Publications by authors named "Christopher Cook"

166 Publications

Classification of human chronic inflammatory skin disease based on single-cell immune profiling.

Sci Immunol 2022 Apr 15;7(70):eabl9165. Epub 2022 Apr 15.

Department of Dermatology, University of California, San Francisco, San Francisco, CA 94107, USA.

Inflammatory conditions represent the largest class of chronic skin disease, but the molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting the complex mixture of immune and stromal cell perturbations in inflammatory skin disease states. We single-cell-profiled CD45 immune cell transcriptomes from skin samples of 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6 clinical/histopathologically indeterminate rashes, and 7 healthy controls). Our data revealed active proliferative expansion of the T and Trm components and universal T cell exhaustion in human rashes, with a relative attenuation of antigen-presenting cells. Skin-resident memory T cells showed the greatest transcriptional dysregulation in both atopic dermatitis and psoriasis, whereas atopic dermatitis also demonstrated recurrent abnormalities in ILC and CD8 cytotoxic lymphocytes. Transcript signatures differentiating these rash types included genes previously implicated in T helper cell (T2)/T17 diatheses, segregated in unbiased functional networks, and accurately identified disease class in untrained validation data sets. These gene signatures were able to classify clinicopathologically ambiguous rashes with diagnoses consistent with therapeutic response. Thus, we have defined major classes of human inflammatory skin disease at the molecular level and described a quantitative method to classify indeterminate instances of pathologic inflammation. To make this approach accessible to the scientific community, we created a proof-of-principle web interface (RashX), where scientists and clinicians can visualize their patient-level rash scRNA-seq-derived data in the context of our T2/T17 transcriptional framework.
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http://dx.doi.org/10.1126/sciimmunol.abl9165DOI Listing
April 2022

3D transesophageal echocardiography for guiding transcatheter aortic valve replacement without prior cardiac computed tomography in patients with renal dysfunction.

Cardiovasc Revasc Med 2022 Jan 13. Epub 2022 Jan 13.

Department of Cardiology, West Virginia University School of Medicine, Morgantown, WV 26506, USA. Electronic address:

Background: Pre-procedural chronic kidney disease (CKD) and in-hospital acute kidney injury (AKI) are associated with worse outcomes following transcatheter aortic valve replacement (TAVR). We tested the feasibility of reducing overall AKI by avoiding pre-procedural cardiac CT angiography (CCTA) by using direct 3D-TEE guidance in TAVR patients with known CKD.

Methods: An institutional TAVR database was examined from January 2016 to June 2020 to identify 396 patients in whom CCTA sizing was performed and 54 patients with creatinine (Cr) of >1.6 mg/dL in whom direct 3D-TEE, without prior CCTA, was used for TAVR guidance. Baseline demographics, procedural, echocardiographic, and clinical endpoints were compared as defined by the Valve Academic Research Consortium-2 criteria.

Results: Baseline demographics and risk factors were similar in both groups other than the creatinine level in CCTA vs. TEE groups (1.33 ± 1.1 vs 1.76 ± 0.7 mg/dL, p = 0.005). Procedural contrast volume was significantly lower in the TEE group compared to the CCTA group. No differences were noted in echocardiographic and clinical endpoints for both groups. Despite higher baseline Cr, patents in the TEE group experienced a similar pattern of changes in Cr compared to the CCTA group, with an overall renal improvement noted at the time of discharge for both groups.

Conclusions: In patients with baseline CKD, careful avoidance of large contrast loads associated with CCTA and intra-procedural aortography by using TEE guidance may help reduce AKI following TAVR.
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http://dx.doi.org/10.1016/j.carrev.2021.12.026DOI Listing
January 2022

Feasibility of early waking cardiac arrest patients whilst receiving therapeutic hypothermia: The therapeutic hypothermia and early waking (THAW) trial.

Resuscitation 2022 02 27;171:114-120. Epub 2021 Nov 27.

Essex Cardiothoracic Centre, Basildon, Essex, UK; MTRC, Anglia Ruskin School of Medicine, Chelmsford, Essex, UK. Electronic address:

Aim: To determine the safety and feasibility of an early (12 h) waking and extubation protocol for out-of-hospital cardiac arrest (OHCA) patients receiving targeted temperature management (TTM).

Methods: This was a single-centre, prospective, non-randomised, observational, safety and feasibility pilot study which included successfully resuscitated OHCA patients, of presumed cardiac cause. Inclusion criteria were: OHCA patients aged over 18 years with a return of spontaneous circulation, who were going to receive TTM33 (TTM at 33 °C for 24 h and prevention of hyperthermia for 72 h) as part of their post cardiac arrest care. Clinical stability was measured against physiological and neurological parameters as well as clinical assessment.

Results: 50 consecutive patients were included (median age 65.5 years, 82% male) in the study. Four (8%) patients died within the first twelve hours and were excluded from the final cohort (n = 46). Twenty-three patients (46%) were considered clinically stable and suitable for early waking based on the intention to treat analysis; 12 patients were extubated early based on a variety of clinical factors (21.4 ± 8.6 h) whilst continuing to receive TTM33 with a mean core temperature of 34.2 °C when extubated. Of these, five patients were discharged from the intensive care unit (ICU) <48 h after admission with a mean ICU length of stay 1.8 ± 0.4 days. Twenty-eight patients (56%) were discharged from the ICU with a modified Rankin Score of 0-2. The overall intra-hospital mortality was 50% (n = 25).

