent. In some nations, e...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AVdjg1

Trastuzumab emtansine delays and overcomes resistance to the third-generation EGFR-TKI osimertinib in NSCLC EGFR mutated cell lines

Osimertinib is a third-generation EGFR-TKI with a high selective potency against T790M-mutant NSCLC patients. Considering that osimertinib can lead to enhanced HER-2 expression on cell surface and HER-2 overex...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jOZLro

Downregulation of miR-141-3p promotes bone metastasis via activating NF-κB signaling in prostate cancer

Clinically, prostate cancer (PCa) exhibits a high avidity to metastasize to bone. miR-141-3p is an extensively studied miRNA in cancers and downregulation of miR-141-3p has been widely reported to be involved ...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iiS1NY

Hyperpigmentation of the hard palate mucosa in a patient with chronic myeloid leukaemia taking imatinib

Abstract

Background

Imatinib mesylate is an inhibitor of the tyrosine kinase Bcr–Abl and a first-line treatment for Philadelphia chromosome-positive chronic myeloid leukaemia (CML). Dermatological side effects include superficial oedema, pustular eruption, lichenoid reactions, erythroderma, and skin rash. Depigmentation of the skin and/or mucosa is uncommon, and hyperpigmentation is rare.

Case presentation

We present the case of a 63-year-old Caucasian male with widespread hyperpigmentation of the hard palate associated with a 9-year history of imatinib therapy to treat CML. He did not complain of any symptoms. Clinical examination did not reveal any abnormal pigmentation of the skin or other region of the oral mucosa. He did not smoke cigarettes or drink alcohol. His medication regimen was a proton pump inhibitor, a beta-blocker, cardioaspirin, atorvastatin, and imatinib 400 mg/day. Histopathologically, melanin and haemosiderin deposits were evident in the lamina propria. The lesion persisted, with no clinical change, through several follow-ups. We reviewed the literature to explore the possible relationship between oral hyperpigmentation and long-term imatinib mesylate treatment.

Conclusions

We diagnosed oral pigmentation associated with imatinib intake based on the medical history and clinical features of the pigmented macules. Oral pigmentation may have a variety of causes, and differential diagnosis requires nodal analysis. Clinicians should be aware of possible oral mucosal hyperpigmentation in patients taking imatinib mesylate. Such pigmentation is benign and no treatment is needed, but surveillance is advisable.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zN2Fnw

Risk of peritoneal metastases in patients who had negative peritoneal staging and received therapy for localized gastric adenocarcinoma

Background

Positive peritoneal cytology (+PCyt) or gross carcinomatosis (GPC) carries a poor prognosis. Laparoscopic staging to detect +PCyt/GPC is recommended for all ≥T1b gastric adenocarcinoma (GAC). The natural history of patients with GAC who have baseline −PCyt and then undergo multimodality therapy is not well documented, particularly for the risk of subsequent GPC.

Methods

We identified 238 GAC patients with baseline −PCyt who were followed for the development of peritoneal carcinomatosis (PC). Standard statistical methods were employed.

Results

Of 238 patients, 192 had attempted surgery after preoperative therapy. Of these, 13 patients (6.8%) had GPC and one had liver metastases, thus surgery was aborted. We followed 164 patients who had an R0 resection. The median follow-up duration was 3.4 (range, 0.6-18) years. The rate of PC was 13.4%, (22/164 patients) and the median time to PC was 15.6 months. Female gender was associated with PC on multivariate analysis. The 5-year OS rate for patients without subsequent PC was 75%.

Conclusion Even with baseline −Cyt, ∼25% of patients develop PC following multimodality therapy. Patients who do not develop PC have an excellent OS rate. Further research is warranted to detect PC at baseline by the use of biomarkers.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jNxcLd

Perioperative cytokine levels portend early death after pancreatectomy for ductal adenocarcinoma

Background

Soluble signaling molecules may play an important role in malignant pathogenesis. We hypothesize that perioperative cytokine levels are associated with outcomes in patients with pancreatic adenocarcinoma (PDAC) undergoing surgical resection.

Methods

One hundered and eighteen patients with benign or malignant pancreatic disease were enrolled in a prospective study through a protocol for banking biologic samples. Peripheral blood was drawn at time of operation, and a multiplex cytokine assay was performed. Statistical analysis was via χ² and Kaplan Meier methods.

Results

Of 118 patients enrolled, 85 (72%) had a diagnosis of PDAC, and 60 (70%) ultimately underwent partial pancreatectomy. Cytokine levels were not associated with postoperative complications in this initial cohort. A plasma level of monocyte chemoattractant protein-1 (MCP-1) pg/mL ≤118 was associated with better overall survival (OS) (median survival 21 months vs 12.8 months, P = 0.023), as was non-detectable interleukin-8 (IL-8) (19 months) versus detectable IL-8 (12.8 months, P = 0.05). Patients with both MCP-1 >118 pg/mL and detectable IL-8 had a median survival of 10.6 months (P = 0.028).

Conclusions

MCP-1 and IL-8 cytokine levels are associated with decreased survival following pancreatectomy for PDAC, and may be useful biomarkers. Measurement of these cytokine levels at different time points in future investigations will be important to validate these findings.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ii6sSv

Prognostic impact of postoperative pulmonary complications following salvage esophagectomy after definitive chemoradiotherapy

Background

Postoperative complications after esophagectomy for esophageal cancer have a negative effect on patients' survival. Although postoperative complications are more frequently observed after salvage esophagectomy than after planned esophagectomy, the effects of postoperative complications on long-term oncologic outcomes after salvage esophagectomy remain unclear.

