The long-term effect of COVID-19 infection on olfaction and taste; a prospective analysis.

PURPOSE: To estimate long-term prognosis of chemosensory dysfunctions among patients recovering from COVID-19 disease. METHODS: Between April 2020 and July 2022, we conducted a prospective, observational study enrolling 48 patients who experienced smell and/or taste dysfunction during the acute-phase of COVID-19. Patients were evaluated for chemosensory function up to 24 months after disease onset. RESULTS: During the acute-phase of COVID-19, 80% of patients reported anosmia, 15% hyposmia, 63% ageusia, and 33% hypogeusia. At two years' follow-up, 53% still experienced smell impairment, and 42% suffered from taste impairment. Moreover, 63% of patients who reported parosmia remained with olfactory disturbance. Interestingly, we found a negative correlation between visual analogue scale scores for smell and taste impairments during the acute-phase of COVID-19 and the likelihood of long-term recovery. CONCLUSION: Our study sheds light on the natural history and long-term follow-up of chemosensory dysfunction in patients recovering from COVID-19 disease. Most patients who initially suffered from smell and/or taste disturbance did not reach full recovery after 2 years follow-up. The severity of impairment may serve as a prognostic indicator for full recovery.

Patterns of recurrence in patients with CRSwNP who underwent complete FESS.

PURPOSE: To analyze recurrence patterns of chronic sinusitis with nasal polyposis (CRSwNP) in patients who underwent complete FESS and identify predisposing factors for different patterns of recurrence. METHODS: Retrospective analysis of patients with CRSwNP who underwent complete FESS at our tertiary medical center. Recurrence patterns were classified into edema, polyp and normal endoscopy, as well as into early (within 6 months) and late recurrence. Statistical analysis to identify risk factors for recurrence included univariate, multivariate logistic regression and cox regression models. RESULTS: 114 patients were included with an average follow-up of 27 months. 91% were categorized as type-2 inflammation. Recurrence was observed in 65.8% of patients within a mean of 12.9 months. 46.7% had polyp recurrence while 53.3% had edema recurrence. Early recurrence was observed in 41%. Serum eosinophilia > 500 cells/uL was found to be significantly associated with recurrence (RR = 1.62, p-value = 0.046), and particularly with polyp recurrence (RR = 3.9, p-value = 0.001). No predictive factors for early recurrence were identified. Edema recurrence was managed with intranasal corticosteroids while polyp recurrence required systemic therapy including biologic therapy. CONCLUSIONS: In this study, two thirds of patients experienced post operative recurrence, either mucosal edema or nasal polyps, with similar frequency during an average follow up of over 2 years. Early recurrence was noted in 41% of recurrent cases. Serum eosinophils > 500 cells/uL was the only risk factor for recurrence on multivariate analysis, more accurate markers are needed for improved treatment allocation to CRSwNP patients.

Post-radiation middle ear effusion in NPC patients: Analysis of patient, tumour, and radiation factors.

OBJECTIVE: The purpose of this study was to investigate whether patient, tumour and radiation therapy factors are associated with development of middle ear effusion (MEE) in nasopharyngeal carcinoma (NPC) patients. DEIGN, SETTINGS, AND PARTICIPANTS: A retrospective review of NPC patients treated between January 2000 and June 2018 at Rabin Medical Center. Patient factors, tumour factors, radiation doses, and radiation fields were collected and outlined if needed (middle ear, eustachian tube [ET], tensor veli palatini [TVP], and levator palatini [LVP] muscles), then analysed and compared between patients with MEE and those without and between sides in patients with unilateral MEE. MAIN OUTCOME MEASURES AND RESULTS: Seventy-three patients were enrolled. Most were males (71.2%) with advanced-stage diseases (78%). At the time of diagnosis 14 patients (19.2%) presented with MEE. Following radiation, 18 patients, with no evidence of MEE at presentation, developed MEE. Tumour stage, histology, and laterality were not associated with development of MEE. Comparison of mean radiation field dosages including-gross target volume, clinical target volume, and patient target volume showed no association with post-radiation MEE. In addition, no difference was found in the radiation doses to the middle ear, ET or the LVP nor the TVP between ears with and without MEE. CONCLUSIONS: Post-irradiation MEE remains a common adverse effect in NPC patients. Surprisingly, tumour stage, tumour laterality, and histology were not associated with MEE. Similar findings were observed for total radiation doses and specific doses to the middle ear, ET, and ET muscles.

