Effects of hypothermia during propofol anesthesia on learning and memory ability and hippocampal apoptosis in neonatal rats

Abstract

Objective

At present, the harm of hypothermia to the central nervous system has received a great attention from scholars. The present study aimed to investigate the effects of hypothermia on learning and memory abilities and hippocampal apoptosis in neonatal rats and the role of p-ERK and p-CREB in anesthesia.

Methods

In this study, 60 Sprague Dawley newborn rats (age 7-day-old) were randomly divided into 3 groups (n = 20), including Control Group (Group C), Anesthesia Group (Group A), and Anesthesia Hypothermia Group (Group AH). Group C was intraperitoneally injected with 0.1 ml saline, and rectal temperature was maintained in the range of 38–39 °C; Group A was intraperitoneally injected with 25 mg/kg of propofol (0.1 ml), the 1/2 initial dose was added per each period of 20 min, anesthesia was maintained for 2 h, and rectal temperature was kept in the range of 38–39 °C. The anesthesia mode and duration of Group AH were as same as Group A, room temperature was set to 23 °C, which caused body's temperature naturally dropped down. After the anesthesia recovered, each group randomly involved five rats for analyzing by Western blot to detect the expression level of p-ERK and p-CREB, and other five rates were also analyzed by flow cytometry assay to detect hippocampal apoptosis rate. The remaining 10 rats in each group were kept up to 30 days for conducting the Morris water maze test, five rats were tested for detecting the expression level of p-ERK and p-CREB, as well as hippocampal apoptosis rate in each group.

Results

Compared with Group C and Group A, the rectal temperature of Group AH was decreased significantly (P < 0.05); At the age of 7 days, compared with Group C and Group A, apoptosis rate of hippocampal tissue in Group AH was increased (P < 0.05), the expression level of p-ERK and p-CREB proteins in Group AH was significantly reduced (P < 0.05), and there were no significant differences between Group C and Group A. At the age of 36 days, there were no significant differences in the results of behavioral test, apoptotic rates, and expression level of the proteins.

Conclusion

Our findings suggest that hypothermia during anesthesia can increase the apoptosis rate in the hippocampus of neonatal rats, whose mechanism may be related to the downward adjustment of p-ERK and p-CREB. However, it has no obvious influence on the long-term learning and memory abilities.

https://ift.tt/2BdXtfs

Dietary regulation of metastasis

Abstract

The impact of diet and associated lifestyle choices on the risk of developing cancer is well established. However, whether these parameters also affect cancer recurrence and survival is less well investigated. Virtually nothing is known about the impact of diet on the development of metastases. It is therefore significant that a study in this issue of Clinical and experimental metastasis reports that breast cancer-bearing mice fed on a diet rich in long-chain omega-3 fatty acids had a lower incidence of metastasis than control mice, which was associated with modified infiltration of immune cells into the tumors. These findings should form the basis of further pre-clinical evaluation with a view to clinical application.

https://ift.tt/2K8Uact

Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain

Abstract

Inflammation is the body's response to injury and infection, involving a complex biological response of the somatosensory, immune, autonomic, and vascular systems. Inflammatory mediators such as prostaglandin, proinflammatory cytokines, and chemokines induce pain via direct activation of nociceptors, the primary sensory neurons that detect noxious stimuli. Neurogenic inflammation is triggered by nerve activation and results in neuropeptide release and rapid plasma extravasation and edema, contributing to pain conditions such as headache. Neuroinflammation is a localized inflammation in the peripheral nervous system (PNS) and central nervous system (CNS). A characteristic feature of neuroinflammation is the activation of glial cells in dorsal root ganglia, spinal cord, and brain which leads to the production of proinflammatory cytokines and chemokines in the PNS and CNS that drives peripheral sensitization and central sensitization. Here, we discuss the distinct roles of inflammation, neurogenic inflammation, and neuroinflammation in the regulation of different types of pain conditions, with a special focus on neuroinflammation in postoperative pain and opioid-induced hyperalgesia.

https://ift.tt/2FtPBLb

Bridging the gap between vaccination with Bacille Calmette-Guérin (BCG) and immunological tolerance: the cases of type 1 diabetes and multiple sclerosis

Giovanni Ristori | Denise Faustman | Giuseppe Matarese | Silvia Romano | Marco Salvetti

https://ift.tt/2qS6J2I

Progressive annular verrucous erosive plaques on the face

https://ift.tt/2K8G2zF

Voice therapy associated with a decrease in the reflux symptoms index in patients with voice complaints

Objectives/Hypothesis

Patients with muscle tension dysphonia often demonstrate an elevation in Reflux Symptom Index (RSI) and 10‐item Voice Handicap Index (VHI‐10) scores, and may be erroneously diagnosed with laryngopharyngeal reflux disease. In this study we assessed the effects of voice therapy on RSI and VHI‐10 scores in patients with voice complaints not responsive to antireflux medications.

Study Design

Retrospective cohort study.

Methods

A study of patients was conducted at a single tertiary‐care center over 1 year (January 2012–January 2013). Patients were included if they had dysphonia not responsive to proton pump inhibition, did not have neurologic or neoplastic disease, and participated in at least three voice‐therapy sessions in the absence of antireflux therapy. Primary analysis assessed change in RSI scores between the initial and follow‐up visits with a laryngologist.

Results

A total of 18 patients were included (mean age = 49.9 ± 14.5 years, 89% female, 83% with a primary complaint of dysphonia). From initial to follow‐up visit, the median RSI score (18.5 [interquartile range {IQR}, 9.5–22.8] vs. 10.5 [IQR, 4.5–14]; P = .02) and median VHI‐10 score (25.5 [IQR, 11.3–30.0] vs. 13.5 [IQR, 9.5–20.8]; P = .03) significantly decreased. A significant inverse correlation was found between the number of voice therapy sessions/month and change in RSI score (r = −0.4; P = .05).

Conclusions

In this study of patients with muscle tension dysphonia or vocal hyperfunction not responsive to antireflux therapy, RSI and VHI‐10 scores improved following voice therapy. Results suggest that self‐reported symptoms typically attributed to laryngopharyngeal reflux disease may actually be secondary to inefficient voice use patterns or anxiety about dysphonia that are responsive to voice therapy.

Level of Evidence

4 Laryngoscope, 2018

https://ift.tt/2qODmyt

Cutaneous squamous cell carcinoma metastasis to the parotid region lymph nodes

Objective

To determine the effect on survival of periauricular region cutaneous squamous cell carcinomas (cSCC) metastasizing to parotid region and cervical lymph nodes.

Methods

From May 1995 to October 2013, consecutive patients with cSCC undergoing parotidectomy/neck dissection ≥ 18 years without distant metastasis were included. Demographic, clinical, and pathologic data were analyzed. Uni‐ and multivariate analyses of disease‐specific survival and overall survival were performed. Statistical significance was set at P < 0.05.

Results

We evaluated 137 patients. Most patients were Caucasian males with an average age of 71.6 years. The median follow‐up time was 29.4 months.

Thirty‐six percent of patients had pathological evidence of cervical metastasis (N+). Seven percent had metastasis to level I, 21.9% to level II, 14.6% to level III, 8% to level IV, and 9.5% to level V. Thirty‐nine percent of patients had metastasis to parotid region (P+). The average number of positive:total nodes from parotidectomy was 1.9:4.6.

The median overall and disease‐specific survival times were 2.81 and 1.96 years, respectively. Patients with either neck or parotid metastasis (N + or P+) had significantly decreased survival, hazard ratio 2.298 (1.2739, 4.1445), compared to patients without metastasis (N0P0), P < 0.0057.

Conclusion

Patients with periauricular region cSCC metastasizing to parotid and cervical regions lymph nodes have significantly decreased survival compared with patients without cervical and/or parotid metastasis. Metastasis to parotid region should be considered as a distinct head and neck level when staging periauricular cancers. This study provides a basis for further studies to validate these findings.

Level of Evidence

4. Laryngoscope, 2018

https://ift.tt/2FsXyju

Sex bias: Is it pervasive in otolaryngology clinical research?

Objectives/Hypothesis

Recent initiatives highlight substantial sex bias in biomedical research. The objective was to determine whether sex bias is present in otolaryngology and whether sex is appropriately analyzed as an independent variable in otolaryngology clinical research.

Study Design

Literature review.

Methods

We systematically reviewed all 2016 articles in three major otolaryngology journals: The Laryngoscope, JAMA Otolaryngology–Head and Neck Surgery, and Otolaryngology–Head and Neck Surgery. Extracted data included study origin, location, subspecialty, number/sex of subjects, ≥50% sex matching (SM_≥50), and sex‐based statistical analysis.

Results

Six hundred of 1,209 articles comprising original clinical research were reviewed including 8,997,345,495 subjects (males: 3,898,559,264 [43.3%]; females: 5,095,592,583 [56.6%]; and unknown: 3,193,648 [0.04%]). There were 533/600 (88.8%) studies that included both sexes, eight (1.3%) included females only, five (0.8%) included males only, and 56 (9.3%) did not document participant sex. Only 280 studies (46.7%) analyzed data by sex, and 330 studies (60.7%) had SM_≥50. Sex‐based statistical analysis and SM_≥50 were similar in domestic and international studies (48.7% vs. 42.8% and 60.9% vs. 62%, respectively). Database studies performed sex‐based statistical analysis more frequently than single and multi‐institutional studies (79.1% vs. 40.4% and 43.4%, P < .00001). Analysis by sex was more frequently performed in head and neck surgery (53.6%) and pediatric otolaryngology (51.3%), whereas SM_≥50 was highest in pediatric otolaryngology (86.8%) and otology (82.4%).

Conclusions

Sex bias exists in the clinical otolaryngology literature, with less than half the studies analyzing sex. Acknowledging the intertwinement of sex with disease pathophysiology and outcomes is important. Eliminating sex bias in research and clinical care should become a major focus for otolaryngologists.

Level of Evidence

NA Laryngoscope, 2018

https://ift.tt/2qSrQlQ

Tracheostomy demographics and outcomes among pediatric patients ages 18 years or younger—United States 2012

Objectives/Hypothesis

To estimate the number, demographics, and outcomes of pediatric patients who underwent tracheostomy in 2012 and to contrast those outcomes by age, race, and gender.

Study Design

Cross‐sectional study.

Methods

The 2012 Kids Inpatient Database was queried to identify tracheostomy patients using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) procedural codes 311, 3121, and 3129. All patients ≤18 years of age at the time of admission were included and categorized as neonates (≤28 days), infants (>28 days ≤1 year), toddler (1 to 3 years), children (4 to 12 years), adolescents (13 to 17 years), and adults (=18 years). We recorded age, gender, race, insurance status, and zip code of primary residence. We used these variables to contrast the following outcomes: length of stay, total charges, complications of care, and mortality using multiple regression analysis.