Conclusions: It is safe and feasible to wake selected comatose OHCA patients at 12 h, allowing for earlier positive neuro-prognostication and reduced ICU stay.
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http://dx.doi.org/10.1016/j.resuscitation.2021.11.031DOI Listing
February 2022

Rare Presentation of Atypical Hemolytic Uremic Syndrome in an Adult.

Cureus 2021 Sep 22;13(9):e18184. Epub 2021 Sep 22.

Internal Medicine, East Tennessee State University Quillen College of Medicine, Johnson City, USA.

Thrombotic microangiopathies (TMA) are disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microthrombi leading to organ dysfunction. Atypical hemolytic uremic syndrome (aHUS) is a rare subtype of TMA mediated by complement dysregulation. We present a case of a 59-year-old female who presented with acute kidney injury and mild thrombocytopenia but with normal hemoglobin. We highlight the importance of prompt diagnosis of aHUS and initiating appropriate treatment with eculizumab.
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http://dx.doi.org/10.7759/cureus.18184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459801PMC
September 2021

Robotics, imaging, and artificial intelligence in the catheterisation laboratory.

EuroIntervention 2021 Sep;17(7):537-549

The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

The catheterisation laboratory today combines diagnosis and therapeutics, through various imaging modalities and a prolific list of interventional tools, led by balloons and stents. In this review, we focus primarily on advances in image-based coronary interventions. The X-ray images that are the primary modality for diagnosis and interventions are combined with novel tools for visualisation and display, including multi-imaging co-registration modalities with three- and four-dimensional presentations. Interpretation of the physiologic significance of coronary stenosis based on prior angiographic images is being explored and implemented. Major efforts to reduce X-ray exposure to the staff and the patients, using computer-based algorithms for image processing, and novel methods to limit the radiation spread are being explored. The use of artificial intelligence (AI) and machine learning for better patient care requires attention to universal methods for sharing and combining large data sets and for allowing interpretation and analysis of large cohorts of patients. Barriers to data sharing using integrated and universal protocols should be overcome to allow these methods to become widely applicable. Robotic catheterisation takes the physician away from the ionising radiation spot, enables coronary angioplasty and stenting without compromising safety, and may allow increased precision. Remote coronary procedures over the internet, that have been explored in virtual and animal studies and already applied to patients in a small pilot study, open possibilities for sharing experience across the world without travelling. Application of those technologies to neurovascular, and particularly stroke interventions, may be very timely in view of the need for expert neuro-interventionalists located mostly in central areas.
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http://dx.doi.org/10.4244/EIJ-D-21-00145DOI Listing
September 2021

Experience or attribution? Exploring the relationship between personal experience, political affiliation, and subjective attributions with mitigation behavioural intentions and COVID-19 recovery policy support.

J Environ Psychol 2021 Oct 10;77:101685. Epub 2021 Sep 10.

School of Communication, Journalism & Marketing, Massey University, New Zealand.

Scholars argue that personal experience with climate change related impacts can increase public engagement, with mixed empirical evidence. Previous studies have almost exclusively focussed on individuals' experience with extreme weather events, even as scientific research on health impacts of climate change is burgeoning. This article extends previous research in the domain of public perceptions about climate-related public health impacts. Results from a nationally representative sample survey in New Zealand indicates that subjective attribution of infectious disease outbreaks to climate change and to human impact on the environment is positively associated with mitigation behavioural intentions and climate-focussed COVID-19 economic recovery policies. In contrast, knowledge about COVID-19 and self-reported economic impact due to COVID-19 is not associated with policy support. Moreover, significant interaction between political affiliation and subjective attribution to climate change on policy support indicate that learning about the links between health and climate change will particularly help increase mitigation engagement among right-leaning individuals. Subjective attribution may be the key to help translate personal experience to personal engagement.
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http://dx.doi.org/10.1016/j.jenvp.2021.101685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442554PMC
October 2021

Erratum: A 34-Year-Old Male Intravenous Drug User with a Third Episode of Tricuspid Valve Endocarditis Treated with Repeat Valve Surgery.

Am J Case Rep 2021 Aug 17;22:e934383. Epub 2021 Aug 17.

Division of Cardiovascular and Thoracic Anesthesiology, Department of Anesthesiology, West Virginia University, Morgantown, WV, USA.

Figure Legends Corrected: Figure 1. Intraoperative transesophageal echocardiogram, midesophageal right ventricular infow-outflow view, initial operation September 2018. Figure 2. Intraoperative transesophageal echocardiogram, midesophageal right ventricular inflow-outflow view, second operation January 2019. Figure 3. Intraoperative transesophageal echocardiogram, midesophageal right ventricular inflow-outflow view, third operation March 2019. Reference: Jeffrey W. Cannon, J.W. Awori Hayanga, Thomas B. Drvar, Matthew Ellison, Christopher Cook, Muhammad Salman, Harold Roberts, Vinay Badhwar, Heather K. Hayanga. A 34-Year-Old Male Intravenous Drug User with a Third Episode of Tricuspid Valve Endocarditis Treated with Repeat Valve Surgery. Am J Case Rep. 2021; 22: e927385, 10.12659/AJCR.927385.
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http://dx.doi.org/10.12659/AJCR.934383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380853PMC
August 2021

Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes.

Int J Cardiol 2021 Nov 4;342:7-14. Epub 2021 Aug 4.

The Hammersmith Hospital, London, UK.

Objectives: Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis.

Methods: Twenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli.

Results: Mean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44-0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm.sec vs 4.2 ± 1.7 mmHg.cm.sec, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all).

