Spontaneous nasal cerebrospinal fluid leaks: management of 24 patients over 11 years

Abstract

Purpose

Most cases of non-traumatic nasal cerebrospinal fluid (CSF) leaks occur spontaneously without any obvious reason. Severe and life-threatening complications are possible consequences. Endoscopic repair is considered the gold standard; however, diagnosis and therapy of these CSF leaks stay challenging.

Methods

In this retrospective analysis, patients who presented with spontaneous nasal CSF leaks from 2006 to 2017 were included. Symptoms, diagnostics, localization of the skull base defect, surgical method, outcome, and postoperative treatment were recorded.

Results

Twenty four patients were included. 8 patients presented with symptoms of meningitis. The skull base defects were most commonly located in the anterior ethmoid roof—especially in the cribriform plate—and in the lateral part of the sphenoid sinus. 21 patients had a BMI above 25. In only 13 cases the defect could be detected preoperatively via computed tomography or additional magnetic resonance imaging. In all patients intraoperative visualization of the CSF leak was possible using intrathecal application of sodium-fluorescein. Endoscopic repair was the initial surgical method for all patients and proved to be successful in 80% of the cases. In most cases surgical revision was performed endoscopically; however, in two patients an open transpterygoidal approach was necessary.

Conclusions

Spontaneous nasal CSF leaks often initially present with symptomatic meningitis. Imaging does not always clearly identify the skull base defect. Common localizations are the anterior ethmoid roof and the lateral sphenoid sinus. Obesity seems to be a predisposing factor. In most cases, endoscopic repair with low morbidity is possible; however, an individualized approach is necessary.

https://ift.tt/2B9mDOj

Achilles insertion bone pathology not related to pain in a triathlete with cystic fibrosis

Abstract

This report concerns the unusual case of a 48-year old, world-class triathlete who has won 11 ironman competitions. She has reached the top level of international endurance sport in spite of being diagnosed with cystic fibrosis. This patient presented with Achilles pain and severe bony pathology at her left Achilles insertion. Traditionally this condition is treated via tendon detachment and re-attachment or intra-tendinous surgery, followed by a protracted rehabilitation. These procedures were considered risky due to this patient's chronic disease with vulnerability to immobilization. Instead, she was treated by surgical removal of the superficial bursa alone, under local anaesthetic. This allowed the patient to become active and load her Achilles tendon immediately, and resulted in a significant symptomatic improvement. This case illustrates that despite the presence of severe tendon and bone pathology at the Achilles insertion, pain may originate in the superficial bursa; a structure ignored by traditional operations.

https://ift.tt/2BbuRWg

Merkel-cell carcinoma of the upper limb

Abstract

Merkel-cell carcinoma is a rare form of aggressive cutaneous cancer that is associated with a poor prognosis. Despite significant advances, its pathogenesis is still poorly understood, and treatment remains controversial. Timely diagnosis and early management is essential in improving survival rate. We present a case of a 63-year-old patient with a rapidly growing upper limb Merkel-cell carcinoma. It was treated with wide-local excision and adjuvant radiotherapy.

https://ift.tt/2P85KGT

Unusual lymph node metastasis from cancer of the thoracic esophagus

Abstract

A 76-year-old male received concurrent chemoradiotherapy, at a dose of 60 Gy with low-dose 5-fluorouracil, for cT1bN0M0 squamous cell carcinoma of the mid-thoracic esophagus. Because his primary tumor relapsed with mediastinal and right supraclavicular node metastasis 4 months after completion of chemoradiotherapy, right transthoracic esophagectomy with mediastinal and right cervical lymphadenectomy was performed. However, metastatic tumors developed deep beneath the anterior border of the trapezius muscle 2 months after esophagectomy. En bloc dissection of the adipose tissue including the tumor and the transverse cervical artery was performed, followed by adjuvant radiotherapy of 50.4 Gy to the area of dissection. The patient died of pneumonia 11 months after metastasectomy, with locally recurrent disease. We have had three cases of this unusual lymph nodes metastasis from cancer of the thoracic esophagus to date and here present the characteristic imaging findings and the possible mechanism of this unusual lymph node metastasis.

https://ift.tt/2KQaYn8

Age and adenoma size are independent risk factors for the development of carcinoma ex pleomorphic adenoma

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): E.S. Egal, F.V. Mariano, A.M. Altemani, K. Metze

https://ift.tt/2MnbjCO

ERK-TSC2 signalling in constitutively-active HRAS mutant HNSCC cells promotes resistance to PI3K inhibition

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Kara M. Ruicci, Nicole Pinto, Mohammed I. Khan, John Yoo, Kevin Fung, Danielle MacNeil, Joe S. Mymryk, John W. Barrett, Anthony C. Nichols

Abstract

Objectives

The PI3K/AKT/mTOR pathway is frequently altered in head and neck squamous cell cancer (HNSCC), making this pathway a logical therapeutic target. However, PI3K targeting is not universally effective. Biomarkers of response are needed to stratify patients likely to derive benefit and exclude those unlikely to respond.

Materials and methods

We examined the sensitivity of cell lines with constitutively-active (G12V mutant) HRAS and wild-type HRAS to PI3K inhibition using flow cytometry and cell viability assays. We then overexpressed and silenced HRAS and measured sensitivity to the PI3K inhibitor BYL719. Immunoblotting was used to determine activation of the PI3K pathway. MEK and mTOR inhibitors were then tested in HRAS mutant cells to determine their efficacy.

Results

HRAS mutant cell lines were non-responsive to PI3K inhibition. Overexpression of HRAS led to reduced susceptibility to PI3K inhibition, while knockdown improved sensitivity. Immunoblotting revealed suppressed AKT phosphorylation upon PI3K inhibition in both wild-type and HRAS mutant cell lines, however mutant lines maintained phosphorylation of S6, downstream of mTOR. Targeting mTOR effectively reduced viability of HRAS mutant cells and we subsequently examined the ERK-TSC2-mTOR cascade as a mediator of resistance to PI3K inhibition.

Conclusions

HRAS mutant cells are resistant to PI3K inhibition and our findings suggest the involvement of a signalling intersection of the MAPK and PI3K pathways at the level of ERK-TSC2, leading to persistent mTOR activity. mTOR inhibition alone or in combination with MAPK pathway inhibition may be a promising therapeutic strategy for this subset of HNSCC tumors.

https://ift.tt/2MJBd0p

Self-reported oral morbidities in long-term oropharyngeal cancer survivors: A cross-sectional survey of 906 survivors

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Richard C. Cardoso, Ahmad Qazali, Jhankruti Zaveri, Mark S. Chambers, Gary Brandon Gunn, Clifton D. Fuller, Stephen Y. Lai, Frank E. Mott, Katherine A. Hutcheson

Abstract

Objective

The purpose of this study is to estimate the prevalence and severity of late oral morbidities in disease-free oropharyngeal cancer (OPC) survivors using patient reported outcomes.

Materials and methods

Cross-sectional survivorship survey of patients who completed definitive treatment for oropharyngeal carcinoma  > 12-months previously without evidence of recurrence, second primary malignancy, or distant metastasis after index cancer. Using MD Anderson Symptom Inventory- Head and Neck Module (MDASI-HN), scores for 4 self-reported oral morbidities: dry mouth, mucus secretions, mouth and throat sores, and teeth and gum issues were evaluated.

Results

Among 906 survey respondents (57% response rate), (median survival time: 7 years), "dry mouth" and "problems with my mucus" were reported moderate/severe (MDASI-HN item score ≥5) in 39% and 22% of respondents, while 14% reported moderate/severe "problems with teeth and gums". Smoking at the time of survey was significantly associated with the severity of oral symptoms including "mucus" (p = 0.03), "dry mouth" (p = 0.02), "problems with my teeth and gums" (p = 0.001). All the oral morbidities symptom items significantly, positively correlated with the mean interference scores reflecting adverse impact to quality of life (QOL): "mucus" (r = 0.445, p < 0.001), "problems with teeth" (r = 0.446, p < 0.001), "mouth sores" (r = 0.321, p < 0.001) and "dry mouth" (r = 0.459, p < 0.001).

Conclusion

This study showed that 45.5% reported at least one late oral morbidity at moderate/severe level which negatively correlated overall function, even years after treatment.

https://ift.tt/2Mnbdeq

Staging HPV-related oropharyngeal cancer: Validation of AJCC-8 in a surgical cohort

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Mathew Geltzeiler, Marnie Bertolet, William Albergotti, John Gleysteen, Brennan Olson, Michael Persky, Neil Gross, Ryan Li, Peter Andersen, Seungwon Kim, Robert L. Ferris, Umamaheswar Duvvuri, Daniel Clayburgh

Abstract

Importance

The American Joint Committee on Cancer, 8th edition (AJCC-8) contains a new staging system for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Our study aim was to evaluate the effectiveness of the AJCC-8 relative to the AJCC 7th edition (AJCC-7).

Materials and methods

A retrospective chart review was performed on a multi-institutional, prospectively collected dataset from two tertiary referral centers. All patients had HPV+ OPSCC treated primarily with surgery. The prognostic value of AJCC-7 and AJCC-8 were compared for 5-year overall survival (OS) and disease-specific survival (DFS).

Results

AJCC-8 pathological staging effectively risk stratified patients, creating a Cox model with a better fit (lower Akaike's Information Criterion, p < 0.0001) when compared to AJCC-7 pathological stages for both OS and DFS. The AJCC-8 pathologic staging did not produce a better fit than the AJCC-8 clinical staging (p = 0.15) for OS, however, AJCC-8 pathologic was more effective than AJCC-8 clinical for DFS (p < 0.0001). 76% of patients did not change their stage between clinical and pathologic AJCC-8 staging; 14% were upstaged by 1, <1% were upstaged by 2, 7% were downstaged by 1, and 3% downstaged by 2.

Conclusions and relevance

The new AJCC-8 staging system represents a significant improvement over AJCC-7 for risk stratification into groups that predict overall survival and disease-specific survival of surgically treated HPV+ OPSCC patients. The AJCC- 8 pathologic staging system was not significantly better than the AJCC-8 clinical staging system for overall survival, however, the pathologic staging system was better than the clinical for disease free survival.

https://ift.tt/2MHIlKA

Communication of prognosis in head and neck cancer patients; a descriptive qualitative analysis

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Emilie A.C. Dronkers, Arta Hoesseini, Maarten F. de Boer, Marinella P.J. Offerman

Abstract

Objectives

In shared decision making it is important to adequately, timely and actively involve patients in treatment decisions. Sharing prognostic information can be of key importance. This study describes whether and how prognostic information on life expectancy is included during communication on diagnosis and treatment plans between physicians and head and neck (H&N) oncologic patients in different phases of disease.

Methods

A descriptive, qualitative study was performed of n = 23 audiotaped physician-patient conversations in which both palliative and curative treatment options were discussed and questions on prognosis were expected. Verbatim transcribed consultations were systematically analyzed. A distinction was made between prognostic information that was provided (a) quantitatively: by giving numerical probability estimates, such as percentages or years or (b) qualitatively: through the use of words such as 'most likely' or 'highly improbable'.

Results

In all consultations, H&N surgeons provided some prognostic information. In 5.9% of the provided prognostic information, a quantitative method was used. In 94.1% prognostic information was provided qualitatively, using six identified approaches. H&N surgeons possibly affect patients' perception of prognostic content with two identified communication styles: directive (more physician-centered) and affective (more patient-centered).

