Myofascial release induces declines in heart rate and changes to microvascular reactivity in young healthy adults.

OBJECTIVES: The purpose of this study was to compare physiological responses to myofascial release (MFR) and passive limb movement (PLM). DESIGN: Nineteen (23 ± 2.6yrs) adults (10 men and 9 women) completed two experiments on separate days: MFR and PLM. Participation included collecting ultrasound images, blood pressure, and heart rate (HR) as well as performing a vascular occlusion test (VOT). The VOT assessed muscle tissue oxygenation (StO2) with near-infrared spectroscopy. Experiments consisted of moving the upper limb to release subtle barriers of resistance in the muscle/fascia (MFR) and passive, assisted range of motion (PLM). RESULTS: There was a significantly (p = 0.012) greater decrease in HR following MFR (-7.3 ± 5.2 BPM) than PLM (-1.3 ± 0.9 BPM). There was an equivalent change in brachial blood flow (-17.3 ± 23.0 vs. -11.9 ± 14.9 mL min-1; p = 0.37) and vascular conductance (-19.3 ± 31.1 vs. -12.4 ± 15.3 mL min-1 mmHg-1; p = 0.38). Microvascular responses differed between the experiments such that MFR exhibited greater area under the curve (AUC, 1503 ± 499.1%∙s-1 vs. 1203 ± 411.1%∙s-1; p = 0.021) and time to maximum StO2 (40.0 ± 8.4s vs. 35.8 ± 7.3s; p = 0.009). CONCLUSIONS: As evidenced by HR, MFR induced greater parasympathetic activity than PLM. The greater AUC and time to StO2max following MFR suggested a spillover effect to induce prolonged hyper-saturation. These results may be of interest to those investigating possible MFR-related rehabilitative benefits.

Impact of Ketorolac on Reoperation for Hemorrhage After Pediatric Tonsillectomy: A Single-Center Retrospective Propensity-Matched Study.

OBJECTIVE: To determine if perioperative ketorolac is associated with an increased rate of reoperation for hemorrhage after pediatric tonsillectomy at 30 days and 48 hours. STUDY DESIGN: Single-center retrospective propensity-matched study. SETTING: Quaternary pediatric hospital and ambulatory surgery center. METHODS: Patients less than 18 years old undergoing tonsillectomy or adenotonsillectomy between January 1, 2015 and October 1, 2020 were included. Hemorrhage rates between exposed (K+) and unexposed (K-) patients were calculated for the total cohort and a 1:1 propensity-matched cohort. Additional analyses included: multivariable logistic regression, subgroup analysis of ASA 1 and 2 patients, subgroup analysis comparing children with teenagers. RESULTS: There were 5873 patients (42.1% K+) in the full cohort and 4694 patients in the propensity-matched cohort. Reoperation for hemorrhage within 30 days occurred in 1.9% of K+ patients and 1.6% of K- patients (P = 0.455) in the full cohort and 1.9% of K+ patients and 1.7% of K- patients (odds ratio [OR] 1.10, 95% confidence interval [CI] 0.72-1.69, P = 0.662) in the propensity-matched cohort. Reoperation within 48 hours occurred in 0.65% of K+ patients and 0.53% of K- patients (P = 0.679) in the full cohort and 0.68% of K+ patients and 0.51% of K- patients (OR 1.33, 95% CI 0.63-2.81, P = 0.451) in the propensity-matched cohort. There was no association between perioperative ketorolac administration and reoperation for hemorrhage in any of the other analyses. CONCLUSION: Ketorolac at end of surgery should be considered as part of the nonopioid analgesic regimen for pediatric tonsillectomy.

Examining Relationships between Cognitive Flexibility, Exercise Perceptions, and Cardiovascular Disease Risk Factors.

