Financial Toxicity Among Patients With Metastatic Prostate Cancer: A Mixed Methods Approach to Identify Effective Interventions.

INTRODUCTION: Financial toxicity associated with treatments for metastatic prostate cancer remains poorly defined. We sought to understand aspects of financial toxicity not captured in a commonly employed financial toxicity questionnaire and identify potential interventions to help alleviate financial toxicity through a convergent mixed methods approach. METHODS: Patients seen at our institution's advanced prostate cancer clinic were approached for completion of the Comprehensive Score for Financial Toxicity (COST-FACIT) questionnaire (quantitative analysis). A maximal variation purposive sample was chosen to participate in focus group discussions (qualitative analysis). Conventional content analysis was performed using an inductive approach. COST-FACIT scores were compared between patients experiencing high and low financial toxicity using Wilcoxon rank sum test. RESULTS: Three themes were identified through qualitative analysis: (1) workload, (2) coping strategies, and (3) communication. We found alignment with the existing theory of financial capacity across our findings. Two unique aspects of financial toxicity emerged that were not assessed quantitatively and deemed to be significant. Specifically, cost transparency (including health care teams knowledgeable about and willing to discuss costs) and inclusion of informal caregivers in financial toxicity screening and decision-making may guide future interventions aimed at limiting financial toxicity in this population. CONCLUSIONS: Prolonged treatment courses involving multiple lines of treatment with varying costs result in distinct financial toxicity components for patients with metastatic prostate cancer that are not assessed with COST-FACIT. Improving cost transparency, health care team knowledge and engagement, and providing resources to support informal caregivers may have a significant impact on the financial toxicity experienced by these patients.

Preoperative Anemia and Postoperative Outcomes in Cardiac Surgery: A Mediation Analysis Evaluating Intraoperative Transfusion Exposures.

BACKGROUND: Preoperative anemia is associated with adverse outcomes in cardiac surgery, yet it remains unclear what proportion of this association is mediated through red blood cell (RBC) transfusions. METHODS: This is a historical observational cohort study of adults undergoing coronary artery bypass grafting or valve surgery on cardiopulmonary bypass at an academic medical center between May 1, 2008, and May 1, 2018. A mediation analysis framework was used to evaluate the associations between preoperative anemia and postoperative outcomes, including a primary outcome of acute kidney injury (AKI). Intraoperative RBC transfusions were evaluated as mediators of preoperative anemia and outcome relationships. The estimated total effect, average direct effect of preoperative anemia, and percent of the total effect mediated through transfusions are presented with 95% confidence intervals and P -values. RESULTS: A total of 4117 patients were included, including 1234 (30%) with preoperative anemia. Overall, 437 of 4117 (11%) patients went on to develop AKI, with a greater proportion of patients having preoperative anemia (219 of 1234 [18%] vs 218 of 2883 [8%]). In multivariable analyses, the presence of preoperative anemia was associated with increased postoperative AKI (6.4% [4.2%-8.7%] absolute difference in percent with AKI, P < .001), with incremental decreases in preoperative hemoglobin concentrations displaying greater AKI risk (eg, 11.9% [6.9%-17.5%] absolute increase in probability of AKI for preoperative hemoglobin of 9 g/dL compared to a reference of 14 g/dL, P < .001). The association between preoperative anemia and postoperative AKI was primarily due to direct effects of preoperative anemia (5.9% [3.6%-8.3%] absolute difference, P < .001) rather than mediated through intraoperative RBC transfusions (7.5% [-4.3% to 21.1%] of the total effect mediated by transfusions, P = .220). Preoperative anemia was also associated with longer hospital durations (1.07 [1.05-1.10] ratio of geometric mean length of stay, P < .001). Of this total effect, 38% (22%, 62%; P < .001) was estimated to be mediated through subsequent intraoperative RBC transfusion. Preoperative anemia was not associated with reoperation or vascular complications. CONCLUSIONS: Preoperative anemia was associated with higher odds of AKI and longer hospitalizations in cardiac surgery. The attributable effects of anemia and transfusion on postoperative complications are likely to differ across outcomes. Future studies are necessary to further evaluate mechanisms of anemia-associated postoperative organ injury and treatment strategies.

Lung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study.

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870-0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828-0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.

Long-Term Outcomes and Risk of Pancreatic Cancer in Intraductal Papillary Mucinous Neoplasms.

