Renal cell carcinoma represents 3–5% of adult malignant tumors. Metastases are found in 30–40% of patients and brain metastases occurred in more than 10% of them. Despite significant progress in medical treatm...
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Σάββατο 24 Νοεμβρίου 2018
Activity of cabozantinib in radioresistant brain metastases from renal cell carcinoma: two case reports
ILC2s — resident lymphocytes pre-adapted to a specific tissue or migratory effectors that adapt to where they move?
Ronald N Germain | Yuefeng Huang
https://ift.tt/2ScyAGv
Toxicological and Biochemical Analyses of an Autopsy Case Involving Oral Overdose of Multiple Antidiabetic and Antihypertensive Drugs
Oral antidiabetics can cause fatal hypoglycemia; although they can be chemically identified and quantified, biochemical investigations are important for assessing the biological consequences of an overdose. Such cases of overdose involving oral antidiabetics may involve other drugs for treating lifestyle-related diseases, particularly antihypertensives. Here, we report a toxicological and biochemical investigation of drugs and biochemical profiles in a fatal overdose involving multiple oral antidiabetics and antihypertensives. A 55-year-old woman died about 2 days after the ingestion of around 110 tablets of antidiabetics and antihypertensives that had been prescribed for her husband. A forensic autopsy and histological analysis demonstrated no evident pathology as the cause of death. A toxicological analysis suggested hypoglycemia and an overdose of antihypertensives as well as the retention of antidiabetics and diuretics in the pericardial fluid. A relatively low pericardial amlodipine concentration was observed, which may have been the result of its long half-life (slower distribution and reduction rate) and/or possible affinity with the myocardium. In addition, a biochemical analysis indicated hypoglycemia, without increased serum insulin and C-peptide, but with increased glucagon levels, as the possible influence of glibenclamide overdose. These observations suggest the usefulness of a combination of toxicological and biochemical analyses in postmortem investigations involving a fatal overdose of such drugs.
https://ift.tt/2BvJvpe
Nationwide analysis of unplanned 30‐day readmissions after transsphenoidal pituitary surgery
Background
Transsphenoidal pituitary surgery has evolved into a safe procedure with shorter hospitalizations, yet unplanned readmissions remain a quality measure for which there is a paucity of data. We sought to examine rates, timing, etiologic factors, and costs surrounding readmission after transsphenoidal pituitary surgery.
Methods
The Nationwide Readmissions Database (NRD) was queried for patients who underwent transsphenoidal pituitary between January 2013 and November 2013. Patient, procedure, admission, and hospital‐level characteristics were compared for patients with and without unplanned 30‐day readmission. Multivariate logistic regression was used to identify readmission predictors. A total of 8546 patients were included in this retrospective study.
Results
A total of 8546 patients with a median age of 54 years and female predominance were identified, with 742 patients experiencing at least 1 unplanned readmission within 30 days of index admission. Hypertension, hypothyroidism, diabetes, and obesity were common comorbidities among readmitted patients. Readmission was most frequently because of nervous system complications, followed by neurohypophyseal or electrolyte disorders, cerebrospinal fluid leak, hemorrhage, and meningitis. Median length and cost of stay of index admission was greater in the readmission group (p < 0.001). Fluid and electrolyte disorders as well as neurologic disease (most commonly epilepsy or convulsions) present on initial admission were predictive of length of initial stay and readmission (p < 0.001). Median readmission cost was $7723 and was expected to occur within 7 days.
Conclusion
Approximately 8.7% of patients undergoing transsphenoidal pituitary surgery experience an unplanned readmission within 30 days of discharge. Risk factors identified should be considered to reduce preventable readmissions and identify medically complex patients.
https://ift.tt/2PSC44j
Effect of elderly status on postoperative complications in patients with sinonasal cancer
Background
Elderly patients with multiple comorbidities may be at higher risk of postoperative complications. With an increasingly aging population, more data assessing for predisposing factors are needed in this at‐risk group. In this study, we analyzed the effect of elderly status on relative comorbidities and complications of sinonasal cancer (SNC) patients receiving surgery.
Methods
A retrospective database analysis was performed using cases from the Nationwide Inpatient Sample (NIS) from 2003 to 2012. Patients with a diagnosis of malignant neoplasm of the nasal cavity or paranasal sinuses, who received surgery for sinonasal malignancy, including neck dissections, were selected. Demographics of interest included age, sex, race, type of admission, mean length of stay, and median hospital charges. Elderly and nonelderly patients were compared for differences in rates of acute medical complications, acute surgical complications, and relevant procedures during hospitalization.
Results
Of the 920 cases identified in the NIS, 382 (41.5%) were elderly (≥65 years). Cases of SNC were more frequently seen in males than females (p < 0.001). Elderly patients had significantly higher comorbidity rates compared with nonelderly patients, which included congestive heart failure, hypertension, diabetes, chronic pulmonary disease, and chronic renal failure (p < 0.001 for all). Elderly patients more frequently had postoperative cardiac complications (6.0% vs 0.5%, p < 0.001), but this finding was not statistically significant on multivariate analysis when controlling for race, sex, and comorbidities.
Conclusion
Elderly status is not an independent factor for postoperative complications in patients undergoing surgery for sinonasal malignancy.
https://ift.tt/2RgrPnn
Effect of margin design on fracture load of zirconia crowns
Zirconia‐based restorations are showing an increase as the clinicians' preferred choice at posterior sites because of the strength and esthetic properties of such restorations. However, all‐ceramic restorations fracture at higher rates than do metal‐based restorations. Margin design is one of several factors that can affect the fracture strength of all‐ceramic restorations. The aim of this study was to assess the effect of preparation and crown margin design on fracture resistance. Four groups of bilayer zirconia crowns (with 10 crowns in each group) were produced by hard‐ or soft‐machining technique, with the following four different margin designs: chamfer preparation (control); slice preparation; slice preparation with an additional cervical collar of 0.7 mm thickness; and reduced occlusal thickness (to 0.4 mm) on slice preparation with an additional cervical collar of 0.7 mm thickness. Additionally, 10 hard‐machined crowns with slice preparation were veneered and glazed with feldspathic porcelain. In total, 90 crowns were loaded centrally in the occlusal fossa until fracture. The load at fracture was higher than clinically relevant mastication loads for all preparation and margin designs. The crowns on a chamfer preparation fractured at higher loads compared with crowns on a slice preparation. An additional cervical collar increased load at fracture for hard‐machined crowns.
https://ift.tt/2r2ecfR
Proteomic analysis of dentin–enamel junction and adjacent protein‐containing enamel matrix layer of healthy human molar teeth
The dentin–enamel junction (DEJ) is the border where two different mineralized structures – enamel and dentin – meet. The protein‐rich DEJ, together with the inner enamel region of mature teeth, is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the DEJ and the adjacent enamel organic matrix (EOM). We studied proteomes of the DEJ and EOM of healthy human molars and compared them with dentin and enamel proteomes from the same teeth. These tissues were cut out of tooth sections by laser capture microdissection, proteins were extracted and cleaved by trypsin, then processed by liquid chromatography coupled to tandem mass spectrometry to analyze the proteome profiles of these tissues. This study identified 46 proteins in DEJ and EOM. The proteins identified have a variety of functions, including calcium ion‐binding, formation of extracellular matrix, formation of cytoskeleton, cytoskeletal protein binding, cell adhesion, and transport. Collagens were identified as the most dominant proteins. Tissue‐specific proteins, such as ameloblastin and amelogenin, were also detected. Our findings reveal new insight into proteomics of DEJ and EOM, highly mineralized tissues that are obviously difficult to analyze.
https://ift.tt/2FCIjog
Interaction between interferon regulatory factor 6 and glycine receptor beta shows a protective effect on developing nonsyndromic cleft lip with or without cleft palate in the Han Chinese population
Single‐nucleotide polymorphisms (SNPs) in protein‐coding regions of genes which were previously reported to be associated with nonsyndromic cleft lip, with or without palate involvement (NSCL/P), were investigated. Twelve candidate loci [platelet‐derived growth factor C (PDGFC), platelet‐derived growth factor subunit A (PDGFA), platelet‐derived growth factor receptor alpha (PDGFRA), glycine receptor alpha 2 (GLRA2), glycine receptor beta (GLRB), ATP binding cassette subfamily A member 4 (ABCA4), MAF bZIP transcription factor B (MAFB), interferon regulatory factor 6 (IRF6), CCDC26 long non‐coding RNA (CCDC26), paired box 7 (PAX7), ventral anterior homeobox 1 (VAX1), and netrin 1 (NTN1)] covering 1.5 Mbp were sequenced in 136 NSCL/P patients and 54 healthy controls. Twenty‐five genomic variants identified were further validated in another 400 NSCL/P and 200 controls. Two SNPs in IRF6 showed a protective effect against the development of NSCL/P (rs12405750, OR = 0.54, 95% CI: 0.41–0.69; and rs2235371, OR = 0.55, 95% CI: 0.43–0.71). The missense variant, rs2235371, alters the conserved amino acid valine to isoleucine at codon 274 (V274I). We observed that SNPs at IRF6 (rs2235371 and rs12405750) and GLRB (rs73856838 and rs72685584) show consistent interaction effects. The association between the missense SNP rs2235371 in gene IRF6 and NSCL/P suggests that this SNP may play an important role as a risk factor for NSCL/P in the Han Chinese populations. The marginal signal near 4q31 detected in previous genome‐wide association studies might be caused by an interaction between the IRF6 and GLRB genes. This interaction needs to be further validated by experimentation in follow‐up studies.
https://ift.tt/2r2e8wD
The effects of cryotherapy on vocal fold healing in a rabbit model
Objectives/Hypothesis
Cryotherapy has been shown to be a scarless treatment modality for dermal lesions; however, there are limited data addressing the effect of cryotherapy on vocal fold tissue. The aim of this study was to clarify the effectiveness of cryotherapy for prevention of postsurgical vocal fold scarring.
Study Design
Prospective animal study in rabbits.
Methods
The lamina propria of 20 rabbit vocal folds was bilaterally stripped, followed by randomized unilateral cryotherapy. Five larynges were harvested for real‐time polymerase chain reaction (RT‐PCR) analysis at 1 day, 3 days, and 7 days postinjury. The remaining five were harvested for histologic analysis at 3 months. Images of the healing phase were recorded by laryngoscopy. Analyses of RT‐PCR for cyclooxygenase (COX)‐2, interleukin (IL)‐6, collagen I, collagen III, matrix metallopeptidase 1 (MMP1), transforming growth factor β (TGFβ1), α smooth muscle actin (α‐SMA), and hyaluronan synthase 1 (HAS1) were completed. Histological samples were completed for collagen and hyaluronic acid analysis.