Results

An estimated 4,424 pediatric tracheostomies occurred during 2012. Fifty‐one percent of the patients were ≤3 years old, and 62% were male. Forty‐eight percentwere white followed by black (21%), Hispanic (20%), and Asian (3%). The median length of stay was 42 days, and the median total charges were $472,738. The complication rate was 29% and the mortality rate was 8.0%. The length of stay and total charges was predicted by age, with neonates having significantly longer hospitalizations. The complication rate was not associated with age, gender, or ethnicity. However, the mortality rate was associated with younger age.

Conclusions

Pediatric tracheostomies are associated with significant hospital utilizations, complications, and mortality. Increased risk of mortality is observed among neonates and infants. Continued study of tracheostomy outcomes among these subsets of the pediatric population are warranted.

Level of Evidence

4 Laryngoscope, 2018

https://ift.tt/2FptuoY

Long‐term swallowing performance following transoral robotic surgery for obstructive sleep apnea

Objectives/Hypothesis

This study aimed to evaluate the long‐term swallowing performance following transoral robotic surgery (TORS) to the base of tongue (BOT) in the treatment of obstructive sleep apnea (OSA).

Study Design

Retrospective and prospective cohort study.

Methods

Data analysis of 39 patients who underwent BOT reduction via TORS to treat OSA at our center from September 2013 to April 2016. Long‐term swallowing functions were assessed using subjective self‐evaluated swallowing disturbances questionnaire (SDQ) and objective fiberoptic endoscopic evaluation of swallowing (FEES).

Results

Seven patients underwent TORS BOT reduction alone, whereas 32 had also uvulopalatoplasty ± tonsillectomy, with a surgical success rate of 71.4%. Mean time for swallowing evaluation was 27.4 ± 9.43 months. Twenty‐five patients completed the SDQ with an average score of 9.26 ± 10.05. In 32%, the SDQ was positive for dysphagia. In 10 out of 14 patients who underwent FEES, swallowing problems were noticed. The most common pathological findings were food residue in the vallecula followed by early spillage of food into the hypopharynx, penetration of solid food and liquid on the vocal folds surface, and aspiration.

Conclusions

BOT reduction via TORS has a negative effect on long‐term swallowing function. A self‐assessment questionnaire can help detect patients who suffer from swallowing impairment. Postoperative objective swallowing tests are essential not only in the immediate postoperative period but also during late routine follow‐up. Proper patient selection and detailed information about surgery and possible late‐swallowing effect are important factors before scheduling BOT reduction via TORS for OSA treatment.

Level of Evidence

4 Laryngoscope, 2018

https://ift.tt/2qQ7fOQ

Impact of a Formal Patient Safety and Quality Improvement Curriculum: A Prospective, Controlled Trial

Objective

To assess the impact of implementing a dedicated Patient Safety and Quality Improvement (PSQI) curriculum for otolaryngology residents.

Methods

Residents in two otolaryngology residency programs were recruited to participate in the study. Residents at institution A (intervention group) participated in a formal, newly developed, year‐long PSQI curriculum. Residents at institution B (control group) participated in traditional, morbidity, and mortality conference‐based PSQI education, with no formal curriculum in place. Curriculum participants completed anonymous surveys to assess learner satisfaction. Validated instruments were administered to assess for changes in resident confidence in the ability to develop PSQI projects, their attitudes toward patient safety, and PSQI‐related knowledge. The number and quality of PSQI‐related resident projects were also assessed.

Results

Survey responses demonstrated excellent learner satisfaction with the curriculum. Based on validated instrument‐based responses, both programs demonstrated similar confidence scores (P = 0.05), safety attitudes (P = 0.82), and PSQI knowledge (P = 0.29) at the beginning of the year. The residents of institution A demonstrated significant improvement in confidence (P = 0.00009) and knowledge (P = 0.0006) after completing the curriculum, with no improvement noted for residents at institution B in either confidence (P = 0.06) or knowledge (P = 0.79). Neither program demonstrated improvement in attitudes toward patient safety at the end of the year‐long curriculum.

Conclusion

Implementing a formal curriculum dedicated to PSQI led to an improvement in PSQI‐related project development confidence and PSQI knowledge. Attitudes toward safety did not improve over the course of a year. Longer‐term studies involving multiple institutions and other interventions are needed to evaluate the impact and duration of changes that occur.

Level of Evidence

1b. Laryngoscope, 2018

https://ift.tt/2FoEYJy

Evolving phenotype of the head and neck surgeon

Objective

Characterize the evolution of head and neck (H&N) surgical practices in the United States over two decades by using resident case log data as a surrogate.

Methods

National residency case log data from all Accreditation Council for Graduate Medical Education‐accredited otolaryngology residency programs was reviewed for the past 20 academic years (1996–2015). Key indicator procedures in each subcategory of H&N were analyzed to characterize standard ablative H&N surgical practices. Mean number of cases completed per resident each year was calculated.

Results

The proportion of H&N surgeries contributing to the total number of otolaryngology cases performed yearly remained relatively stable during the study period, ranging from 6.4% to 8.7%, indicating concurrent growth of H&N cases with all otolaryngology surgeries. Although each subcategory within H&N demonstrated modest increases in the number of cases performed per resident each year over the study period, the most significant growth occurred in the endocrine surgery subcategory: a 288% increase from 18.4 in 1996 to 71.5 in 2015. The proportion of H&N cases represented by each subcategory decreased, except for endocrine, which more than doubled in proportion from 21% in 1996 to 43% in 2015.

Conclusion

Our findings suggest that the modern H&N surgeon is increasingly becoming an endocrine and H&N surgeon. The proportion of endocrine surgeries performed in residency, which serves as a surrogate for H&N practices, has more than doubled over the past 20 years and now represents the largest subcategory of H&N surgery.

Level of Evidence

NA. Laryngoscope, 2018

https://ift.tt/2qPyvND

Real‐time robotic airway measurement: An additional benefit of a novel steady‐hand robotic platform

Objective

Describe the secondary capability of a robotic system to provide real‐time measurements of airway dimensions with high fidelity.

Methods

Seven unique phantoms of laryngotracheal stenosis (LTS) were modeled using a computer‐aided design tool and were three dimensionally printed. These stenoses were of different dimensions and orientations, and some were purposefully oblique. The dimensions of the stenoses were then measured with the novel Robotic ENT (Ear, Nose, and Throat) Microsurgery System (REMS; Galen Robotics, Inc., Sunnyvale, CA) because it is capable of tool position memory in three dimensional (3D) space. Five participants (two laryngologists, two otolaryngology–head and neck surgery residents, one neurotology fellow) measured each axis of stenosis (anteroposterior, lateral, and craniocaudal) three times for each of the seven stenosis phantoms. These measurements were then compared to the known design dimensions. Mean magnitude of error (MOE) and interrater reliability (IRR) using an intraclass correlation coefficient (ICC) were then calculated.

Results

Mean MOE and standard deviation for all measurements was 0.306 ± 0.247 mm. Mean MOE was 0.374 ± 0.292 mm, 0.300 ± 0.237 mm, and 0.244 ± 0.185 mm for the anteroposterior, lateral, and craniocaudal dimensions of stenosis, respectively. Eighty‐two percent of all measurements had MOE < 0.5 mm. ICC was 0.945 (95% confidence interval [CI]: 0.847–0.989), 0.995 (95% CI: 0.984–0.999), and 0.993 (95% CI: 0.987–0.999) for anteroposterior, lateral, and craniocaudal dimensions, respectively, indicating excellent agreement among participants.

Conclusion

The REMS can be used to reliably and accurately measure airway dimensions in 3D regardless of the orientation of stenosis. This ability may be easily extrapolated to the measurement of any airway lesion during laryngotracheal surgery.

Level of Evidence

4. Laryngoscope, 2018

https://ift.tt/2FB8X0C

Dysfunctional hypoglossal nerve stimulator after electrical cardioversion: A case series

Objectives/Hypothesis

Upper airway stimulation has demonstrated marked improvements in apnea‐hypopnea index, oxygen desaturation index, and quality‐of‐life measures in patients with moderate to severe obstructive sleep apnea (OSA) who cannot tolerate continuous positive airway pressure. Cardiac arrhythmias are common in patients with OSA and can require electrical cardioversion. We describe the first four reported cases of hypoglossal nerve stimulator (HGNS) dysfunction after electrical cardioversion and illustrate our operative approach to device troubleshooting and repair.

Study Design

Retrospective case series.

Methods

A retrospective review of 201 HGNS implantations performed at two academic institutions revealed four cases of HGNS device dysfunction after electrical cardioversion requiring surgical revision. Preoperative and postoperative device performance metrics and electrical cardioversion specifications were retrospectively assessed and compiled for this case series. The senior authors (R.J.S., M.S.B.) detail operative planning and approach for HGNS implantable pulse generator (IPG) replacement.

Results

At least two patients with HGNS device dysfunction had received cardioversion via anterolateral electrode pad placement. Three patients had received multiple shocks. All four patients experienced a change in device functionality or complete cessation of functionality after electrocardioversion. Operatively, each patient required replacement of the IPG, with subsequent intraoperative interrogation revealing proper device functionality.

Conclusion

Counseling for patients with HGNS undergoing external electrical cardioversion should include possible device damage and need for operative replacement. Anteroposterior electrode pad placement should be considered for patients with HGNS who require electrocardioversion. Operative replacement of an HGNS system damaged by electrocardioversion begins with IPG replacement and intraoperative device interrogation.

Level of Evidence

4. Laryngoscope, 2018

https://ift.tt/2qQcL3W

Are chronic cough and laryngopharyngeal reflux more common in obstructive sleep apnea patients?

Objectives/Hypothesis

To assess if there is a significant difference in the prevalence and severity of chronic cough symptoms in obstructive sleep apnea (OSA) patients versus non‐OSA patients and examine this relationship in regard to laryngopharyngeal reflux (LPR) symptoms.

Study Design

Prospective cohort study.

Methods

Patients referred to Northwestern Medicine Sleep Lab for home sleep testing were enrolled. Patients filled out the Leicester Cough Questionnaire (LCQ) and Reflux Symptom Index (RSI) before completing sleep testing. Home sleep testing results were reviewed, and patients were separated into non‐OSA and OSA groups by standard Apnea‐Hypopnea Index (AHI) criteria. Demographic characteristics and questionnaire scores of the two groups were compared. The relationship between OSA severity, as determined by AHI, and LCQ and RSI scores was assessed.

Results

Of the 52 patients enrolled, 33 patients met criteria for OSA and 19 patients did not. Comparing patients without OSA versus those with OSA, there was a significant difference in mean LCQ score (129.9 vs. 120.0, respectively; P = .02), implying worse cough symptoms among OSA patients, and mean RSI score (3.2 vs. 11.2, respectively; P = .0013), implying worse upper‐airway reflux symptoms among OSA patients. There was a significant correlation between LCQ score and AHI (r = –0.39, P = .0061) and between RSI score and AHI (r = 0.37, P = .0078).

