Self-reactive IgE exacerbates interferon responses associated with autoimmunity.

Canonically, immunoglobulin E (IgE) mediates allergic immune responses by triggering mast cells and basophils to release histamine and type 2 helper cytokines. Here we found that in human systemic lupus erythematosus (SLE), IgE antibodies specific for double-stranded DNA (dsDNA) activated plasmacytoid dendritic cells (pDCs), a type of cell of the immune system linked to viral defense, which led to the secretion of substantial amounts of interferon-α (IFN-α). The concentration of dsDNA-specific IgE found in patient serum correlated with disease severity and greatly potentiated pDC function by triggering phagocytosis via the high-affinity FcɛRI receptor for IgE, followed by Toll-like receptor 9 (TLR9)-mediated sensing of DNA in phagosomes. Our findings expand the known pathogenic mechanisms of IgE-mediated inflammation beyond those found in allergy and demonstrate that IgE can trigger interferon responses capable of exacerbating self-destructive autoimmune responses.

Accuracy and reliability of forensic handwriting comparisons.

Forensic handwriting examination involves the comparison of writing samples by forensic document examiners (FDEs) to determine whether or not they were written by the same person. Here we report the results of a large-scale study conducted to assess the accuracy and reliability of handwriting comparison conclusions. Eighty-six practicing FDEs each conducted up to 100 handwriting comparisons, resulting in 7,196 conclusions on 180 distinct comparison sets, using a five-level conclusion scale. Erroneous "written by" conclusions (false positives) were reached in 3.1% of the nonmated comparisons, while 1.1% of the mated comparisons yielded erroneous "not written by" conclusions (false negatives). False positive rates were markedly higher for nonmated samples written by twins (8.7%) compared to nontwins (2.5%). Notable associations between training and performance were observed: FDEs with less than 2 y of formal training generally had higher error rates, but they also had higher true positive and true negative rates because they tended to provide more definitive conclusions; FDEs with at least 2 y of formal training were less likely to make definitive conclusions, but those definitive conclusions they made were more likely to be correct (higher positive predictive and negative predictive values). We did not observe any association between writing style (cursive vs. printing) and rates of errors or incorrect conclusions. This report also provides details on the repeatability and reproducibility of conclusions, and reports how conclusions are affected by the quantity of writing and the similarity of content.

The Relative Reinforcing Value of Menthol Among Young Adult Cigarette Smokers: Results From a Behavioral Choice Task.

INTRODUCTION: Menthol cigarettes are associated with experimentation and progression to regular use. Although reinforcement processes likely underlie menthol's appeal, the reinforcing value of menthol cigarettes remains unknown. AIMS AND METHODS: This study examined the relative reinforcing value (RRV) of menthol versus nonmenthol cigarettes in young adult menthol (n = 54) and nonmenthol (n = 53) smokers, and differences in menthol's RRV by race, ethnicity, and sexual orientation. Overnight abstinent participants completed a choice task assessing willingness to "work" to click targets on a computer screen to earn menthol or nonmenthol cigarette puffs. A progressive ratio schedule was used where the menthol target had to be clicked progressively more times, over 10 trials, to earn a menthol cigarette puff, while clicks for the nonmenthol target were fixed across trials. RRV for menthol was defined by the breakpoint, or the highest trial (out of to 10) completed for a menthol cigarette puff. Number of clicks for menthol and nonmenthol puffs were also examined. RESULTS: Menthol smokers worked harder for menthol versus nonmenthol cigarette puffs (breakpoint = 9.17; ~1236 clicks vs. 24 clicks). Breakpoint was higher among Hispanic (6.49) versus NH White (4.83) and NH non-White smokers (4.43). In exploratory analyses of interactions of menthol preference with race and ethnicity, nonmenthol Hispanic smokers worked harder for menthol cigarette puffs versus NH non-White and NH White nonmenthol smokers. CONCLUSIONS: Menthol cigarettes are highly reinforcing for young adult menthol and Hispanic smokers. A menthol ban may reduce addiction risk among younger individuals and some minoritized groups of smokers. IMPLICATIONS: This study provides evidence of the greater relative reinforcing value of menthol compared to nonmenthol cigarettes among young adults who had a cigarette flavor preference, suggesting increased addiction risk of menthol cigarettes. Young adult menthol smokers and Hispanic (vs. non-Hispanic) smokers worked harder to earn menthol (vs. nonmenthol) cigarette puffs. Findings add to the evidence base supporting the U.S. Food and Drug Administration's (FDA) intent to ban menthol in cigarettes. Further, prevention messaging campaigns and cessation programs should take into account the reinforcing value of menthol in cigarettes, especially in vulnerable and at-risk populations.