Importance: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can give rise to pancreatic cancer (PC). Limited population data exist on their prevalence, natural history, or risk of malignant transformation (IPMN-PC). Objective: To fill knowledge gaps in epidemiology of IPMNs and associated PC risk by estimating population prevalence of IPMNs, associated PC risk, and proportion of IPMN-PC. Design, Setting, and Participants: : This retrospective cohort study was conducted in Olmsted County, Minnesota. Using the Rochester Epidemiology Project (REP), patients aged 50 years and older with abdominal computed tomography (CT) scans between 2000 and 2015 were randomly selected (CT cohort). All patients from the REP with PC between 2000 and 2019 were also selected (PC cohort). Data were analyzed from November 2021 through August 2023. Main outcomes and Measures: CIs for PC incidence estimates were calculated using exact methods with the Poisson distribution. Cox models were used to estimate age, sex, and stage-adjusted hazard ratios for time-to-event end points. Results: The CT cohort included 2114 patients (1140 females [53.9%]; mean [SD] age, 68.6 [12.1] years). IPMNs were identified in 231 patients (10.9%; 95% CI, 9.7%-12.3%), most of which were branch duct (210 branch-duct [90.9%], 16 main-duct [6.9%], and 5 mixed [2.2%] IPMNs). There were 5 Fukuoka high-risk (F-HR) IPMNs (2.2%), 39 worrisome (F-W) IPMNs (16.9%), and 187 negative (F-N) IPMNs (81.0%). After a median (IQR) follow-up of 12.0 (8.1-15.3) years, 4 patients developed PC (2 patients in F-HR and 2 patients in F-N groups). The PC incidence rate per 100 person years for F-HR IPMNs was 34.06 incidents (95% CI, 4.12-123.02 incidents) and not significantly different for patients with F-N IPMNs compared with patients without IPMNs (0.16 patients; 95% CI, 0.02-0.57 patients vs 0.11 patients; 95% CI, 0.06-0.17 patients; P = .62). The PC cohort included 320 patients (155 females [48.4%]; mean [SD] age, 72.0 [12.3] years), and 9.8% (95% CI, 7.0%-13.7%) had IPMN-PC. Compared with 284 patients with non-IPMN PC, 31 patients with IPMN-PC were older (mean [SD] age, 76.9 [9.2] vs 71.3 [12.5] years; P = .02) and more likely to undergo surgical resection (14 patients [45.2%] vs 60 patients [21.1%]; P = .003) and more-frequently had nonmetastatic PC at diagnosis (20 patients [64.5%] vs 130 patients [46.8%]; P = .047). Patients with IPMN-PC had better survival (adjusted hazard ratio, 0.62; 95% CI, 0.40-0.94; P = .03) than patients with non-IPMN PC. Conclusions and Relevance: In this study, CTs identified IPMNs in approximately 10% of patients aged 50 years or older. PC risk in patients with F-N IPMNs was low and not different compared with patients without IPMNs; approximately 10% of patients with PC had IPMN-PC, and they had better survival compared with patients with non-IPMN PC.

Sex-specific associations between daytime sleepiness, chronic diseases and mortality in obstructive sleep apnea.

Objective: Excessive daytime sleepiness (EDS) is common in obstructive sleep apnea (OSA) and has been linked to adverse outcomes, albeit inconsistently. Furthermore, whether the prognostic impact of EDS differs as a function of sex is unclear. We aimed to assess the associations between EDS and chronic diseases and mortality in men and women with OSA. Methods: Newly-diagnosed adult OSA patients who underwent sleep evaluation at Mayo Clinic between November 2009 and April 2017 and completed the Epworth Sleepiness Scale (ESS) for assessment of perceived sleepiness (N = 14,823) were included. Multivariable-adjusted regression models were used to investigate the relationships between sleepiness, with ESS modeled as a binary (ESS > 10) and as a continuous variable, and chronic diseases and all-cause mortality. Results: In cross-sectional analysis, ESS > 10 was independently associated with lower risk of hypertension in male OSA patients (odds ratio [OR], 95% confidence interval [CI]: 0.76, 0.69-0.83) and with higher risk of diabetes mellitus in both OSA men (OR, 1.17, 95% CI 1.05-1.31) and women (OR 1.26, 95% CI 1.10-1.45). Sex-specific curvilinear relations between ESS score and depression and cancer were noted. After a median 6.2 (4.5-8.1) years of follow-up, the hazard ratio for all-cause death in OSA women with ESS > 10 compared to those with ESS ≤ 10 was 1.24 (95% CI 1.05-1.47), after adjusting for demographics, sleep characteristics and comorbidities at baseline. In men, sleepiness was not associated with mortality. Conclusion: The implications of EDS for morbidity and mortality risk in OSA are sex-dependent, with hypersomnolence being independently associated with greater vulnerability to premature death only in female patients. Efforts to mitigate mortality risk and restore daytime vigilance in women with OSA should be prioritized.

