Advances in targeted liquid chromatography-tandem mass spectrometry methods for endocannabinoid and N-acylethanolamine quantification in biological matrices: A systematic review.

Liquid chromatography paired with tandem mass spectrometry (LC-MS/MS) is the gold standard in measurement of endocannabinoid concentrations in biomatrices. We conducted a systematic review of literature to identify advances in targeted LC-MS/MS methods in the period 2017-2024. We found that LC-MS/MS methods for endocannabinoid quantification are relatively consistent both across time and across biomatrices. Recent advances have primarily been in three areas: (1) sample preparation techniques, specific to the chosen biomatrix; (2) the range of biomatrices tested, recently favoring blood matrices; and (3) the breadth of endocannabinoid and endocannabinoid-like analytes incorporated into assays. This review provides a summary of the recent literature and a guide for researchers looking to establish the best methods for quantifying endocannabinoids in a range of biomatrices.

Essentiality of dietary cholesterol and its interactions with phospholipid in juvenile slipper lobster (Thenus australiensis).

This study was conducted to verify the essentiality of dietary cholesterol for early juvenile slipper lobster, Thenus australiensis (initial weight 4.50 ± 0.72 g, mean ± SD, CV = 0.16), and to explore the potential for interactions between dietary cholesterol and phospholipid. An 8-week experiment was conducted using six experimental feeds containing three supplemental cholesterol concentrations (0, 0.2 and 0.4% dry matter) at two supplemental phospholipid concentrations (0% and 1.0% dry matter). Dietary cholesterol concentrations of ≥ 0.2% resulted in up to threefold greater weight gain compared to 0% dietary cholesterol, but without any significant main or interactive dietary phospholipid effect. An interaction was observed for lobster survival with lowest survival (46%) recorded for combined 0% cholesterol and 0% phospholipid compared to every other treatment (71-100%). However, all surviving lobsters at 0% dietary cholesterol, regardless of dietary phospholipid level, were in poor nutritional condition. Apparent feed intake (AFI) was significantly higher at dietary cholesterol ≥ 0.2% but was lower for each corresponding dietary cholesterol level at 1% dietary phospholipid. This implied that the feed conversion ratio was improved with supplemental phospholipid. In conclusion, this study confirms the essential nature of dietary cholesterol and that dietary phospholipid can provide additional benefits.

Longitudinal improvements in clinical and functional outcomes following initiation of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis.

Background: Use of elexacaftor/tezacaftor/ivacaftor (ETI) for treatment of cystic fibrosis (CF) has resulted in unprecedented clinical improvements necessitating development of outcome measures for monitoring disease course. Intranasal micro-optical coherence tomography (µOCT) has previously helped detect and characterize mucociliary abnormalities in patients with CF. This study was done to determine if µOCT can define the effects of ETI on nasal mucociliary clearance and monitor changes conferred to understand mechanistic effects of CFTR modulators beyond CFTR activation. Methods: 26 subjects, with at least 1 F508del mutation were recruited and followed at baseline (visit 1), +1 month (visit 2) and +6 months (visit 4) following initiation of ETI therapy. Clinical outcomes were computed at visits 1, 2 and 4. Intranasal µOCT imaging and functional metrics analysis including mucociliary transport rate (MCT) estimation were done at visits 1 and 2. Results: Percent predicted forced expiratory volume in 1 s (ppFEV1) showed a significant increase of +10.9 % at visit 2, which sustained at visit 4 (+10.6 %). Sweat chloride levels significantly decreased by -36.6 mmol/L and -41.3 mmol/L at visits 2 and 4, respectively. µOCT analysis revealed significant improvement in MCT rate (2.8 ± 1.5, visit 1 vs 4.0 ± 1.5 mm/min, visit 2; P = 0.048). Conclusions: Treatment with ETI resulted in significant and sustained clinical improvements over 6 months. Functional improvements in MCT rate were evident within a month after initiation of ETI therapy indicating that µOCT imaging is sensitive to the treatment effect of HEMT and suggests improved mucociliary transport as a probable mechanism of action underlying the clinical benefits.

Alterations in the fecal microbiota in patients with advanced cystic fibrosis liver disease after 6 months of elexacaftor/tezacaftor/ivacaftor.

