An international, multicenter, survey-based analysis of practice and management of acute liver failure.

INTRODUCTION: Acute liver failure (ALF) is an acute liver dysfunction with coagulopathy and hepatic encephalopathy in a patient with no known liver disease. As ALF is rare and large clinical trials are lacking, the level of evidence regarding its management is low-moderate, favoring heterogeneous clinical practice. In this international multicenter survey study, we aimed to investigate the current practice and management of patients with ALF. METHODS: An online survey targeting physicians who care for patients with ALF was developed by the International Liver Transplantation Society ALF Special-Interest Group. The survey focused on management and liver transplantation (LT) practices of ALF. Survey questions were summarized overall and by geographic region. RESULTS: A total of 267 physicians completed the survey with a survey response rate of 21.36%. Centers from all continents were represented. More than 90% of physicians were specialized in either transplant hepatology/surgery or anesthesiology/critical care. Two hundred and fifty-two (94.4%) respondents' institutions offered LT. A total of 76.8% of respondents' centers had a dedicated liver- or transplant- intensive care unit (p<0.001). Median time to LT was within 48 hours in 12.7% of respondents' centers, 72 hours in 35.6%, one week in 37.6%, and more than one week in 9.6% (p<0.001). Deceased-donor liver graft (49.6%) was the most common type of graft offered. For consideration of LT, 84.8% of physicians used King's College Criteria and 41.6% used Clichy Criteria. Significant differences were observed between Asia, Europe, and North America for offering LT, number of LTs performed, volume of ALF patients, admission to a dedicated intensive care unit, median time to LT, type of liver graft, monitoring hepatic encephalopathy and intracranial pressure, management of coagulopathy, and utilization of different criteria for LT. DISCUSSION: In our study, we observed significant geographic differences in the practice and management of ALF. As ALF is rare multicenter studies are valuable to identify global practice.

Clinician response after receipt of abnormal pediatric ambulatory blood pressure monitoring - characteristics associated with inertia and action.

BACKGROUND: Ambulatory Blood Pressure Monitoring (ABPM) is recommended for diagnosis and management of hypertension. We aimed to identify characteristics associated with physician action after receipt of abnormal findings. METHODS: This was a retrospective cross-sectional analysis of patients 5-22 years old who underwent 24-h ABPM between 2003-2022, met criteria for masked or ambulatory hypertension, and had a pediatric nephrology clinic visit within 2 weeks of ABPM. "Action" was defined as medication change/initiation, lifestyle or adherence counseling, evaluation ordered, or interpretation with no change. Characteristics of children with/without 1 or more actions were compared using Student t-tests and Chi-square. Regression analyses explored the independent association of patient characteristics with physician action. RESULTS: 115 patients with masked (n = 53) and ambulatory (n = 62) hypertension were included: mean age 13.0 years, 48% female, 38% Black race, 21% with chronic kidney disease, and 25% overweight/obesity. 97 (84%) encounters had a documented physician action. Medication change (52%), evaluation ordered (40%), and prescribed lifestyle change (35%) were the most common actions. Adherence counseling for medication and lifestyle recommendations were documented in 3% of encounters. 24-h, wake SBP load, and sleep DBP load were significantly higher among those with physician action. Patients with > 1 action had greater adiposity, SBP, and dipping. Neither age, obesity, nor kidney disease were independently associated with physician action. CONCLUSIONS: While most abnormal ABPMs were acted upon, 16% did not have a documented action. Greater BP load was one of the few characteristics associated with physician action. Of potential actions, adherence counseling was underutilized.

Accuracy and Performance of Triage Blood Pressure Measurements in A Real-World Clinic Setting.