Methods

This retrospective study of 70 esophageal cancer patients after definitive chemoradiotherapy (dCRT) compared long-term outcomes between those with and without complications. The association between morbidity and overall survival (OS) was evaluated by a Cox regression analysis. To identify the risk factors for pulmonary complications, logistic regression analysis was carried out.

Results

Postoperative complications occurred in 42 (60.0%) patients. Pulmonary complications and anastomotic leakage occurred in 23 (32.9%) and 9 (12.9%) patients, respectively. Overall complications and anastomotic leakage did not affect long-term outcomes. Survival was significantly worse for patients with pulmonary complications. Radiation dose (<60 Gy), response to dCRT (complete), ypStage (0-II), residual disease (R0), and pulmonary complications (negative) were independent factors related to a favorable OS. BMI (<20 kg/m²), ASA-PS (2-3), and radiation dose (>60 Gy) were significant factors affecting the occurrence of pulmonary complications.

Conclusions

Development of postoperative pulmonary complications was independently associated with poor prognosis in patients who underwent salvage esophagectomy after dCRT.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jPnwjp

Oncologic effects of preoperative biliary drainage in resectable hilar cholangiocarcinoma: Percutaneous biliary drainage has no adverse effects on survival

Background and Objectives

The objective of the current study was to define long-term survival of patients with resectable hilar cholangiocarcinoma (HCCA) after preoperative percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD).

Methods

Between 2000 and 2014, 240 patients who underwent curative-intent resection for HCCA were identified at 10 major hepatobiliary centers. Postoperative morbidity and mortality, as well as disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed among patients.

Results

The median decrease in total bilirubin levels after biliary drainage was similar comparing PTBD (n = 104) versus EBD (n = 92) (mg/dL, 4.9 vs 4.9, P = 0.589) before surgery. There was no difference in baseline demographic characteristics, type of surgical procedure performed, final AJCC tumor stage or postoperative morbidity among patients who underwent EBD only versus PTBD (all P > 0.05). Patients who underwent PTBD versus EBD had a comparable long-term DSS (median, 43.7 vs 36.9 months, P = 0.802) and RFS (median, 26.7 vs 24.0 months, P = 0.571). The overall pattern of recurrence relative to regional or distant disease was also the same among patients undergoing PTBD and EBD (P = 0.669)

Conclusions

Oncologic outcomes including DSS and RFS were similar among patients who underwent PTBD versus EBD with no difference in tumor recurrence location.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ij8Ubu

Characteristics and long-term survival of patients diagnosed with pure tubular carcinoma of the breast

Background and Objectives

Pure tubular carcinomas (TC) of the breast are generally considered to have an excellent prognosis. This study aimed to analyze the characteristics and survival of patients with TC.

Methods

This was a retrospective study conducted at the CHU de Québec—Université Laval. Databases were searched for all cases treated between April 1997 and December 2010. Survival was retrieved from the Province of Quebec Ministry of Health. Follow-up was censored on December 31, 2011. Overall survival (OS) was compared to patients with invasive ductal carcinoma (ICD) matched for age, tumor size, lymph node involvement, year of diagnosis, ER, PgR, and HER2, histological grade, lymphovascular invasion, and chemotherapy.

Results

The frequency of TC was 2.9% (n = 223/7563). Tumors size was 7.4 ± 8.8 mm, without lymphovascular invasion (95.1%), ER-positive (98.2%), PgR-positive (69.5%), and HER2-negative (100%). Patients were followed up for 7.1 ± 2.7 years. The actuarial 13-year OS was 89.0% for TC, compared to 85.8% for IDC (P = 0.13). For TC, the 13-year OS was 95.8% in NO patients compared to 90.0% for N1-3 (P = 0.01).

Conclusion

Despite the general popular belief that patients with TC fare better than patients with IDC, the 13-year OS of TC was similar to that of grade I IDC.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ii6j1p

Effects of local multivisceral resection for clinically locally advanced rectal cancer on long-term outcomes

Introduction

Multivisceral resection is occasionally needed to obtain clear margins in patients with transmural rectal cancer. Most series demonstrate equivalent outcomes between those patients who undergo multivisceral resections and those who do not, provided an R0-resection is achieved. This study focuses solely on patients who received neoadjuvant treatment for clinically transmural rectal cancers and underwent a local multivisceral R0-resection.

Methods

A retrospective, single center analysis of consecutive series of patients who received a surgical R0-resection after neoadjuvant treatment for a clinically transmural, non-metastatic, primary rectal cancer. All patients were operated on between 2004 and 2015.

Results

A total of 279 patients was included, of whom 29 patients underwent a local multivisceral R0-resection (LMVR). These patients were more often female and less often diagnosed through screening. Pathologic AJCC-staging was significantly lower for non-LMVR patients, with more favorable tumor characteristics. LMVR patients demonstrated higher rates of distant disease recurrence, and impaired survival, even after adjusting for disease stage.

