Uncertainty of stochastic parametric approach to bone marrow dosimetry of 89,90Sr.

The objective of this study is to evaluate the uncertainties of the dosimetric modeling of active marrow (AM) exposure from bone-seeking 89,90Sr. The stochastic parametric skeletal dosimetry (SPSD) model was specifically developed to study the long-term effects resulting from chronic 89,90Sr exposure in populations of the radioactively contaminated territories of the Southern Urals region of the Russian Federation. The method permits the evaluation of the dose factors (DF(AM ← TBV) and DF(AM ← CBV)), which convert the radionuclide activity concentration in trabecular (TBV) and cortical (CBV) bone volumes into dose rate in the AM, and their uncertainties. The sources of uncertainty can be subdivided into inherent uncertainties related to the individual variability of the simulated objects and introduced uncertainties related to model simplifications. Inherent uncertainty components are the individual variability of bone chemical composition, bone density, bone micro- and macro-architecture as well as AM distribution within the skeleton. The introduced uncertainties may result from the stylization of bone segment geometry, assumption of uniform cortical thickness, restriction of bone geometry and the selection of the applied voxel resolution. The inherent uncertainty depends on a number of factors of influence. Foremost, it is the result of variability of AM distribution within the skeleton. Another important factor is the variability of bone micro- and macro-architecture. The inherent uncertainty of skeletal-average dose factors was found to be about 40-50%. The introduced uncertainty associated with the SPSD model approach does not exceed 16% and mainly depends on the error of bone-shape stylization. The overall inherent and introduced uncertainties of DF(AM ← TBV) and DF(AM ← CBV) are below 55% and 63%, respectively. The results obtained will be incorporated into the stochastic version of the Techa River Dosimetry System (TRDS-2016MC) that provides multiple realizations of the annual doses for each cohort member to obtain both a central estimate of the individual dose and information on the dose uncertainty.

Cannabis Use Differences Among Sexual Minority Versus Heterosexual Females and Males in Oklahoma: The Roles of Mental Health, Cannabis Perceptions, and Cannabis Marketing Exposure.

INTRODUCTION: Despite the high cannabis use rates among sexual minority (SM) individuals, less research has examined factors related to cannabis use among SM (vs. heterosexual) individuals, especially in places with legal medical cannabis retail markets and high structural stigma, like Oklahoma. METHODS: Data were from a survey of Oklahoma adults, including 3020 females (18.6% SM) and 2279 males (10.1% SM). Bivariate analyses examined associations of sexual identity with cannabis-related factors (i.e., perceived harm, positive attitudes, marketing exposure, depressive symptoms, anxiety symptoms) and cannabis use and use severity (i.e., past 30-day use, daily/near-daily use, cannabis use disorder [CUD] symptoms). Logistic regression examined associations of sexual identity and cannabis-related factors with cannabis use and use severity among females and males, separately. RESULTS: SM (vs. heterosexual) females reported greater odds of past 30-day cannabis use and daily/near-daily use, lower harm perceptions, greater marketing exposure, and higher rates of depressive/anxiety symptoms. Lower harm perceptions and greater marketing exposure were associated with greater odds of past 30-day use, whereas marketing exposure was associated with greater odds of daily/near-daily use. SM (vs. heterosexual) males reported greater odds of daily/near-daily use and higher rates of depressive/anxiety symptoms. CONCLUSIONS: SM (vs. heterosexual) females reported higher rates of cannabis use, whereas SM (vs. heterosexual) females and males reported higher rates of daily/near-daily cannabis use. Potential targets for cannabis-related health campaigns aimed at reducing use differences include correcting misinterpretations of harm that may emanate from cannabis marketing efforts among females and addressing depressive symptoms among males.

Perioperative implications of amyloidosis and amyloid cardiomyopathy: A review for anesthesiologists.

