Comparison of Induced Fields in Virtual Human and Rat Heads by Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) shows significant values in both brain research and therapeutic applications of cognitive neuroscience, neurophysiology, and psychiatry. Animal studies of TMS provide a potential way for learning the biological mechanisms of actions of TMS. In this paper, we presented the comparison of human TMS and rat TMS by using the conventional figure-of-eight coil for the first time. Three-dimensional distributions of magnetic flux density and induced electric field in both virtual human and rat heads were obtained through the 3D impedance method. The results indicated that smaller TMS coils are needed for stimulation of the rat brain. A rat-specific figure-of-eight coil was designed by considering the coil radii, number of coil turns, and the injected coil currents. We found that the numerically designed Fo8 coil can be applied to the rat TMS with improved focality while also keeping high stimulation intensities.

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Cancers, Vol. 11, Pages 32: Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model

Cancers, Vol. 11, Pages 32: Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model

Cancers doi: 10.3390/cancers11010032

Authors: Amy L. Wilson Kirsty L. Wilson Maree Bilandzic Laura R. Moffitt Ming Makanji Mark D. Gorrell Martin K. Oehler Adam Rainczuk Andrew N. Stephens Magdalena Plebanski

Ovarian cancers (OCs) are the most lethal gynaecological malignancy, with high levels of relapse and acquired chemo-resistance. Whilst the tumour–immune nexus controls both cancer progression and regression, the lack of an appropriate system to accurately model tumour stage and immune status has hampered the validation of clinically relevant immunotherapies and therapeutic vaccines to date. To address this need, we stably integrated the near-infrared phytochrome iRFP720 at the ROSA26 genomic locus of ID8 mouse OC cells. Intrabursal ovarian implantation into C57BL/6 mice, followed by regular, non-invasive fluorescence imaging, permitted the direct visualization of tumour mass and distribution over the course of progression. Four distinct phases of tumour growth and dissemination were detectable over time that closely mimicked clinical OC progression. Progression-related changes in immune cells also paralleled typical immune profiles observed in human OCs. Specifically, we observed changes in both the CD8+ T cell effector (Teff):regulatory (Treg) ratio, as well as the dendritic cell (DC)-to-myeloid derived suppressor cell (MDSC) ratio over time across multiple immune cell compartments and in peritoneal ascites. Importantly, iRFP720 expression had no detectible influence over immune profiles. This new model permits non-invasive, longitudinal tumour monitoring whilst preserving host–tumour immune interactions, and allows for the pre-clinical assessment of immune profiles throughout disease progression as well as the direct visualization of therapeutic responses. This simple fluorescence-based approach provides a useful new tool for the validation of novel immuno-therapeutics against OC.

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JAMA Otolaryngology,Head & Neck Surgery,The Most Talked About Articles of 2018 : Association of Long-Term Risk of Respiratory, Allergic, and Infectious Diseases With Removal of Adenoids and Tonsils in Childhood, Association of Age-Related Hearing Loss With Cognitive Function, Cognitive Impairment, and Dementia, Association Between Hearing Aid Use and Health Care Use and Cost Among Older Adults With Hearing Loss, Factors Associated With Phantom Odor Perception, Association of Continuous Positive Airway Pressure Treatment With Sexual Quality of Life in Patients With Sleep Apnea, Traumatic Tympanic Membrane Perforations Diagnosed in Emergency Departments, Association Between Portable Music Player Use and Hearing Loss Among Children of School Age, Association of Gastroesophageal Reflux With Malignancy of the Upper Aerodigestive Tract in Elderly Patients, Association of Tinnitus and Other Cochlear Disorders With a History of Migraines, Incidence of Thyroid Cancer Among Ch

Association of Long-Term Risk of Respiratory, Allergic, and Infectious Diseases With Removal of Adenoids and Tonsils in Childhood

Sean G. Byars, PhD1,2; Stephen C. Stearns, PhD3; Jacobus J. Boomsma, PhD2

Author Affiliations Article Information

JAMA Otolaryngol Head Neck Surg. 2018;144(7):594-603. doi:10.1001/jamaoto.2018.0614

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Questions  Are there long-term health risks after having adenoids or tonsils removed in childhood?

Findings  In this population-based cohort study of almost 1.2 million children, removal of adenoids or tonsils in childhood was associated with significantly increased relative risk of later respiratory, allergic, and infectious diseases. Increases in long-term absolute disease risks were considerably larger than changes in risk for the disorders these surgeries aim to treat.

Meaning  The long-term risks of these surgeries deserve careful consideration.

Abstract

Importance  Surgical removal of adenoids and tonsils to treat obstructed breathing or recurrent middle-ear infections remain common pediatric procedures; however, little is known about their long-term health consequences despite the fact that these lymphatic organs play important roles in the development and function of the immune system.

Objective  To estimate long-term disease risks associated with adenoidectomy, tonsillectomy, and adenotonsillectomy in childhood.

Design, Setting, and Participants  A population-based cohort study of up to 1 189 061 children born in Denmark between 1979 and 1999 and evaluated in linked national registers up to 2009, covering at least the first 10 and up to 30 years of their life, was carried out. Participants in the case and control groups were selected such that their health did not differ significantly prior to surgery.

Exposures  Participants were classified as exposed if adenoids or tonsils were removed within the first 9 years of life.

Main Outcomes and Measures  The incidence of disease (defined by International Classification of Diseases, Eighth Revision [ICD-8] and Tenth Revision [ICD-10] diagnoses) up to age 30 years was examined using stratified Cox proportional hazard regressions that adjusted for 18 covariates, including parental disease history, pregnancy complications, birth weight, Apgar score, sex, socioeconomic markers, and region of Denmark born.

Results  A total of up to 1 189 061 children were included in this study (48% female); 17 460 underwent adenoidectomy, 11 830 tonsillectomy, and 31 377 adenotonsillectomy; 1 157 684 were in the control group. Adenoidectomy and tonsillectomy were associated with a 2- to 3-fold increase in diseases of the upper respiratory tract (relative risk [RR], 1.99; 95% CI, 1.51-2.63 and RR, 2.72; 95% CI, 1.54-4.80; respectively). Smaller increases in risks for infectious and allergic diseases were also found: adenotonsillectomy was associated with a 17% increased risk of infectious diseases (RR, 1.17; 95% CI, 1.10-1.25) corresponding to an absolute risk increase of 2.14% because these diseases are relatively common (12%) in the population. In contrast, the long-term risks for conditions that these surgeries aim to treat often did not differ significantly and were sometimes lower or higher.

Conclusions and Relevance  In this study of almost 1.2 million children, of whom 17 460 had adenoidectomy, 11 830 tonsillectomy, and 31 377 adenotonsillectomy, surgeries were associated with increased long-term risks of respiratory, infectious, and allergic diseases. Although rigorous controls for confounding were used where such data were available, it is possible these effects could not be fully accounted for. Our results suggest it is important to consider long-term risks when making decisions to perform tonsillectomy or adenoidectomy.

Association of Age-Related Hearing Loss With Cognitive Function, Cognitive Impairment, and Dementia

A Systematic Review and Meta-analysis

David G. Loughrey, BA(Hons)1,2; Michelle E. Kelly, DPsychBAT1,3; George A. Kelley, DA4; et al Sabina Brennan, PhD1; Brian A. Lawlor, MD, FRCPI, FRCPsych1,2,5

Author Affiliations Article Information

1NEIL (Neuro Enhancement for Independent Lives) Programme, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland

2School of Medicine, Trinity College Dublin, Dublin, Ireland

3Department of Psychology, National University of Ireland Maynooth, Kildare, Ireland

4Meta-Analytic Research Group, School of Public Health, Department of Biostatistics, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown

5Mercer's Institute for Successful Ageing, St James Hospital, Dublin, Ireland

JAMA Otolaryngol Head Neck Surg. 2018;144(2):115-126. doi:10.1001/jamaoto.2017.2513

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Key Points

Question  Is age-related hearing loss associated with an increased risk for cognitive decline, cognitive impairment, and dementia?

Findings  In this systematic review and meta-analysis of 36 epidemiologic studies and 20 264 unique participants, age-related hearing loss was significantly associated with decline in all main cognitive domains and with increased risk for cognitive impairment and incident dementia. Increased risks for Alzheimer disease and vascular dementia were nonsignificant.

Meaning  Age-related hearing loss is a possible biomarker and modifiable risk factor for cognitive decline, cognitive impairment, and dementia.

Abstract

Importance  Epidemiologic research on the possible link between age-related hearing loss (ARHL) and cognitive decline and dementia has produced inconsistent results. Clarifying this association is of interest because ARHL may be a risk factor for outcomes of clinical dementia.

