Treatment strategies for postviral olfactory dysfunction: A systematic review.

Background: The coronavirus disease 2019 (COVID-19) pandemic has been associated with a dramatic increase in postviral olfactory dysfunction (PVOD) among patients who are infected. A contemporary evidence-based review of current treatment options for PVOD is both timely and relevant to improve patient care. Objective: This review seeks to impact patient care by qualitatively reviewing available evidence in support of medical and procedural treatment options for PVOD. Systematic evaluation of data quality and of the level of evidence was completed to generate current treatment recommendations. Methods: A systematic review was conducted to identify primary studies that evaluated treatment outcomes for PVOD. A number of medical literature data bases were queried from January 1998 to May 2020, with completion of subsequent reference searches of retrieved articles to identify all relevant studies. Validated tools for the assessment of bias among both interventional and observational studies were used to complete quality assessment. The summary level of evidence and associated outcomes were used to generate treatment recommendations. Results: Twenty-two publications were identified for qualitative review. Outcomes of alpha-lipoic acid, intranasal and systemic corticosteroids, minocycline, zinc sulfate, vitamin A, sodium citrate, caroverine, intranasal insulin, theophylline, and Gingko biloba are reported. In addition, outcomes of traditional Chinese acupuncture and olfactory training are reviewed. Conclusion: Several medical and procedural treatments may expedite the return of olfactory function after PVOD. Current evidence supports olfactory training as a first-line intervention. Additional study is required to define specific treatment recommendations and expected outcomes for PVOD in the setting of COVID-19.

AMP-activated protein kinase inhibits transforming growth factor-ß-mediated vascular smooth muscle cell growth: implications for a Smad-3-dependent mechanism.

Dysfunctional vascular growth is a major contributor to cardiovascular disease, the leading cause of morbidity and mortality worldwide. Growth factor-induced activation of vascular smooth muscle cells (VSMCs) results in a phenotypic switch from a quiescent, contractile state to a proliferative state foundational to vessel pathology. Transforming growth factor-ß (TGF-ß) is a multifunctional signaling protein capable of growth stimulation via Smad signaling. Although Smad signaling is well characterized in many tissues, its role in VSM growth disorders remains controversial. Recent data from our lab and others implicate the metabolic regulator AMP-activated protein kinase (AMPK) in VSM growth inhibition. We hypothesized that AMPK inhibits VSMC proliferation by reducing TGF-ß-mediated growth in a Smad-dependent fashion. Treatment of rat VSMCs with the AMPK agonist AICAR significantly decreased TGF-ß-mediated activation of synthetic Smad2 and Smad3 and increased inhibitory Smad7. Flow cytometry and automated cell counting revealed that AICAR reversed TGF-ß-mediated cell cycle progression at 24 h and elevated cell numbers at 48 h. TGF-ß/Smad signaling increased the G0/G1 inducers cyclin D1/cyclin-dependent kinase (CDK) 4 and cyclin E/CDK2; however, AICAR reversed these events while increasing cytostatic p21. The specific role of Smad3 in AMPK-mediated reversal of TGF-ß-induced growth was then explored using adenovirus-mediated Smad3 overexpression (Ad-Smad3). Ad-Smad3 cells increased cell cycle progression and cell numbers compared with Ad-GFP control cells, and these were restored to basal levels with concomitant AICAR treatment. These findings support a novel AMPK target in TGF-ß/Smad3 for VSMC growth control and support continued investigation of AMPK as a possible therapeutic target for reducing vascular growth disorders.

Exoscope-assisted temporal bone resection: operative videos of the lateral and total techniques.

Skull base malignancies arising from the parotid gland, skin, or external auditory canal (EAC) can potentially involve the temporal bone. Management of these invasive tumors represents a true challenge considering the critical neurovascular relationships. Exoscope-assisted temporal bone resection (TBR) plays a crucial role in addressing such malignancies. The extent of disease is evaluated using the Pittsburgh staging system, which then guides the boundaries of resection. Lateral TBR (LTBR) relies on removal of the EAC and lateral ossicles and is generally appropriate for stage T1 and T2 tumors. Total TBR (TTBR) is reserved for high-grade tumors involving the petrous apex. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23135.

Biportal Endoscopic TransOrbital and transMaxillary Approach to the Cranio-Orbital Region and Middle Cranial Fossa: A Preliminary Analysis of Maneuverability.

