Expanded statistical analysis plan for legacy and long-term effects of aspirin in the ASPREE-XT observational follow-up study of participants in the ASPREE randomized trial.

The ASPREE randomized controlled trial (2010-2017) of 19,114 community-dwelling older adults without cardiovascular disease and significant disability compared daily 100mg aspirin to placebo. A total of 16,317 (93%) of 17,546 surviving and non-withdrawn participants agreed to continue regular study follow-up visits in the post-trial phase, named ASPREE-XT (2017-2024). We present a statistical analysis plan to underpin three main papers to report aspirin effects through to the fourth post-trial ASPREE-XT study visit with focus areas of: (1) death, dementia, and disability, (2) CVD events and bleeding, and (3) cancer. The focus of the plan is to estimate long-term (entire timespan of RCT plus post-trial) and legacy (post-trial period only) effects of aspirin in the setting of primary prevention for older individuals. Preliminary insights to these effects are presented that are based on data that has been reported to the study's observational study monitoring board however formal data lock is not expected until October 2023.

Transient exposure to rotenone causes degeneration and progressive parkinsonian motor deficits, neuroinflammation, and synucleinopathy.

Individuals with Parkinson's disease (PD) typically receive a diagnosis once they have developed motor symptoms, at which point there is already significant loss of substantia nigra dopamine neurons, α-synuclein accumulation in surviving neurons, and neuroinflammation. Consequently, the point of clinical presentation may be too late to initiate disease-modifying therapy. In contrast to this clinical reality, animal models often involve acute neurodegeneration and potential therapies are tested concurrently or shortly after the pathogenic insult has begun rather than later when diagnostic clinical symptoms emerge. Therefore, we sought to develop a model that reflects the clinical situation more accurately. Middle-aged rats (7-9 months-old) received a single daily intraperitoneal injection of rotenone for 5 consecutive days and were observed over the next 8-9 months. Rotenone-treated rats showed transient motor slowing and postural instability during exposure but recovered within 9 days of rotenone cessation. Rats remained without behavioral deficits for 3-4 months, then developed progressive motor abnormalities over the ensuing months. As motor abnormalities began to emerge 3 months after rotenone exposure, there was significant loss of nigral dopaminergic neurons and significant microglial activation. There was delayed accumulation of α-synuclein in neurons of the substantia nigra and frontal cortex, which was maximal at 9 months post-rotenone. In summary, a brief temporally-remote exposure to rotenone causes delayed and progressive behavioral and neuropathological changes similar to Parkinson's disease. This model mimics the human clinical situation, in which pathogenesis is well-established by the time diagnostic motor deficits appear. As such, this model may provide a more relevant experimental system in which to test disease-modifying therapeutics.

Evolving Endotracheal Tube Preferences and Practices: Intensivist Knowledge Gaps and Sex Disparities.

OBJECTIVES: The complex management of intubation-related laryngeal injury makes prevention vital. The purpose of this study is to assess endotracheal tube (ETT) practices and preferences among intensivists at our institution. METHODS: Chart review of intubated patients and intensivist survey were simultaneously performed in January 2016 and August 2022. A height-to-ETT size ratio (H:ETT) was calculated for each patient in the 2022 cohort. Intubated patients were followed until tracheostomy, extubation, or death occurred. Surveys assessed intensivist preferences for ETT size and management of intubated patients. RESULTS: 300 ICU patients were included. The mean ETT size for males decreased from 7.73 ± 0.30 in 2016 to 7.57 ± 0.25 in 2022 (p < 0.001). The average H:ETT of men was higher than females (p = 0.004), indicating that females in this population were intubated with larger ETTs relative to their height compared to males. Whereas the majority (66.7%) of intensivists endorse 7.0 ETTs as the standard for women, the majority (70%) of women at our institution are intubated with a 7.5 ETT or larger. Of intubated patients in the ICU, 23 (19.5%) were intubated for 11 days or longer. CONCLUSIONS: Compared to men, women are intubated with larger-than-preferred ETTs relative to height. Additionally, patients in our study were intubated for longer than preferred based on intensivist surveys, putting this population at higher risk for acute laryngeal injury (AlgI)-related laryngotracheal stenosis (LTS). Further studies should seek to identify similar trends and barriers to reducing ALgI-related LTS. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3080-3086, 2023.

