bluuebunny/crossref_metadata_2025 huggingface dataset:
914 ATRIAL AND VENTRICULAR FUNCTIONAL MITRAL REGURGITATION: CLINICAL CHARACTERISTICS AND OUTCOMES IN MITRACLIP TREATED PATIENTS
Authors: Scalzi Giuseppe , Aquila Iolanda , Polimeni Alberto , Lucchino Alessandro , Ielapi Jessica , Volpe Lorenzo , Velato Letizia , Vizzari Francesca , Mascaro Giuseppina , Spaccarotella Carmen , Indolfi Ciro , Mongiardo Annalisa
Published: December 2022

Background

mitral regurgitation (MR) is the second most common valvular heart disease in Europe. In the contest of functional (or secondary) MR recently has emerged a new entity, the atrial functional MR. This form is due to left atrial dilatation, it has no significant degenerative change in mitral valve complex or significant LV systolic disfunction. Conversely the ventricular functional mitral regurgitation (V-FMR) is due to systolic disfunction and left ventricular dilatation.

Aim

the aim of this study was to evaluate the differences in clinical characteristics and outcomes of patients with AFMR and VFMR treated with Mitraclip.

Methods

a retrospective analysis collected consecutive patients with functional MR who underwent transcatheter mitral valve repair using Mitraclip system in our division. A total of 161 patients were divided into the following two categories: VFMR (127 patients), defined as EF<40% or EF ≥40% with history of myocardial infarction, and AFMR (34 patients) identified as EF≥50% and LAVi >48 mL/m2. Baseline and clinical characteristics, echocardiographic parameters and 12 months clinical outcomes (overall mortality at 12 months, MACE at 12 months, re-hospitalization for heart failure (HF), re-hospitalization from other causes at 12 months and number of re-hospitalization at 12 months) were analyzed.

Results

compared to AFMR, patients with VFMR were younger (73 vs 78 years) had a higher man prevalence (72,4% vs 50%), higher rate of: hypercholesterolemia (79,5% vs 67,6%), smokers (14,2% vs 5,9%), diabetes (39,4% vs 20,6%), chronic kidney disease (55,9% vs 47,1%), NT-proBNP mean value (4403,437 pg/ml vs 2063,409 pg/ml), NYHA class ≥III (84.3 vs 52.9%) and lower rate of hypertension (85% vs 97.1%). In AFMR population there was higher prevalence of atrial fibrillation (70.6% vs 45.7%) and tricuspid valve regurgitation ≥2+ (82.3% vs 68,5%). Moreover, in this group, was lower the all-cause mortality rate at 12 months (9.4 vs 22%), MACE at 12 months (4.5 vs 24.5%), re-hospitalization for HF (15.6% vs 33.1%), re-hospitalization from other causes at 12 months (18.8% vs 31.6%) and number of re-hospitalization at 12 months ≥1 (31,3% vs 59.9%).

Conclusion

our analysis demonstrated that clinical outcomes at 12 months were lower for the AFMR group. These data are consistent with the literature, where AFMR is considered to have a better prognosis than VFMR, and underline the importance of differentiating these two types of population.
900 PREDICTORS OF OUTCAMES IN PATIENTS WITH MITRAL REGURGITATION UNDERGOING PERCUTANEOUS VALVE REPAIR
Authors: Serafino Sergio , Polimeni Alberto , Mongiardo Annalisa , Spaccarotella Carmen , Sorrentino Sabato , Mascaro Giuseppina , Aquila Iolanda , Lucchino Alessandro , Vizzari Francesca , Serratore Serena , Messina Chiara , Di Costanzo Assunta , Velato Letizia , Ciliberto Federica , Indolfi Ciro
Published: December 2022

Aims

Mitral regurgitation is the second-most frequent VHD in Europe. According to the latest ESC Guidelines, transcatheter edge-to-edge repair (TEER) was included as a treatment option in patients with severe symptomatic MR at high risk for surgery (Class IIb recommendation) for primary MR and a Class IIa recommendation for secondary MR.

We sought to investigate predictors of clinical outcome in patients with mitral regurgitation undergoing percutaneous valve repair.

Methods and Results

The MITRA-UMG study, a single-center registry, retrospectively collected consecutive patients with symptomatic moderate-to-severe or severe MR undergoing MitraClip therapy between March 2012 to October 2021 at Magna Graecia University. Clinical, echocardiographic and procedural data were collected and compared with post procedural outcomes. Procedural success was defined as successful implantation of one or more clip(s) with a post-procedure reduction of MR of 2 + or less at discharge. The primary endpoint was the composite of cardiovascular death or rehospitalization for heart failure.

The median follow-up was 456 days (IQR 372–1130 days) with a complete 1-year follow- up in 188 of 200 (97%) patients. A functional aetiology was classified in 75% of patients. Procedural success was obtained in 98% of patients. The composite primary endpoint of cardiovascular death or rehospitalization for HF was met in 77 patients (36%) with cumulative incidences of 7% at 30 days and 25% at 1 year. In the Cox multivariate model, NYHA functional class and left ventricular end-diastolic volume index (LVEDVi), independently increased the risk of the primary endpoint at long-term follow-up. At Kaplan–Meier analysis, a LVEDVi > 92 ml/m2 was associated with an increased incidence of the primary endpoint (HR 3.55, 95%CI [2.03, 6.18], P<0.0001) (Figure).