Objectives  To examine and estimate the association between ARHL and cognitive function, cognitive impairment, and dementia through a systematic review and meta-analysis.

Data Sources and Study Selection  A search of PubMed, the Cochrane Library, EMBASE, and SCOPUS from inception to April 15, 2016, with cross-referencing of retrieved studies and personal files for potentially eligible studies was performed. Keywords included hearing, cognition, dementia, and Alzheimer disease. Cohort and cross-sectional studies published in peer-reviewed literature and using objective outcome measures were included. Case-control studies were excluded.

Data Extraction and Synthesis  One reviewer extracted and another verified data. Both reviewers independently assessed study quality. Estimates were pooled using random-effects meta-analysis. Subgroup and meta-regression analyses of study-level characteristics were performed.

Main Outcomes and Measures  Hearing loss measured by pure-tone audiometry only and objective assessment measures of cognitive function, cognitive impairment, and dementia. Cognitive function outcomes were converted to correlation coefficients (r value); cognitive impairment and dementia outcomes, to odds ratios (ORs).

Results  Forty studies from 12 countries met our inclusion criteria. Of these, 36 unique studies with an estimated 20 264 unique participants were included in the meta-analyses. Based on the pooled maximally adjusted effect sizes using random-effects models, a small but significant association was found for ARHL within all domains of cognitive function. Among cross-sectional studies, a significant association was found for cognitive impairment (OR, 2.00; 95% CI, 1.39-2.89) and dementia (OR, 2.42; 95% CI, 1.24-4.72). Among prospective cohort studies, a significant association was found for cognitive impairment (OR, 1.22; 95% CI, 1.09-1.36) and dementia (OR, 1.28; 95% CI, 1.02-1.59) but not for Alzheimer disease (OR, 1.69; 95% CI, 0.72-4.00). In further analyses, study, demographic, audiometric, and analyses factors were associated with cognitive function. Vascular dysfunction and impaired verbal communication may contribute to the association between hearing loss and cognitive decline.

Conclusions and Relevance  Age-related hearing loss is a possible biomarker and modifiable risk factor for cognitive decline, cognitive impairment, and dementia. Additional research and randomized clinical trials are warranted to examine implications of treatment for cognition and to explore possible causal mechanisms underlying this relationship.

Association Between Hearing Aid Use and Health Care Use and Cost Among Older Adults With Hearing Loss

Elham Mahmoudi, PhD1,2; Philip Zazove, MD1,2; Michelle Meade, PhD2,3; et al Michael M. McKee, MD, MPH1,2

Author Affiliations Article Information

1Department of Family Medicine, School of Medicine, University of Michigan, Ann Arbor

2Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor

3Department of Physical Medicine & Rehabilitation, School of Medicine, University of Michigan, Ann Arbor

JAMA Otolaryngol Head Neck Surg. 2018;144(6):498-505. doi:10.1001/jamaoto.2018.0273

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Question  Is the use of hearing aids associated with the probability of hospitalizations and emergency department visits as well as health care use and spending among older people with self-reported hearing loss?

Findings  In this cohort study of nationally representative data from 1336 US Medicare beneficiaries who reported hearing loss, self-reported use of hearing aids was associated with reducing any visits to the emergency department and hospitalizations, both by means of 2 percentage points. Use of hearing aids increased the number of office visits, if any, by 1.40 days and reduced the number of nights in the hospital, if any, by 0.46 nights; hearing aids also increased total health care spending by $1125 and out-of-pocket costs by $325 but decreased Medicare spending by $71.

Meaning  This information might be useful for the Centers for Medicare & Medicaid in deciding on insurance coverage of hearing aids for older adults with hearing loss.

Abstract

Importance  Hearing loss (HL) is common among older adults and is associated with poorer health and impeded communication. Hearing aids (HAs), while helpful in addressing some of the outcomes of HL, are not covered by Medicare.

Objective  To determine whether HA use is associated with health care costs and utilization in older adults.

Design, Setting, and Participants  This retrospective cohort study used nationally representative 2013-2014 Medical Expenditure Panel Survey data to evaluate the use of HAs among 1336 adults aged 65 years or older with HL. An inverse propensity score weighting was applied to adjust for potential selection bias between older adults with and without HAs, all of whom reported having HL. The mean treatment outcomes of HA use on health care utilization and costs were estimated.

Exposures  Encounter with the US health care system.

Main Outcomes and Measures  (1) Total health care, Medicare, and out-of-pocket spending; (2) any emergency department (ED), inpatient, and office visit; and (3) number of ED visits, nights in hospital, and office visits.

Results  Of the 1336 individuals included in the study, 574 (43.0%) were women; mean (SD) age was 77 (7) years. Adults without HAs (n = 734) were less educated, had lower income, and were more likely to be from minority subpopulations. The mean treatment outcomes of using HAs per participant were (1) higher total annual health care spending by $1125 (95% CI, $1114 to $1137) and higher out-of-pocket spending by $325 (95% CI, $322 to $326) but lower Medicare spending by $71 (95% CI, −$81 to −$62); (2) lower probability of any ED visit by 2 percentage points (PPs) (24% vs 26%; 95% CI, −2% to −2%) and lower probability of any hospitalization by 2 PPs (20% vs 22%; 95% CI, −3% to −1%) but higher probability of any office visit by 4 PPs (96% vs 92%; 95% CI, 4% to 4%); and (3) 1.40 more office visits (95% CI, 1.39 to 1.41) but 0.46 (5%) fewer number of hospital nights (95% CI, −0.47 to −0.44), with no association with the number of ED visits, if any (95% CI, 0.01 to 0).

Conclusions and Relevance  This study demonstrates the beneficial outcomes of use of HAs in reducing the probability of any ED visits and any hospitalizations and in reducing the number of nights in the hospital. Although use of HAs reduced total Medicare costs, it significantly increased total and out-of-pocket health care spending. This information may have implications for Medicare regarding covering HAs for patients with HL.

Factors Associated With Phantom Odor Perception Among US Adults

Findings From the National Health and Nutrition Examination Survey

Kathleen E. Bainbridge, PhD, MPH1; Danita Byrd-Clark, BBA2; Donald Leopold, MD3

Author Affiliations Article Information

1National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland

2Social & Scientific Systems, Inc, Silver Spring, Maryland

3University of Vermont Medical Center, Burlington

JAMA Otolaryngol Head Neck Surg. 2018;144(9):807-814. doi:10.1001/jamaoto.2018.1446

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Key Points

Question  How does the prevalence of phantom odor perception vary by age, sex, socioeconomic position, health status, health behaviors, smell function, and oral and sinonasal symptoms among US adults?

Findings  In this cross-sectional study of 7417 adults, the prevalence of phantom odor perception was 6.5% (n = 534) and was greater among women, younger age groups, and those of lower socioeconomic position. Phantom odor perception was more common among those with poorer health, a history of head injury, or dry mouth symptoms.

Meaning  Epidemiologic characterization may provide clues to cause and alert clinicians to the importance of this disorder.

Abstract

Importance  Phantom odor perception can be a debilitating condition. Factors associated with phantom odor perception have not been reported using population-based epidemiologic data.

Objective  To estimate the prevalence of phantom odor perception among US adults 40 years and older and identify factors associated with this condition.

Design, Setting, and Participants  In this cross-sectional study with complex sampling design, 7417 adults 40 years and older made up a nationally representative sample from data collected in 2011 through 2014 as part of the National Health and Nutrition Examination Survey.

Exposures  Sociodemographic characteristics, cigarette and alcohol use, head injury, persistent dry mouth, smell function, and general health status.

Main Outcomes and Measures  Phantom odor perception ascertained as report of unpleasant, bad, or burning odor when no actual odor exists.

Results  Of the 7417 participants in the study, 52.8% (3862) were women, the mean (SD) age was 58 (12) years, and the prevalence of phantom odor perception occurred in 534 participants, which was 6.5% of the population (95% CI, 5.7%-7.5%). Phantom odor prevalence varied considerably by age and sex. Women 60 years and older reported phantom odors less commonly (7.5% [n = 935] and 5.5% [n = 937] among women aged 60-69 years and 70 years and older, respectively) than younger women (9.6% [n = 1028] and 10.1% [n = 962] among those aged 40-49 years and 50-59 years, respectively). The prevalence among men varied from 2.5% (n = 846) among men 70 years and older to 5.3% (n = 913) among men 60 to 69 years old. Phantom odor perception was 60% (n = 1602) to 65% (n = 2521) more likely among those with an income-to-poverty ratio of less than 3 compared with those in the highest income-to-poverty ratio group (odds ratio [OR], 1.65; 95% CI, 1.06-2.56; and OR, 1.60; 95% CI, 1.01-2.54 for income-to-poverty ratio <1.5 and 1.5-2.9, respectively). Health conditions associated with phantom odor perception included persistent dry mouth (OR, 3.03; 95% CI, 2.17-4.24) and history of head injury (OR, 1.74; 95% CI, 1.20-2.51).