Results
RT‐PCR results revealed that higher expressions of HAS1 and MMP1 and lower expressions of COX‐2, IL‐6, collagen I, collagen III, TGFβ1, and α‐SMA were observed, and histological examination showed significantly increased hyaluronic acid, decreased deposition, and more organized configuration of collagen in injury with the cryotherapy cohort compared with the injury cohort.
Conclusions
Cryotherapy can inhibit the inflammatory reaction and simulate a fetal healing environment in extracellular matrix synthesis to regenerate vocal fold tissue with less fibrosis. Histological results showed that cryotherapy achieves a mature healing result with less scar, which tends to return to normal. In summary, the findings of this study suggest that administration of cryotherapy at the time of injury has the potential to minimize vocal fold scarring.
Level of Evidence
NA Laryngoscope, 2018
https://ift.tt/2R9XWVr
Acute inflammatory response to contrast agent aspiration and its mechanisms in the rat lung
Objectives/Hypothesis
Contrast agent (CA) aspiration is an established complication of upper gastrointestinal and videofluoroscopic swallow studies. The underlying molecular biological mechanisms of acute response to CA aspiration in the respiratory organs remain unclear. The aims of this study were to elucidate the histological and biological influences of three kinds of CAs on the lung and to clarify the differences in acute responses.
Study Design
Animal model.
Methods
Eight‐week‐old male Sprague Dawley rats were divided into five groups (n = 6 in each group). Three groups underwent tracheal instillation of one of three different CAs: barium (Ba) sulfate, nonionic contrast agents (NICAs), and ionic contrast agents (ICAs). A control group was instilled with saline and a sham group was instilled with air. All animals were euthanized on day 2 after treatment and histological and gene analysis was performed.
Results
No animal died after CA or control/sham aspiration. Ba caused severe histopathologic changes and more prominent inflammatory cell infiltration in the lungs compared with the two other iodinated contrast agents. Increases in expressions of inflammatory cytokines (tumor necrosis factor [Tnf], interleukin‐1β [Il1b], and interferon‐γ [Ifng]) were observed in Ba aspiration rats, and upregulation of Il1b was seen in ICA aspiration rats. NICA did not cause obvious histologic changes or expressions of inflammatory cytokines and fibrosis‐related genes in the lungs.
Conclusions
Ba caused significantly more acute lung inflammation in a rodent model than did ioinic and nonionic iodinated CAs. Nonionic contrast did not cause any discernible inflammatory response in the lungs, suggesting that it may be the safest contrast for videofluoroscopic swallow studies.
Level of Evidence
NA
https://ift.tt/2PRTY7y
Physician impact on the patient and family experience in a pediatric otolaryngology practice
Objective
On the Press Ganey (PG) survey, the item "likelihood of recommending practice" is a proxy for patient satisfaction because only the most satisfied patients will recommend a practice to friends and family. The objective of this study is to determine which other items on the PG survey best correlate with "likelihood of recommending practice" as a measure of patient satisfaction in pediatric otolaryngology.
Study Design
Retrospective analysis of a survey database.
Methods
The PG survey, consisting of 24 questions scaled from 1 to 5 representing (1) very poor, (2) poor, (3) fair, (4) good, and (5) very good, was sent to 28 different pediatric otolaryngology practices. Using the Pearson correlation coefficient, the statistical relationship of each PG survey question was analyzed in its association to the PG question "likelihood of recommending practice." Factors with a correlation coefficient greater than 0.65 were considered significant.
Results
Ten of 24 questions on the PG survey correlated with a top "likelihood of recommending practice" score. Eight of these 10 items were from the Care Provider category and were related to the physician–patient/family interaction.
Conclusion
Patient satisfaction surveys are utilized as a quality metric of the patient and family experience. These scores serve as one of several measures that affect reimbursement. The results demonstrate that most of the factors correlated with "likelihood of recommending practice" are provider‐based. In conclusion, the physician–patient interaction strongly influences the potential for a practice to earn top box scores on the PG item "likelihood of recommending practice" and thereby achieve the highest patient satisfaction.
Level of Evidence
NA. Laryngoscope, 2018
https://ift.tt/2Rbeeh3
Validation of a septoplasty deformity grading system for the evaluation of nasal obstruction
Objectives/Hypothesis
We developed and validated a septal deformity grading (SDG) system that accounts for anatomic location and grading of deformity severity.
Study Design
Retrospective cohort study.
Methods
Subjects were patients with nasal obstruction presenting to University of California, Irvine Medical Center. Subjects were given pre‐ and postoperative Nasal Obstruction Symptom Evaluation (NOSE) questionnaires and were evaluated by a facial plastic surgeon using our septal deformity grading (SDG) system. Validity and reliability analyses were conducted on the SDG results. Statistical analyses were conducted on SDG and NOSE data to assess and compare instruments, and to validate the SDG instrument using the NOSE instrument.
Results
One hundred thirty‐five patients met inclusion criteria. Cronbach's α was ≥ 0.7 for SDG and pre‐ and postoperative NOSE scores. There was a significant difference in pre‐ and postoperative NOSE scores (Z score = −7.21, P < .001). Correlations between postoperative NOSE and SDG scores were significant (P = .014), and convergent construct validity was achieved. There was a significant difference in SDG scores between primary versus revision operations (P < .001), history versus no history of nasal trauma, and nasal/septal surgery (P = .025, P = .003, respectively). The odds of having a revision operation were 2.3 times higher for high SDG scores (P < .001), of having a history of nasal trauma were 1.33 times higher for high SDG scores (P = .014), and of having a history of nasal/septal surgery were 2.9 times higher for low SDG scores.
Conclusions
Our SDG system addresses the challenge of providing objective anatomic information on the severity of nasal septal deformities, and may be valuable when used in conjunction with subjective data gathered from the NOSE questionnaire.
Level of Evidence
4 Laryngoscope, 2018
https://ift.tt/2RbTQvY
Medialization laryngoplasty/arytenoid adduction: U.S. outcomes, discharge status, and utilization trends
Objectives/Hypothesis
To evaluate trends, outcomes, and healthcare utilization following medialization laryngoplasty (ML) with or without arytenoid adduction (AA) over 10 years.
Study Design
Retrospective observational study.
Methods
Using OptumLabs Data Warehouse, trends, outcomes, and healthcare utilization from 2006 to 2015 were examined with a focus on discharge type (same day or not). Predictors of postoperative emergency department (ED) use and hospitalization were determined by multivariable logistic regression.
Results
Overall rate of ML was 1.09 per 100 thousand enrollees per year. Of these, 7.8% ML were combined with an AA. Outpatient same‐day discharge represented 62.0% (1,142 of 1,843) of total patients, steadily increasing over the 10‐year period (P < 0.01). There was a 5.9% revision ML rate and 1.0% rate of tracheotomy within 1 day of ML. A total of 5.6% visited an ED, and 5.4% were admitted to a hospital following initial discharge within 30 days. Same‐day discharge was found to be a predictor of hospitalization within 30 days after ML (odds ratio [OR] 1.74, P = 0.0452), along with Elixhauser comorbidity index of 4 + (OR 5.74, P = 0.0001). Pulmonary embolism, pulmonary hypertension, and weight loss were top predictors of ED visit or hospitalization.
Conclusion
To our knowledge, this is the first search evaluating national claims data for ML with or without AA. Overall rate of ML is low, and same‐day discharge has become more common over a 10‐year period, with an associated higher 30‐day hospital admission risk. Correct patient selection criteria for disposition status cannot be fully determined based on current data, but a high Elixhauser comorbidity index clearly carries increased risk for hospitalization after initial discharge.
Level of Evidence
4. Laryngoscope, 2018
https://ift.tt/2PPqN4W
Analysis of patient factors associated with 30‐day mortality after tracheostomy
Objective
Mortality has been reported to be 22% to 45% in patients with a tracheostomy. To better counsel patients and families, we aimed to determine the effect of body mass index (BMI), socioeconomic status (SES), and the 17 conditions of the Charlson comorbidity index (CCI) on 30‐day survival posttracheostomy.
Methods
This retrospective cohort study identified adult patients enrolled from our institution in the Global Tracheostomy Collaborative database from March 2014 to June 2015. Data collected included age, BMI, residential zip code, and comorbidities. Cox proportionate univariate and multivariate analyses were used to measure the impact of BMI, SES, and CCI variables with 30‐day posttracheostomy survival. We used geocoding as a surrogate for patients' SES. We used Deyo's modification of the CCI, which utilized International Classification of Diseases, 9th Revision, codes to identify comorbidities.
Results
Of 326 tracheostomies identified, the 30‐day mortality rate was 15.6%. No significant differences were noted in BMI or in any of the SES categories between survivors and nonsurvivors. CCI was significantly higher in the 30‐day mortality group. Congestive heart failure (hazard ratio [HR] = 2.39), severe liver disease (HR = 3.15), and peripheral vascular disease (HR = 2.62) were found to significantly impact 30‐day survival.
Conclusion
Higher CCI and specifically severe liver disease, congestive heart failure, and peripheral vascular disease were associated with increased 30‐day mortality posttracheostomy. No association was found between BMI or SES and 30‐day survival. This study identified three comorbidities that independently affect mortality in tracheostomy patients, which should be discussed with patients and families before tracheostomy.
Level of Evidence
3. Laryngoscope, 2018
https://ift.tt/2RahFEE
Second primary lung malignancy following head and neck squamous cell carcinoma
Objectives/Hypothesis
Analyze the characteristics of second primary lung malignancies (SPLMs) following an index head and neck squamous cell carcinoma (HNSCC).
Study Design
Retrospective cohort study.
Methods
The Surveillance, Epidemiology and End Results database was queried for all cases of HNSCC between 1973 and 2014 (N = 101,856). This population was compared to a standard population to assess relative risk for lung cancer, calculated as the standardized incidence ratio (SIR). Patients who developed SPLMs were extracted (N = 8,116) and compared to all other cases of lung cancer (N = 1,160,853) to assess histopathological differences. SPLM subpopulations divided by head and neck primary site were compared for lung cancer histology and time interval between cancer diagnoses.
Results
Overall, 8.0% of HNSCC patients developed SPLMs (SIR = 4.22, P < .001), diagnosed an average of 6.7 years later. Patients with HNSCC of the supraglottis and hypopharynx were at the highest risk relative to a standard population, with SIRs of 8.10 and 6.34, respectively. When comparing SPLMs to all other lung cancers, there was no difference in the distribution of lung lobe affected, but SPLMs were significantly more likely to be of squamous cell carcinoma histology (42.0% vs. 21.0%, P < .001). Among head and neck subsites, lung cancers following larynx tumors had a significantly higher proportion of small cell histology, and those following oropharyngeal or hypopharyngeal tumors had significantly higher proportions of squamous cell histology.