BACKGROUND: Cystic fibrosis associated liver disease (CFLD) carries a significant disease burden with no effective preventive therapies. According to the gut-liver axis hypothesis for CFLD pathogenesis, dysbiosis and increased intestinal inflammation and permeability permit pathogenic bacterial translocation into the portal circulation, leading to hepatic inflammation and fibrosis. Evaluating the effect of CFTR (cystic fibrosis transmembrane conductance regulator) modulation with elexacaftor/tezacaftor/ivacaftor (ETI) may help determine the role of CFTR in CFLD and increase understanding of CFLD pathogenesis, which is critical for developing therapies. We aimed to characterize the fecal microbiota in participants with CF with and without advanced CFLD (aCFLD) before and after ETI. METHODS: This is an ancillary analysis of stool samples from participants ages ≥12 y/o enrolled in PROMISE (NCT04038047). Included participants had aCFLD (cirrhosis with or without portal hypertension, or non-cirrhotic portal hypertension) or CF without liver disease (CFnoLD). Fecal microbiota were defined by shotgun metagenomic sequencing at baseline and 1 and 6 months post-ETI. RESULTS: We analyzed 93 samples from 34 participants (11 aCFLD and 23 CFnoLD). Compared to CFnoLD, aCFLD had significantly higher baseline relative abundances of potential pathogens Streptococcus salivarius and Veillonella parvula. Four of 11 aCFLD participants had an initially abnormal fecal calprotectin that normalized 6 months post-ETI, correlating with a significant decrease in S. salivarius and a trend towards decreasing V. parvula. CONCLUSIONS: These results support an association between dysbiosis and intestinal inflammation in CFLD with improvements in both post-ETI, lending further support to the gut-liver axis in aCFLD.

Trauma film viewing and intrusive memories: Relationship between salivary alpha amylase, endocannabinoids, and cortisol.

The endogenous cannabinoid (ECB) system is a small molecule lipid signalling system that is involved in stress response activation and is associated with PTSD, but it is unclear whether salivary ECBs are part of the sympathetic nervous system response to stress. We conducted an adapted trauma film paradigm, where participants completed a cold pressor test (or control) while watching a 10-minute trauma film. We also collected saliva and hair samples and tested them for ECBs, cortisol, and salivary alpha amylase (sAA). As hypothesised, there were significant positive correlations between sAA activity and salivary ECB levels, particularly 2-arachidonoyl glycerol (2-AG), though ECBs were not correlated with sAA stress reactivity. Participants who had a significant cortisol response to the trauma film/stressor reported less intrusive memories, which were also less distressing and less vivid. This effect was moderated by arachidonoyl ethanolamide (AEA), where decreases in AEA post-stress were associated with more intrusive memories in cortisol non-responders only. This study provides new evidence for the role of ECBs in the sympathetic nervous system.

The effect of discontinuing hypertonic saline or dornase alfa on mucociliary clearance in elexacaftor/tezacaftor/ivacaftor treated people with cystic fibrosis: The SIMPLIFY-MCC Study.

Many people with CF (pwCF) desire a reduction in inhaled treatment burden after initiation of elexacaftor/tezacaftor/ivacaftor. The randomized, open-label SIMPLIFY study showed that discontinuing hypertonic saline (HS) or dornase alfa (DA) was non-inferior to continuation of each treatment with respect to change in lung function over a 6-week period. In this SIMPLIFY substudy, we used gamma scintigraphy to determine whether discontinuation of either HS or DA was associated with deterioration in the rate of in vivo mucociliary clearance (MCC) in participants ≥12 years of age. While no significant differences in MCC endpoints were associated with HS discontinuation, significant improvement in whole and peripheral lung MCC was observed after discontinuing DA. These results suggest that pwCF on ETI with mild lung disease do not experience a subclinical deterioration in MCC that could later impact health outcomes after discontinuing HS, and in fact may benefit from improved MCC after stopping DA treatment.

Repetitive sulfur dioxide exposure in mice models post-deployment respiratory syndrome.

Soldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than nondeployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). Since many of the subjects in this cohort reported exposure to sulfur dioxide (SO2), we developed a model of repetitive exposure to SO2 in mice that phenocopies many aspects of PDRS, including adaptive immune activation, airway wall remodeling, and pulmonary vascular (PV) disease. Although abnormalities in small airways were not sufficient to alter lung mechanics, PV remodeling resulted in the development of pulmonary hypertension and reduced exercise tolerance in SO2-exposed mice. SO2 exposure led to increased formation of isolevuglandins (isoLGs) adducts and superoxide dismutase 2 (SOD2) acetylation in endothelial cells, which were attenuated by treatment with the isoLG scavenger 2-hydroxybenzylamine acetate (2-HOBA). In addition, 2-HOBA treatment or Siruin-3 overexpression in a transgenic mouse model prevented vascular remodeling following SO2 exposure. In summary, our results indicate that repetitive SO2 exposure recapitulates many aspects of PDRS and that oxidative stress appears to mediate PV remodeling in this model. Together, these findings provide new insights regarding the critical mechanisms underlying PDRS.NEW & NOTEWORTHY We developed a mice model of "post-deployment respiratory syndrome" (PDRS), a condition in Veterans with unexplained exertional dyspnea. Our model successfully recapitulates many of the pathological and physiological features of the syndrome, revealing involvement of the ROS-isoLGs-Sirt3-SOD2 pathway in pulmonary vasculature pathology. Our study provides additional knowledge about effects and long-term consequences of sulfur dioxide exposure on the respiratory system, serving as a valuable tool for future PDRS research.

Prospective evaluation of nontuberculous mycobacteria disease in cystic fibrosis: The design of the PREDICT study.

BACKGROUND: Nontuberculous mycobacteria (NTM) are an important cause of airway infections in people with cystic fibrosis (pwCF). Isolation of NTM from respiratory specimens of pwCF do not mandate treatment in the absence of clinical and radiologic features of NTM pulmonary disease (NTM-PD), as some pwCF clear the infection without treatment and others do not appear to progress to NTM-PD despite persistent infection. An evidence-based protocol to standardize diagnosis of NTM-PD is needed to systematically identify pwCF who may benefit from treatment. METHODS: In this multicenter observational study, eligible pwCF who are 6 years of age and older and who have had a recent positive NTM culture are systematically evaluated for NTM-PD. Participants are identified based on positive NTM culture results obtained during routine clinical care and following enrollment are evaluated for NTM-PD and CF-related comorbidities. Participants are followed in PREDICT until they meet NTM-PD diagnostic criteria and are ready to initiate NTM treatment, or until study termination. Active participants who have not met these criteria are re-consented every 5 years to enable long-term participation. RESULTS: The primary endpoint will summarize the proportion of participants who meet the NTM-PD diagnosis definition. The time from enrollment to NTM-PD diagnosis will be derived from Kaplan-Meier estimates. CONCLUSION: A prospective protocol to identify NTM-PD in pwCF will test if this standardized approach defines a cohort with signs and symptoms associated with NTM-PD, to assist with clinical decision making and to build a framework for future therapeutic trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02073409.

Effect of elexacaftor/tezacaftor/ivacaftor on mucus and mucociliary clearance in cystic fibrosis.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (E/T/I) is highly effective clinically for those with at least one F508del-CFTR allele. The effects of E/T/I on mucociliary clearance (MCC) and sputum properties are unknown. We, therefore, sought to characterize the effects of E/T/I on in vivo MCC and sputum characteristics hypothesized to impact mucus transport. METHODS: Forty-four participants ≥12 years of age were enrolled into this prospective, observational trial prior to initiation of E/T/I and had baseline measurement of MCC and characterization of induced sputum and exhaled breath condensate (EBC) samples. Study procedures were repeated after 1 month of E/T/I treatment. RESULTS: Average age was 27.7 years with baseline forced expiratory volume in 1 second (FEV1) of 78.2 % predicted. 52 % of subjects had previously been treated with a 2-drug CFTR modulator combination. The average whole lung MCC rate measured over 60 min (WLAveClr60) significantly improved from baseline to post-E/T/I (14.8 vs. 22.8 %; p = 0.0002), as did other MCC indices. Sputum% solids also improved (modeled mean 3.4 vs. 2.2 %; p<0.0001), whereas non-significant reductions in sputum macrorheology (G', G") were observed. No meaningful changes in exhaled breath condensate endpoints (sialic acid:urea ratio, pH) were observed. CONCLUSIONS: E/T/I improved the hydration of respiratory secretions (% solids) and markedly accelerated MCC. These data confirm the link between CFTR function, mucus solid content, and MCC and help to define the utility of MCC and mucus-related bioassays in future efforts to restore CFTR function in all people with CF.

The cost of simplifying treatments for cystic fibrosis: Implications of the SIMPLIFY trial.