Downregulation of a tumor suppressor gene LKB1 in lung transplantation as a biomarker for chronic murine lung allograft rejection.

BACKGROUND: We recently demonstrated decreased tumor suppressor gene liver kinase B1 (LKB1) level in lung transplant recipients diagnosed with bronchiolitis obliterans syndrome. STE20-related adaptor alpha (STRADα) functions as a pseudokinase that binds and regulates LKB1 activity. METHODS: A murine model of chronic lung allograft rejection in which a single lung from a B6D2F1 mouse was orthotopically transplanted into a DBA/2J mouse was employed. We examined the effect of LKB1 knockdown using CRISPR-CAS9 in vitro culture system. RESULTS: Significant downregulation of LKB1 and STRADα expression was found in donor lung compared to recipient lung. STRADα knockdown significantly inhibited LKB1, pAMPK expression but induced phosphorylated mammalian target of rapamycin (mTOR), fibronectin, and Collagen-I, expression in BEAS-2B cells. LKB1 overexpression decreased fibronectin, Collagen-I, and phosphorylated mTOR expression in A549 cells. CONCLUSIONS: We demonstrated that downregulation of LKB1-STRADα pathway accompanied with increased fibrosis, results in development of chronic rejection following murine lung transplantation.

Serum neurofilament light chain levels at attack predict post-attack disability worsening and are mitigated by inebilizumab: analysis of four potential biomarkers in neuromyelitis optica spectrum disorder.

OBJECTIVE: To investigate relationships between serum neurofilament light chain (sNfL), ubiquitin C-terminal hydrolase L1 (sUCHL1), tau (sTau) and glial fibrillary acidic protein (sGFAP) levels and disease activity/disability in neuromyelitis optica spectrum disorder (NMOSD), and the effects of inebilizumab on these biomarkers in N-MOmentum. METHODS: N-MOmentum randomised participants to receive inebilizumab or placebo with a randomised controlled period (RCP) of 28 weeks and an open-label follow-up period of ≥2 years. The sNfL, sUCHL1, sTau and sGFAP were measured using single-molecule arrays in 1260 scheduled and attack-related samples from N-MOmentum participants (immunoglobulin G (IgG) autoantibodies to aquaporin-4-positive, myelin oligodendrocyte glycoprotein-IgG-positive or double autoantibody-negative) and two control groups (healthy donors and patients with relapsing-remitting multiple sclerosis). RESULTS: The concentration of all four biomarkers increased during NMOSD attacks. At attack, sNfL had the strongest correlation with disability worsening during attacks (Spearman R2=0.40; p=0.01) and prediction of disability worsening after attacks (sNfL cut-off 32 pg/mL; area under the curve 0.71 (95% CI 0.51 to 0.89); p=0.02), but only sGFAP predicted upcoming attacks. At RCP end, fewer inebilizumab-treated than placebo-treated participants had sNfL>16 pg/mL (22% vs 45%; OR 0.36 (95% CI 0.17 to 0.76); p=0.004). CONCLUSIONS: Compared with sGFAP, sTau and sUCHL1, sNfL at attack was the strongest predictor of disability worsening at attack and follow-up, suggesting a role for identifying participants with NMOSD at risk of limited post-relapse recovery. Treatment with inebilizumab was associated with lower levels of sGFAP and sNfL than placebo. TRIAL REGISTRATION NUMBER: NCT02200770.

Morbidity of antireflux surgery in lung transplant and matched nontransplant cohorts is comparable.