The implications of concomitant mucosal inflammation on clinical manifestations and outcomes of sinonasal inverted papilloma.

PURPOSE: This study examines the impact of concomitant mucosal inflammation on clinical manifestations and long-term outcomes of Inverted Papilloma (IP). METHODS: This retrospective cohort study was conducted in five tertiary medical centers. The included patients underwent an attachment-oriented surgical resection for IP with a minimum follow-up of 3 years. RESULTS: Of 185 patients with IP, 65 patients (35.1%) had synchronous mucosal inflammation with polypoid changes. The mean age was 56.7 years, and 69% were males. Most tumors originated from the maxillary sinus. Age, gender, Krouse stage, and tumor attachment site did not differ between the mucosal inflammation and IP-only groups. IP recurrence rate was twofold in the patients with mucosal inflammation (15.4% vs. 7.5%, p = 0.092). However, the difference was not significant, with a similar median time to recurrence between the two groups [15.5 (3-36) months vs. 16(6-96) months, p = 0.712]. In revision cases, IP recurred only in patients with mucosal inflammation (19% vs. 0%, p = 0.07). This group had a significantly worse 5-years recurrence-free survival than revision cases without mucosal inflammation (80.6% vs. 100%, p = 0.04). CONCLUSIONS: IP in the setting of mucosal inflammation might be associated with a higher recurrence rate, predominantly after revision surgery. Otolaryngologists should consider this during these patients' diagnosis, surgical planning, and follow-up.

Is intraoperative margin sampling necessary in inverted papilloma resection?

PURPOSE: To explore the association between intraoperative surgical margin sampling by the frozen sections and recurrence in inverted papilloma surgery. METHODS: A multicenter, retrospective study of patients who underwent attachment-oriented IP resection in four tertiary care medical centers with a minimal follow-up of 36 months. RESULTS: The study included 220 surgeries with a mean follow-up period of 49 months (range 36-204). The endoscopic approach was used in all but 4 cases; 73% of procedures were primary. Overall recurrence was 10.45% (n = 23). Squamous cell carcinoma was found in 5 cases (2.2%). Intraoperative margin sampling was obtained in 145 cases. There was no difference in the recurrence rate between frozen section and no-frozen section groups (p = 0.44). Furthermore, margin sampling in various sites of tumor origin, in cases with concomitant nasal polyps (p = 0.53) and in revision cases (p = 0.08) showed no correlation with recurrence. In 26 cases when the surgery was extended following a positive frozen section, there was a significantly higher recurrence rate (OR = 6.94). CONCLUSIONS: According to our results, intraoperative margin sampling did not affect the recurrence rate of IP, and therefore, its routine use should be questioned.

The bacteriology of recurrent acute exacerbations of chronic rhinosinusitis: a longitudinal analysis.

PURPOSE: The purpose of this study was to describe the microbiology of recurrent acute exacerbations of chronic rhinosinusitis over time. METHODS: Retrospective review of patients with recurrent acute exacerbations of chronic rhinosinusitis who underwent endoscopic-guided cultures during acute exacerbations of chronic rhinosinusitis. RESULTS: 386 cultures were obtained from 112 patients during recurrent acute exacerbations of CRS. A change of bacterial isolates during the course of recurrent exacerbations was observed in 68% (76/112) of patients, necessitating a change of treatment in 40% (45/112). The main risk factor for the subsequent change in cultures was polymicrobial growth. Sinus surgery was not associated with subsequent change in cultured isolates. Resistant strains developed in 11.6% (13/112) of patients, of whom those with abnormal mucociliary clearance being at the highest risk. CONCLUSION: Repeated middle meatal cultures should be considered in patients with recurrent exacerbations of CRS, particularly in cases not responding to standard therapy.

