Mayo Clinic Rochester Research Articles

Health Care Costs and Utilization Predictions by the Skilled Nursing Facility Readmission Risk Instrument

ObjectivesHealth care providers at hospitals and skilled nursing facilities (SNFs) are increasingly expected to optimize care of post-acute patients to reduce hospital readmissions and contain costs. To achieve these goals, providers need to understand their patients’ risk of hospital readmission and how this risk is associated with health care costs. A previously developed risk prediction model identifies patients’ probability of 30-day hospital readmission at the time of discharge to an SNF. With a computerized algorithm, we translated this model as the Skilled Nursing Facility Readmission Risk (SNFRR) instrument. Our objective was to evaluate the relationship between 30-day health care costs and hospital readmissions according to the level of risk calculated by this model. DesignThis retrospective cohort study used SNFRR scores to evaluate patient data. Setting and ParticipantsThe patients were discharged from Mayo Clinic Rochester hospitals to 11 area SNFs. MethodsWe compared the outcomes of all-cause 30-day standardized direct medical costs and hospital readmissions between risk quartiles based on the distribution of SNFRR scores for patients discharged to SNFs for post-acute care from April 1 through November 30, 2017. ResultsMean 30-day all-cause standardized costs were positively associated with SNFRR score quartiles and ranged from $9199 in the fourth quartile (probability of readmission, 0.27-0.66) to $2679 in the first quartile (probability of readmission, 0.07-0.13) (P ≤ .05). Patients in the fourth SNFRR score quartile had 5.68 times the odds of 30-day hospital readmission compared with those in the first quartile. Conclusions and ImplicationsThe SNFRR instrument accurately predicted standardized direct health care costs for patients on discharge to an SNF and their risk for 30-day hospital readmission. Therefore, it could be used to help categorize patients for preemptive interventions. Further studies are needed to confirm its validity in other institutions and geographic areas.

Central Sensitization Phenotypes in Post Acute Sequelae of SARS-CoV-2 Infection (PASC): Defining the Post COVID Syndrome.

ObjectiveTo develop and implement criteria for description of post COVID syndrome based on analysis of patients presenting for evaluation at Mayo Clinic Rochester between November 2019 and August 2020.MethodsA total of 465 patients with a history of testing positive for COVID-19 were identified and their medical records reviewed. After a thorough review, utilizing the DELPHI methods by an expert panel, 42 (9%) cases were identified with persistent central sensitization (CS) symptoms persisting after the resolution of acute COVID-19, herein referred to as Post COVID syndrome (PoCoS). In this report we describe the baseline characteristics of these PoCoS patients.ResultsAmong these 42 PoCoS patients, the mean age was 46.2 years (median age was 46.5 years). Pain (90%), fatigue (74%), dyspnea (43%), and orthostatic intolerance (38%) were the most common symptoms. The characteristics of an initial 14 patients were utilized for the development of clinical criteria via a modified Delphi Method by a panel of experts in central sensitization disorders. These criteria were subsequently applied in the identification of 28 additional cases of suspected PoCoS. A 2-reviewer system was used to analyze agreement with using the criteria, with all 28 cases determined to be either probable or possible cases by the reviewers. Inter-reviewer agreement using these proposed defining criteria was high with a Cohen’s alpha of .88.ConclusionsHere we present what we believe to be the first definitional criteria for Post COVID syndrome. These may be useful in clinical phenotyping of these patients for targeted treatment and future research.

Editorial introductions.

Editorial introductions.

Hypertensive disorders of pregnancy and menopausal symptoms: a cross-sectional study from the data registry on experiences of aging, menopause, and sexuality.

Hypertensive disorders of pregnancy and menopausal symptoms, specifically vasomotor symptoms, have both been associated with cardiovascular disease risk in women. However, data are sparse on the association between these two female-specific cardiovascular risk factors. This study was conducted to investigate the association between a history of a hypertensive disorder of pregnancy and menopausal symptoms. This was a cross-sectional study of women aged 40 to 65 years seen for specialty consultation in women's health clinics at Mayo Clinic Rochester, MN and Scottsdale, AZ, between May, 2015 and September, 2019. A self-reported history of hypertensive disorders of pregnancy served as the independent variable, and menopause symptoms as assessed by the Menopause Rating Scale were the primary outcome measure. Of 2,684 women included in the analysis, 180 had a self-reported history of a hypertensive disorder of pregnancy. The total menopausal symptom scores as well as somatic and psychological domain scores were higher in women with a history of a hypertensive disorder of pregnancy compared to women without a history of a hypertensive disorder of pregnancy or to women without a pregnancy. On multivariable analysis, women with a hypertensive disorder of pregnancy using hormone therapy had significantly higher total menopause symptom scores than women with no such history. In this large cross-sectional study, a history of hypertensive disorders of pregnancy was associated with more bothersome menopausal symptoms. Additional study is needed to determine the strength of this association, underlying mechanisms of the association, and clinical implications for cardiovascular risk prediction in women.

