Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Tuesday, February 16, 2021

Expression of ACE2 and TMPRSS2 Proteins in the Upper and Lower Aerodigestive Tracts of Rats: Implications on COVID 19 Infections

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Objective

Patients with coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), exhibit not only respiratory symptoms but also symptoms of chemo‐sensitive disorders. Cellular entry of SARS‐CoV‐2 depends on the binding of its spike protein to a cellular receptor named angiotensin‐converting enzyme 2 (ACE2), and the subsequent spike protein‐priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 is considered to enhance the invading capacity of SARS‐CoV‐2.

Methods

To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS‐CoV‐2, we investigated the expression of ACE2 and TMPRSS2 proteins using immunohistochemistry, in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, and lung of rats.

Results

Co‐expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal epithelium, trachea, bronchioles, and alveoli with varying degrees of expression. Remarkably, TMPRSS2 expression was more distinct in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID‐19, such as the loss of taste, loss of olfaction, and respiratory dysfunction.

Conclusions

A wide range of organs have been speculated to be affected by SARS‐CoV‐2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID‐19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID‐19.

Level of Evidence

NA Laryngoscope, 131:E932–E939, 2021

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Outcomes of Primary Versus Salvage Surgery for Sinonasal Malignancies: A Population‐Based Analysis

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Objectives/Hypothesis

There exists a lack of consensus on the optimal sequence of treatment for many sinonasal malignancies (SNMs). This study compares the overall survival (OS) outcomes for primary surgery (PS) versus salvage surgery (SS) in SNM patients across stage, histology, and primary site.

Study Design

Retrospective database review.

Methods

The National Cancer Database was queried for all SNM cases treated with multimodal surgical and nonsurgical therapy between 2004 and 2015. Logistic regression identified predictors of SS. Cox proportional hazards models evaluated predictors of mortality, and Kaplan‐Meier log‐rank test assessed OS outcomes.

Results

Our SNM cohort consisted of 3,011 patients (PS = 2,804; SS = 207). SS patients had significantly longer postoperative hospital stays (P = .009) and increased rates of 30‐day (P < .001) and 90‐day mortality (P < .001) compared to PS. On multivariate logistic regression, predictors of undergoing SS included sinonasal undifferentiated carcinoma histology (odds ratio = 2.72; 95% confidence interval [CI]: 1.16‐6.66; P = .024). On multivariate Cox proportional hazards analyses among SS patients, late‐stage disease (hazard ratio [HR] = 4.80; 95% CI: 1.46‐15.8; P = .01) and positive surgical margins (HR = 2.31; 95% CI: 1.29‐4.13; P = .005) portended significantly worse OS. In the propensity score–matched cohort controlling for stage and histology, PS had significantly improved OS compared to SS (P = .007). Compared to SS, PS also had improved OS in subgroup analyses for patients with late‐stage disease (P = .026) and squamous cell carcinoma histology (P = .006).

Conclusions

In our SMN cohort, PS resulted in improved OS outcomes compared to SS independent of stage and histology. Consideration may be given to primary surgical resection for SMN whenever feasible, though a targeted, individualized approach is warranted.

Level of Evidence

3 Laryngoscope, 131:E710–E718, 2021

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Communication Chaos from Discrepancies in Personal Protective Equipment and Preoperative Guidelines

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Objectives/Hypothesis

To compare personal protective equipment (PPE) guidelines, specifically respirator use, among international public health agencies, academic hospitals, and otolaryngology‐head and neck surgery (OHNS) departments in the United States for the care of coronavirus‐19 (COVID‐19) patients.

Study Design

Cross sectional survey.

Methods

Review of publicly available public health and academic hospitals guidelines along with review of communication among otolaryngology departments.

Results

Among 114 academic institutions affiliated with OHNS residencies, 20 (17.5%) institutions provided public access to some form of guidance on PPE and 73 (64%) provided information on screening or diagnostic testing. PPE guidelines were uniquely described based on several variables: location of care, COVID‐19 status, involvement of aerosol generating or high‐risk procedures, and physical distance from the patient. Six hospital guidelines were highlighted. Across these six institutions, there was agreement that N95 respirators were needed for high‐risk patients undergoing high‐risk procedures. Variations existed among institutions for scenarios with low‐risk patients. Definitions of the low‐risk patient and high‐risk procedures were inconsistent among institutions. Three of the highlighted institutions had OHNS departments recommending higher level of airway protection than the institution.