OBJECTIVES: To investigate the agreement and accuracy of triage blood pressure (BP) in a real-world clinic setting, compared with the reference standard. STUDY DESIGN: Paired triage and standardized BP measurements from patients 4 through 21 years old evaluated in an obesity-related hypertension clinic were obtained via chart-review. Triage BPs were measured by a medical assistant or nurse, often by automated device. Triplicate manual BPs were obtained by the clinic physician. Bland-Altman analyses determined mean differences between paired triage and mean standardized BPs. GEE-based multivariable relative risk (RR) regression determined the RR of triage BP overestimation by ≥ 5 mmHg. Overall agreement, sensitivity, specificity, positive predictive value, and negative predictive value of triage BP measurements identifying hypertensive BP were determined. RESULTS: One hundred thirty participants with 347 clinic encounters were included. Mean age was 13.3 years (SD 3.94), 76% were Black, and 58% were male. Overall mean systolic and diastolic BP difference was 8.7 mmHg (95% limits on agreement: -16.66, 34.07) and 4.1 mmHg (95% limits on agreement: -18.56, 26.68), respectively. Triage systolic BP was more likely overestimated by ≥ 5 mmHg when a large adult (RR = 1.49; 95% CI: 1.00, 2.21) or thigh cuff (RR = 1.94; 95% CI: 1.08, 3.51) was required compared with when a child/adult cuff was required. Overall agreement in identifying hypertensive BP was 57.6%. Sensitivity (52.6%), specificity (63.4%), positive predictive value (60.8%), and negative predictive value (55.3%) were low across all cuffs. CONCLUSIONS: There was poor agreement between usual triage and standardized BP measurements, with potential for significant clinical implications. CLINICAL TRIAL REGISTRATION: ReNEW Clinic Cohort Study (ReNEW), NCT03816462, https://clinicaltrials.gov/ct2/show/NCT03816462.

The effect of elexacaftor/tezacaftor/ivacaftor on non-pulmonary symptoms in adults with cystic fibrosis.

Background: Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a CFTR modulator that has led to large benefits in lung function, pulmonary exacerbation rates, and respiratory symptoms. Less is known about the effect of ETI on non-pulmonary symptoms. The objective of this study was to examine the changes in patient reported outcomes after starting ETI in multiple non-pulmonary symptoms. Methods: This was a prospective cohort study of adults with CF. Participants completed questionnaires prior to starting ETI and then at weeks 2, 4, 6, 8, 10, 12, and 14 after starting ETI. They completed the following validated instruments: PROMIS Pain Intensity, PROMIS Pain Interference, FACIT Fatigue, SNOT22, PAC-SYM, PHQ8, GAD7 and Pittsburgh Sleep Quality Index. Longitudinal changes for outcomes were modelled using linear regression based on general estimating equations. Results: 22 participants enrolled who answered questionnaires before and after starting ETI. The median age was 35.3 years (IQR 11.1) and 13 (59.1%) were male. In models adjusted for age, sex, and baseline value there were significant improvements in pain interference (ß = -2.57; 95% CI -4.92, -0.23), sinus symptoms (ß = -4.50; 95% CI -7.59, -1.41), and sleep disturbance (ß = -1.90; 95% CI -2.71, -1.09) over 14 weeks after starting ETI. No symptom areas worsened over the study period. Conclusions: In this prospective study we found statistically significant improvements in three different non-pulmonary symptom areas in people with CF started on ETI. While this was a small, uncontrolled study it suggests that use of highly effective CFTR modulators can result in benefits for patients beyond pulmonary symptoms.

Intravenous BCG vaccination reduces SARS-CoV-2 severity and promotes extensive reprogramming of lung immune cells.

Bacillus Calmette-Guérin (BCG) confers heterologous immune protection against viral infections and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here, we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model. BCG vaccination conferred a modest reduction on lung SCV2 viral load, bronchopneumonia scores, and weight loss, accompanied by a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. BCG uniquely recruited immunoglobulin-producing plasma cells to the lung suggesting accelerated local antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, with a transcriptional shift away from exhaustion markers and toward antigen presentation and repair. Similarly, BCG enhanced recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, that show reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.

Indicators of Neighborhood-Level Socioeconomic Position and Pediatric Critical Illness.

