Metabolic characteristics of human hearts preserved for 12 hours by static storage, antegrade perfusion, or retrograde coronary sinus perfusion

ObjectiveMachine perfusion of donor hearts is a promising strategy to increase the donor pool. Antegrade perfusion is effective but can lead to aortic valve incompetence and nonnutrient flow. Experience with retrograde coronary sinus perfusion of donor hearts has been limited. We tested the hypothesis that retrograde perfusion could support myocardial metabolism over an extended donor ischemic interval.MethodsHuman hearts from donors that were rejected or not offered for transplantation were preserved for 12 hours in University of Wisconsin Machine Perfusion Solution by: (1) static hypothermic storage; (2) hypothermic antegrade machine perfusion; or (3) hypothermic retrograde machine perfusion. Myocardial oxygen consumption (MVO2), and lactate accumulation were measured. Ventricular tissue was collected for proton and phosphorus 31 magnetic resonance spectroscopy (MRS) to evaluate the metabolic state of the myocardium. Myocardial water content was determined at the end of the experiment.ResultsStable perfusion parameters were maintained throughout the perfusion period with both perfusion techniques. Lactate/alanine ratios were lower in perfused hearts compared with static hearts (P < .001). Lactate accumulation (antegrade 2.0 ± 0.7 mM, retrograde 1.7 ± 0.1 mM) and MVO2 (antegrade 0.25 ± 0.2 mL, retrograde 0.26 ± 0.3 mL O2/min/100 g) were similar in machine-perfused groups. High-energy phosphates were better preserved in both perfused groups (P < .05). Left ventricular myocardial water content was increased in retrograde perfused hearts (80.2 ± 0.8%) compared with both antegrade perfused hearts (76.6 ± 0.8%, P = .02) and static storage hearts (76.7 ± 1%, P = .02).ConclusionsMachine perfusion by either the antegrade or the retrograde technique can support myocardial metabolism over long intervals. Machine perfusion seems promising for long-term preservation of human donor hearts

Assessment of aortic regurgitation by transesophageal color Doppler imaging of the vena contracta: validation against an intraoperative aortic flow probe

AbstractOBJECTIVESThis study was performed to validate the accuracy of color flow vena contracta (VC) measurements of aortic regurgitation (AR) severity by comparing them to simultaneous intraoperative flow probe measurements of regurgitant fraction (RgF) and regurgitant volume (RgV).BACKGROUNDColor Doppler imaging of the vena contracta has emerged as a simple and reliable measure of the severity of valvular regurgitation. This study evaluated the accuracy of VC imaging of AR by transesophageal echocardiography (TEE).METHODSA transit-time flow probe was placed on the ascending aorta during cardiac surgery in 24 patients with AR. The flow probe was used to measure RgF and RgV simultaneously during VC imaging by TEE. Flow probe and VC imaging were interpreted separately and in blinded fashion.RESULTSA good correlation was found between VC width and RgF (r = 0.85) and RgV (r = 0.79). All six patients with VC width >6 mm had a RgF >0.50. All 18 patients with VC width <5 mm had a RgF <0.50. Vena contracta area also correlated well with both RgF (r = 0.81) and RgV (r = 0.84). All six patients with VC area >7.5 mm2had a RgF >0.50, and all 18 patients with a VC area <7.5 mm2had a RgF <0.50. In a subset of nine patients who underwent afterload manipulation to increase diastolic blood pressure, RgV increased significantly (34 ± 26 ml to 41 ± 27 ml, p = 0.042) while VC width remained unchanged (5.4 ± 2.8 mm to 5.4 ± 2.8 mm, p = 0.41).CONCLUSIONSVena contracta imaging by TEE color flow mapping is an accurate marker of AR severity. Vena contracta width and VC area correlate well with RgF and RgV obtained by intraoperative flow probe. Vena contracta width appears to be less afterload-dependent than RgV

Packed Red Blood Cell Transfusion Associates with Acute Kidney Injury After Transcatheter Aortic Valve Replacement

Background: Acute kidney injury after cardiac surgery significantly associates with morbidity and mortality. Despite not requiring cardiopulmonary bypass, transcatheter aortic valve replacement patients have an incidence of post-procedural acute kidney injury similar to patients who undergo open surgical aortic valve replacement. Packed red blood cell transfusion has been associated with morbidity and mortality after cardiac surgery. We hypothesized that packed red blood cell transfusion independently associates with acute kidney injury after transcatheter aortic valve replacement, after accounting for other risk factors. Methods: This is a single-center retrospective cohort study of 116 patients undergoing transcatheter aortic valve replacement. Post-transcatheter aortic valve replacement acute kidney injury was defined by Kidney Disease: Improving Global Outcomes serum creatinine-based criteria. Univariate comparisons between patients with and without post-transcatheter aortic valve replacement acute kidney injury were made for clinical characteristics. Multivariable logistic regression was used to assess independent association of packed red blood cell transfusion with post-transcatheter aortic valve replacement acute kidney injury (adjusting for pre-procedural renal function and other important clinical parameters). Results: Acute kidney injury occurred in 20 (17.2%) subjects. Total number of packed red blood cells transfused independently associated with post-procedure acute kidney injury (OR = 1.67 per unit, 95% CI 1.13–2.47, P = 0.01) after adjusting for pre-procedure estimated glomerular filtration rate (OR = 0.97 per ml/min/1.73m2, 95% CI 0.94–1.00, P = 0.05), nadir hemoglobin (OR = 0.88 per g/dL increase, CI 0.61–1.27, P = 0.50), and post-procedure maximum number of concurrent inotropes and vasopressors (OR = 2.09 per inotrope or vasopressor, 95% CI 1.19–3.67, P = 0.01). Conclusion: Packed red blood cell transfusion, along with post-procedure use of inotropes and vasopressors, independently associate with acute kidney injury after transcatheter aortic valve replacement. Further studies are needed to elucidate the pathobiology underlying these associations

