Management of Post-transplant Infections in Collaborating Hospitals (MATCH) Programme: a prospective cohort of all transplant recipients at Copenhagen University Hospital–Rigshospitalet, Denmark

Purpose
The Management of Post-transplant Infections in Collaborating Hospitals (MATCH) programme, initiated in 2011 and still ongoing, was created to 1) optimise the implementation of existing preventive strategies against viral infections in solid organ transplant (SOT) recipients and allogenic haematopoietic stem-cell transplant (HSCT) recipients and 2) advance research in the field of transplantation by collecting data from a multitude of sources.

Participants
All SOT and HSCT recipients at Copenhagen University Hospital, Rigshospitalet, are followed in MATCH. By February 2021, a total of 1192 HSCT recipients and 2039 SOT recipients have been included. Participants are followed life long. An automated electronic data capture system retrieves prospective data from nationwide registries. Data from the years prior to transplantation are also collected.

Findings to date
Data entries before and after transplantation include the following: biochemistry: 13 995 222 and 26 127 817; microbiology, cultures: 242 023 and 410 558; other microbiological analyses: 265 007 and 566 402; and pathology: 170 884 and 200 394. There are genomic data on 2431 transplant recipients, whole blood biobank samples from 1003 transplant recipients and faeces biobank samples from 207 HSCT recipients. Clinical data collected in MATCH have contributed to 50 scientific papers published in peer-reviewed journals and have demonstrated success in reducing cytomegalovirus disease in SOT recipients. The programme has established international collaborations with the Swiss Transplant Cohort Study and the lung transplant cohort at Toronto General Hospital.

Future plans
Enrolment into MATCH is ongoing with no planned end date for enrolment or follow-up. MATCH will continue to provide high-quality data on transplant recipients and expand and strengthen international collaborations.

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Novembre 2024

Trajectories of functional limitations, health-related quality of life and societal costs in individuals with long COVID: a population-based longitudinal cohort study

Objectives
To examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics.

Design
A population-based longitudinal cohort study using real-time user data.

Setting
35 specialised long COVID clinics in the UK.

Participants
4087 adults diagnosed with long COVID in primary or secondary care deemed suitable for rehabilitation and registered in the Living With Covid Recovery (LWCR) programme between 4 August 2020 and 5 August 2022.

Main outcome measures
Generalised linear mixed models were fitted to estimate trajectories of functional limitations, using the Work and Social Adjustment Scale (WSAS); scores of ≥20 indicate moderately severe limitations. Other outcomes included fatigue using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) reversed score (scores of ≥22 indicate impairment), HRQL using the EQ-5D-5L, and long COVID-related societal costs, encompassing healthcare costs and productivity losses.

Results
The mean WSAS score at 6 months after registration in the LWCR was 19.1 (95% CI 18.6, 19.6), with 46% of the participants (95% CI 40.3%, 52.4%) reporting a WSAS score above 20 (moderately severe or worse impairment). The mean change in the WSAS score over the 6-month period was –0.86 (95% CI –1.32, –0.41). The mean reversed FACIT-F score at 6 months was 29.1 (95% CI 22.7, 35.5) compared with 32.0 (95% CI 31.7, 32.3) at baseline. The mean EQ-5D-5L score remained relatively constant between baseline (0.63, 95% CI 0.62, 0.64) and 6 months (0.64, 95% CI 0.59, 0.69). The monthly societal cost per patient related to long COVID at 6 months was £931, mostly driven by the costs associated with working days lost.

Conclusions
Individuals referred to long COVID clinics in the UK reported small improvements in functional limitations, fatigue, HRQL and ability to work within 6 months of registering in the LWCR programme.

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Novembre 2024

ICU follow-up services and their impact on post-intensive care syndrome: a scoping review protocol

Introduction
Post-intensive care syndrome (PICS) seriously affects the quality of life of intensive care unit (ICU) survivors, their ability to return to work and society and the quality of life of their families, increasing overall care costs and healthcare expenditures. ICU follow-up services have important potential to improve PICS. However, the best clinical practice model of ICU follow-up service has not been fully defined and its benefits for ICU survivors are not clear. This review will synthesise and map the current types of follow-up services for ICU survivors and summarise the impact of follow-up services on PICS.