Conclusion

This study is first in providing examples of how H&N surgeons communicate with their patients regarding prognosis in all stages of disease. They often exclude specific prognostic information. The study outcomes can be used as a first step in developing a guideline for sharing prognostic information in H&N oncologic patients, in order enable the process of shared decision making.

https://ift.tt/2P5UUAU

Survival benefit of post-operative chemotherapy for intermediate-risk advanced stage head and neck cancer differs with patient age

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Michelle M. Chen, A. Dimitrios Colevas, Uchechukwu Megwalu, Vasu Divi

Abstract

Objectives

The National Comprehensive Cancer Network (NCCN) guidelines state that surgical patients with advanced-stage head and neck cancer (HNC) and risk factors other than extranodal extension (ENE) or positive margins should consider post-operative chemoradiation (POCRT). The goal of our study was to determine if POCRT is associated with overall survival (OS) compared with post-operative radiation therapy (PORT) and whether this varies with patient age.

Material and Methods

We conducted a retrospective study of 5319 adult patients with stage III-IV HNC who received primary surgical treatment with POCRT or PORT in the National Cancer Database (2010–2013). Patients with distant metastases, ENE, and positive margins were excluded. Intermediate risk features included pT3-T4, pN2-N3 disease, and lymphovascular invasion. Our main outcome was overall survival (OS). Statistical analysis included chi-squared tests and Cox proportional hazards regressions.

Results

On multivariable analysis for non-oropharyngeal cancer patients <70 years, POCRT was associated with improved OS for T1-4N2-3 disease (hazard ratio [HR], 0.73, 95% confidence interval [CI]; 0.58–0.93) but was not associated with OS for T3-4N0-1 disease (HR, 0.92; 95% CI, 0.71–1.19). For patients ≥70 years, POCRT was not associated with improved OS for patients with T1-4N2-3 disease (HR, 1.21; 95% CI, 0.79–1.86) or T3-4N0-1 disease (HR, 1.08; 95% CI, 0.71–1.65). For oropharyngeal cancer patients with HPV-positive disease, POCRT was associated with decreased OS (HR, 9.52; 95% CI, 2.38–38.08).

Conclusion

Chemoradiation may offer a survival benefit for non-oropharyngeal intermediate-risk advanced-stage HNC patients <70 years of age with T1-4N2-3 disease, but may not benefit those ≥70 years of age or those with T3-4N0-1 disease.

https://ift.tt/2BhdMKK

Induction chemotherapy with carboplatin, nab-paclitaxel and cetuximab for at least N2b nodal status or surgically unresectable squamous cell carcinoma of the head and neck

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Jared Weiss, Jill Gilbert, Allison Mary Deal, Mark Weissler, Chris Hilliard, Bhishamjit Chera, Barbara Murphy, Trevor Hackman, Jay Justin Liao, Juneko Grilley Olson, David Neil Hayes

Abstract

Background

Although induction studies of TPF in SCCHN have not improved outcomes compared to chemoradiotherapy alone, phase II studies of weekly carboplatin (CbP), paclitaxel and cetuximab (C225) have shown promising results. Nano-albumin-paclitaxel (nab-paclitaxel) based chemotherapy has demonstrated a higher response rate (RR) than solvent-based paclitaxel in squamous cell carcinoma of the lung with favorable toxicity.

Materials and methods

Patients with treatment naïve SCCHN of any site with ≥N2b disease or that was unresectable by strict criteria were eligible. Patients were treated with nab-paclitaxel 100 mg/m², CbP area under the curve (AUC) 2 and C225 400 mg/m² week 1 then 250 mg/m² for six weeks, followed by standard of care chemoradiotherapy (CRT). The primary endpoint was clinical response rate to induction therapy as defined by RECIST version 1.1. Secondary measures included toxicity, progression-free survival, overall survival and quality of life as measured by FACT-HN.

Results

38 eligible subjects were treated. Primary sites were: oropharynx (OPX) (25), larynx (3) oral cavity (OC) (9), hypopharynx (1). The most common grade 3 or 4 toxicity during induction was acneiform rash (26%) followed by neutropenia (16%). RR was 76.3%. Median PFS and OS have not been reached (median follow-up of 3.3 years); they were superior in patients with response.

Conclusions

The combination of nab-paclitaxel, CbP and C225 is feasible, tolerable and active against locally advanced SCCHN.

https://ift.tt/2MnaB8C

Low versus high activity radioiodine remnant ablation for differentiated thyroid carcinoma with gross extrathyroidal extension invading only strap muscles

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): So Young Park, Hye In Kim, Joon Young Choi, Jun-Ho Choe, Jung-Han Kim, Jee Soo Kim, Young Lyun Oh, Soo Yeon Hahn, Jung Hee Shin, Soo Hyun Ahn, Kyunga Kim, Jong Gill Jeong, Sun Wook Kim, Jae Hoon Chung, Tae Hyuk Kim

Abstract

Objectives

The efficacy of radioiodine remnant ablation (RRA) for patients with differentiated thyroid carcinoma (DTC) with gross extrathyroidal extension (ETE) is well described in observational studies. However, its role in gross ETE invading only strap muscles, T3b category in the newly proposed eighth edition of the TNM staging system, is currently unknown.

Methods

This study retrospectively analyzed 260 DTC patients with ETE invading only strap muscles who underwent thyroidectomy at a tertiary Korean hospital between 1994 and 2005. Cancer-specific survival (CSS) and recurrence-free survival (RFS) in the no RRA (n = 13), low RRA activity (<3.7 GBq, n = 80), and high RRA activity (≥3.7 GBq, n = 167) groups were studied.

Results

No significant differences were observed between low and high activity RRA groups in terms of 10-year CSS (97.3% versus 99.3%; HR 0.23, 95% CI 0.02–2.57; p = .235) and RFS (86.8% versus 88.8%; 0.90, 0.40–2.03; p = .804). In the no RRA group, no patients died of cancer, and only one developed structural recurrence. In Cox regression analyses with inverse probability of treatment weighting adjusted for clinicopathologic risk factors, high activity RRA was not related to recurrence outcomes compared to low activity (HR 0.60, 95% CI 0.26–1.35; p = .214).

Conclusions

Long term oncologic outcomes did not significantly differ between low versus high activity RRA groups, which suggests that low activity RRA might be sufficient in patients with DTC with gross ETE invading only strap muscles. Further studies are needed to clarify the optimal activity of RRA in these patients.

https://ift.tt/2MGEEFa

Prospective evaluation of patient reported swallow function with the Functional Assessment of Cancer Therapy (FACT), MD Anderson Dysphagia Inventory (MDADI) and the Sydney Swallow Questionnaire (SSQ) in head and neck cancer patients

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Luke C. Peng, Xuan Hui, Zhi Cheng, Michael R. Bowers, Joseph Moore, Emilie Cecil, Amanda Choflet, Alex Thompson, Mariah Muse, Ana P. Kiess, Brandi R. Page, Christine G. Gourin, Carole Fakhry, Michal Szczesniak, Julia Maclean, Peter Wu, Ian Cook, Todd R. McNutt, Harry Quon

Abstract

Objectives

The Functional Assessment of Cancer Therapy (FACT) instrument is comprised of a group of related and overlapping quality of life (QoL) questionnaires including a core general form, head and neck cancer (HNC)-specific items, and an expert-selected index (FACT-HNSI). Understanding how these relate to more HNC-specific instruments such as the MD Anderson Dysphagia Inventory (MDADI) and Sydney Swallow Questionnaire (SSQ) is vital for guiding their use in clinical trials.

Materials and methods

HNC patients concurrently completed MDADI, SSQ, and FACT questionnaires at radiation oncology clinic visits (2015–2016). Spearman correlation coefficients were calculated between each FACT instrument and MDADI or SSQ. Unsupervised k-means cluster analyses were performed to identify clusters of similar QoL responses. Principal component analysis (PCA) identified the degree of variability explained by each instrument.

Results

We identified 631 instances (363 patients) where the questionnaires were completed concurrently. Correlations between the various FACT measures and SSQ or MDADI were all significant (p < 0.001), but FACT HNC-specific subscale and FACT-HNSI showed the strongest correlation with MDADI and SSQ. Clustering identified 3 distinct groups of responses when combining instruments either pairwise or three-way. PCA revealed that MDADI and FACT HNC-specific subscale provide similar and likely redundant information.

Conclusion

FACT HNC-subscale and FACT-HNSI may be preferable over other FACT measures for use in clinical trials where patient-reported swallow function is evaluated. MDADI and FACT provide similar insights into HNC patient QoL while SSQ provides additional, complementary information which could serve to better stratify patients into groups with high, medium, and low QoL outcomes.

Graphical abstract

https://ift.tt/2P4qVJH

Clinical analysis of second primary gingival squamous cell carcinoma after radiotherapy

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Xiaoyan Fu, Shuwei Chen, Weichao Chen, Zhongyuan Yang, Ming Song, Hao Li, Huayong Zhang, Fan Yao, Xuan Su, Tianrun Liu, An-Kui Yang

Abstract

Introduction

Clinically, we have observed that some oral cancer patients have a history of radiotherapy for head and neck cancer; we have named this condition radiotherapy-associated cancer (RAC). Gingival cancer, which is usually juxtaposed with other oral cancer subtypes, is seldom reported individually, and there are few reports on the association between the incidence of oral cancer and history of radiation therapy. Therefore, this study aimed to elucidate the clinicopathological features and prognosis of second primary gingival squamous cell carcinoma after head and neck radiotherapy.

Materials and methods

The data collected included 450 patients diagnosed with gingival squamous cell carcinoma from 1964 to 2012 at Sun Yat-sen University Cancer, among whom 52 patients had a history of radiotherapy for head and neck cancer. We retrospectively analysed the differences in the clinicopathological characteristics and prognosis between sporadic gingival squamous cell carcinoma and radiation-associated gingival carcinoma, with an emphasis on gingival carcinoma.

Results

Sporadic gingival squamous cell carcinoma is less likely to have more advanced T stage, and the second primary tumour is more likely to be located in the molar area of the maxillary gingiva than in the mandibular gingiva (75.6% vs 24.4%, P < 0.05). The 5-year overall survival of patients with second primary gingival carcinoma was influenced by age distribution, T classification, N classification, clinical TNM stage, histological grade and radiation history in head and neck. Mandibular gingival carcinoma was more likely to have an increased neck lymph node metastasis than maxillary gingival carcinoma (P = 0.001), but there was no significant difference in 5-year overall survival between these two groups (P = 0.828). The main therapy for gingiva carcinoma is surgery or comprehensive treatment based on surgery.

Conclusions

Second primary gingival squamous cell carcinoma after radiotherapy demonstrated particular clinicopathologic features, such as prominent sites and TNM stage; and there was statistically significant difference in 5-year overall survival and prognosis between second primary gingival carcinoma after radiotherapy and sporadic gingival carcinoma.

https://ift.tt/2MJmZwB

Survival impact and toxicity of metformin in head and neck cancer: An analysis of the SEER-Medicare dataset

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): William A. Stokes, Megan Eguchi, Arya Amini, Mohammad K. Hararah, Ding Ding, Jessica D. McDermott, Cathy J. Bradley, Sana D. Karam

Abstract

Objectives

Recent preclinical research has renewed interest in the interplay between glucose dysregulation and cancer. Metformin holds promise as an adjunctive antineoplastic agent in head and neck cancer (HNC). We aimed to explore the impact of metformin in HNC patients from a population-based dataset.

