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Context: Toxicity from radiation therapy for laryngeal squamous cell carcinoma includes dysphagia, mucositis, laryngeal edema, weight loss and pain. Hypofractionation (HF) regimens shorten the overall treatment time to lower the risk for accelerated repopulation of tumor cells following initiation of radiotherapy (RT) demonstrated improved overall survival and locoregional control. Objective: To examine the early toxicity of HF to the larynx, compared with standard fractionated (SF) RT. Methods: Retrospective analysis of 127 laryngeal SCC patients who were treated with RT; Early glottic cancer (50%) received hypofractionation (2.25Gy/fr, 63Gy) only to the glottis while advanced stage disease (50%) received standard fractionation (2Gy/fr, 70Gy) to the glottis and to bilateral neck, with or without concurrent chemotherapy (CRT). Results: Patients in HF group consumed significantly higher dosages of both Fentanyl (15 mg versus 8 mg) and Oxycodone (2.9 mg versus 2.1) due to increased pain and discomfort (PConclusions: HF-treated patients tend to consume significantly higher doses of opioids than patients treated with SF, representing higher levels of pain. Treatment regimens for patients undergoing HF should include proper pain management, and when possible, steroids.

Introduction Unilateral vocal cord paralysis (UVCP) is a known complication of thyroid surgery, due to iatrogenic recurrent laryngeal nerve injury, with reported rates of 2%–5% in children. The gold standard for assessing vocal cord function in flexible nasendoscopy (FNE) examination, which is considered high‐risk for contraction of the COVID‐19 virus. Intraoperative ultrasonographic assessment (IUA) of vocal cord function is a non‐invasive and relatively simple procedure performed in a supine position, performed during spontaneous breathing, following reversed anaesthesia, while the patient is still sedated. Objectives To evaluate the validity of IUA modality in children undergoing thyroidectomy and to compare it to the standard FNE. Design A prospective double‐blind study covering 24 months (March 2019–March 2021). Twenty thyroid lobectomies were performed, during 15 surgeries. Vocal cord function was assessed three times: Pre‐operatively by FNE, intraoperative (IUA) following extubation, and a second FNE on the first post‐operative day. Settings A tertiary paediatric hospital. Results The overall accuracy of IUA results in our study was 92%. IUA sensitivity, specificity, positive and negative predictive values were 100%, 89%, 33% and 100%, respectively. Patient's age demonstrated borderline significance (p = .08). The resident's experience was associated with a better correlation between IUA and FNE results (p

Background Binaural hearing is of utmost importance for communicating in noisy surroundings and localizing the direction of sound. Unilateral hearing loss (UHL) affects the quality of life in both childhood and adulthood, speech development, and academic achievements. Sound amplification using air-conducting hearing aids (HAs) is a common option for hearing rehabilitation of UHL. The processing time of digital HAs can significantly delay the acoustic stimulation in 3 to 10 milliseconds, which is far longer than the maximal natural interaural time difference (ITD) of 750 microseconds. This can further impair spatial localization in these patients. Purpose We sought to assess whether HA effects on ITD and interaural level difference (ILD) impair localization among subjects with unilateral conductive hearing loss (UCHL). Research Design “Normal”-hearing participants underwent localization testing in different free field settings. Study Sample Ten volunteers with “normal”-hearing thresholds participated. Intervention Repeated assessments were compared between “normal” (binaural) hearing, UCHL induced by insertion of an inactivated HA to the ear canal (conductive HL), and amplification with a HA. Results In UCHL mode, with HA switched-off, localization was significantly impaired compared to “normal” hearing (NH; η2 = 0.151). Localization error was more pronounced when sound was presented from the front and from the side of the occluded ear. When switched-on, amplification with HAs significantly improved localization for all participants compared to UCHL. Better localization with HAs was seen in high frequencies compared to low frequencies (η2 = 0.08, 0.03). Even with HAs, localization did not reach that of NH (η2 = 0.034). Conclusions Mild UCHL caused localization to deteriorate. HAs significantly improved sound localization, albeit the delay caused by the device processing time. Most of the improvements were seen in high-frequency sounds, representing a beneficial effect of amplification on ILD. Our results have potential clinical value in situations of mild CHL, for instance, otitis media with effusion.