A Midwest COVID-19 Cohort for the Evaluation of Multimorbidity and Adverse Outcomes from COVID-19.

ObjectiveTo describe the process and outcome of creating a patient cohort in the early stages of the COVID-19 pandemic in order to better understand the process of and predict the outcomes of COVID-19.Patients and MethodsA total of 1169 adults aged 18 years of age or older who tested positive in Mayo Clinic Rochester or the Mayo Clinic Midwest Health System between January 1 and May 23 of 2020.ResultsPatients were on average 43.9 years of age and 50.7% were female. Most patients were white (69.0%), and Blacks (23.4%) and Asians (5.8%) were also represented in larger numbers. Hispanics represented 16.3% of the sample. Just under half of patients were married (48.4%). Common comorbid conditions included: cardiovascular diseases (25.1%), dyslipidemia (16.0%), diabetes mellitus (11.2%), chronic obstructive pulmonary disease (6.6%), asthma (7.5%), and cancer (5.1%). All other comorbid conditions were less the 5% in prevalence. Data on 3 comorbidity indices are also available including the: DHHS multi-morbidity score, Charlson Comorbidity Index, and Mayo Clinic COVID-19 Risk Factor Score.ConclusionIn addition to managing the ever raging pandemic and growing death rates, it is equally important that we develop adequate resources for the investigation and understanding of COVID-19-related predictors and outcomes.

The Impact of Obesity on the Outcomes of Adult Patients with Acute Lymphoblastic Leukemia - A Single Center Retrospective Study.

IntroductionObesity is a worldwide problem that is related to cardiac disease, thrombosis and cancer. However, little is known about the impact of obesity on the outcomes of adult acute lymphoblastic leukemia (ALL) patients.MethodsWe retrospectively evaluated a cohort of 154 newly diagnosed adult ALL patients between 1994 and 2011 at Mayo Clinic (Rochester). According to the World Health Organization (WHO) international BMI classification, patients were stratified as underweight, normal weight, overweight, and obese. For some analyses, patients were also stratified according to a two-sided non-obese or obese classification.ResultsThe median follow-up time was 8.37 years. Obese patients were more likely to be women (p=0.024) and ≥60 years old (p=0.003). Five-year mortality rates were higher in obese patients than non-obese [HR 95% CI: 1.60 (1.03–2.50) p=0.035]. This was also the case in subgroup analysis among T-cell patients although the number of patients was small [HR 95% CI: 5.42 (1.84–15.98) p<0.001]. There was no difference in mortality among the B-cell patients. After adjusting for baseline variables, the difference in mortality remained in several models. There was no difference in EFS or cumulative incidence of relapse rates between obese and non-obese patients among the overall population.DiscussionIn conclusion, our study suggests that adult ALL patients with obesity have lower survival rates, especially in T-cell ALL.

Music Therapy for Anxiety and Pain After Spinal Cord Injury: A Pilot Study.

BackgroundMusic therapy (MT) programs have been used in various health care settings to reduce patients’ pain, anxiety, and stress. However, few studies have investigated its effects on patients with spinal cord injury (SCI), a frequently serious event requiring extensive rehabilitation.ObjectiveThis pilot study evaluated the feasibility of offering music-assisted relaxation (MAR) during rehabilitation for patients with SCI. We also measured the effect of MAR on the patients’ pain, anxiety, and stress levels.MethodsPatients were hospitalized at Mayo Clinic (Rochester, Minnesota) from September 2015 through September 2017 for rehabilitation of an SCI. Eligible patients received 2, 20-minute, personalized MAR sessions. Interventions were facilitated by a board-certified music therapist (MT-BC) and included diaphragmatic breathing, guided imagery, and passive muscle relaxation with live guitar accompaniment and spoken, improvised, or singing voice. Two surveys (Generalized Anxiety Disorder [GAD-7] and Perceived Stress Scale [PSS-10]) were used at the time of study consent and again upon hospital dismissal. Pain, anxiety, and relaxation were assessed before and after both MT sessions with visual analog scales (VASs), scored from 0 to 10. Participants completed a 7-question satisfaction survey after the second MAR session.ResultsTwenty patients were enrolled (12 men, 8 women); 13 (65%) completed the MAR interventions. The mean (SD) age was 53.7 (17.7) years. VAS scores for pain significantly improved after both sessions (P ≤ .02). VAS scores for anxiety also significantly improved after both sessions (P ≤ .02), as did VAS scores for relaxation (P ≤ .02 for both). The satisfaction survey indicated that patients generally believed that they benefited from MT. Rehabilitation staff indicated that MT did not interfere with routine clinical care.ConclusionMT with live MAR is a feasible treatment for patients with SCI and may be effective for reducing their pain and anxiety.