Patients & Methods

Patients diagnosed with HNC from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked dataset and categorized into three groups: non-diabetics (nD), diabetics not taking metformin (DnM), and diabetics taking metformin (D + M). Overall survival (OS) and cancer-specific survival (CSS) were compared between groups using Kaplan-Meier and Cox regression controlling for sociodemographic, clinical, and treatment covariates. The incidence of toxicities associated with HNC therapy was compared among groups using χ² analysis.

Results

Among 1646 patients, there were 1144 nD, 378 DnM, and 124 D + M. 2-year OS rates was 65.6% for nD, 57.7% for DnM, and 73.4% for D + M by Kaplan-Meier (p < 0.01), and corresponding rates of 2-year CSS were 73.7%, 66.1%, and 88.8% (p < 0.01), respectively. On Cox multivariable analysis, OS among the three groups did not significantly differ; however, CSS was significantly worse among both nD versus DnM as compared to D + M. Toxicity rates were not significantly increased among D + M.

Conclusion

HNC patients with diabetes taking metformin experience improved CSS. Prospective investigation of the addition of metformin to standard-of-care HNC therapy is warranted.

https://ift.tt/2MqFLf4

Oral tongue carcinoma among young patients: An analysis of risk factors and survival

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Douglas R. Farquhar, April M. Tanner, Maheer M. Masood, Sagar R. Patel, Trevor G. Hackman, Andrew F. Olshan, Angela L. Mazul, Jose P. Zevallos

Abstract

Introduction

The incidence of oral tongue squamous cell carcinoma (OTSCC) in younger adults has rapidly increased over the past two decades. While tobacco and alcohol use may be less likely to cause these tumors, it remains controversial whether differences also exist in their prognosis. Our aim is to examine the risk factors for cancer among young (<45 years old) OTSCC patients at our institution, and to compare their recurrence and survival with older patients in a matched cohort.

Materials and methods

All OTSCC patients seen at our institution between 2000 and 2015 were reviewed. Patients under 45 who with sufficient treatment information were matched 1:1 on race, T-stage, and N-stage with patients 45 and older. Three-year recurrence and survival were determined in stratified and adjusted Cox regression models.

Results

Of 397 OTSCC patients were seen at our institution, 117 (29%) were less than 45 years old. Younger patients were significantly more likely to be female, (50% vs. 39%; p = 0.04) and to abstain from tobacco (51% vs. 39%; p < 0.01). Young patients in the matched cohort were significantly more likely to have a recurrence (HR 3.9 95% CI 1.4–10.5). There was no difference in overall survival.

Conclusion

Younger OTSCC patients in a matched cohort were more likely to recur within 3 years, although there was no difference in overall mortality. Differences in risk factors and recurrence between older and younger patients suggest that some cancer among younger patients may be distinct from traditional OTSCC.

https://ift.tt/2MJmRND

Radiation-induced nasopharyngeal ulcers after intensity modulated radiotherapy in primary nasopharyngeal carcinoma patients: A dose-volume-outcome analysis

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Yujiao Li, Tingting Xu, Wei Qian, Xueguan Lu, Chaosu Hu

Abstract

Objective

This is a retrospective dose-volume-outcome analysis of radiation-induced nasopharyngeal ulcers after intensity modulated radiotherapy in primary nasopharyngeal carcinoma (NPC) patients, with the aim to determine how the radiation doses to nasopharynx influence the occurence of radiation-induced nasopharyngeal ulcer (RINU) and predict the most serious complication of radiotherapy for NPC.

Methods

Data from 6023 consecutive and nonselected histologically proven primary NPC patients treated with definitive IMRT were collected and 25 patients were diagnosed with nasopharyngeal ulcer and met the diagnosis criteria of RINU. Predictive dosimetric factors were identified by using univariate and multivariate analysis.

Results

Paired samples t-tests showed all dosimetric factors were significantly correlated with the development of RINU, and these factors were associated with each other closely. (P < 0.001) Multivariate analysis revealed D3cc (dose to 3 mL of the nasopharynx) was an independent predictor for RINU (P = 0.01); the area under the ROC curve for D3cc was 0.87 (P < 0.001), and the cutoff point 73.67 Gy may be the dose tolerance of the nasopharynx. The primary tumor location, distribution of high dose regions and the location of RINU were consistent.

Conclusions

The study indicates that radiation-induced nasopharyngeal ulcer is consistent with primary tumor location and 'hottest spots' regions and we suggest a D3cc limit of 73.67 Gy for the nasopharynx. Physicians should be cautious of such 'hot spots' in the nasopharynxduring IMRT treatment plan optimization, review and approval to avoid the most serious complication of radiotherapy for NPC.

https://ift.tt/2P88WlV

Clarithromycin as the empiric antibiotic therapy for medication-related osteonecrosis of the jaw in multiple myeloma patients

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Yehuda Zadik

Abstract

About half of individuals diagnosed with medication-related osteonecrosis of the jaw (MRONJ) are multiple myeloma (MM) patients, and most are treated using antibiotics for long-term courses. The penicillin group is recommended as the empiric drug of choice, and quinolones, metronidazole, clindamycin, doxycycline, and erythromycin as alternatives. This paper suggests the macrolide clarithromycin as the empiric antibiotic therapy of MRONJ in MM patients because of its better pharmacologic properties in comparison to erythromycin, and the beneficial effect of this agent in MM. This empiric antibiotic regimen should be later adjusted according to the response and findings of the microbial cultures.

https://ift.tt/2MJu4x1

Clinical outcomes with therapies for previously treated recurrent/metastatic head-and-neck squamous cell carcinoma (R/M HNSCC): A systematic literature review

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Mallika Lala, Diana Chirovsky, Jonathan D. Cheng, Kapil Mayawala

Abstract

Objectives

A wide range of objective response rates (ORRs: 0–53%) among available treatments in patients with R/M HNSCC with progression on or after platinum-based chemotherapy (PBT) renders treatment selection a challenge. This systematic literature review (SLR) was intended to aid clinical decision-making by classifying historical studies to accurately characterize the response in second-line (progression on/after platinum-based therapy), and third-line (progression on/after platinum and cetuximab/other drug) settings.

Methods

SLR was performed to characterize the ORR, duration of response (DOR), progression-free survival (PFS) and overall survival (OS) with therapies recommended by the National Comprehensive Cancer Network (NCCN) guidelines. Clinical trials published in English between January 1, 1985, and September 30, 2016 were identified by searching the PubMed (Medline), Cochrane, and Embase databases.

Results

The SLR identified 34 key studies in second-line R/M HNSCC patients, and one of these included a third-line patient cohort. However, several studies did not enrol a strictly second-line population. Response in a true second-line setting was elucidated by categorizing the studies using a novel framework defined according to the extent to which enrolled patients were second-line. Only seven studies were strictly second-line, with an estimated pooled ORR of 4% (95% CI = 2–8%; N = 414) for methotrexate and 11% (95% CI = 7–15%; N = 235) for cetuximab, and a reported ORR of 14% (N = 78) from a single study of paclitaxel. The median DOR was limited with cetuximab (∼4 months) and paclitaxel (∼7 months), and not reported for methotrexate. Median PFS or time to progression (TTP) ranged from 1.7 to 3.5 months, and median OS from 4.3 to 6.7 months. The ORR in the only third-line study was 0% (95% CI = 0–7; N = 53) for the platinum + cetuximab combination.

Conclusion

These findings emphasize the historically bleak prognoses in patients with R/M HNSCC following PBT progression. Anti-PD-1 therapies, namely pembrolizumab and nivolumab, represent novel treatment options that may improve clinical outcomes.

https://ift.tt/2P7Y0o3

Cellular-based immunotherapy in Epstein-Barr virus induced nasopharyngeal cancer

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Andrea Zhe Ern Lee, Louise Soo Yee Tan, Chwee Ming Lim

Abstract

Undifferentiated Nasopharyngeal carcinoma (NPC) is ubiquitously identified with the Epstein-Barr virus (EBV), making this cancer a suitable candidate for cellular-based immunotherapy (CBI) due to its expression of potentially targetable tumor-associated viral antigens. Various preclinical and clinical studies have explored the use of cytotoxic T cells (CTLs), tumor-infiltrating lymphocytes (TILs), natural killer (NK) cells, and dendritic cells (DCs) in the treatment of both refractory and locally advanced NPC with some success. Notably, immune-mediated antitumor effects were observed even in heavily pre-treated NPC patients, suggesting potential clinical benefit of CBI in this group of patients. These immune anti-tumor effects may be even more clinically evident when used as a first-line treatment, since there may not be an intense immunosuppressive environment which is typically encountered in refractory cancer patients. Additionally, CBI may exert an effect in priming the immune system and diminishing the cancer's acquired resistance to exert a more robust response to previously failed chemotherapy. Although these results are encouraging, further refinements of clinical protocols to boost anti-tumor response and benefit a larger subset of patients proved necessary. Herein, we aim to review the rational of developing CBI in EBV-induced NPC and summarize its current applications in clinical studies.

https://ift.tt/2MJmC5b

Accuracy of computer-assisted surgery in mandibular reconstruction: A systematic review

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Gustaaf J.C. van Baar, Tymour Forouzanfar, Niels P.T.J. Liberton, Henri A.H. Winters, Frank K.J. Leusink

Abstract

Computer-assisted surgery (CAS) for mandibular reconstruction was developed to improve conventional treatment methods. In the past years, many different software programs have entered the market, offering numerous approaches for preoperative planning and postoperative evaluation of the CAS process of mandibular reconstruction. In this systematic review, we reviewed planning and evaluation methods in studies that quantitatively assessed accuracy of mandibular reconstruction performed with CAS. We included 42 studies describing 413 mandibular reconstructions planned and evaluated using CAS. The commonest software was Proplan/Surgicase CMF (55%). In most cases, the postoperative virtual 3-dimensional model was compared to the preoperative 3-dimensional model, revised to the virtual plan (64%). The commonest landmark for accuracy measurements was the condyle (54%). Accuracy deviations ranged between 0 mm and 12.5 mm and between 0.9° and 17.5°. Because of a lack of uniformity in planning (e.g., image acquisition, mandibular resection size) and evaluation methodologies, the ability to compare postoperative outcomes was limited; meta-analysis was not performed. A practical and simple guideline for standardizing planning and evaluation methods needs to be considered to allow valid comparisons of postoperative results and facilitate meta-analysis in the future.

https://ift.tt/2P6F2hO

Salivary exosomes as potential biomarkers in cancer

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s): Soumyalekshmi Nair, Kai Dun Tang, Liz Kenny, Chamindie Punyadeera

Abstract

Over the past decade, there has been emerging research in the field of extracellular vesicles, especially those originating from endosomes, referred to as 'exosomes. Exosomes are membrane-bound nanovesicles secreted by most cell types upon fusion of multivesicular bodies (MVBs) to the cell plasma membrane. These vesicles are present in almost all body fluids such as blood, urine, saliva, breast milk, cerebrospinal and peritoneal fluids. Exosomes participate in intercellular communication by transferring the biologically active molecules like proteins, nucleic acids, and lipids to neighboring cells. Exosomes are enriched in the tumour microenvironment and growing evidence demonstrates that exosomes mediate cancer progression and metastasis. Given the important biological role played by these nanovesicles in cancer pathogenesis, these can be used as ideal non-invasive biomarkers in detecting and monitoring tumours as well as therapeutic targets. The scope of the current review is to provide an overview of exosomes with a special focus on salivary exosomes as potential biomarkers in head and neck cancers.