BACKGROUND: With recent prioritization of equity in pediatric health outcomes, a shift to examine neighborhood-level health care disparities within pediatric populations has occurred, specifically in the context of critical illness. RESEARCH QUESTION: Does an association exist between individual indicators of neighborhood-level disadvantage and incidence of PICU admission? STUDY DESIGN AND METHODS: Pediatric patients younger than 18 years admitted to a PICU in a large urban tertiary pediatric hospital from January 1, 2016, through December 31, 2019, with a residential address in the city of Baltimore or Baltimore County on the day of admission were included in this ecological study. Demographic and clinical characteristics of children admitted to the PICU were summarized, with the primary outcome being PICU admission. Unadjusted negative binomial regression was used to examine the association between census tract-level PICU admissions and the previously described census tract-level indicators of neighborhood socioeconomic position. Regression models included an offset term for the population younger than 18 years for each census tract; results of models are reported as incidence rate ratios (IRRs) with corresponding 95% CIs. RESULTS: We identified 2,476 PICU admissions: 1,351 patients from the city of Baltimore (10.25 per 1,000 children) and 1,125 patients from Baltimore County (6.31 per 1,000 children). Most PICU admissions (n = 906 [68%]) for the city of Baltimore represented an area deprivation index (ADI) of > 60, whereas most Baltimore County PICU admissions (n = 919 [82.3%]) represented an ADI of < 60. At the neighborhood level, the percentage of families living below the poverty line was associated with greater incidence of PICU admission in the city of Baltimore (IRR, 1.09; 95% CI, 1.00-1.18) and Baltimore County (IRR, 1.19; 95% CI, 1.05-1.36). For every $10,000 increase in median household income, PICU admission rates dropped by 9% for the city of Baltimore (IRR, 0.91; 95% CI, 0.86-0.95) and Baltimore County (IRR, 0.91; 95% CI, 0.88-0.94). Neighborhoods with vacant housing units also were associated with a higher incidence of PICU admission in the city of Baltimore (IRR, 1.10; 95% CI, 1.01-1.21) and Baltimore County (IRR, 1.46; 95% CI, 1.21-1.77), as was a 10% increase in occupied homes without vehicles (city of Baltimore: IRR, 1.14; 95% CI, 1.07-1.21; Baltimore County: IRR, 1.23; 95% CI, 1.11-1.37). INTERPRETATION: Health outcomes of pediatric critical illness should be examined in the context of structural determinants of health, including neighborhood-level and environmental characteristics.

Declining Use of Prone Positioning After High Initial Uptake in COVID-19 Adult Respiratory Distress Syndrome.

OBJECTIVES: Prone positioning for acute respiratory distress syndrome (ARDS) has historically been underused, but was widely adopted for COVID-19-associated ARDS early in the pandemic. Whether this successful implementation has been sustained over the first 3 years of the COVID-19 pandemic is unknown. In this study, we characterized proning use in patients with COVID-19 ARDS from March 2020 to December 2022. DESIGN: Multicenter retrospective observational study. SETTING: Five-hospital health system in Maryland, USA. PATIENTS: Adults with COVID-19 supported with invasive mechanical ventilation and with a P ao2 /F io2 ratio of less than or equal to 150 mm Hg while receiving F io2 of greater than or equal to 0.6 within 72 hours of intubation. INTERVENTIONS: None. MEASUREMENTS: We extracted demographic, clinical, and positioning data from the electronic medical record. The primary outcome was the initiation of proning within 48 hours of meeting criteria. We compared proning use by year with univariate and multivariate relative risk (RR) regression. Additionally, we evaluated the association of treatment during a COVID-19 surge period and receipt of prone positioning. MAIN RESULTS: We identified 656 qualifying patients; 341 from 2020, 224 from 2021, and 91 from 2022. More than half (53%) met severe ARDS criteria. Early proning occurred in 56.2% of patients in 2020, 56.7% in 2021, and 27.5% in 2022. This translated to a 51% reduction in use of prone positioning among patients treated in 2022 versus 2020 (RR = 0.49; 95% CI, 0.33-0.72; p < 0.001). This reduction remained significant in adjusted models (adjusted RR = 0.59; 95% CI, 0.42-0.82; p = 0.002). Treatment during COVID-19 surge periods was associated with a 7% increase in proning use (adjusted RR = 1.07; 95% CI, 1.02-1.13; p = 0.01). CONCLUSIONS: The use of prone positioning for COVID-19 ARDS is declining. Interventions to increase and sustain appropriate use of this evidence-based therapy are warranted.

Race-Specific Interpretation of Spirometry: Impact on the Lung Allocation Score.