Conclusions
Patients who undergo curative treatment of HNSCC are at high risk for developing SPLMs. Subsite‐specific differences may help elucidate the degree of risk attributable to smoking, genetic susceptibility, human papillomavirus infection, or metastasis masquerading as an SPLM.
Level of Evidence
4 Laryngoscope, 2018
https://ift.tt/2PTAkaY
Levator claviculae muscle: Anatomic variation found during neck dissection
The levator claviculae muscle is a variant of the anatomy of the posterior triangle of the neck. It is reported in 2% to 3% of all humans. All previous articles described this muscle as an incidental finding during cadaveric or radiological examinations. We report here, for the first time, a case discovering this muscle variation intraoperatively during a modified radical neck dissection. The muscle was identified on the left side, originating from the transverse processes of the upper cervical vertebrae (C2‐C3), attached to the upper aspect of the middle part of the clavicle. This muscle was innervated by the supraclavicular nerve, coming from the third and fourth rami of the cervical spinal nerves. Blood supply to the muscle could not be identified clearly during the surgical procedure. Surgeons and radiologists should be aware of the presence of this rare variant muscle so as not to misinterpret the anatomy. Laryngoscope, 2018
https://ift.tt/2RbTCVE
Feasibility of shotgun metagenomics to assess microbial ecology of pediatric tracheostomy tubes
Objective
Biofilm formation on medical devices such as tracheostomy tubes (TTs) is a serious problem. The clinical impact of biofilms on the airway is still unclear. Biofilms may play a role in granulation tissue development, recurrent airway infections, and failure of laryngotracheal reconstructions. The microbial ecology on TTs has yet to be elucidated. The purpose of this study was to determine the feasibility of shotgun metagenomics to assess the biodistribution of microorganisms on TTs.
Methods
Four TTs were collected from pediatric patients (1.4–10.2 years) with (n = 2) and without (n = 2) granulation tissue formation. Duration of TT placement prior to retrieval from patients ranged from 5 to 365 days. DNA extraction was performed using the MO BIO UltraClean Microbial Isolation (Mo Bio Laboratories, Carlsbad, CA). Library generation using Nextera XT adapters (Illumina Inc., San Diego, CA) and metagenomic shotgun sequencing was performed using the Illumina NextSeq500 (Illumina Inc, San Diego, CA). Salinibacter ruber, a species not found in mammalian microbiome communities, was used as a DNA standard and represented 0.7% to 5.7% of the microbiome, ensuring good quality and abundance of sample DNA.
Results
Metagenomic shotgun sequencing was successful for all patients. In TTs associated with granuloma, Fusobacterium nucleatum, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae were predominant, most of which are considered pathogens. From TTs without granulomas, Neisseria mucosa, Neisseria sicca, Acinetobacter baumannii, and Haemophilus parainfluenzae were identified, primarily consistent with respiratory microbiome.
Conclusion
This study reveals that metagenomic shotgun sequencing of biofilms formed on pediatric TTs is feasible with an apparent difference in microbiome for patients with granulation tissue. Further studies are necessary to elucidate the pathogenesis of microbial ecology and its role in airway disease in patients with TTs.
Level of Evidence
2c. Laryngoscope, 2018
https://ift.tt/2PT55Nt
The Impact of a Stepwise Approach to Primary Tumor Detection in Squamous Cell Carcinoma of the Neck With Unknown Primary
Objectives/Hypothesis
To examine the cumulative effect of diagnostic steps for primary tumor identification in patients with head and neck squamous cell carcinoma of unknown primary (HNSCCUP), including lingual tonsillectomy, and the impact of primary tumor identification on subsequent treatment.
Study Design
Retrospective analysis.
Methods
We reviewed the records of 110 patients diagnosed with HNSCCUP between 2003 and 2015. Results of diagnostic imaging (fluorodeoxyglucose‐positron emission tomography/computed tomography [FDG‐PET/CT]), tumor detection with direct laryngoscopy with biopsies, palatine tonsillectomy, and transoral robotic surgery (TORS) lingual tonsillectomy were recorded. Associations between demographic and treatment variables with overall survival (OS) and progression‐free survival (PFS) were modeled with Cox proportional hazards models.
Results
FDG‐PET/CT was suspicious for a primary site in 23/77 (30%) patients. Direct laryngoscopy identified a primary tumor in 34/110 patients (31%). Forty‐seven patients underwent palatine tonsillectomy, which identified 17 primaries (36%), yielding a cumulative primary tumor identification of 51/110 (46%). Fourteen patients underwent TORS lingual tonsillectomy, which identified eight primaries (57%), resulting in a cumulative identification of 59/110 (53%). The detection rate increased from 28/63 (44%) to 31/47 (66%) after the addition of TORS lingual tonsillectomy to our institutional approach. Detection rates varied by HPV status. Primary tumor identification altered subsequent radiation planning, as patients with an identified primary tumor received radiation to a smaller volume of tissue than did those without an identified primary tumor. However, there was no significant association between primary tumor identification and OS or PFS.
Conclusions
A stepwise approach to primary tumor identification identifies a primary tumor in a majority of patients.
Level of Evidence
4 Laryngoscope, 2018
https://ift.tt/2RcmAVx
Olfactory function in mild cognitive impairment and Alzheimer's disease: A meta‐analysis
Objective
Olfactory function is altered in mild cognitive impairment (MCI) and Alzheimer's disease (AD); therefore, it may serve as a useful tool for the early detection of MCI before its advancement to AD. The aim of this meta‐analysis was to investigate olfactory deficits in patients with MCI and AD.
Study Design
Literature search.
Methods
A search was conducted of the electronic databases PubMed, Embase, and Web of Science from their inception until 2017. We included original articles with adequate data on the identification, threshold, and/or discrimination of olfactory function in MCI or AD. The standard mean difference and 95% confidence interval (CI) were calculated. The studies were weighted according to inverse variance estimates. The effect sizes were categorized as small [Cohen's d = 0.2], medium (d = 0.5), or large (d ≥ 0.8) based on these methods. Subgroup analyses were performed based on mean age and sex differences between the groups.
Results
Twelve articles (reporting 21 effects) examining 563 patients with MCI and 788 patients with AD, were included in the meta‐analysis. Compared to MCI, AD had moderate to large heterogeneous effects on olfactory function (Cohen's d = 0.64, 95% CI: 0.50, 0.78). Olfactory identification tests demonstrated larger effects (d = 0.71, 95% CI: 0.51, 0.91) than did tests of other olfactory domains.
Conclusions
Meta‐analysis results revealed that olfactory identification was more profoundly impaired in patients with AD than in those with MCI. These findings suggest that a simple test of odor identification is valuable in differentiating individuals at a risk of AD.
Level of Evidence
NA Laryngoscope, 2018
https://ift.tt/2PRrvOV
Over–under versus medial tympanoplasty: Comparison of benefit, success, and hearing results
Objectives/Hypothesis
A hybrid variation of a tympanoplasty technique, termed over–under tympanoplasty (OUT), was evaluated to demonstrate the long‐term outcomes and complications compared to medial tympanoplasty.
Study Design
Retrospective review.
Methods
Patients who underwent a tympanoplasty between 2010 and 2015 were included. Primary outcome measures included graft healing at 18 months, change in air‐bone gap (ABG), and change in high‐frequency hearing at 8 kHz. The Shapiro‐Wilk test, Student t test, and nonparametric Mann‐Whitney test were used to compare results. Univariate logistic regression analysis was used to identify potential predictors of surgical success.
Results
One hundred eleven patients were included; 84 underwent the over–under technique and 27 underwent medial tympanoplasty. At the 18‐month follow‐up, 100% of patients in the medial tympanoplasty group had closure of the TM perforation compared to 84% (71/84) in the over–under group. In the over–under group, 12% of patients developed small or pinpoint perforations, and 4% developed larger, recurrent perforations. Mean improvement in ABG was similar between the two groups (11.6 dB for the medial group vs. 11.9 dB for the over–under group, P < .001). No hearing loss was noted in either group. No lateralization of the graft or anterior blunting was noted.
Conclusions
In this series, the OUT technique had a high success rate with TM perforations, including anterior, near total, and total perforations. Hearing loss from dissection on the malleus was not found. This approach blends the advantages and minimizes the disadvantages of the classic techniques and is well suited for all types of tympanic membrane perforations.
Level of Evidence
3b Laryngoscope, 2018
https://ift.tt/2RbTuFE
Novel approach using transoral robotic surgery for resection of cervical spine chordoma
Chordomas are rare, infiltrative neoplasms of notochordal origin that present along the spinal canal; en bloc surgical resection is paramount to successful treatment. Limited visualization and complex anatomy are major challenges to resection of upper cervical spine chordomas and often require invasive surgery. A 27‐year‐old male presented with an incidentally discovered chordoma of the midline second cervical vertebra of the spine. To obtain en bloc resection of the lesion while both overcoming limitations due to access and without introducing morbidity from traditional anterior approaches, we elected using transoral robotic surgery for resection. Due to complete resection, the patient remains disease‐free and was spared adjuvant radiation. Laryngoscope, 2018
https://ift.tt/2PQzcFp
Airway anomalies in patients with craniosynostosis
Objectives
1) Characterize the spectrum of airway anomalies in patients with craniosynostosis, and 2) identify clinical characteristics of these patients that may be associated with the development of airway anomalies.
Methods
This study is a retrospective case series assessing the type and frequency of airway anomalies in all patients with craniosynostosis seen at a tertiary‐care children's hospital between 2000 and 2016. Cohort analyses were then performed to identify differences in airway anomalies dependent on syndromic associations, multisutural fusion, and location of suture fusion. Clinical characteristics examined included demographics and additional neurologic and craniofacial abnormalities.
Results
Four hundred and ninety‐six patients with craniosynostosis (83.5% white, 64.5% male; 33.9% sagittal, 28.8% metopic, 11.5% coronal, 1.2% lambdoid, and 24.6% multisutural) were included. Notable airway anomalies included the following: 13.3% adenotonsillar hypertrophy, 8.9% laryngomalacia, 7.3% tracheomalacia, 7.1% subglottic stenosis, 4.0% bronchomalacia, 3.8% laryngeal cleft, and 1.2% vocal fold paresis. Multisutural craniosynostosis patients (n = 122) were more likely to have obstructive sleep apnea (P = 0.005), adenotonsillar hypertrophy (P = 0.014), tracheomalacia (P = 0.011), subglottic stenosis (P < 0.001), and epiglottic/base of tongue collapse (P = 0.003) and require tracheostomy (P = 0.001) and mechanical ventilation (P = 0.017) compared with single suture craniosynostosis. Syndromic craniosynostosis patients (n = 33) were more likely to have obstructive sleep apnea (P < 0.001), laryngomalacia (P = 0.047), and subglottic stenosis (P = 0.009) compared with nonsyndromic patients.
Conclusion
Airway anomalies are prevalent in patients with craniosynostosis; patients with multisutural or syndromic types have an increased risk of developing certain abnormalities. There should be a lower threshold for referral for airway evaluation in these populations.
Level of Evidence
4. Laryngoscope, 2018
https://ift.tt/2Ri1Aws
Progression of hearing loss in neurofibromatosis type 2 according to genetic severity
Objectives/Hypothesis
This study set out to describe the progression of hearing loss in patients with neurofibromatosis type 2 (NF2), treated in a quaternary multidisciplinary clinic. It also aimed to compare hearing loss across patients grouped according to a known genetic severity score to explore its utility for prognostication.
Study Design
Retrospective cohort study.
Methods
We conducted a study of 147 patients with confirmed NF2 diagnosis for a mean observational period of 10 years. Pure‐tone average (PTA), optimum discriminations scores (ODS), and genotype data were collected. Patients were classified according to hearing class (American Academy of Otolaryngology), their candidacy for auditory implantation (UK National NF2 consensus) and grouped by genetic severity as: 1 = tissue mosaic, 2A = mild classic, 2B = moderate classic, and 3 = severe. Survival analysis investigated the effect of genetic severity on the age of loss of serviceable hearing.
Results
Genetic severity was a significant predictor of hearing outcomes such as ODS, hearing classification, and maximum annual PTA deterioration. Although the overall median age of loss of serviceable hearing was 78 years, there was significant variation according to the genetic severity; the median for severe patients was 32 years compared to a median of 80 for tissue mosaic patients.
Conclusions
This is the first description of long‐term hearing outcomes in a clinical setting across a large heterogeneous cohort of patients with NF2. The results highlight the potential importance and benefit of considering the genetic severity score of patients when undertaking treatment decisions, as well as planning future natural history studies.
Level of Evidence
2c Laryngoscope, 2018
https://ift.tt/2PT54ZV
Using word clouds to Re‐envision letters of recommendation for residency applicants
Objectives/Hypothesis
To develop a "word cloud"–based visual letter of recommendation (VLOR) and to evaluate its efficiency in discerning applicant quality compared to narrative letters of recommendation (NLORs).
Study Design
Cross‐sectional cohort study.
Methods
NLORs for 48 otolaryngology residency applicants interviewed from the 2016 application cycle were identified and mined for descriptive terms to generate a word cloud, referred to as a VLOR. Eight individuals reviewed and rated a total of 187 blinded NLORs and 48 VLORs on a four‐point scale (negative to exceptional). Median VLOR and NLOR scores and the time to review for each candidate were compared using the Wilcoxon signed rank test.
Results
It took significantly more time to review the NLORs in comparison to the VLORs (67 seconds, interquartile range [IQR]: 41–98 seconds vs. 17 seconds, IQR: 11–26 seconds, P < .001). There was no significant difference between median scores for VLORs and NLORs (P = .136). Review time and score correlated positively for VLORs and was statistically significant (ρ = 0.459, P = .001), indicating that more time spent reviewing equates to higher scores. The same relationship appeared with NLORs, but was not statistically significant (ρ = 0.276, P = .058).
Conclusions
VLORs are a novel and efficient additive tool for screening candidates for otolaryngology residency interview slots. Their scores do not significantly vary from NLOR scores and are significantly faster to evaluate.
Level of Evidence
2b Laryngoscope, 2018
https://ift.tt/2R6Ac4t
Student and foundation doctor perspectives on promoting entry to ENT specialist training
Abstract
In recent years, there has been a decline in the number of applications per ST3 post for ENT. The majority of medical students and foundation doctors have a limited exposure to ENT during undergraduate medical training. This is a common issue in smaller surgical specialties, and is acknowledged as one factor deterring students from surgical careers.
This article is protected by copyright. All rights reserved.
https://ift.tt/2DJ9WcU
Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma development and growth in vivo
Abstract
Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for Braf V600E ‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (Tyr Cre ERT 2/+ ; Braf LSL ‐V600E/+ ; Pten flox/flox ) to Sirt5 ‐/‐ knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5 ‐/‐ mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for Braf V600E ‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.
This article is protected by copyright. All rights reserved.
https://ift.tt/2PX7mr6
c‐Rel is a cell cycle modulator in human melanoma cells
Abstract
Melanoma progression and resistance to therapy is associated with faulty regulation of signaling molecules including the central transcription factor NF‐κB. Increased expression of the c‐Rel subunit of NF‐κB has been described in progressing melanoma, though mechanistic implications of this up‐regulation remain unclear. To elucidate the functional role of c‐Rel in melanoma biology, we have assessed its expression in human melanoma as well as in melanoma cell lines. Suppression of c‐Rel expression in four melanoma cell lines resulted in reduced growth and altered cell cycle regulation, namely G2/M and polyploid phase induction. Moreover, mitotic spindle morphology was profoundly altered in three of the cell lines with a predominance of monopolar structures. These findings suggest that c‐Rel is involved in G2/M phase regulation, prevention of polyploidy and, consequently, in chromosomal stability. Our results highlight a novel tumor‐promoting function of c‐Rel in human melanoma cells through governing cell cycle regulation.
This article is protected by copyright. All rights reserved.
https://ift.tt/2R7TDtO
What's new in the treatment of atopic dermatitis?
Atopic dermatitis (AD) is a pruritic, chronic and inflammatory skin disease, with an usual onset in the pediatric age. Several drugs are used in the treatment of this skin disease. Drugs as steroid, calcineurin inhibitors, and moisturizing creams are widely used in the treatment of this disease but often patients are not satisfied with the obtained results. New drugs like dupilumab or crisaborole seems to be a promising option for moderate and severe forms of AD. This paper analyzes the newest therapy available today for the treatment of AD.
This article is protected by copyright. All rights reserved.
https://ift.tt/2r3486n
Review of Future Insights of Dragon's Blood in Dermatology
Objective
To assess the possible clinical implication of Dragon's Blood in dermatology.
Design
A pubmed search was conducted using the keyword "Dragon's Blood", "Croton lechleri", and more.
Results
Dragon's Blood from Croton lechleri is an Amazonian medicinal plant with a characteristic red sap. Its array of phytochemical action in preclinical studies include anti‐inflammatory, anti‐oxidant, antimicrobial, antifungal, and antineoplastic properties. Clinical studies reflect wound healing and antiviral properties.
Conclusion
Although its popularity is rising in western medicine, C. lechleri offers limited use in dermatology and further investigation is necessary to gain further insight into its potential clinical implication.
This article is protected by copyright. All rights reserved.
https://ift.tt/2FCPHzS
Salutogenesis and beyond
In this hypothesis paper on paradoxes in preventive medicine, which also deals with the indocility of biological functions, the following issues will be addressed. First, a definition of salutogenesis will be given, providing the origin of this notion of health preservation and disease prevention. Then four paradoxes of the biology of health will be discussed. The first deals with the biomarkers of aging. The second addresses the good and bad of the much praised anti‐oxidants. The third details how the mTOR (mammalian transporter of rapamycin) pathway plays a discreet but fundamental role. The fourth explores the yin and yang effects of the secretory profile of senescent cells. In conclusion, the need for a new paradigm in preventive medicine will be proposed.
This article is protected by copyright. All rights reserved.
https://ift.tt/2FEPTin
Frontal pattern hair loss among Chinese women is frequently associated with ponytail hairstyle
Female alopecia patients in China often present with a frontal pattern hair loss. This feature is seen less frequently in western women. Women in China frequently style their hair in a ponytail. Thus, we hypothesized that the high prevalence of frontal pattern hair loss in Chinese women is due to traction alopecia. To better understand this, we studied forty‐three women presenting frontal alopecia at a hospital hair clinic. Among the women presenting frontal alopecia, 79% reported styling their hair in a ponytail four or more days per week for an average period of 10 years. To our knowledge, this is the first study to elucidate the cause of frequent frontal alopecia in Chinese women. While cultural style changes are difficult to change, we believe that awareness of the medical implications of frequent ponytail styling will reduce the rate of frontal alopecia among Chinese women.
This article is protected by copyright. All rights reserved.
https://ift.tt/2r4OAz2
Response of localized, resistant, tingling vitiligo to pregabalin: A case report
Abstract
Vitiligo is a common depigmenting disease with complex pathogenesis. One of the proposed pathogenesis is the neural hypothesis, which suggests an altered reaction to neuropeptides, catecholamines, and their metabolites affecting melanocytes. Here, we report a case of 26‐year‐old female patient, whose vitiligo patches were associated with unusual crawling and tingling sensation and responded to a clinical trial of pregabalin.
https://ift.tt/2r1uANw
Overview of high‐risk Food and Drug Administration recalls for cosmetics and personal care products from 2002 to 2016
Summary
Background
There have been several recent controversies surrounding cosmetic products that have impacted health. Dermatologists are often the first to encounter these issues, and recalls are one metric of a safety profile of cosmetics and their impact on health.
Objective
To analyze all recalls of cosmetic and personal care products from 2002 to 2016.
Methods
This observational study describes all FDA cosmetic and personal care product recalls, acquired via a Freedom of Information Act request, from 2002 to 2016. The total number of Class I, Class II, and Class III recalls, number and origin of manufacturers, number of products affected, and main reason for recall were collected.
Results
A total of 14 Class I, 266 Class II, and 33 Class III recalls were recorded. Baby products comprised the largest product category accounting for 24% of all recalls (76/313). 76% of recalls were due to bacterial contamination (237/313), followed by unapproved components, labeling issues, and skin irritation. The 14 Class I recalls accounted for 1.9 million products in distribution.
Conclusions
Cosmetic recalls impacted millions of products and had the potential to cause serious harm. Dermatologists have the ability to strengthen public safety by reporting adverse events, encouraging recalls of harmful products, and lobbying through dermatology organizations for meaningful change to current cosmetic regulation.
https://ift.tt/2PR7R5H
An open‐label, single‐site study to evaluate the tolerability, safety, and efficacy of using a novel facial moisturizer for preparation and accelerated healing pre and post a single full‐face radiofrequency microneedling treatment
Summary
Background
Skincare cosmeceutical products have been shown to address intrinsic and extrinsic skin aging. Radiofrequency (RF) with microneedling is effective and safe in improving skin laxity and texture. Pairing skincare cosmeceutical products pre‐ and post‐procedure is beneficial as it enhances patient results, patient results, patient experience, and reduces patient downtime.