Coping Mechanisms for Financial Toxicity Among Patients With Metastatic Prostate Cancer: A Survey-based Assessment.

PURPOSE: Assessments of financial toxicity among patients with metastatic prostate cancer are lacking. Using patient surveys, we sought to identify coping mechanisms and assess characteristics associated with lower financial toxicity. MATERIALS AND METHODS: Surveys were administered to all patients seen at a single center's Advanced Prostate Cancer Clinic over a 3-month period. Surveys included the COST-FACIT (COmprehensive Score for Financial Toxicity) and coping mechanism questionnaires. Patients with metastatic disease (lymph nodes, bone, visceral) were included for analysis. Coping mechanisms were compared between patients experiencing low (COST-FACIT >24) vs high (COST-FACIT ≤24) financial toxicity using Fisher's exact test. Multivariable linear regression was used to evaluate characteristics associated with lower financial toxicity. RESULTS: Overall, 281 patients met inclusion criteria of which 79 reported high financial toxicity. In multivariable analysis, characteristics associated with lower financial toxicity included older age (estimate: 0.36, 95%CI: 0.21-0.52), applying for patient assistance programs (estimate: 4.42, 95%CI: 1.72-7.11), and an annual income of at least $100,000 (estimate: 7.81, 95%CI: 0.97, 14.66). Patients with high financial toxicity were more likely to decrease spending on basic goods (35% vs 2.5%, P < .001) and leisure activities (59% vs 15%, P > .001), as well as use savings (62% vs 17%, P < .001) to pay for their treatment. CONCLUSIONS: In this cross-sectional study, patients with metastatic prostate cancer and high financial toxicity were more likely to decrease spending on basic goods and leisure activities and use savings to pay for care. Understanding the impact of financial toxicity on patients' lives is crucial to inform shared decision-making and interventions designed to mitigate financial toxicity in this population.

Effect of Preoperative Multiparametric Magnetic Resonance Imaging on Oncologic and Functional Outcomes Following Radical Prostatectomy.

Background: Advancements in imaging technology have been associated with changes to operative planning in treatment of localized prostate cancer. The impact of these changes on postoperative outcomes is understudied. Objective: To compare oncologic and functional outcomes between men who had computed tomography (CT) and those who had multiparametric magnetic resonance imaging (mpMRI) prior to undergoing radical prostatectomy. Design setting and participants: In this retrospective cohort study, we identified all men who underwent radical prostatectomy (n = 1259) for localized prostate cancer at our institution between 2009 and 2016. Of these, 917 underwent preoperative CT and 342 mpMRI. Outcome measurements and statistical analysis: Biochemical recurrence-free survival, positive margin status, postoperative complications, and 1-yr postprostatectomy functional scores (using the 26-item Expanded Prostate Cancer Index Composite [EPIC-26] questionnaire) were compared between those who underwent preoperative CT and those who underwent mpMRI using propensity score weighted Cox proportional hazard regression, logistic regression, and linear regression models. Results and limitations: Baseline and 1-yr follow-up EPIC-26 data were available for 449 (36%) and 685 (54%) patients, respectively. After propensity score weighting, no differences in EPIC-26 functional domains were observed between the imaging groups at 1-yr follow-up. Positive surgical margin rates (odds ratio 1.03, 95% confidence interval [CI] 0.77-1.38, p = 0.8) and biochemical recurrence-free survival (hazard ratio 1.21, 95% CI 0.84-1.74, p = 0.3) were not significantly different between groups. Early and late postoperative complications occurred in 219 and 113 cases, respectively, and were not different between imaging groups. Our study is limited by a potential selection bias from the lack of functional scores for some patients. Conclusions: In this single-center study of men with localized prostate cancer undergoing radical prostatectomy, preoperative mpMRI had minimal impact on functional outcomes and oncologic control compared with conventional imaging. These findings challenge the assumptions that preoperative mpMRI improves operative planning and perioperative outcomes. Patient summary: In this study, we assessed whether the type of prostate imaging performed prior to surgery for localized prostate cancer impacted outcomes. We found that urinary and sexual function, cancer control, and postoperative complications were similar regardless of whether magnetic resonance imaging or computed tomography was utilized prior to surgery.

Hemodynamic course during ablation and selective hepatic artery embolization for metastatic liver carcinoid: a retrospective observational study.

