Ocular Surface Adverse Events are not Associated with Dupilumab use in Nasal Polyp Treatment.

OBJECTIVES: Ocular surface reactions (OSR) have been associated with dupilumab for atopic dermatitis (AD) treatment. However, the association of dupilumab-associated OSR (DA-OSR) for nasal polyps (CRSwNP) treatment has not been studied. We evaluated DA-OSR for CRSwNP treatment using the FDA Adverse Event Reporting System (FAERS). METHODS: FAERS was queried for any general ocular reactions (DA-GOR) from 2019Q1 to 2022Q4. DA-OSR were subcategorized from DA-GOR and compared between treatment groups (CRSwNP, asthma, AD). Logistic regression was used to predict DA-OSR. Disproportionality analysis (DPA) of DA-OSR was performed using OpenVigil. RESULTS: There were 60,198 total observations, of which 5344 were treated for CRSwNP. The prevalence of DA-GOR and DA-OSR was greatest for AD (15.3%, 7.8%), followed by CRSwNP (12.2%, 6.7%) and asthma (9.2%, 3.5%). The most commonly reported OSRs were dry eyes (35.9%), conjunctivitis (15.7%), and increased lacrimation (11.0%). The reported odds ratio (ROR) of CRSwNP-treated DA-OSR was 0.84 (0.73-0.97; p = 0.015), compared to 1.29 (1.20-1.40; p < 0.001) for AD and 0.66 (0.59-0.73; p < 0.001) for asthma. For CRSwNP treatment, the DA-OSR ROR was 0.97 (0.90-1.03; p = 0.3) for men and 0.78 (0.73-0.83, p < 0.001) for older adults (age > 50). ROR in the DPA for DA-OSR was 12.5 (12.2-12.8; p < 0.001) for any indication and 0.58 (0.53-0.64; p < 0.001) for CRSwNP treatment only. CONCLUSIONS: While there are limitations to FAERS, this study confirms the association between dupilumab and OSR for AD treatment, and does not support an association between dupilumab and OSR for CRSwNP treatment. Younger adults experience more DA-OSR in CRSwNP treatment without a specific predilection for sex. LEVEL OF EVIDENCE: IV Laryngoscope, 2023.

Venous Thromboembolism in Metastatic Uterine Leiomyosarcoma: A Case Report and Review of the Literature.

We report an unusual case of extensive deep vein thrombosis (DVT) and pulmonary embolism (PE) in the setting of metastatic uterine leiomyosarcoma. Recognition of the associated sequelae of this condition may improve short- and long-term outcomes. A 56-year-old black female with a history of uterine leiomyosarcoma diagnosed incidentally after total abdominal hysterectomy for fibroid uterus without initiation of chemoradiation treatment presented to the emergency department complaining of generalized weakness and progressively worsening stridor for 2 weeks. The patient was experiencing shortness of breath, dysphagia, and hoarseness. Physical exam was remarkable for rhonchi but was otherwise normal. Diagnostic imaging via CT of the abdomen, pelvis, and chest revealed DVTs of the left common and external iliac veins, the superior mesenteric artery, multiple pulmonary emboli of the right pulmonary artery, several nodular lesions within the lungs, and scattered peritoneal necrotic lesions, which were suspicious for metastatic disease. Additionally, CT of the neck showed an exophytic mass protruding into the airway from the subglottic region and thyromegaly with bilateral thyroid lobe nodules. The patient was subsequently started on Eliquis and chemotherapy. The rarity of this case is rooted in the extent of the patient's DVTs and PEs secondary to hypercoagulability in metastatic cancer. This presentation should be further evaluated to exclude thrombophilias or underlying malignancies. Drawing from the lessons of this case will help guide future clinical management regarding the care of metastatic uterine leiomyosarcoma.

Are Large Intraoperative Fill Volumes Associated With Increased Complications After Tissue Expander Placement?