1255. In Vitro Activity of Vancapticin against Methicillin-Resistant Staphylococcus aureus from Periprosthetic Joint Infection

BackgroundThe vancapticins are modified vancomycin derivatives developed by adding membrane targeting motifs to the C-terminus of vancomycin. We determined the in vitro activity of a lead vancapticin candidate against periprosthetic joint infection-associated methicillin-resistant Staphylococcus aureus (MRSA) in the planktonic and biofilm states, and the effect of adding 0.002% polysorbate 80 (P-80; Sigma-Aldrich) on vancapticin susceptibility testing.MethodsThirty-seven clinical isolates of MRSA collected at Mayo Clinic (Rochester, Minnesota) were studied. Vancapticin minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institutes guidelines. Minimum biofilm bactericidal concentrations (MBBCs) were determined using a pegged lid microtiter plate assay. Vancapticin MIC and MBBC values were assessed with and without P-80. Vancapticin, vancomycin, and dalbavancin biofilm time-kill assays were performed using biofilms formed by 10 MRSA isolates on Teflon coupons.ResultsVancapticin MICs with and without P-80 ranged from 0.015 to 0.12 μg/mL and 0.25 to 1 μg/mL, respectively. Vancapticin MBBCs with and without P-80 ranged from 0.25 to 4 μg/mL and 1 to 8 μg/mL, respectively. Reductions of biofilm bacterial densities on Teflon coupons after 8 and 24 hours of incubation with vancapticin, vancapticin with P-80, vancomycin, or dalbavancin with P-80 were less than 3-log10 cfu/cm2 for all isolates tested.ConclusionVancapticin has promising in vitro activity against planktonic MRSA and MRSA in a pegged lid biofilm assay, but was not bactericidal against biofilms on Teflon coupons. P-80 decreased vancapticin MICs and MBBCs.Disclosures Mark A. Blaskovich, PhD, MAB Consulting (Consultant)The University of Queensland (Employee, Grant/Research Support, Other Financial or Material Support, Inventor on patent) Robin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)

How do we assess resilience and grit among internal medicine residents at the Mayo Clinic? A longitudinal validity study including correlations with medical knowledge, professionalism and clinical performance

BackgroundThere has been limited research on the positive aspects of physician wellness and to our knowledge there have been no validity studies on measures of resilience and grit among internal...

Patient Discomfort in Relation to Thyroid Nodule Fine-Needle Aspiration (FNA) Performed with or without Parenteral and/or Topical Anesthetic

There is much reported variation in the impact of local anesthesia on thyroid fine-needle aspiration (FNA) related discomfort. We compare patients undergoing thyroid FNA with subcutaneous injection or topical anesthetic to no anesthetic. We conducted a retrospective review of 585 sequential ultrasound guided thyroid FNA procedures in Mayo Clinic. Group 1 (n = 200), no anesthetic; Group 2 (n = 185), subcutaneous injection anesthetic; and Group 3 (n = 200), topical anesthetic. Patient demographics, number of FNA passes, needle gauge, and cytopathology were recorded plus a discomfort score (0 to 10) before and immediately post procedure in all 3 groups and peak discomfort during the FNA in Groups 1 and 2. There were no differences among the 3 groups in age, sex, FNA sufficiency rate, cytopathology, and FNA passes number. There was no significant difference between Groups 1 and 2 in peak discomfort score during the FNA: 0 (45%, 42.2%), 1 to 2 (19%, 24.9%), 3 to 5 (23.5%, 20.5%), 6 to 8 (9.5%, 10.8%), 9 to 10 (3%, 1.6%), respectively. Discomfort score post procedure: 0 (78.5%, 77.8%, 53.5%), 1 to 2 (13%, 13%, 36.5%), 3 to 5 (7%, 7%, 9%), 6 to 8 (1.5%, 2.2%, 1%), 9 to 10 (0%, 0%, 0%) for groups 1, 2, and 3, respectively. There were no significant differences among the 3 groups for a discomfort score ≥3. FNA associated patient discomfort was comparable during and after the procedure regardless of the use of anesthetic or the type utilized. Approximately 90% of patients experienced mild to moderate discomfort during the procedure. And 90% reported no more than a level 2 discomfort post procedure. End = endocrinology; FNA = fine-needle aspiration; MCF = Mayo Clinic Florida; MCR = Mayo Clinic Rochester.

Diagnostic Yield of Neck CT Angiography in Young Adults With Anterior Circulation Ischemic Stroke: A Community Based Study.