A prospective, feasibility study to evaluate the efficacy and usability of a novel drivable endoscope in patients with chronic rhinosinusitis.

PURPOSE: To carry out a pilot study to evaluate the efficacy of a novel, drivable endoscope (the Peregrine™ Drivable ENT Scope), compared to standard rigid endoscopes in the access, visualization, and irrigation of the paranasal sinus anatomy. METHODS: A prospective, multi-center, feasibility study was conducted on seventeen subjects who underwent primary functional endoscopic sinus surgery and were evaluated with the drivable endoscope and standard, rigid endoscopes (0°, 30° and 70°, as applicable). A CT scan was available for image guidance, as needed. The primary efficacy endpoint was the ability to access and visualize sinonasal anatomic landmarks. Secondary endpoints included device usability, as measured by a usability questionnaire given to surgeons postoperatively; the device's ability to irrigate the sinuses and patient reports of tolerability and pain during postoperative procedures. RESULTS: The drivable endoscope success rate in visualizing all paranasal sinus anatomic landmarks was 55.6% better than the standard rigid endoscopes: 98.3% (178/181) versus 42.7% (76/178); p < 0.001. Surgeons rated scores of over 4 (on a 1-5 scale) for the usability of the drivable endoscope to enter the maxillary, frontal and sphenoid sinuses. The ability to irrigate the sinuses using the drivable endoscope was given a mean score of 4.3, and image quality was given a mean score of 3.4. The three patients evaluated postoperatively reported low pain and high tolerability scores with the drivable endoscope. CONCLUSIONS: These preliminary results indicate that the drivable endoscope is effective, easy to use and highly tolerable in sinonasal endoscopy.

Sinonasal debridement versus no debridement for the postoperative care of patients undergoing endoscopic sinus surgery.

BACKGROUND: Endoscopic sinus surgery (ESS) is often recommended for symptomatic patients with recurrent acute or chronic rhinosinusitis who have failed conservative treatment. Postoperative care has been felt to be critical for both maintaining the surgical patency of the operated sinuses and improving patient symptoms. Debridement of the sinonasal cavities is one such postoperative care measure that has frequently been studied in the literature, often with conflicting conclusions. OBJECTIVES: To assess the effects of postoperative sinonasal debridement versus no debridement following endoscopic sinus surgery. SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL, via the Cochrane Register of Studies); PubMed; EMBASE; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 21 May 2018. SELECTION CRITERIA: Randomised controlled trials comparing postoperative nasal debridement versus no debridement in adult patients with recurrent acute or chronic rhinosinusitis undergoing endoscopic sinus surgery. We included studies in which the patients acted as self-controls (i.e. one side of the nose underwent debridement and the other side did not) only for the secondary endoscopy outcomes. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcome measures were: health-related quality of life, disease severity (patient-reported symptom scores) and significant adverse effects (bleeding requiring intervention, severe pain, iatrogenic injury). Secondary outcomes were: postoperative endoscopic appearance of the sinonasal surgical cavities (endoscopic scores), recorded use of postoperative medical treatment and rate of revision surgery. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: We included four studies (152 participants), with a follow-up duration ranging from three months to 12 months. In two studies patients acted as self-controls, i.e. one side of the nose underwent debridement and the other side did not ('split-nose' studies). The risk of bias in all studies was high, mostly due to the inability to blind the patients to the debridement procedure.Primary outcomesDisease-specific health-related quality of life scoresOnly one study (58 participants) provided data for disease-specific health-related quality of life. At six months follow-up, lower disease-specific health-related quality of life scores, measured using the Sino-Nasal Outcome Test-22 (SNOT-22, range 0 to 110), were noted in the debridement group but the difference was not statistically significant (9.7 in the debridement group versus 10.3 in the control group, P = 0.47) (low-quality evidence).Disease severity (patient-reported symptom score)Only one study (60 participants) provided data for disease severity measured by visual analogue scale (VAS) score. No significant differences in total symptom score were observed between groups postoperatively (low-quality evidence).Significant adverse effectsSignificant adverse effects related to the debridement procedure were not reported in any of the included studies, however it is not clear whether data regarding adverse effects were not collected or if none were indeed observed in any of the included studies.Secondary outcomesAll four studies assessed thepostoperative endoscopic appearance of the sinonasal cavities using the Lund-Kennedy score (range 0 to 10). A pooled analysis of endoscopic scores in the two non 'split-nose' studies revealed better endoscopic scores in the debridement group, however this was not a statistically significant difference (mean difference -0.31, 95% confidence interval (CI) -1.35 to 0.72; I² = 0%; two studies; 118 participants) (low-quality evidence). A sub-analysis of the adhesion formation component of the endoscopic score was available for all four studies and revealed a significantly lower adhesion rate in the debridement group (risk ratio 0.43, 95% CI 0.28 to 0.68; I² = 29%; four studies; 152 participants). Analysis of the number needed to treat to benefit revealed that for every three patients undergoing debridement, the endoscopic score would be decreased by one point in one patient. For every five patients undergoing debridement adhesion formation would be prevented in one patient.Use of postoperative medical treatment was reported in all studies, all of which recommended nasal douching. Steroids (systemic or nasal) were administered in two studies. However, the data were very limited and heterogeneous, therefore we could not analyse the impact of concomitant postoperative medical treatment.The rate of revision surgery was not reported in any of the included studies, however it is not clear whether these data were not recorded or if there were no revision surgeries in any of the included studies. AUTHORS' CONCLUSIONS: We are uncertain about the effects of postoperative sinonasal debridement due to high risk of bias in the included studies and the low quality of the evidence. Sinonasal debridement may make little or no difference to disease-specific health-related quality of life or disease severity. Low-quality evidence suggests that postoperative debridement is associated with a significantly lower risk of adhesions at three months follow-up. Whether this has any impact on longer-term outcomes is unknown.