BACKGROUND: Manipulation of carcinoid tumors during ablation or selective hepatic artery embolization (transarterial embolization, TAE) can release vasoactive mediators inducing hemodynamic instability. The main aim of our study was to review hemodynamics and complications related to minimally invasive treatments of liver carcinoids with TAE or ablation. METHODS: Electronic medical records of all patients with metastatic liver carcinoid undergoing ablation or TAE from 2003 to 2019 were abstracted. Noted were severe hypotension (mean arterial pressure [MAP] ..± 55.ßmmHg), severe hypertension (systolic blood pressure ... 180.ßmmHg), and perioperative complications. Associations of procedure type and pre-procedure octreotide use with intraprocedural hemodynamics were assessed using linear regression. A robust covariance approach using generalized estimating equation method was used to account for multiple observations. RESULTS: A total of 161 patients underwent 98 ablations and 207 TAEs. Severe hypertension was observed in 24 (24.5%) vs. 15 (7.3%), severe hypotension in 56 (57.1%) vs. 6 (2.9%), and cutaneous flushing observed in 2 (2.0%) vs. 48 (23.2%) ablations and TAEs, respectively. After adjusting for preprocedural MAP, ablation was associated with lower intraprocedural MAP compared to TAE (estimate -27.ßmmHg, 95%CI -30 to -24.ßmmHg, p.ß<.ß0.001). Intraprocedural declines in MAP were not affected by preprocedural use of octreotide (p.ß=.ß0.7 for TAE and p.ß=.ß0.4 for ablation). CONCLUSIONS: Ablation of liver carcinoids was associated with substantial hemodynamic instability, especially hypotension. In contrast, a higher number of TAE patients had cutaneous flushing. Preprocedural use of octreotide was not associated with attenuation of intraprocedural hypotension.

Hemodynamic course during ablation and selective hepatic artery embolization for metastatic liver carcinoid: a retrospective observational study

Abstract Background: Manipulation of carcinoid tumors during ablation or selective hepatic artery embolization (transarterial embolization, TAE) can release vasoactive mediators inducing hemodynamic instability. The main aim of our study was to review hemodynamics and complications related to minimally invasive treatments of liver carcinoids with TAE or ablation. Methods: Electronic medical records of all patients with metastatic liver carcinoid undergoing ablation or TAE from 2003 to 2019 were abstracted. Noted were severe hypotension (mean arterial pressure [MAP] ≤ 55 mmHg), severe hypertension (systolic blood pressure ≥ 180 mmHg), and perioperative complications. Associations of procedure type and pre-procedure octreotide use with intraprocedural hemodynamics were assessed using linear regression. A robust covariance approach using generalized estimating equation method was used to account for multiple observations. Results: A total of 161 patients underwent 98 ablations and 207 TAEs. Severe hypertension was observed in 24 (24.5%) vs. 15 (7.3%), severe hypotension in 56 (57.1%) vs. 6 (2.9%), and cutaneous flushing observed in 2 (2.0%) vs. 48 (23.2%) ablations and TAEs, respectively. After adjusting for preprocedural MAP, ablation was associated with lower intraprocedural MAP compared to TAE (estimate −27 mmHg, 95%CI −30 to −24 mmHg, p < 0.001). Intraprocedural declines in MAP were not affected by preprocedural use of octreotide (p = 0.7 for TAE and p = 0.4 for ablation). Conclusions: Ablation of liver carcinoids was associated with substantial hemodynamic instability, especially hypotension. In contrast, a higher number of TAE patients had cutaneous flushing. Preprocedural use of octreotide was not associated with attenuation of intraprocedural hypotension.

Guideline-Directed Medical Therapy in Newly Diagnosed Heart Failure With Reduced Ejection Fraction in the Community.