Objective
To evaluate the tolerability, safety, and efficacy of a multi‐ingredient anti‐aging facial moisturizer when applied pre‐ and post‐procedure consisting of a single RF microneedling treatment.
Method
Fifteen female patients, aged 37‐60, Fitzpatrick skin types I‐IV, with mild‐to‐moderate wrinkles were included in the study. Patients applied a multi‐ingredient anti‐aging facial moisturizer twice a day (morning and night) two weeks prior to RF microneedling and four weeks post‐RF microneedling (twice a day). At each time point, investigator objective assessment, self‐assessments, and clinical photography were taken.
Result
There were no adverse events as evaluated by the investigator. For this combined treatment and procedure patient scored comfort as the highest for satisfaction. Tolerability parameters erythema and edema were reported after RF microneedling treatment and were significant compared to the pre‐procedure timepoint. Eighty percent of patients showed an improvement in Glogau Wrinkle Scale, but improvement was not statistically significant between baseline and end of study. Improvements in all skin attributes (radiance, tone, smoothness, texture, redness, dryness, and overall appearance) were statistically significant at the end of the study. Self‐perceived skin attribute improvements included overall improvement, brightness, texture, pigmentation, redness, and tightness. The combination of the anti‐aging facial moisturizer and RF microneedling was recommended by the patients in this study.
Conclusion
This clinical study positively supports the hypothesis that combining the multi‐ingredient anti‐aging facial moisturizer pre‐ and post‐RF microneedling was safe and tolerable for the patients.
https://ift.tt/2RcYMky
SIG‐1273 protects skin against urban air pollution and when formulated in AgeIQ™ Night Cream anti‐aging benefits clinically demonstrated
Abstract
Background
SIG‐1273 is a novel cosmetic active that provides a broad spectrum of benefits to the skin. Considering the chronic skin exposure to pollution in urban areas, we sought to determine if SIG‐1273 could provide additional protection against skin aging by inhibiting pollutant‐induced cytotoxicity and inflammation.
Objective
Determine if SIG‐1273 possesses antipollution properties in vitro and evaluate the potential anti‐aging benefits of Age IQ™ Night Cream clinically in human subjects.
Methods
In vitro studies utilizing normal human epidermal keratinocytes (NHEKs), were co‐treated with urban dust (SRM 1649b) and SIG‐1273 (toxicity protection measured by MTS assay). A water‐soluble fraction of urban dust (UD‐WS) induces pro‐inflammatory cytokine release (IL‐8) from NHEKs (measured via ELISA). An 8‐week, 37‐subject clinical trial was performed with 0.05% SIG‐1273 formulated in Age IQ™ Night Cream and applied topically to assess its potential to reduce the appearance of aging.
Results
In vitro studies using NHEKs demonstrate SIG‐1273 protects against urban dust‐induced cell toxicity, reducing cell death by 66% and concentration dependently inhibits UD‐WS‐induced IL‐8 production (IC50 = 20 nmol/L), outperforming niacinamide, ascorbic acid, and α‐tocopherol, commonly used actives in antipollution skin‐care products. Clinical assessment of Age IQ™ Night Cream shows it is effective in improving the appearance of facial skin aging including fine lines and wrinkles, skin texture, skin clarity/brightness, and firmness/elasticity.
Conclusions
SIG‐1273, is demonstrated here for the first time to possess antipollution properties. Included as a key active ingredient in Age IQ™ Night Cream, this novel topical formulation provides benefits to individuals with aging skin.
https://ift.tt/2PR7Xdz
Effects of a topical lotion containing aminophylline, caffeine, yohimbe, l‐carnitine, and gotu kola on thigh circumference, skinfold thickness, and fat mass in sedentary females
Abstract
Background and objective
Topical aminophylline, caffeine, yohimbe, l‐carnitine, and gotu kola (Centella asiatica) may aid in reducing body fat. Lipoxyderm™ contains these ingredients and was used to test if fat loss of the thigh, in conjunction with a low intensity exercise program and restricted calorie intake, was enhanced via the topical application of this lotion.
Methods
This was a double‐blind, placebo‐controlled, within‐group study that investigated the effects of Lipoxyderm™ on thigh fat mass, circumference, and skinfold thickness. Seven participants underwent pre/post‐exercise testing for weight, bilateral thigh circumference/skinfold thickness, and body composition/thigh fat mass assessment via dual‐energy X‐ray absorptiometry. Participants followed a hypocaloric diet, walked 150 minutes/wk, and were randomly assigned to apply a placebo to one leg and Lipoxyderm™ to their other leg for 28 days. Separate two‐way mixed factorial repeated measures ANOVAs were used to compare the effects of Lipoxyderm™ to the placebo on thigh circumference, skinfold thickness, and fat mass.
Results
A significant time x group interaction was found for thigh circumference (F 1,6 = 18.2, P = 0.005), skinfold thickness (F 1,6 = 14.6, P = 0.009), and fat mass (F 1,6 = 37.1, P = 0.001).
Conclusions
A twice‐daily topical application of Lipoxyderm™ for 28 days compared to a placebo combined with a walking program and a restricted caloric intake is more effective at reducing thigh circumference (1.2 vs 0.8 cm), thigh skinfold thickness (3.7 vs 2.0 mm), and thigh fat mass (100.0 g vs 57.3 g).
https://ift.tt/2R7oIhj
Whole‐ and partial‐body cryotherapy in aesthetic dermatology: Evaluating a trendy treatment
Abstract
This manuscript addresses the use of whole‐ and partial‐body cryotherapy in aesthetic dermatology. Over the past several years, these have become trendy treatments that have been marketed for many purported benefits in overall skin appearance and skin health. With increased access through cryotherapy facilities and medical spas, whole‐ and partial‐body cryotherapy have grown in popularity. Unfortunately, many of the advertised claims have little, if any, scientific evidence behind them. Here, we summarize the data available in the literature. As trends evolve, clinicians should continue to be knowledgeable about them and their evidence in order to properly counsel patients appropriately.
https://ift.tt/2PTkqh4
The spectrum of cutaneous adverse events during Encorafenib and Binimetinib treatment in BRAF mutant advanced melanoma
Abstract
Background
BRAF inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF mutated melanoma patients. So far, the range of cutaneous adverse events has been characterized only for established BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (trametinib, cobimetinib).
Objective
The aim of this study was to investigate cutaneous adverse events emerging in melanoma patients treated with encorafenib and binimetinib.
Methods
Patients treated with BRAF and MEK inhibitors in clinical trials at the University Hospital of Zurich were identified. Frequency and features of cutaneous adverse events as well as their management were assessed based on the prospectively collected clinical and histopathological data. The events emerging during encorafenib and/or binimetinib therapy were compared to other BRAF and MEK inhibitors at the institution and in the literature.
Results
The most frequent cutaneous adverse events observed in patients treated with encorafenib alone (n=24) were palmoplantar hyperkeratosis (54%), palmoplantar erythrodysesthesia (58%) and alopecia (46%). Drug‐induced papulopustular eruptions prevailed in patients with binimetinib monotherapy (n=25). The most frequent cutaneous adverse events in patients treated with encorafenib/binimetinib (n=49) was palmoplantar hyperkeratosis (10%).
Conclusion
Compared to data published for established BRAFi, encorafenib monotherapy showed less hyperproliferative cutaneous adverse events. In contrast, palmoplantar hyperkeratosis and palmoplantar erythrodysesthesia seem to occur more often. The combination encorafenib with binimetinib is well tolerated and induces few cutaneous adverse events.
This article is protected by copyright. All rights reserved.
https://ift.tt/2DTwFnf
A survey among dermatologists: Diagnostics of superficial fungal infections – what is used and what is needed to initiate therapy and assess efficacy?
Abstract
Background
Superficial fungal infections are common. It is important to confirm the clinical diagnosis by mycological laboratory methods before initiating systemic antifungal treatment, especially as antifungal sensitivity and in vitro susceptibility may differ between different genera and species. For many years the gold standard for diagnosis of superficial fungal infections has been direct fungal detection in the clinical specimen (microscopy) supplemented by culturing. Lately newer molecular based methods for fungal identification have been developed.
Objective
This study was initiated to focus on the current usage of mycological diagnostics for superficial fungal infections by dermatologists. It was designed to investigate if it was necessary to differentiate between initial diagnostic tests and those used at treatment follow‐up in specific superficial fungal infections.
Methods
An online questionnaire was distributed among members of the EADV mycology Task Force and other dermatologists with a special interest in mycology and nail disease.
Results
The survey was distributed to 62 dermatologists of whom 38 (61%) completed the whole survey, 7 (11%) partially completed and 17 (27%) did not respond.
Nearly all respondents (82‐100%) said that ideally they would use the result of direct microscopy (or histology) combined with a genus / species directed treatment of onychomycosis, dermatophytosis, Candida‐ and Malassezia‐related infections. The majority of the dermatologists used a combination of clinical assessment and direct microscopy for treatment assessment and the viability of the fungus was at this visit than when initiating the treatment. Molecular based methods were not available for all responders.
Conclusion
The available diagnostic methods are heterogeneous and their usage differs between different practices as well as between countries. The survey confirmed that dermatologists find it important to make a mycological diagnosis, particularly prior to starting oral antifungal treatment in order to confirm the diagnose and target the therapy according to genus and species.
This article is protected by copyright. All rights reserved.
https://ift.tt/2SbBqvA
Diagnosis validation and clinical characterization of atopic dermatitis in Nurses’ Health Study 2
Abstract
Background
Epidemiologic studies of atopic dermatitis are often limited by case definitions that have not been validated.
Objective
In this study, we assessed the accuracy of self‐report of atopic dermatitis in a large cohort of US female nurses, the Nurses' Health Study 2 (NHS2). We also provide clinical characteristics of atopic dermatitis in the cohort.
Methods
We sent an electronic questionnaire to NHS2 participants who previously reported ever having a diagnosis of atopic dermatitis. This questionnaire was designed to confirm cases of atopic dermatitis using previously validated algorithms with >85% specificity. We assessed the association of atopic dermatitis with asthma, comparing the results when different definitions of atopic dermatitis were applied. We also inquired about various aspects of participants' atopic dermatitis.
Results
Responses were received from 2,509 of 5,126 (49%) nurses who were sent the questionnaire, with an average age of 62. Most participants (1,996/2,509, 80%) reiterated their previously reported clinician diagnosis of atopic dermatitis. Application of the two diagnostic algorithms yielded confirmation of 1,538 and 1,293 prevalent cases, respectively. The association of atopic dermatitis with asthma was stronger when more stringent atopic dermatitis case definitions were applied. Participants generally reported mild disease (92% with ≤10% maximal body surface area involved) and a high proportion (57%) reported adult‐onset disease.
