Chronic invasive fungal rhinosinusitis and granulomatous invasive fungal sinusitis: A systematic review of symptomatology and outcomes.

INTRODUCTION: Chronic invasive fungal rhinosinusitis (CIFRS) and granulomatous invasive fungal sinusitis are two uncommon diseases differentiated primarily by the pathologic finding of non-caseating granulomas in GIFRS. Both share many similarities in presentation. We aim to characterize the symptomatology and outcomes of these diseases. METHODS: A comprehensive search strategy was designed to identify studies in the Cochrane, EMBASE and PubMed databases from database inception to January 2022. Inclusion criteria included all patients with a diagnosis of either CIFRS or GIFRS. All studies were screened by two reviewers. Chi-square analyses were used where appropriate. RESULTS: 51 studies were included totaling 513 patients. The majority were diagnosed with CIFRS (389, 75.8 %) compared to GIFRS (124, 24.4 %). CIFRS was more common in immunocompromised or diabetic patients (p < 0.0001; p = 0.02). Patients with CIFRS were more likely to exhibit nasal symptoms including discharge (p = 0.0001), obstruction (p = 0.03) and congestion (p = 0.001) as well as systemic symptoms including fever, which no GIFRS patient exhibited, facial pain (p = 0.007), headache (p = 0.004). Aspergillus was the most common organism identified in both groups with a slight predominance among GIFRS patients (p = 0.01). GIFRS patients were also more likely to present with no identifiable organisms (p = 0.0006). CIFRS patients were more likely to die of disease (p = 0.0008). CONCLUSIONS: CIFRS generally presents with more symptoms and is associated with poorer outcomes primarily occurring in an immunocompromised population. GIFRS likely follows a more insidious course in immunocompetent patients. Understanding the key differences in symptomatology and outcomes for these two populations is critical for appropriate diagnosis and prognostication.

Efficiency of microvascular free flap reconstructive surgery: An observational study.

OBJECTIVE: We aimed to assess operative workflow and efficiency in microvascular free flaps via a direct observational study based on Lean principles of quality improvement (QI). METHODS: Observers monitored the workflow of twenty-three free flaps. Pre-operative preparation and surgical duration was recorded with supplemental data provided from our institution's surgical tracking database. Traffic patterns of operating room (OR) staff were documented as "entries" and "exits" from the OR and classified by role and the reason that the entry or exit was required. Patient data was obtained via chart review. RESULTS: The mean surgical time was 9.0 h. Approximately 20% of OR time was dedicated to the pre-incision process, averaging 1.6 h per case. One third of entries and exits occurred during this period. In total, 180.2 surgical hours were observed during which 6215 "entries" and "exits" occurred. The mean number of entries and exits per case was 270; the most common reasons were supplies and communication. No association was observed between elapsed surgical time or total number of entries and exits with post-operative infection rates. CONCLUSION: Comprehensive observational workflow studies of free flaps are challenging to execute due to lengthy procedure times. At our high-volume institution, a significant portion of OR time is devoted to the pre-incision period, largely due to inadequate supply availability and pre-operative communication. These findings will serve as a foundation for QI interventions at our institution, while our observational model provides a broadly applicable framework for assessing surgical efficiency.

Acute myeloid leukemia: An unusual manifestation of the trachea.

Objectives: Hematologic malignancy involving the trachea is rare. It is even less common for tracheal involvement to be the initial manifestation of this disease. We present a case report highlighting an unusual diagnosis of acute myeloid leukemia (AML) that first presented with prominent tracheal manifestations. There have been only three other published case reports of extramedullary AML with involvement of the trachea. Methods: We discuss direct laryngoscopy and bronchoscopy findings, including pinkish-white irregular lesions, which were similar to findings described in the available literature for tracheal AML. Results: Laboratory findings from our case are reported, including peripheral smear demonstrating 57% blasts and bone marrow biopsy confirming the diagnosis of AML, and the relevance of these findings is discussed. Conclusion: In patients with unusual airway lesions, laboratory testing and a comprehensive airway evaluation including biopsy are necessary to narrow the differential diagnosis. Level of Evidence: 5.

Nonendemic rhinoscleroma: An unusual manifestation of the trachea.