BACKGROUND: Safety data on perioperative outcomes of laparoscopic antireflux surgery (LARS) after lung transplantation (LT) are lacking. We compared the 30-day readmission rate and short-term morbidity after LARS between LT recipients and matched nontransplant (NT) controls. METHODS: Adult patients who underwent LARS between January 1, 2015, and October 31, 2021, were included. The participants were divided into two groups: LT recipients and NT controls. First, we compared 30-day readmission rates after LARS between the LT and NT cohorts. Next, we compared 30-day morbidity after LARS between the LT cohort and a 1-to-2 propensity score-matched NT cohort. RESULTS: A total of 1328 patients (55 LT recipients and 1273 NT controls) were included. The post-LARS 30-day readmission rate was higher in LT recipients than in the overall NT controls (14.5% vs. 2.8%, p < 0.001). Compared to matched NT controls, LT recipients had a lower prevalence of paraesophageal hernia, a smaller median hernia size, and higher peristaltic vigor. Also compared to the matched NT controls, the LT recipients had a lower median operative time but a longer median length of hospital stay. The proportion of patients with a post-LARS event within 30 postoperative days was comparable between the LT and matched NT cohorts (21.8% vs 14.5%, p = 0.24). CONCLUSIONS: Despite a higher perceived risk of comorbidity burden, LT recipients and matched NT controls had similar rates of post-LARS 30-day morbidity at our large-volume center with expertise in transplant and foregut surgery. LARS after LT is safe.

Single-use, co-use, and polysubstance use of alcohol, tobacco, and cannabis in sexual minority and heterosexual females.

BACKGROUND AND OBJECTIVE: Alcohol, tobacco, and cannabis use are more prevalent in sexual minority females than heterosexual females, and their use is associated with adverse consequences. Identifying disparities in substance use patterns by sexual identity may inform interventions targeting this vulnerable group. This study examined differences between heterosexual and sexual minority females on patterns of past 30-day tobacco, alcohol, and cannabis use. METHODS: N = 3020 females (18.8% sexual minority) completed an online survey (September 2020-October 2021) that queried about past 30-day tobacco/nicotine (cigarettes, e-cigarettes, large cigar/LCCs, and other products), alcohol, and cannabis use. Participants were classified into one of eight patterns: no use, tobacco/nicotine-only, alcohol-only, cannabis-only, alcohol and tobacco/nicotine, tobacco/nicotine and cannabis, alcohol and cannabis, and polysubstance use. A multinomial logistic regression model examined the association between sexual identity and each substance use group, controlling for demographics. RESULTS: Across both groups, no substance use was the most common pattern. Polysubstance use was the most common substance use pattern among sexual minority females. In adjusted regression models, sexual minority females were more likely to report cannabis-only (adjusted odds ratio [AOR] = 2.58), tobacco/nicotine and cannabis co-use (AOR = 1.74), alcohol and cannabis co-use (AOR = 2.50), and polysubstance use (AOR = 2.60), compared to heterosexual females. [Correction added on 23 November 2022, after first online publication: In the preceding paragraph, the AOR and CI values were corrected.] DISCUSSION AND CONCLUSIONS: Substance use patterns that involve cannabis are more common among sexual minority females. SCIENTIFIC SIGNIFICANCE: This study extends prior research by using a large sample of females to examine differences based on sexual identity in patterns of tobacco/nicotine, alcohol, and cannabis use beyond single substance use and considers co-use and polysubstance use.

Seeing is believing: How cannabis marketing exposure is associated with cannabis use attitudes and behavior in a permissive medical cannabis policy environment.