Selective expansion of human regulatory T cells in nasal polyps, and not adjacent tissue microenvironments, in individual patients exposed to steroids.

Severe forms of chronic rhinosinusitis (CRS), a common upper airway inflammatory disorder, are associated with nasal polyps (NPs). NP disease is ameliorated by glucocorticoid (GC) treatment, whose cellular effects are poorly understood. We therefore assessed the influence of GC therapy on NPs in CRS patients, focusing on regulatory T (Treg) cells. Treg cell populations were analyzed by flow cytometry in NPs and control tissues from GC-treated CRS patients and controls. After GC exposure, selective expansion of Treg cells was seen within NPs, and not blood or adjacent ethmoid tissues. To confirm direct GC effects, NPs from the same patients were biopsied prior to, and following, 1week of oral GC exposure. Direct expansion of Tregs into the same NP bed was detected in 4/4 CRS patients following GC exposure. Treg cell spikes into NPs were secondary to cellular recruitment given limited Ki67 expression within these regulatory cells. Chemokine gene expression profiling identified several chemokines, notably CCL4, induced within NPs upon GC treatment. Neutralization of chemokine receptor/ligand interactions using CCR4 small molecule antagonists reduced Treg migration towards GC-treated NPs in an ex vivo migration assay. Our findings suggest that the common use of GCs in the treatment of NP disease leads to recruitment of Treg cells from peripheral sites into NP tissues, which may be critical to the anti-inflammatory effect of GCs. Mechanistically Treg expansion appears to be conferred, in part, by chemokine receptor/ligand interactions induced following corticosteroid therapy.