Few community-based studies investigating young adult strokes exist. The aim of this study was to determine the diagnostic yield of head and neck CTA in evaluation of anterior circulation ischemic stroke in young adults. This retrospective review is limited to patients between the ages of 18-50 presenting to the Mayo Clinic Rochester emergency department or referred from smaller institutions in adjacent counties. Patients with posterior circulation infarcts, amaurosis fugax, central retinal artery occlusion or transient ischemic attacks were excluded. The presence of carotid dissection, webs, plaque, or other high-risk lesions were recorded. A total of 136 patients met inclusion criteria. Mean degree of carotid stenosis ipsilateral to infarct was 14.1%, compared to 6.5% on the contralateral side (p = .006). Ipsilateral mean carotid wall thickness measured .79 mm, compared to contralateral thickness of .80 mm (p = .51). Ipsilateral low-density plaque was observed in 22 patients (16.2%), and 21 patients (15.4%) on the contralateral side (p = .87). Ipsilateral calcified plaque was observed in 37 patients (27.2%), and 29 patients (21.3%) on the contralateral side (p = .31). 20 (14.7%) ipsilateral dissections were noted, compared to 4 (2.9%) contralateral dissections (p = .001). 3 (2.2%) ipsilateral carotid webs were identified, compared to 0 contralateral webs (p = .25). Carotid dissection was the most common cause of anterior circulation infarct identified on cervical CTA in this population. Carotid webs and atherosclerosis were not common findings.

Abstract 15979: Utility of Post-extraction Follow-up Blood Cultures in Patients With Cardiovascular Implantable Electronic Device Infection

Introduction: Cardiovascular implantable electronic devices (CIED) infections are frequently complicated with bloodstream infection (BSI). Complete device removal and prolonged antimicrobial therapy is essential for cure. The frequency of persistent BSI after source control (device extraction) is not well described. This study aims to assess the utility of repeat blood cultures (BC) after device extraction as recommended by the American Heart Association (AHA) guidelines. Methods: We selected patients who presented with BSI in the setting of CIED infection and underwent device removal at Mayo Clinic Rochester between 2012 and 2017. Cases where BC were not drawn prior to extraction, or repeated within 72 hours of device extraction, or met criteria for contamination were excluded. Results: Of 656 patients who underwent CIED extraction for device infection, 190 with post-extraction BC met study criteria. Among the final study cohort (Table 1), 159 patients had negative BC, while 31 had positive BC following CIED extraction. Pre-extraction, the most common causative organism was Staphylococcus aureus (91/190, 48%) (Figure 1a). Post-extraction, 22 of the 31 (71%) cases of persistent BSI were due to S. aureus (Fig 1b). The median duration of BSI was not significantly different between negative and positive BC groups (3 versus 4 days, p=0.92). Conclusions: Majority of patients had resolution of BSI after CIED extraction. S. aureus was the most common cause of persistent BSI post-extraction. Our findings support the AHA guidelines of repeating BC after device extraction, especially for S aureus .

Predictors of Survival and Time to Progression to Myeloid Neoplasm in Patients with Clonal Cytopenias

Background: Clonal cytopenias of Undetermined Significance (CCUS) have a higher risk of progression to myeloid neoplasm (MN) compared to idiopathic cytopenias of undetermined significance (ICUS) (Malcovati et al., Blood, 2017). The implementation of flow cytometric (FC) immune-phenotyping and next generation sequencing (NGS) in clinical practice has improved the diagnosis of these entities but the clinical significance and interaction of these abnormal results are still unknown. In this study we investigated predictive factors that play role in survival and progression to MN in patients with ICUS/CCUS. Methods: Patients (Pts) who had undergone evaluation for unexplained cytopenia and had undergone FC and bone marrow morphological assessment between 3/2015-3/2020 at Mayo Clinic Rochester were included. Pts were excluded if a malignant hematological disorder was diagnosed prior to the time of FC. FC included evaluation of the following parameters: Abnormal expression of HLA-DR/CD13, CD2, CD7, CD45, and CD56 on blasts; and abnormal CD13/CD16 expression and side scatter on granulocytic cells. NGS panel up to 2018 included 34 genes, ASXL1, BCOR, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA1, GATA2, IDH1, IDH2, JAK2, KIT, KRAS, MPL, MYD88, NOTCH1, NPM1, NRAS, PHF6, PTPN11, RUNX1, SETBP1, SF3B1, TERT, TET2, TP53, U2AF1, WT1, and ZRSR2; in 2018, BRAF was omitted and 12 genes were added, ANRD26, DDX41, ELANE, ETNK1, KDM6A, MYD88, NOTCH1, RAD21, SH2B3, SRP72, SMC3, and STAG2. Results: Characteristics: Of 490 consecutive pts, 238 (median age 69 years (range 19-92), 66% males) met our inclusion criteria as ICUS. 86 (36%) pts had CCUS (abnormal cytogenetics and/or tested positive for pathogenic mutations on NGS). After a median follow-up of 28 months (95% CI: 20 to 31 months), 21 (25%) patients developed MN and 23 (27%) died during follow-up. Comparing ICUS vs CCUS: upon comparing CCUS pts to ICUS, several factors were found to be significantly different: CCUS pts were older (p= .02); majority male (p= .04), had more abnormal HLA-DR/CD13 (p &amp;lt;.0001), more side-scattered light by FC (p &amp;lt;.0001), more pancytopenia on follow up (p= .02) and more morphologic atypia (&amp;lt;.0001). Overall survival (OS) outcomes in CCUS: Several covariates were significant in univariate models, and model selection was used to generate a risk score based on abnormal CD7, abnormal CD13/CD16, abnormal HLA-DR/CD13, splenomegaly and history of prior chemotherapy or radiotherapy (range: 0 - 4; HR=2.58, [95 CI: 1.69 - 3.94], p&amp;lt;.0001). Risk scores were grouped as low risk (score=0), intermediate risk (score=1), and high risk (score=2+), with estimated 2-yr-OS of 95%, 84%, 40%, respectively (Figure 1). An extended risk score model including NGS factors added ASXL1 and IDH1 mutation status to the previous model (range: 0 - 6; HR=2.72, [95 CI 1.82 - 4.06], p&amp;lt;0.0001). MN-free survival (MNFS) in CCUS: 37 pts either progressed to MN and/or died with a median follow up time for MNFS of 22.4 months. Similar for OS, model selection approaches yielded a composite risk score: splenomegaly, BCOR mutation status, mutation in RAS signaling pathway, abnormal expression of flow markers CD13/CD16, HLA-DR/CD13 or CD7 (HR=3.23, [95 CI: 1.90 - 5.49], p=&amp;lt;0.0001). Risk scores were grouped as low risk (score=0), intermediate risk (score=1), and high risk (score ≥ 2), with estimated 1-yr MNFS of 84%, 74%, and 31%, respectively (Figure 2). Conclusion: CCUS has unique features compared to ICUS. Several factors, including clinical characteristics, immune-phenotyping by FC, and somatic mutations have important impact on risk of progression to MN and on overall survival. Our findings serve as proof-of-concept that such integrated models could help identify CCUS patients at higher risks for progression to MN or death. They can guide treatment accordingly and should be evaluated further. Disclosures Shah: Dren Bio: Consultancy.