BACKGROUND AND OBJECTIVES: Traditional and well-established transcranial approaches to the spheno-orbital region and middle cranial fossa guarantee optimal intracranial exposure, and additional orbital and zygomatic osteotomies provide further control over extracranial components to be resected; however, these techniques come at the cost of additional morbidity. The introduction of minimally invasive endoscopic approaches and the conceptualization of the so-called "multiportal" paradigm might provide an alternative route. This preliminary study investigates the feasibility of the combined Biportal Endoscopic TransOrbital and transMaxillary Approach (bETOMA) approach to the spheno-orbital and middle cranial fossa regions. METHODS: Using 4 silicon-injected adult cadaver heads (8 sides; 16 approaches), we systematically dissected through superior eyelid ETOA and endoscopic TMA approaches. The analysis focused on pterygopalatine, infratemporal, anterior and middle cranial fossae, Meckel cave, and cavernous sinus access. We evaluated the feasibility of bETOMA using linear distances, angles of attack, and exposure areas. We also introduced volume of operative maneuverability, its standardized derivative (sVOM), target distance, visuo-operative angle, and working zone volume as novel metrics. RESULTS: The analysis revealed comparable angles of attack between approaches. ETOA and TMA exposure areas were 918.38 ± 223.93 mm2 and 257.07 ± 86.07 mm2, respectively. TMA showed a larger VOM in the greater sphenoid wing, but ETOA offered superior distal maneuverability (sVOM: 5.39 ± 1.94 vs 2.54 ± 0.79 cm3) and closer intracranial space access (27.45 vs 50.83 mm). The combined approaches yielded a mean working zone volume of 13.75 ± 3.73 cm3 in the spheno-orbital interface. CONCLUSION: The bETOMA approach provides adequate neurovascular exposure and maneuverability to the spheno-orbital region, infratemporal, and anterior and middle cranial fossae, addressing significant limitations of previously investigated monoportal techniques (ie, optic nerve decompression, hyperostotic bone resection, and infratemporal exposure). This combined minimally invasive approach might help manage lesions harbored within the cranio-orbital interface region invading the extracranial space.

Submental Island Flaps for Lateral Reconstruction: Technical Refinements for Optimal Outcomes and Resource Efficiency.

Objective: To describe our modifications to the submental island flap (SMIF) in a case series that demonstrates improved reproducibility, shortened length of stay (LOS), and reduced utilization of hospital resources. Study Design: This retrospective case series with chart review included adult patients who underwent resection of malignant or benign tumors resulting in lateral facial, parotid, or temporal bone defects, which were reconstructed with SMIF. Setting: A tertiary-care academic referral center. Methods: Retrospective case series included all adult patients who underwent SMIF reconstruction between March 2020 and August 2021. Patient demographic and clinical data were collected. Primary outcomes were measures of hospital utilization including duration of surgery, LOS, and postoperative outcomes. Results: Twenty-eight patients were included with a mean age of 71.7 years. Eighty percent were male. All patients underwent parotidectomy, and the mean operative time was 347 minutes. The median LOS was 2.5 days (range 0-16 days). Seventy-five percent of the flaps drained into the internal jugular vein, and 25% drained into the external jugular vein. No patients required reoperation or readmission. All flaps survived. Conclusion: SMIFs are a safe and effective option for reconstruction of lateral facial, parotid, and temporal bone defects. Compared to free flap reconstruction, SMIFs offer reduced length of surgery, decreased use of health care resources, and lower rate of reoperation. As health care resource allocation is increasingly important, the SMIF offers an excellent alternative to free flap reconstruction of lateral defects.

Olfaction Preservation and Long-Term Outcomes in Patients with Unilateral Endoscopic Resection of Olfactory Neuroblastoma: A Systematic Review and Institutional Experience.