Heat shock proteins HSP90, HSP70 and GRP78 expression in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma management consists mainly of surgical resection and is largely chemoresistant. There is ongoing effort to discover novel therapies for medullary thyroid carcinoma. Increased levels of heat shock proteins have been associated with multiple cancers and are being studied as potential therapeutic targets. The purpose of this study was to determine the expression levels of heat shock proteins 90 and 70 and of glucose related protein 78 in medullary thyroid carcinoma tissues compared with normal thyroid tissues. METHODS: 20 tissue specimens of medullary thyroid carcinoma and 10 specimens of thyroids without malignancy were analyzed by immunohistochemistry. RESULTS: Medullary thyroid carcinoma specimens showed 27% higher expression level of heat shock protein 90 immunostaining, and a 43% higher expression level of heat shock protein 70 immunostaining versus normal controls. These differences, however, were not statistically significant. A significantly higher expression level was noted for glucose related protein 78 in the medullary thyroid carcinoma specimens than in the controls. CONCLUSION: This study indicates increased expression levels of heat shock proteins 90 and 70 and glucose related protein 78 levels in medullary thyroid carcinoma. These findings, though preliminary imply that these proteins may have a role in medullary thyroid carcinoma's tumor biology and may have and future therapeutic options. Larger cohorts are needed to corroborate these results.

Prenatal exposure to tobacco smoke leads to increased mitochondrial DNA content in umbilical cord serum associated to reduced gestational age.

We investigated if prenatal exposures to tobacco smoke lead to changes in mitochondrial DNA content (mtDNA) in cord serum and adversely affect newborns' health. Umbilical cord serum cotinine levels were used to determine in utero exposure to smoking. Cord serum mtDNA was measured by quantitative polymerase chain reaction analysis of the genes coding for cytochrome c oxidase1 (MT-CO1) and cytochrome c oxidase2 (MT-CO2). Log transformed levels of mtDNA coding for MT-CO1 and MT-CO2 were significantly higher among infants of active smokers with higher serum level of cotinine (p < 0.05) and inversely associated with gestational age (p = 0.08; p = 0.02). Structural equation modeling results confirmed a positive association between cotinine and MT-CO1 and2 (p < 0.01) and inverse associations with gestational age (p = 0.02) and IGF-1 (p < 0.01). We identified a dose-dependent increase in the level of MT-CO1 and MT-CO2 associated to increased cord serum cotinine and decreased gestational age.

Malignant external otitis: Factors predicting patient outcomes.

OBJECTIVE: Malignant external otitis (MEO) is an aggressive infection, primarily affecting elderly diabetic patients. It begins in the external ear canal and spreads to adjacent structures. This study investigated the clinical characteristics of patients diagnosed and treated for MEO and analyzed factors affecting patient outcomes. STUDY DESIGN: Historical cohort. SETTING: Tertiary medical center. METHODS: Medical records of all patients diagnosed and treated for MEO from 1990 to 2013, were retrospectively reviewed. Clinical features, laboratory, imaging and outcomes were analyzed. RESULTS: 88 patients were included, mean age was 73±11.5years, 61 (69%) were male. Of these, 75% had diabetes. Mean follow-up was 60months. The most common presenting symptoms were otalgia (89%), external ear canal edema (86%) and otorrhea (84%). Pseudomonas aeruginosa was isolated in 61% of ear cultures. All patients were treated with antibiotics, 22% had surgery and 8% hyperbaric oxygen. Overall survival rate was 38% in 5years, with disease specific mortality 14%. DM, facial nerve palsy, positive CT scan and age above 70 were found to correlate and predict disease-specific mortality. CONCLUSIONS: MEO carries a grave prognosis. The presence of two or more of the following features, DM, facial nerve palsy, positive CT scan and age above 70, predicts poor outcome, and highlights the need for prolonged, vigorous treatment.

Bacteriology of the Middle Meatus in Chronic Rhinosinusitis with and without Polyposis.

