Publications by authors named "Paul Cremer"

218 Publications

Local Electric Fields in Aqueous Electrolytes.

J Phys Chem B 2021 Jul 27. Epub 2021 Jul 27.

Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.

Vibrational Stark shifts were explored in aqueous solutions of organic molecules with carbonyl- and nitrile-containing constituents. In many cases, the vibrational resonances from these moieties shifted toward lower frequency as salt was introduced into solution. This is in contrast to the blue-shift that would be expected based upon Onsager's reaction field theory. Salts containing well-hydrated cations like Mg or Li led to the most pronounced Stark shift for the carbonyl group, while poorly hydrated cations like Cs had the greatest impact on nitriles. Moreover, salts containing I gave rise to larger Stark shifts than those containing Cl. Molecular dynamics simulations indicated that cations and anions both accumulate around the probe in an ion- and probe-dependent manner. An electric field was generated by the ion pair, which pointed from the cation to the anion through the vibrational chromophore. This resulted from solvent-shared binding of the ions to the probes, consistent with their positions in the Hofmeister series. The "anti-Onsager" Stark shifts occur in both vibrational spectroscopy and fluorescence measurements.
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http://dx.doi.org/10.1021/acs.jpcb.1c03257DOI Listing
July 2021

PET/CT for endocarditis in the ACC/AHA 2020 valve guidelines: Ready for prime time?

J Nucl Cardiol 2021 Jul 22. Epub 2021 Jul 22.

Section of Cardiovascular Imaging, Heart, Vascular and Thoracic Institute, Cleveland Clinic, 9500 Euclid Avenue, Main Campus J1-5, Cleveland, OH, 44195, USA.

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http://dx.doi.org/10.1007/s12350-021-02748-xDOI Listing
July 2021

Coronavirus disease and the cardiovascular system: a narrative review of the mechanisms of injury and management implications.

Cardiovasc Diagn Ther 2021 Jun;11(3):939-953

Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Coronavirus disease (COVID-19), first identified in Wuhan, China, in December 2019, is now a pandemic, having already spread to 188 countries, with more than 28,280,000 infections worldwide. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the responsible infectious agent, and similar to other human coronaviruses, uses membrane-bound angiotensin-converting enzyme 2 (membrane-bound ACE2) for entry into the host cells. COVID-19 has important cardiovascular implications, especially for patients with pre-existing cardiovascular co-morbidities, potentially mediated through several mechanisms, including direct myocardial injury, worsening of those pre-existing cardiovascular co-morbidities, and adverse cardiovascular effects of potential therapies for COVID-19. The disease is causing a significant burden on health systems worldwide. Elective surgeries and procedures were postponed for a considerable period of time, and many patients with known cardiovascular disease (CVD) risk factors presented late to hospitals, for fear of contracting COVID-19, with serious adverse consequences. Significant negative impact on a population level is highlighted by prolonged isolation, decreased exercise and physical activity, and higher levels of depression and anxiety, all predisposing to elevated cardiovascular risk. This article provides a timely overview of COVID-19 and its impact on the cardiovascular system, focusing on the pathogenesis, potential adverse cardiovascular events, the potential treatment options, protection for health care providers and patients, and what the cardiovascular community could do to mitigate the impact of COVID-19.
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http://dx.doi.org/10.21037/cdt-20-779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261751PMC
June 2021

US Database Study of Clinical Burden and Unmet Need in Recurrent Pericarditis.

J Am Heart Assoc 2021 Jul 21:e018950. Epub 2021 Jul 21.

Kiniksa Pharmaceuticals Lexington MA.

Background Patients with recurrent pericarditis (RP) may develop complications, multiple recurrences, or inadequate treatment response. This study aimed to characterize disease burden and unmet needs in RP. Methods and Results This retrospective US database analysis included newly diagnosed patients with RP with ≥24 months of continuous history following their first pericarditis episode. RP was defined as ≥2 pericarditis episodes ≥28 days apart. Some patients had ≥2 recurrences, while others had a single recurrence with a serious complication, ie, constrictive pericarditis, cardiac tamponade, or a large pericardial effusion with pericardiocentesis/pericardial window. Among these patients with multiple recurrences and/or complications, some had features relating to treatment history, including long-term corticosteroid use (corticosteroids started within 30 days of flare, continuing ≥90 consecutive days) or inadequate treatment response (pericarditis recurring despite corticosteroids and/or colchicine, or other drugs [excluding NSAIDs] within 30 days of flare, or prior pericardiectomy). Patients (N=2096) had hypertension (60%), cardiomegaly (9%), congestive heart failure (17%), atrial fibrillation (16%), autoimmune diseases (18%), diabetes mellitus (21%), renal disease (20%), anxiety (21%), and depression (14%). Complications included pericardial effusion (50%), cardiac tamponade (9%), and constrictive pericarditis (4%). Pharmacotherapy included colchicine (51%), NSAIDs (40%), and corticosteroids (30%), often in combination. This study estimates 37 000 US patients with RP; incidence was 6.0/100 000/year (95% CI, 5.6‒6.3), and prevalence was 11.2/100 000 (95% CI, 10.6‒11.7). Conclusions Patients with RP may have multiple recurrences and/or complications, often because of inadequate treatment response and persistent underlying disease. Corticosteroid use is frequent despite known side-effect risks, potentially exacerbated by prevalent comorbidities. Substantial clinical burden and lack of effective treatments underscore the high unmet need.
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http://dx.doi.org/10.1161/JAHA.120.018950DOI Listing
July 2021

Incidence and Clinical Significance of Worsening Tricuspid Regurgitation Following Surgical or Transcatheter Aortic Valve Replacement: Analysis From the PARTNER IIA Trial.

Circ Cardiovasc Interv 2021 Jul 16:CIRCINTERVENTIONS120010437. Epub 2021 Jul 16.

Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, OH (P.C.C., T.K.M.W., L.L.R., W.A.J.).

Background: Aortic valve replacement (AVR) is recommended for severe symptomatic aortic stenosis. However, the incidence of worsening tricuspid regurgitation (TR) following transcatheter compared with surgical AVR (TAVR, SAVR), and the impact of worsening TR on outcomes, is ill-defined. Accordingly, among patients randomized to TAVR or SAVR, we describe the differential incidence of worsening TR and its association with survival.

Methods: From the PARTNER IIA trial (Placement of Aortic Transcatheter Valves IIA), 1334 patients were included with baseline and 30-day postprocedure core-lab echocardiograms. Worsening TR was defined as deterioration of ≥1 grade from baseline to 30 days. Outcomes included cardiovascular and all-cause death between 30 days and 2 years. Multivariable logistic regression was performed to identify associations with worsening TR; survival analyses were performed to assess associations with mortality.

Results: Worsening TR occurred in 17.3% (125/721) of TAVR and 27.0% (165/611) of SAVR patients. On multivariable analysis, SAVR (odds ratio, 2.09 [95% CI, 1.40-3.11]), female sex (odds ratio, 2.22 [95% CI, 1.44-3.42]), atrial fibrillation (odds ratio, 1.61 [95% CI, 1.03-2.51]), and right ventricular enlargement (odds ratio, 2.25 [95% CI, 1.17-4.31]) were associated with worsening TR. Cardiovascular and all-cause death occurred in 9.0% (26/290) and 17.9% (52/290) of patients with worsening TR, compared with 4.8% (50/1042) and 10.9% (114/1042) without worsening TR, respectively. In patients with worsening TR, cardiovascular and all-cause death were similar in TAVR compared with SAVR, (hazard ratio, 1.09 [95% CI, 0.55-2.16]) and (hazard ratio, 1.07 [95% CI, 0.62-1.87]), respectively. After adjustment, worsening TR was independently associated with cardiovascular (hazard ratio, 3.62 [95% CI, 2.08-6.29]) and all-cause death (hazard ratio, 2.11 [95% CI, 1.37-3.27]).

Conclusions: Worsening TR is associated with female sex, atrial fibrillation, right ventricular enlargement, and SAVR. Regardless of mode of AVR, worsening TR is similarly associated with a poor prognosis. Future studies should focus on whether preventing or treating worsening TR improves outcomes.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01314313.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.010437DOI Listing
July 2021

Functional and radiological outcome after forearm plating in children and adolescent fracture.

Acta Orthop Belg 2021 Mar;87(1):143-149

The literature on forearm overgrowth after plating in traumatic conditions is relatively poor though this technique can be useful when intra-medullary nailing is not sufficient in pediatric cases. The goal of this study was to assess a potential overgrowth after plating and identify impact on function. We conducted a retrospective study of all pediatric patients who underwent open surgery of the radius and/or ulna diaphysis with internal fixation by plating, in our institution, between October 2013 and July 2019. At last follow-up, functional and radiological outcomes were compared between the operated and uninjured forearm. Range of motion (ROM) of the wrist and elbow, clinical scores, radial and ulnar length were measured. A positive bone length discrepancy of more than 2mm was considered as an overgrowth. Were also studied the radio-ulnar index, radial inclination and radiocarpal angle. Thirteen patients were included. The mean age was 12.1 years old (±3.0 years), they were plated on the radius (10 cases) or on the ulna (3 cases). Mean follow- up was 4.4 years (± 1.8). In two cases, the plated bone (radius) was significantly longer than the uninjured one. There was no significant difference regarding radio-ulnar index, radial inclination and radiocarpal angle. The only statistically significant difference between the operated and uninjured forearm was the pronation/supination range, which was greater in the uninjured forearm (mean 160 ±48° versus 175 ±49°, p=0.01). This study confirms the good functional and radiological outcomes after plating even in a skeletally immature forearm. Level of evidence : IV.
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March 2021

Utility of nuclear cardiovascular imaging in the cardiac intensive care unit.

J Nucl Cardiol 2021 Jun 9. Epub 2021 Jun 9.

Cleveland Clinic Heart, Thoracic, Institute Cleveland Clinic, 9500 Euclid Ave. J1-5, Cleveland, OH, 44195, USA.

The contemporary Cardiac Intensive Care Unit (CICU) has evolved into a complex unit that admits a heterogeneous mix of patients with a wide range of acute cardiovascular diseases often complicated by multi-organ failure. Although electrocardiography (ECG) and echocardiography are well-established as first-line diagnostic modalities for assessing patients in the CICU, nuclear cardiology imaging has emerged as a useful adjunctive diagnostic modality. The versatility, safety and accuracy of nuclear imaging (e.g., perfusion, metabolism, inflammation) for the assessment of patient with coronary artery disease, ventricular arrhythmias, infiltrative cardiomyopathies, infective endocarditis and inflammatory aortopathies has been proven useful and now often incorporated into the best practices for the management of critically ill cardiac patients. Thus, clinicians must familiarize themselves with the value and current and future applications of nuclear imaging in the management of the cardiac patient in the CICU.
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http://dx.doi.org/10.1007/s12350-021-02665-zDOI Listing
June 2021

Pericardial Diseases in COVID19: a Contemporary Review.

Curr Cardiol Rep 2021 06 3;23(7):90. Epub 2021 Jun 3.

Center for the Diagnosis and Treatment of Pericardial Diseases, Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.

Purpose Of Review: Coronavirus disease 2019 (COVID19) involves the heart, including pericardium. This article reviews the possible pathophysiological mechanisms in pericardial involvement in COVID19 and pericardial manifestations of COVID19. It also summarizes the patients with pericarditis secondary to COVID19 and outlines the contemporary treatment strategies in this patient population.

