Advancing Cancer Workforce Capacity for American Indians and Alaska Natives: The Development of a Validated System to Optimize Trainee Participation and Outcome Tracking.

Although American Indian and Alaska Native (AIAN) students are the most underrepresented group in the U.S. in biomedical and health sciences relative to population size, little is known about long-term research education programs and outcome tracking. For over 20 years, the Partnership for Native American Cancer Prevention (NACP) has been supported under the National Cancer Institute's (NCI)-funded Comprehensive Partnerships to Advance Cancer Health Equity (CPACHE) program. Programming included hands-on mentored research and an array of development opportunities. A validated tracking system combining participation records, institutional records, and enrollment/degree attainment from the National Student Clearinghouse documents outcomes. Collectively (2002-2022) NACP engaged 367 AIAN trainees, of whom 237 individuals earned 220 bachelors, 87 masters, and 34 doctoral/professional degrees. Approximately 45% of AIAN doctoral recipients are currently engaged in academic or clinical work, and 10% in industry or tribal leadership. A total of 238 AIAN students participated in mentored research, with 85% demonstrating strong outcomes; 51% attained a degree, and 34% are currently enrolled. Implementation of a robust tracking system documented acceleration in degree attainment over time. Next steps will evaluate the most impactful training activities on student outcomes.

Changes in vaccine hesitancy among parents of children aged 6 months - 17 Years, National Immunization Surveys, 2019-2022.

BACKGROUND: Vaccine hesitancy (VH) has been a major contributor to large outbreaks of vaccine-preventable diseases globally, including in the United States. METHODS: Data from the 2019-2022 National Immunization Surveys were analyzed to assess parental hesitancy toward routine vaccination of their children aged 6 months -17 years. Joinpoint regression was employed to investigate trends in VH from 2019 to 2022 nationally overall and among socio-demographic subgroups. Using logistic regression, the difference between the prevalence of VH before and after the authorization of the COVID-19 vaccine for children aged 6 months-4 years, 5-11 years, and 12-17 years was computed. Both unadjusted and adjusted estimates were reported. VH was also compared within each socio-demographic subgroup with a reference level, at two-time points- before and after the authorization of the COVID-19 vaccine for each age group. RESULTS: Overall, VH remained around 19.0 % from Q2 2019 to Q3 2022. Parents of non-Hispanic Black children had the largest average quarterly decrease in VH (ß = -0.55; p < 0.05 by test for trend). After the authorization of the COVID-19 vaccine for children aged 6 months to 4 years, the adjusted percentage of children having parents that reported VH decreased by 2.2 (95 % CI: -3.9, -0.6) percentage points (pp) from 21.6 % to 19.4 %. Conversely, for children aged 5-11 years, VH increased by 1.2 (95 % CI: 0.2, 2.3) pp, from 19.8 % to 21.0 %. VH among parents of non-Hispanic Black children decreased after the authorization of the COVID-19 vaccine for adolescents aged 12-17 years but remained significantly higher compared to parents of non-Hispanic White children before and after authorization of the COVID-19 vaccine for all age groups. DISCUSSION: About 1 in 5 children had parents reporting VH from 2019 to 2022. Parental VH increased after the authorization of the COVID-19 vaccine for children aged 5-11 years and declined for children aged 6 months-4 years.

Human Factors Contributing to Infection Prevention in Outpatient Hemodialysis Centers: A Mixed Methods Study.