BACKGROUND AND OBJECTIVES: Oklahoma has a fast-growing medical cannabis industry, showing a proliferation of industry marketing. While cannabis marketing exposure (CME) is a risk factor for cannabis use and positive attitudes about use, no studies have examined the impact of CME on attitudes and use behavior in a permissive cannabis policy environment, like Oklahoma. METHODS: N = 5428 Oklahoma adults ages 18 and older completed assessments of demographics, past 30-day cannabis use, and past 30-day exposure to each of four types of cannabis marketing: outdoor (billboards, signs), social media, print (magazines), and Internet. Regression models examined associations of CME with positive attitudes towards cannabis use, cannabis harm perceptions, interest in obtaining a medical cannabis license (among nonlicensed participants), and past 30-day cannabis use. RESULTS: Three quarters (74.5%) reported any past 30-day CME. Outdoor CME was most prevalent (61.1%), followed by social media (46.5%), Internet (46.1%), and print (35.2%). Correlates of CME included younger age, higher educational attainment and income, and medical cannabis license. In adjusted regression models, past 30-day CME and number of sources of CME were associated with current cannabis use behavior, positive attitudes about cannabis, lower cannabis harm perceptions, and greater interest in obtaining a medical cannabis license. Similar associations between CME and positive attitudes about cannabis were shown among noncannabis users. DISCUSSION AND CONCLUSIONS: Public health messaging should be employed to minimize the potential adverse impacts of CME. SCIENTIFIC SIGNIFICANCE: No studies have examined correlates of CME in a rapidly growing and relatively unrestrained marketing environment.

Diagnosis and management of anastomotic leaks after Ivor Lewis esophagectomy: a single-center experience.

PURPOSE: Esophageal anastomotic leaks (ALs) after esophagectomy are a common and serious complication. The incidence, diagnostic approach, and management have changed over time. We described the diagnosis and management of patients who developed an esophageal AL after an Ivor Lewis esophagectomy at our center. METHODS: After IRB approval, we queried our prospectively maintained database for patients who developed an esophageal AL after esophagectomy from August 2016 through July 2022. Data pertaining to demographics, comorbidities, surgical and oncological characteristics, and clinical course were extracted and analyzed. RESULTS: During the study period, 145 patients underwent an Ivor Lewis esophagectomy; 10 (6.9%) developed an AL, diagnosed a median of 7.5 days after surgery, and detected by enteric contents in wound drains (n = 3), endoscopy (n = 3), CT (n = 2), and contrast esophagogram (n = 2). Nine patients (90%) had an increasing white blood cell count and additional signs of sepsis. One asymptomatic patient was identified by contrast esophagography. All patients received enteral nutritional support, intravenous antibiotics, and antifungals. Primary treatment of ALs included endoscopic placement of a self-expanding metal stent (SEMS; n = 6), surgery (n = 2), and SEMS with endoluminal vacuum therapy (n = 2). One patient required surgery after SEMS placement. The median length of ICU and total hospital stays were 11.5 and 22.5 days, respectively. There was no 30-day mortality. CONCLUSION: The incidence of esophageal ALs at our center is similar to that of other high-volume centers. Most ALs can be managed without surgery; however, ALs remain a significant source of postoperative morbidity despite clinical advancements that have improved mortality.

Novel role for tumor suppressor gene, liver kinase B1, in epithelial-mesenchymal transition leading to chronic lung allograft dysfunction.

Epithelial-mesenchymal transition (EMT) has been implicated to play a role in chronic lung allograft dysfunction (CLAD). Liver kinase B1 (LKB1), a tumor suppressor gene, can regulate EMT. However, its role in CLAD development following lung transplantation remains unknown. Using qRT-PCR, biopsies from lung transplant recipients with bronchiolitis obliterans syndrome (BOS) demonstrated significant downregulation of LKB1 (p = .0001), compared to stable biopsies. To determine the role of LKB1 in EMT development, we analyzed EMT in human bronchial epithelial cell line BEAS-2B. Knockdown of LKB1 by siRNA significantly dysregulated mesenchymal markers expression in BEAS-2B cells. Following incubation of human primary bronchial epithelial cell or BEAS-2B cells with exosomes isolated from BOS or stable lung transplant recipients, LKB1 expression was inhibited when incubated with BOS-exosome. Incubation with BOS-exosomes also decreased LKB1 expression and induced EMT markers in air-liquid interface culture method. Our results provide novel evidence that exosomes released from transplanted lungs undergoing chronic rejection are associated with inactivated tumor suppressor gene LKB1 and this loss induces EMT leading to the pathogenesis of CLAD following human lung transplantation.

Serum Glial Fibrillary Acidic Protein: A Neuromyelitis Optica Spectrum Disorder Biomarker.

