Objectives Dupilumab was the first biologic approved to treat chronic rhinosinusitis with nasal polyps (CRSwNP). While the risk of adverse events in phase‐III clinical trials was low, dupilumab‐associated adverse reactions (DAR) with real‐world use is unknown and potentially under‐reported. We aimed to evaluate DAR for CRSwNP treatment (CRSwNP‐tx) using the FDA Adverse Event Reporting System (FAERS). Study Design Retrospective database study. Methods FAERS was queried for DAR from 2019Q1 to 2021Q2. Individual DAR (iDAR) were categorized and quantitatively compared between treatment groups (CRSwNP, asthma, atopic dermatitis). Zero‐truncated Poisson regression was modeled to predict the number of iDAR, and logistic regression was modeled to predict serious DARs. Results There were 15,411 DAR observations; 911 for CRSwNP‐tx, of which 121 (13.3%) had serious reactions and 3 died. Common CRSwNP‐tx iDAR were dermatologic (13.9%), generalized (13.3%), and injection‐site (10.8%) symptoms. The number of CRSwNP‐tx iDAR was 2.99 [2.81, 3.17], compared to 3.44 [3.32, 3.56] for asthma and 3.18 [3.13, 3.24] for atopic dermatitis (Kruskal‐Wallis test, P < .001). For CRSwNP‐tx, iDAR reported‐risk‐ratio was 0.84 [0.77, 0.92] among men and 1.12 [1.04, 1.22] among older adults (>50). Serious DAR reported‐odds‐ratio was 1.37 [0.91, 2.04] among men and 1.39 [0.93, 2.08] among older adults. Conclusions While there are limitations with FAERS, this analysis suggests CRSwNP‐tx is associated with fewer iDAR compared with other treatment indications. More iDAR are experienced among women and older adults, but men tend to have more serious DAR. Level of Evidence 3 Laryngoscope, 132:2307–2313, 2022

Objective. The interruption of vascular supply to the inner ear is one of several proposed etiologies of sudden sensorineural hearing loss (SSNHL). The increased presence of cardiovascular risk factors may predispose patients to SSNHL through this pathway. This systematic review and meta-analysis studies the presence of cardiovascular risk factors in patients diagnosed with SSNHL.Data Sources. Databases included PubMed/Medline, OVID, EMBASE, Cochrane, and Web of Science.Review Methods. Inclusion criteria included studies featuring SSNHL patients presenting with 1+ cardiovascular risk factors. Exclusion criteria included case reports and studies without outcome measures. Two investigators independently reviewed all manuscripts and performed quality assessments using validated tools.Results. Of 532 identified abstracts, 27 studies met inclusion criteria (19 case-control, 4 cohorts, 4 case series). Of these, 24 underwent meta-analysis encompassing a total of 77,566 patients (22,620 SSNHL patients, 54,946 matched controls). The mean age was 50.43 years. SSNHL patients were more likely to have concomitant diabetes (odds ratio [OR] 1.61 [95% confidence interval [CI]: 1.31, 1.99; p < .00001]) and hypertension (OR 1.5 [95% CI: 1.16, 1.94; p = .002]). An increased standard mean difference of total cholesterol of 11.09 mg/dL (95% CI; 3.51, 18.67; p = .004) was noted in the SSNHL group compared with the controls. No significant differences in smoking, high-density lipoprotein, triglycerides, or body mass index were detected. Conclusion.Patients presenting with SSNHL have a significantly higher risk of concomitant diabetes, hypertension, and higher total cholesterol in comparison to matched controls. This may indicate a higher cardiovascular risk profile in this population. More prospective and matched cohort studies are needed to understand the role of cardiovascular risk factors in SSNHL.

Purpose We aimed to measure 1) the dynamics of locomotor fatigue during constant supra-critical power cycling and 2) the magnitude of any reserve in locomotor power at intolerance to constant and ramp-incremental cycling in recreationally active volunteers. Methods Fifteen participants (7 women and 8 men, 22 ± 3 yr, 3.34 ± 0.67 L·min−1 V˙O2peak) completed ramp-incremental and very-heavy constant power (205 ± 46 W) exercise to the limit of tolerance. Immediately after intolerance, the ergometer was switched into the isokinetic mode, and participants completed a short (~5 s) maximal isokinetic effort at 70 rpm. The time course of locomotor fatigue during constant supra-critical power exercise was characterized with these short maximal isokinetic sprints at 30, 60, 120, and 180 s and at the limit of tolerance. Each bout was terminated after the isokinetic sprint. Results Constant power exercise duration was 312 ± 37 s. Isokinetic power production values at 30, 60, 120, and 180 s and at the limit of tolerance (at 312 ± 37 s) was 609 ± 165, 503 ± 195, 443 ± 157, 449 ± 133, and 337 ± 94 W, respectively. Of the total decline in isokinetic power, ~36% occurred within the first minute of exercise, and significant (P < 0.05) reductions in isokinetic power occurred at all time points versus the baseline maximal isokinetic power (666 ± 158 W). In addition, a significant power reserve of 132 ± 74 W (64% of the task requirement) and 119 ± 80 W (47%) was present at the limit of constant power and ramp-incremental exercise, respectively. Conclusions Locomotor fatigue occurred rapidly during supracritical power exercise with pseudo-exponential kinetics. Instantaneous isokinetic power production at the limit of tolerance exceeded that of the task requirement, regardless of the constant or ramp work rate profile. Thus, the perceptual and physiologic limits were dissociated at the limit of tolerance in recreationally active volunteers.