Evaluation of Soluble Fibrin Monomer Complex in Patients with Sars-Cov-2 COVID-19 Infection

Introduction: In patients with SARS-CoV-2 COVID-19 infection elevated D-dimers are associated with a poor prognosis. Although suggestive of DIC, the majority of patients do not fulfil ISTH criteria for DIC. Studies have demonstrated that when compared to D-dimer, fibrin monomers are more sensitive and specific when differentiating overt DIC from non-overt DIC. Our special coagulation laboratory (SCL) routinely measures soluble fibrin monomer complex (SFMC) as part of our DIC profile in samples with elevated D-dimers. Here we aimed to investigate the percentage of patients with COVID-19 infection with elevated SFMC as performed as part of the DIC profile.Methods: Between April 1st 2020 and July 26, 2020 inpatients at the Mayo Clinic Rochester, MN campus with COVID-19 infection who underwent DIC testing in SCL were identified through SCL database. Patients were excluded if SARS-CoV2 PCR results were not available in the Mayo Clinic electronic medical record (EMR). DIC profile components include prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen and D-dimer. Reflex SFMC is performed if D-dimer is elevated. Data abstracted from EMR included results of laboratory tests, date of COVID-19 symptom onset, date of SARS-CoV2 PCR positivity, and death within 30 days of hospital admission. The ISTH DIC score was calculated and patients were labeled as overt DIC or non-overt DIC based off of ISTH DIC score ≥5.Results: 35 patients (19 female), median age 59 years (28-91) met our study criteria DIC profiles were obtained 6.5 (1-37) days after COVID-19 symptom onset (n=33) with 28 obtained within 14 days of symptom onset. Time to DIC profile from SARS-CoV2 PCR testing was 4 (0-37) days (n=35) with 31 having testing completed within 14 days of PCR positivity. 8 patients were intubated during hospitalization and of the remaining 27, 67% required supplemental oxygen.21/35 (60%) patients had an elevated fibrinogen (526.5 mg/dL (201-800)) while 19/35 (54%) had a prolonged PT (12.8 seconds (10.1-99.6) and 5/35 (14%) had a prolonged APTT (31 seconds (24-68)). 17 patients with prolonged PT and 3 patients with prolonged APTT had factor activity assays performed (Figure 1A). 9/35 (25%) had thrombocytopenia (230 x 109/L (12-709) and 27/35 (77%) patients had an elevated D-dimer (895 ng/ml FEU (220- >100,000). D-dimer was higher in males than in females (p: 0.049). Of those with elevated D-dimer only 5/27 (18.5%) had an elevated SFMC (5 mcg/ml (5- >1100) (Figure 1B).4/35 (11%) patients had ISTH DIC scores ≥ 5 and all had score of 5. All of these patients had D-dimer > 2000 ng/ml while only 2 had elevated SFMC however SFMC in both of these patients was < 15 mcg/ml. Of these, one patient with SFMC of 12 mcg/ml had known cirrhosis and the other with an SFMC of 11 mcg/ml had acute decompensation and associated shock liver. This patient also had venous thrombosis 3 days prior to DIC profile and died from complications related to COVID-19 infection. Of the two other patients with high ISTH score and normal SFMC, one had previous chronic thrombocytopenia of < 50 x109/L while the other had concomitant admission for acute and recurrent pancreatitis in the setting of alcoholism with acute intoxication. Six patients died within 30 days of admission and in 2/5 performed SFMC was elevated (Figure1C).Conclusion: Compared to 77% of patients with elevated D-dimers, of those tested only 18.5 % of patients had elevated SFMC. It has been hypothesized that the elevated D-dimer noted in COVID-19 pulmonary infection is a direct consequence of acute lung injury and not overt DIC. Although preliminary, the small percentage of patients with overt DIC by ISTH criteria and normal SFMC in the majority of the current cohort support this hypothesis; however studies in a larger more controlled cohort are needed to confirm these findings.DisclosuresSridharan:Alexion: Honoraria. Pruthi:Merck: Honoraria; Instrumentation Laboratory: Honoraria; HEMA Biologics: Honoraria; Bayer Healthcare: Honoraria; Genentech Inc.: Honoraria; CSL Behring: Honoraria.

