Epidemiological assessment of non-tuberculous mycobacterial cervicofacial lymphadenitis: A PHIS database study.

OBJECTIVE: Cervicofacial lymphadenitis caused by non-tubercular mycobacterial (NTM) infections has the highest infection rate in children. Our objective was to assess patient demographics, treatment methods, and the impact of weather and geography on the incidence of disease in patients with NTM cervicofacial lymphadenitis. METHODS: The Pediatric Health Information System (PHIS) database was queried for data on all patients diagnosed with concurrent cervicofacial lymphadenopathy and NTM infection from 2004 to 2022. We assessed the association between weather patterns and NTM cervicofacial lymphadenitis by collecting monthly weather data from the NOAA National Center for Environmental Information. Incidence rates were calculated by dividing the number of cases by the total hospital discharges during the study period. RESULTS: Among 47 PHIS hospitals, there were 992 diagnoses of NTM cervicofacial lymphadenitis. The average age at diagnosis was 2 [IQR, 2-4], with 59 % female. Drainage of skin abscesses or lesions was performed for 93 (9.4 %) patients, while 15 (1.5 %) had an excisional procedure of the CPT codes assessed. The most common antibiotics utilized were cephalosporins (28 %), macrolides (27 %), and rifampin (12 %). The most common treatment method was surgery with antibiotics (37 %) followed by no treatment at all (35 %), surgery alone (17 %), and antibiotics alone (10 %). Of the 28 states included in the analysis, Washington (IR: 3.5) and Nebraska (IR: 3.3) had the highest incidence rates (IR) of NTM cervical lymphadenitis. The cases were relatively equally distributed across the different weather seasons within each U.S. geographic region. However, the overall average wind speed was weakly associated with increasing the risk of diagnosis when utilizing a mixed effect zero-inflated negative binomial model (Incidence Ratio: 1.07, 95 % CI: (1.01-1.14), p = 0.035). CONCLUSIONS: Our results indicate that the most common treatment method utilized in patients within our cohort with NTM cervicofacial lymphadenitis was the concurrent use of surgery and antibiotics. Our results also indicate there may be variation in the incidence rate among different states, but additional studies are needed as our cohort only included approximately 50 % of states within the U.S.

Obesity is Associated with Increased Risk of New-Onset Chronic Rhinosinusitis: A United States Population-Based Cohort Study.

OBJECTIVE: The aim of this study was to determine the risk of a new-encounter diagnosis of unspecified chronic rhinosinusitis (CRS), CRS with nasal polyps (CRSwNP), and eosinophilic granulomatosis with polyangiitis (EGPA) 1 and 2 years following body mass index (BMI) classification of obesity utilizing a large-population-based analytics platform. STUDY DESIGN: Retrospective cohort analysis SETTING: The U.S. Collaborative Network within the TriNetX Analytics platform contains deidentified electronic health record (EHR) data of more than 100 million patients and was used to determine the association between obesity and a new encounter diagnosis of 3 CRS phenotypes in this study. RESULTS: After 1:1 propensity score matching, patients with an overweight BMI and obesity were at a higher risk for a new-encounter diagnosis of unspecified CRS and CRSwNP compared to healthy-weight individuals. The obesity cohort had the greatest increased risk of new-onset unspecified CRS with a relative risk of 1.23 (95% CI: 1.20-1.25) and 1.26 (95% CI: 1.24-1.28) 1 and 2 years following BMI classification, respectively. CONCLUSION: Our study indicates an association between obesity and new-onset unspecified CRS and CRSwNP. With the increasing prevalence of obesity in the United States population, it will be important to understand how obesity-associated CRS may affect treatment response. Future prospective studies are needed to assess causality and define a mechanistic link.

Assessing the Association Between Head and Neck Cancer and Granulomatosis with Polyangiitis.