RATIONALE & OBJECTIVE: Infection prevention efforts in dialysis centers can avert patient morbidity and mortality but are challenging to implement. The objective of this study was to better understand how the design of the work system might contribute to infection prevention in outpatient dialysis centers. STUDY DESIGN: Mixed methods, observational study. SETTING & PARTICIPANTS: Six dialysis facilities across the United States visited by a multidisciplinary team over 8 months. ANALYTICAL APPROACH: At each facility, structured macroergonomic observations were undertaken by a multidisciplinary team using the SEIPS 1.0 model. Ethnographic observations were collected about staff encounters with dialysis patients including the content of staff conversations. Selective and axial coding were used for qualitative analysis and quantitative data were reported using descriptive statistics. RESULTS: Organizational and sociotechnical barriers and facilitators to infection prevention in the outpatient dialysis setting were identified. Features related to human performance, (eg, alarms, interruptions, and task stacking), work system design (eg, physical space, scheduling, leadership, and culture), and extrinsic factors (eg, patient-related characteristics) were identified. LIMITATIONS: This was an exploratory evaluation with a small sample size. CONCLUSIONS: This study used a systematic macroergonomic approach in multiple outpatient dialysis facilities to identify infection prevention barriers and facilitators related to human performance. Several features common across facilities were identified that may influence infection prevention in outpatient care and warrant further exploration.

The Association of Post-Lung Transplant Pulmonary Embolism With the Development of Chronic Lung Allograft Dysfunction.

Background: Pulmonary embolism (PE) is a rare yet serious postoperative complication for lung transplant recipients (LTRs). The association between timing and severity of PE and the development of chronic allograft lung dysfunction (CLAD) has not been described. Methods: A single-center, retrospective cohort analysis of first LTRs included bilateral or single lung transplants and excluded multiorgan transplants and retransplants. PEs were confirmed by computed tomography angiography or ventilation/perfusion (VQ) scans. Infarctions were confirmed on computed tomography angiography by a trained physician. The PE severity was defined by the Pulmonary Embolism Severity Index (PESI) score, a 30-d post-PE mortality risk calculator, and stratified by low I and II (0-85), intermediate III and IV (85-125), and high V (>125). PE and PESI were analyzed in the outcomes of overall survival, graft failure, and chronic lung allograft dysfunction (CLAD). Results: We identified 57 of 928 patients (6.14%) who had at least 1 PE in the LTR cohort with a median follow-up of 1623 d. In the subset with PE, the median PESI score was 85 (75.8-96.5). Most of the PESI scores (32/56 available) were in the low-risk category. In the CLAD analysis, there were 49 LTRs who had a PE and 16 LTRs (33%) had infarction. When treating PE as time-dependent and adjusting for covariates, PE was significantly associated with death (hazard ratio [HR] 1.8; 95% confidence interval [CI], 1.3-2.5), as well as increased risk of graft failure, defined as retransplant, CLAD, or death (HR 1.8; 95% CI, 1.3-2.5), and CLAD (HR 1.7; 95% CI, 1.2-2.4). Infarction was not associated with CLAD or death. The PESI risk category was not a significant predictor of death or CLAD. Conclusions: PE is associated with decreased survival and increased hazard of developing CLAD. PESI score was not a reliable predictor of CLAD or death in this lung transplant cohort.

Development and validation of primary graft dysfunction predictive algorithm for lung transplant candidates.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Accurate prediction of PGD risk could inform donor approaches and perioperative care planning. We sought to develop a clinically useful, generalizable PGD prediction model to aid in transplant decision-making. METHODS: We derived a predictive model in a prospective cohort study of subjects from 2012 to 2018, followed by a single-center external validation. We used regularized (lasso) logistic regression to evaluate the predictive ability of clinically available PGD predictors and developed a user interface for clinical application. Using decision curve analysis, we quantified the net benefit of the model across a range of PGD risk thresholds and assessed model calibration and discrimination. RESULTS: The PGD predictive model included distance from donor hospital to recipient transplant center, recipient age, predicted total lung capacity, lung allocation score (LAS), body mass index, pulmonary artery mean pressure, sex, and indication for transplant; donor age, sex, mechanism of death, and donor smoking status; and interaction terms for LAS and donor distance. The interface allows for real-time assessment of PGD risk for any donor/recipient combination. The model offers decision-making net benefit in the PGD risk range of 10% to 75% in the derivation centers and 2% to 10% in the validation cohort, a range incorporating the incidence in that cohort. CONCLUSION: We developed a clinically useful PGD predictive algorithm across a range of PGD risk thresholds to support transplant decision-making, posttransplant care, and enrich samples for PGD treatment trials.