Conclusion

An R0-resection after neoadjuvant therapy led to comparative local control of disease; however, patients with multivisceral resection had more distant recurrence and impaired survival, compared to those did not undergo a multivisceral resection. Further research should determine optimal postoperative care.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jPdA9l

Clinical outcomes in breast angiosarcoma patients: A rare tumor with unique challenges

Background

Breast angiosarcoma (AS) accounts for less than 1% of all breast cancers. The goal of this study was to determine patient outcomes in radiation-associated angiosarcoma of the breast (RAAS) and sporadic AS. We evaluated patterns of recurrence and predictors of breast AS survival.

Methods

Patients with pathologically confirmed AS from 1994 to 2014 referred to Mount Sinai Hospital/Princess Margaret Cancer Centre were included. Primary outcome was overall survival (OS). Secondary outcomes were disease-free survival (DFS), clinicopathologic characteristics, patterns of recurrence and factors predictive of survival. Kaplan-Meier and log-rank tests were used for OS and DFS.

Results

Twenty-six patients were included: 6 with sporadic AS and 20 with RAAS. Median follow-up was 24 months. Five-year OS for RAAS and sporadic subgroups were 44% and 40%, respectively (P = ns). Five-year DFS for RAAS and sporadic subgroups were 23% and 20%, respectively (P = ns). Overall recurrence rate was 67% with median time to recurrence of 11 months. Age, tumor depth, margin status, and tumor size were not statistically significant predictive factors for OS and DFS.

Discussion

Breast AS is associated with poor survival and high recurrence rates. Prognosis may be mainly determined by its aggressive biology. Referral to tertiary care centers for multimodality treatment is recommended.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ihvPE1

Repair of Occipital Bone Defects in Neurofibromatosis Type 1 by Means of CAD/CAM Prefabricated Titanium Plates

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0037-1608699

Certain skeletal defects may develop in neurofibromatosis type 1 (NF1), a common tumor-suppressor syndrome, such as cranial lesions confined to the lambdoid suture region. Here, we report on the repair of osseous defects of occipital bone in a NF1 patient with history of skull trauma and tumorous hemorrhage. Computer-aided design and computer-aided manufacturing (CAD/CAM)-assisted devices were applied to safely close the bone defects. The variable phenotype of NF1 in the occipital skull region is discussed and a brief review is presented on NF1-related therapies for tumors and malformations of the occipitoparietal skull region.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ikI3fj

Metastasierung kutaner Plattenepithelkarzinome im HNO-Bereich

Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-122745

Hintergrund Kutane Plattenepithelkarzinome können lymphogen sowohl nach intraparotideal, als auch nach zervikal metastasieren. Prognostisch scheinen sich gemäß mehreren Studien die beiden Metastasierungswege zu unterscheiden. Wir möchten mit klinikeigenen Daten das Metastasierungsverhalten hinsichtlich der Prognose untersuchen. Material und Methoden In die retrospektive Studie aufgenommen wurden 29 Kaukasier mit einem Plattenepithelkarzinom der Haut im Kopf-Halsbereich, welche sich zwischen 2004 und 2016 an unserer Hals-Nasen-Ohren-Klinik vorgestellt haben. Bei allen Patienten wurde eine Tumorresektion mit Neck dissection durchgeführt. Sowohl das präoperative Staging, wie auch die Nachsorge erfolgten mittels Ultraschall oder Computertomographie (konventionell oder PET Scan). Die Patienten wurden nach Metastasierungsverhalten eingeteilt und die entsprechenden Überlebensraten wurden ermittelt. Ergebnisse 11 Patienten hatten zervikale Metastasen, 4 Patienten parotideale Metastasen, 5 Patienten hatten beides. Bei 9 Patienten wurde eine prophylaktische Neck dissection bei cN0 durchgeführt. Ein lokoregionäres Tumorrezidiv trat in insgesamt 24 % der Fälle auf, davon waren alle mit einer zervikalen Metastasierung assoziiert. Die 5-Jahres Überlebensrate betrug in diesen Fällen 71 %. Im Gegensatz dazu betrug diese bei alleiniger parotidealer Metastasierung 100 %. Im Rahmen der prophylaktischen Neck dissection wurden in einem Fall okkulte Metastasen diagnostiziert. Schlussfolgerungen Eine zervikale Metastasierung geht im Gegensatz zu einer alleinigen parotidealen Metastasierung mit einer schlechteren Prognose einher. Die Überlebensrate nach chirurgischer Therapie, sowie gegebenenfalls zusätzlichen adjuvanten Radiotherapie ist insgesamt gut (79 %). Die Rolle einer prophylaktischen Neck dissection bei cN0 und entsprechenden Risikofaktoren ist nicht abschließend geklärt.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kkkqHL

IgG4-related disease presenting as hoarseness and postcricoid ulcer

Immunoglobulin G4–related disease (IgG4-RD) is an uncommon immune-mediated disorder with heterogeneous clinicopathologic features and variable disease manifestations.1 IgG4-RD is characterized by single-organ or multiorgan involvement, and tissue infiltration with IgG4 plasma cells and associated fibrosclerosis.2–5 Autoimmune pancreatitis represents the prototype of IgG4-RD, yet involvement of almost all organs has been reported.1–7 Elevated IgG4 serum concentration is noted in the majority of patients with IgG4-RD and is generally related to the more severe disease phenotype.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iPyGbo