Conclusions

OSA patients demonstrate worse chronic cough and LPR‐related quality of life versus non‐OSA patients. Furthermore, the severity of these quality‐of‐life measures was correlated with the severity of the AHI. Chronic cough and particularly the pharyngeal LPR symptoms may be associated with the presence and severity of OSA.

Level of Evidence

2 . Laryngoscope, 2018

https://ift.tt/2FoEYt2

Applying Artificial Intelligence to Address the Knowledge Gaps in Cancer Care

AbstractBackground.Rapid advances in science challenge the timely adoption of evidence‐based care in community settings. To bridge the gap between what is possible and what is practiced, we researched approaches to developing an artificial intelligence (AI) application that can provide real‐time patient‐specific decision support.Materials and Methods.The Oncology Expert Advisor (OEA) was designed to simulate peer‐to‐peer consultation with three core functions: patient history summarization, treatment options recommendation, and management advisory. Machine‐learning algorithms were trained to construct a dynamic summary of patients cancer history and to suggest approved therapy or investigative trial options. All patient data used were retrospectively accrued. Ground truth was established for approximately 1,000 unique patients. The full Medline database of more than 23 million published abstracts was used as the literature corpus.Results.OEA's accuracies of searching disparate sources within electronic medical records to extract complex clinical concepts from unstructured text documents varied, with F1 scores of 90%–96% for non‐time‐dependent concepts (e.g., diagnosis) and F1 scores of 63%–65% for time‐dependent concepts (e.g., therapy history timeline). Based on constructed patient profiles, OEA suggests approved therapy options linked to supporting evidence (99.9% recall; 88% precision), and screens for eligible clinical trials on ClinicalTrials.gov (97.9% recall; 96.9% precision).Conclusion.Our results demonstrated technical feasibility of an AI‐powered application to construct longitudinal patient profiles in context and to suggest evidence‐based treatment and trial options. Our experience highlighted the necessity of collaboration across clinical and AI domains, and the requirement of clinical expertise throughout the process, from design to training to testing.Implications for Practice.Artificial intelligence (AI)‐powered digital advisors such as the Oncology Expert Advisor have the potential to augment the capacity and update the knowledge base of practicing oncologists. By constructing dynamic patient profiles from disparate data sources and organizing and vetting vast literature for relevance to a specific patient, such AI applications could empower oncologists to consider all therapy options based on the latest scientific evidence for their patients, and help them spend less time on information "hunting and gathering" and more time with the patients. However, realization of this will require not only AI technology maturation but also active participation and leadership by clincial experts.

https://ift.tt/2BbardY

EGFR Mutation Testing: Changing Patterns of Molecular Testing in Brazil

AbstractBackground.In Brazil, cancer is the second most common cause of death. Most patients in resource‐limited countries are diagnosed in advanced stages. Current guidelines advocate for EGFR mutation testing in all patients with metastatic adenocarcinoma. Tyrosine kinase inhibitors are recommended in patients with advanced or metastatic disease harboring sensitizing mutations. In Brazil, there are limited data regarding the frequency of EGFR testing and the changes in patterns of testing overtime.Materials and Methods.This was an observational, retrospective study. We obtained deidentified data from a commercial database, which included 11,684 patients with non‐small cell lung cancer treated between 2011 and 2016 in both public and private settings. We analyzed the frequency of EGFR mutation testing over time. We also directly studied 3,664 tumor samples, which were analyzed between 2011 and 2013. These samples were tested for EGFR mutations through an access program to tyrosine kinase inhibitors in Brazil.Results.Overall, 38% of patients were tested for EGFR mutations; 76% of them were seen in the private sector, and 24% were seen in the public center. The frequency of testing for EGFR mutations increased significantly over time: 13% (287/2,228 patients) in 2011, 34% (738/2,142) in 2012, 39% (822/2,092) in 2013, 44% (866/1,972) in 2014, 53% (1,165/2,184) in 2015, and 42% (1,359/3,226) in 2016. EGFR mutations were detected in 25.5% of analyzed samples (857/3,364). Deletions in Exon 19 were the most frequent mutations, detected in 54% of patients (463/857).Conclusion.Our findings suggest that the frequency of EGFR mutation in this cohort was lower than that found in Asia but higher than in North American and Western European populations. The most commonly found mutations were in Exon 19 and Exon 21. Our study shows that fewer than half of patients are being tested and that the disparity is greater in the public sector.Implications for Practice.These data not only indicate the shortage of testing but also show that the rates of positivity in those tested seem to be higher than in other cohorts for which data have been published. This study further supports the idea that awareness and access to testing should be improved in order to improve survival rates in lung cancer in Brazil.

https://ift.tt/2K9JhXG

Tobacco Use Assessment and Treatment in Cancer Patients: A Scoping Review of Oncology Care Clinician Adherence to Clinical Practice Guidelines in the U.S.

AbstractBackground.Smoking after a cancer diagnosis negatively impacts health outcomes; smoking cessation improves symptoms, side effects, and overall prognosis. The Public Health Service and major oncology organizations have established guidelines for tobacco use treatment among cancer patients, including clinician assessment of tobacco use at each visit. Oncology care clinicians (OCCs) play important roles in this process (noted as the 5As: Asking about tobacco use, Advising users to quit, Assessing willingness to quit, Assisting in quit attempts, and Arranging follow‐up contact). However, OCCs may not be using the "teachable moments" related to cancer diagnosis, treatment, and survivorship to provide cessation interventions.Materials and Methods.In this scoping literature review of articles from 2006 to 2017, we discuss (1) frequency and quality of OCCs' tobacco use assessments with cancer patients and survivors; (2) barriers to providing tobacco treatment for cancer patients; and (3) the efficacy and future of provider‐level interventions to facilitate adherence to tobacco treatment guidelines.Results.OCCs are not adequately addressing smoking cessation with their patients. The reviewed studies indicate that although >75% assess tobacco use during an intake visit and >60% typically advise patients to quit, a substantially lower percentage recommend or arrange smoking cessation treatment or follow‐up after a quit attempt. Less than 30% of OCCs report adequate training in cessation interventions.Conclusion.Intervention trials focused on provider‐ and system‐level change are needed to promote integration of evidence‐based tobacco treatment into the oncology setting. Attention should be given to the barriers faced by OCCs when targeting interventions for the oncologic context.Implications for Practice.This article reviews the existing literature on the gap between best and current practices for tobacco use assessment and treatment in the oncologic context. It also identifies clinician‐ and system‐level barriers that should be addressed in order to lessen this gap and provides suggestions that could be applied across different oncology practice settings to connect patients with tobacco use treatments that may improve overall survival and quality of life.

https://ift.tt/2BcspN3

Progressive annular verrucous erosive plaques on the face

https://ift.tt/2K8G2zF

Give Thyroid Health on #GivingTuesday, November 27

This year, #GivingTuesday falls on November 27.

It inspires people to take collective action to improve their communities and to give back to the charities and causes they believe in to help create a healthier world.

Your Donation on Giving Tuesday Supports

• Vital Research for Thyroid Diseases and Thyroid Cancer
• Reliable Thyroid Information for Patients and Families
• Expert Clinical Practice Guidelines

Give Together, Give Thyroid Health on #GivingTuesday.

#GIVE2THYROID

The post Give Thyroid Health on #GivingTuesday, November 27 appeared first on American Thyroid Association.

https://ift.tt/2zhjCIi

Give Thyroid Health on #GivingTuesday, November 27

This year, #GivingTuesday falls on November 27.

It inspires people to take collective action to improve their communities and to give back to the charities and causes they believe in to help create a healthier world.

Your Donation on Giving Tuesday Supports

• Vital Research for Thyroid Diseases and Thyroid Cancer
• Reliable Thyroid Information for Patients and Families
• Expert Clinical Practice Guidelines

Give Together, Give Thyroid Health on #GivingTuesday.

#GIVE2THYROID

The post Give Thyroid Health on #GivingTuesday, November 27 appeared first on American Thyroid Association.

https://ift.tt/2zhjCIi

Postoperative myxedema coma in patients undergoing major surgery: Case series

Myxedema coma is a serious complication of hypothyroidism that can be precipitated by major surgery. It is extremely rare, with only a few reports in the literature. This study aims to present a relatively large case series of post-surgical myxedema coma and to analyze medical and surgical risk factors.

https://ift.tt/2OKoKd2

MiR-196b affects the progression and prognosis of human LSCC through targeting PCDH-17

To explore the effect of miR-196bon the biological features of human laryngeal squamous cell carcinoma (LSCC) through targeting PCDH-17.

https://ift.tt/2zdooqi

What is melasma?

Melasma causes dark patches to appear on the skin. It is a pigmentation disorder that is more common in women. Learn about the symptoms, risk factors, and treatments here.

https://ift.tt/2qPapCD

What is melasma?

Melasma causes dark patches to appear on the skin. It is a pigmentation disorder that is more common in women. Learn about the symptoms, risk factors, and treatments here.

https://ift.tt/2qPapCD

Shaved hair style scalp medical tattooing technique for treatment of advanced male pattern baldness patients

Abstract

Background

The most infallible approach to male pattern baldness (MPB) is hair transplantation in the thinning area in parallel to medical treatment to prevent further alopecia progression. For an individual with advanced stage hair loss, a megasession surgery is recommended to meet the high donor hair requirement. Yet a most effective therapeutic regimen for alopecia, hair transplantation inevitably has its advantages and disadvantages for it is done with the expense of donor hair sacrifice, intraoperative and postoperative pain, and unavoidable scars. Also, with poor donor condition, surgery may not even be an option. Nowadays, more patients with such limitations are undergoing shaved style scalp medical tattoo (SMT).

Objective

To assess the effectiveness of SMT technique for shaved hair style.

Methods and materials

A total of 80 patients who were included in the study underwent SMT for shaved hair style between June 2014 and June 2017 and were followed for at least 6 months afterward. Patients and the surgeon completed a survey about donor and recipient site surgical results using a 5‐point Likert scale.

Results

The average satisfaction scores of patients and surgeon were 4.8 and 4.9, respectively.

Conclusion

Shaved style SMT can be considered one of the most effective treatment methods for patients with advanced stage hair loss.