It is well recognized that amyloid protein can infiltrate many regions of the body. This can include the peripheral nerves, the liver, kidney, spleen, the gastrointestinal tract, and most importantly the myocardium. The amyloid proteins that cause cardiomyopathy may come from genetically altered liver genes (transthyretin amyloid, ATTR) or from the bone marrow with malignant plasma cells (light chain amyloid, AL) generating the aberrant protein. These two types of amyloidosis cause significant damaging effects on both the myocardial cells as well as the conduction system of the heart. The resultant changes can produce dyspnea and exercise intolerance which is thought to be secondary to diastolic dysfunction and reduced stroke volume. This subclinical decompensation poses a significant problem for members of a care team as it often goes unrecognized. In the operating room patients are exposed to dramatic hemodynamic changes and may have difficult airways, autonomic dysfunction, and conduction abnormalities. Although the topic of amyloidosis is well described in cardiology literature, it is underdiagnosed. The purpose of this review is to describe some of the pathophysiology behind the principle proteins that cause cardiac amyloidosis and to comprehensively describe perioperative considerations for anesthesia providers.

Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of FCGR3A polymorphism.

Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B-cells, is approved to treat aquaporin 4 (AQP4) IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III-A (FCGR3A) receptors on natural killer cells to maximize antibody-dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG-binding affinity and reduce rituximab (anti-CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab-treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.

Immune responses of lung transplant recipients against SARS-CoV-2 and common respiratory coronaviruses: Evidence for pre-existing cross-reactive immunity.

Humoral and cellular immune responses to SARS-CoV-2 and other coronaviruses in lung transplant recipients are unknown. We measured antibodies and T cell responses against the SARS-CoV-2 spike S2 and nucleocapsid antigens and spike antigens from common respiratory coronaviruses (229E, NL63, OC43, and HKU1) after vaccination or infection of LTxRs. 148 LTxRs from single center were included in this study: 98 after vaccination and 50 following SARS-CoV-2 infection. Antibodies were quantified by enzyme-linked immunosorbent assay. The frequency of T cells secreting IL2, IL4, IL10, IL17, TNFα, and IFNγ were enumerated by enzyme-linked immunospot assay. Our results have shown the development of antibodies to SARS-CoV-2 spike protein in infected LTxRs (39/50) and vaccinated LTxRs (52/98). Vaccinated LTxRs had higher number of T cells producing TNFα but less cells producing IFNγ than infected LTxRs in response to the nucleocapsid antigen and other coronavirus spike antigens. We didn't find correlation between the development of antibodies and cellular immune responses against the SARS-CoV-2 spike protein after vaccination. Instead, LTxRs have pre-existing cellular immunity to common respiratory coronaviruses, leading to cross-reactive immunity against SARS-CoV-2 which likely will provide protection against SARS-Cov-2 infection.

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.

Association of plasma volume status with outcomes in hospitalized Covid-19 ARDS patients: A retrospective multicenter observational study.

PURPOSE: To evaluate the association of estimated plasma volume (ePV) and plasma volume status (PVS) on admission with the outcomes in COVID-19-related acute respiratory distress syndrome (ARDS) patients. MATERIALS AND METHODS: We performed a retrospective multi-center study on COVID-19-related ARDS patients who were admitted to the Mayo Clinic Enterprise health system. Plasma volume was calculated using the formulae for ePV and PVS, and these variables were analyzed for correlation with patient outcomes. RESULTS: Our analysis included 1298 patients with sequential organ failure assessment (SOFA) respiratory score ≥ 2 (PaO2/FIO2 ≤300 mmHg) and a mortality rate of 25.96%. A Cox proportional multivariate analysis showed PVS but not ePV as an independent correlation with 90-day mortality after adjusting for the covariates (HR: 1.015, 95% CI: 1.005-1.025, p = 0.002 and HR 1.054, 95% CI 0.958-1.159, p = 0.278 respectively). CONCLUSION: A lower PVS on admission correlated with a greater chance of survival in COVID-19-related ARDS patients. The role of PVS in guiding fluid management should be investigated in future prospective studies.