Conclusions

In this study, patients presenting with dilatated ventricles (LVEDVi > 92 ml/m2) and advanced heart failure symptoms (NYHA IV) carried the worst prognosis after TEER.
1056 AN OUT OF ORDINARY CASE OF ACUTE SEVERE AORTIC REGURGITATION IN SPONTANEOUS AORTIC VALVE LACERATION
Authors: Cava Francesco , Cosentino Nicola , Lauri Gianfranco , De Metrio Monica , Marenzi Giancarlo
Published: December 2022

A 77-year-old male presenting with acute chest pain and syncope was sent to our emergency room by ambulance. An echocardiogram revealed severe pericardial effusion, thoracic aortic ectasia, and mild aortic regurgitation (AR). Computed tomography (CT) scan did not demonstrate aortic dissection. He underwent emergency pericardiocentesis for acute cardiac tamponade. After three hours of clinical monitoring, the transthoracic echocardiogram revealed de-novo severe AR, and CT scan showed a probable laceration of left ventricular wall at the level of left sinus of Valsalva. The lesion was confirmed during urgent cardiac surgery and it was successfully repaired using stitches intertwined with double pledglet and aortic bioprosthesis implant.
520 AN UNEXPECTED SURPRISE
Authors: Soriente Lucia , Santopietro Mario , Aliberti Chiara , Di Fonzo Rosanna , Vecchione Carmine , Di Muro Michele Roberto
Published: December 2022

Aortic Pseudoaneurysms often represent a complication of reconstructive surgery of the aortic valve and ascending aorta due to dehiscence of the surgical suture, especially in correspondence of reimplanted coronary ostia. We present the case of a 74-year-old patient with a recent feverish episode and positive blood cultures for Serratia marcescens, who came to our attention to perform a transesophageal echocardiogram for suspected endocarditis.

In history, previous aortic valve replacement with biological prosthesis about 6 months before, complicated by pseudoaneurysm of the ascending aorta caused by dehiscence of sutures, treated by pseudoaneurismectomy and reconstruction of aortic continuity.

Transesophageal echo showed a normopositioned bioprosthesis in the aortic location and absence of formations compatible with vegetations. During the examination, a subtle drop-out of echoes in the anterior wall of the ascending aorta was observed at approximately 2 cm from the aortic valve plane, raising suspicion of communication with a large pseudoaneurysmal sac. The Colordoppler showed a jet of discrete turbulence between the two cavities; for these reasons it was indicated to perform an urgent angioTC, which documented the presence of fissuring of the proximal ascending aorta with active overflow of contrast media with a collar of about 12 mm and considerable blood collection in the anterior mediastinum of about 51×38×60mm.

The patient underwent false lumen exclusion surgery by percutaneous amplatzer device placement. Currently, the patient is asymptomatic and in good clinical condition.
1157 WITCHING FROM DUAL ANTIPLATELET THERAPY WITH ASPIRIN PLUS A P2Y12 INHIBITOR TO DUAL PATHWAY INHIBITION WITH ASPIRIN PLUS VASCULAR-DOSE RIVAROXABAN: THE SWITCHING ANTI-PLATELET AND ANTI-COAGULANT THERAPY (SWAP-AC) STUDY
Authors: Giordano Salvatore , Ortega-paz Luis , Franchi Francesco , Rollini Fabiana , Galli Mattia , Been Latonya , Ghanem Ghussan , Shalhoub Awss , Ossi Tiffany , Rivas Andrea , Zhou Xuan , Pineda Andres M. , Suryadevara Siva , Soffer Daniel , Zenni Martin M. , Jennings Lisa K , Angiolillo Dominick J.
Published: December 2022

Aims

To assess the feasibility of switching from dual antiplatelet therapy (DAPT) to dual pathway inhibition (DPI) and to compare the pharmacodynamic (PD) profiles of these treatment regimens.

Methods and results

This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81 mg/qd) plus a P2Y12 inhibitor [clopidogrel (75 mg/qd; n = 30), ticagrelor (90 mg/bid; n = 30), or prasugrel (10 mg/qd; n = 30)]. Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81 mg/qd plus rivaroxaban 2.5 mg/bid). PD assessments included: VerifyNow P2Y12 reaction units; light transmittance aggregometry following stimuli with adenosine diphosphate (ADP), tissue factor, and a combination of collagen, ADP, and TF (CATF, maximum platelet aggregation %); thrombelastograph coagulation analyzer; thrombin generation (TG). Assays were performed at baseline (on DAPT) and 30 days post-randomization (trough and peak). Switching from DAPT to DPI occurred without major side effects. DAPT was associated with enhanced P2Y12 inhibition, while DPI with reduced TG. Platelet-mediated global thrombogenicity (primary endpoint) showed no differences between DAPT and DPI in the ticagrelor (14.5% [0.0–63.0] vs. 20.0% [0.0–70.0]; p = 0.477) and prasugrel (20.0% [0.0–66.0] vs. 4.0% [0.0–70.0]; p = 0.482), but not clopidogrel (27.0% [0.0–68.0] vs. 53.0% [0.0–81.0]; p = 0.011), cohorts.

Conclusion

In patients with CCS, switching from different DAPT regimens to DPI was feasible, showing enhanced P2Y12 inhibition with DAPT and reduced TG with DPI, with no differences in platelet-mediated global thrombogenicity between DPI and ticagrelor- and prasugrel, but not clopidogrel-, based DAPT.
1156 CANGRELOR IN PATIENTS WITH CORONARY ARTERY DISEASE PRE-TREATED WITH TICAGRELOR: THE SWITCHING ANTIPLATELET (SWAP)-5 STUDY
Authors: Giordano Salvatore , Franchi Francesco , Ortega-paz Luis , Rollini Fabiana , Galli Mattia , Been Latonya , Ghanem Ghussan , Shalhoub Awss , Ossi Tiffany , Rivas Andrea , Zhou Xuan , Pineda Andres M , Suryadevara Siva , Soffer Daniel , Zenni Martin M , Reiter Birgit , Jilma Bernd , Angiolillo Dominick J
Published: December 2022

Objectives

To rule out a drug-drug interaction (DDI) among cangrelor-treated patients who have been pre-treated with ticagrelor.