Level of evidence

IV.

https://ift.tt/2FqlR1B

Secretory carcinoma: the eastern Canadian experience and literature review

Secretory Carcinoma (SC) is a recently described malignancy affecting salivary glands of the head and neck, with a paucity of evidence regarding the natural history, morbidity, and mortality. This study aimed ...

https://ift.tt/2Q0wFrq

The Cervicofacial lift under Pure local anaesthesia diminishes the incidence of postoperative haematoma

The cervicofacial lift is a frequently performed procedure in plastic surgery. It is the reference technique for facial rejuvenation and restoration of the oval form of the face and it is essential to treat excess skin. One of the most frequent complications of this procedure is the formation of haematomas. The aim of this article is to analyze the incidence of bleeding in the standard cervicofacial lift carried out under pure local anaesthesia. The entire operation, including liposuction and tightening of the SMAS, can be done under local anaesthesia.

https://ift.tt/2OOiroH

Skin Diseases of the Breast and Nipple Part 2: Inflammatory and Infectious Diseases

Certain dermatologic conditions are unique to the breast and nipple, whereas others may incidentally involve these structures. All require a nuanced approach to diagnosis and treatment due to the functional, sexual and aesthetic importance of this area. The lactating patient requires special management since certain treatment options are contraindicated. All dermatologic conditions involving the breast and nipple require careful evaluation since breast malignancy can be mistaken for a benign condition or may trigger the development of certain dermatologic conditions.

https://ift.tt/2QJrCIS

Skin Diseases of the Breast and Nipple Part I: Benign and Malignant Tumors

Evaluation and management of dermatologic diseases of the breast and nipple requires an understanding of the unique anatomy of the breast and nipple as well as an awareness of the significant emotional, cultural, and sexual considerations that may come into play when treating this anatomic area. Part I of this 2 Part CME Series reviews breast anatomy, congenital breast anomalies, and benign and malignant breast tumors. Specifically, an emphasis is placed on inflammatory breast cancer and breast cancer with non-inflammatory skin involvement as well as on cutaneous metastases to the breast and from breast cancer.

https://ift.tt/2Py1qV5

A simple technique to increase field of view (FOV) of a USB dematoscope

https://ift.tt/2QOBnFM

SELF-ASSESSMENT

No abstract available

https://ift.tt/2OLE7lq

North American Contact Dermatitis Group Patch Test Results: 2015–2016

Background Patch testing is an important diagnostic tool for the assessment of allergic contact dermatitis (ACD). Objective This study documents the North American Contact Dermatitis Group (NACDG) patch testing results from January 1, 2015, to February 28, 2017. Methods At 13 centers in North America, patients were tested in a standardized manner with a screening series of 70 allergens. Data were manually verified and entered into a central database. Descriptive frequencies were calculated, and trends were analyzed using χ2 test. Results A total of 5597 patients were tested. There were 3725 patients (66.6%) who had at least 1 positive reaction, and 2798 patients (50.2%) were ultimately determined to have a primary diagnosis of ACD. A total of 572 patients (10.2%) had occupationally related skin disease. There were 10,983 positive allergic reactions. Nickel remained the most commonly detected allergen (17.5%). Methylisothiazolinone, which was added to the screening series for the 2013–2014 cycle, had the second highest positive reaction rate of allergens tested (13.4%). Compared with the previous reporting periods (2013–2014) and (2005–2014), positive reaction rates for the top 35 screening allergens statistically increased for only 1 allergen: hydroxyethyl methacrylate (3.4%; risk ratios, 1.24 [confidence interval, 1.00–1.54] and 1.46 [confidence interval, 1.23–1.73]). Three newly added allergen preparations—ammonium persulfate (1.7%), chlorhexidine (0.8%), and hydroquinone (0.3%)—all had a reaction rate of less than 2%. Twenty-three percent of the tested patients had at least 1 relevant allergic reaction to an allergen not on the NACDG series; 12% of these were occupationally related. T.R.U.E. Test (SmartPractice Denmark, Hillerød, Denmark) would have hypothetically missed one quarter to almost 40% of reactions detected by the NACDG screening series. Conclusions These results confirm that the epidemic of sensitivity to methylisothiazolinone has continued in North America. Patch testing with allergens beyond a screening tray is necessary for a complete evaluation of occupational and nonoccupational ACD.

https://ift.tt/2zbYMKE

Orthodontic Appliance Intolerance Due to Dental Adhesive Allergy

No abstract available

https://ift.tt/2ONZDpH

Trends in Patch Testing With the Mayo Clinic Standard Series, 2011–2015

Background Patch testing to a standard (baseline) series of allergens is the screening tool used to identify culprit allergens in patients with contact dermatitis. The allergens and concentrations used in a standard series are constantly evolving to be most relevant to the patients being patch tested. Objective The aim of this study was to analyze the 2011–2015 patch test results of the Mayo Clinic standard series. Methods We retrospectively reviewed patch test reactions of standard series allergens from 2011 through 2015 and compared these results with the 2011–2012 and 2013–2014 North American Contact Dermatitis Group (NACDG) reports. Conclusions Of 2582 patients included, 1566 (60.7%) had at least 1 positive reaction, and 516 (20.0%) had at least 1 irritant reaction. The 15 allergens with the highest reaction rates (from highest to lowest) were nickel sulfate hexahydrate, methylisothiazolinone, Myroxylon pereirae resin, neomycin sulfate, cobalt (II) chloride hexahydrate, benzalkonium chloride, fragrance mix I, potassium dichromate, bacitracin, methylchloroisothiazolinone/methylisothiazolinone, carba mix, formaldehyde, p-phenylenediamine, quaternium-15, and methyldibromo glutaronitrile. Twelve (80%) of these allergens were also in the top 15 of the most recent NACDG report; the 3 allergens not in the NACDG top 15 allergens were potassium dichromate, benzalkonium chloride, and methyldibromo glutaronitrile (the latter 2 allergens are not included in their series).

https://ift.tt/2zfBe7H

Dupilumab as a Treatment for Allergic Contact Dermatitis

No abstract available

https://ift.tt/2OOOViz

Associations of Nickel Co-Reactions and Metal Polysensitization in Adults

Background Allergic contact dermatitis to metals is a significant clinical and public health problem. Little is known about the determinants of polysensitization to metals. Objective The aim of the study was to determine the frequency and predictors of nickel co-reactions and metal polysensitization. Methods This is a retrospective chart review of 686 adults (age ≥ 18 years) who were patch tested from 2014 to 2017. Results Overall, 267 patients (38.9%) had 1 or more positive patch-test reactions to a metal allergen, most commonly nickel (17.4%), mercury (12.3%), and palladium (9.2%). Nickel reactions were inversely associated with age (logistic regression; adjusted odds ratio [95% confidence interval], 0.39 [0.29–0.78]). Among patients with positive reactions to nickel, 34.5%, 15.1%, and 5.0% had positive reactions to 1, 2, or 3 additional metals, respectively. The most common nickel co-reactors were palladium, mercury, and gold. Polysensitization to metals occurred in 11.8% of patients. Polysensitization to metal allergens was associated with female sex (6.67 [1.01–44.21]) and inversely associated with age (0.40 [0.18–0.88]). Conclusions Nickel-sensitized patients have high rates of metal co-reactions. Polysensitization to metals is common in adults. These results may help guide future strategies for allergen avoidance.

https://ift.tt/2z97E3u

Patch Testing by Anton C. de Groot

No abstract available

https://ift.tt/2OOc84G

Comparison of Nickel Sulfate 2.5% and Nickel Sulfate 5% for Detecting Nickel Contact Allergy

Background Nickel is among the most common contact allergens found on patch testing worldwide and, because of its ubiquitous nature in our environment, often has important implications for allergen avoidance strategies. In both North America and Europe, nickel positivity is found in approximately 20% of patients who undergo patch testing. Whereas in North America, nickel sulfate is typically tested at a concentration of 2.5%, in Europe, it is tested at a 5% concentration. Objective The primary objective was to assess the differences in patch test positivity to nickel sulfate 2.5% and 5%. Methods We investigated 205 consecutive patients between September 2017 and February 2018 who were tested to nickel sulfate at concentrations of both 2.5% and 5%. Results Among the 205 patients tested, 33% were positive (+, ++, or +++) to at least 1 concentration of nickel sulfate, 20% were positive to nickel sulfate 2.5%, and 31% were positive to nickel sulfate 5% (χ21(N = 205) = 16.1, P = 0.0001). Patients were 6.5 times more likely to have a positive reaction to nickel sulfate 5% than 2.5% (odds ratio 95% confidence interval, 2.3–25.6). Conclusions Given our findings, we propose an additional evaluation of nickel sulfate 5% as a standard allergen for patch testing in North America.

https://ift.tt/2z97x84

Cannabidiol-Induced Acute Generalized Exanthematous Pustulosis

No abstract available

https://ift.tt/2ONjuVW

Skin Sensitization Induction Potential From Daily Exposure to Fragrances in Personal Care Products

Background Many chemicals used for fragrance purposes in a diversity of products have allergenic potential. Based on such concerns, industry groups developed concentration limits for use of fragrance chemicals in personal care and cosmetic products. Objective The aim of this study was to use a quantitative risk assessment to evaluate the potential for skin sensitization induction resulting from daily exposure to fragrance chemicals present in personal care and cosmetic products. Methods Product-specific dermal consumer exposure levels were calculated based on product use data in US adult females and benchmarked against acceptable exposure levels based on reported no expected sensitization induction levels to determine a margin of safety for each fragrance under evaluation. Conclusions The results demonstrate an increased risk of skin sensitization induction for several leave-on products (lipstick, solid antiperspirant, eye shadow, face cream) for most of the evaluated fragrance chemicals, particularly under high-use exposure scenarios. In contrast, rinse-off products (shampoo, conditioner, facial cleanser) were not associated with risk of skin sensitization induction. Because the approach was based on maximum use limits for fragrance chemicals with skin sensitization concerns, the results suggest these limits may not be protective, particularly in the United States.

https://ift.tt/2z97qcE

Erythema Multiforme Major After Immunotherapy With Diphenylcyclopropenone for Alopecia Areata

No abstract available

https://ift.tt/2OObXX4

Isothiazolinone in Residential Interior Wall Paint: A High-Performance Liquid Chromatographic–Mass Spectrometry Analysis

Background There is limited information regarding isothiazolinone content in residential wall paints in the United States. Objective The aim of this study was to evaluate the prevalence of 5 isothiazolinones—methylisothiazolinone (MI), methylchloroisothiazolinone, benzisothiazolinone (BIT), butyl BIT, and octylisothiazolinone—in US residential wall paints. Methods Forty-seven paints were obtained from retailers in Minneapolis/St Paul, Minnesota. Paint samples were assessed for the presence of the 5 isothiazolinones using high-performance liquid chromatographic–mass spectrometry. Results At least 1 isothiazolinone was detected in all 47 paints. However, no paint contained butyl BIT, and only 1 paint had octylisothiazolinone. The MI and BIT were found in 96% and 94% of the paints, respectively. Methylisothiazolinone ranged in concentration from 17 to 358 ppm, whereas BIT varied from 29 to 1111 ppm. Methylchloroisothiazolinone was found solely in oil-based paints. Isothiazolinones were declared in 15% of Safety Data Sheets but did not correlate with high-performance liquid chromatographic–mass spectrometry. One "preservative-free" paint had BIT at 71.5 ppm. Paint sheen was not statistically associated with BIT or MI concentrations. Unpigmented paints and paints with volatile organic compound claims had significantly lower concentrations of MI, but not BIT. Conclusions All paints contained at least 1 isothiazolinone. Methylisothiazolinone and BIT were the most common. Safety Data Sheets are insufficient for ascertaining isothiazolinone content in US paints.