Adults do not engage in enough physical activity. Investigating cognitive and physiological factors related to improving this behavior-and reducing health risks-remains a public health priority. Our objective was to assess whether cognitive flexibility influenced perceptions and choice of exercise programs and whether flexibility was associated with cardiovascular disease (CVD) risk factors. Independent sample groups of college-aged adults (18-24 yrs) participated in two studies. Data were collected on individuals' degree of cognitive flexibility (both self-reported and objectively measured), perceptions and choice of exercise programs, and health status markers known to be associated with CVD (vascular function, muscular strength, and body composition). Vascular function was assessed with a near-infrared spectroscopy device, strength was defined as handgrip, and body composition was estimated via digital circumferences. Self-reported flexibility reliably predicted individuals' choice of exercise program and perceptions of effort required for success on an exercise program. The relationships among CVD risk factors and objectively measured cognitive flexibility were not significant, demonstrating that identifying a healthy individual's degree of performance-based cognitive flexibility does not predict health status. Furthermore, although greater self-reported trait flexibility (rigidity) is known to predict higher (lower) likelihood of physical activity, this finding should not be extrapolated to also assume that flexibility (rigidity), as measured by objective cognitive tests, is associated with reduced CVD risk in healthy adults. We posit a rationale for how understanding cognitive flexibility and rigidity can play an impactful role in improving adherence to exercise prescriptions targeted to reducing risks.

Racial, Ethnic, Sex, and Age Differences in COVID-19 Cases, Hospitalizations, and Deaths Among Incarcerated People and Staff in Correctional Facilities in Six Jurisdictions, United States, March-July 2020.

OBJECTIVES: To examine disparities by sex, age group, and race and ethnicity in COVID-19 confirmed cases, hospitalizations, and deaths among incarcerated people and staff in correctional facilities. METHODS: Six U.S. jurisdictions reported data on COVID-19 confirmed cases, hospitalizations, and deaths stratified by sex, age group, and race and ethnicity for incarcerated people and staff in correctional facilities during March 1- July 31, 2020. We calculated incidence rates and rate ratios (RR) and absolute rate differences (RD) by sex, age group, and race and ethnicity, and made comparisons to the U.S. general population. RESULTS: Compared with the U.S. general population, incarcerated people and staff had higher COVID-19 case incidence (RR = 14.1, 95% CI = 13.9-14.3; RD = 6,692.2, CI = 6,598.8-6,785.5; RR = 6.0, CI = 5.7-6.3; RD = 2523.0, CI = 2368.1-2677.9, respectively); incarcerated people also had higher rates of COVID-19-related deaths (RR = 1.6, CI = 1.4-1.9; RD = 23.6, CI = 14.9-32.2). Rates of COVID-19 cases, hospitalizations, and deaths among incarcerated people and corrections staff differed by sex, age group, and race and ethnicity. The COVID-19 hospitalization (RR = 0.9, CI = 0.8-1.0; RD = -48.0, CI = -79.1- -16.8) and death rates (RR = 0.8, CI = 0.6-1.0; RD = -11.8, CI = -23.5- -0.1) for Black incarcerated people were lower than those for Black people in the general population. COVID-19 case incidence, hospitalizations, and deaths were higher among older incarcerated people, but not among staff. CONCLUSIONS: With a few exceptions, living or working in a correctional setting was associated with higher risk of COVID-19 infection and resulted in worse health outcomes compared with the general population; however, Black incarcerated people fared better than their U.S. general population counterparts.

The Burden of Proof studies: assessing the evidence of risk.

Exposure to risks throughout life results in a wide variety of outcomes. Objectively judging the relative impact of these risks on personal and population health is fundamental to individual survival and societal prosperity. Existing mechanisms to quantify and rank the magnitude of these myriad effects and the uncertainty in their estimation are largely subjective, leaving room for interpretation that can fuel academic controversy and add to confusion when communicating risk. We present a new suite of meta-analyses-termed the Burden of Proof studies-designed specifically to help evaluate these methodological issues objectively and quantitatively. Through this data-driven approach that complements existing systems, including GRADE and Cochrane Reviews, we aim to aggregate evidence across multiple studies and enable a quantitative comparison of risk-outcome pairs. We introduce the burden of proof risk function (BPRF), which estimates the level of risk closest to the null hypothesis that is consistent with available data. Here we illustrate the BPRF methodology for the evaluation of four exemplar risk-outcome pairs: smoking and lung cancer, systolic blood pressure and ischemic heart disease, vegetable consumption and ischemic heart disease, and unprocessed red meat consumption and ischemic heart disease. The strength of evidence for each relationship is assessed by computing and summarizing the BPRF, and then translating the summary to a simple star rating. The Burden of Proof methodology provides a consistent way to understand, evaluate and summarize evidence of risk across different risk-outcome pairs, and informs risk analysis conducted as part of the Global Burden of Diseases, Injuries, and Risk Factors Study.