Background: With the increased adoption of skin-sparing mastectomies, immediate 2-stage breast reconstruction is a common option for breast cancer patients. During the first stage of the procedure with tissue expander placement, higher intraoperative percent fill has been identified as a risk factor for complications. However, the postoperative outcomes of higher intraoperative fill volumes are not well established. The authors sought to evaluate if a higher initial intraoperative tissue expander fill volume is associated with higher complication rates in patients undergoing immediate breast reconstruction with tissue expander placement. Methods: A retrospective review of patients who underwent immediate breast reconstruction with a tissue expander placement from 2016 to 2018 was conducted. Patient demographics and perioperative data were recorded. Large intraoperative fill was defined as saline fill volume greater than 350 mL. The primary outcome evaluated was skin and nipple necrosis. Secondary outcomes were major infections, minor infections, seroma, and hematoma. Results: A total of 147 breasts in 86 patients were included. Mean intraoperative fill volume was 246.4 ± 106.6 mL. Thirty-five tissue expanders were filled with greater than 350 mL of saline intraoperatively. Patients with large intraoperative fill volume were older (mean age, 52.6 vs 47.9 years; P = .04), had a higher mean body mass index (BMI; 33.2 vs 25.9 kg/m2; P < .0001), and had larger preoperative breast anthropometrics (P < .0001). During a mean follow-up period of 20.1 months (range, 3-55 months), 9 breasts were noted to have skin/nipple necrosis. After multivariate analysis, large tissue expander fill volume was not a significant predictor of skin or nipple necrosis (P = .62). Hypertension and anticoagulant use were associated with increased skin and nipple necrosis (P = .04 and P = .03, respectively). Large fill volume was not associated with statistically significant increases in rates of other complications like major infections, minor infections, seroma, or hematoma. Conclusions: Larger fill volumes are often required and benefit patients with higher BMI or bra sizes. This also reduces the number of postoperative fills required. In this patient population, larger intraoperative tissue expander saline fill volume (greater than 350 mL) was not associated with increased postoperative complications. After careful patient selection and perfusion evaluation, larger fill volumes may be considered a safe option to improve the aesthetic outcomes in patients with high BMI.

Cardiovascular Risk Factors in Patients With Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis.

OBJECTIVE: The interruption of vascular supply to the inner ear is one of several proposed etiologies of sudden sensorineural hearing loss (SSNHL). The increased presence of cardiovascular risk factors may predispose patients to SSNHL through this pathway. This systematic review and meta-analysis studies the presence of cardiovascular risk factors in patients diagnosed with SSNHL. DATA SOURCES: Databases included PubMed/Medline, OVID, EMBASE, Cochrane, and Web of Science. REVIEW METHODS: Inclusion criteria included studies featuring SSNHL patients presenting with 1+ cardiovascular risk factors. Exclusion criteria included case reports and studies without outcome measures. Two investigators independently reviewed all manuscripts and performed quality assessments using validated tools. RESULTS: Of 532 identified abstracts, 27 studies met inclusion criteria (19 case-control, 4 cohorts, 4 case series). Of these, 24 underwent meta-analysis encompassing a total of 77,566 patients (22,620 SSNHL patients, 54,946 matched controls). The mean age was 50.43 years. SSNHL patients were more likely to have concomitant diabetes (odds ratio [OR] 1.61 [95% confidence interval [CI]: 1.31, 1.99; p < .00001]) and hypertension (OR 1.5 [95% CI: 1.16, 1.94; p = .002]). An increased standard mean difference of total cholesterol of 11.09 mg/dL (95% CI; 3.51, 18.67; p = .004) was noted in the SSNHL group compared with the controls. No significant differences in smoking, high-density lipoprotein, triglycerides, or body mass index were detected. CONCLUSION: Patients presenting with SSNHL have a significantly higher risk of concomitant diabetes, hypertension, and higher total cholesterol in comparison to matched controls. This may indicate a higher cardiovascular risk profile in this population. More prospective and matched cohort studies are needed to understand the role of cardiovascular risk factors in SSNHL.

Characteristics of Adults Undergoing Soft Tissue and Orthognathic Surgery for Obstructive Sleep Apnea.

OBJECTIVE: To identify clinical and demographic characteristics of adults with obstructive sleep apnea (OSA) undergoing soft tissue and orthognathic sleep surgery, assess temporal trends in surgery type and proportion of women undergoing surgery, and provide clinical perspective before wide-spread implementation of hypoglossal nerve stimulation (HGNS). METHODS: In a retrospective cohort study, adults diagnosed with OSA from 2009 to 2016 were identified in a large integrated healthcare system. Characteristics between cohort members who did and did not undergo sleep surgeries were compared. Multivariable logistic regression models examined associations of different characteristics with whether surgery was performed. RESULTS: Of 172,216 adults with OSA, 2,262 (1.3%) underwent sleep surgery during 2009-2017. The most common sleep surgery was palate surgery (56.9%), which decreased proportionately over time. In multivariable analysis, older age and obesity were associated with lower odds of undergoing surgery. Those who underwent tonsillectomy and adenoidectomy were more likely to have larger tonsils and not require additional surgery, whereas tongue reduction recipients were more likely to have severe OSA and require multiple surgery types. The proportion of women undergoing surgery increased over time (p < 0.001 from trend test). CONCLUSION: Clinical and demographic characteristics associated with soft tissue and orthognathic sleep surgery were identified in a large adult cohort prior to widespread implementation of HGNS. An increase in sleep surgery among women and a decrease in palate surgery over time were observed. The findings provide clinical perspective on sleep surgery performed prior to implementation of HGNS and may inform future studies examining its associations with patient characteristics. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1262-1270, 2023.