Pharmacologic Management of Cancer-Related Pain in Pregnant Patients.

Despite being an essential part of whole-person care, patients with cancer often experience complex and under-treated pain. Managing cancer-related pain in patients who are also pregnant compounds the challenge for adequate pain management, as studies have largely excluded this population. Therapy for pain management should be guided by the cause and mechanism of pain. The objective of this review is to provide clinicians with an understanding of pain experienced by pregnant patients with cancer and medications that may be used to help manage cancer-related pain. Nociceptive pain results from damage to somatic or visceral tissues that may be directly caused by cancer. This type of pain can be managed in pregnant patients using acetaminophen and/or nonsteroidal antiinflammatory drugs as first-line agents. In nociceptive pain not managed by non-opioid analgesics, buprenorphine is recommended for those requiring chronic opioids to help manage their pain. Neuropathic pain that results from damage to the peripheral or central nervous system may also be directly caused by cancer, particularly chemotherapy. In pregnant patients, duloxetine and gabapentin should be considered first. Venlafaxine, pregabalin, tricyclic antidepressants, and sodium channel blockers should be avoided, if possible. Nociplastic pain is not directly caused by cancer but may be caused by ongoing peripheral nociceptive input or a condition that predates the cancer diagnosis. Duloxetine and gabapentin are reasonable agents to consider for treatment of nociceptive pain in pregnant patients. Cyclobenzaprine may also be helpful for nociplastic pain.

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.

Shared and Distinctive Transcriptomic and Proteomic Pathways in Adult and Juvenile Dermatomyositis.

OBJECTIVE: Transcript and protein expression were interrogated to examine gene locus and pathway regulation in the peripheral blood of active adult dermatomyositis (DM) and juvenile DM patients receiving immunosuppressive therapies. METHODS: Expression data from 14 DM and 12 juvenile DM patients were compared to matched healthy controls. Regulatory effects at the transcript and protein level were analyzed by multi-enrichment analysis for assessment of affected pathways within DM and juvenile DM. RESULTS: Expression of 1,124 gene loci were significantly altered at the transcript or protein levels across DM or juvenile DM, with 70 genes shared. A subset of interferon-stimulated genes was elevated, including CXCL10, ISG15, OAS1, CLEC4A, and STAT1. Innate immune markers specific to neutrophil granules and neutrophil extracellular traps were up-regulated in both DM and juvenile DM, including BPI, CTSG, ELANE, LTF, MPO, and MMP8. Pathway analysis revealed up-regulation of PI3K/AKT, ERK, and p38 MAPK signaling, whose central components were broadly up-regulated in DM, while peripheral upstream and downstream components were differentially regulated in both DM and juvenile DM. Up-regulated components shared by DM and juvenile DM included cytokine:receptor pairs LGALS9:HAVCR2, LTF/NAMPT/S100A8/HSPA1A:TLR4, CSF2:CSF2RA, EPO:EPOR, FGF2/FGF8:FGFR, several Bcl-2 components, and numerous glycolytic enzymes. Pathways unique to DM included sirtuin signaling, aryl hydrocarbon receptor signaling, protein ubiquitination, and granzyme B signaling. CONCLUSION: The combination of proteomics and transcript expression by multi-enrichment analysis broadened the identification of up- and down-regulated pathways among active DM and juvenile DM patients. These pathways, particularly those which feed into PI3K/AKT and MAPK signaling and neutrophil degranulation, may be potential therapeutic targets.

Cytosolic EpCAM cooperates with H-Ras to regulate epithelial to mesenchymal transition through ZEB1.

