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Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD.
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Angina pectoris may arise from obstructive coronary artery disease (CAD) or in the absence of significant CAD (ischemia with nonobstructed coronary arteries [INOCA]). Therapeutic strategies for patients with angina and obstructive CAD focus on reducing cardiovascular events and relieving symptoms, whereas in INOCA the focus shifts toward managing functional alterations of the coronary circulation. In obstructive CAD, coronary revascularization might improve angina status, although a significant percentage of patients present angina persistence or recurrence, suggesting the presence of functional mechanisms along with epicardial CAD. In patients with INOCA, performing a precise endotype diagnosis is crucial to allow a tailored therapy targeted toward the specific pathogenic mechanism. In this expert opinion paper, we review the evidence for the management of angina, highlighting the complementary role of coronary revascularization, optimal medical therapy, and lifestyle interventions and underscoring the importance of a personalized approach that targets the underlying pathobiology.
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Angina Estable , Revascularización Miocárdica , Atención Dirigida al Paciente , Humanos , Angina Estable/terapia , Revascularización Miocárdica/métodos , Estilo de Vida , Manejo de la Enfermedad , Enfermedad de la Arteria Coronaria/terapiaRESUMEN
Background: With the spread of SARS-CoV-2 impacting upon public health directly and socioeconomically, further information was required to inform policy decisions designed to limit virus spread during the pandemic. This study sought to contribute to serosurveillance work within Northern Ireland to track SARS-CoV-2 progression and guide health strategy. Methods: Sera/plasma samples from clinical biochemistry laboratories were analysed for anti-SARS-CoV-2 antibodies. Samples were assessed using an Elecsys anti-SARS-CoV-2 or anti-SARS-CoV-2 S ECLIA (Roche) on an automated cobas e 801 analyser. Samples were also assessed via an anti-SARS-CoV-2 ELISA (Euroimmun). A subset of samples assessed via the Elecsys anti-SARS-CoV-2 ECLIA were subsequently analysed in an ACE2 pseudoneutralisation assay using a V-PLEX SARS-CoV-2 Panel 7 for IgG and ACE2 (Meso Scale Diagnostics). Results: Across three testing rounds (June-July 2020, November-December 2020 and June-July 2021 (rounds 1-3 respectively)), 4844 residual sera/plasma specimens were assayed for anti-SARS-CoV-2 antibodies. Seropositivity rates increased across the study, peaking at 11.6 % (95 % CI 10.4 %-13.0 %) during round 3. Varying trends in SARS-CoV-2 seropositivity were noted based on demographic factors. For instance, highest rates of seropositivity shifted from older to younger demographics across the study period. In round 3, Alpha (B.1.1.7) variant neutralising antibodies were most frequently detected across age groups, with median concentration of anti-spike protein antibodies elevated in 50-69 year olds and anti-S1 RBD antibodies elevated in 70+ year olds, relative to other age groups. Conclusions: With seropositivity rates of <15 % across the assessment period, it can be concluded that the significant proportion of the Northern Ireland population had not yet naturally contracted the virus by mid-2021.
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Mycobacterium bovis the main agent of bovine tuberculosis (bTB), presents as a series of spatially-localised micro-epidemics across landscapes. Classical molecular typing methods applied to these micro-epidemics, based on genotyping a few variable loci, have significantly improved our understanding of potential epidemiological links between outbreaks. However, they have limited utility owing to low resolution. Conversely, whole-genome sequencing (WGS) provides the highest resolution data available for molecular epidemiology, producing richer outbreak tracing, insights into phylogeography and epidemic evolutionary history. We illustrate these advantages by focusing on a common single lineage of M. bovis (1.140) from Northern Ireland. Specifically, we investigate the spatial sub-structure of 20 years of herd-level multi locus VNTR analysis (MLVA) surveillance data and WGS data from a down sampled subset of isolates of this MLVA type over the same time frame. We mapped 2108 isolate locations of MLVA type 1.140 over the years 2000-2022. We also mapped the locations of 148 contemporary WGS isolates from this lineage, over a similar geographic range, stratifying by single nucleotide polymorphism (SNP) relatedness cut-offs of 15 SNPs. We determined a putative core range for the 1.140 MLVA type and SNP-defined sequence clusters using a 50 % kernel density estimate, using cattle movement data to inform on likely sources of WGS isolates found outside of core ranges. Finally, we applied Bayesian phylogenetic methods to investigate past population history and reproductive number of the 1.140 M. bovis lineage. We demonstrate that WGS SNP-defined clusters exhibit smaller core ranges than the established MLVA type - facilitating superior disease tracing. We also demonstrate the superior functionality of WGS data in determining how this lineage was disseminated across the landscape, likely via cattle movement and to infer how its effective population size and reproductive number has been in flux since its emergence. These initial findings highlight the potential of WGS data for routine monitoring of bTB outbreaks.