The Impact of Donor Smoking on Primary Graft Dysfunction and Mortality after Lung Transplantation.

Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012 and 2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined using accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression, and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11.5% (95% confidence interval [CI], 3.8% to 19.2%) by urinary cotinine, 5.7% (95% CI, -3.4% to 14.9%) by urinary NNAL, and 6.5% (95% CI, -2.8% to 15.8%) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability. Clinical trial registered with www.clinicaltrials.gov (NCT00552357).

Statewide Implementation of Universal Third-Trimester Repeat HIV Testing in Illinois.

OBJECTIVE: This article aims to assess statewide uptake of HIV repeat testing in the first 2 years after the implementation of an amendment to the Illinois Perinatal HIV Prevention Act (IPHPA) mandating universal repeat HIV testing in the third trimester. STUDY DESIGN: This is a retrospective, population-based study of all birthing individuals in Illinois (2018-2019). Data were collected using the state-mandated closed system of perinatal HIV test reporting. We evaluated the incidence of mother-infant pairs with negative early tests and repeat third-trimester tests (RTTTs) performed in adherence with the law, as well as the timing of the performance of the RTTTs (outpatient vs. inpatient). Chi-square tests of trend by quarter were performed to ascertain sustainability. RESULTS: Of 138,805 individuals delivered in 2018, 80.6% presented with early test and RTTTs. In 2018, outpatient RTTTs improved from 71.8% (quarter 1) to 85.1% (quarter 4; p < 0.001). In 2018, the proportion of mother-infant dyads who received testing that was adherent to the IPHPA Amendment was 92.1, 95.5, 96.7, and 96.4% in quarters 1 through 4, respectively (p < 0.001). In 2019, outpatient RTTTs performance remained high (87.4%) and stable (p = 0.06). In 2019, 99.9% of mother-infant dyads had testing adherent to the mandate in quarters 1 through 4 (p = 0.39). Of individuals who presented without RTTTs, 93.5% (2018) and 98.8% (2019) underwent inpatient testing before delivery. CONCLUSION: Implementation of RTTTs in Illinois was rapid, successful, and sustained in its first 2 years. Public health methodologies from Illinois may benefit other states implementing RTTT programs. KEY POINTS: · In 2018, Illinois enacted statewide RTTT for HIV among all parturients.. · In 2019, over 99% of mother-infant dyads had documentation of both early and repeat HIV testing before hospital discharge.. · Implementation of repeat third-trimester HIV testing in Illinois was rapid, successful, and sustained in its first 2 years.. · Public health methodologies from Illinois may benefit other states implementing similar programs..

Estimating county-level vaccination coverage using small area estimation with the National Immunization Survey-Child.

The National Immunization Survey-Child (NIS-Child) provides annual vaccination coverage estimates in the United States for children aged 19 through 35 months, nationally, for each state, and for select local areas and territories. There is a need for vaccination coverage estimates for smaller geographic areas to support local authority planning and identify counties with potentially low vaccination coverage for possible further intervention. We describe small area estimation methods using 2008-2018 NIS-Child data to generate county-level estimates for children up to two years of age born 2007-2011 and 2012-2016. We applied an empirical best linear unbiased prediction method to combine direct estimates of vaccination coverage with model-based prediction using county-level predictors regarding health and demographic characteristics. We review the predictors commonly selected for the small area models and note multiple predictors related to barriers to vaccination.

Report From a Multidisciplinary Symposium on the Future of Living Kidney Donor Transplantation.

