Magnetic Resonance Imaging Prognostic Findings for Visual and Mortality Outcomes in Acute Invasive Fungal Rhinosinusitis.

PURPOSE: To identify initial, preintervention magnetic resonance imaging (MRI) findings that are predictive of visual and mortality outcomes in acute invasive fungal rhinosinusitis (AIFRS). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with histopathologically or microbiologically confirmed AIFRS cared for at a single, tertiary academic institution between January 2000 and February 2020. METHODS: A retrospective review of MRI scans and clinical records of patients with confirmed diagnosis of AIFRS was performed. For each radiologic characteristic, a modified Poisson regression with robust standard errors was used to estimate the risk ratio for blindness. A multivariate Cox proportional hazards model was used to study AIFRS-specific risk factors associated with mortality. MAIN OUTCOME MEASURE: Identification of initial, preintervention MRI findings associated with visual and mortality outcomes. RESULTS: The study comprised 78 patients (93 orbits, 63 with unilateral disease and 15 with bilateral disease) with AIFRS. The leading causes of immunosuppression were hematologic malignancy (38%) and diabetes mellitus (36%). Mucormycota constituted 56% of infections, and Ascomycota constituted 37%. The overall death rate resulting from infection was 38%. Risk factors for poor visual acuity outcomes on initial MRI included involvement of the orbital apex (relative risk [RR], 2.0; 95% confidence interval [CI], 1.1-3.8; P = 0.026) and cerebral arteries (RR, 1.8; 95% CI, 1.3-2.5; P < 0.001). Increased mortality was associated with involvement of the facial soft tissues (hazard ratio [HR], 4.9; 95% CI, 1.3-18.2; P = 0.017), nasolacrimal drainage apparatus (HR, 5.0; 95% CI, 1.5-16.1; P = 0.008), and intracranial space (HR, 3.5; 95% CI, 1.4-8.6; P = 0.006). Orbital soft tissue involvement was associated with decreased mortality (HR, 0.3; 95% CI, 0.1-0.6; P = 0.001). CONCLUSIONS: Extrasinonasal involvement in AIFRS typically signals advanced infection with the facial soft tissues most commonly affected. The initial, preintervention MRI is prognostic for a poor visual acuity outcome when orbital apex or cerebral arterial involvement, or both, are present. Facial soft tissues, nasolacrimal drainage apparatus, intracranial involvement, or a combination thereof is associated with increased mortality risk, whereas orbital soft tissue involvement is correlated with a reduced risk of mortality.

Retrobulbar Injection of Amphotericin B for Orbital Mucormycosis.

A 68-year-old immunocompromised man with rhino-orbital-cerebral mucormycosis was treated with retrobulbar injections of amphotericin B deoxycholate in conjunction with intravenous antifungals and endoscopic sinus debridement. Transient episodes of orbital inflammation were noted after retrobulbar injections, but progression of orbital infection was halted and visual acuity restored with eventual hospital discharge. To the authors' knowledge, clearance of orbital mucormycosis with retrobulbar amphotericin B injections has not been previously reported. This intervention may be a viable therapeutic option in cases of orbital mucormycosis where aggressive orbital debridement is not favored and/or the burden of orbital disease is not substantial. However, physicians should be aware of the risk of transient orbital inflammation secondary to retrobulbar amphotericin B deoxycholate.

Transcutaneous Retrobulbar Amphotericin B Injection for Invasive Fungal Sinusitis with Orbital Involvement: A Systematic Review.