https://ift.tt/2z97l8Q

Contact Allergy to Propylene Glycol and Cross-Reactions

No abstract available

https://ift.tt/2OKpSND

Moisturizers: A Comparison Based on Allergens and Economic Value

Background The economic burden of cosmetics, such as moisturizers, has been increasing. Despite the high price of some market moisturizers, there have been no studies evaluating the allergenicity of these products. Objective The aim of this study was to evaluate the potential allergens within moisturizers based on economic value, by analyzing the substances found in moisturizers available online at the largest drugstore chain—CVS Health (CVS Health, Woonsocket, RI). Methods In this cross-sectional study, ingredients found in 50 expensive and 50 inexpensive moisturizers were matched with sensitizers within the Core Allergen Series published by the American Contact Dermatitis Society and the North American Contact Dermatitis Group. Student t test was used to compare the mean number of allergens present in each group. A χ2 test or Fisher exact test, where necessary, was used to compare the rates of specific allergen groups between the expensive and inexpensive products. Results Twenty-six allergenic substances were present overall in the 100 total products surveyed. The expensive moisturizers averaged significantly more allergens per product (8.28 vs 5.60, P = 0.003) than the inexpensive products. Conclusions The sensitizing potential of expensive moisturizers may be higher than that of inexpensive moisturizers. Physicians may counsel cosmetic-induced allergic contact dermatitis (ACD) patients that monetary value is not a suitable proxy for evaluating the risk of ACD.

https://ift.tt/2zdVJRV

Long-term Likelihood of Patch Testing, Academic Practice, and American Contact Dermatitis Society Membership Among North American Alexander Fisher Award Winners From 1989 to 2012

Background The Alexander Fisher Award (AFA) recognizes excellence in research among dermatology residents or medical students who make formal presentations at the annual American Contact Dermatitis Society (ACDS) meeting. Objective The aim of the study was to investigate long-term likelihood of patch testing, academic practice, and society membership among Alexander Fisher Award winners (AFAWs). Methods The AFAWs from 1989 to 2012 were identified with Internet searches to obtain their current practice location. Each practice was contacted by phone, and staff was asked whether the AFAW performed patch testing. Current ACDS membership was confirmed by ACDS leadership. Academic status was assessed by university association on practice Web sites. Results Sixty-two awards were presented to 60 individuals from 1989 to 2012. Fifty AFAWs are actively practicing dermatology in the United States (n = 43) and Canada (n = 7). Of 50 practicing AFAWs, 18 (36%) are active patch testers, 29 (58%) do not perform patch testing, and 3 (6%) could not be reached or staff declined to answer. Of the 50, 14 (28%) practice in an academic setting, and 10 (20%) are current ACDS members.

https://ift.tt/2OLlG0l

Complements from the Lung

Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information by sharing relevant background and reasoning with the reader (regular type). The authors' commentary follows. Stage. A 26-year-old man…

https://ift.tt/2DsVEwW

Does Poverty Cause Dental Caries?

Abstract

Dental caries generates significant health, financial and social costs to individuals and communities, but risk factors are not spread randomly and evenly throughout populations. People from lower socioeconomic status (SES) and disadvantaged groups suffer a disproportionately greater disease burden. Clinicians and public health experts view this problem through a different lens. Dentists at the clinical coalface consider individual risk factors and behaviours, for example sugar consumption, cariogenic bacteria and poor oral hygiene, as major causes of dental caries. However, considerable evidence suggests that low SES, via traditional individual risk factors as mediators and through additional independent pathways, is another significant cause. Progressive clinical practice uses education, prevention and treatment to reduce the impact of individual risk factors. Policy makers and health administrators use population‐based approaches to improve the health of societies. The authors use literature review to argue for both a greater awareness of the upstream socioeconomic determinants of dental caries, and action from key community sectors to redress the societal inequalities contributing to dental health inequalities.

This article is protected by copyright. All rights reserved.

https://ift.tt/2Q0Eygd

Real-World Use and Outcomes of Olaparib: a Population-Based Cohort Study

Abstract

Background

Although olaparib, the first poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor approved, has been used in routine clinical practice for over three years, little has been published on its uptake, utilization patterns, and clinical outcomes.

Objective

To examine real-world use and outcomes of olaparib treatment in Swedish patients during the first three years following regulatory approval.

Patients and Methods

This is a population-based cohort study using data from the Swedish national registers. All individuals initiating olaparib treatment from regulatory approval to 31 December 2017 were included. The extent of off-label use was assessed based on recorded diagnoses. Ovarian cancer patients were followed until death or the end of the study period. Starting dose and dose adjustments were assessed. Time to olaparib discontinuation and overall survival were plotted using Kaplan–Meier survival curves.

Results

We identified 109 patients to whom olaparib was dispensed in Sweden during the study period. Nine of these were prescribed olaparib off-label for either breast or prostate cancer and were excluded from further analyses. Median age among the remaining 100 patients with ovarian cancer was 59 years (range: 42–83). Almost all patients (96%) started on the recommended dose (400 mg [eight capsules] taken twice daily). Dose reductions were explicitly recorded for 14% of patients. Median time to discontinuation was 289 days (95% confidence interval [CI]: 226; 338). Median overall survival from olaparib initiation was 1002 days (95% CI: 676; not calculable).

Conclusions

To our knowledge, this is the first population-based study of olaparib real-world use and outcomes. During the first three years following regulatory approval, olaparib was mainly prescribed to ovarian cancer patients. Ovarian cancer patients stayed on olaparib for a median of 9.5 months and the treatment appeared to be well tolerated.

https://ift.tt/2OQ948h

Follow‐up of patients with negative drug provocation tests to betalactams

Abstract

Drug allergy work‐up in betalactam (BL) allergy is probably the most‐developed drug‐allergy evaluation at present [1]. During the last few years, the debate on whether one‐day or several‐day (prolonged) drug provocation test (DPT) should be performed in non‐immediate reactions (i.e., occurring >1h after the last administered dose) in order to increase sensitivity has been ongoing and groups working in drug allergy diagnosis have been deploying pro and con arguments and studies in favour of either option [2‐5]. The most acceptable way to validate a negative DPT is by studying its negative predictive value (NPV) in patients who are re‐challenged to the negatively tested drug, in real‐life therapeutic conditions [6,7].

This article is protected by copyright. All rights reserved.

https://ift.tt/2Q1Tzi5

Th2 cell differentiation from naive CD4+ T cells is enhanced by autocrine CC chemokines in atopic diseases

Abstract

Background

Chemokines are involved not only in regulating leukocyte recruitment, but also in other activities. However, functions other than cell recruitment remain poorly understood. We have already shown that the production of CC chemokine ligand (CCL)17 and CCL22 by antigen‐stimulated naïve CD4⁺ T cells was higher in asthmatic patients than in healthy controls. However, the role of these chemokines in stimulated naïve CD4⁺ T cells remains unclear.

Objective

To clarify the biological function of CCL17 and CCL22 on naïve CD4⁺ T, we examined effects of these two chemokines on naïve CD4⁺ T cells expressing CC chemokine receptor (CCR)4 (a receptor for CCL17 and CCL22) during differentiation of Th2 cells in asthmatic patients as allergic subjects.

Methods

Naïve CD4⁺ T cells were prepared from healthy controls and patients with asthma. We analyzed effect of CCL17 and CCL22, and blocking their receptor on differentiation of Th2 cells.

Results

Production of CCL17 and CCL22 by activated naive CD4⁺ T cells under Th2 condition was much more in asthmatic patients than in healthy controls. Proliferation and survival of the Th2 differentiating cells and restimulation‐induced IL‐4 production were much greater in asthmatic patients than in healthy controls. These cell biological phenomena were inhibited by blockade of CCR4. The biological effects of exogenous CCL17 and CCL22 were apparently observed in both healthy controls and asthmatic patients. The effectiveness of these chemokines on naïve CD4⁺ T cells from healthy controls was stronger than those from asthmatic patients. We found that thymic stromal lymphopoietin (TSLP), a Th2 promoting chemokine, is involved in the activation of CD4⁺ naïve T cells via production of CCL17 and CCL22.

Conclusions & Clinical Relevance

These data suggest that CCL17 and CCL22 produced by TSLP‐primed naïve CD4⁺ T cells in asthma might contribute to an increase in Th2 cells via autocrine loops.

This article is protected by copyright. All rights reserved.

https://ift.tt/2Douyaa

The Quality of Reporting Randomised Controlled Trials in the Dermatology Literature in an Era where the CONSORT Statement is a Standard

Abstract

Background

The quality of reporting randomised controlled trials (RCTs) in the dermatology literature has not received much consideration since the late 2000s.

Objectives

We aimed to assess the quality of recently reported RCTs published in dermatology journals, focusing on randomisation processes, blinding, and trial registration.

Methods

We reviewed 2,042 original articles and identified 141 primary reports of RCTs in four dermatology journals (The Journal of the American Academy of Dermatology, JAMA Dermatology, The Journal of Investigative Dermatology, and The British Journal of Dermatology) from January 2015 to December 2017. Details were extracted from articles, supplements, and public trial registries. A multivariable logistic regression analysis was conducted to identify factors associated with optimal reporting quality.

Results

Among the 141 RCTs, 99 (70·2%), 82 (58·2%), and 69 (48·9%) RCTs described methods used for randomisation, allocation concealment, and implementation, respectively. Most trials (n = 126, 89·4%) reported blinding status; however, one‐third did not state similarity of intervention. Furthermore, 52 (36·9%) RCTs were not registered prospectively. Trials published in The British Journal of Dermatology and using central randomisation were significantly associated with optimal reporting quality after adjusting for covariates.

Conclusions

Several critical items in reporting RCTs, including allocation concealment, similarity of interventions in blinded trials, or prospective trial registration have remained unsatisfactory in the recent dermatology literature.