Conclusions
Self‐report of atopic dermatitis diagnosis has good reliability, and future analyses will be strengthened by our ability to conduct sensitivity analyses with refined confirmed atopic dermatitis subgroups.
This article is protected by copyright. All rights reserved.
https://ift.tt/2DVb8e6
Accuracy of dermoscopy in distinguishing erythroplasia of Queyrat from common forms of chronic balanitis: results from a multicentric observational study
Abstract
Background
Clinical differentiation of erythroplasia of Queyrat (EQ) and chronic forms of balanitis may be challenging, especially in early phases or in overlapping cases. Dermoscopy has been shown to be a useful supportive tool in facilitating the distinction between tumoral and inflammatory skin conditions, yet data on EQ and balanitis are scarce or sparse.
Objectives
To systematically assess the dermoscopic features of both EQ and common forms of chronic balanitis and to investigate the accuracy of dermoscopy in distinguishing these conditions.
Methods
Subjects with EQ or chronic balanitis confirmed histologically or microbiologically (for infectious forms) were recruited. A representative dermoscopic image of a target lesion was retrospectively assessed for the presence of specific morphological findings. A correlation matrix was created using Spearman's rho. Proportions of dermoscopic variables scoring among different conditions were compared with the non‐parametric Pearson's Chi Square test.
Results
A total of 81 lesions (14 EQ, 23 psoriasis, 31 Zoon plasma cell balanitis, and 13 candidal balanitis) from 81 patients were included in the study. Glomerular vessels (both clustered and diffusely distributed) were highly predictive for the diagnosis of EQ, while diffuse dotted vessels were strongly associated with psoriatic balanitis. Finally, Zoon plasma cell balanitis was characterized by orange structureless areas (focal or diffuse) and focused linear curved vessels, whereas cottage cheese‐like structures (sparse white coating corresponding to Candida yeast colonies growth) showed a strong correlation with candidal balanitis.
Conclusions
EQ and balanitis may display different dermoscopic patterns, thereby bearing the usefulness of dermoscopy as a supportive non‐invasive tool for the recognition and differential diagnosis of such conditions.
This article is protected by copyright. All rights reserved.
https://ift.tt/2SbBlbg
“High dose” versus “medium dose” uva1 phototherapy in italian patients with severe atopic dermatitis
Abstract
Background
the current evidences attest UVA1 phototherapy as effective in the treatment of severe atopic dermatitis (AD). Furthermore in this indication, "medium dose" is as effective as "high dose" regimen. To date, a randomized comparison study evaluating the effectiveness as well as safety of different UVA1 protocols in different skin types in the treatment of adult patients with severe AD is still lacking.
Objective
The aim of the present study was to compare the safety and the efficacy of medium and high dose UVA1 either in fair or in dark skin types.
Methods
Twenty‐seven adult patients with severe AD were consecutively included in a randomized, controlled, open, two arms trial. Severity of AD was determined by means of SCORAD index and clinical improvement was also monitored. A total of 13/27 patients were treated with High Dose (130 J/cm2) UVA1 protocol while 14/27 patients received Medium Dose (60 J/cm2) UVA1 protocol. Phototherapy was performed 5 times weekly up to 3 weeks. Before and after UVA1 treatment each patient was evaluated for skin pigmentation through Melanin Index (MI) quantitative evaluation.
Results
Skin status improved in all patients resulting in a reduction of SCORAD index in all groups. Our results demonstrated that among patients with darker skin types and higher MI, High dose UVA1 was significantly more effective than Medium Dose (p < 0.0001) while within the groups with skin type II, no significant differences between high and medium dose protocols were observed.
Conclusion
Our study, confirms previous observations that UVA1 phototherapy should be considered among the first approaches in the treatment of patients with severe generalized atopic dermatitis and also demonstrates that in darker skin types, high dose UVA1 phototherapy is more effective than medium dose in the treatment of adult patients with severe AD.
This article is protected by copyright. All rights reserved.
https://ift.tt/2DUH1Dr
A Comparative Study of Onychomycosis and Traumatic Toenail Onychodystrophy Dermoscopic Patterns
Summary
Background
Onychomycosis (OM) and traumatic onychodystrophy (OD) are common causes of toenail changes. A clinical diagnosis is often impossible without mycology. Dermoscopy is helpful in this setting but yet under‐explored. Prospective comparative studies between OM and OD onychoscopic findings have not been previously performed.
Objectives
We sought to determine distinguishing dermoscopic presentations of OM and traumatic OD.
Methods
We performed a prospective, observational study including patients presenting with ≥1 toenail onychodystrophy. All underwent onychoscopy, clinical and mycological examination. Based on these results, patients received a final diagnosis of OM or OD. Dermoscopic presentations of OM and OD patients were classified in patterns and compared.
Results
In all, 110 cases of OM and 82 of traumatic OD were compared. Statistical analyses revealed that the distal pulverized and the irregular spiked macular dermoscopic patterns were predictors of an OM diagnosis. The regular macular, the non‐classifiable, the total and partial homogeneous background dermoscopic patterns, correlated with traumatic OD diagnosis.
Conclusions
We demonstrated that OM and traumatic OD have distinctive onychoscopic presentations. Dermoscopy may be an important ancillary tool to guide their differential.
This article is protected by copyright. All rights reserved.
https://ift.tt/2SbBewm
Onychoscopy of non‐infectious nail abnormalities in patients after allogeneic hematopoietic stem cell transplantation
Abstract
Nail abnormalities after allogeneic hematopoietic stem cell transplantation procedure (alloHSCT) are often reported. Usually they are related to chronic graft‐versus‐host disease (cGvHD). So far, only clinical manifestations of selected nail abnormalities have been described, without the presentation of dermoscopic images. In this article we present morphologic and dermoscopic manifestations of potential non‐infectious nail abnormalities in patients after alloHSCT procedure based on reviewed literature and our own experience with dermoscopic iconography. In majority of studies published till now nail changes are not connected to severity of other cGvHD symptoms, however, e.g. the presence of pterygium inversum unguis may be an indicator of lung dysfunction. As nail changes may be an early sign of cGvHD and always present in association with other manifestations, routine clinical assessment should include nails examination. Knowledge of possible presentation of nail involvement after alloHSCT may be valuable for treating physician.
This article is protected by copyright. All rights reserved.
https://ift.tt/2DV3Oiw
Autochthonous and persistent cutaneous larva migrans in an infant successfully treated by topic albendazole ointment
Abstract
Cutaneous larva migrans (CLM) is a skin infestation clinically characterized by erythematous, serpiginous and pruriginous lesions caused by accidental percutaneous penetration and migration of animal hookworm larvae. This zoonotic dermatitis is endemic in tropical countries. In Western Europe, cases are usually seen in returning travelers and cases acquired locally remain rare. Herein we report a case of CLM contracted in France by a 10‐month‐old infant, successfully treated by albendazole ointment after 6 months of evolution. This case emphasizes the fact that Western physicians do not have sufficient knowledge of this dermatitis.
This article is protected by copyright. All rights reserved.
https://ift.tt/2SbBag6
Teledermatology diagnosis of the first Italian patient affected with restrictive dermopathy due to ZMPSTE24 homozygous mutation
Abstract
Restrictive dermopathy (RD, OMIM #275210) is a rare genodermatosis, caused by ZMPSTE24 or, less frequently, LMNA mutations.1 It is characterized by an extremely poor prognosis resulting in stillbirth or early neonatal death.1,2 Clinical features comprise prematurity, intrauterine growth retardation, thin rigid skin with lacerations at flexural regions, facial dysmorphism and joint ankyloses. We report the first Italian case due to a ZMPSTE24 homozygous recurrent mutation.
This article is protected by copyright. All rights reserved.
https://ift.tt/2DVSVwK
Subclinical atherosclerosis in psoriatic disease: relation to endocan, TNF‐α, age of onset, and body fat
Abstract
Background
Psoriasis is a common multisystem inflammatory disease with several associated comorbidities. Serological markers to detect associated subclinical atherosclerosis in psoriatic patients are needed. We aimed to study serum endocan levels in psoriasis vulgaris and its relation to severity of psoriasis, systemic inflammation, associated atherosclerosis, obesity, and the possible factors affecting its level in psoriatic patients.
Methods
This study was conducted on 30 moderate‐severe psoriasis vulgaris patients and 30 healthy controls. Body mass index, body fat percent, and PASI assessments were done. Serum endocan and tumor necrosis factor‐α levels were measured by ELISA. Carotid artery intima‐media thickness measurement by high‐resolution ultrasound was performed.
Results
Psoriasis patients showed significantly higher serum tumor necrosis factor‐α and endocan levels (P1 = 0.008, P2 = 0.003). Additionally, there was a statistically significant difference between mean carotid artery intima‐media thickness of both groups (P = 0.005). Serum endocan levels positively correlated with PASI score (P = 0.002), tumor necrosis factor‐α levels (P < 0.001), mean carotid artery intima‐media thickness (P = 0.001), and body mass index (P < 0.001) in the patients group. Additionally, the age of onset of disease negatively correlated with serum endocan (P = 0.003).
Conclusion
Serum endocan is a promising marker of severity of psoriasis and associated atherosclerosis. Early onset psoriasis is associated with higher serum endocan levels. Body mass index is positively correlated with serum endocan levels. The positive correlation of endocan and tumor necrosis factor‐α supports the regulatory effect of the cytokine on endocan production and suggests the role of endocan as an inflammatory marker.
https://ift.tt/2DVmD54
Is there an association between indoor allergens and the severity of atopic dermatitis?
Abstract
Background
Atopic dermatitis (AD) is a multifactorial inflammatory skin disease with frequent hypersensitivity to allergens. However, the role of exposure to indoor allergens on AD severity is unclear.
Methods
Children aged 0–17 years with active AD from central Chile were recruited; disease severity was evaluated with SCORAD and POEM scores. A home environment survey was applied to parents. Bedroom dust samples were collected for all subjects and analyzed by multiplex assay to quantify dust mite (Der p1, Der f1), dog (Can f1), cat (Fel d1), and alternaria alternata (Alt a1) allergens.
Results
Twenty‐five children aged 3.9 ± 3.8 years were included. Fifty‐two percent were female. Mean SCORAD was 29 ± 14 (range 11–61), and mean POEM was 10.7 ± 6.2. No direct association was found between tobacco exposure, pet ownership, aerosol use, visible dust, or home carpets/rugs with SCORAD (all P > 0.05). Dust samples from all homes had Can f1 and Fel d1 allergens, regardless of pet ownership. Homes that had indoor dogs or cats had significantly higher amounts of these allergens (P < 0.001). Forty percent of homes had dust mite allergens, and none had alternaria alternata. Children with AD living in homes with elevated dust mite and animal dander allergen concentrations had higher SCORAD than those from homes with low allergen concentrations (40 ± 13 vs. 26 ± 13, P = 0.025).