Conclusions: In patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.
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http://dx.doi.org/10.1016/j.ijcard.2021.07.064DOI Listing
November 2021

Phasic flow patterns of right versus left coronary arteries in patients undergoing clinical physiological assessment.

EuroIntervention 2022 Feb;17(15):1260-1270

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Background: Coronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest that this is less pronounced or even reversed in the right coronary artery (RCA).

Aims: This study aimed to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment.

Methods: We analysed data from the Iberian-Dutch-English Collaborators (IDEAL) study. A total of 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis.

Results: On average, coronary flow was higher in diastole both at rest and during hyperaemia in both the RCA and LCA (mean diastolic-to-systolic velocity ratio [DSVR] was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCA, LCA, RCA and RCA, p<0.001 for between-vessel comparisons). Although the type of RCA dominance affected the DSVR magnitude (RCA=1.55±0.35, RCA=1.40±0.27, RCA=1.35; standard deviation not reported as n=3), systolic flow was very rarely predominant (DSVR was greater than or equal to 1.00 in 472/482 cases [97.9%] overall), with equal prevalence in the LCA. Stenosis severity or microvascular dysfunction had a negligible impact on DSVR in both the RCA and LCA (DSVR x hyperaemic stenosis resistance R =0.018, p=0.03 and DSVR x coronary flow reserve R <0.001, p=0.98).

Conclusions: In patients with coronary artery disease undergoing physiological assessment, diastolic flow predominance is seen in both left and right coronary arteries. Clinical interpretation of coronary physiological data should therefore not differ between the left and the right coronary systems.
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http://dx.doi.org/10.4244/EIJ-D-21-00189DOI Listing
February 2022

Successful treatment of intravenous drug abuser with refractory vasoplegic syndrome after mitral valve repair for infective endocarditis.

SAGE Open Med Case Rep 2021 3;9:2050313X211019788. Epub 2021 Jun 3.

Division of Cardiovascular and Thoracic Anesthesiology, West Virginia University, Morgantown, WV, USA.

Vasoplegic syndrome, a possible complication of cardiopulmonary bypass, is a critical state of unregulated systemic vasodilation with decreased vascular resistance and a pathological insensitivity to conventional inotropes and vasoconstrictors. This case demonstrates the use of methylene blue and hydroxocobalamin as medications in the treatment of refractory vasoplegic syndrome in the context of cardiac surgery due to their differences in mechanism of action. A 24-year-old female with history of intravenous drug abuse and hepatitis C infection underwent mitral valve repair for infective endocarditis. Preoperative transesophageal echocardiography showed normal right ventricular function, left ventricular ejection fraction of 65%-75%, and severe mitral regurgitation with vegetation. In order to maintain a mean arterial pressure over 60 mmHg during cardiopulmonary bypass, norepinephrine, epinephrine, and vasopressin infusions were required. Given the patient's minimal response to these medications, a 1.5 mg/kg bolus of intravenous methylene blue was also given intraoperatively; vasoplegic syndrome remained refractory in the post-cardiopulmonary bypass period. A 5 g dose of intravenous hydroxocobalamin was administered in the intensive care unit postoperatively. Postoperative liver function tests were abnormal, and post-cardiopulmonary bypass transesophageal echocardiography revealed mildly decreased right ventricular function. While in the intensive care unit, the patient was placed on venoarterial extracorporeal membrane oxygenation and underwent therapeutic plasma exchange. Vasopressors were weaned over the course of the next 24 h. The patient was able to be transferred out of the intensive care unit on postoperative day 5. Traditional vasoconstrictors activate signal transduction pathways that lead to myosin phosphorylation. Vasodilatory molecules such as nitric oxide (NO) activate the enzyme soluble guanylyl cyclase (sGC), ultimately leading to the dephosphorylation of myosin. Nitric Oxide Synthase (NOS) can potentially increase NO levels 1000-fold when activated by inflammatory cytokines. Methylene blue is a direct inhibitor of NOS. It also binds and inhibits sGC. Hydroxocobalamin is a direct inhibitor of NO, likely inhibits NOS and may also act through additional mechanisms.
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http://dx.doi.org/10.1177/2050313X211019788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182181PMC
June 2021

Correlation of Intravascular Ultrasound and Instantaneous Wave-Free Ratio in Patients With Intermediate Left Main Coronary Artery Disease.

Circ Cardiovasc Interv 2021 06 7;14(6):e009830. Epub 2021 Jun 7.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (S.C.H., T.T., J.N., A.L.).

Background: There is great degree of interobserver variability in the visual angiographic assessment of left main coronary disease (LMCD). Fractional flow reserve and intravascular ultrasound are often used in this setting. The use of instantaneous wave-free ratio (iFR) for evaluation of LMCD has not been well studied. The aim of this study is to evaluate the use of iFR in the assessment of angiographically intermediate LMCD.

Methods: This is an international multicenter retrospective observational study of patients who underwent both iFR and intravascular ultrasound evaluation for angiographically intermediate LMCD. An independent core laboratory performed blinded off-line analysis of all intravascular ultrasound data. A minimum lumen area of 6 mm2 was used as the cutoff for significant disease.

Results: One hundred twenty-five patients (mean age, 68.4±9.5 years, 84.8% male) were included in this analysis. Receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm2 with an area under the curve of 0.77 (77% sensitivity, 66% specificity; P<0.0001). Among the 69 patients without ostial left anterior descending artery or left circumflex artery disease, receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm2 with an area under the curve of 0.84 (70% sensitivity, 84% specificity; P<0.0001). The correlation was not significantly different when the body surface area was considered.

