Faculty Bibliography

BACKGROUND:The novel coronavirus-associated ARDS (COVID-19 ARDS) often requires invasive mechanical ventilation. A spectrum of atypical ARDS with different phenotypes (high vs low static compliance) has been hypothesized in COVID-19. METHODS:test, chi-square test, ANOVA test, and Pearson correlation was used to identify relationship between subject variables and respiratory mechanics. The primary outcome was duration of mechanical ventilation. Secondary outcomes were correlation between fluid status, C- reactive protein, PEEP, and D-dimer with respiratory and ventilatory parameters. RESULTS:= .02). CONCLUSIONS:In our cohort of mechanically ventilated COVID-19 ARDS subjects, high PEEP and D-dimer were associated with increase in physiologic dead space without significant effect on oxygenation, raising the question of potential microvascular dysfunction.

The associations between covariates and the outcomes often vary over time, regardless of whether the covariate is time-varying or time-invariant. For example, we hypothesize that the impact of chronic diseases, such as diabetes and heart disease, on people's physical functions differ with aging. However, the age-varying effect would be missed if one models the covariate simply as a time-invariant covariate (yes/no) with a time-constant coefficient. We propose a fused lasso-based time-varying linear mixed effect (FTLME) model and an efficient two-stage parameter estimation algorithm to estimate the longitudinal trajectories of fixed-effect coefficients. Simulation studies are presented to demonstrate the efficacy of the method and its computational efficiency in estimating smooth time-varying effects in high dimensional settings. A real data example on the Health and Retirement Study (HRS) analysis is used to demonstrate the practical usage of our method to infer age-varying impact of chronic disease on older people's physical functions.

Background: While ~50% of patients (pts) with AML aged >60 years attain complete remission (CR) with intensive chemotherapy (IC), up to 90% who do will eventually relapse. In the continuum of AML care, the highest costs are related to relapsed/refractory disease, and hospitalization is the largest component (~70%) of direct healthcare costs. In the randomized, phase 3 QUAZAR AML-001 trial, maintenance treatment (Tx) with Oral-AZA significantly prolonged overall and relapse-free survival vs. PBO for pts with AML in first remission after IC.
Aim(s): Determine rates of hospitalization and days (d) in hospital with Oral-AZA and PBO for all pts in QUAZAR AML-001, and estimate associated hospitalization costs in Spain from the Spanish National Health System (NHS) perspective, and in the UK from the UK NHS perspective.
Method(s): Eligible pts were age >=55 yrs, had intermediate- or poor-risk cytogenetics and ECOG PS <=3, and were not candidates for transplant. Within 4 months (mo) of achieving CR or CR with incomplete blood count recovery (CRi) after induction +/- consolidation, pts were randomized 1:1 to Oral-AZA 300-mg or PBO QD for 14d/28d cycle. Pts who received >=1 study drug dose were followed for hospitalization from informed consent through 28d after last dose. The mean number of hospital days/mo (30d) was the total number of days in hospital divided by the number of ongoing pts each mo. Hospitalization rates and durations were adjusted for total drug exposure. Confidence intervals (CI) for relative risk (RR) estimates and related P values are based on asymptotic methods. Unit cost of hospitalization in Spain was derived from literature (Arenaza et al. Clinicoecon Outcomes Res, 2019), and in the UK from NHS reference costs (https://urldefense.com/v3/__https://improvement.nhs.uk/resources/reference-__;!!MXfaZl3l!OpCoLHQ2rqK1VsMStsOKp86IRR8bqfjG0A-Ot_EG-SQDYIPd2IxVXtpVGoEKdoxE$ costs/#rc1718), as the average total AML-related hospitalization costs per day, adjusted for inflation to 2019 prices, using the medical component of the consumer price index for each country.
Result(s): 469 pts received Oral-AZA (n=236) or PBO (n=233); median time on Tx was 11.6 vs 5.7 mo, respectively, and total exposures were 363.8 pt-years (PY) and 234.9 PY. Similar proportions of patients were hospitalized during the study: Oral-AZA 46% (n=108), PBO 51% (n=118). Total number of hospitalization events was numerically higher in the Oral-AZA arm (173 vs 151 in the PBO arm), but the exposure-adjusted hospitalization rate was significantly lower with Oral-AZA: 0.48/ PY vs. 0.64/PY (RR 0.740 [95%CI 0.595, 0.920]; P=0.0068). Total days hospitalized were 2,872 in the Oral-AZA arm and 3,139 in the PBO arm; the exposure-adjusted rate was also significantly lower with Oral-AZA (7.89 vs. 13.36 d/PY, respectively; RR 0.591 [95%CI 0.562, 0.621]; P<0.0001). Mean hospitalization cost in Spain was 1,398/d. Using exposure-adjusted days-in-hospital, estimated mean costs of hospitalization in Spain were 11,030/PY with Oral-AZA and 18,676/PY with PBO. Cumulative cost savings with Oral-AZA vs. PBO ranged from 557 at mo 2 to 8,025 by mo 24 (Figure). In the UK, mean hospitalization cost was ?696/d, resulting in estimated exposure-adjusted mean costs of ?5,490/PY with Oral-AZA and ?9,296/ PY with PBO. Cumulative cost savings with Oral-AZA in the UK ranged from ?277 at mo 2 to ?3,995 by mo 24 (Figure). Summary/Conclusion: Compared with PBO, Oral-AZA was associated with significantly reduced exposure-adjusted rates of hospitalization and days in hospital, and considerable estimated cost savings in Spain and the UK. Delaying relapse with Oral-AZA may lead to substantial economic benefits due to lower hospitalization costs