Background: Immunosuppression is strongly associated with an increased risk of developing cutaneous squamous cell carcinoma (cSCC). Studies on solid organ transplant recipients (SOTR) and chronic lymphocytic leukemia (CLL) patients have already demonstrated higher rates of aggressive cSCC tumors in these populations compared to immunocompetent controls. Studies on other immunosuppressed patient groups are scarce. This study was aimed at assessing the effects of different immunomodulating conditions on patients diagnosed with cSCC. We sought to compare the clinical features, treatments, and survival rates among the different study groups, as well as outcomes to those of immunocompetent controls with cSCC. Methods: A retrospective analysis of 465 cSCC patients, both immunosuppressed (IS) and immunocompetent controls. Etiologies for immunosuppression included SOTR, CLL, chronic kidney disease (CKD), psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). Results: Compared to the control group, IS patients demonstrated several significant differences. These include higher rates of positive resection margins, higher recurrence rates, and multiple SCC tumors. Patients in the IS group, who were also given immunomodulating agents, demonstrated even lower survival rates. Cox regression analysis demonstrated statistically significant decreased overall survival (OS) rates for IS patients compared to the controls (OR = 1.9, p = 0.031). SOTR patients tend to have multiple cSCC tumors (35%), with the highest number of primary tumors compared to controls (2.54 tumors per patient on average, p < 0.001), but also compared to all other IS groups. The average SCC lesion size in the SOTR group was the smallest, measuring at 13.5 mm, compared to the control group and all other IS groups. Decreased survival rates were seen on Cox regression analysis compared to controls (HR = 2.4, p = 0.001), but also to all other IS groups. CLL patients also had the highest rates of positive margins compared to controls (36% vs. 9%, p < 0.01) and to all other IS groups. They were also most likely to get adjuvant or definitive oncological treatments, either radiotherapy or chemotherapy, compared to controls (36% vs. 15%, p = 0.02) and to other IS groups. Patients in the CKD group demonstrated the highest rates for multiple cSCC (OR = 4.7, p = 0.001) and the worst rates of survival on Cox regression analysis (HR = 3.2, p = 0.001). Both rheumatoid arthritis and psoriasis patients demonstrated the shortest disease-free survival rates (2.9y ± 1.1, 2.3y ± 0.7, respectively), compared to controls (4.1y ± 2.8) and to all other IS groups. Conclusions: Among cSCC patients, immunosuppression due to SOTR, CLL, CKD, RA, and psoriasis is associated with worse outcomes compared to controls and other IS groups. These patients should be regarded as high-risk for developing aggressive cSCC tumors. This study is the first to assess and compare cSCC outcomes among multiple IS patient groups.

Objective The role of bilateral bone conduction amplification in patients with bilateral conductive hearing loss is unclear because cranial attenuation is usually considered negligible, and both cochleae can be stimulated with similar efficacy by each device. The aim of the study was to determine if bilateral bone-conduction hearing aids can improve hearing in noise in a homogeneous group of normal-hearing subjects with bilateral pseudo-conductive hearing loss. Study design Prospective, comparative. Setting Department of Communication Sciences and Disorders in University of Haifa, Israel. Subjects Department of Communication Sciences and Disorders in University of Haifa, Israel. Interventions Induction of bilateral pseudo-conductive hearing loss of more than 35 dB using earplugs and earmuffs. Main outcome measures Hearing quality on blinded comparison of unilateral versus bilateral amplification with bone-conduction hearing aids under different locations of noise. Results Unilateral and bilateral amplification had similar efficacy when both signal and noise were presented from the front. However, bilateral amplification was significantly better when signals were presented from the front and noise was presented from both sides (SNR -10: 92% vs. 84%, p = 0.001; SNR -15: 84% vs. 78%, p = 0.005). Analysis of subject responses on blinded questionnaires revealed that 81% found hearing easier with bilateral amplification. Noise was reported to be more disturbing with unilateral amplification by 55% of the subjects and with bilateral amplification, by 9%. Conclusions Bilateral amplification with bone conduction devices can improve understanding in noise in the binaural squelch setting. Subjective improvements with bilateral bone-conduction aids included better sound quality and reduced noise disturbance. These findings are consistent with the binaural mechanism of spectral release from masking.