Associations of body size with all-cause and cause-specific mortality in healthy older adults.

In the general population, body mass index (BMI) and waist circumference are recognized risk factors for several chronic diseases and all-cause mortality. However, whether these associations are the same for older adults is less clear. The association of baseline BMI and waist circumference with all-cause and cause-specific mortality was investigated in 18,209 Australian and US participants (mean age: 75.1 ± 4.5 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) study, followed up for a median of 6.9 years (IQR: 5.7, 8.0). There were substantially different relationships observed in men and women. In men, the lowest risk of all-cause and cardiovascular mortality was observed with a BMI in the range 25.0-29.9 kg/m2 [HR25-29.9 vs 21-24.9 kg/m2: 0.85; 95% CI, 0.73-1.00] while the highest risk was in those who were underweight [HRBMI <21 kg/m2 vs BMI 21-24.9 kg/m2: 1.82; 95% CI 1.30-2.55], leading to a clear U-shaped relationship. In women, all-cause mortality was highest in those with the lowest BMI leading to a J-shaped relationship (HRBMI <21 kg/m2 vs BMI 21-24.9 kg/m2: 1.64; 95% CI 1.26-2.14). Waist circumference showed a weaker relationship with all-cause mortality in both men and women. There was little evidence of a relationship between either index of body size and subsequent cancer mortality in men or women, while non-cardiovascular non-cancer mortality was higher in underweight participants. For older men, being overweight was found to be associated with a lower risk of all-cause mortality, while among both men and women, a BMI in the underweight category was associated with a higher risk. Waist circumference alone had little association with all-cause or cause-specific mortality risk.Trial registration ASPREE https://ClinicalTrials.gov number NCT01038583.

GFR Variability, Survival, and Cardiovascular Events in Older Adults.

Rationale & Objective: Variability in estimated glomerular filtration rate (eGFR) over time is often observed, but it is unknown whether this variation is clinically important. We investigated the association between eGFR variability and survival free of dementia or persistent physical disability (disability-free survival) and cardiovascular disease (CVD) events (myocardial infarction, stroke, hospitalization for heart failure, or CVD death). Study Design: Post hoc analysis. Setting & Participants: 12,549 participants of the ASPirin in Reducing Events in the Elderly trial. Participants were without documented dementia, major physical disability, previous CVD, and major life-limiting illness at enrollment. Predictors: eGFR variability. Outcomes: Disability-free survival and CVD events. Analytical Approach: eGFR variability was estimated using the standard deviation of eGFR measurements obtained from participants' baseline, first, and second annual visits. Associations between tertiles of eGFR variability with disability-free survival and CVD events occurring after the eGFR variability estimation period were examined. Results: During median follow-up of 2.7 years after the second annual visit, 838 participants died, developed dementia, or acquired a persistent physical disability; 379 had a CVD event. The highest tertile of eGFR variability had an increased risk of death/dementia/disability (HR, 1.35; 95% CI, 1.14-1.59) and CVD events (HR, 1.37; 95% CI, 1.06-1.77) compared with the lowest tertile after covariate adjustment. These associations were present in patients with and without chronic kidney disease at baseline. Limitations: Limited representation of diverse demographics. Conclusions: In older, generally healthy adults, higher variability in eGFR over time predicts increased risk of future death/dementia/disability and CVD events.

Overt and Occult Hypoxemia in Patients Hospitalized With COVID-19.