Objectives: Rhinoscleroma is classically described as a chronic granulomatous disease caused by Klebsiella rhinoscleromatis which primarily affects the nose and nasopharynx. When present, tracheal manifestations will be seen late in the disease course rather than on initial presentation. We describe a rare case of nonendemic rhinoscleroma that presented with tracheal lesions as an initial manifestation of disease. Methods: Case report and literature review. Results: An 88-year-old male presented with longstanding dysphonia. Flexible laryngoscopy demonstrated a septal perforation and diffuse glottic lesions. CT neck demonstrated a nonobstructive polypoid tracheal lesion and mucosal thickening of the paranasal sinuses. Biopsy confirmed an atypical lympho-histiocytic proliferation and microorganisms within macrophages on Grocott methenamine silver and Steiner stains consistent with rhinoscleroma. He was referred for rheumatology and pulmonology consultation. Conclusion: Systemic diseases rarely affect the trachea, and even less frequently is a tracheal lesion identified as the initial manifestation of disease. The most common systemic diseases that affect the trachea include relapsing polychondritis, granulomatosis with polyangiitis, amyloidosis, and inflammatory bowel disease. The literature surrounding nasolaryngotracheal rhinoscleroma is limited, especially in nonendemic areas. It is necessary to include unusual etiologies of airway lesions in the differential diagnosis, which warrants comprehensive airway evaluation including biopsy. Level of Evidence: 4.

Long-term upper aerodigestive sequelae as a result of infection with COVID-19.

Objectives: Respiratory, voice, and swallowing difficulties after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result secondary to upper airway disease from prolonged intubation or mechanisms related to the virus itself. We examined a cohort who presented with new laryngeal complaints following documented SARS-CoV-2 infection. We characterized their voice, airway, and/or swallowing symptoms and reviewed the clinical course of their complaints to understand how the natural history of these symptoms relates to COVID-19 infections. Methods: Retrospective review of patients who presented to our department with upper aerodigestive complaints as sequelae of prior infection with, and management of, SARS-CoV-2. Results: Eighty-one patients met the inclusion criteria. Median age was 54.23 years (±17.36). Most common presenting symptoms were dysphonia (n = 58, 71.6%), dysphagia/odynophagia (n = 16, 19.75%), and sore throat (n = 9, 11.11%). Thirty-one patients (38.27%) presented after intubation. Mean length of intubation was 16.85 days (range 1-35). Eighteen patients underwent tracheostomy and were decannulated after an average of 70.69 days (range 23-160). Patients with history of intubation were significantly more likely than nonintubated patients to be diagnosed with a granuloma (8 vs. 0, respectively, p < .01). Fifty patients (61.73%) were treated for SARS-CoV-2 without requiring intubation and were significantly more likely to be diagnosed with muscle tension dysphonia (19 vs. 1, p < .01) and laryngopharyngeal reflux (18 vs. 1, p < .01). Conclusion: In patients with persistent dyspnea, dysphonia, or dysphagia after recovering from SARS-CoV-2, early otolaryngology consultation should be considered. Accurate diagnosis and prompt management of these common underlying etiologies may improve long-term patient outcomes. Level of evidence: 4.

Displacement of a Total Ossicular Replacement Prosthesis Following Ossicular Chain Reconstruction.

OBJECTIVE: Herein we describe the diagnosis and management of total ossicular replacement prosthesis (TORP) displacement following tympanoplasty with ossicular chain reconstruction (OCR). METHODS: Case report with literature review. RESULTS/CASE: A 40-year-old male with otorrhea and tympanic membrane perforation underwent a right revision tympanoplasty with OCR using a TORP with a tragal chondroperichondrial graft. On postoperative day (POD) 4, he developed vertigo and profound right-sided hearing loss. Temporal bone computed tomography showed the prosthesis in the vestibule. After a steroid taper with mild improvement in symptoms, the TORP was removed two weeks later and the patient continued to improve. CONCLUSION: TORP displacement into the vestibule is a very rare complication following OCR. Conservative management with high dose steroids may improve symptoms, however further middle ear exploration and surgical management may be warranted depending on the depth of displacement into the inner ear as well as symptom severity.