Health effects associated with smoking: a Burden of Proof study.

As a leading behavioral risk factor for numerous health outcomes, smoking is a major ongoing public health challenge. Although evidence on the health effects of smoking has been widely reported, few attempts have evaluated the dose-response relationship between smoking and a diverse range of health outcomes systematically and comprehensively. In the present study, we re-estimated the dose-response relationships between current smoking and 36 health outcomes by conducting systematic reviews up to 31 May 2022, employing a meta-analytic method that incorporates between-study heterogeneity into estimates of uncertainty. Among the 36 selected outcomes, 8 had strong-to-very-strong evidence of an association with smoking, 21 had weak-to-moderate evidence of association and 7 had no evidence of association. By overcoming many of the limitations of traditional meta-analyses, our approach provides comprehensive, up-to-date and easy-to-use estimates of the evidence on the health effects of smoking. These estimates provide important information for tobacco control advocates, policy makers, researchers, physicians, smokers and the public.

Diverse geroprotectors differently affect a mechanism linking cellular aging to cellular quiescence in budding yeast.

We propose a hypothesis of a mechanism linking cellular aging to cellular quiescence in chronologically aging budding yeast. Our hypothesis posits that this mechanism integrates four different processes, all of which are initiated after yeast cells cultured in a medium initially containing glucose consume it. Quiescent cells that develop in these cultures can be separated into the high- and low-density sub-populations of different buoyant densities. Process 1 of the proposed mechanism consists of a cell-cycle arrest in the G1 phase and leads to the formation of high-density quiescent cells. Process 2 results in converting high-density quiescent cells into low-density quiescent cells. Processes 3 and 4 cause a fast or slow decline in the quiescence of low- or high-density quiescent cells, respectively. Here, we tested our hypothesis by assessing how four different geroprotectors influence the four processes that could link cellular aging to cellular quiescence. We found that these geroprotectors differently affect processes 1 and 2 and decelerate processes 3 and 4. We also found that a rise in trehalose within quiescent yeast contributes to chronological aging and quiescence maintenance. These data collectively provide conclusive evidence for a mechanistic link between cellular aging and cellular quiescence.

Life Expectancy for White, Black, and Hispanic Race/Ethnicity in U.S. States: Trends and Disparities, 1990 to 2019.

BACKGROUND: Life expectancy (LE) differences within and between states by race/ethnicity have not been examined. OBJECTIVE: To estimate LE for selected race/ethnicity groups in states from 1990 to 2019. DESIGN: Cross-sectional time-series analysis. SETTING: United States. PARTICIPANTS: Deidentified death records and Census data were used to construct regression models with smoothed time series of mortality from 1990 to 2019. MEASUREMENTS: LE at birth, by sex and year, for subgroups of people reporting Hispanic, non-Hispanic Black, or non-Hispanic White race/ethnicity. RESULTS: Disparities in LE across states were 8.0 years for females and 12.2 years for males in 1990 and 7.9 years for females and 7.8 years for males in 2019. When race/ethnicity groups were accounted for, disparities across states were 20.7 years for females and 24.5 years for males in 1990, decreasing to 18.5 years for females and 23.7 years for males in 2019. Disparities across states increased within each race/ethnicity group between 1990 and 2019, with the largest increase for non-Hispanic White males and the smallest for Hispanic females. The disparity between race/ethnicity groups within states decreased for most of the 23 states with estimates for all 3 groups but increased for females in 7 states and males in 5 states. LIMITATION: Because of small sample size, LE was not estimated for 37 of 153 state-race/ethnicity groups. CONCLUSION: Disparity in LE across states was greater when race/ethnicity groups were considered. Disparities across all state-race/ethnicity groups in general have decreased over the past 3 decades. Within each race/ethnicity group, disparities across states have increased. Although racial/ethnic disparities decreased in most of the 23 states for which LE was estimated for all 3 groups, they increased for females in 7 states and males in 5 states. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Lean methodology in quality improvement.