Conclusions

OHNS departments typically had more stringent PPE guidance than their institution. Discrepancies in communicating PPE use were frequent and provide inconsistent information on how healthcare workers should protect themselves in the COVID‐19 pandemic. Identification of these inconsistencies serves as an opportunity to standardize communication and develop evidence‐based guidelines.

Level of Evidence

V Laryngoscope, 131:E746–E754, 2021

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Congenital Orocutaneous Fistula Associated With Ectopic Salivary Glands and Submandibular Gland Aplasia

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Free Flap Inset Techniques in Salvage Laryngopharyngectomy Repair:

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Objective

To characterize pharyngocutaneous fistula (PCF) rates and functional outcomes following microvascular free tissue transfer (MVFTT) reconstruction of salvage total laryngectomy (STL) with a review of two different flap inset techniques and a review of the literature.

Methods

Retrospective review.

Results

Review of the literature revealed 887 patients who underwent STL MVFTT from 14 references. Ninety‐six STL MVFTTs were performed by the authors, with 36 (38%) patients undergoing multilayer fascial underlay (MLFU) closure and 60 (62%) a standard single layer closure (SLC). One (3%) PCF occurred in the MLFU group compared to 12 (20%) in the SLC cohort (P = .03). Postoperative gastrostomy (G)‐tube dependence was lower following MLFU closure compared to SLC (25% vs. 57%, P < .01), whereas pharyngoesophageal stricture (PES) (28% vs. 38%), tracheoesophageal puncture (TEP) placement (42% vs. 42%), and TEP usage (87% vs. 88%) did not significantly differ (P > .05). Compared to pooled rates from the literature, patients who underwent a MLFU MVFTT inset technique demonstrated significantly lower PCF incidence (3% vs. 23%, P < .01) without significant differences in PES (28% vs 23%, P = .55), G‐tube dependence (25% vs. 23%, P = .25), or TEP placement (42% vs. 59%, P = .09).

Conclusion

Despite MVFTT reconstruction after STL, G‐tube dependence, PCF formation, and limitations of speaking rehabilitation (TEP) remain a significant issue. Modification of MVFTT inset may provide an opportunity to reduce PCF incidence without affecting other functional outcomes.

Level of Evidence

4 Laryngoscope, 131:E875–E881, 2021

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Impact of Cochlear Implant With Diametric Magnet on Imaging Access, Safety, and Clinical Care

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Objectives/Hypothesis

Review safety and effectiveness of magnetic resonance imaging (MRI) of patients implanted with a cochlear implant (CI) containing a diametric magnet housed within the undersurface of the device.

Study Design

Retrospective chart review with additional review of MRI at a tertiary‐care children's hospital.

Methods

Seven patients with mean age of 8.4 years (range = 1.3–19 years) with a diametric magnet in situ during MRI. The intervention comprised one or more sessions of 1.5 T or 3.0 T MRI without a head wrap. The main outcome measures were the occurrence of magnet‐related complications including discomfort and magnet displacement, use of anesthesia or sedation, and clinical usefulness of MRI studies.

Results

Seven CI recipients underwent 17 episodes of 1.5 or 3.0 T MRI with an in situ diametric magnet. Thirteen of 17 (76%) MRI sessions were completed in awake patients. No patients had device‐related discomfort. No magnet‐related complications occurred. Thirteen of 14 (93%) brain studies were clinically useful despite artifacts.

Conclusions

The diametric magnet enabled MRI with magnet in situ without the discomfort or magnet displacement associated with removable axial magnets. The reduction in MRI magnet‐related complications occurred because torque is not directed perpendicular and outward from the plane of the magnet, and the magnet is securely contained within its housing. The design of this device increased access and reduced the need for sedation or anesthesia.

Level of Evidence

4 Laryngoscope, 131:E952–E956, 2021

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Patterns and Predictors of Metastatic Spread to the Neck in Pediatric Thyroid Carcinoma

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Objective

Evaluate patterns and predictors of spread to the neck in pediatric metastatic differentiated thyroid carcinoma (DTC).

Methods

Patients <18 years old undergoing thyroidectomy by a single surgeon from January 2015 to December 2019 were included. Neck sublevels were removed separately according to AJCC boundaries. Clinical outcomes included nerve injury, hypocalcemia, hematoma, and residual tumor.