Pre- Transplant Ferritin Predicts Overall Survival and Non-Relapse Mortality in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis

Background: Elevated serum ferritin (SF) is common in patients with myelofibrosis (MF) given the frequent red-cell transfusion requirements and impaired iron metabolism. The dysregulation of iron metabolism is associated with increased hepcidin levels which predict for inferior survival in patients with MF (Pardanani et al AJH 2013). High pre-transplant SF negatively impacts overall survival and non-relapse mortality in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for hematological malignancies (Chee et al BMT 2017 &amp; Yan et al 2018). However, the impact of elevated pre-transplant SF specifically on post-alloHCT outcomes has not been described in MF. Methods: We conducted a retrospective study of patients with MF undergoing allo-HCT at Mayo clinic Rochester, Arizona, and Florida from January 1st 2012 - December 31st 2019. We abstracted demographic and outcome variables to evaluate the impact of pre-transplant ferritin levels on post-transplant outcomes. We used a Receiver Operand Characteristic Curve to identify a pre-transplant serum ferritin (SF) of ≥ 1,123 ng/mL as the cutoff which best correlated with poor survival. Results: We identified 67 patients with MF who underwent allo-HCT during the study period with readily available data. Patients with a pre-transplant ferritin ≥ 1,123 ng/mL (n=18) had a median age of 59.4 years and were predominantly male (n=9, 50%) with primary myelofibrosis (n=12, 67%), had a DIPSS-plus int-2 (n=10, 56%) and high (n=6, 33%) risk categories and received a reduced-intensity conditioning (n=14, 78%) from a matched-unrelated donor (n=7, 50%) Table1. Patients with SF ≥ 1,123 ng/mL had a worse overall survival (OS) (median OS= 12.64 months [95%CI=6.08-19.20 months] vs. not-reached (NR) p=0.001). Patients with elevated SF had an increased non-relapse mortality (NRM) rate at 6 months (16.7%, [95%CI=0.4-37.2%]) vs 8.2%,[95%CI= 2.6-18.1%] p=0.021) and 12 months (33.3% [95%CI=13.0-55.4%] vs 10.4% [95%CI=3.8-21.0%] p=0.021) Patients with ≥ 1,123 ng/mL SF had a non-statistically significant higher rate of acute graft-vs-host disease grades 3-4 (28% vs 12.2% p=0.13) but similar rates of moderate to severe chronic graft-vs-host disease (31% vs 28% p=0.78). In the univariate analysis, SF ≥1,123 ng/mL and a Hematopoietic stem cell transplant comorbidity index (HCT-CI) ≥3 were associated with an increased risk of mortality (Hazard ratio [HR]=4.18 [95%CI=1.64-10.62] p=0.003] and HR=4.42 [95%CI=1.70-11.46] p=0.003, respectively). Both retained significance in multivariate analysis SF ≥1,123 ng/mL (HR= 2.80 [95%CI= 1.0-7.6], p=0.04)] and HCT-CI score ≥ 3 (HR 3.10 [95%CI= 1.12-8.62, p=0.03]) after adjusting for age, DIPSS-plus score, conditioning regimen intensity, donor type, CMV risk, prior use of ruxolitinib, and ABO mismatch. We grouped the patients into low, intermediate and high risk categories using SF level and HCT-CI scores as detailed in Figure 1. The risk category based on SF and HCT-CI was statistically significant in impacting OS and NRM in this cohort. The 12 month OS rate was lower in the high risk category (44.4% [95%CI= 13.6%-71.9%]) when compared to the intermediate (64.6%, [95%CI=39.7%-81.3%]) and low risk (91.9%, [95%CI= 76.9%-97.3%], p=0.0002) categories. Similarly, the 12 month NRM rate was higher in the high risk category (44.4%, [95%CI=11.0%-74.2%]) when compared to the intermediate (25%, [95%CI=8.7%-45.5%]) and low risk (5.3% [95%CI=0.9%-15.9%], p=0.0046) categories. Conclusion: In patients undergoing allogeneic SCT for myelofibrosis, serum ferritin ≥ 1,123 ng/mL is a predictor of high NRM and inferior OS. Combining ferritin serum levels with HCT-CI may help in better patient selection for allo-HCT in MF population. Larger patient cohort is warranted to confirm our findings. Disclosures Kharfan-Dabaja: Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Shah:Dren Bio: Consultancy.