Virtually all clinicians agree that living donor renal transplantation is the optimal treatment for permanent loss of kidney function. Yet, living donor kidney transplantation has not grown in the United States for more than 2 decades. A virtual symposium gathered experts to examine this shortcoming and to stimulate and clarify issues salient to improving living donation. The ethical principles of rewarding kidney donors and the limits of altruism as the exclusive compelling stimulus for donation were emphasized. Concepts that donor incentives could save up to 40 000 lives annually and considerable taxpayer dollars were examined, and survey data confirmed voter support for donor compensation. Objections to rewarding donors were also presented. Living donor kidney exchanges and limited numbers of deceased donor kidneys were reviewed. Discussants found consensus that attempts to increase living donation should include removing artificial barriers in donor evaluation, expansion of living donor chains, affirming the safety of live kidney donation, and assurance that donors incur no expense. If the current legal and practice standards persist, living kidney donation will fail to achieve its true potential to save lives.

Vaccination Coverage by Age 24 Months Among Children Born in 2019 and 2020 - National Immunization Survey-Child, United States, 2020-2022.

National Immunization Survey-Child data collected in 2022 were combined with data from previous years to assemble birth cohorts and assess coverage with routine vaccines by age 24 months by birth cohort. Overall, vaccination coverage was similar among children born during 2019-2020 compared with children born during 2017-2018, except that coverage with both the birth dose of hepatitis B vaccine and ≥1 dose of hepatitis A vaccine increased. Coverage was generally higher among non-Hispanic White (White) children (2-21 percentage points higher than coverage for non-Hispanic Black or African American, Hispanic or Latino, and non-Hispanic American Indian/Alaska Native [AI/AN] children), children living at or above poverty (3.5-22 percentage points higher than coverage for children living below the federal poverty level), privately insured children (2.4-38 percentage points higher than coverage for children with Medicaid, other insurance, or no insurance), and children in urban areas (3-16.5 percentage points higher than coverage for children living in rural areas). Coverage with the full series of Haemophilus influenzae type b conjugate vaccine was lower among AI/AN children compared with White children. Trends in vaccination coverage disparities across categories of race and ethnicity, health insurance status, poverty status, and urbanicity were evaluated for the 2016-2020 birth cohorts. Fewer than 5% of 168 trends examined were statistically significant, including six increases (widening of the coverage gap) and one decrease (narrowing of the gap). Analyses revealed a widening of the gap between children living at or above the poverty level (higher coverage) and those living below poverty (lower coverage), for several vaccines. Socioeconomic, demographic, and geographic disparities in vaccination coverage persist; addressing them is important to ensure protection for all children against vaccine-preventable disease.

With Comparable Outcomes, Should Early-Stage Lung Cancer Be a Contraindication to Lung Transplant?

BACKGROUND: Active primary lung malignancy remains a strong contraindication to lung transplantation (LTx). However, outcomes are unclear for patients with early-stage non-small cell lung cancer (NSCLC) who undergo LTx. We hypothesize that patients with early-stage NSCLC incidentally discovered in the explanted lungs have survival comparable to LTx recipients without incidental cancer identified. METHODS: We performed a single-center retrospective analysis of all LTx recipients from May 2007 to September 2021 with incidental cancer identified in the explanted lungs by pathologist report. Survival statistics were estimated using Kaplan-Meier analysis. RESULTS: Of the 1586 LTx performed, 23 patients (1.5%) were found to have incidental lung cancer in the explanted lungs. The most common indications for LTx were interstitial lung disease (n = 13) and chronic obstructive pulmonary disease (n = 7), and the most common histologic diagnosis was adenocarcinoma (n = 14). In the cohort with stage I disease (n = 9), the 1- and 5-year unadjusted Kaplan-Meier survival rates were 88.9% and 51.9%, respectively. The 1- and 5-year survival rates for transplant recipients without incidental cancer findings at LTx during this period were 86.7% and 59.4%, respectively, and did not differ significantly between the 2 strata (P = .96). CONCLUSIONS: Survival rates at 1 and 5 years were comparable between LTx recipients with incidentally noted pathologic stage I NSCLC and contemporary recipients without cancer. All cancer-related deaths occurred in recipients with incidentally noted advanced NSCLC. These results suggest that patients with pathologic stage I lung cancer at the time of transplant have outcomes comparable to those without cancer findings at the time of transplant.