Hyalinizing clear cell carcinoma of salivary gland origin in the head and neck: clinical and histopathological analysis

Hyalinizing clear cell carcinoma (HCCC) is an extremely rare neoplasm of salivary gland origin with a low-grade indolent nature. It is difficult to distinguish from other malignant salivary gland tumours. Clinical outcomes following surgery are generally reported as good. The aim of this study was to further determine the features of HCCC. This study was approved by Medical ethics review of affiliated hospital of jiangsu university. Fourteen new cases of HCCC are reported. The clinical and histopathological data of these 14 cases were analysed alongside those of 141 cases identified in a systematic review of the literature (up to 2016).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2km2JYC

The effect of prone and supine treatment positions for the pre-operative treatment of rectal cancer on organ-at-risk sparing and setup reproducibility using volumetric modulated arc therapy

Abstract

Background and purpose

To compare organ-at-risk doses and setup reproducibility using the prone and supine orientations in volumetric modulated arc therapy (VMAT) for rectal cancer.

Materials and methods

Seventeen consecutive rectal cancer patients undergoing preoperative radiation were selected and setup in either the prone (N = 8) or supine (N = 9) position. All patients were treated using posteriorly-applied VMAT. Bladder and small bowel dose and cone beam CT (CBCT) reproducibility metrics were retrospectively collected.

Results

Dose metrics for bladder and small bowel did not show significant differences between the prone and supine orientations. The prone data had a trend for smaller irradiated volumes than supine for the small bowel at lower doses—V20 (prone: 135 ± 99 cm³; supine: 201 ± 162 cm³) and V30 (prone: 78 ± 71 cm³; supine: 105 ± 106 cm³). At higher doses, the trend reversed as exemplified by the small bowel V50.4 (prone: 20 ± 28 cm³; supine: 10 ± 14 cm³). CBCT data showed that rotational errors in pitch and roll were significantly larger for the prone vs. supine orientation (pitch: 2.0° ± 1.3° vs. 0.8° ± 1.1° p < 0.001; roll: 1.0° ± 0.9° vs. 0.3° ± 0.5°, p < 0.001).

Conclusions

Bladder and small bowel doses were not significantly different when comparing VMAT plans developed for the prone and supine orientations. The supine orientation demonstrated improved setup reproducibility.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BHJDAj

Usefulness of our proposed olfactory scoring system during endoscopic sinus surgery in patients with chronic rhinosinusitis

Abstract

Introduction

The primary aim of the current study was to examine the usefulness of our proposed olfactory scoring system in chronic rhinosinusitis (CRS) patients with olfactory disorders (n = 213) receiving endoscopic sinus surgery (ESS).

Materials and methods

Analyzed patients were divided into two groups: an eosinophilic CRS (ECRS) group (n = 153); and a non-ECRS group (n = 60). The T&T recognition threshold test was used to evaluate olfaction at baseline and at 3 and 12 months after ESS. Patients with mean recognition threshold < 2.0 at 3 or 12 months or with a decrease of ≥ 1.0 as compared with baseline were defined as showing clinical improvement. We scored mucosal conditions as normal (0 points), edema (1 point), and polyp (2 points) at the canopy of olfactory cleft (OC), middle and superior turbinates, superior nasal meatus, and sphenoethmoidal recess during ESS. The total score of OCs (SOCs) was calculated (range 0–20 points). We compared SOCs between ECRS and non-ECRS groups. Factors related to olfactory improvement were also investigated using uni- and multivariate analyses.

Results

SOCs in the ECRS and non-ECRS groups showed significant correlations with mean recognition thresholds at baseline and at 3 and 12 months. In the multivariate analysis for predicting improvement of mean recognition threshold, lower SOCs were significantly associated with olfactory improvement factors at 3 and 12 months postoperatively in the ECRS group.

Conclusion

SOCs appears promising for estimating olfactory prognosis after ESS in CRS patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A1k3cd

Sialendoscopy in treating pediatric salivary gland disorders: a systematic review

Abstract

Objective

The primary aim of this study is to conduct a systematic review in order to evaluate the use of sialendoscopy in treating pediatric salivary gland disorders.

Methods

Eligible articles were identified through a comprehensive search of electronic databases. Using predefined inclusion criteria, published articles on sialendoscopy in children were selected and reviewed.

Results

17 articles including 323 pediatric patients and 424 salivary glands managed by sialendoscopy were identified. The most common salivary gland disorder affected was the parotid (83% of cases), followed by the submandibular gland (16.5% of cases). Juvenile recurrent parotitis (68.9%) was the most frequent diagnosis followed by sialolithiasis (14.7%). The most common complication was ductal perforation. During a pooled mean follow-up time of 18.3 months, recurrences were reported in 14.5% of patients mostly in patients diagnosed with juvenile recurrent parotitis.

Conclusion

Sialendoscopy is a minimally invasive diagnostic and therapeutic tool for inflammatory salivary gland disorders in pediatric patients. Based on the current review, sialendoscopy can be successfully implemented in cases of pediatric salivary gland disorders.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AWvFgQ

Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status

Abstract

Objective

Lymph node ratio (LNR) was shown to be a prognostic factor in laryngeal and oral cavity primaries. The purpose of this study was to investigate the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR was evaluated as an additional predictive parameter to the 8th edition of AJCC TNM staging system.