OBJECTIVE: Blood tests to monitor disease activity, attack severity, or treatment impact in neuromyelitis optica spectrum disorder (NMOSD) have not been developed. This study investigated the relationship between serum glial fibrillary acidic protein (sGFAP) concentration and NMOSD activity and assessed the impact of inebilizumab treatment. METHODS: N-MOmentum was a prospective, multicenter, double-blind, placebo-controlled, randomized clinical trial in adults with NMOSD. sGFAP levels were measured by single-molecule arrays (SIMOA) in 1,260 serial and attack-related samples from 215 N-MOmentum participants (92% aquaporin 4-immunoglobulin G-seropositive) and in control samples (from healthy donors and patients with relapsing-remitting multiple sclerosis). RESULTS: At baseline, 62 participants (29%) exhibited high sGFAP concentrations (≥170 pg/ml; ≥2 standard deviations above healthy donor mean concentration) and were more likely to experience an adjudicated attack than participants with lower baseline concentrations (hazard ratio [95% confidence interval], 3.09 [1.6-6.1], p = 0.001). Median (interquartile range [IQR]) concentrations increased within 1 week of an attack (baseline: 168.4, IQR = 128.9-449.7 pg/ml; attack: 2,160.1, IQR = 302.7-9,455.0 pg/ml, p = 0.0015) and correlated with attack severity (median fold change from baseline [FC], minor attacks: 1.06, IQR = 0.9-7.4; major attacks: 34.32, IQR = 8.7-107.5, p = 0.023). This attack-related increase in sGFAP occurred primarily in placebo-treated participants (FC: 20.2, IQR = 4.4-98.3, p = 0.001) and was not observed in inebilizumab-treated participants (FC: 1.1, IQR = 0.8-24.6, p > 0.05). Five participants (28%) with elevated baseline sGFAP reported neurological symptoms leading to nonadjudicated attack assessments. INTERPRETATION: Serum GFAP may serve as a biomarker of NMOSD activity, attack risk, and treatment effects. ANN NEUROL 2021;89:895-910.

Outcomes after lung transplantation in recipients aged 70 years or older.

BACKGROUND: The proportion of lung transplant (LTx) recipients older than 70 years is increasing, thus we assessed long-term survival after LTx in this cohort relative to younger counterparts. PATIENTS AND METHODS: We retrospectively reviewed charts of patients who underwent LTx between 2012 and 2016 at our center and divided patients by age: group A (<65 years), B (65-69 years), and C (≥70 years). Survival statistics were evaluated using the Kaplan-Meier method and Cox regression. RESULTS: The study included 375 LTx recipients: 221 (58.9%) in group A, 109 (29.1%) in group B, and 45 (12.0%) in group C. Group C was mostly men (37/45 [82.2%]; P = 0.003) and had the highest mean serum creatinine at listing (P = 0.02). Survival at 1, 3, and 5 years after transplant in group A (93.2%, 70.1%, 58.8%) was significantly higher than group B (83.5%, 59.6%, 44.0%; P = 0.005, 0.028, 0.006, log-rank test) and was similar to group C (86.7%, 64.4%, 57.8%), although trended higher at 1 year (P = 0.139, 0.274, 0.489, log-rank test). Groups B and C had comparable survival at all time points. CONCLUSIONS: Although survival decreased after age 65, long-term survival was comparable between LTx recipients aged 65-69 years and recipients ≥70 years.

Elevated levels of hair cortisol concentrations in professional dementia caregivers.

Providing care for people with dementia can be a highly stressful profession. Hair Cortisol Concentration (HCC) levels have been used as a biological marker for HPA axis activity to demonstrate that informal caregivers of people with dementia could be vulnerable to chronic stress. The current study aimed to progress the findings of research conducted with informal caregivers and is the first study to assess HCC as a biological indicator of stress in professional carers of people with dementia. HCC levels were compared between 32 professional dementia caregivers (30 females with a mean age of 45.83 and 2 males with a mean age of 24.50), 45 employees working in higher education settings (42 females with a mean age of 38.66 and 3 males with a mean age of 31.89) and 88 undergraduate students (67 females with a mean age of 24.04 and 21 males with a mean age of 23.91). Analysis of HCC was used to assess HPA axis activity over 1 month. A one-way ANCOVA, with age and gender being included as covariates, revealed that higher levels of HCC were observed in professional dementia carers than people who worked within higher education settings and undergraduate students. The results indicated that professional dementia caregivers may experience stress to the extent of activating biological stress responses at a greater frequency in comparison to people who work in higher education and undergraduate students. However, no significant differences were observed in the perceived stress levels reported across dementia caregivers, professionals working in higher education, and undergraduate students. These findings highlight the requirement to ascertain the extent to which work-related tasks or other factors, specific to the profession of caring for people with dementia, could elicit heightened HPA stress reactivity.

