Current Opinion in Otolaryngology & Head and Neck Surgery最新文献

Purpose of review: This review summarizes recent advances in the use of botulinum toxin (BoNT) for laryngeal disorders. It highlights the growing therapeutic relevance of BoNT across both motor and sensory conditions, focusing on novel indications, evolving mechanisms of action, and innovations in injection techniques.

Recent findings: BoNT remains the primary treatment for laryngeal dystonia, with increasing personalization in dosing, target selection, and outcome assessment. New evidence supports its application in functional dysphonia, vocal process granuloma, chronic cough, inducible laryngeal obstruction, and abnormal throat sensation. Studies suggest both peripheral and central neuromodulatory effects, including modulation of afferent input and neuroplastic changes. Guidance techniques such as electromyography, ultrasound, and flexible endoscopy are improving injection accuracy. Adjunctive therapies, including pharmacological agents and sensory retraining approaches, show promise for partial or nonresponders.

Summary: BoNT is an increasingly versatile and well tolerated treatment across a broadening spectrum of laryngeal disorders. As knowledge of laryngeal neurobiology expands, BoNT is being redefined as both a focal therapeutic and a neuromodulator with broad implications for voice and airway management.

Purpose of review: Management of fetal airway obstruction requires a multidisciplinary approach to optimize the safety of the pregnant patient and fetus. For severe cases of fetal airway obstruction, ex-utero intrapartum treatment (EXIT) is recommended. This review highlights indications and rationale for EXIT and presents an approach to fetal airway management from an otolaryngologic perspective.

Recent findings: Approach to the fetus with airway obstruction differs in the literature. Recent studies have sought to identify prenatal risk factors that portend the need for surgical intervention at delivery, with identification of three fetal anomalies that justify delivery modification: micrognathia, congenital high airway obstruction, and head and neck masses. There remains heterogeneity within this cohort, contributing to the varied approach to fetal airway obstruction. What remains consistent is the need for early identification of at-risk fetuses and multidisciplinary input throughout pregnancy to ensure that the appropriate teams are present at delivery.

Summary: EXIT is a mainstay in the management of fetal airway obstruction, as it enables airway intervention while preserving uteroplacental circulation. Further research is needed to define indications for EXIT and develop management algorithms starting from identification of airway obstruction on prenatal imaging. Multidisciplinary collaboration is tantamount to a successful procedure.

Purpose of review: This review aims to provide a comprehensive analysis of the pathophysiology and treatment of middle ear myoclonus (MEM), a rare and under-recognized cause of objective and subjective tinnitus.

Recent findings: MEM is increasingly recognized as a distinct subset in tinnitus patients, with symptoms arising from involuntary contractions of the stapedius and/or tensor tympani muscles. Pharmacological management currently centres around agents such as clonazepam, carbamazepine, and piracetam. Surgical resection of middle ear tendons has yielded highly encouraging results, albeit with risks such as hyperacusis and symptom recurrence due to tendon reattachment. Endoscopic surgical techniques offer improved visualization and reduced invasiveness. Emerging data support the potential role of botulinum toxin as a less invasive and reversible therapeutic option, particularly with intratympanic delivery methods demonstrating early safety and efficacy in recent studies.

Summary: MEM is a complex otologic condition with limited high-quality data guiding its diagnosis and management. Due to its variable presentations and response to treatment, a multidisciplinary and individualized approach remains essential. While pharmacological treatments and surgical outcomes are generally favourable, interest in botulinum toxin continues to grow. Further large-scale, controlled studies are needed to clarify pathophysiological mechanisms, optimize diagnostic accuracy, and standardize treatment protocols.

Purpose of review: Drug delivery to the cochlea has been hampered by the very mechanisms that exist to protect its delicate neurosensory epithelium from pathogens. The blood-brain barrier restricts the distribution of systemic therapies, while local administration is constrained by basal to apical gradients. As we progress towards restorative and regenerative therapies, precise delivery of therapeutics to their target site is required. This review discusses the surgical approaches to cochlear therapeutic delivery that can overcome these barriers.

Recent findings: Recent advancements in microneedle technology have facilitated nondestructive round window membrane penetration that overcomes restrictive diffusion. Direct intracochlear catheterisation provides a solution to traditional basal to apical gradients along the cochlear duct, particularly when combined with fenestration for allowance of efflux. Drug-eluting implants present a unique opportunity for direct intrascalar administration, which may be extended in a sustained-release format. Finally, surgical approaches for direct injection to the modiolus have been detailed, allowing maximum survival of stem cell grafts.

Summary: The evolution of precise pharmacotherapy to specific subsites of the cochlea demands precise methods of administration. These novel strategies often require a surgical approach and can overcome the protective barriers of the cochlea that traditionally restrict pharmacodynamics and pharmacokinetics.

Purpose of review: Preclinical auditory research uncovers mechanisms underlying hearing loss and reveals novel therapeutic targets. Inner ear gene therapy offers an attractive alternative to current treatments for deafness. An in-depth understanding of the principles of gene therapy is essential to the design of cochlear gene therapy studies, which must be meticulously selected based on the etiology, pathophysiology, and mechanisms of hearing loss. The purpose of our article is to provide an updated and succinct review of cochlear gene therapy.

Recent findings: Advances in molecular technology have enabled numerous proof-of-principle studies in recent years, testing the feasibility of protective, restorative, and regenerative cochlear gene therapy. Recent findings have demonstrated how the delivery of neurotrophic factor transgenes can potentially improve hearing in hidden hearing loss. Restorative gene therapy, carrying the OTOF gene, has restored hearing in human subjects in clinical trials. Additionally, ongoing efforts are underway to regenerate sensory cells in the cochlea using cocktails of transcription factors in postdeafened animal models.