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Mycobacterium bovis , Tuberculosis Bovina , Animales , Bovinos , Mycobacterium bovis/genética , Teorema de Bayes , Filogenia , Tuberculosis Bovina/epidemiología , Epidemiología MolecularRESUMEN
BACKGROUND AND AIMS: The increased likelihood and severity of storm events has brought into focus the role of coastal ecosystems in provision of shoreline protection by attenuating wave energy. Canopy-forming kelps, including giant kelp (Macrocystis pyrifera), are thought to provide this ecosystem service, but supporting data are extremely limited. Previous in situ examinations relied mostly on comparisons between nominally similar sites with and without kelp. Given that other factors (especially seafloor bathymetry and topographic features) often differ across sites, efforts to isolate the effects of kelp on wave energy propagation confront challenges. In particular, it can be difficult to distinguish wave energy dissipation attributable to kelp from frictional processes at the seabed that often covary with the presence of kelp. Here, we use an ecological transition from no kelp to a full forest, at a single site with static bathymetry, to resolve unambiguously the capacity of giant kelp to damp waves. METHODS: We measured waves within and outside rocky reef habitat, in both the absence and the presence of giant kelp, at Marguerite Reef, Palos Verdes, CA, USA. Nested within a broader kelp restoration project, this site transitioned from a bare state to one supporting a fully formed forest (density of 8 stipes m-2). We quantified, as a function of incident wave conditions, the decline in wave energy flux attributable to the presence of kelp, as waves propagated from outside and into reef habitat. KEY RESULTS: The kelp forest damped wave energy detectably, but to a modest extent. Interactions with the seabed alone reduced wave energy flux, on average, by 12â ±â 1.4 % over 180 m of travel. The kelp forest induced an additional 7â ±â 1.2 % decrease. Kelp-associated declines in wave energy flux were slightly greater for waves of longer periods and smaller wave heights. CONCLUSIONS: Macrocystis pyrifera forests have a limited, albeit measurable, capacity to enhance shoreline protection from nearshore waves. Expectations that giant kelp forests, whether extant or enhanced through restoration, have substantial impacts on wave-induced coastal erosion might require re-evaluation.
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Kelp , Macrocystis , Ecosistema , Bosques , ReproducciónRESUMEN
Aims: Cardiac catheterization procedures are typically performed with local anaesthetic and proceduralist guided sedation. Various fasting regimens are routinely implemented prior to these procedures, noting the absence of prospective evidence, aiming to reduce aspiration risk. However, there are additional risks from fasting including patient discomfort, intravascular volume depletion, stimulus for neuro-cardiogenic syncope, glycaemic outcomes, and unnecessary fasting for delayed/cancelled procedures. Methods and results: This is an investigator-initiated, multicentre, randomized trial with a prospective, open-label, blinded endpoint (PROBE) assessment based in New South Wales, Australia. Patients will be randomized 1:1 to fasting (6â h solid food and 2â h clear liquids) or to no fasting requirements. The primary outcome will be a composite of hypotension, hyperglycaemia, hypoglycaemia, and aspiration pneumonia. Secondary outcomes will include patient satisfaction, contrast-induced nephropathy, new intensive care admission, new non-invasive or invasive ventilation requirement post procedure, and 30-day mortality and readmission. Conclusions: This is a pragmatic and clinically relevant randomised trial designed to compare fasting verse no fasting prior to cardiac catheterisation procedures. Routine fasting may not reduce peri-procedural adverse events in this setting.
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Bacille Calmette-Guerin (BCG) is a potential tool in the control of Mycobacterium bovis in European badgers (Meles meles). A five year Test and Vaccinate or Remove (TVR) research intervention project commenced in 2014 using two BCG strains (BCG Copenhagen 1331 (Years 1-3/ BadgerBCG) and BCG Sofia SL2222 (Years 4-5). Badgers were recaptured around 9 weeks after the Year 5 vaccination and then again a year later. The Dual-Path Platform (DPP) Vet TB assay was used to detect serological evidence of M. bovis infection. Of the 48 badgers, 47 had increased Line 1 readings (MPB83 antigen) between the Year 5 vaccination and subsequent recapture. The number of BCG Sofia vaccinations influenced whether a badger tested positive to the recapture DPP VetTB assay Line 1 (p < 0.001) while the number of BadgerBCG vaccinations did not significantly affect recapture Line 1 results (p = 0.59). Line 1 relative light units (RLU) were more pronounced in tests run with sera than whole blood. The results from an in_house MPB83 ELISA results indicated that the WB DPP VetTB assay may not detect lower MPB83 IgG levels as well as the serum DPP VetTB assay. Changes in interferon gamma assay (IFN-γ) results were seen in 2019 with significantly increased CFP-10 and PPDB readings. Unlike BadgerBCG, BCG Sofia induces an immune response to MPB83 (the immune dominant antigen in M. bovis badger infection) that then affects the use of immunodiagnostic tests. The use of the DPP VetTB assay in recaptured BCG Sofia vaccinated badgers within the same trapping season is precluded and caution should be used in badgers vaccinated with BCG Sofia in previous years. The results suggest that the DPP VetTB assay can be used with confidence in badgers vaccinated with BadgerBCG as a single or repeated doses.