Objective: To determine the odds of head and neck cancer (HNC) in patients with a concurrent or prior diagnosis of granulomatosis with polyangiitis (GPA). Methods and Materials: The TriNetX Analytics Network, a federated research platform that aggregates de-identified electronic health record data of over 130 million patients worldwide, was queried for patients with at least one ICD-10 encounter diagnosis of GPA. Patients within this group with an encounter diagnosis of cancer of the sinonasal, oral cavity, oropharynx, nasopharynx, and larynx concurrent or after the initial encounter diagnosis of GPA were recorded and compared to a standardized control population to determine odds ratios with a 95% confidence interval (CI). Relevant confounding variables, including human papillomavirus, Epstein Barr virus, tobacco, and alcohol exposure, were balanced between cohorts by 1:1 propensity matching. Results: Of the patients in the GPA cohort, 126 (0.48%) had an ICD-10 diagnosis of HNC. When stratifying by head and neck subsites, 20 (0.08%), 18 (0.07%), 23 (0.09%), 70 (0.27%), and 22 (0.084%) GPA patients had an ICD-10 encounter diagnosis of cancer involving the sinonasal, nasopharynx, larynx, oral cavity, and oropharynx. When comparing the experimental GPA group with the standardized control population after matching, patients in the GPA group had 1.3 times (95% CI: 1.03-1.175) greater odds of HNC when including cases diagnosed after or concurrently with the diagnosis of the vasculitis. There was no statistical difference in the odds of cancer at each anatomical subsite between the GPA and control cohort after matching. Conclusion: Our study identifies a statistically significant increase in the odds of HNC encounter diagnoses in patients with GPA.

Evaluating the Association of Obesity and Chronic Rhinosinusitis: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this Meta-analysis and systematic review was to perform a comprehensive assessment of the association of chronic rhinosinusitis (CRS) with overweight/obesity, leptin hormone, and its associated metabolic dysregulation. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, were searched for studies from 1946 to October 2022, using predefined syntax. REVIEW METHODS: Outcome data for the meta-analysis were extracted on odds ratios (OR) of CRS prevalence based on the presence of overweight/obesity and mean serum leptin levels. A Meta-analysis was performed using the DerSimonian-Laird estimator to pool extracted data by the generalized inverse variance approach. Random effect models were utilized due to the small sample size. A qualitative synthesis was performed on articles that did not meet the inclusion criteria for the Meta-analysis. RESULTS: Thirty-six studies met the systematic review inclusion criteria out of 1113 articles screened. A total of 6 studies were included in the pooled Meta-analysis of the various outcome variables. Our pooled meta-analysis observed a positive association between overweight/obesity and the prevalence of CRS (OR = 1.33, 95% confidence interval [CI]: 1.17-1.51). The pooled ratio of the means analysis of the mean serum leptin levels between CRS with nasal polyposis and control patients was 2.21 (95% CI: 1.45; 3.36). CONCLUSION: Our pooled Meta-analysis indicates a positive association between overweight/obesity and CRS. Future prospective studies are needed to explore the association between CRS and obesity with an understanding of potential confounding comorbidities, including studies focused on assessing the underlying immunologic mechanism of this association.

Assessing the clinico-immunological profile of patients with obesity and chronic rhinosinusitis.

BACKGROUND: No studies have investigated the systemic and local sinonasal profile of obesity-related chronic rhinosinusitis (CRS), despite its observed association in recent retrospective studies. The objectives of our study were to assess the impact of obesity on the clinical and cytokine profile of patients with CRS and evaluate treatment response with functional endoscopic sinus surgery. METHODS: This was a prospective observational study at the Cleveland Clinic that included patients with CRS (n = 54) between December 2021 and September 2022. Data collection included demographics, body mass index (BMI), comorbidities, baseline sinonasal outcome test scores, baseline radiologic scores (Lund-Mackay), postoperative sinonasal outcome test scores (at 3-4 months), and local and systemic alarmins/T-helper cytokines. RESULTS: Out of the 54 CRS patients, there were 20 CRS patients without nasal polyps (37%) and 34 with nasal polyps (63%). Patients were categorized based on obesity (BMI ≥ 30 kg/m2 ). Obese CRS patients had lower systemic alarmins (interleukin [IL]-33 and Thymic stromal lymphopoietin (TSLP)) compared to non-obese CRS patients (IL-33: 744.2 ± 1164.6 pg/mL vs. 137.5 ± 320.0 pg/mL, p = 0.005; TSLP: 627.7 ± 1806.3 pg/mL vs. 28.1 ± 85.4 pg/mL, p = 0.017). CRS patients with nasal polyps with BMI ≥30 kg/m2 had higher postoperative sinonasal outcome test scores and lower levels of nasal eotaxin-3 and IL-33 compared to BMI <30 kg/m2 counterparts. CONCLUSIONS: In conclusion, patients with obese CRS and nasal polyps displayed diminished levels of intranasal alarmins and reduced intranasal eotaxin-3. These results potentially imply the presence of a unique, obese type 2-low CRS phenotype that warrants further exploration.

Prognostic significance of time trends in treatment of head and neck squamous cell carcinoma.

PURPOSE: To analyze the impact of demographic, clinical, and management variables on time to treatment initiation (TTI) and overall survival (OS). STUDY DESIGN: Retrospective chart review. MATERIALS AND METHODS: Medical records of patients diagnosed with head and neck cancer from 2018 to 2020 were reviewed. Univariate linear and Cox-regressions identified predictors of TTI and OS. Kaplan Meier (KM) curves assessed the difference in survival by diagnostic year and TTI. RESULTS: 381 patients met eligibility criteria. Median TTI was 35.0 days (IQR: 25.0-49.0). Only 10.8 % of all patients reported any treatment delay, with TTI exceeding 90 days found in 3.7 % of patients. TTI increased with African American race (p = 0.02), ED referrals (p = 0.02), and direct admission status (p = 0.01). When compared to treatment with surgery alone, TTI was shorter in patients undergoing surgery with adjuvant radiation (p = 0.02), adjuvant chemoradiation (p = 0.04), and salvage surgery (p = 0.04). Univariate Cox-regressions found smoking (p = 0.01), direct admission status (p = 0.02), increased duration of symptoms (p = 0.02), placement of PEG tubes (p < 0.01) and tracheostomies (p < 0.01), combination treatment (p < 0.01), and surgery with adjuvant chemoradiation treatment (p = 0.01) to increase mortality risk. Disease characteristics, including tumor size (p < 0.01), presence of nodal disease (p = 0.02), and late-stage disease (p < 0.01), increased mortality risk. TTI and diagnostic year did not impact survival. CONCLUSIONS: Our analysis determined several demographic, referral, and treatment factors impacted TTI. However, increased TTI did not impact survival. Characteristics consistent with advanced disease worsened OS. Despite the pandemic burden, patients diagnosed in 2020 showed no difference in short-term survival compared to prior years.

Continuous multi-membrane chromatography of large viral particles.

Continuous multi-column chromatography (CMCC) has been successfully implemented to address biopharmaceutical biomolecule instability, to improve process efficiency, and to reduce facility footprint and capital cost. This paper explores the implementation of a continuous multi-membrane chromatography (CMMC) process, using four membrane units, for a large viral particle in just few weeks. CMMC improves the efficiency of the chromatography step by enabling higher loads with smaller membranes for multiple cycles of column use and enables steady-state continuous bioprocessing. The separation performance of CMMC was compared to a conventional batch chromatographic capture step used at full manufacturing scale. The product step yield was 80% using CMMC versus 65% in batch mode while increasing slightly the relative purity. Furthermore, the total amount of membrane area required for the CMMC approach was approximately 10% of the area needed for batch operation, while realizing similar processing times. Since CMMC uses smaller membrane sizes, it can take advantage of the high flow rates achievable for membrane chromatography that are not typically possible at larger membrane scales due to skid flow rate limitations. As such, CMMC offers the potential for more efficient and cost-effective purification trains.

Revision Rates and Symptom Trends Following Endoscopic Sinus Surgery: Impact of Race on Outcomes.

OBJECTIVE: The purpose of this study is to determine the impact of demographics and sinonasal comorbidities on the revision rate of functional endoscopic sinus surgery (FESS) for chronic rhinosinusitis (CRS). BACKGROUND: Although endoscopic sinus surgery (ESS) is often successful in providing long-term relief for patients suffering from CRS, revision surgery can occur. There is conflicting literature on the impact of race on FESS outcomes. METHODS: A single-center retrospective cohort study of patients that underwent FESS for CRS between January 1, 2015 and June 1, 2021 at a single tertiary care academic center. RESULTS: A total of 682 patients between the ages of 18 and 89 underwent primary ESS between January 1, 2015 and June 1, 2021 and were included in this study. Of these patients, 388 (56.9%) were female, with an average age of 48.6 ± 16.7. Thirty-eight patients (5.6%) underwent revision sinus surgery during the study period. Patients that identified as White had significantly lower rates of revision sinus surgery (4.1%) than non-White patients (10.7%), including those identifying as Asian, Black, multiracial, or other. On multivariate analysis, non-White race (OR 4.933), polyposis (3.175), and high preoperative SNOT-22 scores (OR 1.029) were independently associated with revision sinus surgery. The mean preoperative SNOT-22 for all participants was 39.1 ± 22.0, whereas the mean postoperative SNOT-22 was 20.6 ± 17.5 (p < 0.001). CONCLUSION: Race plays an important role in outcomes following revision sinus surgery that is independent of location and insurance status. More studies are required to assess the reason race plays an important role in outcomes following revision sinus surgery. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 133:2878-2884, 2023.

A diagnostic algorithm for early diagnosis and management of acute invasive fungal sinusitis.

PURPOSE: To define different risk groups of patients suspected of having acute invasive fungal sinusitis (AIFS) and develop a goal-directed diagnostic approach. MATERIALS AND METHODS: Forty patients with suspected AIFS biopsied from 2010 to 2020 were included in this study. Patients diagnosed with chronic invasive fungal sinusitis or without biopsy results were excluded. A recursive partitioning analysis (RPA) model was performed to define patient cohorts with the highest risk of having a positive biopsy for AIFS. RESULTS: There were a total of 26 patients with biopsy-proven AIFS. Patient characteristics significantly associated with an increased likelihood of a positive biopsy for AIFS on bivariate analysis included facial pain (p = 0.047), platelet count <50,000 cells/mm3 (p = 0.028), and abnormal CT findings, most commonly, bilateral sinus opacification (p = 0.003). The RPA model identified three risk factors for predicting a patient's probability of having a positive biopsy for AIFS, resulting in four-terminal nodes. In the twenty-six patients who had biopsy-proven AIFS, the post-operative 30-day all-cause mortality was 50 % (13/26) and overall mortality was 88.5 % (23/26). Predictors of 30-day all-cause mortality included prolonged interval between biopsy and operative start time (p = 0.042) and earlier initiation of antifungals prior to the operative start time (p = 0.042). CONCLUSION: Our findings indicate that patients with a fever of unknown origin, low platelet count, and/or ANC are at an increased risk of being diagnosed with biopsy-proven AIFS. Using these risk factors, we propose a diagnostic approach that may expedite the treatment of patients with AIFS; however, future prospective studies are needed for validation.

The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration.

Throughout their lifetime, fish maintain a high capacity for regenerating complex tissues after injury. We utilized a larval tail regeneration assay in the zebrafish Danio rerio, which serves as an ideal model of appendage regeneration due to its easy manipulation, relatively simple mixture of cell types, and superior imaging properties. Regeneration of the embryonic zebrafish tail requires development of a blastema, a mass of dedifferentiated cells capable of replacing lost tissue, a crucial step in all known examples of appendage regeneration. Using this model, we show that tail amputation triggers an obligate metabolic shift to promote glucose metabolism during early regeneration similar to the Warburg effect observed in tumor forming cells. Inhibition of glucose metabolism did not affect the overall health of the embryo but completely blocked the tail from regenerating after amputation due to the failure to form a functional blastema. We performed a time series of single-cell RNA sequencing on regenerating tails with and without inhibition of glucose metabolism. We demonstrated that metabolic reprogramming is required for sustained TGF-ß signaling and blocking glucose metabolism largely mimicked inhibition of TGF-ß receptors, both resulting in an aberrant blastema. Finally, we showed using genetic ablation of three possible metabolic pathways for glucose, that metabolic reprogramming is required to provide glucose specifically to the hexosamine biosynthetic pathway while neither glycolysis nor the pentose phosphate pathway were necessary for regeneration.