Methods

From December 2009 to August 2015, patients diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively enrolled. After tumor resection with uni- or bilateral neck dissection, patients with ≥ 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis.

Results

137 patients underwent tumor resection with uni- or bilateral neck dissection. The proportion of HPV-associated disease was 42%. Most patients (n = 96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of pN + cases was significantly increased compared to p16-negative OPSCC (86% vs. 58%, p = 0.007). Patients with LNR ≤ 10% had a significant better overall survival (OS) and disease-specific survival (DSS). However, when stratified for p16-status, LNR ≤ 10% had a significant impact on OS only for HPV-associated tumors (p = 0.027), whereas LNR of ≤ 10% was not a significant predictor for better OS in p16-negative OPSCC (p = 0.143).

Conclusion

The LNR with a cut-off value of 10% serves as an additional prognostic parameter in HPV-related OPSCC and may help to improve risk stratification in combination with the revised AJCC 8th edition TNM classification.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A3DLUQ

Reply to the Letter to the Editor concerning “Combined microscopic/endoscopic management of petrous apex lesions”

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AWnmSj

The Influence of Target and Masker Characteristics on Infants' and Adults' Detection of Speech

Purpose

Several investigators have compared infants' detection of speech in speech and nonspeech maskers to evaluate developmental differences in masking. Such comparisons have produced contradictory results, possibly because each investigation used different stimuli. The current study examined target and masker effects on infants' and adults' detection of speech.

Method

An observer-based procedure was used to compare infants' and adults' detection of the vowel /ʌ/ and the word "baby" in a 2-talker speech masker and matched speech-spectrum noise. The measure of performance was d′. A total of 43 7-month-old infants and 41 young adults were randomly assigned to 1 target–masker combination condition, and mean performance was compared across conditions at each age.

Results

Adults' detection was influenced by an interaction between the target and the masker: Adults detected the vowel better in the 2-talker masker than in speech-spectrum noise but detected the word equally well in the 2 maskers. In contrast, infants detected both targets better in speech-spectrum noise than in the 2-talker masker.

Conclusions

The relative effects of the masker on target detection by infants and adults depend on the target to be detected. Thus, conclusions drawn about differences between infants and adults in the mechanisms responsible for masking will depend on the stimuli. Standardization of speech stimuli in developmental research would help clarify the nature of infants' segregation difficulties.

Supplemental Material

http://ift.tt/2jDMsKA

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_JSLHR-H-16-0464/2665222/The-Influence-of-Target-and-Masker-Characteristics

Diagnostic and treatment effects of sialendoscopy for patients with swelling of the parotid gland when sialoliths are undetected with computed tomography

Between August 2009 and May 2016, 74 patients underwent sialoendoscopic surgery. 32 patients had parotid gland disease and 9 patients had intermittent swelling of the parotid gland and sialoliths were not detected with CT imaging. 4 patients were diagnosed with idiopathic Stensen's duct stenosis. Sialendoscopy directly confirmed Stensen's duct stenosis in 2 patients. However, the sialendoscope was unable to be inserted in the other 2 patients, who had stenosis of the orifice of the Stensen's duct.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A3UYxm

Glycogen Synthase Kinase-3 Modulates Cbl-b and Constrains T Cell Activation [IMMUNE REGULATION]

The decision between T cell activation and tolerance is governed by the spatial and temporal integration of diverse molecular signals and events occurring downstream of TCR and costimulatory or coinhibitory receptor engagement. The PI3K–protein kinase B (PKB; also known as Akt) signaling pathway is a central axis in mediating proximal signaling events of TCR and CD28 engagement in T cells. Perturbation of the PI3K–PKB pathway, or the loss of negative regulators of T cell activation, such as the E3 ubiquitin ligase Cbl-b, have been reported to lead to increased susceptibility to autoimmunity. In this study, we further examined the molecular pathway linking PKB and Cbl-b in murine models. Our data show that the protein kinase GSK-3, one of the first targets identified for PKB, catalyzes two previously unreported phosphorylation events at Ser⁴⁷⁶ and Ser⁴⁸⁰ of Cbl-b. GSK-3 inactivation by PKB abrogates phosphorylation of Cbl-b at these two sites and results in reduced Cbl-b protein levels. We further show that constitutive activation of PKB in vivo results in a loss of tolerance that is mediated through the downregulation of Cbl-b. Altogether, these data indicate that the PI3K–PKB–GSK-3 pathway is a novel regulatory axis that is important for controlling the decision between T cell activation and tolerance via Cbl-b.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A2aMRk

Ubc9 Binds to ADAP and Is Required for Rap1 Membrane Recruitment, Rac1 Activation, and Integrin-Mediated T Cell Adhesion [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