BACKGROUND CONTEXT: The inter-relationship between the hip and spine has been increasingly studied in recent years, particularly as it pertains to the effect of spinal deformity and hip osteoarthritis (OA). Changing from standing (ST) to seated (SE) requires rotation of the femur from an almost vertical plane to the horizontal. OA of the hip significantly limits hip extension, resulting in less ability to recruit pelvic tilt (PT) in ST, and requiring increased PT in SE to compensate for loss of hip flexion. To date, the effect of total hip arthroplasty (THA) in altering spinopelvic SE and ST mechanics has not been reported. PURPOSE: To investigate the change in spinopelvic alignment parameters between seated and standing positions in pre and post THA patients. STUDY DESIGN/SETTING: Retrospective review at a single academic institution. PATIENT SAMPLE: Adult patients undergoing THA with full body sitting and standing radiographs pre- and post-THA. OUTCOME MEASURES: Spinopelvic alignment measures including pelvic incidence (PI), pelvic tilt (PT), T1 pelvic angle (TPA), sacral slope (SS), sagittal vertical axis (SVA), pelvic incidence and lumbar lordosis mismatch (PI-LL), and lumbar lordosis (LL).
METHOD(S): Patients >=18yo undergoing THA for hip OA with full spine SE and ST radiographs pre and post THA were included. Spinopelvic alignment was analyzed pre-THA and post-THA in both ST and SE positions in a relaxed posture with the fingers on the clavicles. Paired t-test analysis was performed to compare Pre-and Post-THA groups. The effect of TL deformity (SVA>50, TPA>20, PI-LL>10) on these changes was also analyzed. Statistical significance set at p<0.05.
RESULT(S): There were 192 patients assessed. 179 patients had thoracolumbar (TL) deformity; TPA>20 (N=46), PI-LL>10 (N=55), and SVA>50 (N=78). In standing position, patients have a significant reduction in SVA post THA vs pre THA (34.09+/-42.69 vs 45.03+/-46.87, p=0.001) as a result of an increase in PT (15.7+/-9.74 o vs 14.6+/-9.88o,p=0.028), without significant changes in spinal alignment parameters including lumbar lordosis (-51.26+/-14.59 vs -50.26+/-14.87, p=0.092), thoracic kyphosis (35.98+/-12.72 vs 35.40+/-13.16, p=0.180), sacral slope (38.15+/-10.77 vs 38.83+/-11.31, p=0.205), T1 pelvic angle (14.22+/-9.94 vs 14.51+/-10.13, p=0.053) and PI-LL mismatch (2.59+/-14.61 vs 3.35+/-14.92, p=0.183). This change in ST_SVA was larger in patients with TL deformity, specifically in those with SVA>50 (61.29+/-45.69 vs 89.48+/-35.91, p=0.001), in PI-LL > 10 (59.08+/-45.49 vs 73.36+/-48.50, p=0.001) and in TPA>20 subsets (62.14+/-49.94 vs 82.28+/-49.55, p=0.001). When moving from ST to SE, the DELTAPT was reduced post THA (16.70+/-15.27o vs 20.85+/-17.27o, p=0.001) in addition to a smaller SE_PT vs pre-THA (32.41+/-14.47 vs 35.46+/-14.20, p=0.006).
CONCLUSION(S): Post Total Hip Arthroplasty (THA), patients demonstrated an increased recruitment of pelvic retroversion to achieve a better global balance by reduction in standing SVA. This compensation was achieved solely by greater mobility of their hip and pelvis, and without a significant change in spinal alignment. ST_SVA reduction was more pronounced in patients with thoracolumbar (TL) spinal deformity (SVA>50, TPA>20, PI-LL>10). On the converse, PT was reduced in sitting (SE) post-THA compared to pre-THA, and the compensatory change in PT was also reduced between ST and SE as a result of restoration of hip flexion. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
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BACKGROUND:Recent preclinical data suggest that there may be therapeutic synergy between immune checkpoint blockade and inhibition of the coagulation cascade. Here, we investigate whether patients who received immune checkpoint inhibitors (ICI) and were on concomitant anticoagulation (AC) experienced better treatment outcomes than individuals not on AC.Affiliation: Kindly confirm if corresponding authors affiliation is identified correctly.The corresponding author's affiliation is correct. METHODS:We studied a cohort of 728 advanced cancer patients who received 948 lines of ICI at NYU (2010-2020). Patients were classified based on whether they did (n = 120) or did not (n = 828) receive therapeutic AC at any point during their treatment with ICI. We investigated the relationship between AC status and multiple clinical endpoints including best overall response (BOR), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of bleeding complications.Affiliations: Journal instruction requires a country for affiliations; however, this is missing in affiliations 1 to 5. Please verify if the provided country is correct and amend if necessary.The country is correct for all affiliations (1 - 5). RESULTS:Treatment with AC was not associated with significantly different BOR (P = 0.80), ORR (P =0.60), DCR (P =0.77), PFS (P = 0.59), or OS (P =0.64). Patients who received AC were significantly more likely to suffer a major or clinically relevant minor bleed (P = 0.05). CONCLUSION/CONCLUSIONS:AC does not appear to impact the activity or efficacy of ICI in advanced cancer patients. On the basis of our findings, we caution that there is insufficient evidence to support prospectively evaluating the combination of AC and immunotherapy.