There are only limited data in the literature, and none specifically from the Middle East, on the pathogenic bacteria in chronic rhinosinusitis (CRS) as opposed to healthy nasal cavities and their association with disease severity. The present study was conducted in the department of head and neck surgery of a tertiary medical center. Middle meatal swabs were taken preoperatively from patients with CRS with nasal polyposis (CRSwNP) (n = 60), CRS without nasal polyposis (CRSsNP) (n = 50), and control patients with septal deviation (n = 26) or no nasal abnormalities (n = 27). Culture findings were compared among the groups and correlated with CRS severity. Positive pathogenic culture rates were 78% in the CRSwNP group and 64% in the CRSsNP group. Twenty pathogenic bacterial species were identified; the most common was Staphylococcus aureus (27%). The most common Gram-negative isolate was Citrobacter spp. (17%). Gram-negative species were significantly more prevalent in the CRSwNP group than the others. Mean Lund-Mackay scores were 12.8 in the CRSwNP group and 6.9 in the CRSsNP group, and were unrelated to the culture findings. Positive culture rates were significantly higher in the septal deviation (54%) than the nasal healthy group (26%), although both values were significantly lower than in the CRS groups. In conclusion, patients with CRS have higher rates of bacterial isolates than patients without CRS. CRSwNP is associated with more Gram-negative bacteria than CRSsNP, regardless of disease severity. The relatively high positive culture rate in patients with septal deviation merits investigation.

Experience with intraoperative navigation and imaging during endoscopic transnasal spinal approaches to the foramen magnum and odontoid.

OBJECT: In this study the authors share their experience using intraoperative spinal navigation and imaging for endoscopic transnasal approaches to the odontoid in 5 patients undergoing C1-2 surgery for basilar invagination at Stanford Hospital and Clinics from 2010 to 2013. METHODS: Of these 5 patients undergoing C1-2 surgery for basilar invagination, 4 underwent a 2-tiered anterior C1-2 resection with posterior occipitocervical fusion during a first stage surgery, followed by endoscopic endonasal odontoidectomy in a separate setting. Intraoperative stereotactic navigation was performed using a surgical navigation system in all cases. Navigation accuracy, characterized as target registration error, ranged between 0.8 mm and 2 mm, with an average of 1.2 mm. Intraoperative imaging using a CT scanner was also performed in 2 patients. RESULTS: Endoscopic decompression of the brainstem was achieved in all patients, and no intraoperative complications were encountered. All patients were extubated within 24 hours after surgery and were able to swallow within 48 hours. After appropriate initial reconstruction of the defect at the craniocervical junction, no postoperative CSF leakage, arterial injury, or need for reoperation was encountered; 1 patient developed mild postoperative velopharyngeal insufficiency that resolved by the 6-month follow-up evaluation. There were no deaths and no patients required tracheostomy placement. The average inpatient stay after surgery varied between 72 and 96 hours, without extended intensive care unit stays for any patient. CONCLUSIONS: Technologies such as intraoperative CT scanning and merged MRI/CT can provide the surgeon with detailed, virtual real-time information about the extent of complex endoscopic vertebral segment resection and brainstem decompression and lessens the prospect of revision or secondary procedures in this challenging surgical corridor. Moreover, patients experience limited morbidity and can tolerate early oral intake after transnasal endoscopic odontoidectomy. Essential to the successful undertaking of these endoscopic adventures is 1) an understanding of the endoscopic nasal, skull base, and neurovascular anatomy; 2) advanced and extended-length instrumentation including navigation; and 3) a team approach between experienced rhinologists and spine surgeons comfortable with endoscopic skull base techniques.

Long-Term Follow-Up of Post Radiation Complete Sinus Opacification in Sinonasal Cancer Patients.

OBJECTIVE: Treatment of sinonasal malignancies most often requires primary or postoperative radiation treatment. Post radiation sinonasal morbidity has been previously described; however, none addressed post-radiation sinus obstruction. Our objective was to investigate the long-term outcomes of post radiation complete isolated sinus opacification (CISO). METHODS: A retrospective analysis of sinonasal cancer patients treated with radiation therapy during the years 2002 to 2022. Clinical, imaging and treatment data were collected from patients' medical records. Only patients with at least 12 months of follow-up and available imaging for review were included. RESULTS: Out of 109 patients, 37 patients were identified to meet the inclusion criteria. Mean follow-up was 58 months. 35% of patients were diagnosed with persistent post radiation CISO with a mean onset of 4 months. All these patients remained asymptomatic, and their imaging remained stable during follow-up with none developing an expanding mucocele. Ethmoid sinus tumor involvement was found to be more prevalent in the CISO group (62% vs. 25%, p-value = 0.048) as well as chemotherapy/immunotherapy (54% vs. 38%, p-value = 0.046). Multivariant analysis revealed that ethmoid sinus involvement (OR = 9.516, p-value = 0.047) and adjuvant therapy, either chemotherapy/immunotherapy (OR = 10.75, p-value = 0.036) were found to be a predictive factor for complete opacification. CONCLUSION: Our study revealed that a substantial number of post-radiation patients develop a stable and persistent CISO, often in the frontal and sphenoid sinuses. These patients remained asymptomatic, and none required surgical intervention during nearly 5 years of follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Long-Term outcomes of pediatric dacryocystorhinostomy in a single medical center- a retrospective study.