Conclusions: In this study, in patients with intermediate LMCD, iFR of ≤0.89 correlates with intravascular ultrasound minimum lumen area <6 mm2 regardless of body surface area. The current study supports the use of iFR for the evaluation of intermediate LMCD.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206001PMC
June 2021

Congenital Absence of the Patellar Tendon: A Report of 2 Cases.

JBJS Case Connect 2021 04 14;11(2). Epub 2021 Apr 14.

Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, New York.

Case: Isolated unilateral congenital patellar tendon absence is a rare condition that has not been well described. We report on 2 patients with congenital patellar tendon absence that underwent soft-tissue reconstruction of their patellar tendon. We present the clinical and radiographic features, surgical management with both single-stage and multistage approaches, and postoperative outcomes for the treatment of this condition.

Conclusion: Soft-tissue reconstruction of the patellar tendon led to satisfactory outcomes, providing active knee extension and improved ambulation in both cases. In cases of significant superior migration, multiple procedures may be required to mobilize the patella to an appropriate position.
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http://dx.doi.org/10.2106/JBJS.CC.20.00776DOI Listing
April 2021

Supercharging Prions via Amyloid-Selective Lysine Acetylation.

Angew Chem Int Ed Engl 2021 06 26;60(27):15069-15079. Epub 2021 May 26.

Department of Chemistry and Biochemistry, Baylor University, Waco, TX, USA.

Repulsive electrostatic forces between prion-like proteins are a barrier against aggregation. In neuropharmacology, however, a prion's net charge (Z) is not a targeted parameter. Compounds that selectively boost prion Z remain unreported. Here, we synthesized compounds that amplified the negative charge of misfolded superoxide dismutase-1 (SOD1) by acetylating lysine-NH in amyloid-SOD1, without acetylating native-SOD1. Compounds resembled a "ball and chain" mace: a rigid amyloid-binding "handle" (benzothiazole, stilbene, or styrylpyridine); an aryl ester "ball"; and a triethylene glycol chain connecting ball to handle. At stoichiometric excess, compounds acetylated up to 9 of 11 lysine per misfolded subunit (ΔZ =-8100 per 10 subunits). Acetylated amyloid-SOD1 seeded aggregation more slowly than unacetylated amyloid-SOD1 in vitro and organotypic spinal cord (these effects were partially due to compound binding). Compounds exhibited reactivity with other amyloid and non-amyloid proteins (e.g., fibrillar α-synuclein was peracetylated; serum albumin was partially acetylated; carbonic anhydrase was largely unacetylated).
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http://dx.doi.org/10.1002/anie.202103548DOI Listing
June 2021

A 34-Year-Old Male Intravenous Drug User with a Third Episode of Tricuspid Valve Endocarditis Treated with Repeat Valve Surgery.

Am J Case Rep 2021 03 29;22:e927385. Epub 2021 Mar 29.

Division of Cardiovascular and Thoracic Anesthesiology, Department of Anesthesiology, West Virginia University, Morgantown, WV, USA.

BACKGROUND Intravenous drug use is an epidemic in the United States. One of the complications of intravenous drug use can be infective endocarditis. The treatment for this disease is a combination of intravenous antibiotics, cardiac surgery consultation, and multidisciplinary psychiatric care. Despite surgical intervention, recurrence of disease is common. In the setting of recurrent infective endocarditis in the setting of intravenous drug use, the ethics of redo cardiac surgery has not been well-established. CASE REPORT A 34-year-old man with history of intravenous drug use presented on 3 separate occasions with infective endocarditis resulting in 3 tricuspid valve surgeries within fewer than 7 months. He said he had not injected drugs since before his first operation, he was considered to have a strong social support system, and he completed his postoperative antibiotic regimens each time. However, prior to his last operation, the patient had a urine drug screen positive for opiates without recorded prescribed opioids. Pathology reports from the 3 intraoperative specimens showed different pathogens each time. An extensive interprofessional discussion ensued. CONCLUSIONS Infective endocarditis in the setting of intravenous drug use and its treatments continue to be a point of ethical and medical discussion for all professionals involved with the care of these patients. This case could be used as an example of individualized decision-making, with rigorous ethical and medical discussion factoring into each decision for cardiac surgery. The ongoing treatment for patients with recurrent endocarditis in the setting of intravenous drug use requires more research and guidelines to help medical professionals better care for this patient population.
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http://dx.doi.org/10.12659/AJCR.927385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021270PMC
March 2021

Randomized Blinded Placebo-Controlled Trials of Renal Sympathetic Denervation for Hypertension: A Meta-Analysis.

Cardiovasc Revasc Med 2022 01 30;34:112-118. Epub 2021 Jan 30.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Background: The efficacy of renal denervation has been controversial, but the procedure has now undergone several placebo-controlled trials. New placebo-controlled trial data has recently emerged, with longer follow-up of one trial and the full report of another trial (which constitutes 27% of the total placebo-controlled trial data). We therefore sought to evaluate the effect of renal denervation on ambulatory and office blood pressures in patients with hypertension.

Methods: We systematically identified all blinded placebo-controlled randomized trials of catheter-based renal denervation for hypertension. The primary efficacy outcome was ambulatory systolic blood pressure change relative to placebo. A random-effects meta-analysis was performed.