Progressive hypoxemia is the predominant mode of deterioration in COVID-19. Among hypoxemia measures, the ratio of the Pao2 to the Fio2 (P/F ratio) has optimal construct validity but poor availability because it requires arterial blood sampling. Pulse oximetry reports oxygenation continuously (ratio of the Spo2 to the Fio2 [S/F ratio]), but it is affected by skin color and occult hypoxemia can occur in Black patients. Oxygen dissociation curves allow noninvasive estimation of P/F ratios (ePFRs) but remain unproven. OBJECTIVES: Measure overt and occult hypoxemia using ePFR. DESIGN SETTING AND PARTICIPANTS: We retrospectively studied COVID-19 hospital encounters (n = 5,319) at two academic centers (University of Virginia [UVA] and Emory University). MAIN OUTCOMES AND MEASURES: We measured primary outcomes (death or ICU transfer within 24 hr), ePFR, conventional hypoxemia measures, baseline predictors (age, sex, race, comorbidity), and acute predictors (National Early Warning Score [NEWS] and Sequential Organ Failure Assessment [SOFA]). We updated predictors every 15 minutes. We assessed predictive validity using adjusted odds ratios (AORs) and area under the receiver operating characteristic curves (AUROCs). We quantified disparities (Black vs non-Black) in empirical cumulative distributions using the Kolmogorov-Smirnov (K-S) two-sample test. RESULTS: Overt hypoxemia (low ePFR) predicted bad outcomes (AOR for a 100-point ePFR drop: 2.7 [UVA]; 1.7 [Emory]; p < 0.01) with better discrimination (AUROC: 0.76 [UVA]; 0.71 [Emory]) than NEWS (0.70 [both sites]) or SOFA (0.68 [UVA]; 0.65 [Emory]) and similar to S/F ratio (0.76 [UVA]; 0.70 [Emory]). We found racial differences consistent with occult hypoxemia. Black patients had better apparent oxygenation (K-S distance: 0.17 [both sites]; p < 0.01) but, for comparable ePFRs, worse outcomes than other patients (AOR: 2.2 [UVA]; 1.2 [Emory]; p < 0.01). CONCLUSIONS AND RELEVANCE: The ePFR was a valid measure of overt hypoxemia. In COVID-19, it may outperform multi-organ dysfunction models. By accounting for biased oximetry as well as clinicians' real-time responses to it (supplemental oxygen adjustment), ePFRs may reveal racial disparities attributable to occult hypoxemia.

Physiological predictors of morbidity and mortality in COPD: the relative importance of reduced inspiratory capacity and inspiratory muscle strength.

Low resting inspiratory capacity (IC) and low maximal inspiratory pressure (MIP) have previously been linked to exertional dyspnea, exercise limitation, and poor survival in chronic obstructive pulmonary disease (COPD). The interaction and relative contributions of these two related variables to important clinical outcomes are unknown. The objective of the current study was to examine the interaction between resting IC and MIP (both % predicted), exertional dyspnea, exercise capacity, and long-term survival in patients with COPD. Two hundred and eighty-five patients with mild to advanced COPD completed standard lung function testing and a cycle cardiopulmonary exercise test. Multiple regression determined predictors of the exertional dyspnea-ventilation slope and peak oxygen uptake (V̇o2peak). Cox regression determined predictors of 10-year mortality. IC was associated with the dyspnea-ventilation slope (standardized ß = -0.42, P < 0.001), whereas MIP was excluded from the regression model (P = 0.918). IC and MIP were included in the final model to predict V̇o2peak. However, the standardized ß was greater for IC (0.43) than MIP (0.22). After adjusting for age, sex, body mass index, cardiovascular risk, airflow obstruction, and diffusing capacity, resting IC was independently associated with 10-year all-cause mortality (hazard ratio = 1.25, confidence interval5%-95% = 1.16-1.34, P < 0.001), whereas MIP was excluded from the final model (all P = 0.829). Low resting IC was consistently linked to heightened dyspnea intensity, low V̇o2peak, and worse survival in COPD even after accounting for airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important physiological biomarker closely linked to key clinical outcomes in COPD.NEW & NOTEWORTHY To our knowledge, this study is the first to show an independent association between low resting inspiratory capacity (IC) and, severe exertional dyspnea, exercise limitation, and increased mortality risk, after accounting for the severity of airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important independent physiological biomarker closely linked to key clinical outcomes in COPD.

