Novel MAGIC composite scores using both clinical symptoms and biomarkers best predict treatment outcomes of acute GVHD.

Acute graft-vs-host disease (GVHD) grading systems that use only clinical symptoms at treatment initiation such as Minnesota risk identify standard and high risk categories but lack a low risk category suitable to minimize immunosuppressive strategies. We developed a new grading system that includes a low risk stratum based on clinical symptoms alone and determined whether the incorporation of biomarkers would improve the model's prognostic accuracy. We randomly divided 1863 patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) who were treated for GVHD into training and validation cohorts. Patients in the training cohort were divided into 14 groups based on similarity of clinical symptoms and similar NRM; we used a classification and regression tree (CART) algorithm to create three Manhattan risk groups that produced a significantly higher area under the receiver operating characteristic curve (AUC) for 6-month NRM than the Minnesota risk classification (0.69 vs. 0.64, P=0.009) in the validation cohort. We integrated serum GVHD biomarker scores with Manhattan risk using patients with available serum samples and again used a CART algorithm to establish three MAGIC composite scores that significantly improved prediction of NRM compared to Manhattan risk (AUC, 0.76 vs. 0.70, P=0.010). Each increase in MAGIC composite score also corresponded to a significant decrease in day 28 treatment response (80% vs. 63% vs. 30%, P<0.001). We conclude that the MAGIC composite score more accurately predicts response to therapy and long term outcomes than systems based on clinical symptoms alone and may help guide clinical decisions and trial design.

A measurement of the equation of state of carbon envelopes of white dwarfs.

White dwarfs represent the final state of evolution for most stars1-3. Certain classes of white dwarfs pulsate4,5, leading to observable brightness variations, and analysis of these variations with theoretical stellar models probes their internal structure. Modelling of these pulsating stars provides stringent tests of white dwarf models and a detailed picture of the outcome of the late stages of stellar evolution6. However, the high-energy-density states that exist in white dwarfs are extremely difficult to reach and to measure in the laboratory, so theoretical predictions are largely untested at these conditions. Here we report measurements of the relationship between pressure and density along the principal shock Hugoniot (equations describing the state of the sample material before and after the passage of the shock derived from conservation laws) of hydrocarbon to within five per cent. The observed maximum compressibility is consistent with theoretical models that include detailed electronic structure. This is relevant for the equation of state of matter at pressures ranging from 100 million to 450 million atmospheres, where the understanding of white dwarf physics is sensitive to the equation of state and where models differ considerably. The measurements test these equation-of-state relations that are used in the modelling of white dwarfs and inertial confinement fusion experiments7,8, and we predict an increase in compressibility due to ionization of the inner-core orbitals of carbon. We also find that a detailed treatment of the electronic structure and the electron degeneracy pressure is required to capture the measured shape of the pressure-density evolution for hydrocarbon before peak compression. Our results illuminate the equation of state of the white dwarf envelope (the region surrounding the stellar core that contains partially ionized and partially degenerate non-ideal plasmas), which is a weak link in the constitutive physics informing the structure and evolution of white dwarf stars9.

Measurements of Arterial Occlusion Pressure Using Hand-Held Devices.

ABSTRACT: Vehrs, PR, Reynolds, S, Allen, J, Barrett, R, Blazzard, C, Burbank, T, Hart, H, Kasper, N, Lacey, R, Lopez, D, and Fellingham, GW. Measurements of arterial occlusion pressure using hand-held devices. J Strength Cond Res 38(5): 873-880, 2024-Arterial occlusion pressure (AOP) of the brachial artery was measured simultaneously using Doppler ultrasound (US), a hand-held Doppler (HHDOP), and a pulse oximeter (PO) in the dominant (DOM) and nondominant (NDOM) arms of males ( n = 21) and females ( n = 23) using continuous (CONT) and incremental (INCR) cuff inflation protocols. A mixed-model analysis of variance revealed significant ( p < 0.05) overall main effects between AOP measured using a CONT (115.7 ± 10.9) or INCR (115.0 ± 11.5) cuff inflation protocol; between AOP measured using US (116.3 ± 11.2), HHDOP (115.4 ± 11.2), and PO (114.4 ± 11.2); and between males (120.7 ± 10.6) and females (110.5 ± 9.4). The small overall difference (1.81 ± 3.3) between US and PO measures of AOP was significant ( p < 0.05), but the differences between US and HHDOP and between HHDOP and PO measures of AOP were not significant. There were no overall differences in AOP between the DOM and NDOM arms. Trial-to-trial variance in US measurements of AOP was not significant when using either cuff inflation protocol but was significant when using HHDOP and PO and a CONT cuff inflation protocol. Bland-Altman plots revealed reasonable limits of agreement for both HHDOP and PO measures of AOP. The small differences in US, HHDOP, and PO measurements of AOP when using CONT or INCR cuff inflation protocols are of minimal practical importance. The choice of cuff inflation protocol is one of personal preference. Hand-held Doppler of PO can be used to assess AOP before using blood flow restriction during exercise.

Evidence for Dissociation and Ionization in Shock Compressed Nitrogen to 800 GPa.