Conclusions
High concentrations of indoor allergens may influence AD severity in children. Further studies assessing indoor allergens and allergen sensitization are warranted to fully evaluate the role of indoor allergens on AD.
https://ift.tt/2SdrWQD
Chest radiography or chest CT plus head and neck CT versus 18F-FDG PET/CT for detection of distant metastasis and synchronous cancer in patients with head and neck cancer
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Yehree Kim, Jong-Lyel Roh, Jae Seung Kim, Jeong Hyun Lee, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim
Abstract
Objectives
Current guidelines recommend chest computed tomography (CT) with locoregional CT/magnetic resonance imaging for patients with head and neck squamous cell carcinoma (HNSCC), and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/CT is suggested for stage III–IV patients. However, whole body screening with 18F-FDG PET/CT may provide better detection of distant metastases and synchronous cancer than conventional imaging. We evaluated the utility of 18F-FDG PET/CT in detecting distant metastasis and synchronous cancer.
Methods
This prospective study enrolled 740 consecutive patients with previously untreated HNSCC diagnosed between September 2010 and December 2015. Synchronous cancer was histologically confirmed and distant metastases were confirmed by biopsy or serial imaging follow-ups. McNemar test was used to compare the true-positive detection rates of chest radiography (CXR) + head and neck CT (hnCT) (A) versus 18F-FDG PET/CT (C) and chest CT + hnCT (B) versus 18F-FDG PET/CT.
Results
Distant metastases and synchronous cancer were found in 23 (3.1%) and 55 (7.4%) patients, respectively. A, B, and C detected distant metastases in 10 (1.3%), 19 (2.6%), and 21 (2.8%) patients, respectively. The absolute differences were 1.5% (A versus C, P = 0.003) and 0.3% (B versus C, P = 0.687). A, B, and C detected synchronous cancer in 15 (2.0%), 22 (2.9%), and 36 (4.9%) patients, respectively. The absolute differences were 2.8% (A versus C, P < 0.001) and 1.4% (B versus C, P = 0.013).
Conclusions
18F-FDG PET/CT detected more distant metastases and synchronous cancer than CXR + hnCT and more synchronous cancer than chest CT + hnCT.
https://ift.tt/2zn2vFi
Reproductive history and risk of nasopharyngeal carcinoma: A population-based case–control study in southern China
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Rui-Mei Feng, Ellen T. Chang, Zhiwei Liu, Qing Liu, Yonglin Cai, Zhe Zhang, Guomin Chen, Qi-Hong Huang, Shang-Hang Xie, Su-Mei Cao, Yu Zhang, Jingping Yun, Wei-Hua Jia, Yuming Zheng, Jian Liao, Yufeng Chen, Longde Lin, Ingemar Ernberg, Guangwu Huang, Yi Zeng
Abstract
Objects
Nasopharyngeal carcinoma (NPC) incidence exhibits a remarkable sex disparity, with higher risk among males. Whether this pattern can be partly explained by female reproductive history is unclear.
Methods
A population-based case–control study of NPC was conducted in southern China between 2010 and 2014, including 674 histopathologically verified female NPC cases and 690 female controls randomly selected from population-based registries. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression after adjusting for potential confounders.
Results
Women who had 3, 4, or ≥5 pregnancies compared with 2 pregnancies were at significantly increased risk for NPC (ORs 1.56, 1.45 and 1.88, respectively). History of deliveries was similarly associated with a greater risk of NPC. These positive associations were more prominent in women who were younger than 50 years, had less than 10 years of education, or were white-collar workers. Increasing time since menopause was associated with a diminished NPC risk (Ptrend = 0.010). Women more than 15 years after menopause had a 0.35-fold (95% CI: 0.16–0.75) NPC risk compared with those 0–3 years after menopause.
Conclusion
Contrary to our hypothesis, a history of pregnancy or delivery increased the risk of NPC and the risk decreased with increasing time since menopause. However, the non-linear relationship and no consistent risk patterns across strata indicate that the observed associations are unlikely to be causal, and may at least partially be ascribed to residual confounding by socioeconomic factors.
https://ift.tt/2P1eZY7
Immune microenvironment and evasion mechanisms in adenoid cystic carcinomas of salivary glands
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Carla Mosconi, José Alcides Almeida de Arruda, Ana Caroline Rodrigues de Faria, Gabriella Alves Quixabeira Oliveira, Henrique Moura de Paula, Felipe Paiva Fonseca, Ricardo Alves Mesquita, Tarcília Aparecida Silva, Elismauro Francisco Mendonça, Aline Carvalho Batista
Abstract
Objectives
The objective of the present study was to investigate the expression of immune checkpoints (PD-L1, PD-L2, PD-1 and CTLA-4), immune inhibitory molecule HLA-G, markers of tumor-infiltrating lymphocytes (TIL) and dendritic cells (DC), as well as its association with clinicopathological features of adenoid cystic carcinomas (ACC) of the salivary glands.
Materials and methods
Thirty-six samples from patients with ACC were analyzed immunohistochemically for the expression of PD-L1, PD-L2, PD-1, CTLA-4, HLA-G, CD8, GrB, CD1a and CD83. Positivity of HLA-G, PD-L1 and PD-L2 expression was defined by cut-offs values. CD8+ TIL was measured semiquantitatively and also using cut-off values obtained by the ROC curve considering recurrence of the lesion.
Results
ACC showed low CD8+, GrB+ TIL, CD1a and CD83 populations, as well as scarce positivity for CTLA-4 and PD-1. In contrast, PD-L2 and HLA-G expression was increased, while no PD-L1 expression was detected. Interestingly, cases with lower CD8+ TIL density presented greater recurrence rates.
Conclusion
Our findings suggest that the ACC microenvironment exhibits low immunogenicity, represented by low TIL and DC density. Moreover, there seems to be activation of the immune inhibitory proteins/PD-L2 and HLA-G, a scenario that may favor tumor escape from the immune system and partially explain the poor prognosis of ACC.
https://ift.tt/2zn2npi
Identification of the minimal region of peptide derived from ADP-ribosylation factor1 (ARF1) that inhibits IgE-mediated mast cell activation
Publication date: January 2019
Source: Molecular Immunology, Volume 105
Author(s): Ryota Uchida, Tomonori Egawa, Yoshio Fujita, Kazuyuki Furuta, Hiroaki Taguchi, Satoshi Tanaka, Keigo Nishida
Abstract
Mast cells play a pivotal role in allergic reactions and inflammations. Aggregation of the high affinity IgE receptor (FcεRI) eventually leads to the release of granule components such as histamine, as well as the de novo synthesis of inflammatory cytokines and lipid mediators. These substances are involved in the development of allergy and inflammation. Therefore, efficient inhibitors of mast cell activation would be therapeutically beneficial. We previously demonstrated that the synthetic peptide derived from the NH2-terminal region (2–17: GNIFANLFKGLFGKKE) of a small GTPase ARF1 (ADP-ribosylation factor1) inhibited FcεRI-induced mast cell degranulation. However, detailed structure-activity relationship study of NH2-terminal portion of ARF1 peptide has not been done. In addition, it is still unclear whether the NH2-terminal peptide of ARF1 suppresses FcεRI-induced production of cytokines and lipid mediators such as leukotriene C4 (LTC4) from mast cells.
Here we show that amino acid residues K10-K16 are necessary for ARF1 peptide to efficiently inhibit FcεRI-induced activation of bone marrow-derived mast cells (BMMCs), indicated by decreased mast cell degranulation, cytokine secretion and leukotriene release. Furthermore, we show that ARF1 peptide inhibits IgE-mediated passive cutaneous anaphylaxis reaction. Our results suggest that the peptide derived from ARF1 could be developed into a novel anti-allergic agent for therapeutic intervention in allergy and mast cell-related pathologies.
https://ift.tt/2FDv0DX
A complex auxiliary: IL-17/Th17 signaling during type 1 diabetes progression
Publication date: January 2019
Source: Molecular Immunology, Volume 105
Author(s): Zihan Zheng, Feng Zheng
Abstract
Type 1 diabetes (T1D) is an autoimmune disease centered around the loss of the beta cells of the islets of Langerhans, and consequent inability of the islets to produce the insulin necessary to maintain glycemic control. While most therapeutic approaches have been centered on insulin replacement, newer approaches to target the underlying immune response have become an area of focus. However, the immune landscape in T1D is extremely complex, and the roles played by individual cytokines during disease progression are incompletely understood, making the development of immunotherapies very difficult. In this review, we discuss the complex auxiliary role played by IL-17, both around the islet and in peripheral tissues such as the gut and kidney, which might influence T1D progression. Through our re-analysis of the key factors involved IL-17 signaling in recently published single-cell sequencing and sorted-cell bulk sequencing datasets, we find supporting evidence for the general existence of the signaling apparatus in islet endocrine cells. We also explore the emerging evidence of IL-17 serving as an influential factor in diabetic complications that affect distal tissues. While anti-IL-17 therapies are emerging as an option for psoriasis and other autoimmune disorders, we highlight here a number of questions that would need to be addressed before their potential applicability to treating T1D can be fully evaluated.
https://ift.tt/2r1Zs0F
Development of a Pediatric Asthma Predictive Index for Hospitalization
Publication date: Available online 24 November 2018
Source: Annals of Allergy, Asthma & Immunology
Author(s): Tiffany Jean, Su-Jau Yang, William W. Crawford, Scott H. Takahashi, Javed Sheikh
https://ift.tt/2AkK5EL
Measurement of exhaled nitric oxide in young children with NIOX VERO
Publication date: Available online 23 November 2018
Source: Annals of Allergy, Asthma & Immunology
Author(s): Kathleen Rickard, Margot MacDonald-Berko, Robert Anolik, Neal Jain, Craig La Force, Richard L. Wasserman
https://ift.tt/2TFtuUT
Apolipoprotein E, periodontal disease and the risk for atherosclerosis: a review
Publication date: Available online 23 November 2018
Source: Archives of Oral Biology
Author(s): L.C. Pereira, J.C.R Nascimento, J.M.C. Rêgo, K.M. Canuto, M.E. Crespo-Lopez, J.I. Alvarez Leite, A. Baysan, R.B. Oriá
Abstract
The association between cardiovascular and periodontal diseases is characterized by chronic inflammatory processes, with a high prevalence worldwide and complex genetic-environment interactions. Although apolipoprotein E4 (ApoE4), one of the isoforms coded by a polymorphic APOE gene, has been widely recognized as a risk factor for cardiovascular diseases and as an immunoinflammatory factor, but less is known regarding how ApoE4 affects atherosclerosis in periodontitis patients. The aim of this review was to investigate the potential underlying mechanisms related to APOE4 that could increase the risk of periodontal disease and, ultimately, of atherosclerosis. There have only been a few studies addressing apoE polymorphisms in patients with chronic periodontitis. To date, no studies have been performed that have assessed how ApoE4 affects atherosclerotic disease in chronic periodontitis patients. Although clinical studies are warranted, experimental studies have consistently documented the presence of periodontal pathogens, which are usually found in the oral cavity and saliva, in the atherosclerotic plaques of ApoE-deficient mice. In addition, in this review, the potential role of the APOE4 allele as an example of antagonistic pleiotropy during human evolution and its relation to oral health is discussed.