Overt and occult hypoxemia in patients hospitalized with novel coronavirus disease 2019.

Background: Progressive hypoxemia is the predominant mode of deterioration in COVID-19. Among hypoxemia measures, the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (P/F ratio) has optimal construct validity but poor availability because it requires arterial blood sampling. Pulse oximetry reports oxygenation continuously, but occult hypoxemia can occur in Black patients because the technique is affected by skin color. Oxygen dissociation curves allow non-invasive estimation of P/F ratios (ePFR) but this approach remains unproven. Research Question: Can ePFRs measure overt and occult hypoxemia? Study Design and methods: We retrospectively studied COVID-19 hospital encounters (n=5319) at two academic centers (University of Virginia [UVA] and Emory University). We measured primary outcomes (death or ICU transfer within 24 hours), ePFR, conventional hypoxemia measures, baseline predictors (age, sex, race, comorbidity), and acute predictors (National Early Warning Score (NEWS) and Sepsis-3). We updated predictors every 15 minutes. We assessed predictive validity using adjusted odds ratios (AOR) and area under receiver operating characteristics curves (AUROC). We quantified disparities (Black vs non-Black) in empirical cumulative distributions using the Kolmogorov-Smirnov (K-S) two-sample test. Results: Overt hypoxemia (low ePFR) predicted bad outcomes (AOR for a 100-point ePFR drop: 2.7 [UVA]; 1.7 [Emory]; p<0.01) with better discrimination (AUROC: 0.76 [UVA]; 0.71 [Emory]) than NEWS (AUROC: 0.70 [UVA]; 0.70 [Emory]) or Sepsis-3 (AUROC: 0.68 [UVA]; 0.65 [Emory]). We found racial differences consistent with occult hypoxemia. Black patients had better apparent oxygenation (K-S distance: 0.17 [both sites]; p<0.01) but, for comparable ePFRs, worse outcomes than other patients (AOR: 2.2 [UVA]; 1.2 [Emory], p<0.01). Interpretation: The ePFR was a valid measure of overt hypoxemia. In COVID-19, it may outperform multi-organ dysfunction models like NEWS and Sepsis-3. By accounting for biased oximetry as well as clinicians’ real-time responses to it (supplemental oxygen adjustment), ePFRs may enable statistical modelling of racial disparities in outcomes attributable to occult hypoxemia.

Test-Retest Reliability and Minimal Detectable Change of Four Cognitive Tests in Community-Dwelling Older Adults.

BACKGROUND: Cognitive test-retest reliability measures can be used to evaluate meaningful changes in scores. OBJECTIVE: This analysis aimed to develop a comprehensive set of test-retest reliability values and minimal detectable change (MDC) values for a cognitive battery for community-dwelling older individuals in Australia and the U.S., for use in clinical practice. METHODS: Cognitive scores collected at baseline and year 1, in the ASPirin in Reducing Events in the Elderly clinical trial were used to calculate intraclass correlation coefficients (ICC) for four tests: Modified Mini-Mental State examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), single-letter Controlled Oral Word Association Test (COWAT-F), and Symbol Digit Modalities Test (SDMT). 16,956 participants aged 70 years and over (65 years and over for U.S. minorities) were included. ICCs were used to calculate MDC values for eight education and ethno-racial subgroups. RESULTS: All four cognitive tests had moderate (ICC > 0.5) to good (ICC > 0.7) test-retest reliability. ICCs ranged from 0.53 to 0.63 (3MS), 0.68 to 0.77 (SDMT), 0.56 to 0.64 (COWAT-F), 0.57 to 0.69 (HVLT-R total recall), and 0.57 to 0.70 (HVLT-R delayed recall) across the subgroups. MDC values ranged from 6.60 to 9.95 (3MS), 12.42 to 15.61 (SDMT), 6.34 to 8.34 (COWAT-F), 8.13 to 10.85 (HVLT-R total recall), and 4.00 to 5.62 (HVLT-R delayed recall). CONCLUSION: This large cohort of older individuals provides test-retest reliability and MDC values for four widely employed tests of cognitive function. These results can aid interpretation of cognitive scores and decline instead of relying on cross-sectional normative data alone.