Methods and analysis
This scoping review will be conducted by applying the five-stage protocol proposed by Arksey and O’Malley in an updated version of the Joanna Briggs Institute. Eight academic databases including the Cochrane Library, MEDLINE, Web of Science, Embase, EBSCO Academic, CINAHL, PsycInfo and SinoMed (China Biology Medicine) will be systematically searched from inception to the present. Peer-reviewed literature and grey literature will be included. Qualitative, quantitative and mixed methods studies will be included. Studies published in English or Chinese will be included. There will be no time restriction. Two reviewers will screen and select the articles independently and if there is any disagreement, the two reviewers will discuss or invite a third reviewer to make decisions together. Descriptive analysis will be used to conduct an overview of the literature. The results will be presented in a descriptive format in response to the review questions accompanied by the necessary tables or charts.

Ethics and dissemination
Ethical approval is not required for this scoping review because data could be obtained by reviewing published primary study results and do not involve human participants. Findings should be disseminated at scientific meetings and published in peer-reviewed journals.

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Novembre 2024

Pain control post total knee replacement in patients given local infiltrative analgesia combined with adductor canal block compared to either modality alone: a systematic review and meta-analysis

Objectives
Optimising postoperative pain following knee replacement is important for patients, healthcare professionals and healthcare funders. Adductor canal blocks (ACB) are widely used but there is uncertainty about their efficacy when combined with local infiltration analgesia (LIA) compared with either LIA or ACB alone.

Design
A systematic review and meta-analyses of randomised controlled. The primary outcome was pain over the first 72 hours. Secondary outcomes included morphine use, range of movement, distance walked, length of hospital stay, health economic outcomes and reported adverse events.

Data sources
MEDLINE, Embase, EB Health – KSR Evidence, Cochrane Central Register of Controlled Trials, CINAHL, International HTA database, ClinicalTrials.gov and the International Clinical Trials Registry Platform (WHO) were searched up to June 2023.

Eligibility criteria
Randomised controlled trials involving patients undergoing primary total knee replacement comparing LIA combined with ACB to either LIA or ACB alone.

Data extraction and synthesis
All eligible studies were data extracted independently by two reviewers. Studies were pooled for each outcome at each timepoint in a random effects meta-analysis.

Results
We identified 13 completed studies including 1154 participants. 12 studies compared LIA vs combination and 5 compared ACB vs combination. We identified that participants receiving the combination had lower pain scores at rest at 24 hours compared with LIA alone (SMD 0.42, 95% CI 0.20 to 0.64) or ACB alone (SMD 0.63, 95% CI 0.42 to 0.83). Pain on movement at 24 hours was also lower for patients with combination vs LIA alone (SMD 0.37, 95% CI 0.01 to 0.73) or ACB alone (SMD 0.81, 95% CI 0.35 to 1.26). We also identified that patients on combination used less morphine than on LIA alone (MD 1.06, 95% CI –0.09 to 2.20) or ACB alone (MD 5.94, 95% CI –2.41 to 14.29). The same was seen with range of motion at 24 hours with combination having a larger improvement than LIA alone (MD –5.19, 95% CI –5.55 to –4.83) or ACB alone (MD –3.80, 95% CI –4.37 to –3.23). These findings were consistent across all time points; however, there were no studies deemed to be at a low risk of bias.

Conclusions
Further well-designed and conducted randomised controlled trials are needed to confirm if a combination of LIA and ACB is superior to either option alone for patients undergoing primary total knee arthroplasty.

PROSPERO registration number
CRD42023436895.

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Novembre 2024

COVID-19 Therapeutics for Nonhospitalized Older Adults

This Viewpoint summarizes the factors contributing to increased risk of severe outcomes and hospitalization associated with COVID-19 among older adults, stresses the importance of assessing COVID-19 risk before infection occurs, calls for all immunocompromised older adults to be considered for COVID-19 treatment, and details 3 recommended COVID-19 therapies.

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Novembre 2024

Abstract 4135630: Improving Cardiac Rehab Referral and Enrollment Post-Percutaneous Coronary Intervention Through a Workflow Intervention at the Minneapolis VA: A Quality Improvement Study

Circulation, Volume 150, Issue Suppl_1, Page A4135630-A4135630, November 12, 2024. Introduction:Cardiac rehabilitation (CR) is a Class 1A recommendation post-percutaneous coronary intervention (PCI), yet it remains underutilized. At the Minneapolis VA, the referral and enrollment rates for CR post-PCI are significantly below the national goal of 70%, indicating a need for improved strategies to enhance veteran participation.Research Questions:This study investigates the impact of a workflow intervention on CR enrollment rates and seeks to understand how staffing changes may influence these rates. It also explores the potential for advanced practice providers to affect CR enrollment.Aim:We aim to increase CR enrollment to 40% and referrals to 50% post-PCI at the Minneapolis VA by August 2023, utilizing a nurse practitioner dedicated to interventional cardiology patients post-PCI.Methods:Utilizing the VA CART database, demographic data for patients undergoing PCI between October 2017 and August 2023 were analyzed, excluding those who died within 30 days of PCI. CR referrals within 90 days and enrollments within one year were tracked. Statistical process control charts were used to detect variations in referral and enrollment rates, with a t-test determining significance. The staffing change intervention occurred in May of 2020.Results:The intervention led to a significant increase in both referral and enrollment rates. The average monthly referral rate rose from 24% to 37%, and the enrollment rate from 14% to 28%. A statistical process control chart indicated special cause variation in the sample after the intervention, suggesting meaningful change. Statistical analysis confirmed these increases as significant (p