Although the immune adaptor adhesion and degranulation-promoting adaptor protein (ADAP) acts as a key mediator of integrin inside-out signaling leading to T cell adhesion, the regulation of this adaptor during integrin activation and clustering remains unclear. We now identify Ubc9, the sole small ubiquitin-related modifier E2 conjugase, as an essential regulator of ADAP where it is required for TCR-induced membrane recruitment of the small GTPase Rap1 and its effector protein RapL and for activation of the small GTPase Rac1 in T cell adhesion. We show that Ubc9 interacted directly with ADAP in vitro and in vivo, and the association was increased in response to anti-CD3 stimulation. The Ubc9-binding domain on ADAP was mapped to a nuclear localization sequence (aa 674–700) within ADAP. Knockdown of Ubc9 by short hairpin RNA or expression of the Ubc9-binding–deficient ADAP mutant significantly decreased TCR-induced integrin adhesion to ICAM-1 and fibronectin, as well as LFA-1 clustering, although it had little effect on the TCR proximal signaling responses and TCR-induced IL-2 transcription. Furthermore, downregulation of Ubc9 impaired TCR-mediated Rac1 activation and attenuated the membrane targeting of Rap1 and RapL, but not Rap1-interacting adaptor molecule. Taken together, our data demonstrate for the first time, to our knowledge, that Ubc9 acts as a functional binding partner of ADAP and plays a selective role in integrin-mediated T cell adhesion via modulation of Rap1-RapL membrane recruitment and Rac1 activation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A2laZd

Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt ROR{gamma}t+ and Follicular Phenotypes [CUTTING EDGE]

Regulatory T cells (Tregs) adopt specialized phenotypes defined by coexpression of lineage-defining transcription factors, such as RORt, Bcl-6, or PPAR, alongside Foxp3. These Treg subsets have unique tissue distributions and diverse roles in maintaining organismal homeostasis. However, despite extensive functional characterization, the factors driving Treg specialization are largely unknown. In this article, we show that c-Maf is a critical transcription factor regulating this process in mice, essential for generation of both RORt⁺ Tregs and T follicular regulatory cells, but not for adipose-resident Tregs. c-Maf appears to function primarily in Treg specialization, because IL-10 production, expression of other effector molecules, and general immune homeostasis are not c-Maf dependent. As in other T cells, c-Maf is induced in Tregs by IL-6 and TGF-β, suggesting that a combination of inflammatory and tolerogenic signals promote c-Maf expression. Therefore, c-Maf is a novel regulator of Treg specialization, which may integrate disparate signals to facilitate environmental adaptation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AXk6FW

Cutting Edge: Processing of Oxidized Peptides in Macrophages Regulates T Cell Activation and Development of Autoimmune Arthritis [CUTTING EDGE]

APCs are known to produce NADPH oxidase (NOX) 2–derived reactive oxygen species; however, whether and how NOX2-mediated oxidation affects redox-sensitive immunogenic peptides remains elusive. In this study, we investigated a major immunogenic peptide in glucose-6-phosphate isomerase (G6PI), a potential autoantigen in rheumatoid arthritis, which can form internal disulfide bonds. Ag presentation assays showed that presentation of this G6PI peptide was more efficient in NOX2-deficient (Ncf1^m1J/m1J mutant) mice, compared with wild-type controls. IFN-–inducible lysosomal thiol reductase (GILT), which facilitates disulfide bond–containing Ag processing, was found to be upregulated in macrophages from Ncf1 mutant mice. Ncf1 mutant mice exhibited more severe G6PI peptide-induced arthritis, which was accompanied by the increased GILT expression in macrophages and enhanced Ag-specific T cell responses. Our results show that NOX2-dependent processing of the redox-sensitive autoantigens by APCs modify T cell activity and development of autoimmune arthritis.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A164Df

Lung-Infiltrating Foxp3+ Regulatory T Cells Are Quantitatively and Qualitatively Different during Eosinophilic and Neutrophilic Allergic Airway Inflammation but Essential To Control the Inflammation [ALLERGY AND OTHER HYPERSENSITIVITIES]

Understanding functions of Foxp3⁺ regulatory T cells (Tregs) during allergic airway inflammation remains incomplete. In this study, we report that, during cockroach Ag–induced allergic airway inflammation, Foxp3⁺ Tregs are rapidly mobilized into the inflamed lung tissues. However, the level of Treg accumulation in the lung was different depending on the type of inflammation. During eosinophilic airway inflammation, ~30% of lung-infiltrating CD4 T cells express Foxp3, indicative of Tregs. On the contrary, only ~10% of infiltrating CD4 T cells express Foxp3 during neutrophilic airway inflammation. Despite the different accumulation, the lung inflammation and inflammatory T cell responses were aggravated following Treg depletion, regardless of the type of inflammation, suggesting regulatory roles for Tregs. Interestingly, however, the extent to which inflammatory responses are aggravated by Treg depletion was significantly greater during eosinophilic airway inflammation. Indeed, lung-infiltrating Tregs exhibit phenotypic and functional features associated with potent suppression. Our results demonstrate that Tregs are essential regulators of inflammation, regardless of the type of inflammation, although the mechanisms used by Tregs to control inflammation may be shaped by environmental cues available to them.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AUY1b0

A Protective Function of IL-22BP in Ischemia Reperfusion and Acetaminophen-Induced Liver Injury [IMMUNE REGULATION]