Long-Term Blood Pressure Variability and Kidney Function in Participants of the ASPREE Trial.

BACKGROUND: Whether long-term blood pressure variability (BPV) predicts kidney function decline in generally healthy older adults is unknown. We investigated this association in ASPirin in Reducing Events in the Elderly (ASPREE) trial participants. METHODS: Between 2010 and 2014, Australian and US individuals aged ≥70 years (≥65 if US minority) were recruited and followed with annual study visits for a median of 4.7 years. Time-to-event analyses and linear mixed effects models were used to examine associations between incident chronic kidney disease (CKD), and trajectories of estimated glomerular filtration rate (eGFR) and log albumin-creatinine ratio (log ACR) with systolic BPV as a continuous measure, and, by tertile of SD of systolic blood pressure (BP). BPV was estimated using systolic BP measures from baseline through the second annual visit, and kidney outcomes were assessed following this period. RESULTS: Incident CKD occurred in 1,829 of 6,759 participants (27.2%), and more commonly in BPV tertiles 2 (27.4%) and 3 (28.3%) than tertile 1 (25.5%); however, the risk was not significantly increased after covariate adjustment (tertile 3 hazard ratio = 1.02; 95% confidence interval: 0.91-1.14). Analysis of eGFR (n = 16,193) and log ACR trajectories (n = 15,213) showed individuals in the highest BPV tertile having the lowest eGFR and highest log ACR, cross-sectionally. However, the trajectories of eGFR and log ACR did not differ across BPV tertiles. CONCLUSIONS: CKD and markers of reduced kidney function occur more commonly in individuals with higher BPV; however, BPV does not influence trajectory of decline in kidney function over time in older adults who are in generally good health. CLINICAL TRIALS REGISTRATION: Trial Number NCT01038583 and ISRCTN83772183.

Real-World Outcomes in Cystic Fibrosis Telemedicine Clinical Care in a Time of a Global Pandemic.

BACKGROUND: During the COVID-19 pandemic, the University of Virginia adult cystic fibrosis (CF) center transitioned from in-person clinical encounters to a model that included interdisciplinary telemedicine. The pandemic presented an unprecedented opportunity to assess the impact of the interdisciplinary telemedicine model on clinical CF outcomes. RESEARCH QUESTION: What are the clinical outcomes of a care model that includes interdisciplinary telemedicine (IDC-TM) compared with in-person clinical care for patients with CF during the COVID-19 pandemic? STUDY DESIGN AND METHODS: Adults with CF were included. The prepandemic year was defined as March 17, 2019, through March 16, 2020, and the pandemic year (PY) was defined as March 17, 2020, through March 16, 2021. Patients were enrolled starting in the PY. Prepandemic data were gathered retrospectively. Telemedicine visits were defined as clinical encounters via secured video communication. Hybrid visits were in-person evaluations by physician, with in-clinic video communication by other team members. In-person visits were encounters with in-person providers only. All encounters included previsit screening. Outcomes were lung function, BMI, exacerbations, and antibiotic use. FEV1 percent predicted, exacerbations, and antibiotic use were adjusted for the effect of elexacaftor/tezacaftor/ivacaftor treatment. RESULTS: One hundred twenty-four patients participated. One hundred ten patients were analyzed (mean age, 35 years; range, 18-69 years). Ninety-five percent had access to telemedicine (n = 105). Telemedicine visits accounted for 64% of encounters (n = 260), hybrid visits with telemedicine support accounted for 28% of encounters (n = 114), and in-person visits accounted for 7% of encounters (n = 30). No difference in lung function or exacerbation rate during the PY was found. BMI increased from 25 to 26 kg/m2 (t100 = -4.72; P < .001). Antibiotic use decreased from 316 to 124 episodes (z = 8.81; P < .0001). INTERPRETATION: This CF care model, which includes IDC-TM, successfully monitored lung function and BMI, identified exacerbations, and followed guidelines-based care during the pandemic. A significant decrease in antibiotic use suggests that social mitigation strategies were protective. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04402801; URL: www. CLINICALTRIALS: gov.