Vaccination Coverage Among Adolescents Aged 13-17 Years - National Immunization Survey-Teen, United States, 2022.

Three vaccines are routinely recommended for adolescents to prevent pertussis, meningococcal disease, and cancers caused by human papillomavirus (HPV). CDC analyzed data from the 2022 National Immunization Survey-Teen for 16,043 adolescents aged 13-17 years to assess vaccination coverage. Birth cohort analyses were conducted to assess trends in vaccination coverage by age 13 years (i.e., before the 13th birthday) and by age 14 years (i.e., before the 14th birthday) among adolescents who were due for routine vaccination before and during the COVID-19 pandemic. Cross-sectional analysis was used to assess coverage estimates among adolescents aged 13-17 years. In 2022, vaccination coverage by age 14 years among adolescents born in 2008 continued to lag that of earlier birth cohorts and varied by sociodemographic factors and access to health care compared with coverage among earlier birth cohorts. Vaccination coverage by age 13 years among adolescents born in 2009 was similar to coverage estimates obtained before the COVID-19 pandemic. Among all adolescents aged 13-17 years, 2022 vaccination coverage levels did not differ from 2021 levels; however, initiation of the HPV vaccination series decreased among those who were insured by Medicaid. Coverage with ≥1 dose of tetanus, diphtheria, and acellular pertussis vaccine and ≥1 dose meningococcal conjugate vaccine was high and stable (around 90%). Providers should review adolescent vaccination records, especially among those born in 2008 and those in populations eligible for the Vaccines for Children program, to ensure adolescents are up to date with all recommended vaccines.

External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which novel therapies are needed. External controls (ECs) could enhance IPF trial efficiency, but the direct comparability of ECs versus concurrent controls is unknown. Objectives: To develop IPF ECs by fit-for-purpose data standards to historical randomized clinical trial (RCT), multicenter registry (Pulmonary Fibrosis Foundation Patient Registry), and electronic health record (EHR) data and to evaluate endpoint comparability among ECs and the phase II RCT of BMS-986020. Methods: After data curation, the rate of change in FVC from baseline to 26 weeks among participants receiving BMS-986020 600 mg twice daily was compared with the BMS-placebo arm and ECs using mixed-effects models with inverse probability weights. Measurements and Main Results: At 26 weeks, the rates of change in FVC were -32.71 ml for BMS-986020 and -130.09 ml for BMS-placebo (difference, 97.4 ml; 95% confidence interval [CI], 24.6-170.2), replicating the original BMS-986020 RCT. RCT ECs showed treatment effect point estimates within the 95% CI of the original BMS-986020 RCT. Pulmonary Fibrosis Foundation Patient Registry ECs and EHR ECs experienced a slower rate of FVC decline compared with the BMS-placebo arm, resulting in treatment-effect point estimates outside of the 95% CI of the original BMS-986020 RCT. Conclusions: IPF ECs generated from historical RCT placebo arms result in comparable primary treatment effects to that of the original clinical trial, whereas ECs from real-world data sources, including registry or EHR data, do not. RCT ECs may serve as a potentially useful supplement to future IPF RCTs.

Disrupted Routine Medical Visits in Children and Adolescents During the COVID-19 Pandemic, January-June 2021.