Acute liver injury can be secondary to a variety of causes, including infections, intoxication, and ischemia. All of these insults induce hepatocyte death and subsequent inflammation, which can make acute liver injury a life-threatening event. IL-22 is a dual natured cytokine which has context-dependent protective and pathogenic properties during tissue damage. Accordingly, IL-22 was shown to promote liver regeneration upon acute liver damage. However, other studies suggest pathogenic properties of IL-22 during chronic liver injury. IL-22 binding protein (IL-22BP, IL-22Ra2) is a soluble inhibitor of IL-22 that regulates IL-22 activity. However, the significance of endogenous IL-22BP in acute liver injury is unknown. We hypothesized that IL-22BP may play a role in acute liver injury. To test this hypothesis, we used Il22bp-deficient mice and murine models of acute liver damage induced by ischemia reperfusion and N-acetyl-p-aminophenol (acetaminophen) administration. We found that Il22bp-deficient mice were more susceptible to acute liver damage in both models. We used Il22 x Il22bp double-deficient mice to show that this effect is indeed due to uncontrolled IL-22 activity. We could demonstrate mechanistically increased expression of Cxcl10 by hepatocytes, and consequently increased infiltration of inflammatory CD11b⁺Ly6C⁺ monocytes into the liver in Il22bp-deficient mice upon liver damage. Accordingly, neutralization of CXCL10 reversed the increased disease susceptibility of Il22bp-deficient mice. In conclusion, our data indicate that IL-22BP plays a protective role in acute liver damage, via controlling IL-22–induced Cxcl10 expression.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A2lhnB

Endogenous Calcitriol Synthesis Controls the Humoral IgE Response in Mice [ALLERGY AND OTHER HYPERSENSITIVITIES]

The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)₂D₃ (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D₃-1α-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus. Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR. The data show elevated specific IgE and IgG1 concentrations in the blood of OVA-sensitized Cyp27b1-KO mice compared with wild-type littermates (+898 and +219%). Accordingly, more OVA-specific IgG1-secreting cells are present in spleen and fewer in the bone marrow of Cyp27b1-KO mice. Ag-specific mechanisms are suggested as the leucopoiesis is in general unchanged and activated murine B and T lymphocytes express Cyp27b1. Accordingly, elevated specific IgE concentrations in the blood of sensitized T cell–specific Cyp27b1-KO mice support a lymphocyte-driven mechanism. In an independent IgE-inducing model, i.e., intestinal infection with H. polygyrus, we validated the increase of total and specific IgE concentrations of Cyp27b1-KO compared with wild-type mice, but not those of IgG1 or IgA. We conclude that endogenous calcitriol has an impact on the regulation of IgE in vivo. Our data provide genetic evidence supporting previous preclinical and clinical findings and suggest that vitamin D deficiency not only promotes bone diseases but also type I sensitization.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A3I2I1

Serum IgA Immune Complexes Promote Proinflammatory Cytokine Production by Human Macrophages, Monocytes, and Kupffer Cells through Fc{alpha}RI-TLR Cross-Talk [INNATE IMMUNITY AND INFLAMMATION]

IgA is predominantly recognized to play an important role in host defense at mucosal sites, where it prevents invasion of pathogens by neutralization. Although it has recently become clear that IgA also mediates other immunological processes, little remains known about the potential of IgA to actively contribute to induction of inflammation, particularly in nonmucosal organs and tissues. In this article, we provide evidence that immune complex formation of serum IgA plays an important role in orchestration of inflammation in response to pathogens at various nonmucosal sites by eliciting proinflammatory cytokines by human macrophages, monocytes, and Kupffer cells. We show that opsonization of bacteria with serum IgA induced cross-talk between FcαRI and different TLRs, leading to cell type–specific amplification of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-23. Furthermore, we demonstrate that the increased protein production of cytokines was regulated at the level of gene transcription, which was dependent on activation of kinases Syk and PI3K. Taken together, these data demonstrate that the immunological function of IgA is substantially more extensive than previously considered and suggest that serum IgA–induced inflammation plays an important role in orchestrating host defense by different cell types in nonmucosal tissues, including the liver, skin, and peripheral blood.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A29tSe

Mode of Tolerance Induction and Requirement for Aire Are Governed by the Cell Types That Express Self-Antigen and Those That Present Antigen [ANTIGEN RECOGNITION AND RESPONSES]

Aire controls the fate of autoreactive thymocytes (i.e., clonal deletion or development into regulatory T cells [Tregs]) through transcriptional control of the expression of tissue-restricted self-antigens (TRAs) from medullary thymic epithelial cells (mTECs) and bone marrow (BM)-derived cells. Although TRAs expressed by mTECs and BM-derived cells are suggested to complement each other to generate a full spectrum of TRAs, little is known about the relative contribution of TRAs from each component for establishment of self-tolerance. Furthermore, the precise role of Aire in specific types of Aire-expressing APCs remains elusive. We have approached these issues by generating two different types of transgenic mouse (Tg) model, which express a prefixed model self-antigen driven by the insulin promoter or the Aire promoter. In the insulin-promoter Tg model, mTECs alone were insufficient for clonal deletion, and BM-derived APCs were required for this action by utilizing Ag transferred from mTECs. In contrast, mTECs alone were able to induce Tregs, although at a much lower efficiency in the absence of BM-derived APCs. Importantly, lack of Aire in mTECs, but not in BM-derived APCs, impaired both clonal deletion and production of Tregs. In the Aire-promoter Tg model, both mTECs and BM-derived APCs could independently induce clonal deletion without Aire, and production of Tregs was impaired by the lack of Aire in mTECs, but not in BM-derived APCs. These results suggest that the fate of autoreactive thymocytes together with the requirement for Aire depend on the cell types that express self-antigens and the types of APCs involved in tolerance induction.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AW1PJt