Rationale: Interpretation of spirometry using race-specific reference equations may contribute to health disparities via underestimation of the degree of lung function impairment in Black patients. The use of race-specific equations may differentially affect patients with severe respiratory disease via the use of percentage predicted forced vital capacity (FVCpp) when included in the lung allocation score (LAS), the primary determinant of priority for lung transplantation. Objectives: To determine the impact of a race-specific versus a race-neutral approach to spirometry interpretation on the LAS among adults listed for lung transplantation in the United States. Methods: We developed a cohort from the United Network for Organ Sharing database including all White and Black adults listed for lung transplantation between January 7, 2009, and February 18, 2015. The LAS at listing was calculated for each patient under race-specific and race-neutral approaches, using the FVCpp generated from the Global Lung Function Initiative equation corresponding to each patient's race (race-specific) or from the Global Lung Function Initiative "other" (race-neutral) equation. Differences in LAS between approaches were compared by race, with positive values indicating a higher LAS under the race-neutral approach. Results: In this cohort of 8,982 patients, 90.3% were White and 9.7% were Black. The mean FVCpp was 4.4% higher versus 3.8% lower among White versus Black patients (P < 0.001) under a race-neutral compared with a race-specific approach. Compared with White patients, Black patients had a higher mean LAS under both a race-specific (41.9 vs. 43.9; P < 0.001) and a race-neutral (41.3 vs. 44.3; P < 0.001) approach. However, the mean difference in LAS under a race-neutral approach was -0.6 versus +0.6 for White versus Black patients (P < 0.001). Differences in LAS under a race-neutral approach were most pronounced for those in group B (pulmonary vascular disease) (-0.71 vs. +0.70; P < 0.001) and group D (restrictive lung disease) (-0.78 vs. +0.68; P < 0.001). Conclusions: A race-specific approach to spirometry interpretation has potential to adversely affect the care of Black patients with advanced respiratory disease. Compared with a race-neutral approach, a race-specific approach resulted in lower LASs for Black patients and higher LASs for White patients, which may have contributed to racially biased allocation of lung transplantation. The future use of race-specific equations must be carefully considered.

Patterns of early life somatic growth in infants and children with a history of chronic lung disease of prematurity.

OBJECTIVE: Preterm infants, and especially those with additional comorbidities, are at risk of early life growth failure, which may impact postnatal lung growth and attainment of peak lung function. However, little is known about the early life growth patterns of those with chronic lung disease. The goal of this study was to describe the patterns appreciated in this population and their association with certain clinical characteristics. STUDY DESIGN: Demographic, clinical characteristics, and somatic growth parameters between birth and 3 years were retrospectively reviewed for a cohort of children (n = 616) recruited from an outpatient pulmonary clinic. Group-based trajectory modeling was used to identify unique longitudinal trajectories for each growth parameter. Demographic and clinical characteristics were compared using nonparametric analysis. RESULTS: Four distinct trajectories were appreciated in all three somatic growth domains (weight, length, and weight-for-length), which demonstrated a sizable proportion of subjects with a z-score below zero at 36 months of age, suggesting that the traditional preterm paradigm of "catch-up" growth may not be accurate for this population. CONCLUSIONS: Children with a history of chronic lung disease begin life with somatic growth measurements well below their term peers and display heterogeneous patterns of weight and length growth through the first 3 years of life. Future studies should focus on further understanding the relationship between somatic growth and respiratory outcomes in this population, which will ideally allow for the use of somatic growth measures as surrogate markers to identify individuals at the highest risk of postnatal growth failure and poor respiratory outcomes.

Early life growth trajectories in cystic fibrosis are associated with lung function at age six.