BACKGROUND: Orbital involvement of invasive fungal sinusitis (IFS) is an ominous prognostic marker that should prompt rapid intervention. Transcutaneous retrobulbar administration of amphotericin B (TRAMB) is an off-label adjunctive treatment that can increase drug penetrance into diseased orbital tissue. To date, there is a lack of consensus regarding the use of TRAMB for treatment of IFS with orbital involvement. OBJECTIVE: This systematic review aims to synthesize the indications, efficacy, and potential complications of TRAMB. METHODS: PubMed, EMBASE, and Web of Science databases were probed for systematic review. Article search was conducted through June 2023 using the keywords "invasive fungal sinusitis," "invasive fungal rhinosinusitis," "rhino-orbital mucormycosis," "rhinosinusitis," "orbital," "retrobulbar," and "amphotericin." RESULTS: In suitable cases as determined by radiologic and clinical evaluation, TRAMB administration has the potential to improve orbital salvage rates and improve versus stabilize visual acuity. Treatment complications are more likely with deoxycholate than with liposomal amphotericin formulations. The existing literature describing use of TRAMB is limited due to its retrospective nature, but the increase in IFS cases since 2020 due to the COVID pandemic has broadened the literature. CONCLUSIONS: TRAMB is an effective adjunctive treatment in IFS with mild-to-moderate orbital involvement when used in combination with standard of care debridement, systemic antifungal therapy, and immunosuppression reversal. Prospective longitudinal studies and multi-institutional randomized trials are necessary to determine the definitive utility of TRAMB.

RNA Sequencing and Gene Ontology Analysis in Acute Invasive Fungal Sinusitis.

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is an aggressive and dangerous disease of the paranasal sinuses with high morbidity and mortality. The immune response at the level of the nasal mucosa, the site of entry, has not been previously evaluated. OBJECTIVE: To evaluate differential gene expression in the sinonasal mucosa of AIFS patients as compared to control patients using RNA sequencing. METHODS: Sinonasal tissue samples were prospectively obtained from consenting patients undergoing surgery between November, 2020 and November, 2021. RNA extraction and sequencing were performed and differential expression was analyzed to detect transcriptional differences between patient groups. RESULTS: Tissue samples were collected from 4 patients with active AIFS diagnoses, 2 patients with recovered AIFS, 1 patient with a diagnosis of non-invasive fungal ball, and 4 healthy controls. 255 genes were differentially expressed in AIFS patients as compared to control patients. Specific Gene Ontology (GO) biological processes that were identified as differentially expressed in AIFS patients as compared to controls included the following: 1. GO:0007155 (cell adhesion), 2. GO:0030199 (collagen fibril organization) and 3. GO:0001525 (angiogenesis). CONCLUSION: Transcriptional differences were noted between AIFS and control patients in sinonasal tissue samples. Future work is necessary to determine causes of the differential gene expressions between AIFS and control patients, specifically those who are immunosuppressed, or with preexisting non-invasive forms of fungal sinusitis, to guide treatment and prevention strategies.

Diagnosis, Prognosticators, and Management of Acute Invasive Fungal Rhinosinusitis: Multidisciplinary Consensus Statement and Evidence-Based Review with Recommendations.

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is an aggressive disease that requires prompt diagnosis and multidisciplinary treatment given its rapid progression. However, there is currently no consensus on diagnosis, prognosis, and management strategies for AIFS, with multiple modalities routinely employed. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on AIFS, summarize the existing evidence, and provide recommendations on the management of AIFS. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through January 2022. Studies evaluating management for orbital, non-sinonasal head and neck, and intracranial manifestations of AIFS were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on management principles for AIFS were generated. RESULTS: A review and evaluation of published literature was performed on 12 topics surrounding AIFS (signs and symptoms, laboratory and microbiology diagnostics, endoscopy, imaging, pathology, surgery, medical therapy, management of extrasinus extension, reversing immunosuppression, and outcomes and survival). The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, judicious utilization of a combination of history and physical examination, laboratory and histopathologic techniques, and endoscopy provide the cornerstone for accurate diagnosis of AIFS. In addition, AIFS is optimally managed by a multidisciplinary team via a combination of surgery (including resection whenever possible), antifungal therapy, and correcting sources of immunosuppression. Higher quality (i.e., prospective) studies are needed to better define the roles of each modality and determine diagnosis and treatment algorithms.

The effect of neck muscle fatigue on shoulder humeral rotation joint position sense.