BACKGROUND:Comorbid chronic conditions are common among people with type 2 diabetes. We developed an artificial intelligence algorithm, based on reinforcement learning (RL), for personalized diabetes and multimorbidity management, with strong potential to improve health outcomes relative to current clinical practice. METHODS:We modeled glycemia, blood pressure, and cardiovascular disease (CVD) risk as health outcomes, using a retrospective cohort of 16,665 patients with type 2 diabetes from New York University Langone Health ambulatory care electronic health records in 2009-2017. We trained an RL prescription algorithm that recommends a treatment regimen optimizing patients' cumulative health outcomes using their individual characteristics and medical history at each encounter. The RL recommendations were evaluated on an independent subset of patients. RESULTS:The single-outcome optimization RL algorithms, RL-glycemia, RL-blood pressure, and RL-CVD, recommended consistent prescriptions as that observed by clinicians in 86.1%, 82.9%, and 98.4% of the encounters, respectively. For patient encounters in which the RL recommendations differed from the clinician prescriptions, significantly fewer encounters showed uncontrolled glycemia (A1c > 8% in 35% of encounters), uncontrolled hypertension (blood pressure > 140 mmHg in 16% of encounters), and high CVD risk (risk > 20% in 25% of encounters) under RL algorithms compared with those observed under clinicians (43%, 27%, and 31% of encounters, respectively; all p < 0.001). CONCLUSIONS:A personalized RL prescriptive framework for type 2 diabetes yielded high concordance with clinicians' prescriptions, and substantial improvements in glycemia, blood pressure, and CVD risk outcomes.