BACKGROUND: Higher growth percentiles are associated with more favorable lung function in cystic fibrosis (CF), prompting the creation of CF Foundation (CFF) nutritional guidelines. OBJECTIVES: To describe early childhood growth trajectories within CF, to determine if growth trajectories are associated with differences in lung function at age six, and to identify factors that differ between trajectory groups. METHODS: Retrospective cohort study of children diagnosed with CF and born 2000-2011 using the US CFF Patient Registry. Annualized growth parameters prior to age six were included in group-based trajectory modeling to identify unique early life growth trajectories. FEV1 percent predicted (FEV1pp) at age six was compared between trajectory groups using linear regression. Factors associated with group membership were identified using multinomial logistic regression. RESULTS: 6,809 children met inclusion criteria. Six discrete growth trajectories were identified, including three groups that began with growth parameters >50th percentile, termed: "always high", "gradual decliner", "rapid decliner", and three which began with growth parameters <50th percentile, termed: "rapid riser", "gradual riser", "always low". FEV1pp at age six was highest for the Always High trajectory. The Always Low trajectory was nearly 10% lower than the Always High trajectory. Sex, ethnicity, newborn screening and pancreatic function were associated with trajectory class membership. CONCLUSIONS: Distinct early life growth trajectories were identified within CF. Trajectories that met CFF nutritional guideline recommendations were associated with higher FEV1pp at age six. CF care teams should continue to partner with families to encourage interventions to support optimal growth to improve lung function in CF.

Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation.

STUDY OBJECTIVES: The major goal of the study was to determine whether changes in tongue morphology under selective hypoglossal nerve therapy for obstructive sleep apnea were associated with alterations in airway patency during sleep when specific portions of the hypoglossal nerve were stimulated. METHODS: This case series was conducted at the Johns Hopkins Sleep Disorders Center at Johns Hopkins Bayview Medical Center. Twelve patients with apnea implanted with a multichannel targeted hypoglossal nerve-stimulating system underwent midsagittal ultrasound tongue imaging during wakefulness. Changes in tongue shape were characterized by measuring the vertical height and polar dimensions between tongue surface and genioglossi origin in the mandible. Changes in patency were characterized by comparing airflow responses between stimulated and adjacent unstimulated breaths during non-rapid eye movement sleep. RESULTS: Two distinct morphologic responses were observed. Anterior tongue base and hyoid-bone movement (5.4 [0.4] to 4.1 [1.0] cm (median and [interquartile range]) with concomitant increases in tongue height (5.0 [0.9] to 5.6 [0.7] cm) were associated with decreases in airflow during stimulation. In contrast, comparable anterior hyoid movement (tongue protrusion from 5.8 [0.5] to 4.5 [0.9] cm) without significant increases in height (5.2 [1.6] to 4.6 [0.8] cm) were associated with marked increases in airflow during sleep. CONCLUSIONS: Tongue protrusion with preservation of tongue shape predicted increases in patency, whereas anterior movement with concomitant increases in height were associated with decreased pharyngeal patency. These findings suggest that pharyngeal patency can be best stabilized by stimulating lingual muscles that maintain tongue shape while protruding the tongue, thereby preventing it from prolapsing posteriorly during sleep. CITATION: Fleury Curado T, Pham L, Otvos T, et al. Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation. J Clin Sleep Med. 2023;19(5):947-955.

Post hoc survival analyses using RNAseq data: handle with care.

With the advent of next-generation sequencing technologies, there has been a dramatic increase in the availability of paired clinical and transcriptomic data in a variety of disease states. For basic science researchers, this has provided a valuable opportunity for querying the impact of the transcript levels of a gene on disease survival in humans. However, there are a multitude of methodological and technical considerations to evaluate before embarking on these analyses. Herein, we provide a brief description of statistical considerations involved in these analyses, geared toward basic scientists who may not necessarily routinely use such statistical models as part of their studies.

Association of School Infrastructure on Health and Achievement Among Children With Asthma.

OBJECTIVE: To determine whether school infrastructure is associated with health and academic outcomes among elementary school children with asthma. METHODS: We conducted a retrospective cohort study of linked medical, academic, and facilities data from a large mid-Atlantic school district of the United States. All K-5 students with asthma who were enrolled under the state's Children's Health Insurance Program were included. We estimated associations of the infrastructure quality of the student's school, as assessed by an engineering firm in Summer 2011 and represented by the Facility Condition Index (FCI), with asthma health outcomes, absenteeism, and standardized test scores in math and reading in the 2 academic years thereafter. RESULTS: A total of 6558 students were identified, the majority non-Hispanic Black, across 130 schools. Most schools (97/130, 75%) were in very poor or worse condition. In cluster-adjusted models accounting for demographics, grade, school-specific area deprivation, and inhaled corticosteroid use, a one standard deviation increase in FCI, corresponding to greater infrastructure deficiency, was associated with higher rates of asthma-related hospitalizations (incidence rate ratio [IRR] 1.16; 95% confidence interval [CI] 1.03, 1.32), more absenteeism (IRR 1.05; 95% CI 1.01, 1.08), and lower scores in math (mean difference [MD] -3.3; 95% CI -5.5, -1.2) and reading (MD -3.0; 95% CI -5.1, -0.9). There were no differences in rates of asthma-related emergency visits or steroid prescriptions. CONCLUSIONS: Children with asthma attending schools with poorer infrastructure had worse health and academic outcomes. Public policy emphasizing reinvestment in school infrastructure may be a potential means of addressing asthma disparities.