Objectives—Cochlear implantation has been suggested to be associated with an air-bone gap, possibly secondary to increased middle- and inner-ear stiffness. To explore the effect of possible changes in mechanics due to cochlear implantation, we measured wideband tympanometry (WBT) in individuals with normal hearing and individuals with severe to profound sensorineural hearing loss who underwent unilateral or bilateral cochlear implantation. Our goal was to characterize differences in WBT patterns associated with severe to profound sensorineural hearing loss and with cochlear implantation. Design—The study participants were 24 individuals with normal hearing (48 ears) and 17 with cochlear implants, of which 15 were unilaterally implanted and two were implanted bilaterally. All the participants had normal otoscopy. In the implanted group, inner-ear anatomy was normal according to preoperative imaging. All participants underwent pure-tone audiometric assessment, standard tympanometry (226 Hz probe tone), and WBT to a click stimulus (analyzed from 226 to 8000 Hz). WBT was recorded at ambient and peak pressures. To elucidate the effect of sensorineural hearing loss on WBT, we compared normal-hearing ears with impaired non-implanted ears. The impact of cochlear implantation was assessed by comparing the WBT of the implanted and non-implanted ears of the same participants. Moreover, the effect of the ear (right vs. left) and test–retest reproducibility were evaluated. Results—WBT results for right and left ears showed no statistically significant differences in the normal hearing participants. There were no statistical differences shown between repeated measurements of WBT with removal and re-insertion of the probe in any of the groups—the normal ears, the implanted ears, and the non-implanted ears with hearing impairment. Peak compensated admittance (Ytm) in standard tympanometry was normal in 32 out of 34 (94%) ears with sensorineural hearing loss, with one CI user having bilateral negative middle-ear pressure. Compared to normal-hearing ears, ears with severe to profound SNHL, with or without cochlear implantation, showed a significant decrease in absorbance at high frequencies (4000–5000 Hz). Implanted ears, compared both to normal-hearing and contralateral-non-implanted ears, showed a significant decrease in absorbance at low frequencies (400–800 Hz) and an increase in absorbance around 1600 Hz. Conclusions—WBT analysis revealed that the implanted ears showed a significant decrease in absorbance at low frequencies (400–800 Hz) and an increase at 1600 Hz. This finding is likely a result of an increased stiffness due to the implantation surgery and the presence of the implant in the inner ear. In contrast, the specific decrease in absorbance around 4000–5000 Hz in the implanted and non-implanted ears compared to the normal ears is likely either due to aging or the impact of the severe-to-profound SNHL on the input impedance of the cochlea. The structural and functional changes of both the conductive system and the cochlea associated with aging and SNHL may change the wideband acoustic immittance of the ear and these alterations might be correlated with the hearing loss severity. Additional research is needed to determine how much hearing loss and age influence wideband acoustic immittance of the ear.

Unilateral vocal cord paralysis (UVCP) is a known complication of thyroid surgery, due to iatrogenic recurrent laryngeal nerve injury, with reported rates of 2-5% in children. The gold standard for assessing vocal cord function in flexible nasendoscopy (FNE) examination, which is considered high-risk for contraction of the COVID-19 virus. Intraoperative ultrasonographic assessment (IUA) of vocal cord function is a non-invasive and relatively simple procedure, performed in a supine position under general anesthesia. Objectives: To evaluate the validity of IUA modality in children undergoing thyroidectomy, and to compare it to the standard FNE. Design: A prospective double-blind study covering 24 months (March 2019-March 2021). Twenty thyroid lobectomies were performed, during 15 surgeries. Vocal cord function was assessed three times: Preoperatively by FNE, intraoperative (IUA) following extubation, and a second FNE on the first post-operative day. Settings: A tertiary pediatric hospital. Results: The overall accuracy of IUA results in our study was 92%. IUA sensitivity, specificity, positive and negative predictive values were 100%, 89%, 33%, and 100% respectively. Patient’s age demonstrated borderline significance (p= 0.08). The resident’s experience was associated with a better correlation between IUA and FNE results (p