Triple bonding in the nitrogen molecule (N_{2}) is among the strongest chemical bonds with a dissociation enthalpy of 9.8 eV/molecule. Nitrogen is therefore an excellent test bed for theoretical and numerical methods aimed at understanding how bonding evolves under the influence of the extreme pressures and temperatures of the warm dense matter regime. Here, we report laser-driven shock experiments on fluid molecular nitrogen up to 800 GPa and 4.0 g/cm^{3}. Line-imaging velocimetry measurements and impedance matching method with a quartz reference yield shock equation of state data of initially precompressed nitrogen. Comparison with numerical simulations using path integral Monte Carlo and density functional theory molecular dynamics reveals clear signatures of chemical dissociation and the onset of L-shell ionization. Combining data along multiple shock Hugoniot curves starting from densities between 0.76 and 1.29 g/cm^{3}, our study documents how pressure and density affect these changes in chemical bonding and provides benchmarks for future theoretical developments in this regime, with applications for planetary interior modeling, high energy density science, and inertial confinement fusion research.

Respiration-related variations in Pd/Pa ratio and fractional flow reserve in resting conditions and during intravenous adenosine administration.

AIMS: We evaluated the occurrence and physiology of respiration-related beat-to-beat variations in resting Pd/Pa and FFR during intravenous adenosine administration, and its impact on clinical decision-making. METHODS AND RESULTS: Coronary pressure tracings in rest and at plateau hyperemia were analyzed in a total of 39 stenosis from 37 patients, and respiratory rate was calculated with ECG-derived respiration (EDR) in 26 stenoses from 26 patients. Beat-to-beat variations in FFR occurred in a cyclical fashion and were strongly correlated with respiratory rate (R2  = 0.757, p < 0.001). There was no correlation between respiratory rate and variations in resting Pd/Pa. When single-beat averages were used to calculate FFR, mean ΔFFR was 0.04 ± 0.02. With averaging of FFR over three or five cardiac cycles, mean ΔFFR decreased to 0.02 ± 0.02, and 0.01 ± 0.01, respectively. Using a FFR ≤ 0.80 threshold, stenosis classification changed in 20.5% (8/39), 12.8% (5/39) and 5.1% (2/39) for single-beat, three-beat and five-beat averaged FFR. The impact of respiration was more pronounced in patients with pulmonary disease (ΔFFR 0.05 ± 0.02 vs 0.03 ± 0.02, p = 0.021). CONCLUSION: Beat-to-beat variations in FFR during plateau hyperemia related to respiration are common, of clinically relevant magnitude, and frequently lead FFR to cross treatment thresholds. A five-beat averaged FFR, overcomes clinically relevant impact of FFR variation.

Collagenofibrotic glomerulopathy in a kidney transplant recipient: A first report.

Collagenofibrotic glomerulopathy (CG) is a rare disease characterized by the deposition of collagen type 3 fibrils in the glomeruli. Patients may have proteinuria, hematuria, and/or renal dysfunction. CG is considered a progressive disease with variable rates of progression. The definitive diagnosis is made by electron microscopy with the presence of characteristic subendothelial and mesangial curved, comma-like, banded collagen type 3 fibers of 40-65 nm periodicity. We are reporting the first case of CG in a kidney transplant recipient with kidney disease of unknown cause.

Urine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis.

BACKGROUND: We previously demonstrated that urine interleukin (IL)-9 and tumor necrosis factor (TNF)-α can distinguish acute interstitial nephritis (AIN) from other causes of acute kidney injury. Here we evaluated the role of these biomarkers to prognosticate kidney function in patients with AIN. METHODS: In a cohort of participants with biopsy-proven, adjudicated AIN, we tested the association of histological features and urine biomarkers (IL-9 and TNF-α) with estimated glomerular filtration rate measured 6 months after diagnosis (6 m-eGFR) controlling for eGFR before AIN and albuminuria. We also evaluated subgroups in whom corticosteroid use was associated with 6 m-eGFR. RESULTS: In the 51 (93%) of the 55 participants with complete data, median (interquartile range) eGFR before and 6 m after AIN were 41 (27-69) and 28 (13-47) mL/min/1.73 m2, respectively. Patients with higher severity of interstitial fibrosis had lower 6 m-eGFR, whereas those with higher tubulointerstitial infiltrate had higher 6 m-eGFR. IL-9 levels were associated with lower 6 m-eGFR only in the subset of patients who did not receive corticosteroids [6m-eGFR per doubling of IL-9, -6.0 (-9.4 to -2.6) mL/min/1.73 m2]. Corticosteroid use was associated with higher 6 m-eGFR [20.9 (0.2, 41.6) mL/min/1.73 m2] only in those with urine IL-9 above the median (>0.66 ng/g) but not in others. CONCLUSIONS: Urine IL-9 was associated with lower 6 m-eGFR only in participants not treated with corticosteroids. Corticosteroid use was associated with higher 6 m-eGFR in those with high urine IL-9. These findings provide a framework for IL-9-guided clinical trials to test efficacy of immunosuppressive therapy in patients with AIN.

Transient Reductions in Postoperative Pain and Anxiety with the Use of Virtual Reality in Children.