Recent Findings: A high degree of suspicion is required to identify the pericardial involvement in COVID19 patients. It is proposed that an underlying hyperinflammatory reaction in COVID19 leads to pericardial inflammation. Acute pericarditis with or without myocardial involvement is diagnosed on clinical presentation, serum inflammatory markers, electrocardiogram, and echocardiogram. Multimodality imaging may also have an additional diagnostic value. Patients are usually managed medically, but some patients develop a life-threatening pericardial tamponade necessitating pericardial drainage. Pericardial involvement is an important clinical manifestation of COVID19 requiring a proper workup. Timely diagnosis and a specific management plan based on the presentation and concomitant organ involvement usually lead to a complete recovery.
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http://dx.doi.org/10.1007/s11886-021-01519-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173318PMC
June 2021

Health-related quality of life in patients with recurrent pericarditis: results from a phase 2 study of rilonacept.

BMC Cardiovasc Disord 2021 Apr 21;21(1):201. Epub 2021 Apr 21.

Kiniksa Pharmaceuticals Corp., 100 Hayden Avenue, Lexington, MA, 02421, USA.

Background: Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1β cytokine trap) to treat RP.

Methods: Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n = 16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n = 9). All participants received rilonacept weekly during a 6-week base treatment period (TP) plus an optional 18-week extension period (EP). Tapering of concomitant medications, including corticosteroids (CS), was permitted during EP. HRQoL was assessed using the PROMIS GH, and patient-reported pain and blood levels of c-reactive protein (CRP) were collected at Baseline and follow-up periods. A secondary, descriptive analysis of the Phase 2 trial efficacy results was completed using HRQoL measures to characterize both the impact of RP and the treatment effect of rilonacept.

Results: Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline (mean PROMIS Global Physical Health [GPH] and Global Mental Health [GMH], were lower than population norm average). In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved during EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP).

Conclusion: This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to CS.

Trial Registration: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522 .
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http://dx.doi.org/10.1186/s12872-021-02008-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061027PMC
April 2021

Role of Cardiac CT in Infective Endocarditis: Current Evidence, Opportunities, and Challenges.

Radiol Cardiothorac Imaging 2021 Feb 18;3(1):e200378. Epub 2021 Feb 18.

Section of Cardiovascular Imaging, Imaging Institute (M.B.S., T.K.M.W., P.C., M.A.B.), Section of Cardiovascular Imaging, Heart and Vascular Institute (T.K.M.W., P.C., M.A.B.), and Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute (S.U., G.B.P.), Cleveland Clinic, 9500 Euclid Ave, J1-4, Cleveland, OH 44915; Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands (A.R.W., R.P.J.B.); Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands (A.R.W.); and Department of Cardiology, Haga Hospital, The Hague, the Netherlands (A.R.W.).

Infective endocarditis (IE) can present with variable clinical and imaging findings and is associated with high morbidity and mortality. Substantial improvement of CT technology, most notably improved temporal and spatial resolution, has resulted in increased use of this modality in the evaluation of IE. The aim of this article is to review the potential role of cardiac CT in evaluating IE. Supplemental material is available for this article. © RSNA, 2021.
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http://dx.doi.org/10.1148/ryct.2021200378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977690PMC
February 2021

Implementation of a Myocardial Perfusion Imaging Risk Algorithm to Inform Appropriate Downstream Invasive Testing and Treatment.

Circ Cardiovasc Imaging 2021 Apr 26;14(4):e011984. Epub 2021 Mar 26.

Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic Foundation, OH.

Background: To risk stratify patients undergoing single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in accordance with appropriate use criteria for referral to coronary angiography, we developed a risk classification algorithm incorporating appropriate use criteria-defined risk features. We evaluated the association between this algorithm with downstream angiography, revascularization, and all-cause mortality.

Methods: We studied consecutive patients who underwent SPECT-MPI from January 1, 2015, to December 31, 2017, and assigned a scan risk of low, intermediate, high, or indeterminate. With this stratification, we assessed referral for angiography and revascularization within 3 months of SPECT-MPI and intermediate-term mortality.

Results: Among 12 799 patients, the mean age was 66 years, and a majority were men (56.8%). Most patients were low risk (83.6%) followed by intermediate (9.9%) and high risk (5.2%). Compared with low-risk patients, intermediate- and high-risk patients were more frequently referred for angiography (14.8% and 13.6% versus 2.0%; <0.001) and revascularization (7.7% and 6.8% versus 0.7%; <0.001). In 1008 propensity-matched patients, scan risk was independently associated with angiography after adjustment for ischemia, scar, or stress ejection fraction. At a mean follow-up of 2.3 years, mortality was higher with increased scan risk (high, 10.4%; intermediate, 7.1%; low, 4.1%; <0.001). Compared with low scan risk, intermediate (hazard ratio, 1.37 [95% CI, 1.09-1.72]; =0.008) and high scan risk (hazard ratio, 1.98 [95% CI, 1.53-2.56]; <0.001) were associated with mortality in multivariable analysis. Similar findings were observed for those undergoing pharmacological and exercise SPECT-MPI with comparatively worse prognosis among pharmacological patients.

Conclusions: This appropriate use criteria-derived risk classification algorithm for SPECT-MPI guided referral for coronary angiography and revascularization and was significantly associated with mortality. This algorithm may serve as an important tool to reaffirm appropriate use criteria and direct management of patients with stable ischemic heart disease undergoing stress testing.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.011984DOI Listing
April 2021

Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial.

Lancet Rheumatol 2021 Jun 17;3(6):e410-e418. Epub 2021 Mar 17.

Division of Pulmonary, Critical Care and Sleep Medicine, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.

Background: In patients with COVID-19, granulocyte-macrophage colony stimulating factor (GM-CSF) might be a mediator of the hyperactive inflammatory response associated with respiratory failure and death. We aimed to evaluate whether mavrilimumab, a monoclonal antibody to the GM-CSF receptor, would improve outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation.