Are context-specific measures of positive emotion regulation more predictive of mania risk and mood symptoms than trait measures?

BACKGROUND: A number of strategies used to regulate positive affect (i.e. dampening and positive rumination) have been identified as having particular relevance to hypomanic personality (a proxy measure of mania risk). However, previous findings have been mixed and it is suggested that this may be the result of lack of consideration of the context in which emotion regulation (ER) is occurring. AIMS: This study aimed to investigate (a) if use of specific ER strategies predicts mood across social- and goal-related contexts, and (b) if the relationship between hypomanic personality and mood is moderated by greater use of ER strategies. METHOD: One hundred and seventy-four participants (mean age 20.77 years, SD = 2.2) completed an online survey assessing (i) hypomanic personality, (ii) self-reported tendencies to use ER strategies for positive emotion, (iii) tendencies to use these strategies in response to both high- and moderate-intensity positive affect in personally generated social- and goal-related contexts, and (iv) current affect. RESULTS: Trait use of ER strategies was more predictive of hypomanic personality and mood symptoms than context-specific measures; however, this relationship did not hold up for hypomanic personality and mood symptoms when accounting for current affect. Trait dampening was predictive of low mood symptoms but did not moderate the relationship between hypomanic personality and low mood. DISCUSSION: While trait measures of ER were more predictive of mania risk and mood symptoms than context-specific measures, further work is needed using experience sampling methods in order to capture the regulatory processes individuals are using in particular contexts, in real-time.

The role of miRNA-155 in the immunopathogenesis of obliterative airway disease in mice induced by circulating exosomes from human lung transplant recipients with chronic lung allograft dysfunction.

Human lung transplant recipients undergoing rejection induce circulatory exosomes with lung self-antigens (SAgs), K-alpha 1 Tubulin and Collagen V, and immunization of C57BL/6 mice with exosomes induced obliterative airway disease (HEI-OAD). We analyzed whether exosomes with SAgs induced immunity in microRNA-155 knockout mice (miR-155KO), as microRNA-155 is an immune regulator. C57BL/6 and miR-155KO were immunized with exosomes from stable or chronic rejection (bronchiolitis obliterans syndrome (BOS) and on day 30, induction of exosomes, antibodies (Abs) to SAgs and cellular immunity were determined. C57BL/6 immunized with exosomes from BOS developed OAD. These immunized animals also developed Abs to SAgs and increased frequency of SAg-specific IFNγ and IL17- producing cells. In contrast, Abs to SAgs did not develop in miR-155KO and there was reduction in frequency of cells producing IL10. Upregulation of suppressor of cytokine signaling for lung inflammation was also noted resulting in abrogation of induction of exosomes with SAgs OAD.

Circulating Exosomes with Distinct Properties during Chronic Lung Allograft Rejection.