https://ift.tt/2KAvERP
Apolipoprotein E, periodontal disease and the risk for atherosclerosis: a review
Publication date: Available online 23 November 2018
Source: Archives of Oral Biology
Author(s): L.C. Pereira, J.C.R Nascimento, J.M.C. Rêgo, K.M. Canuto, M.E. Crespo-Lopez, J.I. Alvarez Leite, A. Baysan, R.B. Oriá
Abstract
The association between cardiovascular and periodontal diseases is characterized by chronic inflammatory processes, with a high prevalence worldwide and complex genetic-environment interactions. Although apolipoprotein E4 (ApoE4), one of the isoforms coded by a polymorphic APOE gene, has been widely recognized as a risk factor for cardiovascular diseases and as an immunoinflammatory factor, but less is known regarding how ApoE4 affects atherosclerosis in periodontitis patients. The aim of this review was to investigate the potential underlying mechanisms related to APOE4 that could increase the risk of periodontal disease and, ultimately, of atherosclerosis. There have only been a few studies addressing apoE polymorphisms in patients with chronic periodontitis. To date, no studies have been performed that have assessed how ApoE4 affects atherosclerotic disease in chronic periodontitis patients. Although clinical studies are warranted, experimental studies have consistently documented the presence of periodontal pathogens, which are usually found in the oral cavity and saliva, in the atherosclerotic plaques of ApoE-deficient mice. In addition, in this review, the potential role of the APOE4 allele as an example of antagonistic pleiotropy during human evolution and its relation to oral health is discussed.
https://ift.tt/2KAvERP
The Microbiome in Atopic Dermatitis
Publication date: Available online 23 November 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Amy S. Paller, Heidi H. Kong, Patrick Seed, Shruti Naik, Tiffany C. Scharschmidt, Richard L. Gallo, Thomas Luger, Alan D. Irvine
Abstract
As an interface with the environment, the skin is a complex ecosystem, colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens such as S. aureus and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized, as microorganisms can modulate innate, as well as adaptive, immune responses. Host-commensal interactions also have an impact on the developing immune system in infants and subsequently the occurrence of diseases such as asthma and atopic dermatitis. Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with atopic dermatitis, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria such as S. aureus. Early clinical studies suggest that topical application of commensal organisms (e.g., S. hominis or R. mucosa) reduces atopic dermatitis severity and support an important role for commensals in decreasing S. aureus colonization in patients with atopic dermatitis. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders such as atopic dermatitis may result in novel therapeutic strategies.
https://ift.tt/2TGXbEY
Novel mutations in MYTH4-FERM domains of myosin 15 are associated with autosomal recessive nonsyndromic hearing loss
Publication date: Available online 23 November 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Hoda Mehregan, Marzieh Mohseni, Khadijeh Jalalvand, Sanaz Arzhangi, Nooshin Nikzat, Sussan Banihashemi, Kimia Kahrizi, Hossein Najmabadi
Abstract
Objective
Hereditary hearing loss is the most common neurosensory disorder in humans caused by myriad mutations in numerous genes. Autosomal recessive nonsyndromic hearing loss (ARNSHL) accounts for 80% of hearing impairments of genetic origin and is quite prevalent in societies with a high rate of consanguinity. In the current study, we investigated the causes of sensorineural hearing loss in 24 unrelated Iranian families who were mainly consanguineous and had at least two affected children.
Methods
All probands were initially screened for GJB2 mutations, as the most common causes of ARNSHL in Iran. Verified GJB2-negative samples were subsequently subjected to whole exome sequencing (WES) to identify the underlying causes of hearing impairment, and the variants identified in each family were further confirmed by Sanger sequencing.
Results
WES revealed three previously unreported mutations in MYO15A, the gene encoding the unconventional myosin 15 (Myo15). All variants identified, c.C6436T (p.R2146W), c.C9584G (p.P3195R) and c.G10266C (p.Q3422H), reside in the MYTH4 (myosin tail homology) and FERM (4.1 ezrin, radixin, moesin) domains of the protein.
Conclusion
Globally, mutations in MYO15A are considered to be among the most prevalent genetic causes of ARNSHL, and they rank as the third leading cause of hearing loss in the Iranian population, below GJB2 and SLC26A4. Yet again, these results endorse the importance of MYO15 screening in hearing impaired populations, particularly in Iran.
https://ift.tt/2QcEjPx
The misplaced cochlear implant electrode array
Publication date: Available online 23 November 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Ahmed Mohamed Mehanna, Omneya A. Gamaleldin, Mohamed Fawzi Fathala
Abstract
Objectives
/Hypothesis— Evaluation of the clinical, electrophysiologic findings, the management plans of the misplaced cochlear implant electrode array and the possible causes of misplacement. Also to provide recommendations to prevent a repeat of cochlear implant electrode misplacement into abnormal sites.
Study Design
—Retrospective study.
Methods
—Pediatric cochlear implant recipients implanted from January 2012 till January 2018 whose electrode arrays were misplaced outside the cochlea into the surrounding structures.
Results
—Eight pediatric cochlear implant recipients, were identified to have a misplaced cochlear implant electrode array. Different sites of improper placement included one case in the eustachian tube, another one in the vestibule, one electrode array was found to be in the petrous apex lateral to the internal carotid canal, and another one in the internal auditory canal (IAC), and in three cases the electrode arrays were packed in the hypotympanum, and lastly an electrode array recoiled after perfect insertion and was found to be in the facial recess. Six cases were initially identified immediate because of their poor intraoperative implant testing which prompted imaging while in two cases, the one found in the petrous apex and the other one in the internal auditory canal (IAC) were diagnosed several months after surgery due to unsatisfactory auditory skills development or absent behavioral responses following implantation.
Conclusions
—Electrode array misplacement may be due to either failure to identify the anatomical landmarks during surgery specially the infracochlear air cell track or unidentified inner ear malformation. The routine use of intraoperative electrophysiologic testing and postoperative imaging should help to avoid such complications. Misplacement is a rare but still correctable complication after cochlear implant surgery. The diagnosis of misplacement can be delayed for years and in this occasion, it is suspected when benefit from the implant is limited or absent. Once misplacement is diagnosed revision surgery has to be done.
https://ift.tt/2DIovxm
Evaluation of serum and salivary interferon-gamma levels in oral lichen planus patients: A systematic review and meta-analysis of case-control studies
Publication date: Available online 24 November 2018
Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Hamid Reza Mozaffari, Roohollah Sharifi, Mina Hayati, Mohammad Moslem Imani, Pia Lopez Jornet, Amin Golshah, Hedaiat Moradpoor, Razieh Rezaei, Masoud Sadeghi
Objective
Cytokines have regulatory and leading roles in immunopathogenesis of OLP. Herein, the present meta-analysis evaluates the serum and salivary interferon-gamma (IFN-γ) levels in the OLP patients compared with the controls as well as the correlation of this cytokine with the progression of OLP.
Study design
Four databases including PubMed, Web of Science, Scopus, and Cochrane Library were searched from their start date to November 2017. The studies on the effect of oral lichen planus on salivary and serum IFN-γ were searched without language restriction.
Results
Eleven studies were included and analyzed in this meta-analysis. The pooled mean difference (MD) values were estimated to be 3.60 pg/ml (P=0.23) and -0.02 pg/ml (P=1.00) for serum and salivary levels of IFN-γ in the OLP patients compared to the controls, respectively. The pooled MD values were -2.52 pg/ml (P=0.03) and -2.01 pg/ml (P=0.20) for serum and salivary IFN-γ levels in the erosive type compared with the nonerosive type, respectively.
Conclusion
According to the result of meta-analysis, there was no statistically significant difference of IFN-γ between the OLP patients and the control group both in serum and salivary levels and also between erosive and nonerosive types of OLP in the salivary level; so this cytokine is not considered to have an important role in the pathogenesis or severity of OLP.
https://ift.tt/2POxvYW
Editorial Board
Publication date: December 2018
Source: Clinical Immunology, Volume 197
Author(s):
https://ift.tt/2DL4hmH
Efficiency of the TOF-Cuff™ for the evaluation of rocuronium-induced neuromuscular block and its reversal with sugammadex: a comparative study vs. acceleromyography
Abstract
Purpose
The aim of this study was to compare TOF-Cuff™ (TOF-C) and TOF-Watch™ (TOF-W) data following rocuronium-induced neuromuscular block and its reversal with sugammadex.
Methods
Twenty elderly patients aged 68–82 years scheduled for surgery under general anesthesia were enrolled in this study. After induction of anesthesia, neuromuscular block resulting from administration of 0.6 mg/kg rocuronium was concurrently evaluated using TOF-C and TOF-W. The onset of neuromuscular block and duration until the first twitch response following post-tetanic count (PTC) and 2 Hz train-of-four (TOF) stimulation reappeared were evaluated. When the response to the TOF stimulus was detected with both monitors, additional doses of rocuronium were administered to maintain the neuromuscular block. After surgery, 2 mg/kg sugammadex was administered when 1–2 TOF twitches were observed with the TOF-W and the time required for facilitated recovery to a TOF ratio of > 0.9 was assessed.
Results
Regression analyses revealed no statistically significant differences in the mean [SD] onset of rocuronium-induced neuromuscular block [127.8 (27.2) s, 123.5 (30.5) s], time to recovery of the first PTC twitch [23.9 (8.0) min, 25.4 (8.6) min], time to recovery of the first twitch with TOF stimulation [37.2 (8.8) min, 38.9 (11.1) min] and time to adequate reversal with sugammadex [139.2 (30.6) s, 151.8 (31.5) s] between TOF-C and TOF-W, respectively. Bland–Altman analyses also showed acceptable ranges of the biases and limits of agreement between the two methods.
Conclusions
TOF-C may be clinically applicable for the evaluation of both the depth of neuromuscular block and restoration of neuromuscular function.
https://ift.tt/2DGHvfw
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