Coronary artery calcification and cardiovascular outcomes after chest radiation therapy in breast cancer patients

Abstract Introduction Coronary artery calcification (CAC) is associated with and identifies patients at higher risk of major adverse cardiovascular events (MACE). However, the prevalence, characteristics, and outcomes of cancer patients with CAC on CT before or after chest radiation therapy (RT) are not well addressed. Methods Retrospective cohort study of all breast cancer patients who underwent chest RT at Mayo Clinic Rochester in 2010. All pre-RT CTs were reviewed and the extent of CAC was recorded in addition to history of pre-RT atherosclerotic risk factors (hypertension (HTN), diabetes mellitus (DM), dyslipidemia, and smoking), history of pre-RT cardiovascular disease (CVD), and RT dosage. MACE (sudden cardiac death (SCD), acute coronary syndrome (ACS), and stroke), and CAC progression in follow-up were recorded. CAC extent was quantified before and on 5-year follow-up CT scan in all patients, and a positive change was considered progression. Patients were divided into 2 groups based on the presence of CAC before RT: present (group 1) or absent (group 2). Results Our cohort was comprised of 244 breast cancer patients who received chest RT. A total of 39 patients (16.9%) had evidence of CAC on CT prior to RT. Compared with patients without CAC before RT (n=205), those with CAC before RT were found to be older (71.8±7.7 vs 58.9±11.3, p&amp;lt;0.01), had higher pre-RT history of HTN (84.6% vs 47.8%); p&amp;lt;0.01), DM (20.5% vs 4.4%; p&amp;lt;0.01), dyslipidemia (74.2% vs 40%; p&amp;lt;0.01), CAD (23.1% vs 3.9%; p&amp;lt;0.01), and stroke (7.69% vs 1.45%; p=0.04). Following RT, patients in group 1 were more likely to exhibit ACS (33.3% vs 2.9%; p&amp;lt;0.01), and stroke (22.6% vs 5.2%; p&amp;lt;0.01). Multinomial logistic regression identified pre-RT CAD pre-RT CAC (β=1.01 (0.33–1.69), OR=7.60 (1.93–29.93); p=0.02) pre-RT CAD (β=0.78 (0.06–1.49), OR=4.74 (1.14–19.74); p=0.03) as independent predictors for the development of MACE after RT. Progression in CAC after RT was found in 61.9% of all patients (13/21) who developed MACE. Conclusion MACE in breast cancer patients undergoing RT can be predicted before RT based on the CV risk factor and disease profile. The strongest predictor for MACE, however, is evidence of CAC before RT. These data provide a unique window for the identification and follow-up of breast cancer RT patients who have a risk of MACE. Funding Acknowledgement Type of funding source: None

Cause-specific mortality and heart failure readmissions according to the HFA-PEFF algorithm in patients hospitalised for heart failure with preserved ejection fraction