Surgical Outcomes With Cochlear Implantation in Patients With Enlarged Cochlear Aperture: A Systematic Review.

OBJECTIVE: Evaluate surgical outcomes in patients with enlarged cochlear aperture (ECA) after cochlear implantation. DATABASES REVIEWED: PubMed, EMBASE, and Scopus. METHODS: A systematic review was performed using standardized methodology. Studies were included if they included subjects with ECA who underwent cochlear implantation. Exclusion criteria included non-English articles, abstracts, letters/commentaries, case reports, and reviews. Bias was assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. RESULTS: Out of 1,688 identified articles, 7 articles representing 23 subjects with ECA were included. Publication rates increased between the period of study from 2009 to 2018. Four studies were level 4 evidence and three studies were level 3 evidence. In total, 20 subjects underwent cochlear implantation. Cerebrospinal fluid gushers were encountered in the majority of cases that reported complications (16/17, 94.1%); one patient developed postoperative meningitis, and another experienced postimplantation facial nerve stimulation. No study provided measurements on cochlear aperture size or defined size criteria used to identify ECA. Four studies recognized X-linked deafness to be associated with ECA, and the most common mutation was in POU3F4 gene. CONCLUSION: An association exists between ECA and cerebrospinal fluid gusher, underscoring the importance of reviewing preoperative imaging. Size criteria are not well defined, and there is a paucity of data with respect to normative measurements. Many cases of ECA may give a genetic link. Although level of evidence of current studies remains modest, ECA reports have increased and will likely continue to expand with advancements in imaging and genetic testing.

Effect of Patient Demographics and Tracheostomy Timing and Technique on Patient Survival.

OBJECTIVES: The ideal timing and technique of tracheostomy vary among patients and may impact outcomes. We aim to examine the association between tracheostomy timing, placement technique, and patient demographics on survival. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective review was performed for all patients who underwent tracheostomy in 2016 and 2017 at one urban academic tertiary-care hospital. Kaplan-Meier curves were created based on combinations of tracheostomy timing and technique (early percutaneous, early non-percutaneous, late percutaneous, and late non-percutaneous). Cox proportional hazard models were used to determine multivariable effects of timing, technique, and other demographic factors. Primary outcome measures were tracheostomy-related mortality and overall survival. Secondary outcomes were in-hospital, 30-day, and 90-day mortality. RESULTS: Our study included 523 patients. There were six tracheostomy-related deaths, with hemorrhage and tracheoesophageal fistula being the most common causes. Tracheostomy timing and technique combinations were not associated with differences in all-cause mortality or survival following discharge. Cox proportional hazard models showed that Charlson Comorbidity Index (CCI) and unknown partner status were associated with a decrease in survival (P < .01 and P = .05, respectively). Additionally, patient age, gender, race, CCI, and body mass index were not independently associated with changes in survival. CONCLUSION: Late and non-percutaneous tracheostomies were associated with more tracheostomy-related deaths, but timing and technique were not associated with differences in patient survival. Multiple regression analysis showed that increased patient comorbidities, measured via CCI, and unknown partner status were independently associated with decreased survival. Proceduralists should discuss timing, technique, and patient social factors together with the medical care team when constructing plans for postdischarge management. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1468-1473, 2021.

Influence of Insurance Status and Demographic Factors on Outcomes Following Tracheostomy.

OBJECTIVES/HYPOTHESIS: Little data exists regarding the relationship between socioeconomic and demographic factors and tracheostomy outcomes. The goal of this study was to determine associations between socioeconomic status (SES), demographic factors, and insurance status with hospital length of stay (LOS), intensive care unit (ICU) LOS, and mortality following tracheostomy. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective analysis of all patients who underwent tracheostomy at an urban tertiary-care academic hospital from 2016 to 2017 was performed. Patients were aggregated into low-, middle-, and high-income brackets. Other variables included age, sex, race, ethnicity, body mass index, and Charlson Comorbidity Index (CCI). Outcomes included hospital and ICU LOS, in-hospital mortality, and 30-day mortality following tracheostomy. Outcomes were compared using Kruskal-Wallis tests for continuous variables and χ2 or Fisher exact tests for categorical variables. The α level was set to .05. RESULTS: In total, 523 patients were included in the study. Patients from high-income areas were more likely to be male (P < .01), white (P < .01), and had lower body mass index (P = .04). On multiple regression analysis, Hispanic or Latino ethnicity was associated with an increased odds of 30-day mortality (odds ratio [OR]: 4.43, P = .020). CCI was also associated with increased odds of 30-day mortality (OR: 1.12, P = .039). CONCLUSIONS: Lower SES was not associated with increased morbidity or mortality after tracheostomy. Although Hispanic patients tended to have a lower CCI score, they had increased 30-day mortality, suggesting there are factors specific to this population that may influence outcomes, and future targeted studies are warranted to study these relationships. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1463-1467, 2021.