Clinician attitudes and practices on pregnancy planning and care in cystic fibrosis.

BACKGROUND: People with cystic fibrosis (CF) are living longer and healthier lives as a result of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, and are pursuing pregnancy. As the number of pregnancies in CF continue to increase, clinician attitudes and practices regarding care of pregnant people with CF remain largely unknown. OBJECTIVE: To evaluate the current attitudes and practices of CF clinicians regarding pregnancy planning and care in CF. METHODS: We conducted a national survey investigating practice patterns related to pregnancy care in CF. We used descriptive statistics to summarize responses and paired t-tests to compare population means. RESULTS: A total of 93 clinicians completed the survey. Eighty-six percent of respondents believed family planning and pregnancy discussions should start before the age of 21 years, of which 67% believed these discussions should occur prior to age 18 years. Our results demonstrate variability in CF clinician comfort and management of various aspects of pregnancy care in CF including 1) potential complications of pregnancy 2) continuation of chronic CF therapies 3) continuation of CFTR modulators during pregnancy and lactation, and 4) approach to treatment of pulmonary exacerbation during pregnancy. CONCLUSIONS: As more people with CF pursue pregnancy in the era of CFTR modulators, CF providers should be initiating discussions surrounding pregnancy early and often. Establishing best practices in the management of pregnancy in CF, expanding peri­pregnancy expertise within the CF community, and future studies investigating the maternal-fetal effects of CF therapies are needed.

Lower socioeconomic status is associated with delayed access to care for infantile hemangioma: A cohort study.

BACKGROUND: Early specialist evaluation during rapid proliferative growth of complicated infantile hemangiomas (IHs) is crucial. Health disparities and barriers of access to care for children with IHs have not been examined. OBJECTIVE: To investigate whether socioeconomic status (SES) is associated with age at presentation to a subspecialist for IH evaluation. METHOD: A retrospective cohort study of 804 children presenting to a large academic hospital. The primary outcome was age at initial presentation. Covariates included demographic, socioeconomic, geographic, and clinical characteristics. Medicaid and the Children's Health Insurance Program were proxies for lower SES. Analysis of covariance, chi-square tests, and generalized ordered logistic regressions were performed. RESULTS: Children with lower SES had higher odds of presenting after 3 months of age (odds ratio, 2.11; 95% confidence interval, 1.31-3.38). In the subset that qualified for the institutional care management program (ICMP), no risk factors were associated with delayed presentation. LIMITATIONS: Use of insurance and economic distress as proxies for SES; exclusion of uninsured children, which may have resulted in underestimation of racioethnic effects; and examination of a single academic center, which may limit generalizability. CONCLUSIONS: Children with IHs and lower SES were more likely to present later to specialists, but those enrolled in an ICMP were not, suggesting that integrated ICMPs may mitigate disparities and delayed access to care for IHs among lower-SES populations.

Heterogeneity of Lung Function Phenotypes in Sarcoidosis: Role of Race and Sex Differences.

Rationale: Historically, sarcoidosis was described as a restrictive lung disease, but several alternative phenotypes of pulmonary function have been observed. Pulmonary function phenotypes in sarcoidosis may represent different clinical and/or molecular phenotypes. Objectives: To characterize the prevalence of different pulmonary function phenotypes in a large and diverse sarcoidosis cohort from a tertiary care referral center. Methods: We identified individuals seen between 2005-2015 with a confirmed diagnosis of sarcoidosis. Data were collected from the first pulmonary function test (PFT) performed at our institution which included spirometry and diffusing capacity of the lung for carbon monoxide (DlCO). Demographics and clinical data were collected. Chi-squared analyses and multiple linear regressions were done to assess statistical differences and associations. Global Lung Function Initiative equations were used to calculate percent predicted measurements for spirometry and DlCO. Results: Of 602 individuals with sarcoidosis, 93% (562) had pulmonary involvement, 64% (385) were female, and 57% (341) were Black. Of those with pulmonary involvement, 56% had abnormal pulmonary function. Lung function impairment phenotypes included: 47% restriction, 22% obstruction, 15% isolated reduction in DlCO, and 16% combined obstructive restrictive phenotype. Restriction was the most common PFT phenotype among Black individuals (41%), while no lung impairment was most common among White individuals (66%) (P < 0.001). Males more frequently had obstruction (19%) compared with females (9%) P = 0.001, and females had more restriction (30%) compared with males (21%) P = 0.031. Conclusions: Among individuals with sarcoidosis and pulmonary function impairment, less than half demonstrated a restrictive phenotype. There were significant differences in pulmonary function phenotypes by race and sex.

Prevalence and Risk Factors for Low Bone Mineral Density in Adults With Cystic Fibrosis.

Single-center studies have suggested that up to 70% of adults with cystic fibrosis (CF) have lower than expected bone mineral density (BMD), substantially higher than the 25% prevalence reported from national registries. We determined the prevalence of low BMD in CF adults at our center and assessed risk factors for low BMD. This retrospective cohort study was conducted in all CF patients ≥18 years of age who had a dual-energy X-ray absorptiometry (DXA) scan performed at the Johns Hopkins Adult Cystic Fibrosis center between 2010 and 2018. Prevalence and incidence of low BMD during the study period were determined. Poisson regression based on generalized estimating equations and robust standard errors were used to evaluate selected risk factors and risk of disease progression. A total of 234 individuals underwent an initial DXA scan. At this scan, prevalence of low BMD was 52.6% (95% confidence interval [CI] 46.0-59.1). A total of 43.6% were at risk for CF-related low BMD (AR-CFLBMD) (95% CI 37.1-50.2) and 9.0% had CF-related low BMD (CFRLBMD) (95% CI 5.6-13.4). Of the 25 with normal BMD at initial scan and a subsequent follow-up scan, 8 (32.0%) progressed to AR-CFLBMD. Of the 53 with AR-CFLBMD on initial scan and a subsequent scan, 6 (11.3%) progressed to CFLBMD, 9 (17.0%) returned to normal BMD, and 38 (71.7%) remained AR-CFLBMD. Older age (relative risk [RR] = 1.01; 95% CI 1.00-1.01) and male sex (RR = 1.32; 95% CI 1.04-1.66) were associated with increased risk of low BMD, while higher forced expiratory volume over 1 second (FEV1%) predicted (RR = 0.99; 95% CI 0.99-1.00) and body mass index (BMI; RR = 0.97; 95% CI 0.94-1.00) were associated with lower risk for low BMD. The fact that more than half of all individuals were found to have lower than expected BMD suggests that the actual prevalence may be higher than currently reported in national registries. This supports the importance of universal bone health screening of all CF adults. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Clinical Features, Survival, and Burden of Toxicities in Survivors More Than One Year After Lung Cancer Immunotherapy.

INTRODUCTION: Anti-PD-(L)1 immune checkpoint inhibitors (ICI) improve survival in patients with advanced non-small cell lung cancer (aNSCLC). The clinical features, survival, and burden of toxicities of patients with aNSCLC alive >1 year from ICI initiation are poorly understood. MATERIALS AND METHODS: We defined ICI survivors as patients alive >1 year after ICI start and retrospectively reviewed demographics, treatment, and immune-related adverse events (irAEs). Long-term irAEs were defined as ongoing irAEs lasting >1 year; burden of toxicity measures were based on percentage of days a patient experienced toxicity. Using linear and logistic regression, we evaluated association between demographics and disease characteristics with burden of toxicity. RESULTS: We identified 114 ICI survivors from 317 patients with aNSCLC. Half (52%) experienced an irAE of any grade, and 23.7% developed long-term irAEs. More ICI survivors with irAES in the first year had never smoked (P = .018) or received ICIs as frontline therapy (P = .015). The burden of toxicity in the first year significantly correlated with the burden of toxicity afterward (ρ = 0.72; P < .001). No patients with progressive disease had a high burden of toxicity, and they experienced 30.6% fewer days with toxicity than those with stable disease. Increased duration of therapy was associated with higher odds of experiencing toxicity. Half of ICI survivors with irAEs were still receiving treatment for unresolved irAEs at time of death or last follow-up. CONCLUSION: Significant proportions of ICI survivors have unresolved long-term toxicities. These data support a growing need to understand long-term toxicity to optimize management of those treated with ICIs.