BACKGROUND: Endoscopic endonasal surgical resection is an effective therapeutic approach for olfactory neuroblastoma (ONB). Unilateral excision of ONBs with limited extension has been reported with the purpose of preserving olfactory function. We aimed to review implications of surgical management, olfactory preservation feasibility, and survival outcomes in patients who underwent endoscopic unilateral resection of ONB. METHODS: A systematic literature review was conducted using the search terms [("Olfactory neuroblastoma") OR ("Esthesioneuroblastoma")] AND [("Unilateral resection") OR ("Olfaction preservation")]. Studies reporting cases of unilateral ONB endoscopic resection with postoperative olfaction assessment were included. Concurrently, records of patients who met inclusion criteria at our institution were reviewed retrospectively. The survival and olfactory outcomes were analyzed in both cohorts. RESULTS: Thirty-three patients were identified in the published literature. Twenty-three (69.7%) reported postoperative olfaction preservation. Olfactory function after surgery did not show an association with Kadish stage (P = 0.128). No evidence of disease was observed at the latest follow-up in this group of patients. Nine patients who met inclusion criteria were identified at our institution. The extent of resection influenced the level of olfaction preservation when cribriform plate and nasal septum resection coexisted (P = 0.05). A single patient at our institution developed recurrence after being lost to follow-up for 22 months. CONCLUSIONS: Olfaction preservation can be achieved in patients who undergo endoscopic unilateral resection and adjuvant radiotherapy. The extent of resection should aim for negative margins, particularly in the midline. Larger studies are required to assess the risk of contralateral microscopic disease, and, hence, close follow-up is advised.

AMP-activated protein kinase inhibits vascular smooth muscle cell proliferation and migration and vascular remodeling following injury.

Vascular smooth muscle cell (VSMC) activation promotes a synthetic phenotype that underlies many vessel growth disorders. In this regard it has been suggested that the metabolic sensor adenosine 5'-monophosphate-activated protein kinase (AMPK) has significant antigrowth and antimetastatic properties and may serve as a viable therapeutic target. In the current study we hypothesized that AMPK reduces neointima formation following balloon injury and that this occurs through reduction in VSMC proliferation and migration. Data reveal that local or systemic dosing with the AMPK agonist 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR) significantly increased AMPK activity in vivo and inhibited neointima formation in rat carotid arteries 2 wk after injury. In primary VSMCs, AICAR inhibited migration and induced cytostatic growth arrest through increased protein phosphatase 2A-mediated inhibition of mitosis-promoting cyclin B. AICAR also significantly enhanced AMPK-specific T278 phosphorylation of the actin anticapping vasodilator-activated serum phosphoprotein, increased G- to F-actin ratios and stress fiber formation, and abrogated PDGF-stimulated S397 autophosphorylation of focal adhesion kinase, promigratory cytoplasmic accumulation of paxillin, and extracellular matrix proteolysis by matrix metalloproteinase-9. Together, these results provide compelling evidence that AMPK serves to inhibit vascular smooth muscle migration and proliferation through regulation of cytoskeletal/focal adhesion/ECM stability, increasing our knowledge of this important metabolic regulator and providing support for its continued investigation in the treatment of vascular growth disorders.

Hemostasis in endoscopic sinus and skull base surgery.

PURPOSE OF REVIEW: Bleeding during endoscopic endonasal procedures can quickly obscure critical anatomic landmarks. This increases both the difficulty of the surgical procedure and the risk of complications faced by the patient. As the indications for surgical management of sinonasal pathology grow, it is important to review techniques to minimize bleeding and facilitate safe surgery. RECENT FINDINGS: Evidence continues to accumulate for best practices in the surgical management of sinonasal disease. Recently, international guidelines have attempted to summarize this body of evidence, lending further support to several interventions which have been advocated as methods to decrease bleeding during endoscopic endonasal surgery. Additional studies have specifically investigated the safety of certain commonly employed techniques. The utility of preoperative corticosteroid therapy and the use of total intravenous anesthetic techniques in increasingly validated. Further evidence supports the safety of reverse Trendelenburg positioning for surgical management of inflammatory disease. SUMMARY: Recent wide scale systematic review of the literature regarding perioperative and intraoperative management of hemostasis has reinforced the utility of certain interventions, while others remain ambiguous.

Radial Forearm Free Flap with Parapharyngeal Pedicle Corridor for Reconstruction of Anterior Skull Base Defects.

BACKGROUND: The radial forearm free flap (RFFF) is an indispensable tool for the reconstruction of a range of defects, including those of the skull base. Several options for routing of the RFFF pedicle have been described, and the parapharyngeal corridor (PC) has been proposed as an option and employed for a nasopharyngeal defect. However, there are no reports of its use for the reconstruction of anterior skull base defects. The objective of this study is to describe the technique for free tissue reconstruction of anterior skull base defects using the RFFF and routing of the pedicle via the PC. METHODS: Relevant neurovascular landmarks and critical surgical steps for reconstruction of anterior skull base defects with an RFFF and routing of the pedicle via the PC are reported using an illustrative clinical case and cadaveric dissections. RESULTS: We present a case of a 70-year-old man who underwent endoscopic transcribriform resection of cT4N0 sinonasal squamous cell carcinoma and was left with a large anterior skull base defect that persisted despite several repair attempts. An RFFF was utilized to repair the defect. This report is the first description of the clinical use of the PC for free tissue repair of an anterior skull base defect. CONCLUSIONS: The PC is an option for routing the pedicle during the reconstruction of anterior skull base defects. When the corridor is prepared as described in this case, a direct route exists from the anterior skull base to cervical vessels, simultaneously maximizing the reach of the pedicle and minimizing the risk of kinking.