Methods: This investigator-initiated, multicentre, double-blind, randomised trial was done at seven hospitals in the USA. Inclusion required hospitalisation, COVID-19 pneumonia, hypoxaemia, and a C-reactive protein concentration of more than 5 mg/dL. Patients were excluded if they required mechanical ventilation. Patients were randomly assigned (1:1) centrally, with stratification by hospital site, to receive mavrilimumab 6 mg/kg as a single intravenous infusion, or placebo. Participants and all clinical and research personnel were masked to treatment assignment. The primary endpoint was the proportion of patients alive and off supplemental oxygen therapy at day 14. The primary outcome and safety were analysed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04399980, NCT04463004, and NCT04492514.

Findings: Between May 28 and Sept 15, 2020, 40 patients were enrolled and randomly assigned to mavrilimumab (n=21) or placebo (n=19). A trial of 60 patients was planned, but given slow enrolment, the study was stopped early to inform the natural history and potential treatment effect. At day 14, 12 (57%) patients in the mavrilimumab group were alive and off supplemental oxygen therapy compared with nine (47%) patients in the placebo group (odds ratio 1·48 [95% CI 0·43-5·16]; p=0·76). There were no treatment-related deaths, and adverse events were similar between groups.

Interpretation: There was no significant difference in the proportion of patients alive and off oxygen therapy at day 14, although benefit or harm of mavrilimumab therapy in this patient population remains possible given the wide confidence intervals, and larger trials should be completed.

Funding: Kiniksa Pharmaceuticals.
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http://dx.doi.org/10.1016/S2665-9913(21)00070-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969143PMC
June 2021

Chronic calcific effusive constrictive pericarditis: a rare entity within the spectrum of pericardial diseases-a case report.

Eur Heart J Case Rep 2020 Dec 6;4(6):1-3. Epub 2020 Nov 6.

Heart and Vascular Institute, Center for the Diagnosis and Treatment of Pericardial disease,Cleveland Clinic, OH, USA.

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http://dx.doi.org/10.1093/ehjcr/ytaa322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891280PMC
December 2020

Arrhythmias in Cardiac Sarcoidosis Bench to Bedside: A Case-Based Review.

Circ Arrhythm Electrophysiol 2021 02 16;14(2):e009203. Epub 2021 Feb 16.

University of Washington School of Medicine, Seattle (L.L.V., K.K.P., R.K.C.).

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.
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http://dx.doi.org/10.1161/CIRCEP.120.009203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142901PMC
February 2021

Incorporating coronary calcification by computed tomography into CHA2DS2-VASc score: impact on cardiovascular outcomes in patients with atrial fibrillation.

Europace 2021 Feb 15. Epub 2021 Feb 15.

Section of Cardiovascular Imaging, Heart, Vascular and Thoracic Institute, 9500 Euclid Avenue, Main Campus J1-5, Cleveland Clinic, Cleveland,OH 44195, USA.

Aims: CHA2DS2-VASc score is widely utilized for risk stratification and guiding anticoagulation in patients with atrial fibrillation (AF). Cardiac computed tomography (CCT) routinely performed for pulmonary vein isolation (PVI) can also identify coronary artery calcifications (CAC). We evaluated the frequency and outcomes of incorporating CAC into the CHA2DS2-VASc score in AF patients undergoing PVI.

Methods And Results: Consecutive patients in a prospective PVI registry during 2014-18 having CCT within 1 year of PVI were studied. Reclassification of CHA2DS2-VASc score and associations between CAC as a binary variable detected on CCT with clinical characteristics, stroke as primary endpoint, death, myocardial infarction, and major adverse cardiovascular events (MACE) were analysed. Amongst 3604 AF patients, 2238 (62.1%) had CAC detected on CCT and was associated with most traditional cardiovascular risk factors. Coronary artery calcification was independently associated with all pre-specified endpoints adjusting for clinical parameters in multivariable analysis. Adjusting for CHA2DS2-VASc score, CAC was associated with stroke (hazards ratio 3.64, 95% confidence interval 1.25-10.6, P = 0.018), death (2.26, 1.29-3.98, P = 0.006), and MACE (2.08, 1.36-3.16, P = 0.001) during 2.8 ± 1.6-year follow-up. Incorporating CAC as a vascular disease parameter of CHA2DS2-VASc score, anticoagulation decision-making would be revised in 723 (20.1%) patients, including an additional 488 (13.5%) patients where anticoagulation would be now indicated.

Conclusion: Coronary artery calcification is prevalent in AF patients undergoing PVI and independently associated stroke, death and MACE even when adjusted for traditional CHA2DS2-VASc score. Adding CAC as vascular component to the CHA2DS2-VASc score requires further research as it potentially modified the anticoagulation management in 20% of our AF cohort.
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http://dx.doi.org/10.1093/europace/euab032DOI Listing
February 2021

Characterization of Protein-Phospholipid/Membrane Interactions Using a "Membrane-on-a-Chip" Microfluidic System.

Methods Mol Biol 2021 ;2251:143-156

Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

It is now clear that organelles of a mammalian cell can be distinguished by phospholipid profiles, both as ratios of common phospholipids and by the absence or presence of certain phospholipids. Organelle-specific phospholipids can be used to provide a specific shape and fluidity to the membrane and/or used to recruit and/or traffic proteins to the appropriate subcellular location and to restrict protein function to this location. Studying the interactions of proteins with specific phospholipids using soluble derivatives in isolation does not always provide useful information because the context in which the headgroups are presented almost always matters. Our laboratory has shown this circumstance to be the case for a viral protein binding to phosphoinositides in solution and in membranes. The system we have developed to study protein-phospholipid interactions in the context of a membrane benefits from the creation of tailored membranes in a channel of a microfluidic device, with a fluorescent lipid in the membrane serving as an indirect reporter of protein binding. This system is amenable to the study of myriad interactions occurring at a membrane surface as long as a net change in surface charge occurs in response to the binding event of interest.
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http://dx.doi.org/10.1007/978-1-0716-1142-5_10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212032PMC
March 2021

Improvement in left ventricular mechanics following medical treatment of constrictive pericarditis.