Measurement of quality and improvement in medicine has existed since Florence Nightingale's time. In modern times, medicine has sought to learn from other high-reliability industries such as aviation and nuclear power, where errors can result in catastrophic outcomes. Lean is a unique quality improvement strategy that seeks to improve both quality and safety by driving out waste and, where possible, standardizing work practices. It is a visual system with work aids and signals built into the workspace. An important tenet is that ideas come from the workers and that there is an iterative improvement. The improvement efforts are always viewed from the perspective of the customer, our patients, families, and coworkers. This paper describes the evolution of Lean in healthcare and highlights core principles of Lean. Examples are used to describe how various Lean tools can be applied by pediatric anesthesiologists to solve clinical problems.

Leveraging Real-world Data to Increase Procedure Room Capacity: A Multidisciplinary Quality Improvement Project.

Introduction: In the current healthcare climate, the financial strain created by COVID-19, limited resources, and case backlogs highlight the need to optimize operating and procedure room efficiency and maximize capacity. At Seattle Children's, a clinical multidisciplinary team developed and implemented a data-driven protocol to improve efficiency in a high-volume gastrointestinal (GI) suite. Methods: Key process measures, including all case on-time starts and postanesthesia care unit length of stay, were extracted from the electronic medical record and presented as Statistical Process Control (SPC) charts. Clinicians' performance was stratified by rational subgrouping to better understand variation in the system. We defined an expert clinician as one who performs beyond 3-sigma limits on funnel plot analyses. We developed clinical protocols based on expert clinician clinical practices. We gave clinicians dynamic, daily feedback on this family of measures through continuously updated SPC charts. This real-world data drove system and individual-level plan-do-check-act improvement cycles. Results: Despite significant external challenges over 2 years, procedure volume increased by approximately 25%, on-time starts improved by 36%, turnover time decreased by 34%, and postanesthesia care unit length of stay decreased by 15%. GI laboratory revenue increased by approximately 25% (independent of increased charges per procedure), representing the potential for a $2 million increase in annual revenue. Conclusions: A multidisciplinary clinical team improved efficiency metrics in a busy pediatric GI suite. Access to real-world data through continuously updated SPC charts enabled plan-do-check-act cycles that led to measurable improvement. This data access also served to sustain team motivation and engagement.

Reexamining Rates of Decline in Lung Cancer Risk after Smoking Cessation. A Meta-analysis.

Rationale: Prior studies have questioned whether prevailing eligibility criteria for lung cancer screening are sufficiently inclusive of former smokers who remain at elevated risk of disease outside current screening windows.Objectives: To characterize the percentage of the reducible relative risk (RR) remaining for lung cancer as a function of years since quitting (YSQ).Methods: MEDLINE and PubMed were searched from January 2011 to May 2018; key search terms included "smoking" and "cancer." Current smoker RRs were extracted to represent former smokers at 0 YSQ; data were transformed assuming a lognormal distribution.Results: The main review included 49 prospective cohorts across 18 studies comprising a total of 139 RRs from 20 countries and territories. At 1 year since quitting, the percentage of reducible RR remaining for lung cancer was 81.4% (64.1-98.2%). At 5 YSQ, the percentage of reducible RR remaining was 57.2% (45.7-67.3%); at 10 years, it was 36.9% (28.3-47.9%); at 15 years, it was 26.7% (20.2-34.3%); and at 20 years, it was 19.7% (13.3-26.4%). If eligibility criteria in the United States were broadened to screen former smokers at up to 20 YSQ, we estimate an additional 4.2 (3.9-4.5) million former smokers between 55 and 80 years of age would be eligible for lung cancer screening.Conclusions: At the critical screening threshold of 15 YSQ, the percentage of excess risk for lung cancer remains high and only marginally declines at time points afterward, excluding millions of former smokers who remain at elevated risk of malignancy. A risk-based algorithm for lung cancer screening that deemphasizes time after cessation as a key screening determinant would more likely capture these former smokers who remain at elevated risk of malignancy.