OBJECTIVE: Virtual reality is a promising method to manage pain. Distraction-based virtual reality (VR-D) is thought to reduce pain by redirecting attention. Although VR-D can reduce pain associated with acutely painful procedures, it is unclear whether VR-D can reduce pain after surgery. We assessed the ability of a single VR-D session to decrease postoperative pain and anxiety and explored whether pain catastrophizing and anxiety sensitivity influenced these outcomes in children after surgery. DESIGN: Single-center, prospective, pilot study. SETTING: Cincinnati Children's Hospital Medical Center (CCHMC). SUBJECTS: Fifty children (7-21 years of age) with postoperative pain followed by the Acute Pain Service. METHODS: Patients received one VR-D session after surgery. Before the session, patients completed pain catastrophizing (Pain Catastrophizing Scale for Children) and anxiety sensitivity (Child Anxiety Sensitivity Index) questionnaires. The primary outcome consisted of changes in pain intensity after VR-D (immediately, 15 minutes, and 30 minutes). Secondary outcomes included changes in pain unpleasantness and anxiety. RESULTS: VR-D use was associated with a decrease in pain intensity immediately and 15 minutes after VR-D. Reductions in pain unpleasantness were observed up to 30 minutes after VR-D. VR-D was also associated with a reduction in anxiety immediately and at 15 minutes. Although patients with higher pain catastrophizing had higher baseline pain intensity and unpleasantness, they did not show larger pain reductions after VR-D than those with lower pain catastrophizing. CONCLUSIONS: VR-D may be beneficial in transiently reducing pain intensity, unpleasantness, and anxiety in children with postoperative pain. This study informs the design of a larger, randomized, controlled study assessing VR-D for acute postoperative pain and anxiety management.

Guided Relaxation-Based Virtual Reality for Acute Postoperative Pain and Anxiety in a Pediatric Population: Pilot Observational Study.

BACKGROUND: Distraction-based therapies, such as virtual reality (VR), have been used to reduce pain during acutely painful procedures. However, distraction alone cannot produce prolonged pain reduction to manage sustained postoperative pain. Therefore, the integration of VR with other pain-reducing therapies, like guided relaxation, may enhance its clinical impact. OBJECTIVE: The goal of this pilot study was to assess the impact of a single guided relaxation-based VR (VR-GR) session on postoperative pain and anxiety reduction in children. We also explored the influence of pain catastrophizing and anxiety sensitivity on this association. METHODS: A total of 51 children and adolescents (7-21 years) with postoperative pain and followed by the Acute Pain Service at Cincinnati Children's Hospital were recruited over an 8-month period to undergo a single VR-GR session. Prior to VR, the patients completed 2 questionnaires: Pain Catastrophizing Scale for Children (PCS-C) and the Child Anxiety Sensitivity Index (CASI). The primary outcome was a change in pain intensity following the VR-GR session (immediately, 15 minutes, and 30 minutes). The secondary outcomes included changes in pain unpleasantness and anxiety. RESULTS: The VR-GR decreased pain intensity immediately (P<.001) and at 30 minutes (P=.04) after the VR session, but not at 15 minutes (P=.16) postsession. Reductions in pain unpleasantness were observed at all time intervals (P<.001 at all intervals). Anxiety was reduced immediately (P=.02) but not at 15 minutes (P=.08) or 30 minutes (P=.30) following VR-GR. Patients with higher CASI scores reported greater reductions in pain intensity (P=.04) and unpleasantness (P=.01) following VR-GR. Pain catastrophizing was not associated with changes in pain and anxiety. CONCLUSIONS: A single, short VR-GR session showed transient reductions in pain intensity, pain unpleasantness, and anxiety in children and adolescents with acute postoperative pain. The results call for a future randomized controlled trial to assess the efficacy of VR-GR. TRIAL REGISTRATION: ClinicalTrials.gov NCT04556747; https://clinicaltrials.gov/ct2/show/NCT04556747.

Estimation of Intraglomerular Pressure Using Invasive Renal Arterial Pressure and Flow Velocity Measurements in Humans.

BACKGROUND: Glomerular hyperfiltration resulting from an elevated intraglomerular pressure (Pglom) is an important cause of CKD, but there is no feasible method to directly assess Pglom in humans. We developed a model to estimate Pglom in patients from combined renal arterial pressure and flow measurements. METHODS: We performed hemodynamic measurements in 34 patients undergoing renal or cardiac angiography under baseline conditions and during hyperemia induced by intrarenal dopamine infusion (30 µg/kg). For each participant during baseline and hyperemia, we fitted an adapted three-element Windkessel model that consisted of characteristic impedance, compliance, afferent resistance, and Pglom. RESULTS: We successfully analyzed data from 28 (82%) patients. Median age was 58 years (IQR, 52-65), median eGFR was 95 ml/min per 1.73 m2 (IQR, 74-100) using the CKD-EPI formula, 30% had microalbuminuria, and 32% had diabetes. The model showed a mean Pglom of 48.0 mm Hg (SD=10.1) at baseline. Under hyperemia, flow increased by 88% (95% CI, 68% to 111%). This resulted in a 165% (95% CI, 79% to 294%) increase in afferent compliance and a 13.1-mm Hg (95% CI, 10.0 to 16.3) decrease in Pglom. In multiple linear regression analysis, diabetes (coefficient, 10.1; 95% CI, 5.1 to 15.1), BMI (0.99 per kg/m2; 95% CI, 0.38 to 1.59), and renal perfusion pressure (0.42 per mm Hg; 95% CI, 0.25 to 0.59) were significantly positively associated with baseline Pglom. CONCLUSIONS: We constructed a model on the basis of proximal renal arterial pressure and flow velocity measurements that provides an overall estimate of glomerular pressure and afferent and efferent resistance in humans. The model provides a novel research technique to evaluate the hemodynamics of CKD on the basis of direct pressure and flow measurements. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Functional HEmodynamics in patients with and without Renal Artery stenosis (HERA), NL40795.018.12 at the Dutch national trial registry (toetsingonline.nl).