Background

There are no studies specifically designed to rule out a DDI when cangrelor is used among patients who have been pre-treated with ticagrelor.

Methods

In this prospective, randomized, double-blind, placebo-controlled, cross-over, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (n = 20) were pre-treated with a 180-mg ticagrelor loading dose (LD) and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1-4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included: VerifyNow P2Y12 reaction units (PRU), light transmittance aggregometry vasodilatorstimulated phosphoprotein, and Total Thrombus-Formation Analysis System. PK/PD assessments were performed at 7-time points.

Results

Compared to placebo, adding cangrelor to patients pre-treated with ticagrelor resulted in a significant reduction in PRU at 30 min and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU was low and similar in both groups (16.9 vs. 12.6; mean difference: 4.3; 95%CI: -28.6; 37.3), meeting the non-inferiority primary endpoint (predefined non-inferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite.

Conclusions

Compared with placebo, the use of cangrelor in patients pre-treated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI.
A flexible RecC surface loop required for Chi hotspot control of RecBCD enzyme
Authors: Amundsen Susan K , Richardson Alex , Ha Khoi , Smith Gerald R
Published: December 2022

Escherichia coli RecBCD helicase–nuclease promotes vital homologous recombination-based repair of DNA double-strand breaks. The RecB nuclease domain (Nuc) is connected to the RecB helicase domain by a 19-amino-acid tether. When DNA binds to RecBCD, published evidence suggests that Nuc moves ∼50 Å from the exit of a RecC tunnel, from which the 3′-ended strand emerges during unwinding, to a distant position on RecC's surface. During subsequent ATP-dependent unwinding of DNA, Nuc nicks the 3′-ended strand near 5′-GCTGGTGG-3′ (Chi recombination hotspot). Here, we test our model of Nuc swinging on the tether from the RecC tunnel exit to the RecC distant surface and back to the RecC tunnel exit to cut at Chi. We identify positions in a flexible surface loop on RecC and on RecB Nuc with complementary charges, mutation of which strongly reduces but does not eliminate Chi hotspot activity in cells. The recC loop mutation interacts with recB mutations hypothesized to be in the Chi-activated intramolecular signal transduction pathway; the double mutants, but not the single mutants, eliminate Chi hotspot activity. A RecC amino acid near the flexible loop is also essential for full Chi activity; its alteration likewise synergizes with a signal transduction mutation to eliminate Chi activity. We infer that altering the RecC surface loop reduces coordination among the subunits, which is critical for Chi hotspot activity. We discuss other RecBCD mutants with related properties.
Interferon regulatory factor-2 is required for the establishment of the gut intraepithelial T-cell compartment
Authors: Tokumaru Shigeo , Yamamoto Yuta , Yoshizawa Kazuki , Soejima Yuji , Sanjo Hideki , Taki Shinsuke
Published: December 2022

CD8αα+ intestinal intraepithelial lymphocytes (iIELs) are known for their unique role in keeping the integrity of the intestinal epithelial barrier, but factors affecting the development of these cells have not been thoroughly understood. Here, we found that the transcriptional regulator interferon regulatory factor-2 (IRF-2) plays a cell-intrinsic, indispensable role in establishing iIEL populations. CD8αα+, but not CD8αβ+, iIELs bearing TCRαβ or TCRγδ were severely reduced in numbers in mice lacking this factor (Irf2–/– mice). Moreover, the majority of residual CD8αα+TCRαβ+ iIELs in these mice was immature as judged from their Thy1.2high phenotype and inefficient T-bet expression. Thymic IEL precursors isolated from Irf2–/– mice failed to efficiently generate CD8αα+TCRαβ+ and TCRγδ+ IELs upon transfer in vivo and CD8αα+TCRαβ+ cells in response to IL-15 in vitro. Double mutant mice lacking both interleukin-15 (IL-15) and IRF-2 showed an even more severe iIEL defect than in mice lacking IL-15 alone. Upon increasing agonistic TCR signal strength through OT-II TCR transgenesis, CD8αα+TCRαβ+ iIELs became more abundant but remained immature on the Irf2–/– background. Our current observations, thus, revealed the unique bimodal role that IRF-2 plays in promoting not only generation of IEL progenitors in the thymus but also maturation of iIELs in the periphery in IL-15-dependent and -independent manners.
Asian tropical forests assimilating carbon under dry conditions: water stress or light benefits?
Authors: Yang Lian-Yan , Yu Rui , Wu Jin , Zhang Yongjiang , Kosugi Yoshiko , Restrepo-Coupe Natalia , Huete Afredo , Zhang Jie , Liu Yu-Hai , Zhang Xiang , Liu Wen-Jie , Zhao Jun-Fu , Zeng Jiye , Song Qing-Hai , Chen Ya-Jun , Song Liang , Tan Zheng-Hong
Published: December 2022