Caloric restriction delays yeast chronological aging by remodeling carbohydrate and lipid metabolism, altering peroxisomal and mitochondrial functionalities, and postponing the onsets of apoptotic and liponecrotic modes of regulated cell death.

A dietary regimen of caloric restriction delays aging in evolutionarily distant eukaryotes, including the budding yeast Saccharomyces cerevisiae. Here, we assessed how caloric restriction influences morphological, biochemical and cell biological properties of chronologically aging yeast advancing through different stages of the aging process. Our findings revealed that this low-calorie diet slows yeast chronological aging by mechanisms that coordinate the spatiotemporal dynamics of various cellular processes before entry into a non-proliferative state and after such entry. Caloric restriction causes a stepwise establishment of an aging-delaying cellular pattern by tuning a network that assimilates the following: 1) pathways of carbohydrate and lipid metabolism; 2) communications between the endoplasmic reticulum, lipid droplets, peroxisomes, mitochondria and the cytosol; and 3) a balance between the processes of mitochondrial fusion and fission. Through different phases of the aging process, the caloric restriction-dependent remodeling of this intricate network 1) postpones the age-related onsets of apoptotic and liponecrotic modes of regulated cell death; and 2) actively increases the chance of cell survival by supporting the maintenance of cellular proteostasis. Because caloric restriction decreases the risk of cell death and actively increases the chance of cell survival throughout chronological lifespan, this dietary intervention extends longevity of chronologically aging yeast.

Caloric restriction extends yeast chronological lifespan via a mechanism linking cellular aging to cell cycle regulation, maintenance of a quiescent state, entry into a non-quiescent state and survival in the non-quiescent state.

A yeast culture grown in a nutrient-rich medium initially containing 2% glucose is not limited in calorie supply. When yeast cells cultured in this medium consume glucose, they undergo cell cycle arrest at a checkpoint in late G1 and differentiate into quiescent and non-quiescent cell populations. Studies of such differentiation have provided insights into mechanisms of yeast chronological aging under conditions of excessive calorie intake. Caloric restriction is an aging-delaying dietary intervention. Here, we assessed how caloric restriction influences the differentiation of chronologically aging yeast cultures into quiescent and non-quiescent cells, and how it affects their properties. We found that caloric restriction extends yeast chronological lifespan via a mechanism linking cellular aging to cell cycle regulation, maintenance of quiescence, entry into a non-quiescent state and survival in this state. Our findings suggest that caloric restriction delays yeast chronological aging by causing specific changes in the following: 1) a checkpoint in G1 for cell cycle arrest and entry into a quiescent state; 2) a growth phase in which high-density quiescent cells are committed to become low-density quiescent cells; 3) the differentiation of low-density quiescent cells into low-density non-quiescent cells; and 4) the conversion of high-density quiescent cells into high-density non-quiescent cells.

Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes.

We discovered six plant extracts that increase yeast chronological lifespan to a significantly greater extent than any of the presently known longevity-extending chemical compounds. One of these extracts is the most potent longevity-extending pharmacological intervention yet described. We show that each of the six plant extracts is a geroprotector which delays the onset and decreases the rate of yeast chronological aging by eliciting a hormetic stress response. We also show that each of these extracts has different effects on cellular processes that define longevity in organisms across phyla. These effects include the following: 1) increased mitochondrial respiration and membrane potential; 2) augmented or reduced concentrations of reactive oxygen species; 3) decreased oxidative damage to cellular proteins, membrane lipids, and mitochondrial and nuclear genomes; 4) enhanced cell resistance to oxidative and thermal stresses; and 5) accelerated degradation of neutral lipids deposited in lipid droplets. Our findings provide new insights into mechanisms through which chemicals extracted from certain plants can slow biological aging.

Lithocholic bile acid accumulated in yeast mitochondria orchestrates a development of an anti-aging cellular pattern by causing age-related changes in cellular proteome.

We have previously revealed that exogenously added lithocholic bile acid (LCA) extends the chronological lifespan of the yeast Saccharomyces cerevisiae, accumulates in mitochondria and alters mitochondrial membrane lipidome. Here, we use quantitative mass spectrometry to show that LCA alters the age-related dynamics of changes in levels of many mitochondrial proteins, as well as numerous proteins in cellular locations outside of mitochondria. These proteins belong to 2 regulons, each modulated by a different mitochondrial dysfunction; we call them a partial mitochondrial dysfunction regulon and an oxidative stress regulon. We found that proteins constituting these regulons (1) can be divided into several "clusters", each of which denotes a distinct type of partial mitochondrial dysfunction that elicits a different signaling pathway mediated by a discrete set of transcription factors; (2) exhibit 3 different patterns of the age-related dynamics of changes in their cellular levels; and (3) are encoded by genes whose expression is regulated by the transcription factors Rtg1p/Rtg2p/Rtg3p, Sfp1p, Aft1p, Yap1p, Msn2p/Msn4p, Skn7p and Hog1p, each of which is essential for longevity extension by LCA. Our findings suggest that LCA-driven changes in mitochondrial lipidome alter mitochondrial proteome and functionality, thereby enabling mitochondria to operate as signaling organelles that orchestrate an establishment of an anti-aging transcriptional program for many longevity-defining nuclear genes. Based on these findings, we propose a model for how such LCA-driven changes early and late in life of chronologically aging yeast cause a stepwise development of an anti-aging cellular pattern and its maintenance throughout lifespan.

Mechanism of liponecrosis, a distinct mode of programmed cell death.

An exposure of the yeast Saccharomyces cerevisiae to exogenous palmitoleic acid (POA) elicits "liponecrosis," a mode of programmed cell death (PCD) which differs from the currently known PCD subroutines. Here, we report the following mechanism for liponecrotic PCD. Exogenously added POA is incorporated into POA-containing phospholipids that then amass in the endoplasmic reticulum membrane, mitochondrial membranes and the plasma membrane. The buildup of the POA-containing phospholipids in the plasma membrane reduces the level of phosphatidylethanolamine in its extracellular leaflet, thereby increasing plasma membrane permeability for small molecules and committing yeast to liponecrotic PCD. The excessive accumulation of POA-containing phospholipids in mitochondrial membranes impairs mitochondrial functionality and causes the excessive production of reactive oxygen species in mitochondria. The resulting rise in cellular reactive oxygen species above a critical level contributes to the commitment of yeast to liponecrotic PCD by: (1) oxidatively damaging numerous cellular organelles, thereby triggering their massive macroautophagic degradation; and (2) oxidatively damaging various cellular proteins, thus impairing cellular proteostasis. Several cellular processes in yeast exposed to POA can protect cells from liponecrosis. They include: (1) POA oxidation in peroxisomes, which reduces the flow of POA into phospholipid synthesis pathways; (2) POA incorporation into neutral lipids, which prevents the excessive accumulation of POA-containing phospholipids in cellular membranes; (3) mitophagy, a selective macroautophagic degradation of dysfunctional mitochondria, which sustains a population of functional mitochondria needed for POA incorporation into neutral lipids; and (4) a degradation of damaged, dysfunctional and aggregated cytosolic proteins, which enables the maintenance of cellular proteostasis.

P-glycoprotein inhibition promotes prednisone retention in human sinonasal polyp explants.