BACKGROUND: Guideline-directed medical therapy (GDMT) dramatically improves outcomes in heart failure with reduced ejection fraction (HFrEF). Our goal was to examine GDMT use in community patients with newly diagnosed HFrEF. METHODS AND RESULTS: We performed a population-based, retrospective cohort study of all Olmsted County, Minnesota, residents with newly diagnosed HFrEF (EF ≤ 40%) 2007-2017. We excluded patients with contraindications to medication initiation. We examined the use of beta-blockers, HF beta-blockers (metoprolol succinate, carvedilol, bisoprolol), angiotensin converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIS), and mineralocorticoid receptor antagonists (MRAs) in the first year after HFrEF diagnosis. We used Cox models to evaluate the association of being seen in an HF clinic with the initiation of GDMT. From 2007 to 2017, 1160 patients were diagnosed with HFrEF (mean age 69.7 years, 65.6% men). Most eligible patients received beta-blockers (92.6%) and ACEis/ARBs/ARNIs (87.0%) in the first year. However, only 63.8% of patients were treated with an HF beta-blocker, and few received MRAs (17.6%). In models accounting for the role of an HF clinic in initiation of these medications, being seen in an HF clinic was independently associated with initiation of new GDMT across all medication classes, with a hazard ratio (95% CI) of 1.54 (1.15-2.06) for any beta-blocker, 2.49 (1.95-3.20) for HF beta-blockers, 1.97 (1.46-2.65) for ACEis/ARBs/ARNIs, and 2.14 (1.49-3.08) for MRAs. CONCLUSIONS: In this population-based study, most patients with newly diagnosed HFrEF received beta-blockers and ACEis/ARBs/ARNIs. GDMT use was higher in patients seen in an HF clinic, suggesting the potential benefit of referral to an HF clinic for patients with newly diagnosed HFrEF.

Asymptomatic Pyuria as a Prognostic Biomarker in Autosomal Dominant Polycystic Kidney Disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) has phenotypic variability only partially explained by established biomarkers that do not readily assess pathologically important factors of inflammation and kidney fibrosis. We evaluated asymptomatic pyuria (AP), a surrogate marker of inflammation, as a biomarker for disease progression. Methods: We performed a retrospective cohort study of adult patients with ADPKD. Patients were divided into AP and no pyuria (NP) groups. We evaluated the effect of pyuria on kidney function and kidney volume. Longitudinal models evaluating kidney function and kidney volume rate of change with respect to incidences of AP were created. Results: There were 687 included patients (347 AP, 340 NP). The AP group had more women (65% versus 49%). Median ages at kidney failure were 86 and 80 years in the NP and AP groups (log rank, P=0.49), respectively, for patients in Mayo Imaging Class (MIC) 1A-1B as compared with 59 and 55 years for patients in MIC 1C-1D-1E (log rank, P=0.02), respectively. Compared with the NP group, the rate of kidney function (ml/min per 1.73 m2 per year) decline shifted significantly after detection of AP in the models, including all patients (-1.48; P<0.001), patients in MIC 1A-1B (-1.79; P<0.001), patients in MIC 1C-1D-1E (-1.18; P<0.001), and patients with PKD1 (-1.04; P<0.001). Models evaluating kidney volume rate of growth showed no change after incidence of AP as compared with the NP group. Conclusions: AP is associated with kidney failure and faster kidney function decline irrespective of the ADPKD gene, cystic burden, and cystic growth. These results support AP as an enriching prognostic biomarker for the rate of disease progression.

Prediction of Progression in Barrett's Esophagus Using a Tissue Systems Pathology Test: A Pooled Analysis of International Multicenter Studies.

BACKGROUND & AIMS: Prediction of progression risk in Barrett's esophagus (BE) may enable personalized management. We aimed to assess the adjunct value of a tissue systems pathology test (TissueCypher) performed on paraffin-embedded biopsy tissue, when added to expert pathology review in predicting incident progression, pooling individual patient-level data from multiple international studies METHODS: Demographics, clinical features, the TissueCypher risk class/score, and progression status were analyzed. Conditional logistical regression analysis was used to develop multivariable models predicting incident progression with and without the TissueCypher risk class (low, intermediate, high). Concordance (c-) statistics were calculated and compared with likelihood ratio tests to assess predictive ability of models. A risk prediction calculator integrating clinical variables and TissueCypher risk class was also developed. RESULTS: Data from 552 patients with baseline no (n = 472), indefinite (n = 32), or low-grade dysplasia (n = 48) (comprising 152 incident progressors and 400 non-progressors) were analyzed. A high-risk test class independently predicted increased risk of progression to high-grade dysplasia/adenocarcinoma (odds ratio, 6.0; 95% confidence interval, 2.9-12.0), along with expert confirmed low-grade dysplasia (odds ratio, 2.9; 95% confidence interval, 1.2-7.2). Model prediction of progression with the TissueCypher risk class incorporated was significantly superior than without, in the whole cohort (c-statistic 0.75 vs 0.68; P < .0001) and the nondysplastic BE subset (c-statistic 0.72 vs 0.63; P < .0001). Sensitivity and specificity of the high risk TissueCypher class were 38% and 94%, respectively. CONCLUSIONS: An objective tissue systems pathology test high-risk class is a strong independent predictor of incident progression in patients with BE, substantially improving progression risk prediction over clinical variables alone. Although test specificity was high, sensitivity was modest.

Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.

Disparities in Hypoxemia Detection by Pulse Oximetry Across Self-Identified Racial Groups and Associations With Clinical Outcomes.

OBJECTIVES: To assess disparities in hypoxemia detection by pulse oximetry across self-identified racial groups and associations with clinical outcomes. DESIGN: Observational cohort study from May 5, 2018, to December 31, 2020. SETTING: Three academic medical centers in the United States. PATIENTS: Adults greater than or equal to 18 years who self-identified as White, Black, Asian, or American Indian admitted to the ICU or undergoing surgery during inpatient hospitalization with simultaneous measurements of pulse oximetry-estimated oxygen saturation and arterial blood gas-derived oxygen saturation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariable models were employed to assess the relationships between race, occult hypoxemia (i.e., arterial blood gas-derived oxygen saturation < 88% despite pulse oximetry-estimated oxygen saturation ≥ 92%), and clinical outcomes of hospital mortality and hospital-free days. One-hundred twenty-eight-thousand two-hundred eighty-five paired pulse oximetry-estimated oxygen saturation-arterial blood gas-derived oxygen saturation measurements were included from 26,603 patients. Pulse oximetry-estimated oxygen saturation on average overestimated arterial blood gas-derived oxygen saturation by 1.57% (1.54-1.61%). Black, Asian, and American Indian patients were more likely to experience occult hypoxemia during hospitalization (estimated probability 6.2% [5.1-7.6%], 6.6% [4.9-8.8%], and 6.6% [4.4-10.0%], respectively) compared with White patients (3.6% [3.4-3.8%]). Black patients had increased odds of occult hypoxemia compared with White patients after adjustment (odds ratio, 1.65; 1.28-2.14; p < 0.001). Differences in occult hypoxemia between Asian and American Indian patients compared with White patients were not significant after adjustment (odds ratio, 1.53; 0.95-2.47; p = 0.077 and odds ratio, 1.31; 0.80-2.16; p = 0.288, respectively). Occult hypoxemia was associated with increased odds of mortality in surgical (odds ratio, 2.96; 1.20-7.28; p = 0.019) and ICU patients (1.36; 1.03-1.80; p = 0.033). Occult hypoxemia was associated with fewer hospital-free days in surgical (-2.5 d [-3.9 to -1.2 d]; p < 0.001) but not ICU patients (0.4 d [-0.7 to 1.4 d]; p = 0.500). CONCLUSIONS: Occult hypoxemia is more common in Black patients compared with White patients and is associated with increased mortality, suggesting potentially important outcome implications for undetected hypoxemia. It is imperative to validate pulse oximetry with expanded racial inclusion.

Long-Term Risk of Clinical Progression Utilizing Magnetic Resonance Imaging Findings of Locally Recurrent Prostate Cancer in Patients with Biochemical Recurrence following Radical Prostatectomy.

PURPOSE: Our goal was to evaluate the long-term prognostic value of magnetic resonance imaging of the prostatectomy bed in patients with biochemical recurrence after radical prostatectomy for prostate cancer. MATERIALS AND METHODS: Men with biochemical recurrence after radical prostatectomy who were studied by prostatectomy bed magnetic resonance imaging for suspected local recurrence were retrospectively evaluated. Locally recurrent tumors were noted and measured from imaging reports. Patients with nodal/bone lesions at the time of imaging were excluded. Kaplan-Meier and Cox regression analyses were used to assess systemic progression-free and prostate cancer-specific survival. RESULTS: A total of 896 men were enrolled and the imaging positive and negative groups for local recurrent tumor consisted of 441 and 455 men, respectively. On univariate analysis, preoperative prostate specific antigen (p=0.02), clinical tumor stage (p=0.006), pathological Gleason score from prostatectomy (p=0.02), subsequent salvage radiotherapy (p <0.001), biochemical recurrence to magnetic resonance imaging time interval (p <0.001), age at magnetic resonance imaging (p=0.047) and prostate specific antigen at magnetic resonance imaging (p <0.001) were significantly different between magnetic resonance imaging positive and negative groups. Patients with negative magnetic resonance imaging results had worse systemic progression-free survival rates (p=0.025) and better prostate cancer-specific survival (p=0.016) than those with recurrence. Larger lesion size significantly increased risk of prostate cancer death (hazard ratio: 1.07; p <0.001). On multivariable analysis, pathological Gleason scores ≥7 were independent prognostic factors of systemic progression (p <0.05). CONCLUSIONS: Prostatectomy bed magnetic resonance imaging provides long-term prognostic information for the evaluation of patients with biochemical recurrence after prostatectomy. Post-prostatectomy patients with recurrent lesions on imaging had longer progression-free survival but shorter prostate cancer-specific survival compared to those without lesions. Additionally, those with larger lesions were associated with poorer cancer-specific survival.