INTRODUCTION: Cervical extensor muscle (CEM) fatigue causes decrements in upper limb proprioceptive accuracy during constrained single-joint tasks. This study used a novel humeral rotation joint position sense (JPS) measurement device to compare JPS accuracy in participants who received acute CEM fatigue vs. non-fatigued controls. METHODS: Participants had vision occluded and were passively guided into postures of internal humeral rotation from a baseline posture before and after a CEM fatigue or control protocol. Mixed model repeated measures ANOVAs were used to verify fatigue and compared absolute, constant, and variable JPS error between groups. RESULTS: CEM fatigue was verified via pre-post reduction in CEM strength, and myoelectric indicators of fatigue. However, between-group comparisons of absolute, constant, and variable JPS error were not statistically significant, despite having large effect sizes. DISCUSSION: Contrary to prevailing literature, unconstrained humeral rotation JPS did not appear to be affected by CEM fatigue in this study. However, between-group differences in JPS error were dwarfed by inter-trial variability, which likely arose due to the unconstrained nature of this task, conflating chances for a Type II error. Future research should perform a kinematic analysis of task constraints to highlight potential compensatory mechanisms obscuring significant findings in this otherwise robust effect.

Role of the neurotologist in posterior fossa meningioma surgery.

Posterior fossa meningiomas that impinge on structures of the temporal bone or clivus may be difficult to access for optimal resection that maximizes tumor control and minimizes short- and long-term morbidities. To address this challenge, the contemporary neurosurgery-neurotology team works collaboratively by managing patients jointly at every stage of care: preoperative evaluation, intraoperative intervention, and postoperative treatment. The neurotologist is important at all stages of posterior fossa meningioma surgery. First, detailed preoperative evaluation of auditory, facial, vestibular, and lower cranial nerve integrity enables assessment of new neurologic deficit risk, prognosis of functional recovery, and pros and cons of candidate surgical approaches. Second, intraoperative partitioning of surgical steps by provider and adopting an overlapping tumor resection philosophy creates an efficient and confident surgical team built on trust. Third, postoperative closure of cerebrospinal fluid leak and treatment of facial weakness, audiovestibular dysfunction, and voicing and swallowing impairments organized by the neurotologist reduces the impact of negative outcomes. The role of the neurotologist in posterior fossa meningioma surgery is to deliver nuanced evaluative metrics, facilitate shared decision making, perform precise bone and soft tissue microsurgery, and mitigate perioperative morbidities.

Tracheostomy guidelines developed at a large academic medical center during the COVID-19 pandemic.

BACKGROUND: During the SARS-CoV-2 pandemic, tracheostomy may be required for COVID-19 patients requiring long-term ventilation in addition to other conditions such as airway compromise from head and neck cancer. As an aerosol-generating procedure, tracheostomy increases the exposure of health care workers to COVID-19 infection. Performing surgical tracheostomy and tracheostomy care requires a strategy that mitigates these risks and maintains the quality of patient care. METHODS: This study is a multidisciplinary review of institutional tracheostomy guidelines and clinical pathways. Modifications to support clinical decision making in the context of COVID-19 were derived by consensus and available evidence. RESULTS: Modified guidelines for all phases of tracheostomy care at an academic tertiary care center in the setting of COVID-19 are presented. DISCUSSION: During the various phases of the COVID-19 pandemic, clinicians must carefully consider the indications, procedural precautions, and postoperative care for tracheostomies. We present guidelines to mitigate risk to health care workers while preserving the quality of care.

Immediate Voice and Swallowing Complaints Following Revision Anterior Cervical Spine Surgery.

OBJECTIVE: To report on the incidence of dysphagia, dysphonia, and acute vocal fold motion impairment (VFMI) following revision anterior cervical spine surgery, as well as to identify risk factors associated with acute VFMI in the immediate postoperative period. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care center. SUBJECTS AND METHODS: All patients who underwent 2-team reoperative anterior cervical discectomy and fusion (ACDF) were retrospectively reviewed. Incidence of dysphonia, dysphagia, and acute VFMI was noted. Patient and operative factors were evaluated for association with risk of acute VFMI. RESULTS: The incidence of postoperative dysphonia and dysphagia was 25% (18/72) and 52% (37/72), respectively. The incidence of immediate VFMI was 21% (15/72). Subjective postoperative dysphonia (odds ratio, [OR] 8; 95% CI, 2.2-28; P = .001) and dysphagia (OR, 22; 95% CI, 2.5-168; P = .005) were significantly associated with increased risk of VFMI. Three patients with VFMI required temporary injection medialization for voice complaints and/or aspiration. Infection (OR, 14; 95% CI, 1.4-147, P = .025) and level C7/T1 (OR, 5.5; 95% CI, 1.3-23, P = .02) were significantly associated with an increased risk of acute VFMI on multivariate logistic regression analysis. Number of prior surgeries, laterality of approach, side of approach relative to prior operations, and number of levels exposed were not significant. CONCLUSION: Early involvement of an otolaryngologist in the care of a patient undergoing revision ACDF can be helpful to the patient in anticipation of voice and swallowing changes in the postoperative period. This may be particularly important in those being treated at C7/T1 or those with spinal infections.