Tropical forests are characterized by vast biomass, complex structures and mega-biodiversity. However, the adaptation processes of these forests to seasonal water availability are less understood, especially those located in the monsoonal and mountainous regions of tropical Southeast Asia. This study used four representative tropical forests spanning from 2° N to 22° N in continental Southeast Asia to address dry-condition photosynthesis at the seasonal scale. We first provided novel and reliable estimations of ecosystem photosynthesis (gross primary production; GPP) seasonality at all four sites. As expected, both evergreen and deciduous seasonal forests exhibited higher GPPs during the rainy season than during the dry season. A bimodal pattern corresponding to solar radiation occurred in the GPP of the perhumid forest. The surface conductance (Gs) was consistently lower both in the dry season and during dry spells (DSPs) than during the wet season and non-dry spells. However, this did not prevent GPP from increasing alongside increasing irradiance in the perhumid forest, suggesting that other ecosystem physiological properties, for example, the light-saturated photosynthetic rate, must have increased, thus surpassing the effect of Gs reduction. Thus, perhumid forests could be defined as light-demanding ecosystems with regard to their seasonal dynamics. Seasonal forests are water-stressed ecosystems in the dry season, as shown by the reductions in GPP, Gs and related ecosystem physiological properties. At all four forest sites, we observed a lack of consistent adaptive strategy to fit the water seasonality due to the diversity in leaf phenology, soil nutrient availability, root depth and other potential factors.
Lipid metabolism in tumor-infiltrating T cells: mechanisms and applications
Authors: Ke Xin-Yu , Zou Miaowen , Xu Chenqi
Published: December 2022

As an essential part of adaptive immunity, T cells coordinate the immune responses against pathogens and cancer cells. Lipid metabolism has emerged as a key regulator for the activation, differentiation, and effector functions of T cells. Therefore, uncovering the molecular mechanisms by which lipid metabolism dictates T cell biology is of vital importance. The tumor microenvironment is a hostile milieu, i.e. often characterized by nutrient restriction. In this environment, various cells, such as T cells and cancer cells, reprogram their metabolism, including their lipid metabolism, to meet their energy and functional needs. Here, we review the participation of fatty acid and cholesterol metabolism homeostasis in orchestrating T cell biology. We demonstrate how the tumor microenvironment reshapes the lipid metabolism in T cells. Importantly, we highlight the current cancer therapeutic interventions that target fatty acid and cholesterol metabolism of T cells. By offering a holistic understanding of how lipid metabolic adaption by T cells facilitates their immunosurveillance in the tumor microenvironment, we believe this review and the future studies might inspire the next-generation immunotherapies.
81. Impact of Early Post-Transplant Multidrug-Resistant Organism Detection Among Renal Transplant Recipients, 2005–2021
Authors: Babiker Ahmed , Karadkhele Geeta , Robichaux Chad , Page Alex M , Satola Sarah W , Kraft Colleen S , Larsen Christian P , Pouch Stephanie M , Woodworh Michael H
Published: December 2022

Background

Understanding the impact of multi-drug resistant organism (MDRO) acquisition on renal transplant recipients (RTR) mortality and allograft function is paramount to mitigating deleterious outcomes. Prior studies have been limited by lack of control groups and sample sizes. We aimed to the assess whether the detection of an MDRO or a susceptible organism during the early post-transplant period was associated with increased mortality and allograft failure among RTRs.

Methods

We performed a retrospective cohort study of RTRs at the Emory University Transplant Center between 2005–2022. Early post-transplant culture positivity was defined as a positive culture within 30 days of renal transplant. The primary outcome was a combined composite of one year- allograft loss and/or mortality following renal transplant. A Kaplan–Meier survival analysis was performed, and differences between survival curves for RTRs with an early post-transplant positive culture (stratified by susceptibility status) and negative control RTRs were assessed using the log-rank test. Multivariable cox proportional hazard and a competing risk analysis were performed.

Results

Among 3,233 RTRs, 259 (8%) had a susceptible organism detected and 35 (1%) had an MDRO detected (Figure 1). Demographic and microbiology characteristics are summarized in Table 1 & 2. One hundred and forty-nine (5%) RTRs experienced the composite outcome, this was experienced more frequently among RTRs with an MDRO detected (14%, 5/35) compared to RTRs with a susceptible organism defected (8%, 21/259) and negative controls (4%, 123/2,939) (Table 3). Significant difference between time from transplantation to the composite outcome when comparing negative controls, MDRO and susceptible organisms RTRs was observed (log rank p < 0.001) (Figure 2). Early post-transplant culture positivity (aHR 1.98 [1.30, 3.04]) and MDRO detection (aHR: 3.20 [1.30, 7.84]) were significantly associated with the composite outcome (Table 4).

Conclusion

MDRO as well as susceptible organism acquisition during the early post-transplant period was associated with increased mortality and allograft loss highlighting the need for increased infection prevention efforts within this vulnerable population.

Disclosures

All Authors: No reported disclosures.
735. Contribution of the Oral Cavity and Gastrointestinal Microbiome on Bloodstream Infections inLeukemia Patients
Authors: McMahon Stephanie , Microbiology B S , Galloway-Peña Jessica , Sahasrabhojane Pranoti V , Shelburne Samuel A
Published: December 2022

Background

Blood stream infections (BSI) are a common cause of morbidity and mortality in immunocompromised patients. It was previously reported that intestinal domination (defined as occupation of ≥ 30% of the microbiota by a single bacterial taxon) by

Enterococcus and Proteobacteria often preceded enterococcal and gram-negative BSI.

Methods

16s rRNA sequencing was used to analyze the saliva and stool of 73 acute leukemia patients with BSIs to determine the correlation between the taxa present ( > 0% relative abundance), colonizing ( > 3%) or dominating ( > 30%) a patient’s microbiome and the BSI agent. Species level confirmation of these findings was performed via digital droplet PCR (ddPCR) and LEfSe analysis was used to determine enrichment of infectious taxa at either collection site. Whole genome sequencing and antimicrobial susceptibilities on all BSI isolates.