https://ift.tt/2BkkBv5

Editorial Board/Aims & Scope

Publication date: September 2018

Source: Oral Oncology, Volume 84

Author(s):

https://ift.tt/2P7nke0

The Johns Hopkins Hospital Ranked #3 Nationally by U.S. News

The Johns Hopkins Hospital is ranked #3 in the nation out of nearly 4,700 hospitals reviewed for U.S. News & World Report's 2018–19 Best Hospitals list, which was released today. The publication also ranked 13 specialties at Johns Hopkins among the top 10 in the nation.

https://ift.tt/2BhdsM2

In Vivo Efficacy of VT-1129 against Experimental Cryptococcal Meningitis with the Use of a Loading Dose-Maintenance Dose Administration Strategy [PublishAheadOfPrint]

VT-1129 is a novel fungal-specific Cyp51 inhibitor with potent cryptococcal activity. Because of its long half-life (>6 days in mice) and the desire to quickly reach potent efficacy, we evaluated a VT-1129 loading dose-maintenance dose (LD-MD) strategy against cryptococcal meningitis. VT-1129 plasma and brain pharmacokinetics were first studied in healthy mice, and these data were used to model LD-MD doses to generate different steady-state concentrations. Mice were inoculated intracranially with C. neoformans, and oral treatment began 1 day later. Treatment consisted of placebo, three VT-1129 LD-MD groups: LD of 1, 3, or 30 mg/kg on day 1, followed by MD of 0.15, 0.5, or 5 mg/kg once daily, respectively. In the fungal burden arm, therapy continued for 14 days, and brains were collected on day 15 for fungal burden assessment. In the survival arm, treatment continued for 10 days after which mice were monitored off-therapy until day 30. VT-1129 plasma and brain concentrations were also measured. Each VT-1129 dose significantly improved survival and reduced fungal burden compared to placebo. VT-1129 plasma and brain levels correlated with fungal burden reductions (R² = 0.72 and 0.67, respectively), with plasma concentration of 1 μg/mL yielding a reduction of ~5 log₁₀ CFU/g. With the highest LD-MD dose, fungal burden was undetectable in half of the mice in the fungal burden arm, and in a quarter of the mice in the survival arm, 20 days after final dose. These data support an LD-MD strategy for quickly reaching highly efficacious VT-1129 concentrations in treating cryptococcal meningitis.

https://ift.tt/2MMqEtD

Synthetic Ingenols Maximize Protein Kinase C-Induced HIV-1 Latency Reversal [PublishAheadOfPrint]

Antiretroviral therapy (ART) does not cure HIV-1 infection due to the persistence of proviruses in long-lived resting T cells. Strategies targeting these latently infected cells will be necessary to eradicate HIV-1 in infected individuals. Protein kinase C (PKC) activation is an effective mechanism to reactivate latent proviruses, and allows for recognition and clearance of infected cells by the immune system. Several ingenol compounds, naturally occurring PKC agonists, have been described to have potent latency reversal activity. We sought to optimize this activity by synthesizing a library of novel ingenols via esterification of the C3 hydroxyl group of the ingenol core, which itself is inactive for latency reversal. Newly synthesized ingenol derivatives were evaluated for latency reversal activity, cellular activation and cytotoxicity alongside commercially available ingenols (ingenol-3,20-dibenzoate, ingenol 3-hexanoate and ingenol-3-angelate) in HIV latency cell lines and resting CD4⁺ T cells from aviremic participants. Among the synthetic ingenols that we produced, we identified several compounds that demonstrate high efficacy and represent promising leads as latency reversal agents for HIV-1 eradication.

https://ift.tt/2nBgxg1

Disrupting Gram-negative bacterial outer membrane biosynthesis through inhibition of the lipopolysaccharide transporter MsbA [PublishAheadOfPrint]

There is a critical need for new antibacterial strategies to counter the growing problem of antibiotic resistance. In Gram-negative bacteria, the outer membrane (OM) provides a protective barrier against antibiotics and other environmental insults. The outer leaflet of the outer membrane is primarily composed of lipopolysaccharide (LPS). Outer membrane biogenesis presents many potentially compelling drug targets, as this pathway is absent in higher eukaryotes. Most proteins involved in LPS biosynthesis and transport are essential; however, few compounds have been identified that inhibit these proteins. The inner membrane ABC transporter MsbA carries out the first essential step in the trafficking of LPS to the outer membrane. We conducted a biochemical screen for inhibitors of MsbA, and identified a series of quinoline compounds that kill E. coli through inhibition of its ATPase and transport activity, with no loss of activity against clinical multidrug resistant strains. Identification of these selective inhibitors indicates that MsbA is a viable target for new antibiotics, and the compounds we identified serve as useful tools to further probe the LPS transport pathway in Gram-negative bacteria.

https://ift.tt/2nCsl1w

Encapsulated quinapyramine sulfate-loaded chitosan/mannitol nanoparticles: biocompatibility and targeting efficiency in rabbit model of trypanosomosis [PublishAheadOfPrint]

Quinapyramine sulfate (QS) produces trypanocidal effect against the parasite Trypanosoma evansi, but often poorly tolerated and causes serious local reactions in animals. The encapsulation of QS in chitosan/mannitol to provide the sustained release would improve both the therapeutic effect of QS and the quality of life of animals treated with this formulation. QS was encapsulated into nanoformulation prepared from chitosan, tripolyphosphate and mannitol nanomatrix (ChQS-NPs). ChQS-NPs were well-ordered in shape with nanoparticle size as determined by transmission electron microscopy and atomic force microscopy. Our research revealed a dose-dependent biosafety and DNA damage in mammalian cells treated with ChQS-NPs. ChQS-NPs were absolutely risk-free at effective as well as many times higher doses against T. evansi. ChQS-NPs were effective in rabbits as they killed the parasites, relieving the animals from the clinical symptoms of the disease. The extent of this protection was similar to that observed with the conventional drug at higher dosages (5 mg QS/Kg Bwt). ChQS-NPs are safe, non toxic and effective as compared to QS and offer a promising alternative to drug-delivery against trypanosomosis in animal models. ChQS-NPs may be useful for the treatment of trypanosomosis due to reduced dosages and frequency of administration.

https://ift.tt/2KVwZBe

Successful treatment of extensively drug-resistant Acinetobacter baumannii ventriculitis with intravenous plus intraventricular tigecycline- a case report [PublishAheadOfPrint]

A 70-year-old woman was adimittetd with subarachnoid haemorrhage. The patient underwent cerebral aneurysm embolization. On hospital day 14, the patient underwent a lumbar subarachnoid continuous drain insertion because of fever and enlarged ventricles were showed on the head computed tomography. On hospital day 19, the patient presented with remittent fever (peak at 39.1 °C) associated with altered mental status. Cerebro-Spinal Fluid (CSF) revealed white blood cell (WBC) count of 53484/mm3 (polymorphonucleocytes,75.4%; monocytes, 24.6 %), red blood cells (RBCs) were +++/HP, glucose was 1.26 mg/dL, and the total proteinwas 14.2 g/dL. The lumbar subarachnoid continunous drain was removed. The patient was started on meropenem 1g intravenous(IV) every 8 h and vancomycin 1g (IV ) every 12h. On hospital day 22, the patient's CSF culture showed that A. baumannii (polymyxin susceptibility was not tested) was susceptible only to tigecycline (MIC ≤1 μg/mL) and cefoperazone sulbatan. The same strain of A. baumannii was isolated from the sputum and blood. With permission, the antimicrobial therapy was changed to intravenous tigecycline (100mg first then 50 mg q12h) and cefoperazone sulbatan (3g q8h). Head computed tomography (CT) demonstrated enlarged ventricles compared with previous studies and an external ventricular drain (EVD) was inserted on hospital day 25. On hospital day 28, the blood culture was negative, however the same strain of A. baumannii was still isolated from the CSF. With permission, tigecycline 2mg intraventricular (IVT) every 12 h was started and lasted for 10 days. On hospital day 38, the patient's CSF culture was negative. On hospital day 104, the patient was discharged. Continued 3-month-follow-up showed no recurrence.

https://ift.tt/2MpQiY6

Meropenem combined with ciprofloxacin combats hypermutable Pseudomonas aeruginosa from respiratory infections of cystic fibrosis patients [PublishAheadOfPrint]

Hypermutable Pseudomonas aeruginosa are prevalent in chronic respiratory infections and have been associated with reduced lung function in cystic fibrosis (CF); these isolates can become resistant to all antibiotics in monotherapy. This study aimed to evaluate the time-course of bacterial killing and resistance of meropenem and ciprofloxacin in combination against hypermutable and non-hypermutable P. aeruginosa. Static concentration time-kill experiments over 72h assessed meropenem and ciprofloxacin in mono- and combination therapy against PAO1 (non-hypermutable), PAOmutS (hypermutable), and hypermutable isolates CW08, CW35 and CW44 obtained from CF patients with chronic respiratory infections. Meropenem (1 or 2g q8h as 3h infusion and 3g/day as continuous infusion) and ciprofloxacin (400mg q8h as 1h infusion) in monotherapies and combinations were further evaluated in an 8-day hollow fiber infection model study (HFIM) against CW44. Concentration-time profiles in lung epithelial lining fluid reflecting the pharmacokinetics in CF patients were simulated and counts of total and resistant bacteria determined. All data were analyzed by mechanism-based modeling (MBM). In the HFIM, all monotherapies resulted in rapid regrowth with resistance at 48h. The maximum daily doses of 6g meropenem (T_>MIC 80-88%) and 1.2g ciprofloxacin (AUC/MIC 176), both given intermittently, in monotherapy failed to supress regrowth and resulted in substantial emergence of resistance (≥7.6log₁₀ CFU/mL resistant populations). The combination of these regimens achieved synergistic killing and suppressed resistance. MBM with subpopulation and mechanistic synergy yielded unbiased and precise curve fits. Thus, the combination of 6g/day meropenem plus ciprofloxacin holds promise for future clinical evaluation against infections by susceptible hypermutable P. aeruginosa.

https://ift.tt/2KSyArj

Treatment of Infections with OXA-48 producing Enterobacteriaceae [PublishAheadOfPrint]

Carbapenemase-producing Enterobacteriaceae (CPE) contribute significantly to the global public health threat of antimicrobial resistance. OXA-48, and its variants, are unique carbapenemases with low level hydrolytic activity toward carbapenems, but no intrinsic activity against expanded spectrum cephalosporins. bla_OXA-48 is usually located on a plasmid, but may also be integrated chromosomally, and these genes have progressively disseminated throughout Europe and the Middle East. Despite the inability of OXA-48-like carbapenemases to hydrolyse expanded spectrum cephalosporins, pooled isolates demonstrate high variable resistance to ceftazidime and cefepime, respectively, likely to represent high rates of extended-spectrum beta-lactamase (ESBL) co-production. In-vitro data from pooled studies suggests that avibactam is the most potent beta-lactamase inhibitor when combined with ceftazidime, cefepime, aztreonam, meropenem or imipenem. Resistance to novel avibactam combinations such as imipenem/avibactam or aztreonam/avibactam has not yet been reported in OXA-48 producers, although only few clinical isolates have been tested. Although combination therapy is thought to improve chances of clinical cure and survival in CPE infection, successful outcomes were seen in ~70% of patients with infections caused by OXA-48-producing Enterobacteriaceae treated with ceftazidime/avibactam monotherapy. A carbapenem in combination with either amikacin or colistin has achieved treatment success in a few case reports. Uncertainty remains over the best treatment options and strategies used to manage these infections. Newly available antibiotics such as ceftazidime/avibactam show promise, however recent reports of resistance are concerning. Newer choices of antimicrobial agents will likely be required to combat this problem.