Heart 2021 May 6;107(10):828-835. Epub 2021 Jan 6.

Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA

Objective: Patients with constrictive pericarditis (CP) with active inflammation may show resolution with anti-inflammatory therapy. We aimed to investigate the impact of anti-inflammatory medications on constrictive pathophysiology using echocardiography in patients with CP.

Methods: We identified 35 patients with CP who were treated with anti-inflammatory medications (colchicine, prednisone, non-steroidal anti-inflammatory drugs) after diagnosis of CP (mean age 58±13; 80% male). Clinical resolution of CP (transient CP) was defined as improvement in New York Heart Association class during follow-up. We assessed constrictive pathophysiology using regional myocardial mechanics by the ratio of peak early diastolic tissue velocity (e') at the lateral and septal mitral annulus by tissue Doppler imaging (lateral/septal e') or the ratio of the left ventricular lateral and septal wall longitudinal strain (LS/LS) by two-dimensional speckle-tracking echocardiography. Longitudinal data were analysed using a mixed effects model.

Results: During a median follow-up of 323 days, 20 patients had transient CP, whereas 15 patients had persistent CP. Transient CP had higher baseline erythrocyte sedimentation rates (ESR) (p=0.003) compared with persistent CP. There were no significant differences in LS/LS and lateral/septal e'. During follow-up, only transient CP showed improvement in lateral/septal e' (p<0.001) and LS/LS (p=0.003), and recovery of inflammatory markers was similar between the two groups. In the logistic model, higher baseline ESR and greater improvement in lateral/septal e' and LS/LS were associated with clinical resolution of CP using anti-inflammatory therapy.

Conclusions: Improvement of constrictive physiology detected by lateral/septal e' and LS/LS was associated with resolution of clinical symptoms after anti-inflammatory treatment. Serial monitoring of these markers could be used to identify transient CP.
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http://dx.doi.org/10.1136/heartjnl-2020-317304DOI Listing
May 2021

Contact Ion Pairs in the Bulk Affect Anion Interactions with Poly(-isopropylacrylamide).

J Phys Chem B 2021 01 7;125(2):680-688. Epub 2021 Jan 7.

Eduard-Zintl-Institut für Anorganische und Physikalische Chemie, Technische Universität Darmstadt, D-64287 Darmstadt, Germany.

Salt effects on the solubility of uncharged polymers in aqueous solutions are usually dominated by anions, while the role of the cation with which they are paired is often ignored. In this study, we examine the influence of three aqueous metal iodide salt solutions (LiI, NaI, and CsI) on the phase transition temperature of poly(-isopropylacrylamide) (PNIPAM) by measuring the turbidity change of the solutions. Weakly hydrated anions, such as iodide, are known to interact with the polymer and thereby lead to salting-in behavior at low salt concentration followed by salting-out behavior at higher salt concentration. When varying the cation type, an unexpected salting-out trend is observed at higher salt concentrations, Cs > Na > Li. Using molecular dynamics simulations, it is demonstrated that this originates from contact ion pair formation in the bulk solution, which introduces a competition for iodide ions between the polymer and cations. The weakly hydrated cation, Cs, forms contact ion pairs with I in the bulk solution, leading to depletion of CsI from the polymer-water interface. Microscopically, this is correlated with the repulsion of iodide ions from the amide moiety.
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http://dx.doi.org/10.1021/acs.jpcb.0c11076DOI Listing
January 2021

Screening of Potential Cardiac Involvement in Competitive Athletes Recovering From COVID-19: An Expert Consensus Statement.

JACC Cardiovasc Imaging 2020 12 28;13(12):2635-2652. Epub 2020 Oct 28.

Clinical Research Domain, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

As our understanding of the complications of coronavirus disease-2019 (COVID-19) evolve, subclinical cardiac pathology such as myocarditis, pericarditis, and right ventricular dysfunction in the absence of significant clinical symptoms represents a concern. The potential implications of these findings in athletes are significant given the concern that exercise, during the acute phase of viral myocarditis, may exacerbate myocardial injury and precipitate malignant ventricular arrhythmias. Such concerns have led to the development and publication of expert consensus documents aimed at providing guidance for the evaluation of athletes after contracting COVID-19 in order to permit safe return to play. Cardiac imaging is at the center of these evaluations. This review seeks to evaluate the current evidence regarding COVID-19-associated cardiovascular disease and how multimodality imaging may be useful in the screening and clinical evaluation of athletes with suspected cardiovascular complications of infection. Guidance is provided with diagnostic "red flags" that raise the suspicion of pathology. Specific emphasis is placed on the unique challenges posed in distinguishing athletic cardiac remodeling from subclinical cardiac disease. The strengths and limitations of different imaging modalities are discussed and an approach to return to play decision making for athletes post-COVID-19, as informed by multimodality imaging, is provided.
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http://dx.doi.org/10.1016/j.jcmg.2020.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598679PMC
December 2020

Advanced Respiratory Support in the Contemporary Cardiac ICU.

Crit Care Explor 2020 Sep 17;2(9):e0182. Epub 2020 Sep 17.

TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

The medical complexity and critical care needs of patients admitted to cardiac ICUs are increasing, and prospective studies examining the underlying cardiac and noncardiac diagnoses, the management strategies, and the prognosis of cardiac ICU patients with respiratory failure are needed.

Design: Prospective cohort study.