Urgent Infections of the Head and Neck.

Infections of the head and neck are common and appropriately managed by primary care providers in most cases. However, some infections are associated with significant morbidity and require urgent recognition and management by specialty services. These include deep neck space infections originating in the oral cavity, pharynx, and salivary glands, as well as complicated otologic and sinonasal infection. This article provides a review of these conditions, including the pathophysiology, presenting features, and initial management strategy.

The otolaryngology hospitalist: a novel practice paradigm.

OBJECTIVES/HYPOTHESIS: To define a new clinical hospitalist practice paradigm originating at the University of California, San Francisco. DESIGN: Retrospective administrative database review at a tertiary referral hospital. MATERIALS AND METHODS: A consortium model of an otolaryngologist hospitalist practice was developed. Billing records, including Current Procedural Terminology (CPT) and International Classification of Disease-9 (ICD-9) codes, were reviewed to evaluate the number and type of consultations and surgeries generated during a 2-year period. RESULTS: A total of 375 new inpatient consultations generated 951 patient encounters. The most common diagnoses were respiratory failure (12%), sinusitis (10.6%), stridor (10.6%), and dysphonia (7.6%). Twenty-six percent of consultations involved a procedure or surgical intervention, the most common of which were endoscopic sinus surgery, laryngoscopy, and tracheotomy. CONCLUSIONS: To our knowledge, ours is the first full-time otolaryngology hospitalist model in the United States. The hospitalist practice is a conceptually viable and clinically beneficial paradigm that should be considered at other similar institutions.

Wound botulism presenting as a deep neck space infection.

Otolaryngologists commonly evaluate patients with findings suspicious for deep space soft tissue infections of the neck. In this case, a woman with a history of injection drug use (IDU) presented with dysphagia, odynophagia, and neck pain. Multiple neck abscesses, too small to drain, were seen on imaging. Despite broad-spectrum intravenous antibiotics, she unexpectedly and rapidly developed respiratory failure requiring intubation. Further work-up diagnosed wound botulism (WB). To our knowledge, this is the first report of WB presenting as a deep neck space infection, and illustrates the importance of considering this deadly diagnosis in patients with IDU history and bulbar symptoms.

Synthetic signaling networks for therapeutic applications.

Synthetic signaling networks contain exogenous, modified, or rationally designed components involved in sending, receiving, and processing information from the environment and other cells. Advances in the input, output, and processing elements for such networks hold promise towards developing new therapies and prophylactics for disease. Therapeutic synthetic signaling systems are still in their infancy, but are progressing into mouse models of disease and even into clinical trials. As signaling technology matures, we will see an increase in implanted and ingested cellular therapies capable of autonomously diagnosing and treating disease. These technologies have the potential to reduce some of the burden on both patients and clinicians, contributing to more efficient and eventually personalized medicine.

Bootstrap estimation of confidence intervals on mutation rate ratios.

The fluctuation test is a useful tool for estimating the mutation rate of cells. However, statistical methods for comparing mutation rate estimates between different strains or conditions have not yet been fully developed. Methods exist for placing confidence intervals on estimates of the number of mutational events in cultures for a given strain and set of conditions, but placing confidence intervals on mutation rate is complicated by differences in the final number of cells in culture between parallel cultures. Additionally, confidence intervals on individual mutation rate estimates are not always the most useful statistical tool when comparing two or more different strains or conditions. We present a bootstrap method for estimating confidence intervals on the quotient of two mutation rates determined from two fluctuation test experiments using experimental and control strains or conditions. We use Monte Carlo simulations to validate this method over a wide range of mutation rates and for empirically measured variation in the estimates of final number of cells in culture. Furthermore, we provide the computational tools to implement the bootstrap method described here on experimental fluctuation test data and to evaluate this method for experimental parameters other than those considered herein.