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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.
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COVID-19 , Transtornos do Olfato , COVID-19/complicações , COVID-19/terapia , Humanos , Transtornos do Olfato/etiologia , Transtornos do Olfato/terapia , Olfato , Resultado do TratamentoRESUMO
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.
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Proteínas Quinases Ativadas por AMP/metabolismo , Proliferação de Células/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/enzimologia , Aorta Torácica/patologia , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Ativação Enzimática , Ativadores de Enzimas/farmacologia , Masculino , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/enzimologia , Miócitos de Músculo Liso/patologia , Fosforilação , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/genética , Fatores de Tempo , TransfecçãoRESUMO
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.
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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.
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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 olfactory neuroblastoma. 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 olfactory neuroblastoma 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.
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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.
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Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/lesões , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Actinas/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Animais , Aorta Torácica/citologia , Aorta Torácica/efeitos dos fármacos , Lesões das Artérias Carótidas/patologia , Adesão Celular/fisiologia , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citoesqueleto/metabolismo , Imunofluorescência , Hipoglicemiantes/farmacologia , Imuno-Histoquímica , Masculino , Metaloproteinases da Matriz/metabolismo , Neointima/patologia , Ratos , Ratos Sprague-Dawley , Ribonucleotídeos/farmacologiaRESUMO
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.
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Endoscopia , Seios Paranasais , Humanos , Endoscopia/métodos , Seios Paranasais/cirurgia , Procedimentos Neurocirúrgicos , Base do Crânio/cirurgia , HemostasiaRESUMO
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.