Comparing Prone Positioning Use in COVID-19 Versus Historic Acute Respiratory Distress Syndrome.

Use of prone positioning in patients with acute respiratory distress syndrome (ARDS) from COVID-19 may be greater than in patients treated for ARDS before the pandemic. However, the magnitude of this increase, sources of practice variation, and the extent to which use adheres to guidelines is unknown. OBJECTIVES: To compare prone positioning practices in patients with COVID-19 ARDS versus ARDS treated before the pandemic. DESIGN SETTING AND PARTICIPANTS: We conducted a multicenter retrospective cohort study of mechanically ventilated patients with early moderate-to-severe ARDS from COVID-19 (2020-2021) or ARDS from non-COVID-19 pneumonia (2018-2019) across 19 ICUs at five hospitals in Maryland. MAIN OUTCOMES AND MEASURES: The primary outcome was initiation of prolonged prone positioning (≥ 16 hr) within 48 hours of meeting oxygenation criteria. Comparisons were made between cohorts and within subgroups including academic versus community hospitals, and medical versus nonmedical ICUs. Other outcomes of interest included time to proning initiation, duration of prone sessions and temporal trends in proning frequency. RESULTS: Proning was initiated within 48 hours in 227 of 389 patients (58.4%) with COVID-19 and 11 of 123 patients (8.9%) with historic ARDS (49.4% absolute increase [95% CI for % increase, 41.7-57.1%]). Comparing COVID-19 to historic ARDS, increases in proning were similar in academic and community settings but were larger in medical versus nonmedical ICUs. Proning was initiated earlier in COVID-19 versus historic ARDS (median hours (hr) from oxygenation criteria, 12.9 vs 30.6; p = 0.002) and proning sessions were longer (median hr, 43.0 vs 28.0; p = 0.01). Proning frequency increased rapidly at the beginning of the pandemic and was sustained. CONCLUSIONS AND RELEVANCE: We observed greater overall use of prone positioning, along with shorter time to initiation and longer proning sessions in ARDS from COVID-19 versus historic ARDS. This rapid practice change can serve as a model for implementing evidence-based practices in critical care.

A Pilot Study of Patient Photographs and Handoff Communication.

BACKGROUND AND OBJECTIVES: Safe and effective handoffs have become a national priority. Given that patient photographs have been associated with safety benefits in other settings, we hypothesize they could improve handoff communication. Our objective was to determine whether patient photographs used during simulated handoffs improves information retention, response to clinical scenarios, and familiarity with patients, compared with simulated handoffs without photographs. METHODS: We conducted a pilot mixed-methods study using simulated handoff sessions with pediatric residents. One investigator simulated 2 verbal handoff sessions with participants randomized to receive stock patient photographs in either the first or second session. Participants answered an online questionnaire after each session to assess information recall and familiarity with patients. Primary outcomes included percent correct responses and response time. Participants were interviewed to assess the benefits and challenges of using photographs in handoffs. RESULTS: Forty pediatric residents participated. Correct responses and response time did not differ significantly between sessions. Participants indicated less confusion and more comfort caring for patients after photograph handoff sessions. All participants identified benefits to using patient photographs and 75% identified challenges. Benefits included assisting memory, enhancing connection with patients, and improving patient safety. Challenges included visual distraction, bias concerns, and patient privacy. CONCLUSIONS: In this pilot study, patient photographs did not result in improved information retention or efficiency of response to clinical scenarios but were associated with perceptions of reduced confusion and enhanced comfort. Participants identified benefits and challenges of incorporating photographs in handoffs that could inform use in real-world settings.