Introduction: Recent studies have indicated the coronavirus disease 2019 (COVID-19) pandemic has disrupted routine vaccinations. This study describes the prevalence and characteristics of children and adolescents experiencing disrupted routine vaccination and other medical visits in the United States between January and June 2021. Methods: The National Immunization Surveys were the source of data for this cross-sectional analysis (n= 86,893). Parents/guardians of children aged 6 months through 17 years were identified through random digit dialing of cellular phone numbers and interviewed. Disrupted visits were assessed by asking, "In the last two months, was a medical check-up, well child visit, or vaccination appointment for the child delayed, missed, or not scheduled for any reason?" Respondents answering yes were asked "Was it because of COVID-19?" Sociodemographic characteristics of children/adolescents with (1) COVID-19-related missed visits and (2) non-COVID-19-related missed visits were examined. Statistical differences within demographic subgroups were determined using t-tests, with p<0.05 considered statistically significant. Linear regression models were used to examine trends in disrupted visits over time. Results: An estimated 7.9% of children/adolescents had a missed visit attributed to COVID-19; 5.2% had a missed visit that was not COVID-19-related. Among children/adolescents with a COVID-19-related missed visit, a higher percentage were of minority race or ethnicity, lived below the poverty level, had a mother without a college degree, and lived in the western United States. There was a significant decline in COVID-19-related missed visits over time. Conclusion: COVID-19 disrupted routine vaccination or other medical visits inequitably. Catch-up immunizations are essential for achieving adequate vaccination of all children/adolescents.

Evaluation of host cellular responses to Epstein-Barr virus (EBV) in adult lung transplant patients with EBV-associated diseases.

Epstein-Barr virus (EBV) reactivation is commonly observed in lung transplant recipients (LTRs). However, cellular immune responses to EBV in adult LTRs have not been well described. We aimed to study CD4/CD8 ratio, EBV-specific T cells polyfunctional responses and phenotypic changes in natural killer (NK) cells in adult LTRs presenting with EBV-associated diseases. The CD4/CD8 ratio was significantly decreased in LTRs with EBV DNAemia compared with LTRs without EBV DNAemia and healthy controls (HCs). Stimulation with EBV lytic antigen BZLF1 peptide pools induced significant individual and polyfunctional responses from CD8+ CD69+ T cells. Frequencies of CD8+ CD69+ T cells expressing CD107a were significantly higher in LTRs without EBV DNAemia than in LTRs with DNAemia. Frequencies of CD8+ CD69+ T cells concurrently expressing CD107a, IFN-γ, and TNF-α were significantly greater in LTRs with and without EBV DNAemia than in HCs. Finally, BZLF1 induced significantly higher frequencies of CD8+ CD69+ T cells expressing CD107a and IFN-γ in LTRs without EBV DNAemia when compared with EBNA3B. Frequency of more differentiated CD56dim CD16pos NK cells was significantly decreased in LTRs with EBV DNAemia and PTLD compared with HCs. In conclusion, we noted the presence of significant changes in circulating cellular immune responses to EBV in adult LTRs.

The Association of Reported Experiences of Racial and Ethnic Discrimination in Health Care with COVID-19 Vaccination Status and Intent - United States, April 22, 2021-November 26, 2022.

In 2021, the CDC Director declared that racism is a serious threat to public health,* reflecting a growing awareness of racism as a cause of health inequities, health disparities, and disease. Racial and ethnic disparities in COVID-19-related hospitalization and death (1,2) illustrate the need to examine root causes, including experiences of discrimination. This report describes the association between reported experiences of discrimination in U.S. health care settings and COVID-19 vaccination status and intent to be vaccinated by race and ethnicity during April 22, 2021-November 26, 2022, based on the analysis of interview data collected from 1,154,347 respondents to the National Immunization Survey-Adult COVID Module (NIS-ACM). Overall, 3.5% of adults aged ≥18 years reported having worse health care experiences compared with persons of other races and ethnicities (i.e., they experienced discrimination), with significantly higher percentages reported by persons who identified as non-Hispanic Black or African American (Black) (10.7%), non-Hispanic American Indian or Alaska Native (AI/AN) (7.2%), non-Hispanic multiple or other race (multiple or other race) (6.7%), Hispanic or Latino (Hispanic) (4.5%), non-Hispanic Native Hawaiian or other Pacific Islander (NHOPI) (3.9%), and non-Hispanic Asian (Asian) (2.8%) than by non-Hispanic White (White) persons (1.6%). Unadjusted differences in prevalence of being unvaccinated against COVID-19 among respondents reporting worse health care experiences than persons of other races and ethnicities compared with those who reported that their health care experiences were the same as those of persons of other races and ethnicities were statistically significant overall (5.3) and for NHOPI (19.2), White (10.5), multiple or other race (5.7), Black (4.6), Asian (4.3), and Hispanic (2.6) adults. Findings were similar for vaccination intent. Eliminating inequitable experiences in health care settings might help reduce some disparities in receipt of a COVID-19 vaccine.