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Novembre 2024

Abstract Sa1105: The Effect of a Combination of Neuroprotective Medications on Post-Cardiac Arrest Survival

Circulation, Volume 150, Issue Suppl_1, Page ASa1105-ASa1105, November 12, 2024. Introduction:Reperfusion injury after cardiac arrest (CA) leads to poor survival and neurological outcomes. We hypothesized that a combination of pharmacologic neuroprotection therapies administered 24-72 hours post-CA [“combination therapy”] that target key steps in reperfusion injury; 1) excitotoxicity (Magnesium, Memantine, Perampanel, Minocycline), 2) mitochondrial dysfunction (Thiamine, Coenzyme Q10), 3) oxidative stress (Vitamin C, Vitamin E), and 4) inflammation (Hydrocortisone), would improve survival.AIMS:We compared survival between subjects with combination therapy and those without.Methods:A retrospective analysis of post-CA patients (01/01/2019 – 06/01/2023) was conducted as part of a quality improvement project. Inclusion: in-hospital CA, age ≥ 18 years, non-COVID, ≥ 5 min CPR, sustained ROSC (≥ 20 min). Exclusion: out-of-hospital CA. Combination therapy was at the discretion of the provider and given in addition to current post-CA standard critical care: targeted temperature management (TTM) (32-36°C), glucose (target 140 mg/dL), PaO2 (target 100 mmHg), PaCO2 (target 40 mmHg), and MAP (target 80 – 100 mmHg). Survival was assessed at hospital discharge.Results:Among 196 subjects, 146 received combination therapy (study group) and 50 did not (control group). Demographic variables (age, race, ethnicity) and intra-cardiac arrest variables (initial rhythm, CPR duration, and hospital site) were not statistically different between groups. Post-CA variables (mean PaCO2, PaO2, and glucose) were not statistically different between groups. MAP was 76 (69, 83) for study group and 65 (46, 72) for control group (P=

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Novembre 2024

Abstract 4134309: From Heartache to Headache: Cryptococcal Meningitis Post-Heart Transplant in a Chronic Hepatitis B and Sarcoidosis Patient

Circulation, Volume 150, Issue Suppl_1, Page A4134309-A4134309, November 12, 2024. Introduction:We report the case of a heart transplant patient on chronic immunosuppression diagnosed with cryptococcal meningitis. Up to 5% of solid organ transplant patients develop cryptococcosis, carrying a 50% mortality rate in central nervous system involvement.Case Presentation:This is a 57-year-old male with a past medical history of heart failure with reduced ejection fraction (HFrEF) status post orthotopic heart transplantation (on prednisone 7.5 mg daily, mycophenolate, tacrolimus and sirolimus), pulmonary sarcoid, and chronic hepatitis B (on tenofovir and entecavir) who presented with headache, nausea, vomiting and seizure-like activity. The patient’s heart rate was 129 beats per minute, blood pressure 188/92 mmHg, but was afebrile. He eventually underwent a lumbar puncture with the cerebrospinal fluid (CSF) positive for cryptococcal antigen (1:2560). The patient was started on liposomal amphotericin B and flucytosine. Mycophenolate and sirolimus were held in the setting of his infection. The patient’s hospital course was complicated by acute kidney injury likely secondary to elevated tacrolimus levels while on fluconazole. He was ultimately discharged with plans to repeat CSF studies as an outpatient.Discussion:Here we report a case of cryptococcal meningitis in a heart transplant patient in the context of pulmonary sarcoidosis, chronic hepatitis B and quadruple immunosuppression. Of note, as part of rejection surveillance, the patient undertook serial AlloSure and AlloMap testing. Sirolimus was added to his regimen due to persistently elevated AlloSure scores. Indeed, immunosuppressive agents are the leading risk factor for cryptococcosis in organ transplant patients. Our patient also has two important risk factors for cryptococcal infection. Firstly, sarcoidosis is associated with T-cell dysregulation, compromising cell-mediated immunity. Additionally, hepatitis B carriers have an increased predisposition for cryptococcal infections, notwithstanding that our patient had been on dual antiviral therapy.Conclusion:Quadruple immunosuppression in heart transplant patients, especially in the context of risk factors such as sarcoidosis and hepatitis B infection, can result in cryptococcal meningitis and should be considered in patients with suggestive symptoms. Effective prophylactic regimens for such higher risk patients may be a potential area for further investigation.