Results

We collected simultaneous patient stool and blood isolates from 11 Pseudomonas aeruginosa, 14 Escherichia coli, 4 Klebsiella sp., 8 Enterococcus sp., 18 viridans group streptococci (VGS), 13 Staphylococcus epidermidis, and 5 Staphylococcus aureus BSIs. Mann-Whitney testing confirmed that individuals with P. aeruginosa (oral P =.004, stool P < .001), E. coli (stool P < .001), and VGS infections (oral P =.001) had significantly higher relative abundance of those respective genera compared to other BSI patients, and this appeared to be site specific. LEfSe analysis confirmed enrichment of Pseudomonas in the saliva and stool, Escherichia in the stool, and Streptococcus in the saliva of respective infections. However, while 64 patients showed presence of the infectious genera in the stool and/or saliva at time of BSI, only 7 exhibited domination. ddPCR was used to confirm not only species specificity, but the detection of those antibiotic resistance determinants (CTX-14, CTX-15, Van A and CfrA) found in the BSI isolates within concurrent stool samples.

Conclusion

It appears that GI domination by the infecting organism was not present at the time of most BSIs. However, in scenarios where the etiological agent was detectable in the saliva or stool, so were the antibiotic resistant determinants. Furthermore, certain infections exhibited a significant difference in oral or stool presence by the same bacteria they were infected with.

Disclosures

All Authors: No reported disclosures.
740. Does Natural Language Processing Improve Identification of Hospitalized People Who Use Drugs?
Authors: Sato Taisuke , Murphy Meghan , Miller Robert , Wurcel Alysse Gail
Published: December 2022

Background

In the absence of substance use disorder treatment and harm reduction tools, people who use drugs (PWUD) are at increased risk for severe injection-related infections (SIRI). Health services research characterizing the scope and trends of hospitalizations for SIRI often requires administrative billing records, urine toxicology, and medications to treat opioid use disorder, often supplemented with manual chart review. The goal of this research was to examine the feasibility of using natural language processing (NLP) to augment traditional systems of PWUD. We explored the practicality of using Natural Language Processing as a tool to accurately identify PWUD in electronic medical records (EMR).

Methods

We worked with information technology/computer science specialists to create a cohort of all people hospitalized at Tufts Medical Center from January 1, 2020, to April 1, 2022. Patients entered this cohort through the presence of any of these criteria: ICD10 codes for substance use disorder, positive urine toxicology results for drugs (including opiates, cocaine, amphetamine), prescriptions for medications to treat substance use disorder (at admission, during hospitalization or discharge) and the presence of NLP keywords. The NLP keyword list was created through iterative meetings with IT specialists (Table 1).

Results

There were 3102 patients with 3501 hospitalizations. The Venn Diagram (Figure 1) displays the overlap of the 4 criteria. Only 55 people were identified by NLP terms only. The most frequent criteria filled for cohort entry was the toxicology screen. Only 4.1% of the group had all 4 criteria.

Conclusion

Identifying PWUD using an NLP algorithm was possible, but there was a small number of people who were added to the cohort only on NLP criteria. Improved methodologies of identifying PWUD with medical needs are necessary to better identify gaps in healthcare, facilitate benchmarking of quality care, and improve the lives of PWUD.

Disclosures

All Authors: No reported disclosures.
742. Identification of Barriers to Shifting Management of Diabetic Foot Infections from the Hospital Setting to a Multidisciplinary Wound Clinic
Authors: Lee Michelle , Dillman Nicholas O , Petty Lindsay A , Zhou Shiwei , Nagel Jerod
Published: December 2022

Background

Hospitalized patients with diabetic foot infections (DFI) are commonly stable upon admission and lack signs of sepsis, necrotizing fasciitis, critical limb ischemia, or bacteremia. Patients are admitted for key components of DFI care: non-urgent procedures for source control; radiographic imaging; cultures; consultation with infectious diseases (ID), podiatry, or vascular surgery; and peripherally inserted central catheter (PICC) access. We aimed to identify the proportion of patients with low acuity DFI who were hospitalized and to characterize potential barriers to outpatient management.

Methods

Between 2020 and 2021, data from the medical record were abstracted for adult patients admitted to Michigan Medicine with an ICD-10 admission diagnosis of DFI. Patients were categorized into low and high acuity cohorts. High acuity was defined as sepsis, necrotizing fasciitis, critical limb ischemia, or bacteremia. Low acuity was defined as clinical stability (≤ 1 systemic inflammatory response syndrome (SIRS) criteria) and without high acuity criteria. The primary outcome was the prevalence of low acuity DFIs admitted to the hospital, duration of hospitalization, and associated costs. Secondary outcomes included 30-day all-cause mortality, DFI recurrence, DFI readmission, and time from clinical stability to completion of DFI care (non-urgent procedures; radiographic imaging; cultures; consultation to ID, podiatry, or vascular surgery; and PICC access).

Results

Of 64 hospitalized DFI patients, 37 (58%) were low acuity and 27 (42%) high acuity. All low acuity patients were clinically stable on admission with a median hospitalization length of 6.3 days. Figure 1 shows the time to completion of key components of DFI care from clinical stability. Low acuity group had DFI recurrence of 5.4%; readmission with DFI of 10.8%; and all-cause mortality of 5.4%. The median hospitalization cost for low-acuity DFI was $55,500 per patient.

Conclusion

More than half of hospitalized DFI patients are low acuity, and could have avoided hospitalization. These patients had a median hospitalization length of 6.3 days and total cost of $55,500. Developing a coordinated process to manage low acuity patients outpatient may avoid unnecessary hospitalizations and reduce healthcare cost.