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Mustelidae , Mycobacterium bovis , Tuberculosis Bovina , Animales , Vacuna BCG , Bovinos , Pruebas Inmunológicas , Tuberculosis Bovina/prevención & control , Vacunación/veterinariaRESUMEN
BACKGROUND: Distal radial access (DRA) has been proposed to improve procedure ergonomics and favor radial artery patency. Although promising data, nothing is known on evolving hand function after DRA. OBJECTIVES: This study sought to comprehensively evaluate hand function in patients undergoing DRA. METHODS: Real-world patients undergoing DRA undertook a thorough multimodality assessment of hand function implementing multidomain questionnaires (Disabilities of the Arm, Shoulder and Hand and Levine-Katz), and motor (pinch grip test) and sensory (Semmes-Weinstein monofilaments test) examinations of both hands. All assessments were performed at preprocedural baseline and planned at 1-, 6-, and 12-month follow-up (FU). Adverse clinical and procedural events were documented too. RESULTS: Data of 313 patients (220 men, age 66 ± 10 years) from 9 international centers were analyzed. The Disabilities of the Arm, Shoulder and Hand and the Levine-Katz scores slightly improved from baseline to FU (P = 0.008 and P = 0.029, respectively). Pinch strength mildly improved from baseline to FU (P < 0.001 for both the left and right hands). Similarly, touch pressure threshold appeared to faintly improve in both the left and right hands (P < 0.012 for all the sites). For both motor and sensory function tests, comparable findings were found for the DRA hand and the contralateral one, with no significant differences between them. Repeated assessment of all tests over all FU time points similarly showed lack of worsening hand function. Access-related adverse events included 19 harmless bleedings and 3 forearm radial artery and 3 distal radial artery occlusions. None affected hand function at FU. CONCLUSIONS: In a systematic multidimensional assessment, DRA was not associated with hand function impairment. Moreover, DRA emerges as a safe alternative vascular access.
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Arteriopatías Oclusivas , Arteria Radial , Anciano , Mano , Hemorragia , Humanos , Masculino , Persona de Mediana Edad , Arteria Radial/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Introduction: The relationship between personal spirituality and character strengths has not been adequately explored. We investigate this relationship in an adult sample via latent profile analysis. Methods: Seven-hundred and sixty-three individuals aged 18 to 68years completed a survey of personal spirituality (e.g., Delaney Spirituality Scale), character strengths and virtues (e.g., VIA Inventory), flourishing (i.e., general wellbeing; PERMA Profiler), and various demographic variables (e.g., age, race, sexual orientation, yearly income, education level, religiosity, importance of spirituality and religion, and religious attendance). Latent profile analysis (LPA) was performed to identity profiles of individuals based on their reported levels personal spirituality and character strengths (i.e., VIA virtues). Results: A best-fitting model consisting of four distinct, non-overlapping profiles emerged. In every profile, the degree of personal spirituality was consistently associated with strengths of character. Profiles that exhibited high levels of spirituality and character also reported greater levels of flourishing. Furthermore, profiles high in spirituality and character were associated with the observance of formal religion, report of high levels of spiritual and religious importance, and report of frequent attendance of religious services. Discussion: These findings suggest that spirituality and character go hand in hand, that higher levels of the conjoint spirituality and character or "spiritually grounded character" correspond to greater wellbeing and may be generated or supported by a formal religious identification, practice, and community.