https://ift.tt/2Mu3gUQ

Nitazoxanide Inhibits Human Norovirus Replication and Synergizes with Ribavirin by Activation of Cellular Antiviral Response [PublishAheadOfPrint]

Norovirus is the main cause of viral gastroenteritis worldwide. Although norovirus gastroenteritis is self-limiting in immunocompetent individuals, chronic infections with debilitating and life-threatening complications occur in immunocompromised patients. Nitazoxanide (NTZ) has been empirically used in the clinic and demonstrated effectiveness against norovirus gastroenteritis. In this study we aimed at uncovering the antiviral potential and mechanisms of NTZ and its active metabolite, tizoxanide (TIZ) using a human norovirus (HuNV) replicon. NTZ and TIZ, collectively referred to as thiazolides (TZD) potently inhibited replication of HuNV and a norovirus surrogate feline calicivirus. Mechanistic studies revealed that TZD activated cellular antiviral response and stimulated the expression of a subset of interferon-stimulated genes (ISGs), particularly IRF-1 not only in Huh7-based HuNV replicon but also in naïve Huh7, Caco-2 and novel human intestinal organoids. Overexpression of exogenous IRF-1 inhibited HuNV replication; whereas knockdown of IRF-1 largely attenuated the antiviral activity of TZD, suggesting that IRF-1 mediated TZD inhibition of HuNV. By using a JAK inhibitor CP-690550 and STAT1 knockout approach, we found that TZD induced antiviral response independent of the classical Janus Kinase/signal transducers and activators of transcription (JAK/STAT) pathway. Furthermore, TZD and ribavirin synergized to inhibit HuNV replication and completely depleted the replicons from host cells after long-term treatment. In summary, our results demonstrated that TZD combated HuNV replication through activation of cellular antiviral response, in particular inducing a prominent antiviral effector IRF-1. NTZ monotherapy or combination with ribavirin represented promising options for treating norovirus gastroenteritis, especially in immunocompromised patients.

https://ift.tt/2MGsLPy

Activity of aromathecins against African trypanosomes [PublishAheadOfPrint]

African sleeping sickness is responsible for thousands of deaths annually and new therapeutics are needed. This study evaluated aromathecins, experimental inhibitors of mammalian topoisomerase IB, against Trypanosoma brucei African trypanosomes. The compounds had selectively toxic antiparasitic potency, had in situ poisoning activity against the phylogenetically unique topoisomerase in these parasites, and a representative compound intercalated into DNA with micromolar affinity. DNA intercalation and topoisomerase poisoning may contribute to the antitrypanosomal activity of aromathecins.

https://ift.tt/2MkLS4C

Efficacy and safety of low-dose liposomal amphotericin B in adult patients undergoing unrelated cord blood transplantation [PublishAheadOfPrint]

Liposomal amphotericin B (L-AMB) is widely used for empirical or preemptive therapy and treatment of invasive fungal infection after cord blood transplantation (CBT). We retrospectively examined the efficacy and safety of low-dose L-AMB in 48 adult patients of CBT from between 2006 and 2017 in our institute. Among the entire cohort, 42 (88%) patients received L-AMB as an empirical or preemptive therapy. The median daily dose of L-AMB and the median cumulative dose of L-AMB were 1.20 mg/kg/day (range, 0.62–2.60 mg/kg/day) and 30.6 mg/kg (range, 0.7–241.5 mg/kg), respectively. The median duration of L-AMB administration was 21.5 days (range, 1–313 days). Documented breakthrough fungal infection occurred in 1 patient during L-AMB treatment, and 43 (90%) patients survived for at least 7 days after the end of L-AMB treatment. Grade 3 or higher hypokalemia and hepatotoxicity were frequently observed during L-AMB treatment. However, no patients developed an increase in serum creatinine of grade 3 or higher. In the univariate analysis using a logistic regression model, a duration of L-AMB treatment of more than 21 days and a cumulative dose of L-AMB more than 30 mg/kg were significantly associated with nephrotoxicity and grade 3 hypokalemia. These data suggest that low-dose L-AMB may be safe and effective in adult patients undergoing CBT.

https://ift.tt/2MND6ZK

C. albicans Zn Cluster Transcription Factors Tac1 and Znc1 are Activated by Farnesol to Up Regulate a Transcriptional Program Including the Multi-Drug Efflux Pump CDR1 [PublishAheadOfPrint]

Farnesol, a quorum-sensing molecule, inhibits C. albicans hyphal formation, affects its biofilm formation and dispersal, and impacts its stress response. Several aspects of farnesol's mechanism of action remain incompletely uncharacterized. Among these are a thorough accounting of the cellular receptors and transporters for farnesol. This work suggests these processes are linked through the Zn cluster transcription factors Tac1 and Znc1, and their induction of the multi-drug efflux pump Cdr1. Specifically, we have demonstrated that Tac1 and Znc1 are functionally activated by farnesol through a mechanism that mimics other means of hyperactivation of Zn cluster transcription factors. This is consistent with our observation that many genes acutely induced by farnesol are dependent on TAC1, ZNC1, or both. A related molecule, 1-dodecanol, invokes a similar TAC1/ZNC1 response, while several other proposed C. albicans quorum sensing molecules do not. Tac1 and Znc1 both bind to and up-regulate the CDR1 promoter in response to farnesol. Differences in inducer and DNA binding specificity lead to Tac1 and Znc1 having overlapping, but non-identical, regulons. Induction of genes by farnesol via Tac1 and Znc1 was inversely related to the level of CDR1 present in the cell, suggesting a model in which induction of CDR1 by Tac1 and Znc1 leads to an increase in farnesol efflux. Consistent with this premise, our results show that CDR1 expression, and its regulation by TAC1 and ZNC1, facilitates growth in the presence of high farnesol concentrations in C. albicans, and in certain strains of its close relative C. dubliniensis.

https://ift.tt/2nBg4KN

CAN WE IMPROVE STAVUDINE'S SAFETY PROFILE IN CHILDREN? PHARMACOKINETICS OF INTRACELLULAR STAVUDINE-TRIPHOSPHATE WITH REDUCED-DOSING [PublishAheadOfPrint]

Introduction Stavudine remains a useful replacement option for HIV+ children. WHO reduced the adult dose to 30mg twice-daily, which maintains efficacy and lowers mitochondrial toxicity. We explored intracellular stavudine-triphosphate levels in children receiving a reduced dose of 0.5-0.75mg/kg twice-daily to investigate whether a similar dose optimization can safely be made.

Methods A population pharmacokinetic model was developed to describe the pharmacokinetics of intracellular stavudine-triphosphate in 23 HIV+ children and 24 HIV+ adults who received stavudine at 0.5mg/kg and 20mg twice-daily for 7 days, respectively. Simulations were employed to optimise the paediatric dosing regimen to match exposures in adults receiving the current WHO-recommended dose of 30mg twice-daily.

Results A bi-phasic disposition model with first-order appearance and disappearance described the pharmacokinetics of stavudine-triphosphate. The use of allometric scaling with fat-free mass characterised well the pharmacokinetics in both adults and children, and no other significant effect could be detected. Simulations of 30mg twice-daily in adults predicted median (interquartile range) stavudine-triphosphate C_min and C_max values of 13 (10-19) and 45 (38-53)fmol/10⁶ cells, respectively. Targeting this exposure, simulations in HIV+ children were used to identify a suitable weight-band dosing approach (0.5-0.75mg/kg), which was predicted to achieve C_min and C_max of 13 (9-18) and 49 (40-58)fmol/10⁶ cells, respectively.

Conclusion Weight-band dosing using a stavudine dose of 0.5-0.75mg/kg is proposed and it shows comparable exposures to adults receiving the current WHO recommended dose of 30mg twice-daily. Our pharmacokinetic results suggest that the decreased stavudine dose in children >2years would have a reduced toxic effect while retaining antiretroviral efficacy.

https://ift.tt/2MNCXpa

Minocycline has no clear role in the treatment of Mycobacterium abscessus disease [PublishAheadOfPrint]

Mycobacterium abscessus (Mab) causes difficult-to-treat pulmonary disease (Mab-PD). After the initial intravenous treatment, minocycline is recommended in the oral continuation phase of treatment. We determined minimum inhibitory concentrations, synergy and time-kill kinetics of minocycline against Mab. With MICs of 8-512 mg/l, rapid emergence of tolerance in time-kill assays and no synergy with other drugs used to treat Mab-PD, minocycline appears ineffective against Mab. These in vitro data question its role as a Mab-PD treatment modality.

https://ift.tt/2nB5EL6

Loss of function mutations in epaR confer resistance to phage NPV1 infection in Enterococcus faecalis OG1RF [PublishAheadOfPrint]

Enterococcus faecalis is a Gram-positive opportunistic pathogen that inhabits the human gastrointestinal tract. Because of the high frequency of antibiotic resistance among Enterococcus clinical isolates, interest in using phage to treat enterococcal infections and to decolonize high-risk patients for antibiotic-resistant Enterococcus is rising. Bacteria can evolve phage resistance, but there is little published information on these mechanisms in E. faecalis. In this report, we identified genetic determinants of E. faecalis resistance to NPV1. We found that loss-of-function mutations in epaR confer NPV1 resistance by blocking phage adsorption. We attribute the inability of the phage to adsorb to the modification or loss of an extracellular polymer in strains with inactivated epaR. Phage-resistant epaR mutants exhibited increased daptomycin and osmotic stress susceptibilities. Our results demonstrate that in vitro spontaneous resistance to NPV1 comes at a cost in E. faecalis OG1RF.

https://ift.tt/2KPZMXu

Nontuberculous Mycobacterial Lung Diseases Caused by Mixed Infection with Mycobacterium avium complex and Mycobacterium abscessus complex [PublishAheadOfPrint]

Mycobacterium avium complex (MAC) and M. abscessus complex (MABC) comprise the two most important human pathogen groups causing nontuberculous mycobacterial lung disease (NTM-LD). However, there are limited data regarding NTM-LD caused by mixed NTM infections. This study aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-LD caused by mixed infection with these two major NTM pathogen groups. Seventy-one consecutive patients who had been diagnosed with NTM-LD caused by mixed infection with MAC (M. avium or M. intracellulare) and MABC (M. abscessus or M. massiliense) between January 2010 and December 2015 were identified. Nearly all patients (96%) had the nodular bronchiectatic form of NTM-LD. Mixed infection with MAC and M. massiliense (n = 47, 66%) was more common than mixed infection with MAC and M. abscessus (n = 24, 34%), and among the 43 (61%) patients who were treated for NTM-LD for more than 12 months, sputum culture conversion rates were significantly lower in patients infected with MAC and M. abscessus [25% (3/12)] compared with patients infected with MAC and M. massiliense [61% (19/31), P = 0.033]. Additionally, M. massiliense and M. abscessus showed marked differences in clarithromycin susceptibility (90% vs. 6%, P < 0.001). Of the 23 patients who successfully completed treatment, 11 (48%) redeveloped NTM lung disease, with mycobacterial genotyping results indicating that the majority of cases were due to reinfection. Precise identification of etiologic NTM organisms could help predict treatment outcomes in patients with NTM-LD due to mixed infections.