Conclusions and Relevance  An age-related decline in the prevalence of phantom odor perception is observed in women but not in men. Only 11% (n = 64) of people who report phantom odor perception have discussed a taste or smell problem with a clinician. Associations of phantom odor perception with poorer health and persistent dry mouth point to medication use as a potential explanation. Prevention of serious head injuries could have the added benefit of reducing phantom odor perception.

Association of Continuous Positive Airway Pressure Treatment With Sexual Quality of Life in Patients With Sleep Apnea

Follow-up Study of a Randomized Clinical Trial

Sebastian M. Jara, MD1; Martin L. Hopp, MD, PhD2; Edward M. Weaver, MD, MPH1,3

Author Affiliations Article Information

1Department of Otolaryngology–Head and Neck Surgery, University of Washington, Seattle

2Department of Otolaryngology–Head and Neck Surgery, Cedars-Sinai Medical Center, Los Angeles, California

3Surgery Service, Department of Veterans Affairs Medical Center, Seattle, Washington

JAMA Otolaryngol Head Neck Surg. 2018;144(7):587-593. doi:10.1001/jamaoto.2018.0485

Key Points

Question  What is the association of long-term continuous positive airway pressure with sexual quality of life in patients with sleep apnea?

Findings  In a cohort study of 182 patients with sleep apnea, a significant improvement in sexual quality of life measures was observed among patients who used continuous positive airway pressure vs those who did not at long-term follow-up.

Meaning  In patients with sleep apnea, successful continuous positive airway pressure use may be associated with better improvements in sexual quality of life.

Abstract

Importance  Obstructive sleep apnea reduces sexual quality of life (QOL) as a result of reduced libido and intimacy, erectile dysfunction, and several other mechanisms. Treatment for obstructive sleep apnea may improve sexual QOL.

Objective  To test the association of long-term continuous positive airway pressure (CPAP) treatment with sexual QOL for patients with obstructive sleep apnea.

Design, Setting, and Participants  Prospective cohort study at a single, tertiary medical center of patients with newly diagnosed obstructive sleep apnea who were prescribed CPAP treatment from September 1, 2007, through June 30, 2010 (follow-up completed June 30, 2011). The statistical analysis was performed from February 1 through December 31, 2017.

Exposures  Use of CPAP treatment objectively measured by the number of hours per night. Users of CPAP were defined as patients who used CPAP treatment for more than 4 hours per night, and nonusers were defined as patients who used CPAP treatment for fewer than 0.5 hours per night.

Main Outcomes and Measures  Data were collected from eligible patients before CPAP treatment was prescribed and 12 months later by using the validated Symptoms of Nocturnal Obstruction and Related Events–25 (SNORE-25) QOL instrument. The 2 sex-specific items used to create the sexual QOL domain were taken from the SNORE-25. The sexual QOL domain was scored in a range from 0 to 5 (higher score is worse). The difference in sexual QOL between CPAP users and nonusers was analyzed using a paired, 2-tailed t test and multivariable linear regression adjusted for potential confounders.

Results  Of the 182 participants in the cohort, 115 (63.2%) were men (mean [SD] age, 47.2 [12.3] years) with severe OSA (mean [SD] apnea-hypopnea index, 32.5 [23.8] events per hour). At the 12-month follow-up, 72 CPAP users (mean [SD] use, 6.4 [1.2] hours per night) had greater improvement than 110 nonusers (0 [0] hours per night) in sexual QOL scores (0.7 [1.2] vs 0.1 [1.1]; difference, 0.54; 95% CI, 0.18-0.90; effect size, 0.47). A moderate treatment association was observed after adjustment for age, sex, race/ethnicity, marital status, income level, educational level, body mass index, apnea-hypopnea index, and the Functional Comorbidity Index (adjusted difference, 0.49; 95% CI, 0.09-0.89; effect size, 0.43). Subgroup analysis revealed a large treatment association for women (adjusted difference, 1.34; 95% CI, 0.50-2.18; effect size, 0.87) but not for men (adjusted difference, 0.16; 95% CI, −0.26 to 0.58; effect size, 0.19).

Conclusions and Relevance  Successful CPAP use may be associated with improved sexual QOL. Subgroup analysis revealed a large improvement in women but no improvement in men. Further study is warranted to test other measures of sexual QOL and other treatments.

Trial Registration  ClinicalTrials.gov Identifier: NCT00503802

Traumatic Tympanic Membrane Perforations Diagnosed in Emergency Departments

Eric T. Carniol, MD, MBA1; Amishav Bresler, MD2; Kevin Shaigany, MD3; et al Peter Svider, MD4; Soly Baredes, MD2,5; Jean Anderson Eloy, MD2,5,6,7; Yu-Lan Mary Ying, MD2

Author Affiliations Article Information

1Division of Facial Plastic and Reconstructive Surgery, Department of Otolaryngology–Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada

2Department of Otolaryngology–Head and Neck Surgery, Rutgers New Jersey Medical School, Newark

3Department of Otolaryngology–Head and Neck Surgery, University of Maryland, Baltimore

4Department of Otolaryngology–Head and Neck Surgery, Wayne State University School of Medicine, Detroit, Michigan

5Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, Rutgers New Jersey Medical School, Newark

6Department of Neurological Surgery, Rutgers New Jersey Medical School, Newark

7Department of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, Newark

JAMA Otolaryngol Head Neck Surg. 2018;144(2):136-139. doi:10.1001/jamaoto.2017.2550

Key Points

Question  What are the leading causes of traumatic tympanic membrane perforation in the United States?

Findings  In this cross-sectional analysis of 949 emergency department visits, foreign body instrumentation (including cotton-tipped applicators) was the most frequent cause of traumatic tympanic membrane perforations.

Meaning  The leading cause of traumatic tympanic membrane perforations may be preventable, and patient education may prevent this frequent cause of injury.

Abstract

Importance  Tympanic membrane perforations (TMPs) are frequent events leading to evaluation in the primary care and otolaryngology offices or the emergency department (ED). Despite specific warning labels on packaging of cotton-tipped applicators regarding the risk of injury to the ear canal with personal use, these products are commonly used to remove ear cerumen.

Objective  To analyze the mechanism of injury for traumatic TMPs among patients presenting to the ED.

Design, Setting, and Participants  Cross-sectional analysis of cases from 100 emergency departments in the United States. The National Electronic Injury Surveillance System was searched on April 3, 2015, for ear-related injuries with analysis information regarding patient age, patient sex, time and date of injury, specific injury diagnoses, and specific injury mechanisms that occurred across 5 years, from January 1, 2010, through December 31, 2014.

Main Outcomes and Measures  Diagnoses of traumatic TMP documented in the ED visit record as well as patient demographics, diagnoses, and other aspects of the injury, including mechanism of injury.

Results  There were 949 case entries in the database for traumatic TMP, which extrapolates to 4852 ED visits nationally. Of 949 patients evaluated, 568 (59.8%) were men and 381 (40.2%) were women resulting in a male to female ratio of 1.49:1. Most injuries occurred in patients 18 years or younger (602 of 949 [63.4%]) with children younger than 6 years most at risk (331 of 949 [34.9%]). Ear canal instrumentation including foreign bodies was noted in 581 of 949 cases (61.2%), with cotton-tipped applicators noted in 261 (44.9%) of these cases. While foreign body instrumentation represented the leading cause of traumatic TMP in patients aged 0 to 5 years (284 of 331 cases [85.8%]), 6 to 12 years (108 of 158 [68.4%]), 19 to 36 years (85 of 223 [38.1%]), 37 to 54 years (48 of 91 [52.7%]), and 55 years or older (22 of 33 [66.7%]), water trauma was the leading cause of TMP in patients aged 13 to 18 years (43 of 113 cases [38.1%]).

Conclusions and Relevance  Traumatic TMP represents a common reason for evaluation in the ED. Despite common warnings regarding risk of injury to the tympanic membrane with use of a cotton-tipped applicator, it is still a major cause of traumatic TMPs. Other injury mechanisms also play an important role in the teenage and young adult populations.