Anti-fibrotic therapy and lung transplant outcomes in patients with idiopathic pulmonary fibrosis.

BACKGROUND: It is unclear whether continuing anti-fibrotic therapy until the time of lung transplant increases the risk of complications in patients with idiopathic pulmonary fibrosis. OBJECTIVES: To investigate whether the time between discontinuation of anti-fibrotic therapy and lung transplant in patients with idiopathic pulmonary fibrosis affects the risk of complications. METHODS: We assessed intra-operative and post-transplant complications among patients with idiopathic pulmonary fibrosis who underwent lung transplant and had been treated with nintedanib or pirfenidone continuously for ⩾ 90 days at listing. Patients were grouped according to whether they had a shorter (⩽ 5 medication half-lives) or longer (> 5 medication half-lives) time between discontinuation of anti-fibrotic medication and transplant. Five half-lives corresponded to 2 days for nintedanib and 1 day for pirfenidone. RESULTS: Among patients taking nintedanib (n = 107) or pirfenidone (n = 190), 211 (71.0%) had discontinued anti-fibrotic therapy ⩽ 5 medication half-lives before transplant. Anastomotic and sternal dehiscence occurred only in this group (anastomotic: 11 patients [5.2%], p = 0.031 vs patients with longer time between discontinuation of anti-fibrotic medication and transplant; sternal: 12 patients [5.7%], p = 0.024). No differences were observed in surgical wound dehiscence, length of hospital stay, or survival to discharge between groups with a shorter versus longer time between discontinuation of anti-fibrotic therapy and transplant. CONCLUSION: Anastomotic and sternal dehiscence only occurred in patients with idiopathic pulmonary fibrosis who discontinued anti-fibrotic therapy < 5 medication half-lives before transplant. The frequency of other intra-operative and post-transplant complications did not appear to differ depending on when anti-fibrotic therapy was discontinued. REGISTRATION: clinicaltrials.gov NCT04316780: https://clinicaltrials.gov/ct2/show/NCT04316780.

Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) increases morbidity and mortality for lung transplant recipients. Club cell secretory protein (CCSP), produced by airway club cells, is reduced in the bronchoalveolar lavage fluid (BALF) of lung recipients with CLAD. We sought to understand the relationship between BALF CCSP and early posttransplant allograft injury and determine if early posttransplant BALF CCSP reductions indicate later CLAD risk. METHODS: We quantified CCSP and total protein in 1606 BALF samples collected over the first posttransplant year from 392 adult lung recipients at 5 centers. Generalized estimating equation models were used to examine the correlation of allograft histology or infection events with protein-normalized BALF CCSP. We performed multivariable Cox regression to determine the association between a time-dependent binary indicator of normalized BALF CCSP level below the median in the first posttransplant year and development of probable CLAD. RESULTS: Normalized BALF CCSP concentrations were 19% to 48% lower among samples corresponding to histological allograft injury as compared with healthy samples. Patients who experienced any occurrence of a normalized BALF CCSP level below the median over the first posttransplant year had a significant increase in probable CLAD risk independent of other factors previously linked to CLAD (adjusted hazard ratio 1.95; p = 0.035). CONCLUSIONS: We discovered a threshold for reduced BALF CCSP to discriminate future CLAD risk; supporting the utility of BALF CCSP as a tool for early posttransplant risk stratification. Additionally, our finding that low CCSP associates with future CLAD underscores a role for club cell injury in CLAD pathobiology.