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APX001A in vitro activity against contemporary blood isolates and C. auris determined by the EUCAST reference method [PublishAheadOfPrint]

APX001A is the active moiety of the first-in-class drug candidate APX001. So far, most susceptibility testing studies have examined ≤30 isolates/species, and only one with the EUCAST method. We investigated the in vitro activity of APX001A and five comparators against 540 candidaemia and 122 C. auris isolates.

Isolates (17 Candida and 3 yeast species) were identified using CHROMagar, MALDI-TOF and when needed ITS-sequencing. EUCAST E.Def 7.3.1 susceptibility testing included APX001A, amphotericin B, anidulafungin, micafungin, fluconazole, and voriconazole. Wild-type upper limits (WT-UL) were established following the EUCAST-principles for Epidemiological cut off value setting for APX001A allowing classification as WT or non-WT.

APX001A MIC₅₀ values (mg/L) were: C. albicans, C. dubliniensis and C. tropicalis 0.004-0.008, C. parapsilosis and C. auris 0.016, C. glabrata 0.06 and C. krusei >0.5. APX001A MICs varied against the rare species from C. pelliculosa ≤0.0005 to C. norvegensis >0.5. APX001A was equally or more in vitro active than the comparators against all species except C. krusei and C. norvegensis. Four isolates were APX001A non-WT, all of which were fluconazole resistant. A correlation was observed between APX001A and fluconazole MICs across all species except C. guilliermondii and C. auris, and when comparing high and low fluconazole MIC isolates of C. albicans, C. dubliniensis, C. glabrata, C. tropicalis and C. auris.

APX001A showed promising in vitro activity against most Candida and other yeast species including C. auris when compared to five comparators. WT-ULs were suggested for the common species and a new and un-explained correlation to fluconazole susceptibility was observed.

https://ift.tt/2KSbe51

Treatment of Pseudomonas aeruginosa biofilm present in endotracheal tubes by poly-L-Lysine. [PublishAheadOfPrint]

The endotracheal tube (ETT) is an essential interface between the patient and ventilator in mechanically-ventilated patients. However, a microbial biofilm is formed gradually on this tube and is associated with the development of ventilator-associated pneumonia. Bacteria present in the biofilm are more resistant to antibiotics and current medical practices do not make it possible to eliminate. P. aeruginosa is one of the leading pathogens that cause biofilm infections and ventilator-associated pneumonia. Poly-L-lysine (pLK) is a cationic polypeptide possessing antibacterial properties and mucolytic activity by compacting DNA. We explored here the anti-biofilm activity of pLK to treat P. aeruginosa biofilms on ETT, taking into consideration the necessary constraints for clinical translation in our experimental designs. First, we showed that pLK eradicate P. aeruginosa biofilm formed in vitro on 96-well microplates. We further demonstrated that pLK alters bacterial membrane integrity as revealed by scanning electron microscopy and eventually eradicate biofilm formed either by reference or clinical strains of P. aeruginosa biofilms generated in vitro on ETT. Second, we collected ETT from patients with P. aeruginosa ventilator-associated pneumonia. We observed that a single dose of pLK is able to immediately disrupt the biofilm structure and kills more than 90 % of bacteria present in biofilm. Additionally, we did not observe any lung tolerance issue when pLK solution was instilled into ETT of ventilated-pigs, an animal model particularly relevant to mimic invasive mechanical ventilation in humans. In conclusion, pLK appears as an innovative anti-biofilm molecule which could be applied in the ETT of mechanically-ventilated patients.

https://ift.tt/2nxU9Ei

Screening a Repurposing Library for Inhibitors of Multi-Drug Resistant Candida auris Identifies Ebselen as a Repositionable Candidate for Antifungal Drug Development [PublishAheadOfPrint]

Since its original isolation in 2009, Candida auris has spread across the globe as a causative agent of invasive candidiasis. C. auris is usually intrinsically resistant to fluconazole and can also be resistant to echinocandins and even amphotericin B. Thus, finding new treatment options against this emerging pathogen is urgent. To address this growing problem, we have performed a screen of the Prestwick Chemical Library, a repurposing library of 1,280 small molecules, consisting mostly of approved off-patent drugs, in search for those with activity against a multidrug resistant C. auris isolate. Our initial screen, using standardized susceptibility testing methodologies, identified nine miscellaneous compounds with no previous clinical indication as antifungals or antiseptics that displayed activity against C. auris. Confirmation and follow-up studies identified ebselen as the drug displaying the most potent activity, with 100% inhibition of growth detected at concentrations as low as 2.5 μM. We further evaluated the ability of ebselen to inhibit C. auris biofilm formation and examined the effects of combination therapy of ebselen with clinically used antifungals. We extended our studies to different C. auris strains with varying susceptibility patterns and also confirmed its antifungal activity against C. albicans and clinical isolates of multiple other Candida species. Furthermore, ebselen displays broad antifungal spectrum of action based on its activity against a variety of medically important fungi, including yeasts and molds. Overall our results indicate the promise of ebselen as a repositionable agent for the treatment of candidiasis and possibly other mycoses, and in particular for the treatment of infections refractory to conventional treatment with current antifungals.

https://ift.tt/2MF1DjM

Cyclic nucleotide specific phosphodiesterases as potential drug targets for anti-Leishmania therapy [PublishAheadOfPrint]

The available treatments for leishmaniasis are less than optimal due to inadequate efficacy, toxic side-effects and the emergence of resistant strains, clearly endorsing the urgent need for discovery and development of novel drug candidates. Ideally, these should act via an alternative mechanism-of-action to avoid cross-resistance with the current drugs. As cyclic nucleotide specific phosphodiesterases (PDEs) of L. major have been postulated as putative drug targets, a series of potential inhibitors of Leishmania PDEs was explored. Several displayed potent and selective in vitro activity against L. infantum intracellular amastigotes. One imidazole derivative, compound 35, was shown to reduce the parasite loads in vivo and dose-dependently increase the cellular cAMP level at just 2x and 5x the IC₅₀, indicating a correlation between antileishmanial activity and increased cellular cAMP. Docking studies and molecular dynamics simulations pointed to imidazole 35 exerting its activity through PDE inhibition. This study establishes for the first time that inhibition of cAMP PDEs can potentially be exploited for new antileishmanial chemotherapy.

https://ift.tt/2nBPNfB

Multiple myeloma concealed by adrenal Cushing syndrome: a case report and review of the literature

Cushing syndrome coexisting with multiple myeloma has been previously described in a few reports. Overlapping clinical manifestations can lead to misdiagnoses.

https://ift.tt/2vC8nsj

Timing of infections in patients with primary immunodeficiencies treated with intravenous immunoglobulin (IVIg)

Patients with common variable immune deficiency and X-linked agammaglobulinemia are unable to produce their own antibodies thus leading to a higher incidence of recurrent infections, particularly those involvi...

https://ift.tt/2MFJbYf

Salivary antioxidant capacity of children with severe early childhood caries before and after complete dental rehabilitation

Publication date: Available online 13 August 2018

Source: Archives of Oral Biology

Author(s): Ghazi S. AlAnazi, Sharat Chandra Pani, Hana J. AlKabbaz

Abstract

Objective

There is a need to determine whether total antioxidant capacity (TAC) in severe early childhood caries (S-ECC) is an indicator of inflammatory response to the lesion or a marker of the disease. This study compared TAC levels in children with ECC before and after dental treatment and compared the results with those of caries-free children.

Design

Prospective study.

Setting

A teaching hospital

Patient selection

Salivary samples were obtained from 20 children aged 5 years and diagnosed with S-ECC, and 20 age- and sex-matched controls.

Intervention details

Complete dental rehabilitation under general anesthesia was performed on the children with S-ECC, and follow-up salivary samples were obtained one week and three months postoperatively. TAC was measured using a commercially available Oxygen Radical Absorbance Antioxidant Assay measurement kit (Zen-Bio ORAC™, AMS Biotechnology, Abington, UK).

Outcome measures

Differences between children with and without dental caries were tested using the Mann-Whitney U test; differences before and after dental treatment were analyzed using Friedman test followed by Wilcoxon sign-rank test with Bonferroni correction to compensate for multiple comparisons.

Results

Median TAC (1.54 mcg/L, CI 1.15-1.92) of the control group was significantly lower than that of the treated group prior to treatment (p = 0.003). Treatment of the dental lesions significantly reduced TAC of the treated group, and no significant differences were observed between the test and control groups at either one week (p = 0.076) recall or three-month recall (p = 0.096). TAC in children posttreatment was significantly reduced compared to their pretreatment values (p < 0.001).

Conclusion

Total antioxidant capacity in the saliva of children with severe early childhood caries undergoes significant reduction following treatment of the carious lesions.

https://ift.tt/2MLHTef

Nail apparatus melanoma: Experience of 10 years in a single institution

Background: Nail apparatus melanoma (NAM) is rare. The higher mortality reported in the literature, compared with melanoma on other sites is probably due to advanced disease associated with a delay in diagnosis and treatment.

https://ift.tt/2vGgsvR

Comparison of noninsulated microneedle and noninvasive fractional radiofrequency devices in an animal model of skin rejuvenation

Background: Radiofrequency (RF) devices based on various delivery systems are clinically effective in treating many dermatologic conditions. However, there are few histologic studies identifying the therapeutic mechanism and its effect.

https://ift.tt/2B883Xm

Sodium thiosulfate injection dissolves calcium hydroxylapatite particles: An animal study

Background and objective: Treatment of certain dermal filler–related serious AEs (e.g., vascular occlusion, granulomatous reactions) may include removal of the injected material. Hyaluronidase can be used to degrade hyaluronic acid fillers; however, no agents have yet been shown to fully dissolve calcium hydroxylapatite (CaHA; Merz North America) filler after placement. Sodium thiosulfate (STS) has been shown to decrease calcium mineral deposits associated with calciphylaxis, calcific uremic arteriolopathy, and kidney stones.

https://ift.tt/2MgMXev

Topical oxymetazoline hydrochloride 1.0% effectively reduces persistent facial erythema of rosacea on day 1

Introduction: Persistent facial erythema is a bothersome, therapeutically challenging feature of rosacea; therapies with clear efficacy at treatment onset are needed. In 2 identically designed, phase 3 pivotal, randomized, multicenter, double-blind, parallel-group, vehicle-controlled, 29-day REVEAL trials, topical oxymetazoline cream 1.0% significantly reduced moderate to severe persistent facial erythema of rosacea. A post hoc analysis of pooled data from both trials assessed erythema reduction on day 1.

https://ift.tt/2B87Q6w

Widespread skin necrosis secondary to gemcitabine

Cutaneous side-effects are relatively common in chemotherapy but vary in frequency and severity depending on the medication, dose, duration, pharmacokinetics, and pharmacodynamics. Gemcitabine, a pyrimidine nucleoside analogue, is an oncologic agent used in the treatment of cutaneous T-cell lymphoma (CTCL). Common dermatologic reactions associated with gemcitabine include alopecia, mild skin rash, and mucositis. Rare reports of other cutaneous reactions include lower extremity skin necrosis, lower extremity pseudocellulitis, and scleroderma-like changes.