The COVID-19 Student WorkForce at the Icahn School of Medicine at Mount Sinai: A Model for Rapid Response in Emergency Preparedness.

PROBLEM: In accordance with guidelines from the Association of American Medical Colleges, medical schools across the United States suspended clerkships and transitioned preclinical courses online in March 2020 because of the COVID-19 pandemic. Hospitals and health systems faced significant burdens during this time, particularly in New York City. APPROACH: Third- and fourth-year medical students at the Icahn School of Medicine at Mount Sinai formed the COVID-19 Student WorkForce to connect students to essential roles in the Mount Sinai Hospital System and support physicians, staff members, researchers, and hospital operations. With the administration's support, the WorkForce grew to include over 530 medical and graduate students. A methodology was developed for clinical students to receive elective credit for these volunteer activities. OUTCOMES: From March 15, 2020, to June 14, 2020, student volunteers recorded 29,602 hours (2,277 hours per week) in 7 different task forces, which operated at 7 different hospitals throughout the health system. Volunteers included students from all years of medical school as well as PhD, master's, and nursing students. The autonomous structure of the COVID-19 Student WorkForce was unique and contributed to its ability to quickly mobilize students to necessary tasks. The group leaders collaborated with other medical schools in the New York City area, sharing best practices and resources and consulting on a variety of topics. NEXT STEPS: Going forward, the COVID-19 Student WorkForce will continue to collaborate with student leaders of other institutions and prevent volunteer burnout; transition select initiatives into structured, precepted student roles for clinical education; and maintain a state of readiness in the event of a second surge of COVID-19 infections in the New York City area.

Lymphoma Mimicking Chronic Active Epstein-Barr Virus: A Case Report.

Epstein-Barr virus (EBV) is the main cause of infectious mononucleosis (IM), a self-limiting infection among immunocompetent patients. EBV is also implicated in the development of several malignancies. We describe a case of a previously healthy 34-year-old man who presented with non-tender, enlarging, right cervical lymphadenopathy for over a year that was associated with significant weight loss, fevers, and night sweats. Two fine needle core biopsies showed inconclusive then reactive tissue, respectively. A third excisional biopsy demonstrated a reactive lymph node with EBV-positive IM. There was no evidence of lymphoma by histologic examination or flow cytometry. A diagnosis of chronic active EBV (CAEBV) was rendered. Subsequent lymph node debulking six months later showed classic Hodgkin lymphoma (CHL) positive for EBV. The patient underwent chemotherapy with full treatment response. This is an unusual presentation of EBV infection that led to either a delayed onset or delayed diagnosis of CHL.

Genetic Mutations in Young Nonsmoking Patients With Oral Cavity Cancer: A Systematic Review.

OBJECTIVE: This investigation aims to review the known genetic mutations associated with oral cavity squamous cell carcinoma (OCSCC) in young adults with limited environmental risk factors (YLERs). DATA SOURCES: A comprehensive search strategy was designed to identify studies in MEDLINE (Ovid), Embase (Ovid), and Scopus from database inception to May 2017 that included adults ≤50 years of age with OCSCC and minimal tobacco use history (≤10 pack-years) who had their tumors genetically sequenced or mutational profiles analyzed. REVIEW METHODS: Identified articles were screened by 2 reviewers. Quality of evidence was graded by the MINORS criteria for case-control studies; other studies were graded by assigning a level of evidence for gene mutation literature. RESULTS: Thirteen studies met our inclusion criteria, and 130 patients met our criteria for age and tobacco history. TP53 was the most commonly evaluated gene (10 of 13 studies) and the most frequently observed mutation. One study reported that nonsmokers had significantly fewer TP53 mutations, while 9 studies found no difference in the prevalence of TP53 mutations. No other mutations were found specific to this cohort. CONCLUSIONS: TP53 mutations may occur at a similar rate in YLERs with OCSCC as compared with older patients or those with risk factors. However, few studies have aimed to characterize the genetic landscape of oral cavity tumors in this population, often with small sample sizes. Future studies are needed to explore unidentified genetic alterations leading to tumor susceptibility or alternative mechanisms of carcinogenesis.