BACKGROUND:Although most patients with cutaneous melanoma are non-Hispanic whites (NHWs), minorities consistently suffer worse melanoma-specific survival (MSS). Much of the literature comes from analyses of registries from the 1990s and 2000s. OBJECTIVE:We sought to evaluate whether and to what degree racial disparity in MSS persists since 2010. METHODS:We analyzed 381,035 patients from the Surveillance, Epidemiology, and End Results registry. Race categories included Hispanic, NHW, non-Hispanic black (NHB), non-Hispanic Asian or Pacific Islander (NHAPI), and non-Hispanic American Indian/Alaska Native (NHAIAN). We evaluated the association between MSS and race in 3 time periods: before the year 2000, 2000 to 2009, and 2010 or later. NHW was the reference group for all analyses. RESULTS:Racial disparity worsened from before the year 2000 to 2010 or later for Hispanic (P < .001), NHB (P = .024), and NHAPI (P < .001) patients. Across all minority groups, patients with localized disease suffered increasing disparity (P = .010 for Hispanic, P < .001 for NHB, P = .023 for NHAPI, and P = .042 for NHAIAN patients). Among those with regional and distant disease, Hispanic patients were the only minority to experience worsening disparity (P = .001 and P = .019, respectively). LIMITATIONS/CONCLUSIONS:Lack of immunotherapy and targeted treatment information. CONCLUSIONS:Racial disparity in MSS is worsening. Improving postdiagnosis management for minorities with localized disease is imperative to mitigate disparity and improve survival.

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 6-15% of MI and disproportionately affects women. Scientific statements recommend multi-modality imaging in MINOCA to define the underlying cause. We performed coronary optical coherence tomography (OCT) and cardiac magnetic resonance imaging (CMR) to assess mechanisms of MINOCA. Methods: In this prospective, multicenter, international, observational study, we enrolled women with a clinical diagnosis of MI. If invasive coronary angiography revealed <50% stenosis in all major arteries, multi-vessel OCT was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and/or T1 mapping). Angiography, OCT, and CMR were evaluated at blinded, independent core laboratories. Culprit lesions identified by OCT were classified as definite or possible. The CMR core laboratory identified ischemia-related and non-ischemic myocardial injury. Imaging results were combined to determine the mechanism of MINOCA, when possible. Results: Among 301 women enrolled at 16 sites, 170 were diagnosed with MINOCA, of whom 145 had adequate OCT image quality for analysis; 116 of these underwent CMR. A definite or possible culprit lesion was identified by OCT in 46.2% (67/145) of participants, most commonly plaque rupture, intra-plaque cavity or layered plaque. CMR was abnormal in 74.1% (86/116) of participants. An ischemic pattern of CMR abnormalities (infarction or myocardial edema in a coronary territory) was present in 53.4% of participants undergoing CMR (62/116). A non-ischemic pattern of CMR abnormalities (myocarditis, takotsubo syndrome or non-ischemic cardiomyopathy) was present in 20.7% (24/116). A cause of MINOCA was identified in 84.5% of the women with multi-modality imaging (98/116), higher than with OCT alone (p<0.001) or CMR alone (p=0.001). An ischemic etiology was identified in 63.8% of women with MINOCA (74/116), a non-ischemic etiology was identified in 20.7% (24/116), and no mechanism was identified in 15.5% (18/116). Conclusions: Multi-modality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, three-quarters of which were ischemic and one-quarter of which were non-ischemic, alternate diagnoses to MI. Identification of the etiology of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02905357.