Association Between Portable Music Player Use and Hearing Loss Among Children of School Age in the Netherlands

Carlijn M. P. le Clercq, MD1,2; André Goedegebure, PhD1; Vincent W. V. Jaddoe, MD, PhD2,3,4; et al Hein Raat, MD, PhD, MBA2,5; Robert J. Baatenburg de Jong, PhD, MD1; Marc P. van der Schroeff, PhD, MD1,2

Author Affiliations Article Information

1Department of Otolaryngology and Head–Neck Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands

2The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands

3Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

4Department of Paediatrics, Erasmus University Medical Center–Sophia Children's Hospital, Rotterdam, the Netherlands

5Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands

JAMA Otolaryngol Head Neck Surg. 2018;144(8):668-675. doi:10.1001/jamaoto.2018.0646

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Key Points

Question  What is the prevalence of noise-induced hearing loss among children aged 9 to 11 years in the Netherlands?

Findings  In this cross-sectional, population-based study among 3316 children with normal middle-ear function, audiometry data showed the prevalence of audiometric notches and high-frequency hearing loss was 14.2%. Portable music players, used by 40.0% of the cohort, were associated with high-frequency hearing loss.

Meaning  Signs of noise-induced hearing loss may already be present in children aged 9 to 11 years old and may be associated with portable music player use prior to exposure to known noise hazards, such as club and concert attendance.

Abstract

Importance  Portable music player use may have harmful effects on hearing. The magnitude and effect of frequent music exposure, especially at younger ages, on hearing are unclear.

Objectives  To examine the prevalence of noise-induced hearing loss in a 9- to 11-year-old population and associations with portable music player use and sociodemographic factors.

Design, Setting, and Participants  A cross-sectional study within an ongoing, prospective, birth cohort study within Rotterdam, the Netherlands was conducted. Between ages 9 and 11 years, 5355 children underwent their first audiometric evaluation. Children were excluded if they had missing or failed tympanometry results. The study was conducted from April 16, 2012, to October 25, 2015.

Exposures  Portable music player (PMP) use and sociodemographic factors assessed via parental questionnaires.

Main Outcomes and Measures  Hearing acuity measured by pure-tone audiometry at 0.5 to 8 kHz. Possible noise-induced hearing loss was contingent on a high-frequency notch and/or high-frequency hearing loss in the audiogram, or reported hearing-related symptoms.

Results  The final sample included 3116 participants who were a mean (interquartile range) age of 9.7 (9.6-9.9) years and equally distributed between boys (1550 [49.7%]) and girls (1566 [50.3%]). Of these, 1244 (39.9%) reported no PMP use, 577 (18.5%) reported use 1 or 2 days per week, 254 (8.2%) reported use 3 or more days per week, and for 1041 (33.4%), PMP use was not reported. Audiometric notches and high-frequency hearing loss were present in 443 (14.2%) of all children; 140 (4.5%) fulfilled the criteria of a notch, 238 (7.6%) of high-frequency hearing loss, and 65 (2.1%) of both. Of the cohort, 52 (1.7%) showed bilateral impairment. Hearing-related symptoms were reported for 232 (11.3%) of the respondents, and 831 (40.0%) of the respondents used portable music players. Portable music player use was associated with high-frequency hearing loss (odds ratio [OR], 2.88; 95% CI, 1.36-6.980 for 1 or 2 days per week and OR, 2.74; 95% CI, 1.22-6.96 for ≥3 days per week), but listening time and duration were not. There was no association of music exposure with high-frequency notches.

Conclusions and Relevance  In this study, 14.2% of school-aged children showed audiometric notches or high-frequency hearing loss. This hearing impairment is already present prior to exposure to known noise hazards, such as club and concert attendance, and may have lifelong consequences. Repeated measurements are needed to confirm the association of portable music player use with hearing impairment in children.

Association of Gastroesophageal Reflux With Malignancy of the Upper Aerodigestive Tract in Elderly Patients

Charles A. Riley, MD1; Eric L. Wu, MS1; Mei-Chin Hsieh, PhD2; et al Michael J. Marino, MD1; Xiao-Cheng Wu, MD, MPH2; Edward D. McCoul, MD, MPH1,3,4

Author Affiliations Article Information

1Department of Otolaryngology–Head and Neck Surgery, Tulane University School of Medicine, New Orleans, Louisiana

2Louisiana Tumor Registry, School of Public Health, Louisiana State University Health Sciences Center, New Orleans

3Department of Otorhinolaryngology, Ochsner Clinic Foundation, New Orleans, Louisiana

4Ochsner Clinical School, University of Queensland School of Medicine, New Orleans, Louisiana

JAMA Otolaryngol Head Neck Surg. 2018;144(2):140-148. doi:10.1001/jamaoto.2017.2561

Key Points

Question  Is gastroesophageal reflux disease (GERD) associated with malignancy of the upper aerodigestive tract (UADT)?

Findings  A case-control study of individuals in the United States aged 66 years and older was performed with data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. GERD was associated with a greater odds of developing malignancy of the larynx, hypopharynx, oropharynx, nasopharynx, and paranasal sinuses.

Meaning  GERD is associated with the presence of malignancy of the UADT in the elderly population of the United States.

Abstract

Importance  Chronic inflammatory states have been linked to the development of malignancy. Gastroesophageal reflux disease (GERD) is a known risk factor for esophageal adenocarcinoma as the end result of chronic inflammatory changes.

Objective  To investigate the association of GERD with the risk of malignancy in the upper aerodigestive tract (UADT).

Design, Setting, and Participants  We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to conduct a case-control study of individuals in the United States who had been added from January 2003 through December 2011 and were 66 years or older. The study included patients diagnosed with malignancy of the larynx, hypopharynx, oropharynx, tonsil, nasopharynx, and paranasal sinuses. GERD was examined as an exposure. Controls were matched from a 5% random sample of Medicare beneficiaries without cancer. Multivariable unconditional logistic regression was performed.

Main Outcomes and Measures  Incidence of invasive malignancies of the UADT.

Results  A total of 13 805 patients (median [range] age, 74 [66-99] years; 3418 women [24.76%] and 10 387 men [75.24%]) with malignancy of the UADT were compared with 13 805 patients without disease and were matched for sex, age group, and year of diagnosis. GERD was associated with a greater odds of developing malignancy of the larynx (adjusted odds ratio [aOR], 2.86; 95% CI, 2.65-3.09), hypopharynx (aOR, 2.54; 95% CI 1.97-3.29), oropharynx (aOR, 2.47; 95% CI, 1.90-3.23), tonsil (aOR, 2.14; 95% CI, 1.82-2.53), nasopharynx (aOR, 2.04; 95% CI, 1.56-2.66), and paranasal sinuses (aOR, 1.40; 95% CI, 1.15-1.70).

Conclusions and Relevance  GERD is associated with the presence of malignancy of the UADT in the US elderly population. This epidemiological association requires further examination to determine causality and diagnostic utility.

Association of Tinnitus and Other Cochlear Disorders With a History of Migraines

Juen-Haur Hwang, MD, PhD1,2; Shiang-Jiun Tsai3; Tien-Chen Liu, PhD4; et al Yi-Chun Chen, MD2,5; Jen-Tsung Lai, MD6

Author Affiliations Article Information

1Department of Otolaryngology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chiayi, Taiwan

2School of Medicine, Tzu Chi University, Hualien, Taiwan

3Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chiayi, Taiwan

4Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan

5Department of Nephrology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chiayi, Taiwan

6Department of Otolaryngology, Kuang-Tien General Hospital, Shalu, Taichung, Taiwan

JAMA Otolaryngol Head Neck Surg. 2018;144(8):712-717. doi:10.1001/jamaoto.2018.0939

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Key Points

Question  Does a history of migraines increase the risk of tinnitus and other cochlear disorders?

Findings  In this cohort study of claims data among patients in Taiwan, 1056 patients with a history of migraines and 4224 controls were identified. The cumulative incidence of cochlear disorders, especially tinnitus, was found to be significantly higher among patients with history of migraines than those without a history of migraines.

Meaning  A history of migraines may increase the risk of tinnitus and other cochlear disorders.

Abstract

Importance  A headache is a symptom of a migraine, but not all patients with migraine have headaches. It is still unclear whether a migraine might increase the risk of cochlear disorders, even though a migraine does not occur concurrently with cochlear disorders.

Objective  To investigate the risk of cochlear disorders for patients with a history of migraines.

Design, Setting, and Participants  This study used claims data from the Taiwan Longitudinal Health Insurance Database 2005 to identify 1056 patients with migraines diagnosed between January 1, 1996, and December 31, 2012. A total of 4224 controls were also identified from the same database based on propensity score matching. Statistical analysis was performed from January 23, 1996, to December 28, 2012.