BACKGROUND: Dornase alfa and hypertonic saline are mucoactive therapies that can improve respiratory symptoms in people with cystic fibrosis (CF). A recent randomized control trial showed that participants with well-preserved pulmonary function taking elexacaftor + tezacaftor + ivacaftor (ETI) who discontinued dornase alfa or hypertonic saline for 6 weeks had no clinically meaningful decline in lung function. This may prompt discussions with care providers regarding ongoing use of these medications. OBJECTIVE: To compare the costs of outpatient medications between people taking ETI who continued or discontinued (1) dornase alfa or (2) hypertonic saline from 2 clinical trials and project cost differences in the US CF population if these 2 medications were used only intermittently for symptom relief instead of chronically. METHODS: The SIMPLIFY study was 2 parallel multicenter trials that randomized participants 1:1 to either continue or discontinue therapy. To estimate costs, we used data from the Merative MarketScan Databases to identify people with CF from 2020 to 2021. Our primary outcomes were differences in costs of outpatient prescription drugs among those who continued vs discontinued dornase alfa and, separately, hypertonic saline. We obtained adjusted differences in median costs. To estimate the annual cost savings if the population of people with CF taking ETI used these medications only intermittently, we multiplied the proportion of people in MarketScan with CF diagnoses who were taking each of these medications by the median cost savings per year and subtracted the cost of "rescue" use. RESULTS: A total of 392 participants from the dornase alfa trial and 273 from the hypertonic saline trial were included in analyses. The adjusted difference in median medication costs was not significant for the hypertonic saline trial, but we observed a significantly decreased 6-week cost of medications in the dornase alfa trial (adjusted median difference in costs between discontinue and continue of $5,860 (95% CI = $4,870-$6,850); P < 0.0001). We estimated that two-thirds of people with CF use ETI and dornase alfa in the United States; if they discontinued dornase alfa except for intermittent use, the resulting annual savings would be $1.21 billion. CONCLUSIONS: Although the costs of dornase alfa and hypertonic saline are smaller compared with ETI, reduction in use would lead to substantial prescription drug cost savings and reduce the treatment burden. However, individual benefits of these therapies should be considered, and decisions regarding changes in therapy remain an important discussion between people with CF and their providers. Study registration number: NCT04378153.

Sex-dimorphism in human serum endocannabinoid and n-acyl ethanolamine concentrations across the lifespan.

The endocannabinoid (ECB) system has recently been considered a potential treatment target for various clinical disorders. However, research around age- and sex-related changes within the ECB system is relatively limited. To improve our understanding of these changes, the current study measured arachidonoyl ethanolamide (AEA), 2-arachidonoyl glycerol (2-AG), oleoylethanolamine (OEA), palmitoylethanolamine (PEA), arachidonic acid (AA), cortisol, and progesterone in pooled serum samples stratified by sex (male and female) and age groups (5-15; 15-30; 30-45; 45-60; 60-75; 85+), using liquid-chromatography tandem mass spectrometry. Serum progesterone levels significantly increased in females of the 15-30 and 30-45 age groups, before declining. Significantly higher cortisol, AEA, 2-AG, OEA, and PEA were found in males and in older age, while significantly higher AA was found in females. Our results indicate that ECBs and related hormones exhibit sexual dimorphism in the age ranges that correspond with female pregnancy, menopause, and post menopause. Male testosterone levels most likely influences male ECB changes throughout the lifespan. Future research could capitalise on these findings by performing repeated measurements in individuals in a longitudinal style, to further refine the temporal profile of age-specific changes to the ECB system identified here.

Plant Development in the Garden Pea as Revealed by Mutations in the Crd/PsYUC1 Gene.

In common with other plant species, the garden pea (Pisum sativum) produces the auxin indole-3-acetic acid (IAA) from tryptophan via a single intermediate, indole-3-pyruvic acid (IPyA). IPyA is converted to IAA by PsYUC1, also known as Crispoid (Crd). Here, we extend our understanding of the developmental processes affected by the Crd gene by examining the phenotypic effects of crd gene mutations on leaves, flowers, and roots. We show that in pea, Crd/PsYUC1 is important for the initiation and identity of leaflets and tendrils, stamens, and lateral roots. We also report on aspects of auxin deactivation in pea.

Rapid Remission of Chronic, Progressive Conditions and Reducing Polypharmacy by Utilizing Lifestyle Therapy to Target Insulinemic Lifestyle Components.