Results: 6 studies randomizing 1232 patients were eligible. 713 patients were randomized to renal denervation and 519 to placebo. Renal denervation significantly reduced ambulatory systolic blood pressure (-3.52 mmHg; 95% CI -4.94 to -2.09; p < 0.0001), ambulatory diastolic blood pressure (-1.93 mmHg; 95% CI -3.04 to -0.83, p = 0.0006), office systolic blood pressure size (-5.10 mmHg; 95% CI -7.31 to -2.90, p < 0.0001) and office diastolic pressure (effect size -3.11 mmHg; 95% CI -4.43 to -1.78, p < 0.0001). Adverse events were rare and not more common with denervation.

Conclusions: The totality of blinded, randomized placebo-controlled data shows that renal denervation is safe and provides genuine reduction in blood pressure for at least 6 months post-procedure. If this effect continues in the long term, renal denervation might provide a life-long 10% relative risk reduction in major adverse cardiac events and 7.5% relative risk reduction in all-cause mortality.
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http://dx.doi.org/10.1016/j.carrev.2021.01.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813172PMC
January 2022

Hearing spiritually significant voices: A phenomenological survey and taxonomy.

Med Humanit 2020 Dec 7. Epub 2020 Dec 7.

Institute for Medical Humanities, Durham University, Durham, UK.

Whereas previous research in the medical humanities has tended to neglect theology and religious studies, these disciplines sometimes have a very important contribution to make. The hearing of spiritually significant voices provides a case in point. The context, content and identity of these voices, all of which have typically not been seen as important in the assessment of auditory-verbal hallucinations (AVHs) within psychiatry, are key to understanding their spiritual significance. A taxonomy of spiritually significant voices is proposed, which takes into account frequency, context, affect and identity of the voice. In a predominantly Christian sample of 58 people who reported having heard spiritually significant voices, most began in adult life and were infrequent experiences. Almost 90% reported that the voice was divine in identity and approximately one-third were heard in the context of prayer. The phenomenological characteristics of these voices were different from those in previous studies of voice hearing (AVHs). Most comprised a single voice; half were auditory; and a quarter were more thought-like (the rest being a mixture). Only half were characterful, and one-third included commands or prompts. The voices were experienced positively and as meaningful. The survey has implications for both clinical and pastoral work. The phenomenology of spiritually significant voices may be confused with that of psychopathology, thus potentially leading to misdiagnosis of normal religious experiences. The finding of meaning in content and context may be important in voice hearing more widely, and especially in coping with negative or distressing voices.
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http://dx.doi.org/10.1136/medhum-2020-012021DOI Listing
December 2020

Single-Cell Profiling Reveals Divergent, Globally Patterned Immune Responses in Murine Skin Inflammation.

iScience 2020 Oct 19;23(10):101582. Epub 2020 Sep 19.

Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.

Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45 subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates / expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces / expression in newly infiltrating basophils, and and most prominently in APCs. In contrast, imiquimod broadly upregulates / and /. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures.
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http://dx.doi.org/10.1016/j.isci.2020.101582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648132PMC
October 2020

The Opioid-overdose Reduction Continuum of Care Approach (ORCCA): Evidence-based practices in the HEALing Communities Study.

Drug Alcohol Depend 2020 12 4;217:108325. Epub 2020 Oct 4.

National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Boulevard, Rockville, MD 20892, USA.

Background: The number of opioid-involved overdose deaths in the United States remains a national crisis. The HEALing Communities Study (HCS) will test whether Communities That HEAL (CTH), a community-engaged intervention, can decrease opioid-involved deaths in intervention communities (n = 33), relative to wait-list communities (n = 34), from four states. The CTH intervention seeks to facilitate widespread implementation of three evidence-based practices (EBPs) with the potential to reduce opioid-involved overdose fatalities: overdose education and naloxone distribution (OEND), effective delivery of medication for opioid use disorder (MOUD), and safer opioid analgesic prescribing. A key challenge was delineating an EBP implementation approach useful for all HCS communities.

Methods: A workgroup composed of EBP experts from HCS research sites used literature reviews and expert consensus to: 1) compile strategies and associated resources for implementing EBPs primarily targeting individuals 18 and older; and 2) determine allowable community flexibility in EBP implementation. The workgroup developed the Opioid-overdose Reduction Continuum of Care Approach (ORCCA) to organize EBP strategies and resources to facilitate EBP implementation.

Conclusions: The ORCCA includes required and recommended EBP strategies, priority populations, and community settings. Each EBP has a "menu" of strategies from which communities can select and implement with a minimum of five strategies required: one for OEND, three for MOUD, and one for prescription opioid safety. Identification and engagement of high-risk populations in OEND and MOUD is an ORCCArequirement. To ensure CTH has community-wide impact, implementation of at least one EBP strategy is required in healthcare, behavioral health, and criminal justice settings, with communities identifying particular organizations to engage in HCS-facilitated EBP implementation.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533113PMC
December 2020

Evaluating the clinical dyad leadership model: a narrative review.

J Health Organ Manag 2020 Sep;ahead-of-print(ahead-of-print)

Department of Internal Medicine, Center for Health Services Research, University of Kentucky, Lexington, Kentucky, USA.

Purpose: Dyadic leadership models, in which two professionals jointly lead and share unit responsibilities, exemplifies a recent trend in health care. Nonetheless, much remains unknown about their benefits and drawbacks. In order to understand their potential impact, we conducted a review of literature evaluating dyad leadership models in health systems.

Design/methodology/approach: Our narrative review began with a search of PubMed, CINAHL, Web of Science and Scopus using key terms related to dyads and leadership. The search yielded 307 articles. We screened titles/abstracts according to these criteria: (1) focus on dyadic leadership model, i.e. physician-nurse or clinician-administrator, (2) set in health care environment and (3) peer-reviewed with an evaluative component of dyadic model. This yielded 22 articles for full evaluation, of which six were relevant for this review.