Main Outcomes and Measures  The incidence rate of cochlear disorders (tinnitus, sensorineural hearing impairment, and/or sudden deafness) was compared between the cohorts by use of the Kaplan-Meier method. The Cox proportional hazards regression model was also used to examine the association of cochlear disorders with migraines.

Results  Of the 1056 patients with migraines, 672 were women and 384 were men, and the mean (SD) age was 36.7 (15.3) years. Compared with the nonmigraine cohort, the crude hazard ratio for cochlear disorders in the migraine cohort was 2.83 (95% CI, 2.01-3.99), and the adjusted hazard ratio was 2.71 (95% CI, 1.86-3.93). The incidence rates of cochlear disorders were 81.4 (95% CI, 81.1-81.8) per 1 million person-years for the migraine cohort and 29.4 (95% CI, 29.2-29.7) per 1 million person-years for the nonmigraine cohort. The cumulative incidence of cochlear disorders in the migraine cohort (12.2%) was significantly higher than that in the matched nonmigraine cohort (5.5%). Subgroup analysis showed that, compared with the nonmigraine cohort, the adjusted hazard ratios in the migraine cohort were 3.30 (95% CI, 2.17-5.00) for tinnitus, 1.03 (95% CI, 0.17-6.41) for sensorineural hearing impairment, and 1.22 (95% CI, 0.53-2.83) for sudden deafness.

Conclusions and Relevance  In this population-based study, the risk of cochlear disorders, especially for tinnitus, was found to be significantly higher among patients with a history of migraines. This finding may support the presence and/or concept of "cochlear migraine."

Incidence of Thyroid Cancer Among Children and Young Adults in Fukushima, Japan, Screened With 2 Rounds of Ultrasonography Within 5 Years of the 2011 Fukushima Daiichi Nuclear Power Station Accident

Akira Ohtsuru, MD1,2; Sanae Midorikawa, MD1,2; Tetsuya Ohira, MD2,3; et al Satoru Suzuki, MD2; Hideto Takahashi, PhD2; Michio Murakami, PhD2,4; Hiroki Shimura, MD2,5; Takashi Matsuzuka, MD2,6; Seiji Yasumura, MD2,7; Shin-ichi Suzuki, MD8; Susumu Yokoya, MD9; Yuko Hashimoto, MD10; Akira Sakai, MD2,11; Hitoshi Ohto, MD2; Shunichi Yamashita, MD2,12; Koichi Tanigawa, MD2; Kenji Kamiya, MD2,13

Author Affiliations Article Information

1Department of Radiation Health Management, Fukushima Medical University, Fukushima, Japan

2Radiation Medical Science Center for the Fukushima Health Management Survey, Fukushima Medical University, Fukushima, Japan

3Department of Epidemiology, Fukushima Medical University, Fukushima, Japan

4Department of Health Risk Communication, Fukushima Medical University, Fukushima, Japan

5Department of Laboratory Medicine, Fukushima Medical University, Fukushima, Japan

6Department of Otolaryngology, Fukushima Medical University, Fukushima, Japan

7Department of Public Health, Fukushima Medical University, Fukushima, Japan

8Department of Thyroid and Endocrinology, Fukushima Medical University, Fukushima, Japan

9Thyroid and Endocrine Center, Fukushima Medical University, Fukushima, Japan

10Department of Pathology, Fukushima Medical University, Fukushima, Japan

11Department of Radiation Life Sciences, Fukushima Medical University, Fukushima, Japan

12Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan

13Research Institute of Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

JAMA Otolaryngol Head Neck Surg. Published online November 29, 2018. doi:10.1001/jamaoto.2018.3121

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Comment

Key Points

Question  What is the pattern by age group of cancer detection via ultrasonographic screening of the thyroid among children and young adults within 5 years of the 2011 Fukushima Daiichi nuclear power station accident?

Findings  In this cohort study of 324 301 children and young adults, thyroid cancer was diagnosed in 187 individuals within 5 years when health effects of radiation were hardly conceivable. The distribution pattern of the incidence rate by age group in second-round examinations increased with older age.

Meaning  Large-scale mass screening resulted in the diagnosis of many thyroid cancers even in young age; to avoid overdiagnosis, an improvement in screening strategy based on the understanding of the natural history of thyroid cancer will be urgently needed.

Abstract

Importance  Ultrasonographic (US) screening for thyroid cancer was performed in the Fukushima Health Management Survey after the 2011 Fukushima Daiichi nuclear power station accident. Clinical characteristics of thyroid cancers screened by US among children and young adults during the first 5 years after the accident were analyzed.

Objectives  To evaluate the number of detected thyroid cancers by age group within 5 years of the Fukushima Daiichi nuclear power station accident and to compare the basic clinical characteristics and demographic patterns in first- and second-round examinations.

Design, Setting, and Participants  In this observational study, 324 301 individuals 18 years or younger at the time of accident were included. Patients received a cytologic diagnosis of malignant or suspected malignant thyroid cancer during the first (fiscal years 2011-2013) or second round (fiscal years 2014-2015) of screening. Number of detected cases of cancer was evaluated, correcting for the number of examinees by age group at the time of the accident and for the incidence of detected cancers according to age group at the time of the screening (age groups were divided into 3-year intervals). Results were compared using the age-specific incidence of unscreened cancers from a national cancer registry.

Main Outcomes and Measures  Clinical baseline characteristics of the patients and the age-specific number and incidence of thyroid cancers detected during the second round.

Results  Among 299 905 individuals screened in the first round (50.5% male; mean [SD] age at screening, 14.9 [2.6] years), malignant or suspected thyroid cancer was diagnosed in 116. Among 271 083 individuals screened in the second round (50.4% male; age at screening, 12.6 [3.2] years), malignant or suspected thyroid cancer was diagnosed in 71. The most common pathologic diagnosis in surgical cases was papillary thyroid cancer (149 of 152 [98.0%]). The distribution pattern by age group at the time of the accident, where the number of detected thyroid cancer cases was corrected by the number of examinees, increased with older age in both screening rounds. This demographic pattern was similar between the first and second examinations. The distribution pattern of the incidence rate by age group at the time of screening in the second round also increased with older age. The incidence rate detected by screening was 29 cases per 100 000 person-years for those aged 15 to 17 years, 48 cases per 100 000 person-years for those aged 18 to 20 years, and 64 cases per 100 000 person-years for those aged 21 to 22 years.

Conclusions and Relevance  Large-scale mass US screening of young people resulted in the diagnosis of a number of thyroid cancers, with no major changes in overall characteristics within 5 years of the 2011 Fukushima nuclear power station accident. These results suggest that US screening can identify many detectable cancers from a large pool of nonclinical and subclinical thyroid cancers among individuals of a relatively young age, in an age-dependent manner.

Dermatology Venereology Leprology

Cosmetic dermatology: An integral part of current dermatology curriculum Jasleen Kaur Sandhu Indian Journal of Dermatology, Venereology, and Leprology 2019 85(1):1-2

Methods to overcome poor responses and challenges of laser hair removal in dark skin Shehnaz Zulfikar Arsiwala, Imran M Majid Indian Journal of Dermatology, Venereology, and Leprology 2019 85(1):3-9 Conventional and advance technologies are available for laser hair removal. Complete and permanent hair reduction is not yet possible by treatment with lasers. Ideal patient for any conventional laser hair removal treatment is one who has thick, dark terminal hair, light skin and normal hormonal status. Factors that contribute to variable outcomes in laser hair removal can be broadly divided into patient related ones and the technology related ones. Skin type, hair color, thickness and density, degree of tan, hormonal dysfunction etc., constitute the patient related factors. The wavelength, fluence, spot size and pulse duration of the laser system are the technology related factors. There are some patients who respond variably, unpredictably or poorly to laser hair removal despite ensuring that indication for treatment is appropriate with adequate parameters of the laser system. This article reviews various patient related and technology related factors which lead to variable-to-poor outcomes in laser hair removal; and various challenges and limitations of laser hair removal technology in patients with dark skin types.