Next generation sequencing of human cancer mutations has identified novel therapeutic targets. Activating Ras oncogene mutations play a central role in oncogenesis, and Ras-driven tumorigenesis upregulates an array of genes and signaling cascades that can transform normal cells into tumor cells. In this study, we investigated the role of altered localization of epithelial cell adhesion molecule (EpCAM) in Ras-expressing cells. Analysis of microarray data demonstrated that Ras expression induced EpCAM expression in normal breast epithelial cells. Fluorescent and confocal microscopy showed that H-Ras mediated transformation also promoted epithelial-to-mesenchymal transition (EMT) together with EpCAM. To consistently localize EpCAM in the cytosol, we generated a cancer-associated EpCAM mutant (EpCAM-L240A) that is retained in the cytosol compartment. Normal MCF-10A cells were transduced with H-Ras together with EpCAM wild-type (WT) or EpCAM-L240A. WT-EpCAM marginally effected invasion, proliferation, and soft agar growth. EpCAM-L240A, however, markedly altered cells and transformed to mesenchymal phenotype. Ras-EpCAM-L240A expression also promoted expression of EMT factors FRA1, ZEB1 with inflammatory cytokines IL-6, IL-8, and IL1. This altered morphology was reversed using MEK-specific inhibitors and to some extent JNK inhibition. Furthermore, these transformed cells were sensitized to apoptosis using paclitaxel and quercetin, but not other therapies. For the first time, we have demonstrated that EpCAM mutations can cooperate with H-Ras and promote EMT. Collectively, our results highlight future therapeutic opportunities in EpCAM and Ras mutated cancers.

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.

Loss of IGFBP2 mediates alveolar type 2 cell senescence and promotes lung fibrosis.

Accumulation of senescent cells contributes to age-related diseases including idiopathic pulmonary fibrosis (IPF). Insulin-like growth factor binding proteins (IGFBPs) regulate many biological processes; however, the functional contributions of IGFBP2 in lung fibrosis remain largely unclear. Here, we report that intranasal delivery of recombinant IGFBP2 protects aged mice from weight loss and demonstrated antifibrotic effects after bleomycin lung injury. Notably, aged human-Igfbp2 transgenic mice reveal reduced senescence and senescent-associated secretory phenotype factors in alveolar epithelial type 2 (AEC2) cells and they ameliorated bleomycin-induced lung fibrosis. Finally, we demonstrate that IGFBP2 expression is significantly suppressed in AEC2 cells isolated from fibrotic lung regions of patients with IPF and/or pulmonary hypertension compared with patients with hypersensitivity pneumonitis and/or chronic obstructive pulmonary disease. Altogether, our study provides insights into how IGFBP2 regulates AEC2-cell-specific senescence and that restoring IGFBP2 levels in fibrotic lungs can prove effective for patients with IPF.

Antireflux surgery versus medical management of gastro-oesophageal reflux after lung transplantation.

OBJECTIVES: Gastro-oesophageal reflux disease after lung transplantation may be associated with chronic lung allograft dysfunction. Aspiration may continue on medical management of reflux, but antireflux surgery potentially reduces all reflux. We compared outcomes between medical and surgical management of reflux in lung recipients. METHODS: Lung recipients with an elevated DeMeester score (≥14.72) on post-transplant reflux testing between 2015 and 2020 were included. Patients were divided into 2 groups: group A (underwent surgery) and group B (medically managed). Endpoints were pulmonary function, allograft dysfunction-free survival and overall survival. Further analysis included subgroups: A1 (early surgery, <6 months) and A2 (late surgery, >6 months), and B1 (DeMeester <29.9) and B2 (DeMeester ≥30). RESULTS: A total of 186 included subjects were divided into groups A [n = 46 (A1, n = 36; A2, n = 10)] and B [n = 140 (B1, n = 78; B2, n = 62)]. Compared to medically managed patients, patients who underwent surgery had a higher prevalence of hiatal hernia (P < 0.001) and a lower prevalence of oesophageal motility disorders (P = 0.036). Recipients who underwent surgery had superior pulmonary function at 5 years compared to group B (P < 0.05) and longer allograft dysfunction-free survival than subgroup B2 (P = 0.028). Furthermore, early surgery was associated with longer survival than late surgery (P = 0.021). CONCLUSIONS: Antireflux surgery in recipients with reflux improved long-term allograft function, and early surgery showed a survival benefit. Allograft dysfunction-free survival of lung recipients who underwent surgery was significantly better than that of medically managed patients with DeMeester ≥30. We present an algorithm for appropriate selection of candidates for antireflux surgery after lung transplantation.