B Cells Drive Autoimmunity in Mice with CD28-Deficient Regulatory T Cells [AUTOIMMUNITY]

Follicular regulatory T (T_FR) cells are a newly defined regulatory T cell (Treg) subset that suppresses follicular helper T cell–mediated B cell responses in the germinal center reaction. The precise costimulatory signal requirements for proper T_FR cell differentiation and function are still not known. Using conditional knockout strategies of CD28, we previously demonstrated that loss of CD28 signaling in Tregs caused autoimmunity in mice (termed CD28-Treg mice), characterized by lymphadenopathy, accumulation of activated T cells, and cell-mediated inflammation of the skin and lung. In this study, we show that CD28 signaling is required for T_FR cell differentiation. Treg-specific deletion of CD28 caused a reduction in T_FR cell numbers and function, which resulted in increased germinal center B cells and Ab production. Moreover, residual CD28-deficient T_FR cells showed a diminished suppressive capacity as assessed by their ability to inhibit Ab responses in vitro. Surprisingly, genetic deletion of B cells in CD28-Treg mice prevented the development of lymphadenopathy and CD4⁺ T cell activation, and autoimmunity that mainly targeted skin and lung tissues. Thus, autoimmunity occurring in mice with CD28-deficient Tregs appears to be driven primarily by loss of T_FR cell differentiation and function with resulting B cell–driven inflammation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2A2l5ET

Proinflammatory T Cell Status Associated with Early Life Adversity [CLINICAL AND HUMAN IMMUNOLOGY]

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA (n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69⁺CD8⁺ T cells (p = 0.022), increased numbers of HLA-DR⁺ CD4 and HLA-DR⁺ CD8 T cells (p < 0.001), as well as increased numbers of CD25⁺CD8⁺ T cells (p = 0.036). ELA also showed a trend toward higher numbers of CCR4⁺CXCR3^–CCR6⁺ CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AUs7M2

Broad Susceptibility of Nucleolar Proteins and Autoantigens to Complement C1 Protease Degradation [AUTOIMMUNITY]

Anti-nuclear autoantibodies, which frequently target the nucleoli, are pathogenic hallmarks of systemic lupus erythematosus (SLE). Although the causes of these Abs remain broad and ill-defined, a genetic deficiency in C1 complex (C1qC1r₂C1s₂) or C4 is able to induce these Abs. Considering a recent finding that, in dead cells, nucleoli were targeted by C1q and two nucleolar autoantigens were degraded by C1r/C1s proteases, we considered that C1 could help protect against antinuclear autoimmunity by broadly degrading nucleolar proteins or autoantigens. Nucleoli were isolated to homogeneity and structurally defined. After C1 treatment, cleaved nucleolar proteins were identified by proteomic two-dimensional fluorescence difference gel electrophoresis and mass spectrometry, and further verified by Western blotting using specific Abs. The extent of nucleolar autoantigen degradation upon C1 treatment was estimated using SLE patient autoantibodies. The isolated nucleoli were broadly reactive with SLE patient autoantibodies. These nucleoli lacked significant autoproteolysis, but many nucleolar proteins and autoantigens were degraded by C1 proteases; >20 nucleolar proteins were identified as C1 cleavable. These were further validated by Western blotting using specific Abs. The broad autoantigenicity of the nucleoli may attribute to their poor autoproteolysis, causing autologous immune stimulation upon necrotic exposure. However, C1q targets at these nucleoli to cause C1 protease activation and the cleavage of many nucleolar proteins or autoantigens. This may represent one important surveillance mechanism against antinuclear autoimmunity because C1 genetic deficiency causes anti-nuclear autoantibodies and SLE disease.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AW1M0f

Regnase-1 and Roquin Nonredundantly Regulate Th1 Differentiation Causing Cardiac Inflammation and Fibrosis [IMMUNE REGULATION]

Regnase-1 and Roquin are RNA binding proteins that are essential for degradation of inflammatory mRNAs and maintenance of immune homeostasis. Although deficiency of either of the proteins leads to enhanced T cell activation, their functional relationship in T cells has yet to be clarified because of lethality upon mutation of both Regnase-1 and Roquin. By using a Regnase-1 conditional allele, we show that mutations of both Regnase-1 and Roquin in T cells leads to massive lymphocyte activation. In contrast, mutation of either Regnase-1 or Roquin affected T cell activation to a lesser extent than the double mutation, indicating that Regnase-1 and Roquin function nonredundantly in T cells. Interestingly, Regnase-1 and Roquin double-mutant mice suffered from severe inflammation and early formation of fibrosis, especially in the heart, along with the increased expression of Ifng, but not Il4 or Il17a. Consistently, mutation of both Regnase-1 and Roquin leads to a huge increase in the Th1, but not the Th2 or Th17, population in spleens compared with T cells with a single Regnase-1 or Roquin deficiency. Regnase-1 and Roquin are capable of repressing the expression of a group of mRNAs encoding factors involved in Th1 differentiation, such as Furin and Il12rb1, via their 3' untranslated regions. Moreover, Regnase-1 is capable of repressing Roquin mRNA. This cross-regulation may contribute to the synergistic control of T cell activation/polarization. Collectively, our results demonstrate that Regnase-1 and Roquin maintain T cell immune homeostasis and regulate Th1 polarization synergistically.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AUs5DU