Global Burden of Animal Diseases: a novel approach to understanding and managing disease in livestock and aquaculture.

Investments in animal health and Veterinary Services can have a measurable impact on the health of people and the environment. These investments require a baseline metric that describes the burden of animal health and welfare in order to justify and prioritise resource allocation and from which to measure the impact of interventions. This paper is part of a process of scientific enquiry in which problems are identified and solutions sought in an inclusive way. It poses the broad question: what should a system to measure the animal disease burden on society look like and what value would it add? Moreover, it aims to do this in such a way as to be accessible by a wide audience, who are encouraged to engage in this debate. Given that farmed animals, including those raised by poor smallholders, are an economic entity, this system should be based on economic principles. These poor farmers are negatively impacted by disparities in animal health technology, which can be addressed through a mixture of supply-led and demand-driven interventions, reinforcing the relevance of targeted financial support from government and non-governmental organisations. The Global Burden of Animal Diseases (GBADs) Programme will glean existing data to measure animal health losses within carefully characterised production systems. Consistent and transparent attribution of animal health losses will enable meaningful comparisons of the animal disease burden to be made between diseases, production systems and countries, and will show how it is apportioned by people's socio-economic status and gender. The GBADs Programme will produce a cloud-based knowledge engine and data portal, through which users will access burden metrics and associated visualisations, support for decisionmaking in the form of future animal health scenarios, and the outputs of wider economic modelling. The vision of GBADs, strengthening the food system for the benefit of society and the environment, is an example of One Health thinking in action.

Les investissements réalisés en santé animale et dans les Services vétérinaires ont un impact mesurable sur la santé des personnes et de l'environnement. Le système de mesure appliqué à ces investissements doit reposer sur un référentiel de base décrivant l'impact de la santé et du bien-être animal de manière à justifier et classer par priorités les ressources allouées et à mesurer les effets des interventions. Les auteurs présentent une étude conduite dans le cadre d'une enquête scientifique destinée à identifier les problèmes et à rechercher des solutions de manière inclusive. L'étude pose la question de savoir à quoi devrait ressembler un système conçu pour mesurer l'impact sur la société des maladies animales, et quelle serait sa valeur ajoutée. En outre, l'étude est conduite de manière à être accessible à une large audience afin d'encourager cette dernière à participer aux discussions. Étant donné que les animaux d'élevage constituent une entité économique, y compris les animaux appartenant à des éleveurs pauvres, le système de mesure doit reposer sur des principes économiques. Les exploitants pratiquant une agriculture de subsistance subissent les effets négatifs des disparités entre les différentes technologies applicables à la santé animale, disparités auxquelles il est possible de remédier par le biais d'interventions associant des mesures dictées par l'offre et par la demande et en renforçant l'efficacité du soutien financier ciblé apporté par les organisations gouvernementales et non gouvernementales. Le Programme « L'impact mondial des maladies animales ¼ (GBADs) aura pour tâche de glaner les données existantes afin de mesurer les pertes associées à la santé animale au sein de systèmes de production qui auront été soigneusement caractérisés au préalable. Grâce à l'élucidation cohérente et transparente des pertes imputables à chaque problème de santé animale, des comparaisons pertinentes pourront être effectuées concernant l'impact des maladies animales par maladies, par systèmes de production et par pays, et la répartition de cet impact dans les populations concernées suivant le statut socio-économique et le genre des intéressés sera mieux comprise. Le Programme GBADs entend créer un moteur de recherche et un portail de données qui seront disponibles sur le Cloud et donneront aux utilisateurs l'accès à des outils de mesure de l'impact des maladies et à d'autres informations présentées sous forme graphique, ainsi qu'à des outils d'aide à la décision sous forme de scénarios prospectifs sur la santé animale et aux résultats d'études plus larges de modélisation économique. La vision du GBADs, renforcer le système de production de denrées alimentaires au profit de la société et de l'environnement, est un exemple de mise en oeuvre du concept Une seule santé.