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.

Sociodemographic factors associated with tracheostomy and mortality in bronchopulmonary dysplasia.

OBJECTIVES: We sought to investigate how race, ethnicity, and socioeconomic status relate to tracheostomy insertion and post-tracheostomy mortality among infants with bronchopulmonary dysplasia (BPD). METHODS: The Vizient Clinical Database/Resource Manager was queried to identify infants born ≤32 weeks with BPD admitted to US hospitals from January 2012 to December 2020. Markers of socioeconomic status were linked to patient records from the Agency for Healthcare Research and Quality's Social Determinants of Health Database. Regression models were used to assess trends in annual tracheostomy insertion rate and odds of tracheostomy insertion and post-tracheostomy mortality, adjusting for sociodemographic and clinical factors. RESULTS: There were 40,021 ex-premature infants included in the study, 1614 (4.0%) of whom received a tracheostomy. Tracheostomy insertion increased from 2012 to 2017 (3.1%-4.1%), but decreased from 2018 to 2020 (3.3%-1.6%). Non-Hispanic Black infants demonstrated a 25% higher odds (aOR 1.25, 1.09-1.43) and Hispanic infants demonstrated a 20% lower odds (aOR 0.80, 0.65-0.96) of tracheostomy insertion compared with non-Hispanic White infants. Patients receiving public insurance had increased odds of tracheostomy insertion (aOR 1.15, 1.03-1.30), but there was no relation between other metrics of socioeconomic status and tracheostomy insertion within our cohort. In-hospital mortality among the tracheostomy-dependent was 14.1% and was not associated with sociodemographic factors. CONCLUSIONS: Disparities in tracheostomy insertion are not accounted for by differences in socioeconomic status or the presence of additional neonatal morbidities. Post-tracheostomy mortality does not demonstrate the same relationships. Further investigation is needed to explore the source and potential mitigators of the identified disparities.

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.

Hospitalized patients with irreversible lung injury from COVID-19 have higher morbidity but similar 1-year survival after lung transplant compared to hospitalized patients transplanted for restrictive lung disease.

BACKGROUND: Hospitalized lung transplant (LT) recipients (LTRs) have higher post-LT morbidity and mortality than those who are well enough to wait for transplant at home. Outcomes after LT for COVID-19-associated acute respiratory distress syndrome (CARDS) may be even worse; thus, we compared post-LT outcomes between hospitalized LTRs transplanted for CARDS and those transplanted for restrictive lung disease (RLD). METHODS: Between 2014 and 2021, hospitalized LTRs ≥18 years old with CARDS or RLD were included. Primary and secondary outcomes were 1-year post-LT survival and postoperative morbidity. For each patient in the CARDS group, an analysis of 1-to-1 matched patients from the RLD group was performed using logistic regression modeling. RESULTS: Of 764 LTRs, 163 (21.3%) were hospitalized at the time of LT; 132 met the inclusion criteria: 11 (8.3%) were transplanted for CARDS and 121 (91.7%) for RLD. LTRs with CARDS were younger with longer pre-LT hospitalization stays and higher rates of pretransplant mechanical ventilation, dialysis, and ECMO as a bridge to transplant. A propensity-matched analysis demonstrated comparable rates of intrathoracic adhesions, posttransplant duration of mechanical ventilation, PGD3 at 72 hours, and delayed chest closure. Compared to LTRs with RLD, those with CARDS had significantly longer posttransplant hospital stays and a higher prevalence of ACR ≥A2 and DSA >2000 MFI, but comparable 1-year survival rates. CONCLUSION: Even with careful selection, LT for patients with CARDS was associated with significant morbidity; however, 1-year survival of recipients with CARDS was comparable to that of matched hospitalized recipients with RLD.