https://ift.tt/2MfDJiO

The antiinflammatory properties of ivermectin and brimonidine in the treatment of papulopustular rosacea

Introduction: The pathophysiology of papulopustular rosacea (PPR) is not fully understood; however, there is increasing evidence that immune and inflammatory responses play an important role in the persistent and perilesional erythema of PPR. Multiple trials have demonstrated the efficacy of ivermectin 1% cream (IVM) and brimonidine 0.33% gel (BR) for treatment of the inflammatory lesions and erythema of PPR, respectively. Two recent studies suggest a promising synergy between IVM and BR in PPR.

https://ift.tt/2wdsMn9

Role of activated oligoadenylatesynthetase–ribonuclease L pathways as a novel therapeutic target in psoriasis

Psoriasis (Pso) is predominantly an immune-mediated disease characterized by aberrant epidermal differentiation, surface scale formation, and marked cutaneous inflammation. Immune pathways activated in Pso include amplification of background immune circuits or induction of certain proinflammatory signaling pathways, otherwise latent in normal human skin. These changes include selective induction of antiviral innate immune response genes, differential expression of pathogen associated molecular pattern (PAMP) receptors, cell signaling and cell growth control pathways.

https://ift.tt/2vIhRlQ

Unveiling the hidden: The eclipsed effect of nondermatophyte infection and mixed-infection onychomycosis

Background: Mixed onychomycosis infections with dermatophytes (DMPs) and nondermatophytes (NDMs) have become more common. While the diagnosis of DMPs onychomycosis is based on mycologic laboratory, that of the NDMs onychomycosis still has several other criteria. Moreover, there had been a few studies about the relationship between fungal feet and nail infection.

https://ift.tt/2w3rA5z

Successful vismodegib debulking of a giant basal cell carcinoma of the umbilicus

Introduction: Basal cell carcinoma (BCC) of the umbilicus is an exceptional subtype of BCC with potential slowly progressing deeply invasive and wide growth pattern. Vismodegib is a hedgehog pathway inhibitor indicated for the treatment of large, nonoperable or metastatic BCC.

https://ift.tt/2Mi5Huo

Secukinumab shows sustained efficacy in difficult-to-treat palmoplantar, nail, and scalp psoriasis: Long-term results from three phase III placebo-controlled randomized trials

Introduction: Psoriasis is a chronic, autoimmune inflammatory condition that can affect different parts of the body including scalp, nails, palms and soles. Psoriasis localized in these areas remains difficult-to-treat, and can result in significant physical and psychosocial disability. Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy in the treatment of moderate to severe plaque psoriasis and psoriatic arthritis, demonstrating a rapid onset of action and sustained responses up to 5 years with a favorable safety profile.

https://ift.tt/2B4IGFQ

Venous treatment of lipodermatosclerosis to improve ambulatory function

Introduction: The manifestations of chronic venous insufficiency (CVI), particularly lipodermatosclerosis (LDS) and venous ulcers, can be devastating to patients as it can adversely affect quality of life, and carry significant psychosocial burden.

https://ift.tt/2MgyKOA

Treatment patterns among psoriasis patients newly initiated on etanercept or apremilast in a dermatology specialty electronic medical record (EMR) database

Background: Plaque psoriasis (PSO) is a common inflammatory skin disorder that can require chronic treatment. Etanercept (ETN) is a self-injectable biologic indicated to treat moderate-to-severe PSO. Apremilast (APR) is a nonbiologic oral therapy recently approved to treat moderate-to-severe PSO. We sought to examine the real-world treatment patterns of these agents.

https://ift.tt/2w3cGfJ

The use of silicone gel to enhance skin wound healing by secondary intention following tumor excision on the scalp and extremities: A descriptive study

Secondary intention (SI) healing is advantageous due to shorter surgical time and lower risk of damage to neighboring structures. It is therefore more tolerable in elderly patients with large wounds and is also indicated for lesions at high risk of recurrence as this facilitates closer surveillance. The main disadvantage however is the need for prolonged wound care. Although there is constant effort in adapting materials designed for chronic wounds as an adjunct to SI healing, a recent Cochrane review expounded on the lack of evidence to support any single method.

https://ift.tt/2McnJOk

Systematic review of placebo responses in randomized clinical trials of systemic therapy for atopic dermatitis

Introduction: Atopic dermatitis (AD) is associated with a variable disease severity and symptom burden and intermittent periods of disease remittance, all of which may contribute to increased placebo responses in randomized clinical trials (RCT). However, little is known about the rates and predictors of placebo responses in RCT of systemic therapy in AD.

https://ift.tt/2B9s0gB

Stem cell–conditioned media as a potential antiaging technology in skin care

Stem cell conditioned media (SCCM) is gaining increasing interest and is a promising prospect in the field of regenerative medicine. The beneficial effects of stem cell therapy on damaged tissue have shown to be accredited to their ability to secrete trophic factors, rather than their capacity to differentiate into the needed cells. Various studies on stem cell–derived conditioned media from various cell lines, such as adipose-derived stem cells and bone marrow–derived mesenchymal stem cells, have demonstrated tissue repair in various conditions that involved tissue damage.

https://ift.tt/2vIhjMO

Silver nanoparticles induce Egr-1–dependent psoriasin expression via the ERK and p38 pathways

Background: Silver nanoparticles (Ag-NPs) have been known to prevent bacterial infection and improve a cutaneous wound healing due to their antimicrobial activity. However, the mechanism of Ag-NPs' antimicrobial activity is poorly understood.

https://ift.tt/2w58iMZ

Scabies mimicking pityriasis rosea: Scabies surrepticius

Background: Scabies is a mite infestation caused by Sarcoptes scabiei that is common worldwide. Scabies is diagnosed based on history and exam of the patient, family, and close contacts. Diagnosis is confirmed based on the demonstration of mites, eggs, or mite feces from scrapings of the lesions. The classic presentation of scabies is extreme pruritus and burrows where the mite penetrates the skin and lays eggs. The most common locations of the lesions include the finger webs, flexor surfaces of the wrists, elbows, axillae, buttocks, and genitalia.

https://ift.tt/2vIgVxQ

Relationship between pruritus and quality of life in patients with atopic dermatitis treated with crisaborole

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions and pruritus. Pruritus can lead to exacerbation of disease and reduced quality of life (QoL). Crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate AD. Compared with vehicle, use of crisaborole significantly reduced global disease severity and pruritus in 2 large, identically designed phase 3 clinical studies (AD-301: NCT02118766; AD-302: NCT02118792).

https://ift.tt/2B889hx

White fibrous papulosus of the neck

Introduction: Whıte fibrous papulosus of the neck (WFPON) is a newly defined clinical diagnosis by Shimizu in 1985. It consists of smooth, linear, 2-3 mm papules, independent of the hair follicles on the neck and back. White fibrous papulosus of the neck (WFPON) and pseudoxanthoma elastic-like dermal elastosis (PXE-PDE) are thought to be clinical variants of the same disease. For this reason, some authors have described WFPON, PXE-PDE and other noninflammatory middermal elastosis cases as "fibroelastolytic variants of primary skin aging." These clinical pictures are clinically similar to each other in many ways, but histologically they can be separated by intact elastic fibers and increased amounts of collagen in the midreticulary dermis.

https://ift.tt/2MbKqCi

Using intralesional methotrexate to treat recalcitrant cutaneous Crohn’s disease

Introduction: Cutaneous Crohn's disease (CD) is a rare, and not entirely understood, manifestation of CD that has various clinical presentations. Treatment is difficult, as methods detailed in several case reports over the decades demonstrate mixed efficacy in treating cutaneous CD. Few reports have shown promise using intralesional methotrexate. This case report describes a case of recalcitrant cutaneous CD that resolved with intralesional methotrexate.

https://ift.tt/2w5ylUu

What is labial hypertrophy and is it normal?

Each person's vagina and vulva are unique, and there is wide variation between people. Labial hypertrophy is when one or both vaginal lips, or labia, are larger than usual. This is normal and not a cause for concern. Some people choose to have surgery for cosmetic reasons. Learn more about vaginal hypertrophy here.

https://ift.tt/2vJ7z4K

Preoperative Tranexamic Acid for Treatment of Bleeding, Edema, and Ecchymosis in Patients Undergoing Rhinoplasty: A Systematic Review and Meta-analysis.

Related Articles

Preoperative Tranexamic Acid for Treatment of Bleeding, Edema, and Ecchymosis in Patients Undergoing Rhinoplasty: A Systematic Review and Meta-analysis.

JAMA Otolaryngol Head Neck Surg. 2018 Aug 09;:

Authors: de Vasconcellos SJA, do Nascimento-Júnior EM, de Aguiar Menezes MV, Tavares Mendes ML, de Souza Dantas R, Martins-Filho PRS

Abstract
Importance: Evidence has emerged on the efficacy of tranexamic acid to control blood loss and postoperative complications after rhinoplasty.
Objective: To investigate the results of tranexamic acid use to reduce intraoperative bleeding, postoperative eyelid edema, and periorbital ecchymosis in rhinoplasty.
Data Sources and Study Selection: For this systematic review of randomized clinical trials, searches were performed in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, Science Direct, Google Scholar, OpenThesis, and ClinicalTrials.gov from inception to December 23, 2017. Key words included tranexamic acid, rhinoplasty, and nasal surgical procedures. The following elements were used to define eligibility criteria: (1) population: patients undergoing rhinoplasty surgery; (2) intervention and controls: tranexamic acid vs placebo solution or no-treatment control group; (3) outcomes: intraoperative bleeding, postoperative eyelid edema and periorbital ecchymosis, and thromboembolic events; and (4) study type: randomized clinical trials.
Data Extraction and Synthesis: Two reviewers extracted data and assessed study quality according to the Cochrane guidelines for randomized clinical trials. Treatment effects were defined as weighted mean difference (WMD) and 95% CIs. The strength of evidence was analyzed using the Grading of Recommendations Assessment, Development, and Evaluation rating system.
Main Outcomes and Measures: Intraoperative bleeding, postoperative eyelid edema and periorbital ecchymosis. To calculate the effect sizes, means and SDs were obtained for each study group and outcome of interest.
Results: Five studies comprising 276 patients were included in the systematic review: 177 patients (64.1%) were women, and mean age was 26.8 (range, 16-42) years. Four studies comprising 246 patients estimated the amount in intraoperative bleeding as a primary outcome and were included in the meta-analysis. Eyelid edema and ecchymosis were evaluated as outcomes in 2 studies. Tranexamic acid was associated with reduced bleeding during rhinoplasty was found (WMD, -42.28 mL; 95% CI, -70.36 to -14.21 mL), with differences (P = .01) between oral (WMD, -61.70 mL; 95% CI, -83.02 to -40.39 mL; I2 = 0%) and intravenous (WMD, -23.88 mL; 95% CI, -45.19 to -2.58 mL; I2 = 56%) administration. Eyelid edema and ecchymosis scores in patients receiving tranexamic acid were significantly lower compared with the control group within the first postoperative week: lower eyelid edema, WMD, -0.76; 95% CI, -1.04 to -0.49 and lower eyelid ecchymosis, WMD, -0.94; 95% CI, -1.80 to -0.08. No cases of thromboembolic events were reported.
Conclusions and Relevance: Current available evidence suggests that preoperative administration of tranexamic acid is safe and may reduce intraoperative bleeding as well as postoperative eyelid edema and ecchymosis in patients undergoing rhinoplasty.