Las inversiones en sanidad animal y en los Servicios Veterinarios pueden tener un efecto mensurable en la salud de las personas y el medio ambiente. Para efectuar estas inversiones se precisan parámetros que describan y cuantifiquen la situación de partida y el impacto de los problemas de sanidad y bienestar animales, a fin de poder, a partir de ahí, justificar y jerarquizar la asignación de recursos y medir los efectos de las intervenciones. Este artículo, inscrito en un proceso de indagación científica encaminado a detectar problemas y buscar soluciones de forma incluyente, plantea la cuestión general de cómo debería ser y qué valor añadido aportaría un sistema destinado a medir el impacto que imponen a la sociedad las enfermedades animales. Los autores, además, tratan de exponer la cuestión de manera que sea accesible a un público amplio, al que se alienta a participar en este debate. Dado que los animales de granja (incluidos los de pequeñas explotaciones) constituyen una entidad económica, tal sistema debería estar basado en principios económicos. Los productores que trabajan en régimen de subsistencia se ven negativamente afectados por las disparidades existentes en materia de tecnología zoosanitaria, disparidad que cabe corregir con una combinación de intervenciones marcadas por la oferta y otras marcadas por la demanda, dirigiendo así más selectivamente el apoyo económico de entidades gubernamentales y organizaciones no gubernamentales. El programa GBADs (El impacto global de las enfermedades animales) servirá para compilar datos ya existentes con el fin de medir las pérdidas zoosanitarias dentro de sistemas productivos cuidadosamente caracterizados. La atribución coherente y transparente de estas pérdidas zoosanitarias permitirá efectuar comparaciones significativas del impacto que representan las enfermedades animales en el caso de diferentes dolencias, sistemas productivos o países y pondrá de relieve cómo se distribuye este impacto en función del género y la condición socioeconómica de las personas. Por medio del programa GBADs se creará un motor de conocimiento y portal de datos ubicado en la nube que permita al usuario acceder a mediciones del impacto de enfermedades y representaciones gráficas conexas, a herramientas de apoyo a la adopción de decisiones, en forma de hipotéticas situaciones zoosanitarias futuras, y a los resultados de modelizaciones económicas más generales. La aspiración del programa GBADs ­ reforzar el sistema alimentario en beneficio de la sociedad y el medio ambiente ­ constituye un ejemplo de aplicación en la práctica del pensamiento en clave de Una sola salud.

Differences in Femoral Artery Occlusion Pressure between Sexes and Dominant and Non-Dominant Legs.

Background and Objectives: Blood flow restriction during low-load exercise stimulates similar muscle adaptations to those normally observed with higher loads. Differences in the arterial occlusion pressure (AOP) between limbs and between sexes are unclear. We compared the AOP of the superficial femoral artery in the dominant and non-dominant legs, and the relationship between blood flow and occlusion pressure in 35 (16 males, 19 females) young adults. Materials and Methods: Using ultrasound, we measured the AOP of the superficial femoral artery in both legs. Blood flow at occlusion pressures ranging from 0% to 100% of the AOP was measured in the dominant leg. Results: There was a significant difference in the AOP between males and females in the dominant (230 ± 41 vs. 191 ± 27 mmHg; p = 0.002) and non-dominant (209 ± 37 vs. 178 ± 21 mmHg; p = 0.004) legs, and between the dominant and non-dominant legs in males (230 ± 41 vs. 209 ± 37 mmHg; p = 0.009) but not females (191 ± 27 vs. 178 ± 21 mmHg; p = 0.053), respectively. Leg circumference was the most influential independent predictor of the AOP. There was a linear relationship between blood flow (expressed as a percentage of unoccluded blood flow) and occlusion pressure (expressed as a percentage of AOP). Conclusions: Arterial occlusion pressure is not always greater in the dominant leg or the larger leg. Practitioners should measure AOP in both limbs to determine if occlusion pressures used during exercise should be limb specific. Occlusion pressures used during blood flow restriction exercise should be chosen carefully.

Distal Evaluation of Functional performance with Intravascular sensors to assess the Narrowing Effect-combined pressure and Doppler FLOW velocity measurements (DEFINE-FLOW) trial: Rationale and trial design.

BACKGROUND: It remains uncertain if invasive coronary physiology beyond fractional flow reserve (FFR) can refine lesion selection for revascularization or provide additional prognostic value. Coronary flow reserve (CFR) equals the ratio of hyperemic to baseline flow velocity and has a wealth of invasive and noninvasive data supporting its validity. Because of fundamental physiologic relationships, binary classification of FFR and CFR disagrees in approximately 30%-40% of cases. Optimal management of these discordant cases requires further study. AIM: The aim of the study was to determine the prognostic value of combined FFR and CFR measurements to predict the 24-month rate of major adverse cardiac events. Secondary end points include repeatability of FFR and CFR, angina burden, and the percentage of successful FFR/CFR measurements which will not be excluded by the core laboratory. METHODS: This prospective, nonblinded, nonrandomized, and multicenter study enrolled 455 subjects from 12 sites in Europe and Japan. Patients underwent physiologic lesion assessment using the 0.014" Philips Volcano ComboWire XT that provides simultaneous pressure and Doppler velocity sensors. Intermediate coronary lesions received only medical treatment unless both FFR (≤0.8) and CFR (<2.0) were below thresholds. The primary outcome is a 24-month composite of death from any cause, myocardial infarction, and revascularization. CONCLUSION: The DEFINE-FLOW study will determine the prognostic value of invasive CFR assessment when measured simultaneously with FFR, with a special emphasis on discordant classifications. Our hypothesis is that lesions with an intact CFR ≥ 2.0 but reduced FFR ≤ 0.8 will have a 2-year outcome with medical treatment similar to lesions with FFR> 0.80 and CFR ≥ 2.0. Enrollment has been completed, and final follow-up will occur in November 2019.

Electronic cigarette explosion/burn and poisoning related emergency department visits, 2018-2019.

BACKGROUND: Electronic cigarette (ECIG) use has increased dramatically in recent years. Negative ECIG-related acute health effects have included explosion/burn injuries from battery failure and child ingestion/poisoning of liquid nicotine. However, there is an urgent need for continued surveillance of ECIG health effects to determine whether these outcomes change as ECIG devices and liquids rapidly evolve. This study updates national estimates of ECIG-related emergency department (ED) visits and describes the context of these injuries. METHODS: A keyword search of case narrative text was used to identify ECIG-related ED visits in the National Electronic Injury Surveillance System (NEISS) data. These cross-sectional data are designed to be weighted to provide national estimates of consumer product-related injuries treated in EDs. ECIG-related injuries were described and categorized, and sampling weights applied to model national estimates. RESULTS: From 2015 to 2019 there were an estimated 3369 ED visits from ECIG explosion/burn injuries (95% CI = 2020, 4718), and an estimated 676 visits from 2019 alone (95% CI = 315, 1036). In 2018-2019, there were an estimated 1550 cases of children <5 years old ingesting ECIG liquids (95% CI = 778, 2322). CONCLUSIONS: Despite a notable shift in the US market towards ECIG devices that use lower electrical power and disposable "pods" (e.g., JUUL), liquid chemical ingestion among young children and ECIG explosion/burn injuries persist. Improved product regulations are urgently needed to prevent negative health effects caused by ECIGs, as well as prevent their ingestion and use by children.

Preparing for animal health emergencies: considerations for economic evaluation.

Livestock production systems and the societies in which they are embedded face a set of risks presented by infectious diseases and natural and human-made disasters which compromise animal health. Within this set, threats are posed by natural, deliberate and accidental actions that can cause sudden changes in animal health status, requiring the allocation of additional resources to manage animal health. Determining the benefit of preparing for such emergencies is a challenge when the total set of risks includes the unknown. Any method for analysing the economic costs and benefits of animal health emergencies must not only accommodate this uncertainty, but make it a central feature of the analysis. Cost-benefit analysis is a key approach to economically evaluating animal health interventions. However, the value of this approach in dealing with uncertainty is often called into question. This paper makes the case that, by restricting the outcomes of an emergency event to specified states of nature, boundaries can be placed on the uncertainty space, allowing cost-benefit analysis to be performed. This method, which merges state-contingent analysis with cost-benefit analysis, is presented here. Further discussion on the economic characteristics of emergency events, and the nature of the threats posed to animal health systems, is also provided.

Les systèmes de production animale et les sociétés dans lesquelles ils s'inscrivent doivent faire face à une série de risques associés à des maladies infectieuses ou à des catastrophes d'origine naturelle ou anthropique, qui représentent une menace pour la santé animale. Parmi ces risques, certaines menaces résultant d'actions naturelles, délibérées ou accidentelles peuvent modifier de manière drastique la situation sanitaire des cheptels et imposer d'allouer des ressources supplémentaires à la gestion de la santé animale. Il est difficile de déterminer à l'avance les bénéfices apportés par la préparation aux urgences dès lors que la série complète des risques à envisager comporte des éléments inconnus. Les méthodes d'analyse des coûts et des bénéfices économiques appliquées aux urgences de santé animale doivent non seulement tenir compte de cette incertitude, mais la placer au cœur de l'analyse. L'analyse coûts-bénéfices est une méthode clé pour évaluer les interventions de santé animale dans une perspective économique. Néanmoins, la capacité de cette méthode à traiter l'incertitude est souvent mise en cause. Les auteurs soutiennent qu'en limitant l'analyse des répercussions d'une situation d'urgence à certains états spécifiques de la nature, il devient possible de poser des bornes à l'étendue de l'incertitude, ce qui permet de réaliser une analyse couts-bénéfices. Ils présentent cette méthode, qui consiste à combiner l'analyse des incertitudes dépendantes d'un état de choses donné (state-contingent analysis), avec une analyse coûts-bénéfices. Ils examinent ensuite les caractéristiques économiques des situations d'urgence ainsi que la nature des menaces que ces dernières font peser sur les systèmes de santé animale.