Anticoagulant and antiplatelet medications (ACAP) are known to be associated with an increased risk for epistaxis. There are conflicting results regarding the impact of Novel Oral Anticoagulants (NOAC) on epistaxis and its severity.Retrospective chart review of patients who were admitted to the ED in our tertiary level hospital with a diagnosis of epistaxis during the years 2012 to 2018.Retrospective analysis of patients presenting to tertiary level emergency otolaryngological care during the years 2012 to 2018. The impact of various ACAP medications on epistaxis severity, hospital admission, and recurrence was analyzed.A total of 470 patients were identified. Two hundred and twenty-nine patients (49%), were not on any anticoagulant/antiplatelet (ACAP) medications (controls) and 241 patients (51%) were taking at least one ACAP medication (ACAP group). Patients in the ACAP group were at a higher risk for severe epistaxis (OR = 1.8, P .05) and were more likely to be hospitalized (OR = 2.17, P .05). Surprisingly, the risk for recurrence was similar in the ACAP and control groups (15%, P .05). Compared to controls, Warfarin and Enoxaparin increased the overall risk for severe epistaxis (OR = 4.4, P .05) and for hospital admission (OR = 2.1, P .05). Specifically, an increased risk for posterior tamponade (OR = 19, P .001), significant blood loss (OR = 4.4, P = .032), and blood transfusion (OR = 4.7, P = .007) were identified as well. Interestingly, NOACs were not associated with increased risk for severe epistaxis, hospital admission, tamponade, and significant blood loss or blood transfusion compared to controls.Compared to older generation anticoagulants and antiplatelet medications, NOACs demonstrated an improved safety profile, in terms of epistaxis severity, need for hospital admission and outcomes. These results may suggest a more conservative approach and less hospitalization when treating epistaxis in patients receiving NOACs.4 Laryngoscope, 131:1946-1951, 2021.

OBJECTIVE To evaluate in cochlear implant patients, the feasibility and reliability of angular depth of insertion (aDOI) measurements using plain x-ray scans. STUDY DESIGN Retrospective study where three observers independently evaluated and compared intraoperative anterior-posterior and oblique x-ray scans. SETTING A tertiary pediatric medical center. PATIENTS Included were 50 children (100 ears) who underwent bilateral simultaneous cochlear implantation during 2008 to 2015. MAIN OUTCOME MEASURES Inter-rater agreement of aDOI measured in plain x-ray scans; effect of head position on measured aDOI; and symmetry of aDOI between patients' ears in bilateral simultaneous cochlear implantations. RESULTS Differences in the average aDOI measurements among the three observers ranged between 2 and 7 degrees. There was high inter-rater agreement (R = 0.99, p

High intensity physical exercise has previously been found to lead to a decline in cognitive performance of adults. The aim of this study was to determine the effects of maximal intensity exercise on cognitive performance of children. Using a repeated-measures design, 20 children and adolescents aged 8-17 years completed a battery of tests measuring memory and attention. Forward and Backward Digit Span tests, the Rey Auditory-Verbal Learning Test (RAVLT) and the Digit Symbol Substitution Test (DSST) were performed at baseline, immediately after, and one hour after a maximal cardiopulmonary exercise test. Forward and Backward Digit Span scores significantly improved post-recovery compared with baseline measurements. There was a significant decrease in RAVLT scores post-exercise, which returned to baseline values after recovery. The DSST test scores were mildly elevated from post-exercise to after recovery. Maximal intensity exercise in children and adolescents may result in both beneficial and detrimental cognitive effects, including transient impairment in verbal learning. Cognitive functions applying short term memory improve following a recovery period. Parents, educators and coaches should consider these changes in memory and attention following high-intensity exercise activities in children.