Optimizing Q-switched lasers for melasma and acquired dermal melanoses Sanjeev Jayanth Aurangabadkar Indian Journal of Dermatology, Venereology, and Leprology 2019 85(1):10-17 The Q-switched Nd:YAG laser is an established modality of treatment for epidermal and dermal pigmented lesions. The dual wavelengths of 1064nm and 532nm are suited for the darker skin tones encountered in India. Though this laser has become the one of choice for conditions such as nevus of Ota, Hori's nevus and tattoos, its role in the management of melasma and other acquired dermal melanoses is not clear. Despite several studies having been done on the Q-switched Nd:YAG laser in melasma, there is no consensus on the protocol or number of sessions required. Acquired dermal melanoses are heterogenous entities with the common features of pigment incontinence and dermal melanophages resulting in greyish macular hyperpigmentation. This article reviews the current literature on laser toning in melasma and the role of the Q-switched Nd:YAG laser in stubborn pigmentary disorders such as lichen planus pigmentosus. As the pathology is primarily dermal or mixed epidermal-dermal in these conditions, the longer wavelength of 1064nm is preferred due to its deeper penetration. Generally multiple sessions are needed for successful outcomes. Low fluence Q-switched Nd:YAG laser at 1064nm utilizing the multi-pass technique with a large spot size has been suggested as a modality to treat melasma. Varying degrees of success have been reported but recurrences are common on discontinuing laser therapy. Adverse effects such as mottled hypopigmentation have been reported following laser toning; these can be minimized by using larger spot sizes of 8 to 10mm with longer intervals (2 weeks) between sessions.

Isotretinoin and dermatosurgical procedures Venkataram Mysore, HM Omprakash, Gayatri Nagindas Khatri Indian Journal of Dermatology, Venereology, and Leprology 2019 85(1):18-23 Several early reports suggested that performance of dermatosurgical procedures in patients on oral isotretinoin is associated with abnormal skin healing, keloid or hypertrophic scar formation. However, this association has been recently questioned in some studies. This review examines this issue, analyzes the studies published and concludes that the recommendation made earlier about the need to avoid dermatosurgical procedures in patients on isotretinoin is based on inadequate and insufficient evidence and hence needs revision. The review also suggests that recent studies on the subject establish that performing such procedures is safe.

Complications of laser and light-based devices therapy in patients with skin of color BS Chandrashekar, Chaithra Shenoy, C Madura Indian Journal of Dermatology, Venereology, and Leprology 2019 85(1):24-31 Lasers and light-based devices are indispensable to an aesthetic dermatology practice. The growing popularity of lasers has been matched by a sharp increase in the incidence of complications. The Indian skin with its high melanin content is more prone to injury and careful setting of laser parameters, early detection of complications and immediate therapy are vital to avoiding permanent sequelae. We review the various complications that occur during laser procedures and their management.

Autologous noncultured melanocyte-keratinocyte transplantation in stable vitiligo: A randomized comparative study of recipient site preparation by two techniques Sumit Gupta, Vineet Relhan, Vijay Kumar Garg, Bijaylaxmi Sahoo Indian Journal of Dermatology, Venereology, and Leprology 2019 85(1):32-38 Background: Accurate preparation of recipient area is a critical step in melanocyte-keratinocyte transplantation procedure for vitiligo. It is an important potential step for adaptation in the quest to achieve better results and ablative lasers potentially offer excellent precision over margin and depth control in achieving that. Objective: To compare between the two techniques used for recipient site preparation: Er:YAG laser ablation and mechanical dermabrasion for melanocyte-keratinocyte transplantation procedure in terms of re-pigmentation achieved and adverse effects seen. Methods: A randomized comparative trial was performed among 32 patients of stable vitiligo undergoing melanocyte-keratinocyte transplantation procedure. In Group A (n = 15), recipient site preparation was done with Er:YAG laser, and in Group B (n = 17), it was done with a motorized dermabrader. Patients of both groups were objectively assessed for re-pigmentation at 1, 3 and 6 months. Results: A total of 253.696 cm2 of depigmented surface was operated upon and re-pigmentation of 125.359 cm2 (49.4%) was achieved. On comparison between two groups, no statistical difference was found with respect to total re-pigmentation achieved (Group A: 54.67% vs Group B: 48.841%, P = 0.663) and grades of re-pigmentation achieved (P = 0.796). Occurrence of adverse events was also statistically similar in both the groups. Conclusion: This study did not reveal any statistically different outcome (in terms of re-pigmentation and adverse effects) between the two methods of recipient site preparation – motorized dermabrasion and Er:YAG ablation. Limitations: This study is small and larger studies are needed to ascertain the benefit of Er:YAG for recipient site preparation. Future studies may also ascertain variables such as time taken to prepare the recipient area, nature of bleeding, postoperative healing, difficulties in specific area, cost of the procedure, patient comfort and ease of the surgeon, rather than comparing the re-pigmentation alone.

A randomized, open-label, comparative study of oral tranexamic acid and tranexamic acid microinjections in patients with melasma Vinod K Khurana, Rachita R Misri, Swati Agarwal, Akhilesh V Thole, Sachin Kumar, Tanu Anand Indian Journal of Dermatology, Venereology, and Leprology 2019 85(1):39-43 Background: Melasma poses a great challenge as its treatment modalities are unsatisfactory. Treatment using tranexamic acid is a novel concept. Aim: This study aimed to compare the therapeutic efficacy and safety of oral tranexamic acid and tranexamic acid microinjections in patients with melasma. Methods: This is a prospective, randomized, open-label study with a sample size of 64, 32 in each treatment arm. Thirty-two patients were administered localized microinjections (4 mg/ml) of tranexamic acid monthly in 1 arm, while in the other arm, 32 were given oral tranexamic acid 250 mg twice a day. Patients were followed up for 3 consecutive months. Clinical photographs were taken at each visit, and a modified melasma area and severity index scoring was performed at the beginning and end of treatment. Results: Improvement in melasma area and severity index score in the oral group was 57.5% as compared to 43.5% in the intralesional group. All 32 patients in the oral group (100%) showed >50% improvement, out of which 8 showed >75% improvement. In the intralesional group, 17 (53%) patients had >50% improvement, of which 3 had >75% improvement. The remaining 15 patients in this group had <50% improvement. Thus, the oral group showed a more significant response as compared to the intralesional group. No major adverse effects were observed in both the groups. At 6-month follow-up, two patients (6.2%) in the oral group had recurrence as compared to three patients (9.4%) in the intralesional group. Limitations: A small sample size was one of the limitations in this study. The dose of tranexamic acid in microinjections and the frequency of injections could have been increased. Conclusion: Tranexamic acid provides rapid and sustained improvement in the treatment of melasma. It is easily available and affordable. Oral route is undoubtedly efficacious, but the results of microinjections, while encouraging, can probably be enhanced by either increasing the frequency of injections or increasing the concentration of the preparation.

Safety and efficacy of autologous noncultured dermal cell suspension transplantation in the treatment of localized facial volume loss: A pilot study Alok Kumar Sahoo, Savita Yadav, Vinod K Sharma, Anita Singh Parihar, Surabhi Vyas, Somesh Gupta Indian Journal of Dermatology, Venereology, and Leprology 2019 85(1):44-50 Background: Available options for correction of facial volume loss, such as synthetic fillers, autologous fat and cultured fibroblasts, have limitations viz. temporary effect and high cost. Aim: To assess the use of a novel technique, autologous non-cultured dermal cell suspension transplantation, for correction of localized facial volume loss due to inflammatory pathologies. Methods: It was a pilot study conducted in the Dermatology Outpatient Department, All India Institute of Medical Sciences (AIIMS), New Delhi, India. Autologous non-cultured dermal cell suspension was transplanted in a total of 10 patients, out of which 5 had predominantly dermal loss and the rest had predominantly lipoatrophy. The donor tissue from the gluteal region was digested into a single cell suspension using collagenase-1 and injected into the recipient area. The outcome was assessed subjectively by patients and investigators and objectively using ultrasonography. Cell count, viability testing and measurement of mesenchymal stem cells were also done. Results: On assessment of patients, the median improvement in the predominantly dermal atrophy group at 3 and 6 months was 70% (range: 10–90%) and 80% (range: 0–90%), respectively, and in the predominantly lipoatrophy group, 0% (range: 0–40) and 0% (range: 0–50), respectively. Mean thickness of dermis + subcutis at the baseline was 1.835 mm (range: 0.89–6.04 mm), which increased to 2.912 mm (range: 0.88–7.07 mm, P = 0.03) at 6 months. Limitations: Our pilot study has some limitations such as small sample size and heterogeneity of the recruited patients. Conclusions: Autologous non-cultured dermal cell suspension transplantation appears to be safe and effective in localized facial dermal defects because of inflammatory pathologies, but not effective in deeper defects.