Abstract Background The HFA-PEFF algorithm has been recently developed and is recommended by the European Society of Cardiology to make a diagnosis of heart failure with preserved ejection fraction (HFpEF). Based on functional echocardiography criteria, morphological criteria, and natriuretic peptide levels, a score from 1 to 6 is obtained with higher scores indicating a higher probability of HFpEF. Purpose This study investigates the prognostic value of the HFA-PEFF score in HFpEF patients hospitalised for decompensation. Methods This retrospective cohort study includes consecutive patients with HFpEF, admitted to Mayo Clinic Rochester between 2010–2015 and requiring treatment with intravenous loop diuretics for congestion. The HFA-PEFF score was calculated for all patients with echocardiography data available within 1 year and natriuretic peptide levels obtained upon admission. The study population was subsequently stratified according to HFA-PEFF score ≤4 (n=79), =5 (n=93), or =6 (n=271). Incidence rates of recurrent heart failure admissions per 100 patient-years of follow-up, time to all-cause mortality, and mortality causes were compared among strata. Results In 443 patients with HFpEF (78±12 years; 60% women), higher HFA-PEFF score was associated with older age, female gender, higher systolic blood pressure, and worse renal function. Heart failure readmission rates were higher in patients with HFA-PEFF score =5 [46.0 (38.5–53.5)] or HFA-PEFF score =6 [45.0 (40.1–49.8)] versus HFA-PEFF score ≤4 [28.9 (22.7–35.0); P-value&amp;lt;0.001 for differences; see upper panel figure]. Increasing HFA-PEFF score was associated with a shorter median survival (P-value&amp;lt;0.001), which was 65 months (36–89 months) in HFA-PEFF score ≤4, 45 months (26–59 months) in HFA-PEFF score =5, and 28 months (22–42 months) in HFA-PEFF score =6 (see lower panel figure). The proportions of deaths directly related to heart failure were comparable among HFA-PEFF strata (49% versus 49% versus 52%, respectively; P-value=0.903), as was the contribution of cardiovascular death (60% versus 57% versus 63%, respectively; P-value=0.662). Overall, few differences in patterns of mortality causes were observed among strata. There was a lower contribution of primary respiratory disease (mainly chronic obstructive pulmonary disease) to mortality in patients with a higher HFA-PEFF score (26% versus 19% versus 6%, respectively; P-value&amp;lt;0.001). Conclusions Higher HFA-PEFF score in hospitalized patients with HFpEF is associated with increased risk of subsequent heart failure readmissions and all-cause mortality, which includes both heart failure specific and non-heart failure mortality. Heart failure readmissions &amp; mortality Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Belgian American Educational Foundation (B.A.E.F.); Special Research Fund (BOF) of Hasselt University (Hasselt, Belgium)

Haemodynamic determinants of improved aerobic capacity after tricuspid valve surgery in Ebstein anomaly

BackgroundAlthough tricuspid valve surgery improves functional capacity in patients with Ebstein anomaly, it is not always associated with improvement in aerobic capacity. The purpose of this study was to identify...

Curating Archival Anatomic Pathology Material For Machine Learning Algorithm Development

Abstract Introduction/Objective Advances in whole slide imaging have enabled the application of machine learning algorithms to anatomic pathology. In the current state, the development of accurate algorithms requires robust training data with correctly assigned diagnostic and classification labels. Increasingly, institutions have looked to their archival slides as a source of “ground truth” for algorithm development. However, the curation and use of archival data poses several challenges. Here, we share lessons learned from reviewing head and neck pathology consult cases spanning a 10- year period at Mayo Clinic Rochester. Methods Archived surgical pathology slides from 2,590 consult cases were reviewed. Clinical and demographic information was recorded for each case, including surgical date, surgical procedure, anatomic site, age, gender and diagnosis. Cases were excluded from the curated archive if there was insufficient volume or quality of tissue to render a specific diagnosis (141 cases, 5.6%). Slides with a range of tissue size and quality, from numerable laboratories were included in the curated archive. Selected cases were collated by anatomic site: ear, gnathic, larynx, nasopharynx, neck, oral cavity, oropharynx, salivary gland and sinonasal tract. Results Common diagnostic reconciliations (115 cases, 4.4%) fell within the following categories: (1) novel entities (59 cases, 2.3%), including biphenotypic sinonasal sarcoma and clear cell carcinoma; (2) novel classifications (21 cases, 0.8%), as seen in HPV-related oropharyngeal squamous cell carcinoma and polymorphous adenocarcinoma; and (3) novel grading schema (35 cases, 1.4%), as seen in keratinizing dysplasia and oropharyngeal malignancies. Conclusion Several nuances emerged in the process of reviewing slides, highlighting the need for continual amendment of any machine learning dataset over time. Curating anatomic pathology cases for machine learning algorithm development requires the recognition of emerging entities, with re-classification and re-grading as needed.

Shock in the cardiac intensive care unit: Changes in epidemiology and prognosis over time

We included 1859 unique patients admitted to the Mayo Clinic Rochester CICU from 2007 through 2018 with an admission diagnosis of shock. Temporal trends, including mortality, were assessed across 3-year periods. Shock comprised 15.1% of CICU admissions during the study period, increasing from 8.8% of CICU admissions in 2007 to 21.6% in 2018 (P < .01 for trend). Mean age was 68 ± 14 years (38% females). Shock was cardiogenic in 65%, septic in 10% and mixed cardiogenic-septic in 15%. Concomitant diagnoses in patients with cardiogenic shock (CS) included acute coronary syndrome (ACS) in 17%, heart failure (HF) in 35% and both in 40%. There was no significant change in the prevalence of individual shock subtypes over time (P > .1). Among patients with CS, the prevalence of ACS decreased and the prevalence of HF increased over time (P < .01). Hospital mortality was highest among patients with mixed shock (39%; P = .05). Among patients with CS, hospital mortality was lower among those with HF compared to those without HF (31% vs. 40%, P < .01). Hospital mortality decreased over time among patients with shock (P < .01) and CS (P = .02). The prevalence of shock in the CICU has increased over time, with a substantial prevalence of mixed CS. The etiology of CS has changed over the last decade with HF overtaking ACS as the most common cause of CS in the CICU.