BACKGROUND: P-glycoprotein (P-gp) is an efflux pump, which is part of the innate chemo-immunity defense system and is overexpressed in chronic rhinosinusitis with nasal polyps (CRSwNP). P-gp is capable of regulating corticosteroid retention and thus P-gp upregulation has been implicated in steroid resistance in several inflammatory disorders. The goal of this study is to determine whether P-gp regulates intracellular steroid retention in CRSwNP. METHODS: This was a Massachusetts Eye and Ear Infirmary Institutional Review Board (IRB)-approved study in nasal polyp explants. Polyps were exposed to 50 µg/mL of prednisone for 30 minutes with or without the presence of a P-gp inhibitor (Verapamil 12.5 µM or Zosuquidar 0.31 µM) followed by a 40-minute washout period (n = 16 per group). Intracellular steroid retention was determined by quantifying the concentration of both intracytoplasmic and secreted steroid using an enzyme-linked immunosorbent assay (ELISA). Concentrations relative to control were compared using a Student t test. RESULTS: The intracytoplasmic prednisone concentration was significantly greater relative to control following P-gp inhibition with Verapamil (155.28% ± 22.48%, p < 0.05) and Zosuquidar (125.81% ± 12.41%, p < 0.05). Similarly, the amount of prednisone secreted by the explant was significantly reduced at 30 minutes following P-gp inhibition with Zosuquidar (78.64% ± 2.98%, p < 0.05) and 40 minutes following P-gp inhibition with Verapamil (80.56% ± 5.02%, p < 0.05). CONCLUSION: Inhibition of P-gp enhances the intracellular accumulation of prednisone in nasal polyps. This suggests that P-gp participates in regulation of glucocorticoid retention in sinonasal mucosa. These findings, coupled with the known overexpression of P-gp in CRSwNP, may point to a possible mechanism for steroid resistance in this patient population.

Osteitis is associated with P-glycoprotein overexpression in patients with chronic sinusitis without nasal polyps.

BACKGROUND: P-glycoprotein (P-gp) is a membrane-bound efflux pump that is up-regulated in eosinophilic chronic rhinosinusitis and participates in epithelial cytokine secretion. Osteitis is associated with eosinophilic inflammation and may represent a method to predict patients with P-gp overexpression. The purpose of this article was to determine whether P-gp overexpression and increased osteitis scores are associated in patients with chronic rhinosinusitis (CRS). METHODS: An Institutional Review Board-approved study was performed using sinus tissue in 38 patients with CRS. P-gp expression was calculated using quantitative fluorescent immunohistochemistry to generate an epithelial-to-background staining ratio. Patients were stratified into low and high P-gp expression groups. Osteitis was scored radiologically using the Kennedy Osteitis Score (KOS) and Global Osteitis Score (GOS). Serum eosinophilia was assessed. KOS and GOS were compared using a Pearson's correlation coefficient. Osteitis scores and serum eosinophil concentrations between P-gp expression groups were compared using a nonparametric Mann-Whitney U test (two tailed). RESULTS: Among the 38 patients, 7(18.42%) had high P-gp expression (mean ± SD, 4.86 ± 1.33) whereas 31(81.57%) had low expression ratios (1.93 ± 0.45). No patients in the high P-gp expression group had undergone prior surgery. Median serum eosinophil values were significantly greater in the high versus low P-gp expression group (6.98 ± 2.17 versus 2.36 ± 1.38, p < 0.001). GOS and KOS values were significantly greater in the high versus low P-gp expression group (15.86 ± 4.91 versus 6.29 ± 1.25 and 4.55 ± 4.33 verus 2.23 ± 1.71; p < 0.001). KOS and GOS values were significantly correlated (r = 0.835; p < 0.001). CONCLUSION: Increased osteitis burden as measured by either the KOS or the GOS is associated with increased P-gp membranous expression in CRS. Radiographic quantification of osteitis may therefore be used to identify patients with P-gp overexpression thereby providing a novel potential therapeutic target.