This article is protected by copyright. All rights reserved.

https://ift.tt/2OHWyYh

Antihelix/helix violaceous macules in Japanese patients with anti‐melanoma differentiation–associated protein 5 (MDA5) antibody–associated dermatomyositis

Abstract

The diagnosis of clinically amyopathic dermatomyositis (CADM) essentially depends on cutaneous manifestations. The early diagnosis of CADM associated with the anti‐melanoma differentiation‐associated protein‐5 (MDA5) antibody is especially important because it includes a subset of patients highly at risk for rapidly progressive interstitial lung disease (RP‐ILD) with potentially fatal outcomes. Moreover, the recognition of distinctive rashes for anti‐MDA5 antibody‐positive DM can greatly aid in distinguishing from other DM subsets since serological anti‐MDA5 antibody testing is not yet widely accessible.

This article is protected by copyright. All rights reserved.

https://ift.tt/2zeU2ns

Heterogeneity of PD‐L1 Expression in a Case of Merkel Cell Carcinoma Exhibiting Complete Regression After Multiple Metastases

Abstract

Merkel cell carcinoma (MCC) is a highly malignant skin cancer with a propensity for local recurrence and regional lymph node metastases. Once recurrence occurs, tumour progression becomes hard to be controlled. Overexpression of programmed death‐ligand 1 (PD‐L1) in MCC correlates with better clinical outcomes, in contrast to other solid carcinomas, e.g., malignant melanoma. The successful results of treatment with the immune checkpoint inhibitor avelumab for metastatic MCC highlight this unusual relationship between MCC and PD‐L1 expression.

This article is protected by copyright. All rights reserved.

https://ift.tt/2OJBd0A

Cross‐sectional associations between cutaneous viral infections and regulatory T lymphocytes in circulation

Summary

Background

Cutaneous viral infections and immune suppression are risk factors for some forms of non‐melanoma skin cancer (NMSC), however, their interrelationship is poorly understood. Objective: To examine cross‐sectional associations between cutaneous viral infections and circulating forkhead‐box P3 (FOXP3) expressing T regulatory (Treg) cells, suppressive cells that dampen effective anti‐tumour immunity.

Methods

Blood, eyebrow hair (EBH) and skin swab samples (SSW) were collected from 352 skin screening patients 60 years and older without prevalent skin cancer participating in an ongoing prospective cohort study of cutaneous viral infections and skin cancer. DNA corresponding to 98 cutaneous human papillomavirus (HPV) types and five polyomaviruses (HPyV) was assessed in EBH and SSW. Distinct classes of circulating Treg cell subpopulations were defined by flow cytometry including cutaneous lymphocyte antigen (CLA) and CCR4^high Treg cells, both previously associated with cutaneous diseases. Age‐ and gender‐adjusted associations between circulating T‐cell populations and infection were estimated using logistic regression.

Results

Total Treg cell proportion in peripheral blood was not associated with beta HPV or HPyV infection. However, the proportion of circulating CLA⁺ Treg cells was inversely associated with gamma HPV EB infection (OR= 0·54, 95% CI=0·35‐0·84). Interestingly, circulating Treg cells expressing markers indicative of antigen activation (CD27^‐CD45RA^‐FOXP3⁺CD4⁺) were also inversely associated with gamma HPV infection in SS (OR=0·55, 95% CI=0·30‐0·99) and EB (OR=0·56, 95% CI=0·36‐0·86).

Conclusions

Inverse associations between circulating Treg cells and gamma HPV infection suggest that localised viral infection may promote immunosuppressive cell migration into skin.

This article is protected by copyright. All rights reserved.

https://ift.tt/2zdFvZ3

The views of consultant dermatologists on creating centralised skin lesion units

Abstract

The proportion of United Kingdom (UK) specialist dermatology clinical activity related to skin lesions has been estimated at between 40–50%. With skin cancer incidence rising, this is likely to increase even further. In 2014, The King's Fund conducted research to investigate the sustainability of dermatology services, with participants identifying the need for service reconfiguration to improve efficiency. One suggestion was to create consultant‐led centralised skin lesion units, receiving all referrals within a region. To the best of our knowledge, there has been no published qualitative research on the organisation of dermatology services, and the views of key stakeholders on service reconfiguration remain unexplored. An independent review following the failed takeover of dermatology services in Nottingham by a private provider concluded that staff must be fully involved in service reconfiguration from the outset.

This article is protected by copyright. All rights reserved.

https://ift.tt/2ONFsbg

Unilesional mycosis fungoides is associated with increased expression of microRNA‐17~92, and Th1 skewing

Summary

Background

The molecular basis of unilesional mycosis fungoides (MF), characterized by a solitary lesion which is clinicopathologically indistinguishable from multifocal patch/plaque MF (early MF), is unknown.

Objectives

To investigate the microRNA (miR) profile in unilesional MF distinguishing it from early MF.

Methods

Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix microRNA array, with further comparison to inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyze the gene expression of T‐helper (Th)1 immune markers and immunohistochemistry was used to evaluate C‐X‐C motif cytokine receptor 3 (CXCR3) and GATA binding protein 3 (GATA3), markers for Th1 and Th2 cells, respectively.

Results

Unilesional MF had a significantly higher level of expression of all members of the miR‐17~92 cluster than early MF. Specifically, compared to early MF, unilesional MF was characterized by a higher miR‐17 level and inflammatory dermatoses, downregulation of the expression of phosphatase and tensin homolog (Pten) and cAMP response element binding protein 1 (CREB1), known targets of miR 17~92 members, higher gene expressions of interluekin‐2 (IL‐2), and interferon gamma (IFN‐ɣ), and statistically lower average percentage of GATA3+ dermal cells (6·7% vs 42·3%, respectively). High immunoreactivity of CXCR3 was noted in both unilesional and early MF.

Conclusions

Unilesional MF exhibits a microRNA profile distinct from conventional early MF, with a higher level of miR‐17~92 members along with a Th1 skewing. These findings suggest a robust reactive T‐cell immune response in unilesional MF and might account for the localized nature of this disease.

This article is protected by copyright. All rights reserved.

https://ift.tt/2zcENLR

The Quality of Reporting Randomised Controlled Trials in the Dermatology Literature in an Era where the CONSORT Statement is a Standard

Abstract

Background

The quality of reporting randomised controlled trials (RCTs) in the dermatology literature has not received much consideration since the late 2000s.

Objectives

We aimed to assess the quality of recently reported RCTs published in dermatology journals, focusing on randomisation processes, blinding, and trial registration.

Methods

We reviewed 2,042 original articles and identified 141 primary reports of RCTs in four dermatology journals (The Journal of the American Academy of Dermatology, JAMA Dermatology, The Journal of Investigative Dermatology, and The British Journal of Dermatology) from January 2015 to December 2017. Details were extracted from articles, supplements, and public trial registries. A multivariable logistic regression analysis was conducted to identify factors associated with optimal reporting quality.

Results

Among the 141 RCTs, 99 (70·2%), 82 (58·2%), and 69 (48·9%) RCTs described methods used for randomisation, allocation concealment, and implementation, respectively. Most trials (n = 126, 89·4%) reported blinding status; however, one‐third did not state similarity of intervention. Furthermore, 52 (36·9%) RCTs were not registered prospectively. Trials published in The British Journal of Dermatology and using central randomisation were significantly associated with optimal reporting quality after adjusting for covariates.

Conclusions

Several critical items in reporting RCTs, including allocation concealment, similarity of interventions in blinded trials, or prospective trial registration have remained unsatisfactory in the recent dermatology literature.

This article is protected by copyright. All rights reserved.

https://ift.tt/2OHWyYh

Antihelix/helix violaceous macules in Japanese patients with anti‐melanoma differentiation–associated protein 5 (MDA5) antibody–associated dermatomyositis

Abstract

The diagnosis of clinically amyopathic dermatomyositis (CADM) essentially depends on cutaneous manifestations. The early diagnosis of CADM associated with the anti‐melanoma differentiation‐associated protein‐5 (MDA5) antibody is especially important because it includes a subset of patients highly at risk for rapidly progressive interstitial lung disease (RP‐ILD) with potentially fatal outcomes. Moreover, the recognition of distinctive rashes for anti‐MDA5 antibody‐positive DM can greatly aid in distinguishing from other DM subsets since serological anti‐MDA5 antibody testing is not yet widely accessible.

This article is protected by copyright. All rights reserved.

https://ift.tt/2zeU2ns

Heterogeneity of PD‐L1 Expression in a Case of Merkel Cell Carcinoma Exhibiting Complete Regression After Multiple Metastases

Abstract

Merkel cell carcinoma (MCC) is a highly malignant skin cancer with a propensity for local recurrence and regional lymph node metastases. Once recurrence occurs, tumour progression becomes hard to be controlled. Overexpression of programmed death‐ligand 1 (PD‐L1) in MCC correlates with better clinical outcomes, in contrast to other solid carcinomas, e.g., malignant melanoma. The successful results of treatment with the immune checkpoint inhibitor avelumab for metastatic MCC highlight this unusual relationship between MCC and PD‐L1 expression.

This article is protected by copyright. All rights reserved.

https://ift.tt/2OJBd0A

Cross‐sectional associations between cutaneous viral infections and regulatory T lymphocytes in circulation

Summary

Background

Cutaneous viral infections and immune suppression are risk factors for some forms of non‐melanoma skin cancer (NMSC), however, their interrelationship is poorly understood. Objective: To examine cross‐sectional associations between cutaneous viral infections and circulating forkhead‐box P3 (FOXP3) expressing T regulatory (Treg) cells, suppressive cells that dampen effective anti‐tumour immunity.

Methods

Blood, eyebrow hair (EBH) and skin swab samples (SSW) were collected from 352 skin screening patients 60 years and older without prevalent skin cancer participating in an ongoing prospective cohort study of cutaneous viral infections and skin cancer. DNA corresponding to 98 cutaneous human papillomavirus (HPV) types and five polyomaviruses (HPyV) was assessed in EBH and SSW. Distinct classes of circulating Treg cell subpopulations were defined by flow cytometry including cutaneous lymphocyte antigen (CLA) and CCR4^high Treg cells, both previously associated with cutaneous diseases. Age‐ and gender‐adjusted associations between circulating T‐cell populations and infection were estimated using logistic regression.

Results

Total Treg cell proportion in peripheral blood was not associated with beta HPV or HPyV infection. However, the proportion of circulating CLA⁺ Treg cells was inversely associated with gamma HPV EB infection (OR= 0·54, 95% CI=0·35‐0·84). Interestingly, circulating Treg cells expressing markers indicative of antigen activation (CD27^‐CD45RA^‐FOXP3⁺CD4⁺) were also inversely associated with gamma HPV infection in SS (OR=0·55, 95% CI=0·30‐0·99) and EB (OR=0·56, 95% CI=0·36‐0·86).

Conclusions

Inverse associations between circulating Treg cells and gamma HPV infection suggest that localised viral infection may promote immunosuppressive cell migration into skin.