The asymptote of the hyperbolic power-duration relationship, critical power (CP), demarcates sustainable from non-sustainable exercise. CP is a salient parameter within the theoretical framework determining exercise tolerance. However, measuring CP is time consuming – typically 4 constant-power exercise tests to intolerance, or a 3-min all-out sprint is required.To determine whether 30 s of maximal isokinetic cycling, immediately following the limit of tolerance, approximates CP.Fifteen participants (7 women, 8 men, 23±5 yr, 71±12 kg, V̇O2peak 4.39±1.04 L·min−1; 61±9 mL·kg·min−1) completed 4 constant supra-CP exercise tests to intolerance. Each test was followed immediately by a 30 s maximal isokinetic effort at 80 rpm. Mean isokinetic power was compared to the known CP.Mean±SD CP was 159±47 W (CI95 133, 185 W). Maximal isokinetic power immediately following intolerance was greater (p<0.05) than CP in all but one comparison (181±51 vs. 159±47 W; p>0.07). However, this closest estimation, following the longest duration constant-power test, resulted in 21 W of mean bias and wide limits of agreement (±84 W).Isokinetic power measured immediately following intolerance consistently overestimated critical power. Thus, an adjunct of 30 s maximal isokinetic cycling immediately following the limit of tolerance does not approximate critical power.

(Sadler C, Brett K, Heerboth A, Swisher AR, Mehregani N, Touriel R, Cannon DT. Safety proposals for freediving time limits should consider the metabolic-rate dependence of oxygen stores depletion. Diving and Hyperbaric Medicine. 2020 December 20;50(4):356–362. doi: 10.28920/dhm50.4.356-362. PMID: 33325016.) Introduction: There is no required training for breath-hold diving, making dissemination of safety protocols difficult. A recommended breath-hold dive time limit of 60 s was proposed for amateur divers. However, this does not consider the metabolic-rate dependence of oxygen stores depletion. We aimed to measure the effect of apnoea time and metabolic rate on arterial and tissue oxygenation. Methods: Fifty healthy participants (23 (SD 3) y, 22 women) completed four periods of apnoea for 60 s (or to tolerable limit) during rest and cycle ergometry at 20, 40, and 60 W. Apnoea was initiated after hyperventilation to achieve PETCO2 of approximately 25 mmHg. Pulse oximetry, frontal lobe oxygenation, and pulmonary gas exchange were measured throughout. We defined hypoxia as SpO2 < 88%. Results: Static and exercise (20, 40, 60 W) breath-hold break times were 57 (SD 7), 50 (11), 48 (11), and 46 (11) s (F [2.432, 119.2] = 32.0, P < 0.01). The rise in PETCO2 from initiation to breaking of apnoea was dependent on metabolic rate (time × metabolic rate interaction; F [3,147] = 38.6, P < 0.0001). The same was true for the fall in SpO2 (F [3,147] = 2.9, P = 0.03). SpO2 fell to < 88% on 14 occasions in eight participants, all of whom were asymptomatic. Conclusions: Independent of the added complexities of a fall in ambient pressure on ascent, the effect of apnoea time on hypoxia depends on the metabolic rate and is highly variable among individuals. Therefore, we contend that a universally recommended time limit for breath-hold diving or swimming is not useful to guarantee safety.

Combining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of macrophages is typically neuroprotective, the delay in the resolution of macrophage activity can be a complication if the damaged cochlea is used as a model to study subsequent therapeutic strategies. Here, we applied a high dose combination of systemic gentamicin and furosemide in C57 BL/6 and CBA/CaJ mice and studied the ototoxic consequences in the cochlea, including hair cell survival, ribbon synaptic integrity, and macrophage activation up to 15-day posttreatment. The activity of macrophages in the basilar membrane was correlated to the severity of cochlear damage, particularly the hair cell damage. Comparatively, C57 BL/6 cochleae were more vulnerable to the ototoxic challenge with escalated macrophage activation. In addition, the ribbon synaptic deterioration was disproportionately limited when compared to the degree of outer hair cell loss in CBA/CaJ mice. The innate and differential otoprotection in CBA/CaJ mice appears to be associated with the rapid activation of cochlear macrophages and a certain level of synaptogenesis after the combined gentamicin and furosemide treatment.

Background: Acellular dermal matrices (ADMs) are commonly used in tissue expander and direct-to-implant reconstruction following mastectomy. Few studies have reported outcomes of DermACELL use or compared DermACELL with AlloDerm ADM. This study sought to compare outcomes of DermACELL and AlloDerm in oncologic breast reconstruction and to review the literature reporting outcomes of patients undergoing reconstruction using DermACELL. Methods: We conducted a retrospective cohort study to compare outcomes between DermACELL and AlloDerm ADM, and a systematic review of the literature with a meta-analysis to evaluate clinical outcomes with DermACELL. Results: Seventy-four patients (128 breasts) undergoing immediate reconstruction were evaluated retrospectively. Chi-square analysis revealed no significant difference in postoperative outcomes between the two groups. Our systematic review of the literature yielded 12 total studies reporting DermACELL use for breast reconstruction encompassing 518 patients and 608 total breasts. A pooled analysis of the published data did not reveal a significant change in the rate of explantation when either chemotherapy or radiation was used. Meta-analysis did not show a significant difference in the rate of any of the complications evaluated. Conclusion: DermACELL is safe to use with a relatively consistent complication profile as compared with AlloDerm.

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