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Novembre 2024

Abstract 4136969: Empagliflozin's Role in Post-Myocardial Infarction Management: Insights from a Meta-Analysis

Circulation, Volume 150, Issue Suppl_1, Page A4136969-A4136969, November 12, 2024. Background:Empagliflozin, a Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor, is used to treat type 2 diabetes mellitus and heart failure. Its safety and efficacy in patients with Myocardial Infarction (MI) have been studied recently.Research Questions/Hypothesis:What is the role of Empagliflozin in post-myocardial infarction management by preventing cardiovascular deaths, reducing hospitalization due to heart failure, and minimizing adverse events?Goals/Aims:Role of Empagliflozin in post-myocardial infarction management by preventing cardiovascular deaths, reducing hospitalization due to heart failure, and minimizing adverse eventsMethods:A literature search was done on PubMed, Medline, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials from inception until May 2024. All Randomized Control Trials (RCT) reporting the safety and efficacy of Empagliflozin in MI management were selected. Outcomes were pooled as Mean Difference (MD) or Risk Ratio (RR) with 95% Confidence Intervals (CI) in this meta-analysis using Revman 5.4.Results:Data from ten RCTs, with a combined sample size of 10,560 patients was pooled, and showed that Empagliflozin is superior to placebo in terms of Cardiovascular death (RR=0.75, 95% CI [0.64, 0.88],p < 0.0004) and hospitalization due to heart failure (RR=0.70, 95% CI [0.59, 0.82], p < 0.0001). However, the results were non-significant for both groups in terms of adverse events (RR=1.00, 95% CI [0.96, 1.03], p < 0.78).Conclusion:Empagliflozin significantly lowers the risk of cardiovascular events in patients with MI who are at a high risk of death due to cardiovascular causes.

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Novembre 2024

Abstract 4148095: The Impact of Body-Mass Index on Ventricular Tachycardia Outcomes Post-Catheter Ablation

Circulation, Volume 150, Issue Suppl_1, Page A4148095-A4148095, November 12, 2024. Background:In recent years, catheter ablation has emerged as a sustainable, first-line therapy for the management of ventricular tachycardia (VT). Given the rise of the “obesity paradox” theory in atrial ablation outcomes, we sought to study the effect of BMI on patients undergoing structural VT ablation.Purpose:To assess the outcomes of VT ablation, specifically VT recurrence, in patients with elevated vs. normal BMI.Methods:Clinical characteristics and demographic data were collected for VT patients who underwent ablation at Mayo Clinic Rochester from 2012-2022. Patient BMI was classified as non-obese (

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Novembre 2024

Abstract 4144502: Comparing Readmission Rates and Exercise Capacity Following Left Ventricular Assistive Device Placement With and Without Post-Operative Inpatient Rehabilitation

Circulation, Volume 150, Issue Suppl_1, Page A4144502-A4144502, November 12, 2024. Introduction:Patients with heart failure may undergo mechanical assistive device placement as a bridge to heart transplantation or for destination therapy. Thereafter, patients may be discharged home or admitted to inpatient rehabilitation.Research Question:We hypothesized that within 8 months, patients admitted to inpatient rehabilitation (IR) would have fewer readmissions and greater exercise capacity compared to patients discharged home following left ventricular assistive device (LVAD) placement.Aim:The readmission rates and exercise capacity of patients admitted to (IR) were compared to those discharged home within 8 months of (LVAD) placement.Methods:Readmission rates, impairment percentages (IP) (determined by Activity Measure for Post-Acute Care scores) and walking distance after (LVAD) placement between March 1st, 2020 to November 30th, 2022 were collected via retrospective chart review at Jackson Memorial Hospital.Adults with heart failure and heart assistive device (ICD10 code Z95.811), discharged home or admitted to the Christine E. Lynn Rehabilitation Center for at least 7 consecutive days within 8 months were included. Patients who were noncompliant, expired, transferred, or unable to ambulate were excluded. 24 patients were admitted to rehab, and 16 were discharged home. Statistical significance was denoted at the 0.05 level using the Mann-Whitney U Test.Results:There was a higher proportion of females in the rehab group (45.8%) and males in the no rehab group (93.8%) (p=0.02). The groups were otherwise comparable.Average (IP) at hospital discharge was higher for the rehab group (51.79%, SD 17.65) compared to the no rehab group (14.20%, SD 18.93) (p

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Novembre 2024

Abstract 4144529: Cardiac Allograft Hypertrophy (CAH) at 6 Months Post Transplant Is a Prognostic Marker of Long-Term Outcomes: Are We Missing a Simple Biomarker?

Circulation, Volume 150, Issue Suppl_1, Page A4144529-A4144529, November 12, 2024. Introduction:Cardiac hypertrophy is a known adverse prognostic marker in various non-transplant pathologies. In heart transplant patients, due to many confounders, it has been controversial on the relevance and timing of cardiac hypertrophy as an adverse remodeling vs acute injury pattern in an immunologically hostile environment. Previous studies have shown prognostication of hypertrophy on echocardiogram at 1-year post-heart transplant.Research Questions:Does cardiac hypertrophy within a year after transplant have long-term prognostic implications?Methods:We collected relevant clinical variables for all heart transplants using EPIC EHR’s Clarity database. Hypertrophy was defined based on LV Mass Indexed to body surface area where LV Mass = 0.8 x (1.04 x (((LVIDD + IVSd + PWd)3- LVIDD3))) + 0.6. Relative Wall Thickness was defined as RWT = 2 x PWd / LVIDD. We used a rule-based natural language processing program validated by correlation with manual readings by trained cardiologists (r=0.96, p=0.007) to abstract echo variables.Results:Inclusion criteria were heart transplants performed from 2015 to 2023 at our center, with an echocardiogram closest to 6 months (+/- 1 month). Ten percent (n=33) showed hypertrophy on echocardiograms at 6 months (Table 1). Of these, 20 (61%) had mild, 3 (9%) severe, and 10 (30%) moderate hypertrophy. Of 33 patients, 28 (85%) had concentric, and 5 (15%) had eccentric hypertrophy. Patients with hypertrophy at 6 months had significantly worse survival at 5 years (p=0.01) and 10 years (p=0.05) compared to patients without hypertrophy (Fig 1). Survival at 5 and 10 years was not statistically different for patients with hypertrophy at 3 months (5 yrs p=0.17, 10 yrs p=0.06), 12 months (5 yrs p=0.38, 10 yrs p=0.30), and 18 months (5 yrs p=0.15, 10 yrs p=0.08) compared to those without hypertrophy.Conclusion:Cardiac hypertrophy on echocardiogram at 6 months predicts adverse long-term survival, while other time points did not.

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Novembre 2024

Abstract 4144577: Temporal Trends in Attainment of LDL-c Goals Post Coronary Artery Bypass Grafting (CABG): Data From a Large Integrated Healthcare System

Circulation, Volume 150, Issue Suppl_1, Page A4144577-A4144577, November 12, 2024. Introduction:Multisociety guidelines in secondary atherosclerotic cardiovascular disease (ASCVD) cholesterol goals have evolved over time. We aim to identify temporal trends in low density lipoprotein cholesterol (LDL-c) and statin use in a post coronary artery bypass grafting (CABG) population.Methods:This is a retrospective study of Kaiser Permanente Northern California members who underwent CABG from 2008 to 2019. Patients were stratified according to three time frames (2008-2013, 2014-2018, 2019) based on the release of multisociety guidelines in 1999, 2013 and 2018. LDL-c goal was defined as a last available value less than 70 mg/dL at 1 year follow up. Lipid lowering therapies were identified through pharmacy records. Cox proportional hazard modeling was used to identify major adverse cardiovascular event (MACE) free survival at up to 12 years follow up.Results:The cohort included 6422 patients, mean age 64.9 years, 83% male, with baseline LDL-c 95.9 mg/dL. Of the cohort, 47% of patients achieved an LDL-c < 70 mg/dL at 1-year follow up. Of the stratified groups, the 2019 cohort demonstrated the highest attainment of LDL-c goal (65%, N=392) compared to 2008-2013 cohort (41%, N=1197) and 2014-2018 cohort (57%, N=1406) (Table 1). A relative increase in high dose statin monotherapy and a decrease in low/moderate dose statin monotherapy was temporally demonstrated in recent cohorts. There was a positive correlation between increasing year and attainment of LDL-c goal (R2=0.916) (Figure 1). Attainment of LDL-c

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Novembre 2024