Findings: These six articles contribute an assessment of (1) teamwork and communication perceptions and their changes through dyad implementation, (2) dyad model functionality within the health system, (3) lessons learned from dyad model implementation and (4) dyad model adoption and model fidelity.

Research Limitations/implications: Research in this area remains nascent, and most articles focused on implementation over evaluation. It is possible that some articles were excluded due to our methodology, which excluded nonEnglish articles.

Practical Implications: Findings provide guidance for health care organizations seeking to implement dyadic leadership models. Rigorous studies are needed to establish the impact of dyadic leadership models on quality and patient outcomes.

Originality/value: This review consolidates evidence surrounding the implementation and evaluation of a leadership model gaining prominence in health care.
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http://dx.doi.org/10.1108/JHOM-06-2020-0212DOI Listing
September 2020

Riemannian geometry and statistical modeling correct for batch effects and control false discoveries in single-cell surface protein count data.

Phys Rev E 2020 Jul;102(1-1):012409

Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61820, USA.

Recent advances in next generation sequencing-based single-cell technologies have allowed high-throughput quantitative detection of cell-surface proteins along with the transcriptome in individual cells, extending our understanding of the heterogeneity of cell populations in diverse tissues that are in different diseased states or under different experimental conditions. Count data of surface proteins from the cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) technology pose new computational challenges, and there is currently a dearth of rigorous mathematical tools for analyzing the data. This work utilizes concepts and ideas from Riemannian geometry to remove batch effects between samples and develops a statistical framework for distinguishing positive signals from background noise. The strengths of these approaches are demonstrated on two independent CITE-seq data sets in mouse and human.
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http://dx.doi.org/10.1103/PhysRevE.102.012409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437020PMC
July 2020

Parental divorce in childhood is related to lower urinary oxytocin concentrations in adulthood.

J Comp Psychol 2021 02 13;135(1):74-81. Epub 2020 Aug 13.

Department of Psychiatry, University of North Carolina at Chapel Hill.

Oxytocin has been shown to be important for social behavior and emotional attachments in early life and may also mediate effects of early experiences on social motivation in adulthood. In animal models, early maternal separation results in alterations in the oxytocin system, with effects on sexual, maternal, and stress reactivity behaviors in adulthood. Studies of children experiencing parental divorce find effects on mood disorders, substance abuse, and other behaviors in adulthood. Here, we examine the effect of divorce on adult urine oxytocin levels. To stimulate oxytocin release, participants, aged 18 to 62, were asked to complete a set of questionnaires on attachment style, parental history of divorce (age at parental divorce ranged from 0 to 20), and other measures. A sample of urine was then collected for the oxytocin assay. Urine oxytocin concentrations were substantially lower (p = .016) in subjects who experienced parental divorce (M = 3.70, Standard Error of the Mean = 0.73), compared to those who did not (M = 8.00, Standard Error of the Mean = 1.21), and correlated with responses on several attachment instruments. These results suggest that oxytocin levels are adversely affected by parental divorce in humans and may be related to attachment measures in adulthood. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/com0000248DOI Listing
February 2021

Revascularization Deferral of Nonculprit Stenoses on the Basis of Fractional Flow Reserve: 1-Year Outcomes of 8,579 Patients.

JACC Cardiovasc Interv 2020 08 29;13(16):1894-1903. Epub 2020 Jul 29.

Hospital Clinico San Carlos IDISSC and Universidad Complutense de Madrid, Madrid, Spain. Electronic address:

Background: Intracoronary physiology is increasingly used in nonculprit stenoses of patients with acute coronary syndromes (ACS). However, evidence regarding the safety of fractional flow reserve-based deferral in patients with ACS, compared with patients with stable angina pectoris (SAP), is scarce.

Objectives: The aim of this study was to evaluate the safety of revascularization deferral on the basis of fractional flow reserve interrogation of nonculprit lesions in patients with ACS.

Methods: A pooled analysis was performed of individual patient data included in 5 large international published studies on physiology-guided revascularization. The primary endpoint was major adverse cardiac events (MACE) (a composite of death, nonfatal myocardial infarction, or unplanned revascularization) at 1-year follow-up. Clinical outcomes of patients with ACS and SAP were compared in both the deferred and the revascularized groups.

Results: A total of 8,579 patients were included in the analysis, 6,461 with SAP and 2,118 with ACS and nonculprit stenoses. Using fractional flow reserve, revascularization was deferred in 5,129 patients (59.8%) and performed in 3,450 patients (40.2%). In the deferred ACS group, a higher MACE rate was observed compared with the deferred SAP group (4.46% vs. 2.83%; adjusted hazard ratio [HR]: 1.72; 95% confidence interval [CI]: 1.17 to 2.53; p < 0.01). In particular, early unplanned revascularization (3.34% and 2.04% in ACS and SAP; adjusted HR: 1.81; 95% CI: 1.09 to 3.00; p = 0.02) contributed to this excess in MACE but the difference between the ACS and SAP groups did not reach statistical significance. On the contrary, no differences in outcomes linked to clinical presentation were found in treated patients (MACE rate 6.51% vs. 6.20%; adjusted HR: 1.21; 95% CI: 0.88 to 1.26; p = 0.24).