This case study provides evidence that homeostatic control in a patient with hyperglycemia and other metabolic abnormalities associated with insulin resistance can be rapidly restored utilizing lifestyle therapy. The patient, an overweight, non-Hispanic White male aged 70 years, had been medicated for hypertension and Type 2 diabetes mellitus for 12 years. From baseline during 21 months of follow-up, HbA1c decreased from 6.6% to 5.4%, mean fasting glucose decreased from 125 mg/dL to 94 mg/dL, blood pressure decreased from 130/85 mmHg to 100/64 mmHg, estimated glomerular filtration rate increased from 50 ml/min/1.73m² to 58 ml/min/1.73m², waist circumference decreased from 118.8 cm to 90.8 cm, and liver function improved with aspartate transaminase decreasing from 44 IU/L to 17 IU/L and alanine transaminase decreasing from 34 IU/L to 21 IU/L. Each of these metabolic corrections was observed while eliminating respective disease-specific medications. These metabolic improvements were achieved using primary recommended lifestyle therapy specifically targeting known insulinemic lifestyle components. This case study shows that the utilization of primary recommended, ongoing lifestyle therapy targeting insulinemic lifestyle components can rapidly improve markers of insulin resistance and normalize abnormal laboratory values while eliminating the risk of polypharmacy and the direct costs of medication.

A trait dataset for freshwater mussels of the United States of America.

The United States of America has a diverse collection of freshwater mussels comprising 301 species distributed among 59 genera and two families (Margaritiferidae and Unionidae), each having a unique suite of traits. Mussels are among the most imperilled animals and are critical components of their ecosystems, and successful management, conservation and research requires a cohesive and widely accessible data source. Although trait-based analysis for mussels has increased, only a small proportion of traits reflecting mussel diversity in this region has been collated. Decentralized and non-standardized trait information impedes large-scale analysis. Assembling trait data in a synthetic dataset enables comparison across species and lineages and identification of data gaps. We collated data from the primary literature, books, state and federal reports, theses and dissertations, and museum collections into a centralized dataset covering information on taxonomy, morphology, reproductive ecology and life history, fish hosts, habitats, thermal tolerance, geographic distribution, available genetic information, and conservation status. By collating these traits, we aid researchers in assessing variation in mussel traits and modelling ecosystem change.

Epithelial Yap/Taz are required for functional alveolar regeneration following acute lung injury.

A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ are implicated as essential for type 1 and type 2 alveolar epithelial cell (AT1 and AT2) differentiation in the developing lung, yet aberrant activation of YAP/TAZ is a prominent feature of the dysregulated alveolar epithelium in IPF. In these studies, we sought to define the functional role of YAP/TAZ activity during alveolar regeneration. We demonstrated that Yap and Taz were normally activated in AT2 cells shortly after injury, and deletion of Yap/Taz in AT2 cells led to pathologic alveolar remodeling, failure of AT2-to-AT1 cell differentiation, increased collagen deposition, exaggerated neutrophilic inflammation, and increased mortality following injury induced by a single dose of bleomycin. Loss of Yap/Taz activity prior to an LPS injury prevented AT1 cell regeneration, led to intraalveolar collagen deposition, and resulted in persistent innate inflammation. These findings establish that AT2 cell Yap/Taz activity is essential for functional alveolar epithelial repair and prevention of fibrotic remodeling.

Hematological Adaptations Following a Training Camp in Hot and/or Hypoxic Conditions in Elite Rugby Union Players.

PURPOSE: To investigate the effects of a training camp with heat and/or hypoxia sessions on hematological and thermoregulatory adaptations. METHODS: Fifty-six elite male rugby players completed a 2-week training camp with 5 endurance and 5 repeated-sprint sessions, rugby practice, and resistance training. Players were separated into 4 groups: CAMP trained in temperate conditions at sea level, HEAT performed the endurance sessions in the heat, ALTI slept and performed the repeated sprints at altitude, and H + A was a combination of the heat and altitude groups. RESULTS: Blood volume across all groups increased by 140 mL (95%CI, 42-237; P = .006) and plasma volume by 97 mL (95%CI 28-167; P = .007) following the training camp. Plasma volume was 6.3% (0.3% to 12.4%) higher in HEAT than ALTI (P = .034) and slightly higher in HEAT than H + A (5.6% [-0.3% to 11.7%]; P = .076). Changes in hemoglobin mass were not significant (P = .176), despite a ∼1.2% increase in ALTI and H + A and a ∼0.7% decrease in CAMP and HEAT. Peak rectal temperature was lower during a postcamp heat-response test in HEAT (0.3 °C [0.1-0.5]; P = .010) and H + A (0.3 °C [0.1-0.6]; P = .005). Oxygen saturation upon waking was lower in ALTI (3% [2% to 5%]; P < .001) and H + A (4% [3% to 6%]; P < .001) than CAMP and HEAT. CONCLUSION: Although blood and plasma volume increased following the camp, sleeping at altitude impeded the increase when training in the heat and only marginally increased hemoglobin mass. Heat training induced adaptations commensurate with partial heat acclimation; however, combining heat training and altitude training and confinement during a training camp did not confer concomitant hematological adaptations.