Los sistemas de producción pecuaria y las sociedades en las que están inscritos afrontan una serie de riesgos derivados de enfermedades infecciosas y de desastres de origen natural y humano que ponen en peligro la sanidad animal. Dentro de esta panoplia de riesgos están las amenazas derivadas de sucesos naturales o actos deliberados o accidentales que puedan inducir un cambio repentino de la situación zoosanitaria y exigir recursos adicionales para gestionarla. La determinación de los beneficios que pueda traer consigo la preparación para tales emergencias no es tarea fácil, cuando «lo desconocido¼ forma parte del conjunto de riesgos que se afrontan. Todo método encaminado a analizar los costos económicos y eventuales beneficios en el ámbito de las emergencias zoosanitarias debe no solo integrar esta incertidumbre, sino hacer de ella el elemento central del análisis. El análisis de la relación costo-beneficio es un procedimiento clave para evaluar económicamente las intervenciones de sanidad animal, aunque a menudo se cuestiona su utilidad o idoneidad para manejar la incertidumbre. Los autores postulan que, restringiendo los resultados de un suceso de emergencia a un conjunto especificado de estados de la naturaleza, es posible delimitar el espacio de incertidumbre y, con ello, efectuar un análisis de costos-beneficios. Los autores presentan este método, que consiste en combinar el análisis de las incertidumbres dependientes de un determinado estado de cosas (state-contingent analysis) y el análisis de la relación costo-beneficio. También se detienen a examinar las características económicas de los sucesos de emergencia y el tipo de amenazas que pesan sobre los sistemas de sanidad animal.

The pros and cons of animal health harmonisation.

It has been argued that the global harmonisation of animal health procedures, regulations and responses will improve animal health and provide economic benefits. Harmonisation of regulations can be driven by trade reform, such as multilateral or bilateral agreements, or as a response to private quality assurance programmes. At an international level, trade reform is currently focused on reducing the costs of trading between countries. To achieve this, bilateral agreements, where possible, are harmonising regulations throughout all sectors of the economy. However, as with any new developments, there are both positive and negative outcomes that should be explored to understand the net effect of these changes on animal health, the economy and society. In this article, the authors debate the economic foundations of harmonisation, explore alternative methods to achieve it, and discuss its pros and cons to more fully understand the opportunity costs from countries adopting the same level of risk to animal health.

Il a souvent été avancé qu'en matière de santé animale, l'harmonisation des procédures, des réglementations et des interventions à l'échelle mondiale améliore la situation zoosanitaire globale tout en apportant des bénéfices économiques aux pays. Une telle harmonisation réglementaire peut être le fruit d'une réforme du commerce, notamment par le biais d'accords multilatéraux ou bilatéraux, ou bien constituer une réponse aux programmes d'assurance qualité privés. Au niveau international, la réforme du commerce est actuellement centrée sur la réduction des coûts qu'il entraîne pour les pays. Dans cette perspective, des accords bilatéraux sont conclus chaque fois que possible afin d'harmoniser les réglementations dans tous les secteurs de l'économie. Néanmoins, comme dans toute évolution nouvelle, il en résulte des retombées aussi bien positives que négatives qu'il convient d'analyser afin de bien comprendre l'incidence nette de ces changements sur la santé animale, l'économie et la société. Après avoir débattu des fondements économiques de l'harmonisation, les auteurs examinent les méthodes alternatives qui permettent d'obtenir le même résultat ; ils font aussi le point sur les avantages et les inconvénients de l'harmonisation afin de mieux comprendre le coût d'opportunité qu'elle induit pour les pays adoptant le même niveau de risque en santé animale.

Se ha postulado que la armonización mundial de los procedimientos, reglamentos y respuestas en materia de sanidad animal redundará en un mejor estado sanitario de los animales y reportará beneficios económicos. El impulso para proceder a una armonización reglamentaria puede tener su origen en una reforma del comercio, a raíz por ejemplo de acuerdos multilaterales o bilaterales, o responder a programas privados de garantía de la calidad. A escala internacional, la reforma de los mecanismos comerciales apunta ahora básicamente a reducir los costos del comercio entre países. Para lograrlo se suscriben acuerdos bilaterales que, cuando es posible, entrañan una armonización reglamentaria en todos los sectores de la economía. Sin embargo, como ocurre con todas las novedades, ello tiene repercusiones positivas y negativas, que conviene analizar para aprehender el efecto neto de estos cambios en la sanidad animal, la economía y la sociedad. Los autores examinan los fundamentos económicos de la armonización, plantean métodos alternativos para llevarla adelante y dan cuenta de sus ventajas e inconvenientes para conocer mejor los costos de oportunidad que trae consigo la adopción de un mismo nivel de riesgo zoosanitario por parte de los países.

Whole-Body Vibration as a Warm-up Before Exercise-Induced Muscle Damage on Symptoms of Delayed-Onset Muscle Soreness in Trained Subjects.