Use of plasma late on cardiopulmonary bypass in patients undergoing left ventricular assist device implantation.

Coagulopathy is common during left ventricular assist device (LVAD) implantation, treatment of which can be challenging given the often-limited ability for the right ventricle to accommodate volume transfusion after device initiation with 20% to 40% of patients developing right ventricular failure (RVF). Transfusion of plasma late on cardiopulmonary bypass (CPB) combined with ultrafiltration may replace clotting factors while reducing volume administration. We compared outcomes in patients undergoing LVAD implantation receiving plasma on CPB and ultrafiltration with traditional transfusion practices. Co-primary outcomes needed for blood product transfusion in the first 6 and 24 hours after CPB. Secondary outcomes included metrics of morbidity and mortality. 396 patients were analyzed (59 plasma on CPB). Patients receiving plasma on CPB had a greater volume of blood products transfused (3764 vs. 2741 mL first 6 hours; 6059 vs. 4305 mL first 24 hours) in unadjusted analysis. In adjusted analysis, plasma transfusion on CPB with ultrafiltration had no significant effect on the primary outcomes of blood products given in the first 6 hours (estimated effect size 982 [-428, 2392] mL, P = .17) and 24 hours (estimated effect size 1076 [-904, 3057] mL, P = .29). Patients receiving plasma on CPB were more likely on either vasopressors or inotropes at 24 hours after ICU admission (P = .01), however, indices of coagulopathy and RVF were similar between groups. While prospective studies would be necessary to definitively evaluate the clinical utility of this strategy, no signal for benefit was observed suggesting plasma should not be used for this purpose.

Implementation of a Comprehensive Patient Blood Management Program for Hospitalized Patients at a Large United States Medical Center.

OBJECTIVE: To assess changes in inpatient transfusion utilization and patient outcomes with implementation of a comprehensive patient blood management (PBM) program at a large US medical center. PATIENTS AND METHODS: This is an observational study of graduated PBM implementation for hospitalized adults (age ≥18 years) from January 1, 2010, through December 31, 2017, at two integrated hospital campuses at a major academic US medical center. Allogeneic transfusion utilization and clinical outcomes were assessed over time through segmented regression with multivariable adjustment comparing observed outcomes against projected outcomes in the absence of PBM activities. RESULTS: In total, 400,998 admissions were included. Total allogeneic transfusions per 1000 admissions decreased from 607 to 405 over the study time frame, corresponding to an absolute risk reduction for transfusion of 6.0% (95% confidence interval [CI]: 3.6%, 8.3%; P<.001) and a 22% (95% CI: 6%, 37%; P=.006) decrease in the rate of transfusions over projected. The risk of transfusion decreased for all blood components except cryoprecipitate. Transfusion reductions were experienced for all major surgery types except liver transplantation, which remained stable over time. Hospital length of stay (multiplicative increase in geometric mean 0.85 [95% CI: 0.81, 0.89]; P<.001) and incident in-hospital adverse events (absolute risk reduction: 1.5% [95% CI: 0.1%, 3.0%]; P=.04) were lower than projected at the end of the study time frame. CONCLUSION: Patient blood management implementation for hospitalized patients in a large academic center was associated with substantial reductions in transfusion utilization and improved clinical outcomes. Broad-scale implementation of PBM in US hospitals is feasible without signal for patient harm.

Etiology, incidence, and outcomes of patient-ventilator asynchrony in critically-ill patients undergoing invasive mechanical ventilation.

Patient-ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P < 0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P < 0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P < 0.01). Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.

Sex-Specific Associations Between Preoperative Anemia and Postoperative Clinical Outcomes in Patients Undergoing Cardiac Surgery.