This article is protected by copyright. All rights reserved.

https://ift.tt/2zdFvZ3

The views of consultant dermatologists on creating centralised skin lesion units

Abstract

The proportion of United Kingdom (UK) specialist dermatology clinical activity related to skin lesions has been estimated at between 40–50%. With skin cancer incidence rising, this is likely to increase even further. In 2014, The King's Fund conducted research to investigate the sustainability of dermatology services, with participants identifying the need for service reconfiguration to improve efficiency. One suggestion was to create consultant‐led centralised skin lesion units, receiving all referrals within a region. To the best of our knowledge, there has been no published qualitative research on the organisation of dermatology services, and the views of key stakeholders on service reconfiguration remain unexplored. An independent review following the failed takeover of dermatology services in Nottingham by a private provider concluded that staff must be fully involved in service reconfiguration from the outset.

This article is protected by copyright. All rights reserved.

https://ift.tt/2ONFsbg

Unilesional mycosis fungoides is associated with increased expression of microRNA‐17~92, and Th1 skewing

Summary

Background

The molecular basis of unilesional mycosis fungoides (MF), characterized by a solitary lesion which is clinicopathologically indistinguishable from multifocal patch/plaque MF (early MF), is unknown.

Objectives

To investigate the microRNA (miR) profile in unilesional MF distinguishing it from early MF.

Methods

Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix microRNA array, with further comparison to inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyze the gene expression of T‐helper (Th)1 immune markers and immunohistochemistry was used to evaluate C‐X‐C motif cytokine receptor 3 (CXCR3) and GATA binding protein 3 (GATA3), markers for Th1 and Th2 cells, respectively.

Results

Unilesional MF had a significantly higher level of expression of all members of the miR‐17~92 cluster than early MF. Specifically, compared to early MF, unilesional MF was characterized by a higher miR‐17 level and inflammatory dermatoses, downregulation of the expression of phosphatase and tensin homolog (Pten) and cAMP response element binding protein 1 (CREB1), known targets of miR 17~92 members, higher gene expressions of interluekin‐2 (IL‐2), and interferon gamma (IFN‐ɣ), and statistically lower average percentage of GATA3+ dermal cells (6·7% vs 42·3%, respectively). High immunoreactivity of CXCR3 was noted in both unilesional and early MF.

Conclusions

Unilesional MF exhibits a microRNA profile distinct from conventional early MF, with a higher level of miR‐17~92 members along with a Th1 skewing. These findings suggest a robust reactive T‐cell immune response in unilesional MF and might account for the localized nature of this disease.

This article is protected by copyright. All rights reserved.

https://ift.tt/2zcENLR

Complement C3 and C4, but not their regulators or activated products, are associated with incident metabolic syndrome: the CODAM study

Abstract

Purpose

We investigated the associations of components of the alternative (C3, C3a, Bb, factor D [FD], factor H [FH], properdin) and the classical complement pathway (C4, C1q, C1-inhibitor [C1-INH]) with prevalent and incident metabolic syndrome in a cohort with a moderately increased risk of cardiometabolic disease.

Methods

The study cohort was comprised of 574 participants (61% men, age 59.6 ± 7.0 years) at baseline and 489 participants after 7-year follow-up. Multiple logistic regression analyses were done to investigate the associations of concentrations of baseline plasma complement (standardized values) with prevalent and incident (in those without metabolic syndrome at baseline, n = 189) metabolic syndrome.

Results

C3 (odds ratio (OR) = 1.48 [95% confidence interval: 1.02; 2.14]) and C4 (OR = 1.95 [1.32; 2.88]), but none of the other complement components were associated with incident metabolic syndrome (n = 40 cases). Notably, in the cross-sectional analyses, we did observe higher levels of C3a (OR = 1.25 [1.03; 1.52]), FH (OR = 2.93 [2.24; 3.83]), and properdin (OR = 1.88 [1.50; 2.34]), in addition to C3 (OR = 3.60 [2.73; 4.75]) and C4 (OR = 1.39 [1.13; 1.69]), in those with the metabolic syndrome compared to those without, while no association was observed for FD, Bb, C1q, or C1-INH.

Conclusions

In the cross-sectional analyses, the effects sizes (standardized regression coefficients) for C3 and C4 were similar to those of (some of) the regulators and activators, yet only C3 and C4 were associated with incident disease. These findings suggest a role for C3 and C4, but not their regulators or activated products, in the development of the metabolic syndrome.

https://ift.tt/2QNEptZ

Does quality of life differ in patients with Addison’s disease on different glucocorticoid therapies?

https://ift.tt/2PxKTjR

The effects of metformin on simple obesity: a meta-analysis

Abstract

Objective

To evaluate the efficacy of metformin versus a placebo in the treatment of patients with simple obesity without obesity related diseases.

Methods

A search was done on Pub-Med, EMBASE, Cochrane, and Science Citation Index Expanded databases. The main inclusion criteria included the following:(1) randomized controlled trials. (2) patients diagnosed as being overweight or obese. (3) patients were randomly assigned to receive metformin or control. Exclusion criteria included the following: patients diagnosed with an obesity related disease, such as diabetes mellitus (DM) or polycystic ovary syndrome (PCOS).

Results

Compared with the placebo, weighted mean difference (WMD) was 2.33 (95% CI 0.31, 4.35) kg higher with metformin (p = 0.02). Compared with the placebo, WMD was 0.57 (95% CI 0.35, 0.79) kg/m² higher with metformin(p < 0.00001). There was no significant difference in the reduction of waist circumference between the metformin group and the control group (p = 0.05). The fasting blood glucose levels were significantly lower in the metformin group than in the control group (p < 0.00001). However, no hypoglycemia was noted in the metformin group or the control group.

Conclusion

Metformin is effective in reducing body weight of simple obesity patients, and metformin does not induce hypoglycemia as a side effect.

https://ift.tt/2QPhtu7

30mCi radioactive iodine achieving comparative excellent response in intermediate/high-risk nonmetastatic papillary thyroid cancer: a propensity score matching study

Abstract

Objective

To determine the efficacy of low-dose radioactive iodine (RAI) therapy (30 mCi, 1110 MBq) in Chinese patients with intermediate- to high-risk papillary thyroid cancer (PTC) without distant metastasis.

Design and methods

This large retrospective study included Chinese patients with PTC that tested negative for thyroglobulin antibodies. Patients were categorized into low-dose (30 mCi, 1110 MBq) and high-dose (>100 mCi, 3700 MBq) RAI groups. Ablation rate and long-term response were compared between groups using propensity score matching (PSM) to minimize bias and confounding.

Results

In total, we included 446 patients. No significant difference in ablation success rate was found between groups (P = 0.305) before or after PSM (N = 162; P = 0.200). Excellent response (ER) rate was not significant between groups before (P = 0.917) or after PSM (P = 0.798). Efficacy of low-dose RAI was similar to that of high-dose RAI in N0- (P = 1.000), N1a- (P = 0.981), and N1b-stage (P = 0.903) patients. Low- and high-dose RAI groups achieved similar ER rates in pre-ablative stimulated thyroglobulin level (≤1 ng/mL, P = 1.000; 1 < ps-Tg ≤ 5 ng/mL, P = 0.444; 5 < ps-Tg ≤ 10 ng/mL, P = 0.665; >10 ng/mL, P = 1.000) and BRAF^V600E-positive (P = 0.324) subgroups.

Conclusions

Efficacy of low-dose RAI therapy was similar to that of high-dose for ablation and achieving ER in Chinese nonmetastatic intermediate- to high-risk PTC patients. High-dose RAI could not rectify ablation failure or non-ER rates in PTC patients with BRAF^V600E, lymph node metastases, or unfavorable thyroglobulin levels.

https://ift.tt/2PyLmlO

Tumoral MGMT content predicts survival in patients with aggressive pituitary tumors and pituitary carcinomas given treatment with temozolomide

https://ift.tt/2K9SoaS

Assessing the clinical and molecular diagnosis of inherited forms of impaired sensitivity to thyroid hormone from a single tertiary center

Abstract

Aim

Resistance to thyroid hormone (RTH), characterized by persistent hyperthyroxinemia with non-suppressed thyrotropin (TSH), is mostly caused by mutations in thyroid hormone receptor beta gene (THRB). Two differential diagnoses should be considered due to similar clinical and laboratory findings: TSH-producing pituitary adenoma (TPA) and Familial Dysalbuminemic Hyperthyroxinemia (FDH). The aim of this study is to describe our single tertiary center experience in the molecular diagnosis of RTH in Brazilian patients, analyzing their clinical and laboratory characteristics and the most common differential diagnosis.

Subjects and methods

We enrolled 30 subjects with clinical and laboratory features of RTH. Patient´s evaluations included clinical examination, thyroid hormone profile and imaging tests. Sequencing analysis for THRB hot spot region was conducted on all patients, and those without mutations in beta isoform of the thyroid hormone receptor (TRβ) (non-TR-RTH) were investigated for albumin gene (ALB) mutation.

Results

Seventeen patients presented mutations in TRβ (RTHβ); six were non-TR-RTH, three had a diagnosis of FDH with a mutation in ALB, and four were diagnosed with TPA. Two characteristics were different to what is commonly described in the literature: higher serum TSH levels in RTHβ patients when compared to the non-TR-RTH group, but this difference did not extend to free T4 (FT4) level; also the percentage of non-TR-RTH was higher than what was reported in other series.

Conclusion

In the present series, most cases were RTHβ with higher levels of TSH. We described three novel mutations in THRB (p.M313V, p.R320G and p.R438P) and the first patients with FDH molecular diagnosis (p.R242H) documented in Brazil.

https://ift.tt/2BbgoaF

Fabula (non) acta est….Endocrine

https://ift.tt/2K9S9N0

Journées dermatologiques de Paris 2018

Publication date: Available online 16 November 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): E. Delaporte, au nom du Comité de Sélection

https://ift.tt/2PAYLKf

Secretory carcinoma: the eastern Canadian experience and literature review

Abstract

Background

Secretory Carcinoma (SC) is a recently described malignancy affecting salivary glands of the head and neck, with a paucity of evidence regarding the natural history, morbidity, and mortality. This study aimed to investigate the current treatment options utilized for SC, as well as its presentation and outcomes.

Methods

This study is a retrospective case series and includes patients diagnosed with SC at four Maritime Canadian institutions. Literature review of patient outcomes following treatment of SC is also included.

Results

Thirteen patients were identified. Parotid was the most common subsite (69%), followed by minor salivary gland (23%) and submandibular gland (8%). All patients were S100 positive and had at least one additional positive confirmatory stain, including mammaglobin, CK7, or vimentin. Two patients had N2b disease. All patients were treated with primary surgery, and four were offered adjuvant radiotherapy. There was one instance of locoregional recurrence, and one of metastasis. Three patients displayed perineural invasion on pathology, and one patient displayed lymphovascular invasion.