Complication Rates in Osteotome and Drill Techniques in External Auditory Canal Exostoses: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess and compare complication rates of symptomatic external auditory canal (EAC) exostoses treated with drill versus osteotome canalplasty. DATABASES REVIEWED: PubMed/Medline, OVID, EMBASE, Web of Science, Google Scholar. METHODS: A systematic review and meta-analysis in accordance with PRISMA guidelines and standardized bias assessment using the JBI critical appraisal checklist was performed. Studies containing original outcome data on drill and osteotome canalplasty were included. The primary study outcome was complication rates. RESULTS: Fifteen studies were included, encompassing 1399 total patients (1788 ears) with 530 and 1258 ears in the osteotome and drill groups, respectively. Ten studies used a drill, 2 used an osteotome, and 3 used both. The most frequently reported complications were tympanic membrane (TM) perforation (osteotome group: 5.3% [95% CI: 1.7%-10.9%]; drill group: 3.8% [1.5%-7.1%]), sensorineural hearing loss (SNHL) (0.69% [0.07%-1.9%]; 4.3% [2.2%-7.0%]), and postoperative stenosis (1.1% [0.0005%-4.3%]; 4.1% [1.9%-7.0%]). Use of the osteotome was associated with a lower rate of SNHL (P < .05) and stenosis (P < .05), and a higher rate of TM perforation (P < .05). Heterogeneity of the studies included in the analyzed complications ranged from moderate to high. Level of evidence in the included studies ranged from 2b to 4 and all studies had an overall low risk of bias. CONCLUSION: While an osteotome technique may increase the risk of TM perforation, drill canaloplasty may increase the risk of SNHL and postoperative stenosis in EAC exostectomy. The exact quantity of hearing loss could not be definitively evaluated. Additional research with participant randomization is needed to assess clinical efficacy. LEVEL OF EVIDENCE: Level 8.

Use of a Novel Clinical Decision-Making Tool in Vestibular Schwannoma Treatment.

OBJECTIVE: To determine the usefulness of a personalized tool and its effect on the decision-making process for those with vestibular schwannoma (VS). STUDY DESIGN: Prospective study. SETTING: Single institution, academic tertiary care lateral skull base surgery program. PATIENTS: Patients diagnosed with VS. INTERVENTIONS: A comprehensive clinical decision support (CDS) tool was constructed from a previously published retrospective patient-reported data obtained from members of the Acoustic Neuroma Association from January to March 2017. Demographic, tumor, and treatment modality data, including associated side effects, were collected for 775 patients and integrated in an interactive and personalized web-based tool. MAIN OUTCOME MEASURES: Pre- and posttool questionnaires assessing the process of deciding treatment for VS using a decisional conflict scale (DCS) and satisfaction with decision (SWD) scale were compared. RESULTS: A pilot study of 33 patients evaluated at a single institution tertiary care center with mean ± SD age of 63.9 ± 13.5 years and with average tumor size of 7.11 ± 4.75 mm were surveyed. CDS implementation resulted in a mean ± SD total DCS score decrease from 43.6 ± 15.5 to 37.6 ± 16.4 ( p < 0.01) and total SWD score increase from 82.8 ± 16.1 to 86.2 ± 14.4 ( p = 0.04), indicating a significant decrease in decisional conflict and increase in satisfaction. CONCLUSIONS: Implementing a decision-making tool after diagnosis of VS reduced decisional conflict and improved satisfaction with decision. Patients considered the tool to be an aid to their medical knowledge, further improving their comfort and understanding of their treatment options. These findings provide a basis for developing predictive tools that will assist patients in making informed medical decisions in the future.

Non-surgical Management of Locally Advanced Basal Cell Carcinoma of the Upper Extremity With Vismodegib.

Basal cell carcinoma (BCC) is a common skin malignancy that can present reconstructive challenges in patients with locally advanced diseases of the extremities. This article highlights three cases of locally advanced BCC of the extremities managed with vismodegib (Erivedge, Genentech). Vismodegib is a sonic hedgehog pathway (Shh) inhibitor approved by the FDA for use in metastatic or recurrent BCC. All three patients in our case series demonstrated significant clinical responses with reductions in tumor size which obviated the need for complex reconstructive surgery or amputation.