Disclosures

All Authors: No reported disclosures.
798. Life-years Gained among non-Hispanic Black and White Men who have Sex with Men in the United States with Improvements in the HIV Care Continuum A Simulation Modeling Study
Authors: Rich Katherine M , Reddy Krishna , Ahonkhai Aimalohi , Shebl Fatma , Pandya Ankur , Losina Elena , Freedberg Kenneth , Hyle Emily P
Published: December 2022

Background

Structural barriers and racism result in inequities across the HIV care continuum. We quantified the magnitude of racial disparities in life expectancy (LE) and the potential impact of interventions to improve the HIV care continuum among non-Hispanic Black and White men who have sex with men (MSM) in the US.

Methods

Using the validated CEPAC microsimulation HIV model, we projected LE among non-Hispanic Black MSM (BMSM) and White MSM (WMSM). We estimated average age at HIV infection (BMSM: 26.8y, WMSM: 35.0y) and time from infection to diagnosis (BMSM: 3.4y, WMSM: 3.0y) using US race-stratified data from the Centers for Disease Control and Prevention (CDC) (Table 1). To account for differences in the HIV care continuum, we calibrated input parameters to race-specific estimates of: 1) the proportion of time that MSM with diagnosed HIV are retained in care (BMSM: 75.2%, WMSM: 80.6%), and 2) the % of MSM with diagnosed HIV who attain virologic suppression (VS; BMSM: 82.0%, WMSM: 91.2%). To account for increased risk of non-HIV-related mortality, we adjusted race-stratified life tables for smoking. We then projected LE from age 15 in five scenarios: 1) status quo HIV care (2019 estimates of HIV testing, VS, and retention in care), 2) earlier diagnosis (via annual testing), 3) improved retention in care (95% retention via reduced loss to follow-up), 4) improved VS (95% VS among MSM in care), and 5) a combined strategy (annual testing, 95% retention, 95% VS).

Results

Among MSM in status quo HIV care, we projected LE from age 15 to be 52.2y (BMSM) and 58.5y (WMSM), a difference of 6.3 years (Figure 1). With annual testing, BMSM would gain 0.6 life-years (LY), and WMSM would gain 0.3 LY compared with status quo care. Improving retention in care to 95% would result in a gain of 1.4 LY for BMSM and 1.0 LY for WMSM. BMSM would gain 1.1 LY if VS increased to 95% among those in care, whereas WMSM would gain 0.3 LY. BMSM would gain 3.4 LY (LE from age 15: 55.6y) and WMSM 1.6 LY (LE from age 15: 60.1y) in the combined strategy.

Conclusion

Equity-focused solutions that specifically target investment in HIV care for Black MSM will be critical to reduce disparities in HIV care outcomes and improve LE.

Disclosures

Krishna Reddy, MD, MS, UpToDate, Inc.: Author Aimalohi Ahonkhai, MD, MPH, Bryan Allen Events LLC for Gilead: Advisor/Consultant|ViiV: Advisor/Consultant.
868. In Vitro Activity of Isavuconazole and Other Mould-Active Triazoles Against Aspergillus fumigatus With and Without cyp51 Alterations
Authors: Pfaller Michael A , Carvalhaes Cecilia G , Deshpande Lalitagauri M , Rhomberg Paul , Rhomberg Paul , Castanheira Mariana
Published: December 2022

Background

Azole resistance in Aspergillus fumigatus (AFM) is mainly associated with mutations in cyp51A and its promoter region or its homologue cyp51B. We evaluated the in vitro activity of isavuconazole (ISC), itraconazole (ITC), posaconazole (PSC), and voriconazole (VRC) against 660 AFM collected during 2017–2020.

Methods

Isolates from Europe (EU), North America (NA), Latin America (LA), and Asia-Pacific (APAC) were identified by MALDI-TOF and/or sequencing and tested by CLSI broth microdilution. CLSI epidemiological cut-off values (ECV) were applied. A PSC ECV of 0.5 mg/L was used. Non-wildtype (NWT) isolates to azoles were screened for alterations in the cyp51 genes using whole genome sequencing.

Results

Azoles had similar activities against 660 AFM isolates. Overall, AFM displayed WT MIC values to ISC (92.7%), ITC (92.9%), PSC (97.3%), and VRC (96.7%). Only 66 isolates (10.0%) were NWT to 1 or more of the azoles, and 32 harbored one or more alterations in the cyp51 genes. Of these AFM, 29/32 (90.1%) were NWT to ITC, 25/32 (78.1%) NWT to ISC, 17/32 (53.1%) NWT to VRC, and 11/32 (34.4%) NWT to PSC. The most frequent alteration was CYP51A TR34/L98H, carried by 14 EU isolates, all NWT to ISC and ITC. Four isolates from NA carried the alteration I242V in CYP51A (all NWT to ITC; all WT to ISC). One NA isolate carried the CYP51A alteration G448S (NWT to ISC, VRC, and ITC) and one carried A9T (NWT to ISC). A single isolate from APAC carried a CYP51A G138C alteration and was NWT to all 4 triazoles. Multiple alterations in CYP51A were detected in 5 isolates: 4/5 NWT to ISC or ITC, 1/5 NWT to VRC, all WT to PSC. Alterations in CYP51B were noted in 7 isolates; 6/7 carried Q42L, 3 from NA (all NWT to ITC and 2 NWT to ISC), 2 from APAC (all NWT to VRC or ISC), and 1 from EU (NWT to ISC, ITC, and PSC). Among 34 NWT isolates without cyp51 alterations, 32.4% were WT to ISC, 47.1% WT to ITC, 85.3% WT to VRC, and 82.4% WT to PSC.