Results

Forty‐eight children underwent thyroid surgery. Thirty (63%) were for malignancy, 27 (90%) of which were DTC. Nineteen (70%) patients with DTC underwent 24 neck dissections; 19 central plus lateral and 5 central alone. The female to male ratio increased from 1:1 to 3:1 with age. Two children with lateral neck involvement had sub‐centimeter primaries. Patients requiring neck dissection were more likely to have 1) diffuse sclerosing or tall cell variant, 2) T3 or T4 disease, 3) genetic mutation, 4) lymphatic invasion, 5) extracapsular extension, 6) positive resection margin. Levels IIA (79%), III (89%), IV (84%), VI (100%) were most commonly involved. Levels IB (16%), IIB (16%), VB (16%) were also involved, often without involvement of adjacent levels. Permanent injuries included one unilateral recurrent laryngeal nerve, one mild marginal mandibular nerve and one mild accessory nerve. Hypocalcemia was highest following neck dissection for malignant disease. One patient was re‐ operated for a mediastinal node. Most patients with N1 disease received radioactive iodine. Most patients have no evidence or indeterminate disease on long‐term follow‐up.

Conclusion

Children with lateral nodal spread from DTC should be considered for neck dissection including Levels IB, IIA, IIB, III, IV, VB, bilateral VI.

Level of Evidence

4 Laryngoscope, 131:E1002–E1009, 2021

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Does the Expiratory Disproportion Index Remain Predictive of Airway Stenosis in Obese Patients?

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Objectives/Hypothesis

The expiratory disproportion index (EDI) is the ratio of forced expiratory volume in 1 second divided by peak expiratory flow rate multiplied by 100. An elevated EDI (>50) can help differentiate upper airway stenosis from other dyspnea etiologies, but this has not been verified when considering body habitus. We hypothesize that the predictive value of elevated EDI in diagnosing airway stenosis will be lower in obese patients as compared to nonobese patients.

Study Design

Retrospective cohort study.

Methods

Patients >18 years old with recorded pulmonary function test values, body mass index (BMI), and airway imaging were reviewed retrospectively from January 2011 to October 2018. EDI was recorded for four cohorts: nonobese and nonstenotic, obese and nonstenotic, nonobese and stenotic, and obese and stenotic, to determine the mean EDI and the sensitivity and specificity of an elevated EDI.

Results

Mean EDI values were 66.53 ± 17.66 and 49.55 ± 2.04 in the nonobese stenotic and nonstenotic groups, respectively (P < .01). They were 58.00 ± 10.79 and 45.02 ± 1.42 in the obese stenotic and nonstenotic groups, respectively (P < .01). At a threshold of >50, EDI had a sensitivity of 83.3% and specificity of 56.2% in differentiating between stenotic and nonstenotic cases in the nonobese cohort and 50.0% and 71.9% in the obese cohort.

Conclusions

As previously established, mean EDI values were significantly different in stenotic and nonstenotic patients in both BMI cohorts. However, at the established threshold of >50, EDI was not as sensitive at identifying stenotic cases in obese patients as in nonobese patients. This suggests that the EDI remains useful in obese patients when elevated but should not be relied upon to rule out stenosis.

Level of Evidence

4 Laryngoscope, 131:606–609, 2021

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Multi‐institutional Survey of Squamous Cell Carcinoma of the External Auditory Canal

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Objectives

This study aimed to evaluate the efficacy of chemoradiotherapy (CRT) for patients with advanced cancer of the external auditory canal (EAC) by analyzing the outcome of the patients.

Methods

This is a multi‐institutional retrospective survey, and we reviewed the medical records of the subjects. A total of 181 patients with tumor (T)3 or T4 tumor in 17 institutions were enrolled. Further analysis was performed for 74 patients who underwent CRT under curative intent.

Results

Overall 5‐year survival rates of the patients who underwent CRT (n = 74) were 54.6%. Those of the patients who underwent CRT with modified TPF (docetaxel, cisplatin [CDDP], and 5‐fluorouracil) regimen (n = 50) and CRT with CDDP regimens (n = 24) were 64.4% and 36.7%, respectively. Significant differences were observed between these two groups.

Conclusion

Given the tendency that head and neck surgeons prefer CRT for advanced larger cancer of the EAC, CRT for advanced EAC cancer using the modified TPF regimen showed good clinical outcomes.

Level of Evidence

4 Laryngoscope, 131:E870–E874, 2021

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Endoscopic Findings in Male Prepubertal Choir Singers

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Objectives/Hypothesis

The male singing voice through puberty undergoes many changes that present challenges for the singer and choral director. The purpose of this study was to discuss the endoscopic findings seen in prepubescent choir singers.

Study Design

Single‐institution prospective study.

Methods

Subjects were recruited from the Cincinnati Boychoir and were described as Cooksey stage unchanged or mid‐voice I, as described by the Boychoir artistic director. Vocal history was obtained via questionnaire at the initial visit. Subjects with known laryngeal pathologies were excluded. Endoscopic laryngeal examinations were performed using videoendoscopy. During examination, each subject sang four discrete frequencies. Findings of the endoscopic exam were judged by a board‐certified pediatric otolaryngologist specializing in pediatric voice.

Results

We evaluated 28 subjects prior to vocal maturation. Their age range was 8 to 13 years old (mean = 10.2 ± 1.2 years). The singing voice category of all 28 subjects was described as soprano vocal range by the Boychoir artistic director. The subjects had a mean of 1.7 ± 1.1 years in the Boychoir (0–5 years). None reported history of vocal issues or voice problems in the past; seven (25%) subjects had vocal fold lesions seen at one or more frequencies; 24 (85%) subjects had a posterior gap seen at one or more frequencies. Two subjects (7%) had a posterior gap at one frequency, C3 and G3, respectively. Five subjects (18%) had a posterior gap at two frequencies, seven subjects (25%) at three frequencies, and 10 subjects (36%) in all four frequencies.

Conclusions

Our study aimed to describe the laryngeal examination of dedicated Boychoir singers prior to undergoing pubertal development and vocal maturation. In elite pediatric singers we found that vocal nodules are common (25%) and are not correlated with vocal symptoms. These findings may suggest that asymptomatic lesions may be more prevalent than previously thought. In these individuals, posterior glottic gap is common and can be considered a normal glottal configuration.

Level of Evidence

4 Laryngoscope, 131:592–597, 2021

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Prognostic Value of the Lymphocyte‐to‐Monocyte Ratio in Patients with Parotid Gland Carcinoma

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Objective

Previous studies have evaluated various markers as prognostic predictors in patients with many types of cancers. However, the influence of such factors on the outcomes of patients with parotid gland carcinoma (PGC) is unknown. This study investigated the roles of alternative markers in the prognoses of patients with PGC.

Methods

Overall, 101 patients who underwent curative treatment for PGC were retrospectively evaluated, and their 5‐year overall and disease‐free survival rates were calculated. The prognostic values of clinical and pathologic factors were determined.

Results

The 5‐year overall and disease‐free survival rates were 73.1% and 62.8%, respectively. Multivariate analysis revealed that a low lymphocyte‐to‐monocyte ratio (LMR), high T classification, high N classification, and perineural invasion were independent predictors of poor prognosis.

Conclusions

Thus, we identified LMR as an independent prognostic factor for patients with PGC. Patients with low LMRs who are amenable to treatment may require adjuvant treatment to improve their prognoses.

Level of Evidence

4 Laryngoscope, 131:E864–E869, 2021

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Screening for Obstructive Sleep Apnea in Children With Sickle Cell Disease

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Objectives/Hypothesis

Obstructive sleep apnea (OSA) and sickle cell disease (SCD) represent two complex disease processes. Current guidelines recommend that children with SCD receive polysomnography (PSG) after presenting with signs or symptoms of sleep‐disordered breathing (SDB). Recent studies suggest a disproportionately elevated prevalence of SDB in the population of children with SCD, and traditional risk factors may not be evident within these patients. Further objective testing might be needed to screen all pediatric patients with SCD, even in the absence of overt signs or symptoms of OSA to prevent complications of both conditions.

Study Design

Prospective cohort study.

Methods

Institutional review board approval was obtained. An eight‐question OSA risk assessment screening questionnaire was presented prospectively to 100 consecutive patients with SCD in the pediatric hematology clinic regardless of complaints of SDB.

Results

Out of 100 patients, 51 were female. The average age, body mass index (BMI), BMI percentile, and I'M SLEEPY score of the entire cohort were 3.97 years, 15.97%, 55.4%, and 1.63%, respectively. Nineteen patients had a positive sleep apnea screening score and were referred for PSG. The average age BMI, BMI percentile, and I'M SLEEPY score for those 19 patients were 3.77%, 16.67%, 65%, and 3.95%, respectively. Ten patients completed PSG, with seven diagnosed with OSA.

Conclusions

This pilot study demonstrates a higher incidence of SDB and OSA in children with SCD relative to the general pediatric population. Although more PSG reports and further testing is needed to determine whether the results hold, preliminary data indicate that children with SCD should at least undergo OSA screening in the office regardless of overt symptoms.

Level of Evidence

3 Laryngoscope, 131:E1022–E1028, 2021

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