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AIMS: To provide multi-national, multi-ethnic data on the clinical characteristics and prognosis of patients with microvascular angina (MVA). METHODS AND RESULTS: The Coronary Vasomotor Disorders International Study Group proposed the diagnostic criteria for MVA. We prospectively evaluated the clinical characteristics of patients according to these criteria and their prognosis. The primary endpoint was the composite of major cardiovascular events (MACE), verified by institutional investigators, which included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. During the period from 1 July 2015 to 31 December 2018, 686 patients with MVA were registered from 14 institutes in 7 countries from 4 continents. Among them, 64% were female and the main ethnic groups were Caucasians (61%) and Asians (29%). During follow-up of a median of 398 days (IQR 365-744), 78 MACE occurred (6.4% in men vs. 8.6% in women, P = 0.19). Multivariable Cox proportional hazard analysis disclosed that hypertension and previous history of coronary artery disease (CAD), including acute coronary syndrome and stable angina pectoris, were independent predictors of MACE. There was no sex or ethnic difference in prognosis, although women had lower Seattle Angina Questionnaire scores than men (P < 0.05). CONCLUSIONS: This first international study provides novel evidence that MVA is an important health problem regardless of sex or ethnicity that a diagnosis of MVA portends a substantial risk for MACE associated with hypertension and previous history of CAD, and that women have a lower quality of life than men despite the comparable prognosis.
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Enfermedad de la Arteria Coronaria , Angina Microvascular , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Calidad de Vida , Factores de RiesgoRESUMEN
Tuberculin skin tests remain widely used in the control of bovine tuberculosis (bTB) in cattle. Little is known about the rate of regression of tuberculin reactions after the comparative intradermal cervical test (CICT) in cattle. This study aimed to collect data to describe tuberculin regression in reactors following the CICT at 72 ± 4 h post injection. Reactors were also tested using the interferon gamma (IFN-γ) assay to establish if any pattern existed between these results and the CICT reaction regression. The data were derived from 108 herds, 112 herd-level CICTs and 1008 animals. A multivariable linear mixed model was built to explore the regression of the bovine tuberculin reaction over time and the influence of potential predictors. The results confirmed a proportional decline in the bovine tuberculin reaction occurred over time. The predictors in the final model demonstrated that regression of the tuberculin reaction differed between reactors according to their IFN-γ test results and whether visible lesions were present at slaughter. Follow-up measurement of tuberculin reactions and the serial use of the IFN-γ assay in large breakdowns has the potential to provide both a mechanism for quality assurance of the current CICT bTB surveillance and the identification of atypical breakdowns or reactors requiring further investigation.
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Garantía de la Calidad de Atención de Salud , Prueba de Tuberculina/veterinaria , Tuberculosis Bovina/diagnóstico , Animales , Bovinos , Interferón gamma , Irlanda del Norte/epidemiología , Prueba de Tuberculina/métodos , Prueba de Tuberculina/estadística & datos numéricos , Tuberculosis Bovina/epidemiología , Tuberculosis Bovina/prevención & controlRESUMEN
Bovine tuberculosis (bTB) is one of the globe's most common, multihost zoonoses and results in substantial socioeconomic costs for governments, farming industries, and tax payers. Despite decades of surveillance and research, surprisingly, little is known about the exact mechanisms of transmission. In particular, as a facultative intracellular pathogen, to what extent does survival of the causative agent, Mycobacterium tuberculosis var. bovis (M. bovis), in the environment constitute an epidemiological risk for livestock and wildlife? Due largely to the classical pathology of cattle cases, the received wisdom was that bTB was spread by direct inhalation and exchange of bioaerosols containing droplets laden with bacteria. Other members of the Mycobacterium tuberculosis complex (MTBC) exhibit differing host ranges, an apparent capacity to persist in environmental fomites, and they favour a range of different transmission routes. It is possible, therefore, that infection from environmental sources of M. bovis could be a disease transmission risk. Recent evidence from GPS-collared cattle and badgers in Britain and Ireland suggests that direct transmission by infectious droplets or aerosols may not be the main mechanism for interspecies transmission, raising the possibility of indirect transmission involving a contaminated, shared environment. The possibility that classical pulmonary TB can be simulated and recapitulated in laboratory animal models by ingestion of contaminated feed is a further intriguing indication of potential environmental risk. Livestock and wildlife are known to shed M. bovis onto pasture, soil, feedstuffs, water, and other fomites; field and laboratory studies have indicated that persistence is possible, but variable, under differing environmental conditions. Given the potential infection risk, it is timely to review the available evidence, experimental approaches, and methodologies that could be deployed to address this potential blind spot and control point. Although we focus on evidence from Western Europe, the concepts are widely applicable to other multihost bTB episystems.