Rhinologist Use of Antibiotics With Nasal Packing for Epistaxis.

BACKGROUND: There is limited evidence supporting the usage of prophylactic antibiotics in the setting of nasal packing for epistaxis. It is unclear what current antiobiotic usage patterns are by otolaryngologists. OBJECTIVES: Characterize the antibiotic prescribing practices employed by otolaryngologists in the management of epistaxis patients treated with packing as well as the underlying rationale. Explore the impact of experience, geography, and academic affiliation on treatment decisions. METHODS: An anonymous survey of antibiotic prescribing patterns for patients with epistaxis requiring nasal packing was distributed to all physician members of the American Rhinologic Society. Responses to each question were descriptively summarized including 95% confidence intervals and were linked to demographics using Fisher's exact tests. RESULTS: One thousand one hundred and thirteen surveys were distributed with 307 responses (27.6%). Antibiotic prescription rates varied based on packing type, with 20.0% prescribing antibiotics for dissolvable packing compared to 84.2% to 84.6% for nondissolvable packing. The absorbance of nondissolvable packing does not impact the decision to prescribe antibiotics (P > .999). Precisely 69.7% (95% CI: 64.0%-74.8%) stop antibiotics immediately following packing removal. Precisely 85.6% (95% CI: 81.6%-89.9%) cite the risk of toxic shock syndrome (TSS) when prescribing antibiotics. Notable regional differences include greater utilization of amoxicillin-clavulanate in the Midwest (67.6%) and Northeast (61.4%) as compared with the South (42.1%) and West (45.1%) (P = .013). Further, years in practice were positively associated with several patterns including prescribing antibiotics for patients with dissolvable packing (P = .008), citing prevention of sinusitis as a rationale for antibiotic use (P < .001), and a higher likelihood of having treated a patient with TSS (P = .002). CONCLUSIONS: Antibiotic use in patients with epistaxis controlled with nondissolvable packing is common. Treatment patterns are influenced by geography, years in practice, and practice type. LEVEL OF EVIDENCE: 4.

Contralateral Transmaxillary Approach to Petrous Apex Granuloma with Lateral Maxillotomy: 2-Dimensional Operative Video.

The endoscopic endonasal approach (EEA) has proven to be a valuable tool to access the petrous apex (PA).1 Although lesions located medial to the PA can be easily accessed through an EEA with minimal risk to the internal carotid artery (ICA), more laterally seated lesions represent a surgical challenge. The contralateral transmaxillary approach is an effective extension of the normal EEA to the PA, allowing a more lateral trajectory and thereby reducing the risks connected to paraclival ICA manipulation.2-4 This is a 47-year-old female presenting with tinnitus, hearing loss, and right facial twitching. The preoperative audiogram showed a 60 dB sensorineural hearing loss, and magnetic resonance imaging demonstrated an expansive lesion of the PA with high signal intensity in T1- and T2-weighted sequences. A high-riding jugular bulb ruled out the use of an infracochlear infralabyrinthine approach, and a middle cranial fossa approach was felt to render a high risk of recurrence due to the potential for incomplete resection. Ultimately, a contralateral transmaxillary approach was selected. Due to the extreme lateral position of the lesion, the maxillotomy was created in the lateral wall of the maxillary sinus to allow a coaxial approach to the PA. Postoperatively, the patient did not report new neurologic deficits. Anatomic pathology was consistent with cholesterol granuloma (Video 1). In the surgical management of PA granulomas, recognizing relevant anatomic structures such as the paraclival ICA, cochlea, jugular bulb, and vestibule preoperatively is of paramount importance to tailor the surgical approach and reduce its risks.

Central compartment atopic disease: outcomes compared with other subtypes of chronic rhinosinusitis with nasal polyps.