Toenail concentrations of zinc, selenium and nickel in patients with chronic recurrent warts: A pilot two-group comparative study Mohamed El-Komy, Vanessa Hafez, Rania Abdel Hay, Dina Mehaney, Iman Hafez Indian Journal of Dermatology, Venereology, and Leprology 2019 85(1):51-55 Background: Normal immune functioning requires sufficient levels of trace elements including zinc and selenium, while elements such as nickel can be immunotoxic. Aim: To assess long-term abnormalities in zinc, selenium and nickel levels in patients with chronic recurrent warts. Methods: Toenail samples were taken from 28 patients with chronic recurrent warts and 30 apparently healthy matching controls were analysed. Toenail concentrations of zinc, selenium and nickel were measured using inductively-coupled plasma-optical emission spectroscopy. Results: Selenium levels were significantly higher in patients than in controls (P = 0.03). Levels of trace elements did not correlate with the number or duration of warts. Toenail nickel levels in all subjects were higher than globally reported values. Limitations: A small sample size and the absence of regional reference ranges for concentrations of trace elements in toenails. Conclusion: Zinc does not seem to be involved in the chronicity of warts, and it is unclear if selenium has a protective role against warts. Our finding of high concentrations of nickel in both patients and controls raises concerns about environmental exposure.

Successful treatment of metastatic extramammary Paget's disease with pemetrexed monotherapy systemically and 5-fluorouracil topically Kexu Chen, Hanlin Liang, Jiewen Peng, Yanfang Zheng Indian Journal of Dermatology, Venereology, and Leprology 2019 85(1):56-59 Advanced extramammary Paget's disease does not have a standardized treatment guideline as its incidence is low and has been rarely reported in literature. Here we describe a case of metastatic extramammary Paget's disease successfully treated with topical 5-fluorouracil (5-FU) and systemic pemetrexed. The therapy was safe without any appreciable adverse effects like diarrhea, rash, neutropenia or fatigue; maintaining remission for more than 6 months. Thus, we propose 5-FU and pemetrexed as the first-line therapy for advanced extramammary Paget's disease, especially for aged patients with unresectable skin lesions.

Medical Research

'Infectobesity' in egyptian adolescent women and its relations to carotid intima–media thickness Sahar A El-Masry, Hanan A El Gamal, Muhammad Al-Tohamy, Ayman Nada, Amany H Abdelrahman, Mohamed Kh. Metkees, Amany Ebrahim, Walaa Saad Journal of The Arab Society for Medical Research 2018 13(2):79-88 Background ‘Infectobesity’ is a new term to describe obesity of infectious origin, such as infection by human adenovirus-36 (Adv36). It appears to be a new concept, evolved over the past 20 years. Visceral obesity is associated with a higher risk of cardiovascular disease. Increased carotid intima–media thickness (CIMT), a marker of early-onset atherosclerosis, has been observed in obese children and adolescents. The present study aims to investigate the relationship between visceral obesity, CIMT, and Adv36 in female Egyptian adolescents. Patients and methods The present study included 90 women aged 12–15 years. It was conducted at the Medical Excellence Research Center of the National Research Centre, Cairo, Egypt, during the period between September 2016 and November 2017. Anthropometric assessment was done. Fasting blood samples were withdrawn for the measurement of Qualitative Human Adv36 antibody using a sandwich enzyme-linked immunosorbent assay. Fasting plasma glucose was determined calorimetrically, by the glucose oxidase method and insulin level using the solid-phase enzyme-linked immunosorbent assay and lipid profile. Visceral obesity was measured by an abdominal ultrasound. CIMT for both carotid arteries were measured by high-resolution echo Doppler. Results Girls with visceral obesity (n=26) had higher frequency of increased CIMT at left (96.2 vs. 75%), right carotid artery (84.6 vs. 73.4%) and Adv36 sero-positive antibody (69.2 vs. 56.2%) than among those without visceral obesity (n=64). Among the total samples, visceral obesity had significant positive correlations with BMI, waist and hip circumference, while it had insignificant correlations with age, blood pressure (BP), CIMT at right and left carotid arteries, adenovirus and laboratory findings. CIMT had a significant positive correlation with each other, insulin resistance and total cholesterol, and significant negative correlations with high-density lipoprotein and waist circumference. Adv36 had significant negative correlations with BP (both systolic and diastolic) and significant positive correlation with insulin level. Adv36 and CIMT had insignificant correlations with each other and with the anthropometric measurements, BP, visceral obesity, triglycerides, and low density lipoprotein. Conclusion The frequency of Adv36 and increased CIMT at left carotid artery were higher among girls with visceral obesity than among those without visceral obesity. However, visceral obesity, CIMT at both right and left carotid arteries, and Adv36 had insignificant correlations with each other.

Inhibitory effect of bee venom against potassium bromate causing genetic toxicity and biochemical alterations in mice Abeer H Abd El-Rahim, Omaima M Abd-El-Moneim, Heba A.M. Abd El-Kader, Amira Abd El Raouf Journal of The Arab Society for Medical Research 2018 13(2):89-98 Background/aim Bee venom (BV) therapy is a highly effective treatment, capable of improving one’s health. The present study attempts to assess the effect of BV on the toxicity of oral administration of potassium bromate (KBrO3) which has been widely used in food and cosmetic industries. Materials and methods Sixty adult male mice were gavaged with KBrO3 at two doses (100 and 200 mg/kg body weight) for 10 days. Afterwards, BV at a dose of 120 μg/kg body weight was injected subcutaneously three times per week for two successive weeks. The genetic study was performed using chromosomal aberration and micronucleus formation in the bone marrow, DNA fragmentation in liver cells and by sperm analysis. In addition, serum biochemical markers such as catalase and malondialdehyde, kidney, and liver functions were assessed. Results The results have shown that KBrO3 caused DNA damage that represented the increase in the frequencies of chromosome abnormalities, micronuclei formation, percentage of DNA fragmentation, and sperm morphological abnormalities. Meanwhile, the results showed that KBrO3 exhibited severe toxicity for antioxidant activities for liver and kidney functions. Conversely, BV significantly decreased the frequencies of DNA damage in all aforementioned parameters induced by KBrO3. In addition, it improved the antioxidant activities and the function of the liver and kidneys. Conclusion BV has a potent ameliorating effect against the KBrO3 hazard impacts in animal tissues especially at higher doses. This observation indicated that BV could be a potential therapeutic agent in the treatment of KBrO3 risk.

Impact of nano-TiO2 particles on water sorption and solubility in different denture base materials Wessam M Dehis, Sherihan M Eissa, Ayman F Elawady, Menatallah M Elhotaby Journal of The Arab Society for Medical Research 2018 13(2):99-105 Background/aim Denture base materials with all their diversities and the curing method have a massive impact on their physical, mechanical, and biological traits. This contemplate is aimed to both assess and relate water sorption and solubility of heat-cured and microwave-cured acrylic resin denture base materials with and without the addition of titanium oxide nanoparticles (TiO2 NPs). Materials and methods A total number of 80 circular specimens were fabricated for the two tested groups (n=40). Group I was divided into two subgroups: group IA and group IB (20 each) fabricated from heat-cured and microwave-cured acrylic resin, respectively. Another group (group II) was divided into two subgroups: group IIA and group IIB (20 each) as in group I with the addition of TiO2 NPs. Then, the degree of water sorption and water solubility was calibrated by using an electronic balance for all specimens and determined by the aid of a specific formula. Results The present results indicated that there is a significant difference between all groups using one-way analysis of variance test as the P value was less than 0.05. Moreover, Tukey’s post-hoc test was performed and revealed that there was a significant difference between all subgroups except (group IIA and group IIB) in which there was an insignificant difference regarding water sorption and water solubility. Conclusion Within the limitation of this consideration, microwave-cured acrylic resin is superior to the heat-cured one regarding both water sorption and solubility. Moreover, the addition of TiO2 NPs revealed the best outcome.

Clinical efficacy of nicotine replacement therapy in the treatment of minor recurrent aphthous stomatitis Mai Zakaria, Aliaa El-Meshad Journal of The Arab Society for Medical Research 2018 13(2):106-112 Background/aim Recurrent aphthous stomatitis (RAS) is a common and widely recognized disease involving the oral mucous membrane. Nicotine replacement therapy (NRT) is a dose-dependent safe method for encountering useful effects of nicotine. This study aimed to evaluate the clinical efficacy of NRT in the treatment of minor RAS. Materials and methods A total of 50 patients from Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University, with active minor RAS lasting for less than 48 h were randomly allocated into two groups (25 each): placebo and nicotine groups. They were treated with placebo and 2-mg nicotine chewing gum, correspondingly, twice daily for 2 weeks. All participants were assessed for pain, erythema, and ulcer size sores at 4 and 6 days from baseline. Frequency of recurrence was evaluated at 1-month, 2-month, and 3-month intervals. Results Regarding pain and erythema scores, the nicotine group showed lower mean with significant difference after 6 days in comparison with the placebo group. A lower mean of ulcer size was recorded in the nicotine group, with a significant difference after 4 and 6 days. A lower mean of recurrence score was recorded in nicotine group, with nonsignificant difference compared with the placebo group. Conclusion Low-dosage NRT in the form of chewing gum may be considered as an innovative and safe alternate treatment modality for minor RAS.