PURPOSE: To examine the long-term success rate of pediatric endoscopic DCR surgery via telephone questionnaires, as determined by patients and their parents. METHODS: This is a retrospective cohort study of all patients who underwent DCR surgery at the Schneider Children's Medical Center of Israel between 2010 and 2020. We performed long-term follow-ups to assess the quality of life, surgical complications, and satisfaction with surgical outcomes. RESULTS: Our study includes seventy-nine patients with a total of 108 eyes. The mean age at the time of DCR was 7.05 years (Std = 4, min = 0.3, max = 17.7) Mean follow-up time was 5.7 years (Std =2.5, min = 1.4, max = 11.1). Tubes were inserted for a mean of 129 days (Std = 101). Fifty-seven patients (72%) declared they had no complications after surgery, three patients (4%) reported pain after surgery, and 14 patients (17.7%) reported tube extrusion, which occurred 7-21 days after surgery. Forty-four patients (56%) reported no recurrence of symptoms, 29 (37%) complained of mild epiphora, and 18 (23%) reported some ocular discharge. Sixty-eight patients (86%) stated that they did not undergo additional surgery, while the remaining 11 (14%) reported undergoing a revision operation for symptom control. Satisfaction rate (1-7) mean score reported was 6.15 (Std = 1.6). Sixty-two (78%) reported improved quality of life, while 17 (22%) reported no improvement. Our questionnaire results have been compared with the TEARS scores with similar findings. CONCLUSION: Regardless of its etiology, endoscopic DCR surgery in the pediatric population is safe and efficient, with a high long-term patient satisfaction rate, as reported via a telephone questionnaire.

The Long-Term Implications of Rhinitis and Chronic Rhinosinusitis in Young Adults.

BACKGROUND: The long-term impact of rhinitis and chronic rhinosinusitis (CRS) on general health and medical services utilization in young adults have been limitedly studied. METHODS: A case-control study in the Israeli Defense Forces, between the years 2005 and 2019, of all individuals with either rhinitis or CRS and a matched cohort of healthy individuals with a minimum of 5 years of consecutive follow-up. RESULTS: The study groups included 617 patients with rhinitis and 296 patients with CRS and 2739 healthy controls with an average age of 28 years. During a mean follow-up of 8 years, a significant fraction of patients in both study groups were diagnosed with asthma compared to the control group, (26.1% and 23.3% vs. 3.7%, respectively; CI 95%: 12.1%-14.9%, p < 0.0001). 7.6% of patients with rhinitis developed CRS. Significantly increased loss of productivity and medical system utilization were noted in the study groups compared to controls (p < 0.0001). Moreover, deterioration in general health, manifested as loss of physical fitness for combative service was observed in a third of patients during follow-up. CONCLUSIONS: Rhinitis and CRS significantly impact productivity and medical service utilization in young adults, as well as general health associated with development of asthma and impairment of physical fitness. A minority of rhinitis patients develop CRS overtime, further affecting this patient group. These patients should be followed up and managed to improve disease control and associated outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3299-3303, 2023.

Long-term complications associated with the management of sinonasal malignancies: a single center experience.