Circulating exosomes containing donor HLA and lung-associated self-antigens (SAg) are thought to play an important role in allograft rejection after human lung transplantation. We characterized exosomes isolated from serum of 10 lung transplant recipients (LTxR) diagnosed with bronchiolitis obliterans syndrome (BOS) and compared them with exosomes isolated from serum of 10 stable LTxR. Lung-associated SAg (K-α-1-tubulin [Kα1T] and collagen V [Col-V]), MHC class II molecules, costimulatory molecules CD40, CD80, and CD86, and transcription factors class II MHC trans-activator, NF-κB, hypoxia-inducible factor 1-α, IL-1R-associated kinase 1, MyD88, and 20S proteasome were detected in exosomes from BOS, but not stable LTxR. In contrast, adhesion molecules were present in both groups. C57BL/6 mice immunized with exosomes from BOS but not stable LTxR demonstrated Ab to SAg (Col-V, 33.5 ± 15.7 versus 10.4 ± 6.4, p = 0.021; Kα1T, 925 ± 403 versus 317 ± 285, p = 0.044) and HLA (mean fluorescence intensity: BOS, 8450; stable, 632; p < 0.05). Furthermore, splenic lymphocytes demonstrated increased frequency of lung SAg-specific IL-17 (Col-V, 128 ± 46 versus 31 ± 21, p = 0.013; Kα1T, 194 ± 47 versus 67 ± 43, p = 0.014) and IFN-γ (Col-V, 165 ± 79 versus 38 ± 40, p = 0.042; Kα1T, 232 ± 64 versus 118 ± 39, p = 0.012). Reduced levels of IL-10-producing cells were seen in BOS exosome immunized mice compared with mice immunized with stable exosomes (Col-V, 59 ± 23 versus 211 ± 85, p = 0.016; Kα1T, 78 ± 49 versus 295 ± 104, p = 0.017). Owing to the unique immune-stimulating properties of exosomes induced during rejection, we propose that they play an important role in eliciting both alloantigen- and SAg-specific immunity, leading to chronic rejection after lung transplantation.

Outcomes of Children With Cystic Fibrosis Admitted to PICUs.

OBJECTIVES: Data on outcomes of children with cystic fibrosis admitted to PICUs are limited and outdated. Prior studies cite PICU mortality rates ranging from 37.5% to 100%. Given the advances made in cystic fibrosis care, we expect outcomes for these patients to have changed significantly since last studied. We provide an updated report on PICU mortality and the factors associated with death among critically ill children with cystic fibrosis. DESIGN: Retrospective multicenter cohort analysis utilizing data from the Virtual Pediatric Systems database. SETTING: Data were collected from 135 PICUs from January 1, 2009, to June 20, 2018. PATIENTS: One-thousand six-hundred thirty-three children with cystic fibrosis accounting for 2,893 PICU admissions were studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mortality during PICU admission. Predictors included demographics, anthropometrics, diagnoses, clinical characteristics, and critical care interventions. Odds ratios of mortality were calculated in univariate and multivariable analyses to assess differences in mortality associated with predictor variables. Generalized estimating equation models were used to account for multiple admissions per patient. The overall PICU mortality rate was 6.6%. Factors associated with increased odds of mortality included hemoptysis/pulmonary hemorrhage, pneumothorax, gastrointestinal bleeding, bacterial/fungal infections, lower body mass index/malnutrition, and need for noninvasive or invasive respiratory support. Intubation/mechanical ventilation occurred in 26.4% of the 2,893 admissions and was associated with a 19.1% mortality rate. Of the nonsurvivors, 20.7% died without receiving mechanical ventilation. CONCLUSIONS: The mortality rate during PICU admissions for patients with cystic fibrosis is lower than has been reported in prior studies, both in the overall cohort and in the subset requiring invasive mechanical ventilation. These data provide updated insight into the prognosis for cystic fibrosis patients requiring critical care.

Gospel Music: A Catalyst for Retention, Engagement, and Positive Health Outcomes for African Americans in a Cardiovascular Prevention and Treatment Program.