Conclusion

The majority of AFM were WT to azoles. Ten different cyp51 alterations were detected in 32/66 NWT isolates. Only EU isolates harboured the environmental alteration TR34/L98H that was associated with a NWT phenotype to ISC and ITC. Alterations in AFM cyp51 can have variable effects on the in vitro activity of the azoles that are best delineated by testing all triazoles.

Disclosures

Michael A. Pfaller, MD, Pfizer: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Lalitagauri M. Deshpande, PhD, Melinta: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), Cidara: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), Cidara: Grant/Research Support|Pfizer: Grant/Research Support.
875. Guess Who’s Back: The Return of Seasonal Respiratory Viruses in the State of Wisconsin and Associated Changes in Antibiotic Prescribing for Respiratory Complaints
Authors: Lepak Alexander , Taylor Lindsay , Schulz Lucas , Hanson Erika , Temte Jonathan
Published: December 2022

Background

Return of infections caused by common respiratory viruses (RV) may be expected with the relaxation and/or removal of infection prevention measures instituted during the COVID-19 pandemic. Therefore, we examined respiratory virus detection (RVD) rates in Wisconsin during the COVID-19 period, and whether ambulatory antibiotic prescribing for respiratory complaints has increased with return of typical RVs.

Methods

The Wisconsin State Laboratory of Hygiene’s Viral Surveillance program collects RVD data from >130 laboratories across the state for influenza (FLU), respiratory syncytial virus (RSV), seasonal coronaviruses (sCOR), parainfluenza virus (PARA), enteroviruses/rhinoviruses (E/R), and human metapneumovirus (hMPV). Data were collected from 1/1/2015 to 4/30/2022. Antibiotic prescribing for ambulatory care patients presenting with respiratory complaints was collected from our EHR, which utilizes a required order form for all ambulatory antibiotic prescriptions. Statistical analysis was performed using Mann-Whitney Rank Sum and Spearman’s rank correlation.

Results

In the first year after COVID-19 onset, E/R and sCOR were detected at low levels while other RVs were essentially nil. After 4/2021, when infection prevention measures (i.e. mask mandates) were significantly relaxed or removed, RVDs increased for all viruses. At present, RVDs have returned to typical rates (except of FLU, Fig. 1) and seasonality variation (except of RSV, Fig. 1). Antibiotic prescribing for respiratory complaints has increased 57% in this period (3.5 to 5.5 prescriptions/1000 encounters, Fig. 2) and continues to trend up with RV activity. Prescribing rates are strongly correlated with RVD rates, but most strongly correlated with non-FLU, non-RSV RVD rates (Spearman correlation 0.71).

The dashed vertical line represents relaxation/discontinuation of public infection prevention measures (e.g. masking).

The dashed vertical line represents relaxation/discontinuation of public infection prevention measures (e.g. masking).

* Parainfluenza virus, human metapneumovirus, enterovirus/rhinovirus, or seasonal coronavirus.

Conclusion

In general, RVs have returned to pre-pandemic rates with seasonality. Interestingly, this return was associated with the relaxation/removal of infection prevention measures in the second year post-COVID-19 onset, and does not appear to be impacted by ongoing COVID-19 waves. Antibiotic prescribing in ambulatory care continues to be highly associated with RV activity, indicating this should remain a high priority of ambulatory stewardship education and intervention.

Disclosures

All Authors: No reported disclosures.
1521. Non-faecium Non-faecalis enterococcal bloodstream infections in patients with cancer
Authors: Axell-House Dierdre B , Egge Stephanie L , Tran Cecilia , Shelburne Samuel A , Arias Cesar A
Published: December 2022

Background

Non-E. faecium non-E. faecalis (NFF) enterococci are a heterogeneous group of organisms consisting of enterococci with intrinsic low-level vancomycin resistance as well as several other species known to infect humans. Patients with cancer are at increased risk for bloodstream infections (BSIs) with NFF enterococci, but their optimal treatment and outcomes have not been extensively described.

Methods

We conducted a retrospective review of patients (pts) with blood cultures positive for all NFF by searching the microbiology database at a major cancer center in Houston, TX from 2016 to 2021. Patients were included if they were ≥ 18 years old, had ≥ 1 blood culture with NFF enterococci, and had a repeat blood culture within 7 days (d) of the index culture, to permit outcome analysis. Outcomes were a) in-hospital mortality, b) microbiological failure (blood culture clearance >4 d after index culture), and c) recurrence of bacteremia (new positive blood culture < 14 d after eradication).

Results

Sixty-two unique pts had NFF enterococcal BSI. Patients with hematological malignancy made up 53.2% of the cohort (78% had leukemia). The majority (83%) of solid malignancies were pancreatic, biliary, or intestinal in origin. In the 30 d preceding NFF enterococcal BSI, 79% of pts had exposure to antibiotics. The NFF species isolated were E. gallinarum (50%), E. casseliflavus (30.6%), E. avium (11.3%), E. raffinosus (3.2%), E. hirae (3.2%), and E. durans (1.6%). Only 23.3% of NFF enterococci were susceptible to vancomycin, and 53.8% were susceptible to linezolid. Most (62.9%) pts received combination therapy; the most frequent was daptomycin plus a beta-lactam (33.9%). Bacteremia recurred in 8.1% of pts, 27.4% had in-hospital mortality, and 4.8% had microbiological failure.