Conclusions: Patients with ACS in whom revascularization of nonculprit lesions was deferred on the basis of fractional flow reserve have more MACE at 1 year compared with patients with SAP with deferred revascularization. Unplanned revascularization mainly contributed to this excess of MACE.
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http://dx.doi.org/10.1016/j.jcin.2020.05.024DOI Listing
August 2020

What patient factors and Patient-Reported Outcomes Measurement Information System domains are associated with worse pain coping in pediatric orthopaedic patients in the United States?

J Pediatr Orthop B 2021 Sep;30(5):488-493

Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, New York, USA.

We sought to better understand the relationship between Patient-Reported Outcomes Measurement Information System (PROMIS) mobility, pain interference (PI) and depressive symptoms scores, as well as determine what patient factors and PROMIS domains were associated with worse pain coping (PROMIS PI), in a pediatric orthopaedic population. Between 27 August 2015 and 30 April 2019, new pediatric orthopaedic patients 18 years or younger (or their guardians as a proxy) were asked to complete PROMIS mobility, PI and depressive symptoms domains at an academic medical center pediatric orthopaedic clinic. Pearson correlation coefficients (r) were calculated between each PROMIS domain. Linear multivariate regression analysis was used to determine patient characteristics and PROMIS domains associated with presenting PROMIS PI scores. There was a strong-moderate correlation between PROMIS mobility and PI (r = -0.66, P < 0.001), while the correlation between PROMIS mobility and depressive symptoms was moderate-poor (r = -0.38, P < 0.001). There was a moderate correlation between PROMIS depressive symptoms and PI (r = 0.54, P < 0.001). In multivariate linear regression analysis, female gender (β = 0.82, P < 0.001), self-reported black race (β = 0.94, P < 0.001), Medicaid insurance (β = 0.82, P < 0.001) and worsening depressive symptoms (β = 0.33, P < 0.001) were associated with worse pain coping mechanisms, while increasing mobility (β = -0.47, P < 0.001) was associated with better pain coping mechanisms. Poor mobility and worse depressive symptoms are associated with worse pain coping mechanisms. Additionally, Medicaid insurance status, black race and female gender are also associated with worse physical limitations secondary to pain.
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http://dx.doi.org/10.1097/BPB.0000000000000791DOI Listing
September 2021

Complete Revascularization by Percutaneous Coronary Intervention for Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Coronary Artery Disease: An Updated Meta-Analysis of Randomized Trials.

J Am Heart Assoc 2020 06 1;9(12):e015263. Epub 2020 Jun 1.

Columbia University Medical Center/New York-Presbyterian Hospital New York NY.

Background For patients with ST-segment-elevation myocardial infarction (STEMI) and multivessel coronary artery disease, the optimal treatment of the non-infarct-related artery has been controversial. This up-to-date meta-analysis focusing on individual clinical end points was performed to further evaluate the benefit of complete revascularization with percutaneous coronary intervention for patients with STEMI and multivessel coronary artery disease. Methods and Results We systematically identified all randomized trials comparing complete revascularization with percutaneous coronary intervention to culprit-only revascularization for multivessel disease in STEMI and performed a random-effects meta-analysis. The primary efficacy end point was cardiovascular death analyzed on an intention-to-treat basis. Secondary end points included all-cause mortality, myocardial infarction, and unplanned revascularization. Ten studies (7542 patients) were included: 3664 patients were randomized to complete revascularization and 3878 to culprit-only revascularization. Across all patients, complete revascularization was superior to culprit-only revascularization for reduction in the risk of cardiovascular death (relative risk [RR], 0.68; 95% CI, 0.47-0.98; =0.037; I=21.8%) and reduction in the risk of myocardial infarction (RR, 0.65; 95% CI, 0.54-0.79; <0.0001; I=0.0%). Complete revascularization also significantly reduced the risk of unplanned revascularization (RR, 0.37; 95% CI, 0.28-0.51; <0.0001; I=64.7%). The difference in all-cause mortality with percutaneous coronary intervention was not statistically significant (RR, 0.85; 95% CI, 0.69-1.04; =0.108; I=0.0%). Conclusions For patients with STEMI and multivessel disease, complete revascularization with percutaneous coronary intervention significantly improves hard clinical outcomes including cardiovascular death and myocardial infarction. These data have implications for clinical practice guidelines regarding recommendations for complete revascularization following STEMI.
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http://dx.doi.org/10.1161/JAHA.119.015263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429036PMC
June 2020

Inter-observer differences in interpretation of coronary pressure-wire pullback data by non-expert interventional cardiologists.

Cardiovasc Interv Ther 2021 Jul 19;36(3):289-297. Epub 2020 May 19.

Hammersmith Hospital, Imperial College London, London, UK.

The physiological pattern of coronary artery disease as determined by pressure-wire (PW)-pullback is important for decision-making of revascularization and risk stratification of patients. However, it remains unclear whether inter-observer differences in interpreting PW-pullback data are subject to the expertise of physicians. This study sought to investigate the subjectivity of this assessment among non-experts. Expert interventional cardiologists classified 545 PW-pullback traces into physiologically focal or physiologically diffuse disease pattern. Defining expert-consensus as the reference standard, we evaluated ten non-expert doctors' classification performance. Observers were stratified equally by two ways: (i) years of experience as interventional cardiologists (middle-level vs. junior-level) and (ii) volume of institutions where they belonged to (high-volume center vs. low-volume center). When judged against the expert-consensus, the agreement of non-expert observers in assessing physiological pattern of disease (focal or diffuse) ranged from 69.1 to 85.0% (p for heterogeneity < 0.0001). There was no evidence for a moderating effect of years of experience; the pooled accuracy of middle-level doctors was 78.8% (95% confidential interval [CI] 72.8-84.7%) vs. 79.1% for junior-level doctors (95% CI 75.9-82.2%, p = 0.95 for difference). On the other hand, we observed a significant moderating effect of center volume. Accuracy across non-experts in high-volume centers was 82.7% (95% CI 80.3-85.1%) vs. 75.1% for low-volume centers (95% CI 71.9-78.3%, p = 0.0002 for difference). Interpretation of PW-pullback by non-expert interventional cardiologists was considerably subjective.
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http://dx.doi.org/10.1007/s12928-020-00673-3DOI Listing
July 2021

Safety of Revascularization Deferral of Left Main Stenosis Based on Instantaneous Wave-Free Ratio Evaluation.