Graphene/α\alpha-RuCl3_3: An Emergent 2D Plasmonic Interface

Work function-mediated charge transfer in graphene/$\alpha$-RuCl$_3$ heterostructures has been proposed as a strategy for generating highly-doped 2D interfaces. In this geometry, graphene should become sufficiently doped to host surface and edge plasmon-polaritons (SPPs and EPPs, respectively). Characterization of the SPP and EPP behavior as a function of frequency and temperature can be used to simultaneously probe the magnitude of interlayer charge transfer while extracting the optical response of the interfacial doped $\alpha$-RuCl$_3$. We accomplish this using scanning near-field optical microscopy (SNOM) in conjunction with first-principles DFT calculations. This reveals massive interlayer charge transfer (2.7 $\times$ 10$^{13}$ cm$^{-2}$) and enhanced optical conductivity in $\alpha$-RuCl$_3$ as a result of significant electron doping. Our results provide a general strategy for generating highly-doped plasmonic interfaces in the 2D limit in a scanning probe-accessible geometry without need of an electrostatic gate.Comment: 22 pages, 5 figure

Salivary Gland Hypofunction and/or Xerostomia Induced by Nonsurgical Cancer Therapies:ISOO/MASCC/ASCO Guideline

PURPOSE: To provide evidence-based recommendations for prevention and management of salivary gland hypofunction and xerostomia induced by nonsurgical cancer therapies. METHODS: Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials published between January 2009 and June 2020. The guideline also incorporated two previous systematic reviews conducted by MASCC/ISOO, which included studies published from 1990 through 2008. RESULTS: A total of 58 publications were identified: 46 addressed preventive interventions and 12 addressed therapeutic interventions. A majority of the evidence focused on the setting of radiation therapy for head and neck cancer. For the prevention of salivary gland hypofunction and/or xerostomia in patients with head and neck cancer, there is high-quality evidence for tissue-sparing radiation modalities. Evidence is weaker or insufficient for other interventions. For the management of salivary gland hypofunction and/or xerostomia, intermediate-quality evidence supports the use of topical mucosal lubricants, saliva substitutes, and agents that stimulate the salivary reflex. RECOMMENDATIONS: For patients who receive radiation therapy for head and neck cancer, tissue-sparing radiation modalities should be used when possible to reduce the risk of salivary gland hypofunction and xerostomia. Other risk-reducing interventions that may be offered during radiation therapy for head and neck cancer include bethanechol and acupuncture. For patients who develop salivary gland hypofunction and/or xerostomia, interventions include topical mucosal lubricants, saliva substitutes, and sugar-free lozenges or chewing gum. For patients with head and neck cancer, oral pilocarpine and oral cevimeline, acupuncture, or transcutaneous electrostimulation may be offered after radiation therapy.Additional information can be found at www.asco.org/supportive-care-guidelines

The characterisation of subjective cognitive decline

A growing awareness about brain health and Alzheimer's disease in the general population is leading to an increasing number of cognitively unimpaired individuals, who are concerned that they have reduced cognitive function, to approach the medical system for help. The term subjective cognitive decline (SCD) was conceived in 2014 to describe this condition. Epidemiological data provide evidence that the risk for mild cognitive impairment and dementia is increased in individuals with SCD. However, the majority of individuals with SCD will not show progressive cognitive decline. An individually tailored diagnostic process might be reasonable to identify or exclude underlying medical conditions in an individual with SCD who actively seeks medical help. An increasing number of studies are investigating the link between SCD and the very early stages of Alzheimer's disease and other neurodegenerative diseases

Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples

Introduction: Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer's disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD). Methods: We included three memory clinic SCD samples with available cerebrospinal fluid (CSF) biomaterial (IDIBAPS, Barcelona, Spain, n = 44; Amsterdam Dementia Cohort (ADC), The Netherlands, n = 50; DELCODE multicenter study, Germany, n = 42). CSF biomarkers (amyloid beta (Aβ)42, tau, and phosphorylated tau (ptau181)) were centrally analyzed in Amsterdam using prespecified cutoffs to define prevalence of pathological biomarker concentrations. We used logistic regression analysis in the combined sample across the three centers to investigate center effects with regard to likelihood of biomarker abnormality while taking potential common predictors (e.g., age, sex, apolipoprotein E (APOE) status, subtle cognitive deficits, depressive symptoms) into account. Results: The prevalence of abnormal Aβ42, but not tau or ptau181, levels was different across centers (64% DELCODE, 57% IDIBAPS, 22% ADC; p < 0.001). Logistic regression analysis revealed that the likelihood of abnormal Aβ42 (and also abnormal tau or ptau181) levels was predicted by age and APOE status. For Aβ42 abnormality, we additionally observed a center effect, indicating between-center heterogeneity not explained by age, APOE, or the other included covariates. Conclusions: While heterogeneous frequency of abnormal Aβ42 was partly explained by between-sample differences in age range and APOE status, the additional observation of center effects indicates between-center heterogeneity that may be attributed to different recruitment procedures. These findings highlight the need for the development of harmonized recruitment protocols for SCD case definition in multinational studies to achieve similar enrichment rates of preclinical AD

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis