Circulating Biomarkers for Early Stage Non-Small Cell Lung Carcinoma Detection: Supplementation to Low-Dose Computed Tomography.

Lung cancer is currently the leading cause of cancer death in both developing and developed countries. Given that lung cancer has poor prognosis in later stages, it is essential to achieve an early diagnosis to maximize patients' overall survival. Non-small cell lung cancer (NSCLC) is the most common form of primary lung cancer in both smokers and non-smokers. The current standard screening method, low-dose computed tomography (LDCT), is the only radiological method that demonstrates to have mortality benefits across multiple large randomized clinical trials (RCT). However, these RCTs also found LDCT to have a significant false positive rate that results in unnecessary invasive biopsies being performed. Due to the lack of both sensitive and specific screening methods for the early detection of lung cancer, there is an urgent need for alternative minimally or non-invasive biomarkers that may provide diagnostic, and/or prognostic information. This has led to the identification of circulating biomarkers that can be readily detectable in blood and have been extensively studied as prognosis markers. Circulating microRNA (miRNA) in particular has been investigated for these purposes as an augmentation to LDCT, or as direct diagnosis of lung cancer. There is, however, a lack of consensus across the studies on which miRNAs are the most clinically useful. Besides miRNA, other potential circulating biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNAs) and non-coding RNAs (ncRNAs). In this review, we provide the current outlook of several of these biomarkers for the early diagnosis of NSCLC.

Association of a standardized measure of nasopharyngeal inflammation with Eustachian tube dysfunction questionnaire score.

BACKGROUND: Standardized diagnostic criteria for Eustachian tube (ET) dysfunction (ETD) have not been established. The purpose of this study was to characterize the relationship between ET inflammation and ETD symptoms and to determine the diagnostic performance of a quantitative score. METHODS: Patients were enrolled in a rhinology clinic between October 2018 and June 2019. Patients underwent nasal endoscopy and completed the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7). Nasopharyngeal inflammation identified on endoscopy was quantified using the Endoscopic Evaluation of the Eustachian Tube (3ET) score. Tympanometry was performed as indicated. Comorbid conditions were assigned during the patient encounter. RESULTS: A total of 414 patients were included in the study. Patients with clinically significant ETD symptoms (ETDQ-7 ≥2.1) had higher 3ET scores than those without symptoms. A 1-point increase in 3ET score was associated with a 1.7-fold increase in odds of clinically significant ETD symptoms (adjusted OR [aOR], 1.72; 95% CI, 1.46 to 2.05). The 3ET scores were correlated with ETDQ-7 scores (ρ = 0.54) and 22-item Sino-Nasal Outcome Test (SNOT-22) scores (ρ = 0.52). 3ET scores were not associated with tympanometric peak pressures. Patients with ETD symptoms were more likely to have laryngopharyngeal reflux (aOR, 2.71; 95% CI, 1.24 to 6.18). A 3ET score of 4 predicted symptomatic state in 80% of cases with a specificity of 97.8% and positive predictive value of 96.6%. CONCLUSION: Inflammatory findings at the nasopharyngeal ET orifice are associated with clinically significant ETD symptoms. The 3ET score is specific for a symptomatic state and has potential clinical utility in the evaluation of suspected ETD. ©2021 ARSAAOA, LLC.

Very Late Relapse in Pediatric Acute Myeloid Leukemia: A Case Report and Brief Literature Review.

Acute myeloid leukemia (AML) is a heterogenous group of diseases affecting ~500 children in the United States annually. With current therapy, 90% of these children will obtain complete remission. However, 30% to 40% of these patients will relapse, most commonly within the first 3 years. Very late relapses, defined as relapse occurring >5 years after complete remission, are rare, accounting for 1% to 3% of relapses. We describe a patient with AML harboring an AFDN/KMT2A translocation who relapsed 12 years after matched sibling stem cell transplant, provide a brief review of the relevant literature, and describe proposed mechanisms to explain very late relapse AML.

Interpretation of Normal and Abnormal Tympanogram Findings in Eustachian Tube Dysfunction.

OBJECTIVE: To characterize the relationship between objective tympanogram values and patient-reported symptoms and associations with common comorbid conditions. STUDY DESIGN: Cross-sectional study with prospective data collection. SETTING: Tertiary medical center. METHODS: Patients undergoing routine audiometric evaluation between October 2018 and June 2019 were included. Participants with temporomandibular joint dysfunction, inner ear hydrops, and similar conditions were excluded. Symptoms were assessed with the 7-item Eustachian Tube Dysfunction Questionnaire. Demographics and medical comorbidities were recorded from the medical record. Analysis of tympanometric peak pressure (TPP), demographics, and comorbidities was performed to determine associations with clinically significant eustachian tube dysfunction (ETD) symptoms. RESULTS: A total of 250 patients were included with similar demographics: 101 (40.4%) in the asymptomatic group and 149 (59.6%) in the symptomatic group. The median (interquartile range) TPP was -10 (20) daPa and -25 (100) daPa in the asymptomatic and symptomatic groups, respectively. A diagnosis of rhinitis was more likely to be associated with significant ETD symptoms (adjusted odds ratio, 2.61; 95% CI, 1.23-5.63). A subgroup analysis revealed that symptomatic patients with normal TPP values were negatively skewed as compared with asymptomatic patients. This symptomatic group had a higher prevalence of rhinitis and chronic rhinosinusitis than the asymptomatic group. CONCLUSION: Patients with symptoms of ETD may have a TPP within a range typically considered normal per conventional standards. This suggests that the currently accepted interpretation of tympanometry findings may be insensitive for the diagnosis of less severe cases of ETD.

Neuromodulators for Atypical Facial Pain and Neuralgias: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness of neuromodulating agents for the management of atypical facial pain and primary facial neuralgias. METHODS: We searched MEDLINE, Embase, CINAHL, and ClinicalTrials.gov databases for original research articles that examine the effectiveness and adverse reactions of pharmacologic therapy for the treatment of trigeminal neuralgia and atypical facial pain. Studies that included surgical interventions for atypical facial pain or facial pain secondary to other causes were excluded. Meta-analysis was conducted for reductions in symptom scores and adverse effects. RESULTS: Of 3,409 articles screened, 73 full-text articles were included, consisting of 45 observational studies and 29 randomized controlled trials. Twenty-four different pharmacological agents were assessed; carbamazepine was the most frequently studied while botulinum toxin A demonstrated the highest consistency in reduction of symptom scores. Pooled estimate of three randomized controlled trials revealed that patients with trigeminal neuralgia who received botulinum toxin A had higher odds (odds ratio 7.46; 95% CI 3.53-15.78) of achieving a ≥50% reduction in visual analogue scale scores compared to controls. Pooled estimate of 15 observational studies showed that three-fourths of patients with trigeminal neuralgia who received carbamazepine experienced clinically significant pain reduction (prevalence proportion 0.75; 95% CI 0.66-0.83). CONCLUSIONS: Patients receiving botulinum toxin A for trigeminal neuralgia had higher odds of achieving ≥50% reduction in pain scores. A significant proportion of patients with trigeminal neuralgia experienced positive response to carbamazepine. There was moderate evidence for amitriptyline in patients with atypical facial pain. Standardization of outcome reporting would facilitate future quantitative comparisons of therapeutic effectiveness. Laryngoscope, 131:1235-1253, 2021.

Olfactory Training for Postviral Olfactory Dysfunction: Systematic Review and Meta-analysis.

OBJECTIVE: Olfactory dysfunction is a common problem that is most frequently attributed to upper respiratory infection. Postviral olfactory dysfunction (PVOD) can be prolonged and clinically challenging to treat. Olfactory training (OT) has demonstrated potential benefit for patients with nonspecific olfactory dysfunction. We sought to evaluate the efficacy of OT specifically for PVOD by pooled analysis of the existing evidence. DATA SOURCES: PubMed, Embase, and Web of Science. REVIEW METHODS: Following PRISMA guidelines, PubMed, Embase, and Web of Science databases were queried and abstracts screened independently by 2 investigators. We included studies evaluating the efficacy of OT for PVOD and excluded studies evaluating pharmacologic interventions or olfactory loss from other causes. RESULTS: Of the initial 1981 abstracts reviewed, 16 full-text articles were included. Sniffin' Sticks olfactory testing results were reported in 15 (93%) studies as threshold (T), discrimination (D), and identification (I) subscores and TDI total scores. All studies reported clinically significant results after OT, defined as a score improvement of TDI >5.5. Four studies were included in the meta-analysis, in which pooled estimates revealed that patients with PVOD who received OT had a 2.77 (95% confidence interval, 1.67-4.58) higher odds of achieving a clinically important difference in TDI scores compared to controls. CONCLUSION: Meta-analysis of existing data demonstrates clinically significant improvements in PVOD associated with OT. Variability exists among OT protocols and may benefit from further optimization. Existing data supports the use of OT for the treatment of existing and newly emerging cases of PVOD.

Locally Informed Modeling to Predict Hospital and Intensive Care Unit Capacity During the COVID-19 Epidemic.

Background: In the early phases of the 2019 novel coronavirus (COVID-19) pandemic, health system leaders faced the urgent task of translating the unknown into forecasting models for hospital capacity. Our study objective was to demonstrate the application of a practical, locally informed model to estimate the hospital capacity needed even though the community COVID-19 caseload was unknown. Methods: We developed a susceptible-infected-recovered (SIR) model that was adopted from the University of Pennsylvania COVID-19 Hospital Impact Model for Epidemics and employed at 8 hospitals within Ochsner Health, the largest integrated delivery system in Louisiana, between March 16 and April 15, 2020. Intensive care unit (ICU) admissions of cases in the New Orleans area were used to estimate the community case load when testing was delayed. Results: Initially, the observed ICU census trended near R0=2.0, whereas the ventilator census trended between R0=2.0 and 3.0. After implementing social distancing, both the ICU and ventilator capacity trended toward R0=1.3, while non-ICU medical/surgical beds trended toward R0=1.5. The model accurately predicted peak ICU (n=250) and hospital bed (n=487) usage by April 6, 2020. In response to model trends, Ochsner added 130 ICU beds across its hospitals by opening a new ICU and converting operating rooms and parts of emergency departments to ICU beds. Conclusion: When disease testing is limited or results are delayed, ICU admissions data can inform SIR models of the rate of spread of COVID-19 in a community. Our model used various R0 plots to demonstrate an array of scenarios to guide planning for hospital and political leaders.