Androgen receptor expression in hormone-negative breast cancers and its prognostic significance Dalia M Abouelfadl, Hebat Allah A Amin, Noha N Yassen, Marwa E Shabana, Amir M.H. Salem Journal of The Arab Society for Medical Research 2018 13(2):113-118 Background/aim Breast carcinoma is a common, yet heterogeneous aggressive disease affecting relatively young patients. The androgen receptor (AR) is expressed in majority of breast cancers and across the main breast cancer subtypes. The aim of this study was to evaluate AR expression in hormone-negative breast cancer subtypes. Materials and methods Sixty cases of breast cancer were involved in this study; the samples were received in the Department of Pathology of Kasr El-Aini Hospital, Cairo University, Egypt. The expression of AR and human epidermal growth factor receptor-2 receptors were studied by immunohistochemistry in 60 formalin-fixed paraffin-embedded selected hormone-negative breast cancer surgical specimens. The immunohistochemistry expression of the marker was correlated with the clinicopathological variables. Results Of the hormone-negative cases, 61.6% show positive AR expression, 89% of which are invasive duct carcinoma, 68.3% are associated with ductal carcinoma in situ, and 55% are human epidermal growth factor receptor-2-enriched subtype. A significant correlation was found between the AR expression and tumor type. There is no evident significant correlation with tumor grade, multicentricity or lymphovascular invasion. Conclusion The AR has recently emerged as a useful marker for the further refinement of breast cancer subtype classification. Antiandrogens are thought to markedly enhance treatments and to be the first targeted therapy in hormone-negative breast cancer cases.

Morphometric analysis and immunohistochemical expression of cytochrome C oxidase in colonic adenomas and adenocarcinomas Noha N Yassen, Dalia M Abouelfadl, Amina A Gamal elDin Journal of The Arab Society for Medical Research 2018 13(2):119-128 Background/aim Colorectal cancer is the seventh most common cancer in Egypt, constituting 3.47% of male cancers and 3% of female cancers. The aim of the current study is to evaluate the immunohistochemical expression of cytochrome C oxidase (CcO) as well as the nuclear morphometric measurements in colonic adenomas and adenocarcinomas. Materials and methods Sixty cases of colonic biopsies/specimens were involved in this study. The samples were received in the Department of Pathology of Kasr El-Aini Hospital, Cairo University, Egypt, and they were divided into three groups: 20 cases of normal control, 20 cases of colonic adenoma, and 20 cases of colonic adenocarcinoma. The expression of CcO was studied by immunohistochemistry in 60 formalin-fixed paraffin blocks. Nuclear morphometric parameters were evaluated using an image analysis system. The area percentage of the marker expression was correlated with nuclear morphometric parameters. Results Immunohistochemical study showed that 65% of control biopsies showed a significant difference with colonic adenocarcinoma cases in contrast and adenoma cases showed a nonsignificant difference with normal control biopsies. Mean areas percentages of CcO expression were significantly different between all three studied groups. The means of nuclear area, length, and perimeter showed a significant difference while means nuclear width and roundness showed a nonsignificant difference between all three studied groups. There was significant correlation between mean area percentage of CcO expression with mean nuclear area and perimeter in control, adenoma, and adenocarcinoma cases. Conclusion CcO protein is significantly expressed in the cytoplasm of normal colonic mucosa. It was significantly deficient in colonic adenocarcinoma. Nuclear morphometry can be introduced as a useful morphologic feature of patients with variable colonic lesions specially in combination with CcO.

The antifibrotic effect of Zilla spinosa extracts targeting apoptosis in CCl4-induced liver damage in rats Enayat A Omara, Sayed A El-Toumy, Marwa E Shabana, Abdel-Razik H Farrag, Somaia A Nada, Nermeen Shafee Journal of The Arab Society for Medical Research 2018 13(2):129-143 Background/aim Liver fibrosis and its end-stage cirrhosis are the main reasons of morbidity and mortality all over the world. The current study aimed to evaluate the efficacy of Zilla spinosa (Z. spinosa) on CCl4-induced liver fibrosis, apoptosis, and oxidative stresses in rats. Materials and methods Extract of aerial part of Z. spinosa was used in this study. Thirty male Sprague‑Dawley rats were enrolled in this study and divided into five groups (six each): group 1 served as control and groups 2–5 were treated with CCl4 (1 ml/kg intraperitoneal twice a week for 8 weeks), where group 2 served as a control positive, group 3 received silymarin (50 mg/kg) daily, and groups 4 and 5 were administrated with Z. spinosa (100 and 200 mg/kg, respectively) daily for 8 weeks. At the end of each experiment, liver function tests were analyzed in serum, whereas malondialdehyde (MDA), Nitric oxide (NO), Glutathione (GSH), and hydroxyproline (HA) were analyzed in liver tissues. Liver fibrosis was confirmed histopathologically, and collagen content, caspase-3, and α-smooth muscle actin (α-SMA) were assayed immunhistochemically. Results Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, MDA, NO, and HA levels were increased (P<0.05), whereas total protein and GSH were decreased (P<0.05) in CCl4-administrated rats. Histopathological results showed loss of lobular structure, fibrosis with expansion of portal tract by fibrous tissue together with inflammatory changes confined to portal tract and central vein, and intense centrilobular necrosis and remarkable fatty hydropic degeneration. In addition, extensive accumulation of connective tissue, marked depletion of glycogen, strong expression of α-SMA, and increased of caspase-3 were found in CCl4-administrated rats. Oral administration of Z. spinosa at 100 or 200 mg/kg restored the normal levels of liver function parameters, MDA, NO and GSH; decreased HA; and reduced collagen, glycogen content, caspase-3, and α-SMA in liver tissue of rats. The high dose of 200 mg/kg showed more potent effect than low dose of 100 mg/kg when compared with silymarin treatment group. Conclusion The present study clarified that Z. spinosa extract has antioxidant and antiapoptotic properties in CCl4-induced liver fibrosis in rats, and may be able to exert a therapeutic effect on developing hepatic fibrosis; moreover, high dose of 200 mg/kg appeared to be more potent than low dose (100 mg/kg).

Image analysis and Ki-67 expression in urothelial dysplasia and carcinoma Manal A Badawi, Sonia L El-Sharkawy, Naglaa F Abbas, Wafaa E Abdel-Aal Journal of The Arab Society for Medical Research 2018 13(2):144-150 Background/aim Cancer of the urinary bladder is a worldwide disease in which transitional cell carcinoma is the most common histologic type. The diagnosis of dysplasia is particularly important, as it is the precursor of invasive carcinoma. The present study aimed to investigate the role of image analysis together with Ki-67 immunostaining in bladder dysplasia and invasive urothelial carcinoma. Materials and methods This study was carried out in 80 urinary bladder paraffin blocks that were selected from the Department of Pathology of Kasr El-Aini Hospital, Cairo University, Egypt. The studied cases were divided into four groups: six cases of normal bladder mucosa, 12 cases of chronic cystitis, 18 cases of epithelial dysplasia, and 44 cases with transitional cell carcinoma. Morphometric analysis and Ki-67 expression were studied in all cases using an image analysis system. Results All morphometric parameters, DNA index, and proliferating cells’ percent and Ki-67 index were increasing from normal, chronic cystitis, dysplasia to carcinoma cases. However, nuclear area, length, size, and epithelial stromal ratio showed significant differences between dysplasia and carcinoma cases (P<0.05). High-grade carcinoma showed significant enlargement of nuclear area and size, as compared with low-grade carcinoma. DNA index and proliferating cells’ % showed a significant difference between dysplasia and carcinoma cases. Both parameters were significantly higher in high-grade carcinoma. Normal bladder and chronic cystitis cases exhibited negative stain for Ki-67. However, all cases of dysplasia and carcinoma exhibited a positive stain for Ki-67. The carcinoma cases showed a significantly higher Ki-67 index (68%) than the dysplastic cases (34%). Conclusion The present study revealed the usefulness of image analysis together with Ki-67 expression in discriminating cases of bladder dysplasia and carcinoma.