Objective: The aim of this study was to review the long-term complications associated with treatment of patients with sinonasal malignancies (SNMs) and risk factors for these complications. Methods: A retrospective analysis of all patients treated for SNMs at a tertiary care center between 2001 and 2018. A total of 77 patients were included. The primary outcome measure was post-treatment long-term complications. Results: Overall, long-term complications were identified in 41 patients (53%), and the most common were sinonasal (22 patients, 29%) and orbital/ocular-related (18 patients, 23%). In a multivariate regression analysis, irradiation was the only significant predictor of long-term complications (p = 0.001, OR = 18.86, CI = 3.31-107.6). No association was observed between long-term complications and tumour stage, surgical modality, or radiation dose/modality. Mean radiation dose ≥ 50 Gy to the optic nerve was associated with grade ≥ 3 visual acuity impairment (100% vs 3%; p = 0.006). Radiation therapy for disease recurrence was associated with additional long-term complications (56% vs 11%; p = 0.04). Conclusions: Treatment of SNMs has substantial long-term complications, which are significantly associated with radiation therapy.

Predictors for surgical intervention in orbital complications of pediatric rhinosinusitis.

OBJECTIVES: Orbital complications are the most common complication of acute rhinosinusitis, especially among pediatric patients. While most cases are treated with antibiotics alone, severe presentation may demand surgical intervention. Our goal was to determine which factors predict the need for surgery and to investigate the role of computerized tomography in the decision process. METHODS: A retrospective review of all children hospitalized between 2001-2018 with orbital complications of acute rhinosinusitis in a university-affiliated children's hospital. RESULTS: A total of 156 children were included. Mean age was 7.9 years (1-18 years). Twenty-three children (14.7%) were surgically treated, and the rest were conservatively treated. High fever, ophthalmoplegia and diplopia in association with minimal or no response to conservative treatment were predictive for surgical intervention, as well as higher inflammatory indices. Eighty-nine children (57%) underwent imaging during hospitalization. Presence of a subperiosteal abscess, as well as its size and its location were not found to be predictors for surgery. CONCLUSION: Clinical and laboratory findings in association with minimal or no response to conservative treatment predict the need for surgical intervention in cases of orbital complications of acute rhinosinusitis. As Computerized Tomography scans can have long-term implications in the pediatric population, caution and patience should be practiced when deciding on the timing of imaging in this population. Thus, close clinical and laboratory monitoring should lead the decision-making process in these cases and imaging should be reserved for when the decision for surgery has been made.

Mitochondrial DNA mutations in respiratory complex-I in never-smoker lung cancer patients contribute to lung cancer progression and associated with EGFR gene mutation.

Mitochondrial DNA (mtDNA) mutations were reported in different cancers. However, the nature and role of mtDNA mutation in never-smoker lung cancer patients including patients with epidermal growth factor receptor (EGFR) and KRAS gene mutation are unknown. In the present study, we sequenced entire mitochondrial genome (16.5 kb) in matched normal and tumors obtained from 30 never-smoker and 30 current-smoker lung cancer patients, and determined the mtDNA content. All the patients' samples were sequenced for KRAS (exon 2) and EGFR (exon 19 and 21) gene mutation. The impact of forced overexpression of a respiratory complex-I gene mutation was evaluated in a lung cancer cell line. We observed significantly higher (P = 0.006) mtDNA mutation in the never-smokers compared to the current-smoker lung cancer patients. MtDNA mutation was significantly higher (P = 0.026) in the never-smoker Asian compared to the current-smoker Caucasian patients' population. MtDNA mutation was significantly (P = 0.007) associated with EGFR gene mutation in the never-smoker patients. We also observed a significant increase (P = 0.037) in mtDNA content among the never-smoker lung cancer patients. The majority of the coding mtDNA mutations targeted respiratory complex-I and forced overexpression of one of these mutations resulted in increased in vitro proliferation, invasion, and superoxide production in lung cancer cells. We observed a higher prevalence and new relationship between mtDNA alterations among never-smoker lung cancer patients and EGFR gene mutation. Moreover, a representative mutation produced strong growth effects after forced overexpression in lung cancer cells. Signature mtDNA mutations provide a basis to develop novel biomarkers and therapeutic strategies for never-smoker lung cancer patients.