Summary: Recent successes in clinical trials for cochlear gene therapy are encouraging; however, preclinical auditory research remains a high priority and necessity. Future advancements in basic science research may enable the prevention or cure of deafness through cochlear gene therapy.

Purpose of review: The recent successful otoferlin gene therapy trials have refocused the fields attention on the potential of gene therapy to cure hearing loss. With over 100 known monogenetic causes of hearing loss, the key question is which will be the next set of disorders that are treatable. The current review addresses potentially targetable hearing disorders that can be addressed with current gene therapy technologies.

Recent finding: For gene replacement therapy, we need to consider disorders that have residual targetable cells present in postnatal to adult ages. If a target tissue (i.e. hair cells) degenerates during development, it can no longer be rescued by gene therapy. Disorders such as DFNB8 and certain mutations in DFNB1 could benefit from a gene therapy approach. Other important considerations are the size of the gene being replaced, the availability of appropriate vectors, and the overall incidence of the disease.

Summary: Genetic hearing losses that occur in the postnatal period are currently optimal targets and conversely hearing losses that occur in utero resulting in severe to profound congenital losses for now will not be treatable with gene therapy. Gene replacement therapy for recessive disorders will precede development of gene editing strategies for dominant disorders.

Purpose of review: Autoimmune inner ear disease (AIED) is a rare inner ear disorder characterised by fluctuating, progressive, bilateral sensorineural hearing loss that is responsive to immunomodulatory medications. Due to a lack of widely accepted diagnostic criteria its diagnosis remains elusive. Consequently, little is known about its precise aetiology.

Recent findings: A novel classification system for "immune-mediated inner ear disease" (IMIED) has been proposed, which incorporates additional ear pathologies with identified immune components. This acknowledges the breadth of ear conditions that may respond to immune modulation. A range of diagnostic biomarkers are identified with varied clinical efficacy. This is appraised within the full context of a clinical setting to provide insight into practical utility. The efficacy of traditional steroid therapy is re-appraised and remains first-line therapy., The indication for steroid spring therapies is identified, and modern immunomodulatory medications are discussed.

Summary: AIED should be discussed within the spectrum of "immune-mediated inner ear disease", and therapeutic efficacy may be translated along the spectra. Diagnostic biomarkers must be appraised with caution, and diagnosis still relies on responses to steroids. Steroid sparring agents are efficacious for long-term management, and modern biologics show promise, but further investigation is needed.

Purpose of review: We briefly review the history of surgical innovation in free flap reconstruction of the head and neck. With a specific focus on maximizing patient QoL by prioritizing a 'precision reconstruction', we then posit novel avenues for surgical refinement to usher in the next generation of head and neck free flap reconstruction.

Recent findings: Patients undergoing free flap reconstruction of the head and neck increasingly co-prioritize preservation of quality-of-life (QoL) alongside the desire to survive their diagnosis. In the contemporary era, this fact has prompted microvascular surgeons to customize reconstructive plans to minimize decisional regret and maximize favorable functional and cosmetic outcomes for their patients. Increasingly popular strategies for surgical refinement and innovation in this space include novel flap harvest techniques, unconventional flap donor sites, and use of flow-through configurations, all of which are routinely utilized in our group's practice. Additional strategies gaining traction in head and neck reconstruction include vascular perfusion imaging with indocyanine green fluorescence angiography and 'Jaw-in-a-Day' surgeries leveraging computer-aided design (CAD)/computer-aided manufacturing (CAM) technologies.

Summary: The next frontier of innovation in free flap reconstruction of the head and neck will prioritize custom, patient-specific reconstructions that consider the unique anatomic, functional, and aesthetic needs of each patient (i.e. precision reconstruction).

Purpose of review: To review current intraoperative imaging techniques utilized in head and neck reconstruction, with a focus on applications in vascular perfusion assessment, bony reconstruction, and improved intraoperative visualization and education.

Recent findings: In recent years, there have been both technological advances as well as increased implementation of imaging techniques in head and neck reconstruction. To assess for real-time flap perfusion, indocyanine green fluorescence angiography (ICG) has become increasingly adopted, allowing for early identification of vascular compromise and improved flap viability. In bony reconstruction, intraoperative CT and navigation systems have enhanced the precision of osteotomies and hardware placement. Emerging technologies such as the exoscope system have also contributed to improved intraoperative visualization, surgical planning, and education for trainees and multidisciplinary teams.

Summary: Intraoperative imaging continues to advance the safety and precision of head and neck reconstruction. Techniques such as ICG, intraoperative navigation, and augmented visualization tools support better decision-making, reduced complication rates, and enhanced surgical education. Ongoing investigation is needed to standardize protocols, integrate quantitative thresholds for perfusion and bony alignment, and more widely implement technologies.

Purpose of review: There are currently five groups internationally involved in human clinical gene therapy trials for otoferlin-associated hearing loss. This includes (in alphabetical order) the Eye and ENT Hospital Fudan University (China), Lilly-Akouos (USA), Otovia (China), Regeneron (USA), and Sensorion (France). This review summarizes early work that led to these efforts and highlights early published data on clinical outcomes.

Recent findings: While published outcomes are currently limited, data emerging from each of these clinical trials is highly consistent. Using a dual vector approach to reconstitute full length Otoferlin, all groups report varying degrees of hearing improvement following cochlear gene therapy, with some cases of hearing restoration to normal levels. Recent data suggests that improvement is not limited only to young children but also adolescents and even young adults in some cases. The treatments all appear safe with limited adverse effects associated with the therapies reported.

Summary: Gene therapy for otoferlin-related deafness appears highly successful in most cases with limited reported adverse effects or outcomes. This success will undoubtably usher in a new era of gene therapy for other forms of genetic deafness.