Qualitative Components of Dyspnea during Incremental Exercise across the COPD Continuum.

INTRODUCTION: Evaluation of the intensity and quality of activity-related dyspnea is potentially useful in people with chronic obstructive pulmonary disease (COPD). The present study sought to examine associations between qualitative dyspnea descriptors, dyspnea intensity ratings, dynamic respiratory mechanics, and exercise capacity during cardiopulmonary exercise testing (CPET) in COPD and healthy controls. METHODS: In this cross-sectional study, 261 patients with mild-to-very severe COPD (forced expiratory volume in 1 s, 62 ± 25%pred) and 94 age-matched controls (forced expiratory volume in 1 s, 114 ± 14%pred) completed an incremental cycle CPET to determine peak oxygen uptake (V˙O2peak). Throughout exercise, expired gases, operating lung volumes, and dyspnea intensity were assessed. At peak exercise, dyspnea quality was assessed using a modified 15-item questionnaire. RESULTS: Logistic regression analysis revealed that among 15 dyspnea descriptors, only those alluding to the cluster "unsatisfied inspiration" were consistently associated with an increased likelihood for both critical inspiratory mechanical constraint (end-inspiratory lung volume/total lung capacity ratio ≥0.9) during exercise and reduced exercise capacity (V˙O2peak < lower limit of normal) in COPD (odds ratio (95% confidence interval), 3.26 (1.40-7.60) and 3.04 (1.24-7.45), respectively; both, P < 0.05). Thus, patients reporting "unsatisfied inspiration" (n = 177 (68%)) had an increased relative frequency of critical inspiratory mechanical constraint and low exercise capacity compared with those who did not select this descriptor, regardless of COPD severity or peak dyspnea intensity scores. CONCLUSIONS: In patients with COPD, regardless of disease severity, reporting descriptors in the unsatisfied inspiration cluster complemented traditional assessments of dyspnea during CPET and helped identify patients with critical mechanical abnormalities germane to exercise intolerance.

Clinical trials in otology: Examining trends and framework for prioritization.

OBJECTIVE: To characterize otologic clinical trials and examine otologic clinical trial trends from 2008 to 2018 using the clinicaltrials.gov database. METHODS: Data was collected from clinicaltrials.gov and included all clinical trials that focused on otology from 2008 to 2018. Outcome measures include status of trials, funding sources, details regarding otologic conditions studied, and trends in clinical trials. RESULTS: There were 992 otology clinical trials from 2008 to 2018.457 (46.1%) were completed and 94 (9.5%) were discontinued. Industry remained the highest (76.5%) contributor to otology clinical trials. The otologic conditions studied, from most common to least common, include hearing loss (40.6%), vestibulopathy (18.8%), tinnitus (18.8%), and otitis media (15.1%). The number of otology clinical trials increased by an average of 12.0 trials per year from 2008 to 2018 (p < 0.001). The number of otology clinical trials focusing on hearing loss and vestibulopathy significantly increased over the studied period (p < 0.001), while those focusing on tinnitus and otitis media did not (p = 0.09 and p = 0.20, respectively). The majority of clinical trials on each of these four conditions focused on treatment options. CONCLUSION: Our study describes trends in otology clinical trials registered on clinicaltrials.gov from 2008 through 2018. The total number of clinical trials over this time period increased significantly, driven by trials investigating hearing loss and vestibulopathy. Furthermore, most clinical trials were industry-sponsored and focused on treatment modalities. Our study provides an outline of otology clinical trials registered in a US web-based database, which may be of use for the development of future clinical trials.

Patient-Reported Outcomes of Split-Thickness Skin Grafts for Floor of Mouth Cancer Reconstruction.