JACC Cardiovasc Interv 2020 07 13;13(14):1655-1664. Epub 2020 May 13.

Cardiovascular Science, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom. Electronic address:

Objectives: The aim of this study was to assess the long-term clinical outcomes of patients with left main coronary artery (LM) stenosis in whom treatment strategy was based on the instantaneous wave-free ratio (iFR).

Background: The overall safety of iFR to guide revascularization decision making in patients with stable coronary artery disease has been established. However, no study has examined the safety of deferral of revascularization of LM disease on the basis of iFR.

Methods: This multicenter observational study included 314 patients in whom LM stenosis was deferred (n = 163 [51.9%]) or revascularized (n = 151 [48.1%]) according to the iFR cutoff ≤0.89. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were each individual component of the primary endpoint and also cardiac death.

Results: At a median follow-up period of 30 months, the primary endpoint occurred in 15 patients (9.2%) in the deferred group and 22 patients (14.6%) in the revascularized group (hazard ratio: 1.45; 95% confidence interval: 0.75 to 2.81; p = 0.26), indicating no evidence of a significant difference between the 2 groups. For the secondary endpoints, findings in the iFR-based deferral and revascularization groups were as follows: all-cause death, 3.7% versus 4.6%; cardiac death, 1.2% versus 2.0%; nonfatal myocardial infarction, 2.5% versus 5.3%; and target lesion revascularization, 4.3% versus 5.3% (p > 0.05 for all).

Conclusions: Deferral of revascularization of LM stenosis on the basis of iFR appears to be safe, with similar long-term outcomes to those in patients in whom LM revascularization was performed according to iFR values.
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http://dx.doi.org/10.1016/j.jcin.2020.02.035DOI Listing
July 2020

Difference in functional assessment of individual stenosis severity in serial coronary lesions between resting and hyperemic pressure-wire pullback: Insights from the GIFT registry.

Int J Cardiol 2020 08 3;312:10-15. Epub 2020 May 3.

Cardiovascular Science, Imperial College London, Hammersmith Hospital, London, United Kingdom.

Background: Identifying the individual hemodynamic significance of tandem coronary artery lesions can be complicated by the crosstalk phenomenon which occurs between serial stenoses under hyperemic conditions. Physiological assessments performed under resting conditions are considered to be, theoretically, less affected by the hemodynamic interaction between serial coronary stenoses. The purpose of this study was to assess whether pressure-wire (PW) pullback measurements at rest and during hyperemia provided different information as to which stenosis appeared to be most functionally significant.

Methods: In consecutive patients with angiographically discrete serial lesions, physiological lesion predominance (i.e. proximal or distal) was defined according to the pressure gradient along the vessels on PW-pullback trace. We used instantaneous wave-free ratio (iFR) based assessment as the reference standard and compared fractional flow reserve (FFR) based and hyperemic-iFR based lesion predominance.

Results: Eighty-eight vessels (70 patients, mean age 70.3 ± 9.4 years, 80% male) were included in this study. Median iFR, FFR and hyperemic-iFR were 0.85 (interquartile range [IQR]: 0.74 to 0.91), 0.73 (IQR: 0.65 to 0.80) and 0.60 (IQR: 0.49 to 0.71), respectively. When judged against iFR-pullback based physiological assessment, lesion predominance changed in 22.7% (20/88) in FFR and in 20.5% (18/88) in hyperemic-iFR, respectively. There was no statistical difference between FFR and hyperemic-iFR for the impact on these changes (p = 0.77).

Conclusions: In serial coronary lesions, hyperemic PW-pullback disagreed with resting PW-pullback on the lesion-specific identification of ischemia in approximately 20% of cases, either in whole cardiac cycle or in wave-free period.
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http://dx.doi.org/10.1016/j.ijcard.2020.05.001DOI Listing
August 2020

Per-Vessel Level Analysis of Fractional Flow Reserve and Instantaneous Wave-Free Ratio Discordance - Insights From the AJIP Registry.

Circ J 2020 05 22;84(6):1034-1038. Epub 2020 Apr 22.

Cardiovascular Science, Imperial College London.

Background: The per-vessel level impact of physiological pattern of disease on the discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) has not been clarified.Methods and Results:Using the AJIP registry, vessels with FFR/iFR discordance (133/671 [19.8%]) were analyzed. In the left anterior descending artery (LAD), physiologically diffuse disease, as assessed by pressure-wire pullback, was associated with FFR-/iFR+ (83.3% [40/48]), while physiologically focal disease was associated with FFR+/iFR- (57.4% [31/54]), significantly (P<0.0001). These differences were not significant in non-LAD (P=0.17).

Conclusions: The impact of physiological pattern of disease on FFR/iFR discordance is more pronounced in the LAD.
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http://dx.doi.org/10.1253/circj.CJ-19-0785DOI Listing
May 2020
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