Effects of Combined Gentamicin and Furosemide Treatment on Cochlear Macrophages.

Combining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of macrophages is typically neuroprotective, the delay in the resolution of macrophage activity can be a complication if the damaged cochlea is used as a model to study subsequent therapeutic strategies. Here, we applied a high dose combination of systemic gentamicin and furosemide in C57 BL/6 and CBA/CaJ mice and studied the ototoxic consequences in the cochlea, including hair cell survival, ribbon synaptic integrity, and macrophage activation up to 15-day posttreatment. The activity of macrophages in the basilar membrane was correlated to the severity of cochlear damage, particularly the hair cell damage. Comparatively, C57 BL/6 cochleae were more vulnerable to the ototoxic challenge with escalated macrophage activation. In addition, the ribbon synaptic deterioration was disproportionately limited when compared to the degree of outer hair cell loss in CBA/CaJ mice. The innate and differential otoprotection in CBA/CaJ mice appears to be associated with the rapid activation of cochlear macrophages and a certain level of synaptogenesis after the combined gentamicin and furosemide treatment.

DermACELL Acellular Dermal Matrix in Oncologic Breast Reconstruction: A Cohort Study and Systematic Review.

Acellular dermal matrices (ADMs) are commonly used in tissue expander and direct-to-implant reconstruction following mastectomy. Few studies have reported outcomes of DermACELL use or compared DermACELL with AlloDerm ADM. This study sought to compare outcomes of DermACELL and AlloDerm in oncologic breast reconstruction and to review the literature reporting outcomes of patients undergoing reconstruction using DermACELL. Methods: We conducted a retrospective cohort study to compare outcomes between DermACELL and AlloDerm ADM, and a systematic review of the literature with a meta-analysis to evaluate clinical outcomes with DermACELL. Results: Seventy-four patients (128 breasts) undergoing immediate reconstruction were evaluated retrospectively. Chi-square analysis revealed no significant difference in postoperative outcomes between the two groups. Our systematic review of the literature yielded 12 total studies reporting DermACELL use for breast reconstruction encompassing 518 patients and 608 total breasts. A pooled analysis of the published data did not reveal a significant change in the rate of explantation when either chemotherapy or radiation was used. Meta-analysis did not show a significant difference in the rate of any of the complications evaluated. Conclusion: DermACELL is safe to use with a relatively consistent complication profile as compared with AlloDerm.

Dupilumab Adverse Events in Nasal Polyp Treatment: Analysis of FDA Adverse Event Reporting System.

OBJECTIVES: Dupilumab was the first biologic approved to treat chronic rhinosinusitis with nasal polyps (CRSwNP). While the risk of adverse events in phase-III clinical trials was low, dupilumab-associated adverse reactions (DAR) with real-world use is unknown and potentially under-reported. We aimed to evaluate DAR for CRSwNP treatment (CRSwNP-tx) using the FDA Adverse Event Reporting System (FAERS). STUDY DESIGN: Retrospective database study. METHODS: FAERS was queried for DAR from 2019Q1 to 2021Q2. Individual DAR (iDAR) were categorized and quantitatively compared between treatment groups (CRSwNP, asthma, atopic dermatitis). Zero-truncated Poisson regression was modeled to predict the number of iDAR, and logistic regression was modeled to predict serious DARs. RESULTS: There were 15,411 DAR observations; 911 for CRSwNP-tx, of which 121 (13.3%) had serious reactions and 3 died. Common CRSwNP-tx iDAR were dermatologic (13.9%), generalized (13.3%), and injection-site (10.8%) symptoms. The number of CRSwNP-tx iDAR was 2.99 [2.81, 3.17], compared to 3.44 [3.32, 3.56] for asthma and 3.18 [3.13, 3.24] for atopic dermatitis (Kruskal-Wallis test, P < .001). For CRSwNP-tx, iDAR reported-risk-ratio was 0.84 [0.77, 0.92] among men and 1.12 [1.04, 1.22] among older adults (>50). Serious DAR reported-odds-ratio was 1.37 [0.91, 2.04] among men and 1.39 [0.93, 2.08] among older adults. CONCLUSIONS: While there are limitations with FAERS, this analysis suggests CRSwNP-tx is associated with fewer iDAR compared with other treatment indications. More iDAR are experienced among women and older adults, but men tend to have more serious DAR. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2307-2313, 2022.