PMID: 30098161 [PubMed - as supplied by publisher]

https://ift.tt/2nCHkZA

Utility of Optical Coherence Tomography for Guiding Laser Therapy Among Patients With Recurrent Respiratory Papillomatosis.

Related Articles

Utility of Optical Coherence Tomography for Guiding Laser Therapy Among Patients With Recurrent Respiratory Papillomatosis.

JAMA Otolaryngol Head Neck Surg. 2018 Aug 09;:

Authors: Benboujja F, Bowe S, Boudoux C, Hartnick C

Abstract
Importance: Recurrent respiratory papillomatosis (RRP) is a viral-induced disease caused by human papillomavirus and the second leading cause of dysphonia in children; however, neither a cure nor a definitive surgical treatment is currently available for RRP. Although laser therapy is often used in the treatment of RRP, the lack of real-time laser-tissue interaction feedback undermines the ability of physicians to provide treatments with low morbidity. Therefore, an intraoperative tool to monitor and control laser treatment depth is needed.
Objective: To investigate the potential of combining optical coherence tomography (OCT) with laser therapy for patient-tailored laryngeal RRP treatments.
Design, Setting, and Participants: This in vivo study was performed at the Massachusetts Eye and Ear Infirmary from February 1, 2017, to September 1, 2017. Three-dimensional OCT images were acquired before, during, and after photoangiolytic laser therapy in 10 pediatric patients with a history of papilloma growth who presented with lesions and hoarseness.
Main Outcomes and Measures: Whether intraoperative OCT monitoring of changes in optical scattering and absorption provides quantitative information to control thermal damage in tissue.
Results: Among the 10 pediatric patients (age range, 4-11 years; 6 male) included in the study, high-resolution OCT images revealed epithelial hyperplasia with clear RRP lesion margins. Images acquired during therapy indicated coagulation deep in tissue, and posttherapy images showed the ability to quantify the amount of tissue ablated by the photoangiolytic laser.
Conclusions and Relevance: Concurrent use of OCT imaging and laser therapy may improve postoperative outcomes for patients with RRP by delivering an optimal, patient-tailored treatment. Additional studies investigating the correlation between optical properties with vocal outcomes are required.

PMID: 30098151 [PubMed - as supplied by publisher]

https://ift.tt/2B7KgH2

Cocaine-Induced Midline Destructive Lesions Associated With Erosion of the Eustachian Tube.

Related Articles

Cocaine-Induced Midline Destructive Lesions Associated With Erosion of the Eustachian Tube.

JAMA Otolaryngol Head Neck Surg. 2018 Aug 09;:

Authors: Bacciu A, Ghirelli M, Ingegnoli A, Bozzetti F

PMID: 30098140 [PubMed - as supplied by publisher]

https://ift.tt/2P6b7Gu

Faringoplastia de expansión: utilidad de la somnoscopia (DISE)

Publication date: Available online 13 August 2018

Source: Acta Otorrinolaringológica Española

Author(s): Gabriela Bosco, Nuria Pérez-Martín, Miguel A. Racionero, Guillermo Plaza

Resumen

Objetivos

El objetivo de este estudio es presentar las indicaciones y resultados de la faringoplastia de expansión como tratamiento del síndrome de apnea-hipopnea obstructiva del sueño (SAHOS). En segundo lugar, comparar los hallazgos de la somnoscopia (drug-induced sleep endoscopy –DISE–) antes y después de la cirugía.

Material y métodos

El diseño del estudio fue una cohorte prospectiva de pacientes tratados quirúrgicamente de 2015 a 2016. Todos los pacientes fueron diagnosticados de SAHOS leve a grave y no toleraban la CPAP. Todos tenían DISE y polisomnografía previa a la cirugía, y posterior a la misma. Los criterios de inclusión fueron la edad, entre 18 años y 70 años, amígdalas pequeñas (tamaños 1 y 2), estadio clínico de Friedman II y III, y colapso lateral mayoritario en la DISE preoperatoria. Se les realizó únicamente cirugía del paladar, usando la técnica de faringoplastia de expansión.

Resultados

Se incluyeron 17 pacientes, el 52,94% eran pacientes con SAHOS grave. La edad media fue de 42 años, el índice de masa corporal media fue de 28. La tasa de éxito quirúrgico según los criterios de Sher fue del 82,35%. El 41,17% presentó un índice de apnea-hipopnea postoperatoria inferior a 10. El 75% de los pacientes lograron no tener que usar la CPAP.

Conclusión

La faringoplastia de expansión es una técnica segura como tratamiento del SAHOS en pacientes con amígdalas pequeñas, grado Friedman I y II y colapso de paredes laterales en somnoscopia, en ausencia de colapso multinivel. La DISE postoperatoria demostró la mejoría del colapso lateral obtenida con la expansión.

Abstract

Objectives

The aim of this study was first to present the indications and results using expansion sphincter pharyngoplasty to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS). And second, to compare the findings of drug-induced sleep endoscopy (DISE) before and after the surgery.

Material and methods

The study design was a prospective cohort of patients surgically treated between 2015 and 2016. All patients were diagnosed with mild to severe obstructive sleep apnoea and did not tolerate CPAP. All had pre- and post-surgery DISE and polysomnography. The inclusion criteria were age, between 18 years and 70 years, small tonsils (sizes 1 and 2), Friedman II and III clinical stage, and lateral collapse in preoperative DISE. We performed surgery to the palate only, using expansion sphincter pharyngoplasty.

Results

Seventeen patients were included, 52.94% had severe OSAHS. Average age was 42 years, average body mass index was 28. The surgical success rate according to Sher criteria was 82.35%. 41.17% had a postoperative apnoea-hypopnoea index of less than 10. Seventy-five percent of the patients had no further need for CPAP.

Conclusion

Expansion sphincter pharyngoplasty is a safe technique for treating OSAHS, in patients with small tonsils, Friedman grade I and II and collapse of lateral walls in DISE, in the absence of multilevel collapse. The postoperative DISE showed improvement of the lateral collapse was achieved with the expansion.

https://ift.tt/2OrZwQI

The course of lower cranial nerves within the neck: a cadaveric dissection study

Abstract

Purpose

To evaluate the course of lower cranial nerves (CNs) within the neck in relation to surrounding structures and anatomic landmarks via a cadaveric dissection study.

Methods

A total of 70 neck dissections (31 bilateral, 8 unilateral) were performed on 39 adult fresh cadavers [mean (SD) age: 38.5 (11.2) years, 29 male, 10 female] to identify the course of lower CNs [spinal accessory nerve (SAN), vagus nerve and hypoglossal nerve] within the neck in relation to surrounding structures [internal jugular vein (IJV), common carotid artery (CCA)] and distance to anatomical landmarks (cricoid cartilage, hyoid bone, digastric muscle).

Results

SAN travelled most commonly anterior to IJV (51.4%) at the level of jugular foramen, while travelling lateral to IJV at the post belly of digastric (55.7%) and inferior to digastric muscle (90%) in most neck dissections. Vagus nerve travelled lateral to CCA in majority (94.3%) of dissections, while medial (2.9%), posterolateral (1.4%) and posterior (1.4%) positions were also noted. Average distance of hypoglossal nerve was 27.7 (9.7) mm to carotid bifurcation, 9.3 (3.9) mm to hyoid bone, and 54.7 (18.0) mm to the inferior border of cricoid cartilage.

Conclusion

In conclusion, our findings indicate that anatomic variations are not rare in the course of lower CNs within the neck in relation to adjacent structures, and awareness of these variations together with knowledge of distance to certain anatomic landmarks may help the surgeon to identify lower CNs during neck surgery and prevent potential nerve injuries.

https://ift.tt/2OB9Gin

Intraoral voice recording—towards a new smartphone-based method for vocal rehabilitation

Abstract

After laryngectomy, a new voice is needed. We present the first steps in the development of a smartphone-based method. A microphone is placed in the mouth to record the pseudo-whispering voice of laryngectomized patients. This recording is analyzed by voice recognition software followed by voice synthesis. Eventually, this will be performed on a smartphone. We placed a microphone at 10 different places inside and outside the mouth (two in front of the mouth (at 2 and 20 cm), five on the palate and three on the lower jaw) and made voice recordings in eight healthy men. These recordings were analyzed by voice recognition software. The text generated by the software was compared with the original text. Over all positions, the correct detection of words recorded in the mouth was 19.3% vs. 75.2% (p = 0.01) outside the mouth. In the mouth, recording taken on the maxilla (22.8%) was much better than on the mandible (13.5%) (p = 0.01). The optimum position for a microphone on the maxilla was at the highest point of the palate with 31.9% correct word identification there (p = 0.028). Further investigations have to be undertaken with forthcoming development of smartphone processing power and with development of a smartphone-based voice recognition application.

https://ift.tt/2MlHGBQ

Strahlentherapie bei hepatozellulärem Karzinom

Zusammenfassung

Hintergrund

Das hepatozelluläre Karzinom (HCC) war für die Strahlentherapie lange keine typische Behandlungsindikation, da es erst in den letzten 2 Dekaden möglich wurde, nichttumoröses Lebergewebe ausreichend zu schonen. Daher ist eine radioonkologische Behandlung auf den einschlägigen Behandlungspfaden noch nicht abgebildet.

Fragestellung

Ziel dieser Arbeit ist es, die Möglichkeiten und Grenzen der Strahlentherapie für Patienten mit HCC darzustellen.

Material und Methode

Nach einer knappen Einführung in die Besonderheiten der Radiotherapie für intrahepatische Tumoren wird für die einzelnen Situationen dargestellt, welche Rolle eine perkutane oder interstitielle Radiotherapie bei der Behandlung des HCC spielen kann. Dazu wird eine Einordnung in den verbreiteten Behandlungsalgorithmus nach der Barcelona Clinic Liver Cancer(BCLC)-Klassifikation verwendet.

Ergebnisse

Die Radiotherapie wird bei HCC derzeit v. a. als Körperstereotaxie (SBRT [„stereotactic body radiotherapy"]) eingesetzt, darüber hinaus seltener auch als interstitielle Brachy- sowie als Protonentherapie. Nach der BCLC-Klassifikation kommt sie am häufigsten im Stadium C, gefolgt vom Stadium B zum Einsatz. Auch bei Patienten, bei denen eine Lebertransplantation angestrebt wird, stellt die Radiotherapie eine Möglichkeit für die Überbrückung der Wartezeit („bridging") dar. HCC-Tumoren sind als eher radiosensibel einzustufen, weshalb oft dauerhafte Lokalkontrollen erreicht werden können. Die wichtigste Nebenwirkung, die es durch korrekte Indikationsstellung und optimale Technik gezielt zu vermeiden gilt, ist eine strahleninduzierte Leberkrankheit. Kombinationen der Radiotherapie mit anderen lokalen Verfahren sind nach vorliegender Datenlage im Allgemeinen gut möglich.

Schlussfolgerungen

Die Radiotherapie ist noch nicht als Standardtherapie der ersten Wahl anzusehen, kann aber als wirksame Methode für die Behandlung des HCC angesehen werden. Erste prospektive Studien rechtfertigen diese Einschätzung.

https://ift.tt/2nCKaxn