The impact of elexacaftor/tezacaftor/ivacaftor on fat-soluble vitamin levels in people with cystic fibrosis.

BACKGROUND: While elexacaftor/tezacaftor/ivacaftor (ETI) has improved the pulmonary health of many people with cystic fibrosis (PwCF), less is known about ETI effectiveness for extra-pulmonary manifestations, including fat-soluble vitamin malabsorption. This study aims to evaluate ETI's impact on vitamin A, D, E, and international normalized ratio (INR, an indirect marker for Vitamin K) serum levels. METHODS: Retrospective cohort study of PwCF ≥12 years receiving ETI. Vitamin levels up to four years preceding and up to two years following ETI initiation were collected. Pairwise comparisons of vitamin levels pre/post-ETI initiation were made using Wilcoxon signed rank and McNemar's tests. Linear mixed effect models were used to regress vitamin levels on time since starting ETI, ETI use (yes/no), the interaction between time and ETI use, and age. RESULTS: Two hundred and sixty-four participants met study inclusion, and 169 (64%) had post-ETI initiation vitamin levels. Median vitamin A levels increased from 422.0 to 471.0 mcg/L (p < 0.001), median vitamin D levels increased from 28.5 to 30.8 ng/mL (p = 0.003), and there were no significant changes in median vitamin E or INR. Vitamin A levels rose at a rate of 40.7 mcg/L/year (CI 11.3, 70.2) after ETI start. CONCLUSIONS: ETI initiation is associated with increased median vitamin A and vitamin D levels, but no change in median vitamin E or INR levels. Ongoing monitoring of vitamin levels after ETI initiation is needed to screen for potential deficiencies and toxicities, particularly in light of case reports of hypervitaminosis A following ETI initiation.

Hardware Salvage in the Lower Extremity after Flap Coverage: 10-Year Single Center Outcomes Analysis.

An unanswered question with open tibial fractures is whether the type of flap used affects hardware retention. Flap survival may not equate hardware retention or limb salvage. In this study, we performed a 10-year single institution review and analysis of all patients who had placement of hardware for open tibial fractures followed by flap coverage. Methods: Inclusion criteria consisted of patients who underwent pedicled or free flap coverage of Gustilo IIIB or IIIC tibial fractures requiring open reduction and internal fixation. Outcomes and complications were statistically analyzed based on flap type. Flap type was stratified into free versus pedicled flaps and muscle versus fasciocutaneous flaps. Primary outcome measures included hardware failure and infection requiring hardware removal. Secondary outcome measures included limb salvage, flap success, and fracture union. Results: Overall primary outcome measures were better for pedicled flaps (n = 31), with lower rates of hardware failure and infection (25.8%; 9.7%) compared with free flaps (n = 27) (51.9%; 37.0%). Limb salvage and flap success was not different comparing pedicled and free flaps. There was no significant difference in outcomes between muscle and fasciocutaneous flaps. Multivariable analysis showed that patients who had free versus pedicled flaps or muscle versus fasciocutaneous flaps had a higher chance of hardware failure. A formal orthoplastic team was established in the period from 2017 to 2022, after which flap numbers were higher and hardware failure less for pedicled and fasciocutaneous flaps. Conclusions: Pedicled flaps were associated with lower rates of hardware failure and infection requiring hardware removal. A formal orthoplastic team improves hardware-related outcomes.

Crossing the Quality Chasm and the Ignored Pillar of Health Care Equity.

Although there has been tremendous progress toward the aspiration of delivering quality health care, among the National Academy of Medicine's (previously Institute of Medicine) six pillars of quality (health care should be safe, effective, timely, patient-centered, efficient, and equitable), the last pillar, equity, has been largely ignored. Examples of how the quality improvement (QI) process leads to improvements are numerous and must be applied to the pillar of equity related to race/ethnicity and socioeconomic status. This article describes how equity should be addressed using the QI process.