INTRODUCTION: Patient-reported outcome measures (PROM) on quality of life (QOL) for early-stage floor of mouth carcinoma (FOM-CA) undergoing surgical resection and split-thickness skin graft (STSG) reconstruction have not been established. We have performed a cross-sectional QOL analysis of such patients to define functional postoperative outcomes. METHODS: Patients with pathologic stage T1/T2 FOM-CA who underwent resection and STSG reconstruction at a tertiary academic cancer center reported outcomes with the University of Washington QOL (v4) questionnaire after at least 6 months since surgery. RESULTS: Twenty-four out of 49 eligible patients completed questionnaires with a mean follow-up of 41 months (range: 6-88). Subsites of tumor involvement/resection included the following: (1) lateral FOM (L-FOM) (n = 17), (2) anterior FOM (A-FOM) (n = 4), and (3) alveolar ridge with FOM, all of whom underwent lateral marginal mandibulectomy (MM-FOM) (n = 3). All patients reported swallowing scores of 70 ("I cannot swallow certain solid foods") or better. Ninety-six percent (23/24) reported speech of 70 ("difficulty saying some words, but I can be understood over the phone") or better. A-FOM patients reported worse chewing than L-FOM patients (mean: 50.0 vs. 85.3; p = 0.01). All 4 A-FOM patients reported a low chewing score of 50 ("I can eat soft solids but cannot chew some foods"). Otherwise, there were no significant differences between subsite groups in swallowing, speech, or taste. CONCLUSION: STSG reconstructions for pathologic T1-T2 FOM-CA appear to result in acceptable PROM QOL outcomes with the exception of A-FOM tumors having worse chewing outcomes.

Patient-Reported Quality of Life After Resection With Primary Closure for Oral Tongue Carcinoma.

OBJECTIVES/HYPOTHESIS: For early-stage oral tongue carcinoma and carcinoma in situ (ESOTCCIS), we evaluated patient-reported quality-of-life (QOL) outcomes following resection with primary closure (R-PC). STUDY DESIGN: Retrospective review at an academic cancer center. METHODS: Thirty-nine ESOTCCIS patients (Tis, T1, T2) who underwent R-PC without radiation completed the University of Washington Quality of Life Questionnaire Version 4 (UW-QOL) at least 6 months since R-PC (mean = 2.39 years; range = 0.5-6.7 years). We compared UW-QOL scores for pain, swallowing, chewing, speech, and taste to established normative population scores. Multivariable regression analysis evaluated factors associated with QOL impairment. RESULTS: ESOTCCIS patients who underwent R-PC in comparison to the normative population reported significantly worse mean speech (87.7 vs. 98, P < .001) and taste (85.6 vs. 95, P = .002) scores and no significant differences in mean pain (91.7 vs. 86, P = .96), swallowing (100 vs. 98, P = .98), chewing (97.4 vs. 94, P = .98) scores. For speech and taste, 59% (23/39) reported no postoperative change from baseline, whereas 41% (16/39) and 35.9% (14/39) reported mild impairment, respectively. Overall, postoperative QOL was reported as good, very good, or outstanding by 87.2% (34/39). Higher American Society of Anesthesiologists class, cT1 compared to CIS, and ventral tongue involvement were independently associated with worse speech. Age < 60 years was independently associated with worse taste. CONCLUSIONS: ESOTCCIS patients who undergo R-PC without radiation can expect long-term swallowing, chewing, and pain to be in the normative range. Although a majority of patients can expect to achieve normative speech and taste outcomes, R-PC carries the risks of mild speech and/or taste impairments. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:312-318, 2021.

Low resting diffusion capacity, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease.

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (DlCO) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both DlCO decline and worsening respiratory mechanics, and their relative contribution to dyspnea has not been determined. In a retrospective analysis of 300 COPD patients who completed symptom-limited incremental cardiopulmonary exercise tests, we tested the association between peak oxygen-uptake (V̇o2), DlCO, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV1) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low DlCO [i.e.,

Influences of Age, Gender, and Body Mass Index on the Depth of the Superficial Fascia of the Arm and Thigh.