Setting: The Critical Care Cardiology Trials Network is a research collaborative of cardiac ICUs across the United States and Canada.

Patients: We included all medical cardiac ICU admissions at 25 cardiac ICUs during two consecutive months annually at each center from 2017 to 2019.

Measurements: We evaluated the use of advanced respiratory therapies including invasive mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula versus no advanced respiratory support across admission diagnoses and the association with in-hospital mortality.

Main Results: Of 8,240 cardiac ICU admissions, 1,935 (23.5%) were treated with invasive mechanical ventilation, 573 (7.0%) with noninvasive ventilation, and 281 (3.4%) with high-flow nasal cannula. Admitting diagnoses among those with advanced respiratory support were diverse including general medical problems in patients with heart disease as well as primary cardiac problems. In-hospital mortality was higher in patients who received invasive mechanical ventilation (38.1%; adjusted odds ratio, 2.53; 2.02-3.16) and noninvasive ventilation or high-flow nasal cannula (8.8%; adjusted odds ratio, 2.25; 1.73-2.93) compared with patients without advanced respiratory support (4.6%). Reintubation rate was 7.6%. The most common variables associated with respiratory insufficiency included heart failure, infection, chronic obstructive pulmonary disease, and pulmonary vascular disease.

Conclusions: One-third of cardiac ICU admissions receive respiratory support with associated increased mortality. These data provide benchmarks for quality improvement ventures in the cardiac ICU, inform cardiac critical care training and staffing patterns, and serve as foundation for future studies aimed at improving outcomes.
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http://dx.doi.org/10.1097/CCE.0000000000000182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678799PMC
September 2020

Efficacy and safety of rilonacept for recurrent pericarditis: results from a phase II clinical trial.

Heart 2020 Nov 23. Epub 2020 Nov 23.

Kiniksa Pharmaceuticals Corp, Lexington, Massachusetts, USA.

Objective: Recurrent pericarditis (RP) incurs significant morbidity. Rilonacept inhibits both interleukin-1 alpha (IL-1α) and IL-1β; these cytokines are thought to play a major role in RP. This phase II study evaluated rilonacept efficacy and safety in RP.

Methods: This multicentre, open-label study enrolled adult patients with idiopathic or postpericardiotomy RP, symptomatic (≥2 pericarditis recurrences) or corticosteroid (CS) dependent (≥2 recurrences prior).Patients received rilonacept 320 mg SC load/160 mg SC weekly maintenance in a 6-week base treatment period (TP) followed by an optional 18-week on-treatment extension period (EP) (option to wean background therapy).

Results: Outcomes: pericarditis pain (numeric rating scale (NRS)) and inflammation (C reactive protein (CRP)) for symptomatic patients; disease activity after CS taper for CS-dependent patients.

Secondary Outcomes: health-related quality of life (HRQOL), pericarditis manifestations and additional medications. 25 unique patients enrolled, while 23 completed the EP (seven colchicine failures and five CS failures). In symptomatic patients, NRS and CRP decreased; response was observed after first rilonacept dose. NRS decreased from 4.5 at baseline to 0.7, and CRP decreased from 4.62 mg/dL at baseline to 0.38 mg/dL at end of TP. Median time to CRP normalisation: 9 days. Pericarditis manifestations resolved. 13 patients on CS at baseline completed the EP; 11 (84.6%) discontinued CS, and 2 tapered; CRP and NRS remained low without recurrence. Mean HRQOL scores improved in symptomatic patients. One serious adverse event (SAE) resulted in discontinuation of rilonacept.

Conclusions: Rilonacept led to rapid and sustained improvement in pain, inflammation (CRP and pericarditis manifestations) and HRQOL. CSs were successfully tapered or discontinued; safety was consistent with known rilonacept safety profile.

Trial Registration Number: NCT03980522.
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http://dx.doi.org/10.1136/heartjnl-2020-317928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925818PMC
November 2020

Apical defect following Tendyne valve placement.

J Nucl Cardiol 2020 Nov 19. Epub 2020 Nov 19.

Cleveland Clinic Heart, Vascular and Thoracic Institute, Cleveland, OH, USA.

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http://dx.doi.org/10.1007/s12350-020-02440-6DOI Listing
November 2020

Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis.

N Engl J Med 2021 01 16;384(1):31-41. Epub 2020 Nov 16.

From the Center for the Diagnosis and Treatment of Pericardial Diseases, Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland (A.L.K., P.C.); University Cardiology, Cardiovascular, and Thoracic Department, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino and University of Turin, Turin (M.I.), the Department of Biomedical and Clinical Science, University of Milan, Fatebenefratelli Hospital, Milan (A.B.), and the Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome (A.I.) - all in Italy; Pauley Heart Center, Virginia Commonwealth University, Richmond (A.A.); Kiniksa Pharmaceuticals, Lexington, MA (F.F., A.P., J.F.P.); the Cardiology Unit, University of Vermont Medical Center, Burlington (M.L.); the Cardiovascular Clinical Research Institute, Lady Davis Carmel Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel (B.S.L.); the Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis (D.L.), and the Division of Cardiovascular Ultrasound, Department of Cardiovascular Medicine, Mayo Clinic, Rochester (S.A.L.) - both in Minnesota; the Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Clayton, VIC, Australia (S.J.N.); and Kiniksa Pharmaceuticals, Hamilton, Bermuda (A.W.).

Background: Interleukin-1 has been implicated as a mediator of recurrent pericarditis. The efficacy and safety of rilonacept, an interleukin-1α and interleukin-1β cytokine trap, were studied previously in a phase 2 trial involving patients with recurrent pericarditis.