Conclusion

Secretory Carcinoma remains understudied regarding its natural history, presentation, and treatment options. This study is the largest single case series in Canada, and highlights the young age and possible aggressiveness of SC. As well, we provide the most comprehensive literature review to date, with a focus on treatment and outcomes for this disease entity.

https://ift.tt/2Fouiug

Complement C3 and C4, but not their regulators or activated products, are associated with incident metabolic syndrome: the CODAM study

Abstract

Purpose

We investigated the associations of components of the alternative (C3, C3a, Bb, factor D [FD], factor H [FH], properdin) and the classical complement pathway (C4, C1q, C1-inhibitor [C1-INH]) with prevalent and incident metabolic syndrome in a cohort with a moderately increased risk of cardiometabolic disease.

Methods

The study cohort was comprised of 574 participants (61% men, age 59.6 ± 7.0 years) at baseline and 489 participants after 7-year follow-up. Multiple logistic regression analyses were done to investigate the associations of concentrations of baseline plasma complement (standardized values) with prevalent and incident (in those without metabolic syndrome at baseline, n = 189) metabolic syndrome.

Results

C3 (odds ratio (OR) = 1.48 [95% confidence interval: 1.02; 2.14]) and C4 (OR = 1.95 [1.32; 2.88]), but none of the other complement components were associated with incident metabolic syndrome (n = 40 cases). Notably, in the cross-sectional analyses, we did observe higher levels of C3a (OR = 1.25 [1.03; 1.52]), FH (OR = 2.93 [2.24; 3.83]), and properdin (OR = 1.88 [1.50; 2.34]), in addition to C3 (OR = 3.60 [2.73; 4.75]) and C4 (OR = 1.39 [1.13; 1.69]), in those with the metabolic syndrome compared to those without, while no association was observed for FD, Bb, C1q, or C1-INH.

Conclusions

In the cross-sectional analyses, the effects sizes (standardized regression coefficients) for C3 and C4 were similar to those of (some of) the regulators and activators, yet only C3 and C4 were associated with incident disease. These findings suggest a role for C3 and C4, but not their regulators or activated products, in the development of the metabolic syndrome.

https://ift.tt/2QNEptZ

Does quality of life differ in patients with Addison’s disease on different glucocorticoid therapies?

https://ift.tt/2PxKTjR

The effects of metformin on simple obesity: a meta-analysis

Abstract

Objective

To evaluate the efficacy of metformin versus a placebo in the treatment of patients with simple obesity without obesity related diseases.

Methods

A search was done on Pub-Med, EMBASE, Cochrane, and Science Citation Index Expanded databases. The main inclusion criteria included the following:(1) randomized controlled trials. (2) patients diagnosed as being overweight or obese. (3) patients were randomly assigned to receive metformin or control. Exclusion criteria included the following: patients diagnosed with an obesity related disease, such as diabetes mellitus (DM) or polycystic ovary syndrome (PCOS).

Results

Compared with the placebo, weighted mean difference (WMD) was 2.33 (95% CI 0.31, 4.35) kg higher with metformin (p = 0.02). Compared with the placebo, WMD was 0.57 (95% CI 0.35, 0.79) kg/m² higher with metformin(p < 0.00001). There was no significant difference in the reduction of waist circumference between the metformin group and the control group (p = 0.05). The fasting blood glucose levels were significantly lower in the metformin group than in the control group (p < 0.00001). However, no hypoglycemia was noted in the metformin group or the control group.

Conclusion

Metformin is effective in reducing body weight of simple obesity patients, and metformin does not induce hypoglycemia as a side effect.

https://ift.tt/2QPhtu7

30mCi radioactive iodine achieving comparative excellent response in intermediate/high-risk nonmetastatic papillary thyroid cancer: a propensity score matching study

Abstract

Objective

To determine the efficacy of low-dose radioactive iodine (RAI) therapy (30 mCi, 1110 MBq) in Chinese patients with intermediate- to high-risk papillary thyroid cancer (PTC) without distant metastasis.

Design and methods

This large retrospective study included Chinese patients with PTC that tested negative for thyroglobulin antibodies. Patients were categorized into low-dose (30 mCi, 1110 MBq) and high-dose (>100 mCi, 3700 MBq) RAI groups. Ablation rate and long-term response were compared between groups using propensity score matching (PSM) to minimize bias and confounding.

Results

In total, we included 446 patients. No significant difference in ablation success rate was found between groups (P = 0.305) before or after PSM (N = 162; P = 0.200). Excellent response (ER) rate was not significant between groups before (P = 0.917) or after PSM (P = 0.798). Efficacy of low-dose RAI was similar to that of high-dose RAI in N0- (P = 1.000), N1a- (P = 0.981), and N1b-stage (P = 0.903) patients. Low- and high-dose RAI groups achieved similar ER rates in pre-ablative stimulated thyroglobulin level (≤1 ng/mL, P = 1.000; 1 < ps-Tg ≤ 5 ng/mL, P = 0.444; 5 < ps-Tg ≤ 10 ng/mL, P = 0.665; >10 ng/mL, P = 1.000) and BRAF^V600E-positive (P = 0.324) subgroups.

Conclusions

Efficacy of low-dose RAI therapy was similar to that of high-dose for ablation and achieving ER in Chinese nonmetastatic intermediate- to high-risk PTC patients. High-dose RAI could not rectify ablation failure or non-ER rates in PTC patients with BRAF^V600E, lymph node metastases, or unfavorable thyroglobulin levels.

https://ift.tt/2PyLmlO

Tumoral MGMT content predicts survival in patients with aggressive pituitary tumors and pituitary carcinomas given treatment with temozolomide

https://ift.tt/2K9SoaS

Assessing the clinical and molecular diagnosis of inherited forms of impaired sensitivity to thyroid hormone from a single tertiary center

Abstract

Aim

Resistance to thyroid hormone (RTH), characterized by persistent hyperthyroxinemia with non-suppressed thyrotropin (TSH), is mostly caused by mutations in thyroid hormone receptor beta gene (THRB). Two differential diagnoses should be considered due to similar clinical and laboratory findings: TSH-producing pituitary adenoma (TPA) and Familial Dysalbuminemic Hyperthyroxinemia (FDH). The aim of this study is to describe our single tertiary center experience in the molecular diagnosis of RTH in Brazilian patients, analyzing their clinical and laboratory characteristics and the most common differential diagnosis.

Subjects and methods

We enrolled 30 subjects with clinical and laboratory features of RTH. Patient´s evaluations included clinical examination, thyroid hormone profile and imaging tests. Sequencing analysis for THRB hot spot region was conducted on all patients, and those without mutations in beta isoform of the thyroid hormone receptor (TRβ) (non-TR-RTH) were investigated for albumin gene (ALB) mutation.

Results

Seventeen patients presented mutations in TRβ (RTHβ); six were non-TR-RTH, three had a diagnosis of FDH with a mutation in ALB, and four were diagnosed with TPA. Two characteristics were different to what is commonly described in the literature: higher serum TSH levels in RTHβ patients when compared to the non-TR-RTH group, but this difference did not extend to free T4 (FT4) level; also the percentage of non-TR-RTH was higher than what was reported in other series.

Conclusion

In the present series, most cases were RTHβ with higher levels of TSH. We described three novel mutations in THRB (p.M313V, p.R320G and p.R438P) and the first patients with FDH molecular diagnosis (p.R242H) documented in Brazil.

https://ift.tt/2BbgoaF

Fabula (non) acta est….Endocrine

https://ift.tt/2K9S9N0

Three versus five lumbar paravertebral injections for inguinal hernia repair in the elderly: a randomized double-blind clinical trial

Abstract

Purpose

The objective of the study was to compare three nerve stimulator-guided paravertebral injections versus five injections for elderly patients undergoing inguinal hernia repair in terms of the amount of intraoperative fentanyl and propofol consumption and conversion to general anesthesia. The secondary objective was postoperative pain.

Methods

A prospective, randomized, double-blind clinical trial was performed. 200 elderly patients undergoing unilateral herniorrhaphy were randomized into two groups. Group III received three PVB injections from T₁₂ to L₂ and placebo at T₁₁ and L₃. Group V received five PVB injections from T₁₁ to L₃.

Results

The mean intraoperative fentanyl and propofol consumption were significantly lower in group V (4.9 ± 7.2 µg versus 20.0 ± 12.9 µg and 5.7 ± 11.6 mg versus 34.6 ± 22.9 mg, respectively, p value < 0.0001). Five patients (5.0%) in group III had failed block and were converted to general anesthesia (p value = 0.024). Group V had significantly lower pain scores compared to group III during the first three postoperative days (p value < 0.0001).

Conclusion

The five PVB injection technique is more suitable as a sole anesthetic technique for elderly patients undergoing herniorrhaphy, since it required less intraoperative supplemental analgesia and provided lower postoperative pain scores compared to the three PVB injection technique.

Trial registration

Clinicaltrials.gov identifier: NCT02537860.

https://ift.tt/2K9TSSl

Therapeutic targeting potential of chromatin-associated proteins in MLL -rearranged acute leukemia

Abstract

Background

Acute leukemias (AL) with a Mixed Lineage Leukemia (MLL) gene rearrangement (MLLr) represent a group of leukemic entities conferring intermediate to adverse prognoses. Multiple chromatin-associated proteins have been shown to play essential roles during the genesis of MLLr AL. Some chromatin-associated proteins function as negative regulators of MLLr AL whereas others are required for leukemic initiation or maintenance - the latter group constituting potential therapeutic targets. Most of the identified proteins have been functionally analyzed using experimental models with human/murine normal cells transformed by MLL-AF9 or other MLL fusion products, which may recapitulate most but not all aspects of human AML, such as immune system interactions – features of which the importance is rapidly emerging.

Conclusions

Here, we review chromatin-associated proteins fundamental to MLLr AL development, highlighting those with targeting potential by small molecule inhibitors. In particular, we focus on synthetic targeting of multiple chromatin-associated proteins, a strategy that shows superior therapeutic efficacy and offers hope for overcoming drug resistance.

https://ift.tt/2zfgZ9W

Natural history of untreated squamous cell carcinoma of the head and neck

Abstract

The natural history of untreated head and neck squamous cell carcinoma (SCC) was not well defined.

A total of 206 patients with untreated head and neck SCC were retrospectively enrolled.

The 1‐year survival rate for cancers arising in oral cavity, oropharynx, throat, and hypopharynx was 31%, 20%, 0%, and 3%, respectively, the difference was significant (p<0.001).

57.2% of the patients died within 12 months, median survival time was 11 months.

The prognosis of untreated head and neck SCC patients is extremely unfavorable. T stage is the strongest predictors for the survival time.

This article is protected by copyright. All rights reserved.

https://ift.tt/2DpVtCs