CONTEXT: Mortality associated with cardiovascular disease is significantly higher in African Americans compared with people of other ethnicities, with hypertension being the single most significant risk factor in this population. Underdiagnosis and undertreatment of hypertension is common. Although cardiovascular lifestyle education and self-management programs are available for the general public, many African Americans prefer to learn about health-promoting activities through interactive programs led by church ministries. OBJECTIVE: This study examined the influence of adding a faith-based protocol using creative musical expression as a catalyst for improving retention, engagement, and positive health outcomes for African Americans participating in a 1-y, lifestyle skills program for reducing cardiovascular risk factors. DESIGN: The study was a randomized, controlled trial. SETTING: The study occurred at Rodman Street Missionary Baptist Church (Pittsburgh, PA, USA). PARTICIPANTS: Participants were African Americans with at least 2 of the following medical conditions: high blood pressure, elevated cholesterol and/or triglycerides, heart attack, angina, stroke, irregular heartbeats, palpitations, shortness of breath, dizziness or fainting, diabetes, and tobacco use. INTERVENTION: Intervention and control groups both participated every other week in one 45-min structured cardiovascular risk reduction educational session over the course of 1 year. During alternative weeks, sessions comprised blood pressure checks, coupled with individualized support discussions focused on challenges and identified obstacles to adherence. In addition to the aforementioned sessions, the intervention group participated in a novel gospel music program with weekly, 45-minute vocal and instrumental sessions. OUTCOME MEASURES: Outcome measures include retention, attendance, systolic and diastolic blood pressures, weight, body mass index, hip measurement, and waist measurement as well as the Short Form-12 (SH-12) Health Survey. RESULTS: Subjects in the intervention group demonstrated a statistically significant 83.3% retention rate in the course of 1 year compared with only 54.3% for the control group (cardiovascular lifestyle education sessions alone). Six dropouts were noted in the intervention group in sharp contrast to 16 dropouts in the control group. Participants in the intervention group were 4.21 times more likely to complete the program than the control group. A significant difference was also noted for attendance, which was higher for the intervention group (21.33 sessions for the intervention group vs 17.95 sessions for the control group). Statistically significant systolic blood pressure reductions noted in both groups were sustained 6 mo postprogram conclusion. In addition, a statistically significant pre-between post-between group improvement in SF-12 Physical Component Scores was noted for intervention subjects in sharp contrast with controls who actually demonstrated worsening scores. CONCLUSIONS: The addition of a gospel music program as a catalyst for increase engagement in a sustainable, healthy lifestyle program warrants further consideration and additional study in African American churches.

An experimental investigation into cardiovascular, haemodynamic and salivary alpha amylase reactivity to acute stress in Type D individuals.

Type D personality is characterized by increased social inhibition and negative affectivity. Research demonstrates associations between Type D and poor physical health. Maladaptive sympathetic arousal is suggested as a potential mechanism, however, findings are inconsistent and studies mainly focus on basic cardiovascular parameters. The current study examines cardiovascular and haemodynamic parameters in addition to salivary alpha amylase (sAA) as markers of sympathetic stress reactivity in Type D individuals. Healthy adults (N = 75; 33 Type D; aged 18-42; 64% female) completed a multitasking stressor while continuous beat-to-beat cardiovascular function was measured. Saliva samples were obtained at baseline, pre-task, post-task, +10 min and +20 min post-task. Type Ds exhibited dysfunctional cardiovascular reactivity, characterized by blunted total peripheral resistance, slower stroke volume recovery and potentially unhealthy changes in haemodynamic profile. Alpha amylase reactivity was evident, but group differences were not significant. Findings indicate dysregulated sympathetic reactivity in Type D individuals, exemplified by a maladaptive haemodynamic profile.

Factors associated with skin cancer in lung transplant recipients: A single-center experience.

BACKGROUND: Skin cancer is common after solid organ transplantation, but few have investigated it after lung transplant (LTx). OBJECTIVE: We assessed incidence and predictors of non-melanoma skin cancer (NMSC) post-LTx. METHODS: We studied patients who underwent LTx at our center from 2012 to 2015. RESULTS: Of 287 patients, mean age was 59.6 ± 11 years, 170 (59.2%) were men, and 231 (80.5%) were white. Seventy-six (26.5%) developed NMSC over a median follow-up of 32 months (IQR, 23-45). Of those with NMSC, 37% developed subsequent skin cancer of the same type. Independent predictors of decreased odds of NMSC and squamous cell carcinoma (SCC) were non-white race (P = .002; P = .003) and body mass index >30 kg/m2 compared with underweight patients (P = .001, P = .009). Patients with skin cancer pre-LTx had higher risk of post-LTx skin cancer (P = .02). Voriconazole use ≥100 days was associated with increased risk of SCC (P = .03), but not increased risk of basal cell carcinoma. Out of 76, 4 (5.3%) died from skin cancer. LIMITATIONS: Retrospective, single-center study. CONCLUSION: Squamous cell carcinoma risk post-LTx may increase with prolonged voriconazole use in white patients with pre-LTx history of skin cancer, whereas excess body weight may be protective from NMSC. Regular pre- and post-LTx skin cancer screenings and guidelines are warranted.