BACKGROUND: Preoperative anemia is common in cardiac surgery, yet there were limited data describing the role of sex in the associations between anemia and clinical outcomes. Understanding these relationships may guide preoperative optimization efforts. METHODS: This is an observational cohort study of adults undergoing isolated coronary artery bypass grafting or single- or double-valve surgery from 2008 to 2018 at a large tertiary medical center. Multivariable regression assessed the associations between preoperative hemoglobin concentrations and a primary outcome of postoperative acute kidney injury (AKI) and secondary outcomes of perioperative red blood cell (RBC) transfusion, reoperation, vascular complications (ie, stroke, pulmonary embolism, and myocardial infarction), and hospital length of stay (LOS). Each outcome was a single regression model, using interaction terms to assess sex-specific associations between hemoglobin and outcome. RESULTS: A total of 4117 patients were included (57% men). Linear splines with sex-specific knots (13 g/dL in women and 14 g/dL in men) provided the best overall fit for preoperative hemoglobin and outcome relationships. In women, each 1 g/dL decrease in hemoglobin <13 g/dL was associated with increased odds of AKI (odds ratio = 1.49; 95% confidence interval [CI], [1.23-1.81]; P < .001), and there was no significant association between hemoglobin per 1 g/dL >13 g/dL and AKI (0.90 [0.56-1.45]; P = .67). The association between hemoglobin and AKI in men did not meet statistical significance (1.10 [0.99-1.22]; P = .076, per 1 g/dL decrease <14 g/dL; 1.00 [0.79-1.26]; P = .98 for hemoglobin per 1 g/dL >14 g/dL). In women, lower preoperative hemoglobin (per 1 g/dL decrease <13 g/dL) was associated with increased odds of RBC transfusion (2.90 [2.33-3.60]; P < .001), reoperation (1.27 [1.11-1.45]; P < .001) and a longer hospital LOS (multiplicative increase in geometric mean 1.05 [1.03-1.07]; P < .001). In men, preoperative hemoglobin (per 1 g/dL decrease <14 g/dL) was associated with increased odds of perioperative RBCs (2.56 [2.27-2.88]; P < .001) and longer hospital LOS (multiplicative increase in geometric mean 1.02 [1.01-1.04] days; P < .001) but not reoperation (0.94 [0.85-1.04]; P = .256). Preoperative hemoglobin per 1 g/dL >13 g/dL in women and 14 g/dL in men were associated with lower odds of RBCs transfusion (0.57 [0.47-0.69]; P < .001 and 0.74 [0.60-0.91]; P = .005, respectively). CONCLUSIONS: Preoperative anemia was associated with inferior clinical outcomes after cardiac surgery. The associations between hemoglobin and outcomes were distinct for women and men, with different spline knot points identified (13 and 14 g/dL, respectively). Clinicians should consider data-driven approaches to determine preoperative hemoglobin values associated with increasing risk for adverse perioperative outcomes across sexes.

Bedside Allogeneic Erythrocyte Washing with a Cell Saver to Remove Cytokines, Chemokines, and Cell-derived Microvesicles.

BACKGROUND: Removal of cytokines, chemokines, and microvesicles from the supernatant of allogeneic erythrocytes may help mitigate adverse transfusion reactions. Blood bank-based washing procedures present logistical difficulties; therefore, we tested the hypothesis that on-demand bedside washing of allogeneic erythrocyte units is capable of removing soluble factors and is feasible in a clinical setting. METHODS: There were in vitro and prospective, observation cohort components to this a priori planned substudy evaluating bedside allogeneic erythrocyte washing, with a cell saver, during cardiac surgery. Laboratory data were collected from the first 75 washed units given to a subset of patients nested in the intervention arm of a parent clinical trial. Paired pre- and postwash samples from the blood unit bags were centrifuged. The supernatant was aspirated and frozen at -70°C, then batch-tested for cell-derived microvesicles, soluble CD40 ligand, chemokine ligand 5, and neutral lipids (all previously associated with transfusion reactions) and cell-free hemoglobin (possibly increased by washing). From the entire cohort randomized to the intervention arm of the trial, bedside washing was defined as feasible if at least 75% of prescribed units were washed per protocol. RESULTS: Paired data were available for 74 units. Washing reduced soluble CD40 ligand (median [interquartile range]; from 143 [1 to 338] ng/ml to zero), chemokine ligand 5 (from 1,314 [715 to 2,551] to 305 [179 to 488] ng/ml), and microvesicle numbers (from 6.90 [4.10 to 20.0] to 0.83 [0.33 to 2.80] × 106), while cell-free hemoglobin concentration increased from 72.6 (53.6 to 171.6) mg/dl to 210.5 (126.6 to 479.6) mg/dl (P < 0.0001 for each). There was no effect on neutral lipids. Bedside washing was determined as feasible for 80 of 81 patients (99%); overall, 293 of 314 (93%) units were washed per protocol. CONCLUSIONS: Bedside erythrocyte washing was clinically feasible and greatly reduced concentrations of soluble factors thought to be associated with transfusion-related adverse reactions, increasing concentrations of cell-free hemoglobin while maintaining acceptable (less than 0.8%) hemolysis.