BACKGROUND: Central compartment atopic disease (CCAD) is a variant of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) characterized by polypoid changes of the superior nasal septum, middle (MT), and/or superior turbinates (ST). This study evaluates surgical outcomes in patients with CCAD compared with other CRSwNP subtypes. METHODS: Retrospective analysis was performed at Emory University from May 2012 to November 2019. Patients undergoing primary endoscopic sinus surgery (ESS) for CCAD, aspirin-exacerbated respiratory disease (AERD), allergic fungal rhinosinusitis (AFRS), and CRSwNP not otherwise specified (CRSwNP NOS) were included consecutively, beginning with the earliest date of CCAD patient. Outcome measures included polyp recurrence, revision ESS, oral steroid use, and oral antibiotic use. Pearson chi-square and univariate analysis of variance (ANOVA) were performed for group comparisons. RESULTS: Data was collected for 132 patients (CCAD = 38, AERD = 20, AFRS = 37, CRSwNP NOS = 37; 58 females, mean age 42.9 years [range, 13-85 years]). CCAD patients demonstrated polyp recurrence less frequently than expected, whereas AFRS patients had polyp recurrence more frequently than expected (p = 0.003; phi 0.32). CCAD patients underwent revision ESS less frequently than expected; AFRS and CRSwNP NOS underwent revision ESS more frequently than expected (p = 0.03; phi 0.26). CRSwNP NOS patients received more total antibiotic courses than those with CCAD (p = 0.01; eta-squared 0.09) and more courses of antibiotics per month than those with AFRS (p = 0.03; eta-squared 0.07). There was no significant difference in follow-up measures across groups (number of visits, total months, or visits per month). CONCLUSION: Rates of polyp recurrence and revision ESS were significantly lower in CCAD patients compared with patients with other CRSwNP subtypes, suggesting durable benefit of ESS and postoperative medical therapy in CCAD patients.

Diagnostic Challenges in a Case of IgG4-RD Affecting the Temporal Bone.

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is a recently described fibroinflammatory condition with a characteristic histology. While IgG4-RD can affect a great variety of anatomical sites, it has been seldom described in the temporal bone. METHODS: Herein, a case IgG4-RD occurring in the temporal bone of a 35-year-old woman is reported. DISCUSSION: This case of IgG4-RD of the temporal bone proved a uniquely challenging diagnosis due to slightly atypical histology falling outside of "highly suggestive" criteria. CONCLUSIONS: We suggest that IgG4-RD remains a challenging diagnosis to reach despite increased awareness of the condition. We further suggest that clinicopathologic correlation remain the cornerstone of diagnosis as the spectrum of presentations of this newly described disease may be wider than previously anticipated.

Deletion of the EphA2 receptor exacerbates myocardial injury and the progression of ischemic cardiomyopathy.

EphrinA1-EphA-receptor signaling is protective during myocardial infarction (MI). The EphA2-receptor (EphA2-R) potentially mediates cardiomyocyte survival. To determine the role of the EphA2-R in acute non-reperfused myocardial injury in vivo, infarct size, inflammatory cell density, NF-κB, p-AKT/Akt, and MMP-2 protein levels, and changes in ephrinA1/EphA2-R gene expression profile were assessed 4 days post-MI in B6129 wild-type (WT) and EphA2-R-mutant (EphA2-R-M) mice lacking a functional EphA2-R. Fibrosis, capillary density, morphometry of left ventricular chamber and infarct dimensions, and cardiac function also were measured 4 weeks post-MI to determine the extent of ventricular remodeling. EphA2-R-M infarct size and area of residual necrosis were 31.7% and 113% greater than WT hearts, respectively. Neutrophil and macrophage infiltration were increased by 46% and 84% in EphA2-R-M hearts compared with WT, respectively. NF-κB protein expression was 1.9-fold greater in EphA2-R-M hearts at baseline and 56% less NF-κB after infarction compared with WT. EphA6 gene expression was 2.5-fold higher at baseline and increased 9.8-fold 4 days post-MI in EphA2-R-M hearts compared with WT. EphrinA1 gene expression in EphA2-R-M hearts was unchanged at baseline and decreased by 42% 4 days post-MI compared with WT hearts. EphA2-R-M hearts had 66.7% less expression of total Akt protein and 59% less p-Akt protein than WT hearts post-MI. EphA2-R-M hearts 4 weeks post-MI had increased chamber dilation and interstitial fibrosis and decreased MMP-2 expression and capillary density compared with WT. In conclusion, the EphA2-R is necessary to appropriately modulate the inflammatory response and severity of early injury during acute MI, thereby influencing the progression of ischemic cardiomyopathy.