An Innovative Consulting Group for Sharing Expertise on Launching and Sustaining Student-Run Free Clinics: A Model for Building Student-Run Endeavors.

Student-run, physician-supervised free clinics (SRFCs) provide essential healthcare services for many uninsured and underinsured patients in the USA. While SRFCs serve diverse populations and offer distinct services, they face many similar barriers to successful clinic operation. Historically, the sharing of best practices and development strategies across SRFCs has been limited and insufficient for both new and emerging free clinics. To address these challenges, in 2015, the East Harlem Health Outreach Program (EHHOP) at the Icahn School of Medicine at Mount Sinai formed the EHHOP Consulting Group (ECG), with the goal of providing client SRFCs individualized support from medical students. ECG draws from the experience of EHHOP and other veteran SRFCs to provide customized solutions to best address client SRFC needs. Here, we describe ECG's inception, structure, and consulting work with client SRFCs. We propose that this interactive, longitudinal model can be adapted to other healthcare trainee initiatives where cross-institutional collaboration could prove beneficial.

Generation and characterization of a mitotane-resistant adrenocortical cell line.

Mitotane is the only drug approved for the therapy of adrenocortical carcinoma (ACC). Its clinical use is limited by the occurrence of relapse during therapy. To investigate the underlying mechanisms in vitro, we here generated mitotane-resistant cell lines. After long-term pulsed treatment of HAC-15 human adrenocortical carcinoma cells with 70 µM mitotane, we isolated monoclonal cell populations of treated cells and controls and assessed their respective mitotane sensitivities by MTT assay. We performed exome sequencing and electron microscopy, conducted gene expression microarray analysis and determined intracellular lipid concentrations in the presence and absence of mitotane. Clonal cell lines established after pulsed treatment were resistant to mitotane (IC50 of 102.2 ± 7.3 µM (n = 12) vs 39.4 ± 6.2 µM (n = 6) in controls (biological replicates, mean ± s.d., P = 0.0001)). Unlike nonresistant clones, resistant clones maintained normal mitochondrial and nucleolar morphology during mitotane treatment. Resistant clones largely shared structural and single nucleotide variants, suggesting a common cell of origin. Resistance depended, in part, on extracellular lipoproteins and was associated with alterations in intracellular lipid homeostasis, including levels of free cholesterol, as well as decreased steroid production. By gene expression analysis, resistant cells showed profound alterations in pathways including steroid metabolism and transport, apoptosis, cell growth and Wnt signaling. These studies establish an in vitro model of mitotane resistance in ACC and point to underlying molecular mechanisms. They may enable future studies to overcome resistance in vitro and improve ACC treatment in vivo.

An Atlas of ß-Glucuronidases in the Human Intestinal Microbiome.

Microbiome-encoded ß-glucuronidase (GUS) enzymes play important roles in human health by metabolizing drugs in the gastrointestinal (GI) tract. The numbers, types, and diversity of these proteins in the human GI microbiome, however, remain undefined. We present an atlas of GUS enzymes comprehensive for the Human Microbiome Project GI database. We identify 3,013 total and 279 unique microbiome-encoded GUS proteins clustered into six unique structural categories. We assign their taxonomy, assess cellular localization, reveal the inter-individual variability within the 139 individuals sampled, and discover 112 novel microbial GUS enzymes. A representative in vitro panel of the most common GUS proteins by read abundances highlights structural and functional variabilities within the family, including their differential processing of smaller glucuronides and larger carbohydrates. These data provide a sequencing-to-molecular roadmap for examining microbiome-encoded enzymes essential to human health.