Background and Aims: The increasing prevalence of adolescent obesity affects adult health. We investigated the association of adolescent overweight with colorectal cancer incidence in a large cohort of males. Methods: Body mass index (BMI) was measured in 1.1 million Jewish Israeli males who underwent a general health examination at ages 16 to 19 between 1967 and 2005. Overweight was defined as BMI ≥ 85th percentile of the standard U.S. distribution in adolescence. Colorectal cancer was identified by linkage with the Israel National Cancer Registry up to 2006. The mean follow-up period was 17.6 ± 10.9 years, reflecting 19.5 million person-years. Cox proportional hazards modeling was used. Results: The prevalence of adolescent overweight increased from 9.9% to 16.8% in the first 10 and last 10 annual examination cohorts. Colon (n = 445) and rectal cancer (n = 193) cases were detected. Overweight predicted an increased risk of colon cancer [HR = 1.53; 95% confidence interval (CI), 1.17–2.02, P = 0.002] but not of rectal cancer (HR = 1.09; 95% CI, 0.38–1.73, P = 0.72). The risk was greatest for nonmucinous adenocarcinoma of the colon (HR = 1.68, 95% CI, 1.26–2.23, P = 0.001). The association of BMI ≥ 85th percentile with colon cancer was even more pronounced in analyses that were restricted to men followed until at least 40 years of age [N = 367,478; HR = 1.75 (95% CI, 1.33–2.3, P < 0.001)]. Conclusions: Adolescent overweight is substantially associated with colon cancer incidence in young to middle-aged adults. Impact: These long-term sequelae add to the urgency to seriously address increasing childhood and adolescent obesity with its attendant increasing population impact. Cancer Epidemiol Biomarkers Prev; 20(12); 2524–31. ©2011 AACR.

Natural autoantibodies (NAbs) are a seminal part of the immune system, originating from B-1a cells, and produced in the absence of external antigen stimulation. They exhibit a remarkably conserved repertoire that includes a broad specificity for self-antigens. For this reason, they are believed to be a product of natural selection. NAbs are mostly antibodies of the immunoglobulin (Ig)M isotype that demonstrate polyreactive, low-titer, low antigen-binding affinities, with germline- or close to germline-encoded variable regions that provide reactivity to both microbial and altered self-antigens. NAbs are engaged with a wide range of homeostatic “housekeeping” functions as well as roles in multiple disorders. In terms of homeostatic functions, NAbs are a crucial part of the very early innate immunity, providing an essential first line of defense against pathogens. NAbs also play a key role in clearing apoptotic cells and oxidized cellular damaged structures. Such an example is the clearance of oxidized low-density lipoproteins (OxLDL); this scavenging property contributes to the cardiovascular protection against atherosclerosis. There is also mounting evidence that NAbs take part in tumor surveillance by recognizing oligosaccharides expressed on tumor cells. In addition, the roles of NAbs in the pathogenesis of Alzheimer disease, systemic inflammatory response syndrome (SIRS), ischemia, and cryoglobulinemia are currently being investigated, whereas their significance in autoimmune conditions, such as rheumatoid arthritis and systemic lupus erythematosus, have been extensively described. These understandings may harness NAbs as future tool in the combat of disease.

Testicular cancer incidence is highest among men of northern European ancestry and lowest among men of Asian/African descent. We conducted a large-scale migrant cohort study to assess origin and migrant generation as predictors of testicular germ cell tumors (TGCTs), controlling for possible confounders. Data on 1,092,373 Jewish Israeli males, who underwent a general health examination prior to compulsory military service at ages 16-19 between the years 1967-2005, were linked to Israel National Cancer Registry to obtain incident TGCTs up to 2006. Cox proportional hazards was used to model time to event. Overall, 1,001 incident cases (534 seminoma and 467 nonseminoma) were detected during 19.2 million person-years of follow-up. Origin was a strong independent predictor of TGCTs with remarkably low incidence for North African-born (HR = 0.10, 95% CI: 0.04-0.21) and Asian-born (HR = 0.35, 0.20-0.62), while intermediate for Israeli-born of North African origin (HR = 0.48, 0.40-0.58) and Asian origin (HR = 0.56, 0.47-0.66), compared to European origin. A comparison of Israeli born of North African and Asian origin with North African and Asian-born yielded a HR of 2.31 (1.36-3.93). Significant risk factors controlled for were year of birth, years of education and height. Findings persisted when analyses were stratified by histologic subtypes of TGCTs. The findings of lower rates of TGCTs among men born in North Africa and Asia compared to European ancestry, but a steep increase in next generation migrants, particularly among the Israeli-born migrants from North Africa, provide clues to direct further research on the role of modern lifestyle and environment in the etiology of TGCTs.