Conclusion

This retrospective review provides preliminary insight into the treatments, and outcomes of cancer pts with NFF enterococcal BSIs. The NFF enterococci isolates in this study had a higher rate of linezolid non-susceptibility than previously reported. Molecular investigation of these NFF enterococcal isolates is needed to elucidate the mechanisms and transmission of antibiotic resistance. Comparison of BSIs caused by NFF enterococci to E. faecium/E. faecalis will provide insight to physicians caring for these pts.

Disclosures

Cesar A. Arias, MD, PhD, Entasis: Grant/Research Support|MeMed Diagnostics Ltd: Grant/Research Support|Merck: Grant/Research Support.
1522. Penicillin plus ceftaroline against Enterococcus faecalis blood isolates lacking ampicillin plus ceftriaxone activity
Authors: Nwoye Angella , Bocanegra Jessica , Khan Ruhma , Shah Zeel , Cusumano Jaclyn A
Published: December 2022

Background

Enterococcus faecalis infective endocarditis standard of care treatment, ampicillin plus ceftriaxone, unfortunately has been unable to decrease mortality rates and additionally increases patient risk for vancomycin-resistant enterococci (VRE). Recent data also demonstrates decreased ampicillin plus ceftriaxone activity in E. faecalis isolates with an elevated penicillin MIC of 4 mcg/mL. Penicillin plus ceftaroline is a promising alternative but limited data is available to support.

Methods

Seven E. faecalis clinical blood isolates and one wild-type E. faecalis isolate (i.e., JH2-2) were tested against penicillin plus ceftaroline utilizing 24-hour in vitro time-kill assays. All isolates were penicillin susceptible with minimum inhibitory concentrations (MIC) of either 2 (n=4) or 4 (n=4) mcg/mL, and ceftaroline MICs ranged from 1 to 8 mcg/mL. Penicillin and ceftaroline were tested at subinhibitory concentrations (0.25x and 0.5xMIC) as monotherapy and in combination. Antibacterial activity was described as bactericidal or bacteriostatic, defined as a ≥ 3-log10 colony-forming units (CFU)/mL or < 3-log10 CFU/mL decrease from initial inoculum, respectively. Synergy was defined as a ≥ 2-log10 decrease in CFU/mL at 24 hours from the most active single agent.

Results

Penicillin and ceftaroline monotherapy did not demonstrate any antibacterial activity, except for ceftaroline 0.5xMIC where four isolates demonstrated bacteriostatic activity (Table 1). Penicillin plus ceftaroline was synergistic in all isolates except JH2-2 (penicillin MIC of 2 mcg/mL) due to the bacteriostatic activity of ceftaroline alone. Synergistic and bactericidal activity was also more frequently observed in isolates with a penicillin MIC of 4 mcg/mL with penicillin plus ceftaroline than ampicillin plus ceftriaxone.

Conclusion

Penicillin plus ceftaroline demonstrates synergistic activity against clinical E. faecalis blood isolates including isolates with a penicillin MIC of 4 mcg/mL, where ampicillin plus ceftriaxone less frequently demonstrated synergy. Further research is warranted to support utilization in patients with E. faecalis infective endocarditis.

Disclosures

Jaclyn A. Cusumano, PharmD, BCIDP, Shionogi: Advisor/Consultant.
1527. Use of a SARS-CoV-2 Strand-specific Assay to detect Relapse or Ongoing Infection at a Tertiary Care Center, California 2020–2022
Authors: Contreras Anez Gustavo A , Ferguson Jessica , Contag Caitlin A , Tompkins Lucy S , Shepard John , Rosenthal Ayelet , Subramanian Aruna , Pinsky Benjamin A , Salinas Jorge
Published: December 2022

Background

Determining if a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains infectious can be challenging in patients with severe disease or those profoundly immunosuppressed. We use an assay that detects minus-strand RNA as a surrogate for actively replicating SARS-CoV-2. Here, we describe a cohort of patients who had strand-assay reversion: a detectable minus strand-specific assay after having had an undetectable value which may signify relapse of infection or reinfection.

Methods

We used a 2-step rRT-PCR specific to the minus strand of the SARS-CoV-2 envelope gene. The strand-specific assay is used to evaluate for infectivity in asymptomatic patients with a positive screening admission or pre-procedural test or in cases when ongoing infection was suspected (critical illness or profound immunosuppression). We collected minus strand-specific assays performed at Stanford Healthcare during August 2020–April 2022. We describe basic demographics and clinical characteristics for patients who reverted from undetectable to detectable using the minus strand-specific assay.

Results

A total of 2,505 strand-specific tests were collected from August 2020–April 2022 from 2,064 patients. A total of 292 (14%) had two or more strand-specific tests. Of them, 19 (7%) had an undetected minus strand-specific assay followed by a subsequent detectable value. Of them, seven (37%) had a minus strand-specific CT value of < 33. Most were male (n=4), median age was 54 (range: 8–62). All were profoundly immunosuppressed: Four had hematologic malignancies and three were post transplantation (kidney, lung, bone marrow). Median time from onset of symptoms or first positive test to reversion was 41 days (range:27–159). Median time from undetectable to detectable minus strand specific test was 26 days (range:4–34). All cases were considered relapses or ongoing infection rather than a new infection.

Conclusion

Among patients with SARS-CoV-2 infection and consecutive strand-specific testing, a small proportion reverted from negative to positive. Most were profoundly immunosuppressed. The strand-specific assay can be an important tool in the evaluation of suspected cases of relapse or reinfection.

Disclosures

Aruna Subramanian, MD, Gilead Sciences: Grant/Research Support|Regeneron, Inc: Grant/Research Support.