BACKGROUND: Nonsurgical skin-tightening procedures are increasing in popularity because of their noninvasiveness as the energy is transdermally applied to the subcutaneous tissues. OBJECTIVE: To provide precise data on the depth of the superficial fascia for potentially safer and better targeted treatments of arms and thighs. METHODS: One hundred fifty Caucasian individuals were investigated with an equal distribution of men and women (each n = 75) and a balanced distribution of age (n = 30 per decade). Ultrasound-based measurements were conducted, measuring the distance between skin and the superficial fascia in the posterior arm and the anterior, medial, and posterior thigh. RESULTS: Deep to the skin, 5 layers were consistently and bilaterally identified in both sexes: skin, superficial fat, superficial fascia, deep fat, and deep fascia. The overall mean distance between the skin surface and the superficial fascia was for the posterior arm 4.38 ± 0.9 mm; range (2.60-6.70), for the anterior thigh 7.90 ± 2.3 mm range (3.50-13.20), for the medial thigh 5.74 ± 1.2 mm range (3.10-8.20), and for the posterior thigh 7.77 ± 3.2 mm range (3.60-14.50). CONCLUSION: Knowing the precise depth of the superficial fascia for nonsurgical skin-tightening procedures could potentially guide practitioners toward safer and more effective outcomes.

Treating the Lips and Its Anatomical Correlate in Respect to Vascular Compromise.

Treating the lips to increase facial attractiveness and youthfulness is challenging when trying to consider ethnic differences in an increasingly more diverse society. Multiple injection techniques are currently available for treating lip contour and volume, but a validation in the cadaveric model under the aspects of safety has not been performed yet. The injection techniques presented in this study are based on the experience and personal selection of the authors. The authors have assessed, treated, and evaluated for more than 20 years patients from the Middle East and Central Europe. Cadaveric verification was performed for each of the presented techniques to identify the positioning of the injected product inside the lips and its relation to the superior/inferior labial arteries. The results of the anatomic analyses revealed that in 58.3% of the performed injections, the product was placed close to the superior/inferior labial arteries. In 60.0% of the cases, applications using a needle placed the injected product in endangered locations, whereas 57.1% of the cases using cannulas placed the product in endangered locations (i.e., in the vicinity of the superior/inferior labial arteries). This anatomic study revealed that injected material into the lips is frequently placed in close proximity to labial arteries representing a high risk for intra-arterial applications, leading to tissue loss (necrosis) and potential end-arterial embolism (potential blindness). Nevertheless, treatment of the lips should be a multistep approach focusing first on the far (upper and middle face) and close (labiomandibular and labiomental) perioral regions.

Influence of Age, Sex, and Body Mass Index on the Depth of the Superficial Fascia in the Face and Neck.

BACKGROUND: Nonsurgical skin-tightening procedures are increasing in popularity, as patients seek aesthetic interventions that are safe with minimal downtime. OBJECTIVE: This study was designed to provide precise data on the depth of the superficial fascia-the structure of action-of the face and neck. METHODS: One hundred fifty Caucasian individuals (75 men and 75 women) were investigated with a balanced distribution of age (n = 30 per decade: 20-29, 30-39, 40-49, 50-59, and 60-69 years) and body mass index (BMI) (n = 50 per group: BMI ≤ 24.9 kg/m, BMI between 25.0 and 29.9 kg/m, and BMI ≥ 30 kg/m). The distance between skin surface and the superficial fascia was measured through ultrasound in the buccal region, premasseteric region, and lateral neck. RESULTS: The mean distance between skin surface and superficial fascia was for the buccal region 4.82 ± 0.9 mm, range (2.60-6.90); for the premasseteric region 4.25 ± 0.6 mm, range (2.60-5.80); and for the lateral neck 3.71 ± 0.5 mm, range (2.0-5.0). The depth of the superficial fascia increased with increasing BMI, whereas it decreased with advanced age. CONCLUSION: Knowing the precise depth of the superficial fascia for nonsurgical skin-tightening procedures will guide practitioners toward safer and more effective outcomes.