Methods: We conducted a phase 3 multicenter, double-blind, event-driven, randomized-withdrawal trial of rilonacept in patients with acute symptoms of recurrent pericarditis (as assessed on a patient-reported scale) and systemic inflammation (as shown by an elevated C-reactive protein [CRP] level). Patients presenting with pericarditis recurrence while receiving standard therapy were enrolled in a 12-week run-in period, during which rilonacept was initiated and background medications were discontinued. Patients who had a clinical response (i.e., met prespecified response criteria) were randomly assigned in a 1:1 ratio to receive continued rilonacept monotherapy or placebo, administered subcutaneously once weekly. The primary efficacy end point, assessed with a Cox proportional-hazards model, was the time to the first pericarditis recurrence. Safety was also assessed.

Results: A total of 86 patients with pericarditis pain and an elevated CRP level were enrolled in the run-in period. During the run-in period, the median time to resolution or near-resolution of pain was 5 days, and the median time to normalization of the CRP level was 7 days. A total of 61 patients underwent randomization. During the randomized-withdrawal period, there were too few recurrence events in the rilonacept group to allow for the median time to the first adjudicated recurrence to be calculated; the median time to the first adjudicated recurrence in the placebo group was 8.6 weeks (95% confidence interval [CI], 4.0 to 11.7; hazard ratio in a Cox proportional-hazards model, 0.04; 95% CI, 0.01 to 0.18; P<0.001 by the log-rank test). During this period, 2 of 30 patients (7%) in the rilonacept group had a pericarditis recurrence, as compared with 23 of 31 patients (74%) in the placebo group. In the run-in period, 4 patients had adverse events leading to the discontinuation of rilonacept therapy. The most common adverse events with rilonacept were injection-site reactions and upper respiratory tract infections.

Conclusions: Among patients with recurrent pericarditis, rilonacept led to rapid resolution of recurrent pericarditis episodes and to a significantly lower risk of pericarditis recurrence than placebo. (Funded by Kiniksa Pharmaceuticals; RHAPSODY ClinicalTrials.gov number, NCT03737110.).
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http://dx.doi.org/10.1056/NEJMoa2027892DOI Listing
January 2021

Positioning of the Tibial Tunnel After Single-Bundle ACL Primary Reconstruction on 3D CT scans: A New Method.

Arthrosc Sports Med Rehabil 2020 Oct 9;2(5):e615-e622. Epub 2020 Oct 9.

Centre Albert Trillat, Hôpital de la Croix Rousse, Lyon, France.

Purpose: To assess intra-articular tunnel aperture positioning after primary anterior cruciate ligament (ACL) reconstruction with either the reference standard method or the intercondylar area method in a single center using 3-dimensional (3D) computed tomography (CT) scans and to evaluate the intra-articular position of the tibial tunnel relative to the ACL footprint.

Methods: 3D CT scans were performed after 120 single-bundle primary ACL reconstruction cases. The center of the tibial tunnel aperture and the center of the ACL footprint were referenced on axial views of the tibial plateau in the anteroposterior (AP) and mediolateral (ML) planes according to a centimetric grid system including the whole plateau (reference standard). This was compared with a grid system based on intercondylar area bony anatomy. The posterior aspect of intertubercular fossa, anterior aspect of the tibial plateau, medial intercondylar ridge, and crossing point between lateral intercondylar ridge and posterior margin were used as landmarks to define the grid.

Results: According to the reference standard method, the center of the tibial tunnel aperture was positioned 0.57 ± 2.62 mm more posterior and 0.67 ± 1.55 mm more medial than the center of the footprint. According to the intercondylar area method, the center of the tibial tunnel aperture was positioned 1.32 ± 2.74 mm more posterior and 0.66 ± 1.56 mm more medial than the center of the footprint. The position difference between the center of the tunnel aperture and the center of the footprint were statistically correlated for both grids, with  = -0.887, < .001 for AP positioning and  = 0.615, < .001 for ML positioning.

Conclusion: This intercondylar area method using arthroscopic landmarks can be used to assess tunnel placement on 3D CT scans after ACL reconstruction.

Level Of Evidence: III, retrospective comparative study.
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http://dx.doi.org/10.1016/j.asmr.2020.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588642PMC
October 2020

Molecular Mechanism for the Interactions of Hofmeister Cations with Macromolecules in Aqueous Solution.

J Am Chem Soc 2020 11 30;142(45):19094-19100. Epub 2020 Oct 30.

Laboratory for fundamental BioPhotonics (LBP), Institute of Bioengineering (IBI), and Institute of Materials Science (IMX), School of Engineering (STI), and Lausanne Centre for Ultrafast Science (LACUS), École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.

Ion identity and concentration influence the solubility of macromolecules. To date, substantial effort has been focused on obtaining a molecular level understanding of specific effects for anions. By contrast, the role of cations has received significantly less attention and the underlying mechanisms by which cations interact with macromolecules remain more elusive. To address this issue, the solubility of poly(-isopropylacrylamide), a thermoresponsive polymer with an amide moiety on its side chain, was studied in aqueous solutions with a series of nine different cation chloride salts as a function of salt concentration. Phase transition temperature measurements were correlated to molecular dynamics simulations. The results showed that although all cations were on average depleted from the macromolecule/water interface, more strongly hydrated cations were able to locally accumulate around the amide oxygen. These weakly favorable interactions helped to partially offset the salting-out effect. Moreover, the cations approached the interface together with chloride counterions in solvent-shared ion pairs. Because ion pairing was concentration-dependent, the mitigation of the dominant salting-out effect became greater as the salt concentration was increased. Weakly hydrated cations showed less propensity for ion pairing and weaker affinity for the amide oxygen. As such, there was substantially less mitigation of the net salting-out effect for these ions, even at high salt concentrations.
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http://dx.doi.org/10.1021/jacs.0c07214DOI Listing
November 2020

Does augmented core decompression decrease the rate of collapse and improve survival of femoral head avascular necrosis? Case-control study comparing 184 augmented core decompressions to 79 standard core decompressions with a minimum 2 years' follow-up.