Magoffin, RD, Parcell, AC, Hyldahl, RD, Fellingham, GW, Hopkins, JT, and Feland, JB. Whole-body vibration as a warm-up before exercise-induced muscle damage on symptoms of delayed-onset muscle soreness in trained subjects. J Strength Cond Res 34(4): 1123-1132, 2020-There is no clear scientific evidence that whole-body vibration (WBV) used as a warm-up before performing eccentric exercise mitigates delayed-onset muscle soreness (DOMS) and speeds strength loss recovery. These benefits were observed primarily in nonresistance-trained individuals. The aim of this study was to determine whether WBV could mitigate soreness and expedite strength recovery for resistance-trained individuals when used as a warm-up before eccentric exercise. Thirty resistance-trained males completed 300 maximal eccentric contractions of the quadriceps after warming up with (WBV) or without (CON) WBV. Both CON and WBV experienced significant isometric (26.3 and 30.2%, respectively) and dynamic (50.9 and 46.4%, respectively) strength loss immediately after exercise. Isometric strength was significantly depressed after 24 hours in the CON group (8.2% p < 0.02), but not in the WBV group (5.9% p = 0.7). Isometric strength was no longer significantly depressed after 48 hours in the CON group (6.1% p < 0.07) or the WBV group (4.1% p = 0.20). Dynamic strength was significantly decreased in both the CON and WBV groups at 24 hours (17.7% p < 0.001 and 15.5% p < 0.001, respectively) and 48 hours (17.1% p < 0.01 and 13.6% p < 0.002), but only significant for the CON at 1 week after exercise (8.6% p = 0.05). Pain as measured by a visual analog scale was significant in both groups at 24 and 48 hours after exercise, but WBV experienced significantly less soreness than the CON group after 24 hours (28 vs. 46 mm p < 0.01, respectively) and 48 hours (38 vs. 50 mm p < 0.01). Pain pressure threshold increased significantly in both groups, but there was no difference between groups. These results suggest the use of WBV before eccentric exercise mildly mitigates DOMS in trained individuals. Application of WBV can function as a quick mode of warm-up before resistance training and can decrease pain perception from DOMS. This may be beneficial to athletes undergoing a heavy strength training phase where DOMS is likely.

Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease.

Cisplatin is an effective chemotherapeutic agent, but significant nephrotoxicity limits its clinical use. Despite extensive investigation of the acute cellular and molecular responses to cisplatin, the mechanisms of progression from acute to chronic kidney injury have not been explored. We used functional and morphological metrics to establish a time-point when the transition from acute and reversible kidney injury to chronic and irreparable kidney disease is clearly established. In mice administered 1 or 2 doses of intraperitoneal cisplatin separated by 2 weeks, kidney function returned toward baseline two weeks after the first dose, but failed to return to normal two weeks following a second dose. Multiphoton microscopy revealed increased glomerular epithelial and proximal tubular damage in kidneys exposed to two doses of cisplatin compared with those exposed to a single dose. In contrast, there was no evidence of fibrosis, macrophage invasion, or decrease in endothelial cell mass in chronically diseased kidneys. Pathway analysis of microarray data revealed regulated necrosis as a key determinant in the development of chronic kidney disease after cisplatin administration. Western blot analysis demonstrated activation of proteins involved in necroptosis and increased expression of kidney injury markers, cellular stress response regulators, and upstream activators of regulated necrosis, including Toll-like receptors 2 and 4. These data suggest that unresolved injury and sustained activation of regulated necrosis pathways, rather than fibrosis, promote the progression of cisplatin-induced acute kidney injury to chronic kidney disease.

Update on the Native Kidney Biopsy: Core Curriculum 2019.

The kidney biopsy is an invaluable tool that has become the gold standard for the diagnosis of pathologic kidney diseases since the early 1950s. Throughout the years, immunohistologic and ultrastructural microscopy techniques have improved and provide more information on the cause and classification of kidney diseases than that available from simple light microscopy alone. Kidney biopsy has become a preferred method to obtain critical information that can be used in conjunction with serologic, urinary, and genetic testing to diagnose a variety of kidney diseases, both acute and chronic. The kidney biopsy procedure carries relatively low risk and yields substantial information. Potential complications include bleeding requiring transfusion, gross hematuria, arteriovenous fistula formation, and perinephric hematoma, among others. Percutaneous kidney biopsies are typically performed using real-time ultrasound or computed tomographic imaging. This Core Curriculum briefly outlines the history of the kidney biopsy, then discusses indications, complications, and specific procedural aspects.

Hypergranulotic dyscornification: 30 cases of a striking epithelial reaction pattern.

BACKGROUND: Hypergranulotic dyscornification (HD) is a rarely reported histological reaction pattern that may be observed in solitary benign keratoses. OBJECTIVE AND METHODS: We retrospectively reviewed all cases described as displaying "hypergranulotic dyscornification" at our institution between January 1st 1990 to September 1st 2018. We excluded cases that on retrospective review displayed changes of epidermolytic hyperkeratosis. We conducted electron microscopy (EM) of two lesions. RESULTS: Thirty cases were identified in our search. Eleven patients were men and 19 were women. Their mean age was 56.9 ± 21.2 years. In contrast to previous reports, we found that HD does not spare the head and neck area. Frequent clinical impressions were inflamed seborrheic keratosis, Bowen disease or inflamed verruca. The most distinctive histopathologic finding was the presence of a prominent granular layer with clumped perinuclear keratohyaline granules. Some cases had mounds of rounded, anucleate glassy eosinophilic corneocytes in the stratum corneum. We observed one case of incidental HD occurring in an epidermoid cyst. EM of HD showed dense perinuclear bands which appeared to match areas of positive staining by keratin immunohistochemistry, without evidence of pale cytoplasmic areas devoid of keratin filaments, characteristic of epidermolytic hyperkeratosis. CONCLUSION: HD is a reproducible finding in some benign keratoses, probably because of abnormal keratinization. Awareness of this unique reaction pattern will help prevent misdiagnosis.