Orthop Traumatol Surg Res 2020 12 26;106(8):1561-1568. Epub 2020 Oct 26.

SOFCOT, 56, rue Boissonade, 75014 Paris, France.

Introduction: Avascular necrosis of the femoral head often progresses to femoral head collapse if not treated. Conservative treatment yields highly variable results and is not standardised, mainly because it is typically evaluated in small patient populations. This led us to conduct a large retrospective comparative study with the goals of 1) analysing survival and functional outcomes, 2) looking for differences in survival between core decompression techniques (standard versus augmented), and 3) studying the risk factors for femoral head collapse and revision by arthroplasty.

Hypothesis: Core decompression limits the number of patients who suffer femoral head collapse requiring arthroplasty at 2 years' follow-up.

Methods: This multicentre, comparative, retrospective study analysed 330 patient records (1975-2016) where at least 2 years' follow-up was available. Sixty-two patients were excluded from the analysis: 5 had a stage III with collapse, 5 were lost to follow-up, 2 died within 24 months of the procedure and 50 had incomplete data. The study included 263 patients with a mean age of 42 years (15.7-70). In the Ficat classification, there were 51 cases of stage I necrosis, 186 cases of stage II and 22 cases of stage II with crescent sign (transition stage). The Kerboull angle on radiographs was between 5° and 20° in 40 patients, between 20° and 40° in 107 patients, between 40° and 60° in 52 patients and more than 60° in 29 patients. A standard core decompression was done in 79 patients and an augmented one in 184 patients. The more severe AVN cases (stage II) were more likely to be treated by augmented CD (160/184 patients, 87%) than by standard CD (48/79 patients, 61%) (p<0.001).

Results: In the 263 patients, the overall survival (no arthroplasty at 2 years) was 73% (196/263). At 2 years, the survival rate (without arthroplasty) was 71% (56/79) in the standard CD group versus 76% (140/184) in the augmented CD group. This difference was significant when adjusted for Ficat stage and Kerboull angle [HR=0.457, 95% CI (0.247-0.844) (p=0.012)]. When the survival data was adjusted to the Ficat stage, augmented CD was better than standard CD with 10-year survival of 58.1% vs. 57.9% (p=0.0082). More than 30% necrosis volume increased the risk of failure [HR=3.291 95%CI (1.494-7.248) (p=0.0031)]. Also, a Kerboull angle above 60° increased the risk of failure [HR=3.148 95%CI (1.346-7.5) (p=0.0083)].

Conclusion: After 2 years, CD for non-collapsed femoral head AVN prevents collapse and revision to arthroplasty in 73% of cases (196/268). Augmented CD improves the 2-year survival and the long-term survival after adjusting for preoperative characteristics (Kerboullangle and Ficat stage). The risk of collapse and need for arthroplasty is greater in patients with 30% necrosis volume on MRI and Kerboull angle above 60°.

Level Of Evidence: III; retrospective case-control study.
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http://dx.doi.org/10.1016/j.otsr.2020.03.040DOI Listing
December 2020

Zn Binds to Phosphatidylserine and Induces Membrane Blebbing.

J Am Chem Soc 2020 10 20;142(43):18679-18686. Epub 2020 Oct 20.

Herein, we show that Zn binds to phosphatidylserine (PS) lipids in supported lipid bilayers (SLBs), forming a PS-Zn complex with an equilibrium dissociation constant of ∼100 μM. Significantly, Zn binding to SLBs containing more than 10 mol % PS induces extensive reordering of the bilayer. This reordering is manifest through bright spots of high fluorescence intensity that can be observed when the bilayer contains a dye-labeled lipid. Measurements using atomic force microscopy (AFM) reveal that these spots represent three-dimensional unilamellar blebs. Bleb formation is ion specific, inducible by exposing the bilayer to μM concentrations of Zn but not Mg, Cu, Co, or Mn. Moreover, Ca can induce some blebbing at mM concentrations but not nearly as effectively as Zn. The interactions of divalent metal cations with PS lipids were further investigated by a combination of vibrational sum frequency spectroscopy (VSFS) and surface pressure-area isotherm measurements. VSFS revealed that Zn and Ca were bound to the phosphate and carboxylate moieties on PS via contact ion pairing, dehydrating the lipid headgroup, whereas Mg and Cu were bound without perturbing the hydration of these functional groups. Additionally, Zn was found to dramatically reduce the area per lipid in lipid monolayers, while Mg and Cu did not. Ca could also reduce the area per lipid but only when significantly higher surface pressures were applied. These measurements suggest that Zn caused lipid blebbing by decreasing the area per lipid on the side of the bilayer to which the salt was exposed. Such findings have implications for blebbing, fusion, oxidation, and related properties of PS-rich membranes in biological systems where Zn concentrations are asymmetrically distributed.
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http://dx.doi.org/10.1021/jacs.0c09103DOI Listing
October 2020

Novel dietary protocol prior to 18F-fluorodeoxyglucose positron emission tomography to evaluate for cardiac sarcoidosis.

J Nucl Cardiol 2020 Oct 14. Epub 2020 Oct 14.

Cardiovascular Medicine Department, Cleveland Clinic Foundation, 9500 Euclid Ave, NA3-129, Cleveland, OH, USA.

The diagnosis of cardiac sarcoidosis (CS) is challenging. Recently, guidelines incorporated cardiac positron emission tomography (PET) with 18F-Fluorodeoxyglucose (F18-FDG) as a non-invasive diagnostic modality for the detection and follow-up of CS. However, this technique is dependent of patient dietary preparation to suppress physiological myocardial F18-FDG uptake. We present a case of possible CS which highlights a novel preparation protocol that facilitated appropriate myocardial suppression.
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http://dx.doi.org/10.1007/s12350-020-02392-xDOI Listing
October 2020
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