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A novel five year Test and Vaccinate or Remove (TVR) wildlife research intervention project in badgers (Meles meles) commenced in 2014 in a 100km2 area of Northern Ireland. It aimed to increase the evidence base around badgers and bovine TB and help create well-informed and evidence-based strategies to address the issue of cattle-to-cattle spread and spread between cattle and badgers. It involved real-time trap-side testing of captured badgers and vaccinating those that tested negative for bTB (BadgerBCG-BCG Danish 1331) and removal of those that tested bTB positive using the Dual-Path Platform VetTB test (DPP) for cervids (Chembio Diagnostic Systems, Medford, NY USA). Four diagnostic tests were utilised within the study interferon gamma release assay (IGRA), culture (clinical samples and post mortem), DPP using both whole blood and DPP using serum. BCG Sofia (SL222) was used in the final two years because of supply issues with BadgerBCG. Objectives for this study were to evaluate the performance of the DPP in field conditions and whether any trend was apparent in infection prevalence over the study period. A Bayesian latent class model of diagnostic test evaluation in the absence of a gold standard was applied to the data. Temporal variation in the sensitivity of DPP and interferon gamma release assay (IGRA) due to the impact of control measures was investigated using logistic regression and individual variability was assessed. Bayesian latent class analysis estimated DPP with serum to have a sensitivity of 0.58 (95% CrI: 0.40-0.76) and specificity of 0.97 (95% CrI: 0.95-0.98). The DPP with whole blood showed a higher sensitivity (0.69 (95% CrI: 0.48-0.88)) but similar specificity (0.98 (95% Crl: 0.96-0.99)). The change from BCG Danish to BCG Sofia significantly impacted on DPP serum test characteristics. In addition, there was weak evidence of increasing sensitivity of IGRA over time and differences in DPP test sensitivity between adults and cubs. An exponential decline model was an appropriate representation of the infection prevalence over the 5 years, with a starting prevalence of 14% (95% CrI: 0.10-0.20), and an annual reduction of 39.1% (95% CrI: 26.5-50.9). The resulting estimate of infection prevalence in year 5 of the study was 1.9% (95% CrI: 0.8-3.8). These results provide field evidence of a statistically significant reduction in badger TB prevalence supporting a TVR approach to badger intervention. They give confidence in the reliability and reproducibility in the DPP Whole Blood as a real time trap-side diagnostic test for badgers, and describe the effect of vaccination and reduced infection prevalence on test characteristics.
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Animales Salvajes/microbiología , Vacunas Bacterianas/farmacología , Reservorios de Enfermedades , Modelos Biológicos , Mustelidae/microbiología , Mycobacterium bovis , Tuberculosis Bovina , Vacunación , Animales , Teorema de Bayes , Bovinos , Tuberculosis Bovina/epidemiología , Tuberculosis Bovina/prevención & control , Tuberculosis Bovina/transmisiónRESUMEN
The outbreak of the COVID-19 pandemic, and the subsequent suspension of all football-related activity, caused significant disruption to the daily habits of professional football players and support staff. Even when the most severe restrictions were lifted, strict control measures remained in place which likely continued to impact upon nutrition support and intake of players. Thus, this study aimed to understand how restrictions impacted upon nutrition support within professional football, as well as identify how these experiences could inform future practice. Interviews were conducted with twelve sports nutritionists and twelve male professional football players to explore their perspectives of nutrition provision during the COVID-19 pandemic. Thematic analysis indicated three common outcomes: (a) Sub-optimal Nutrition Provision; (b) Reduction in Time with or Access to Players, and; (c) Adaption of Nutrition Practice and/or Dietary Habits. In sum, football clubs should consider the immediate and short-term impact of COVID-19 restrictive measures as players' transition back to normality. Specifically, clubs should provide sports nutritionists with greater capacity to control the nutrition provision, including portion size and food quality. Looking ahead, sports nutritionists are encouraged to reflect upon the novel opportunities that have emerged and consider how these may enhance long-term practice.
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COVID-19 , Fútbol Americano , Nutricionistas , Atletas , Humanos , Masculino , Pandemias , SARS-CoV-2RESUMEN
Beginning in 2015, the United States Environmental Protection Agency's (EPA's) National Estuary Program (NEP) started a collaboration with partners in seven estuaries along the East Coast (Barnegat Bay; Casco Bay), West Coast (Santa Monica Bay; San Francisco Bay; Tillamook Bay), and the Gulf of Mexico (GOM) Coast (Tampa Bay; Mission-Aransas Estuary) of the United States to expand the use of autonomous monitoring of partial pressure of carbon dioxide (pCO2) and pH. Analysis of high-frequency (hourly to sub-hourly) coastal acidification data including pCO2, pH, temperature, salinity, and dissolved oxygen (DO) indicate that the sensors effectively captured key parameter measurements under challenging environmental conditions, allowing for an initial characterization of daily to seasonal trends in carbonate chemistry across a range of estuarine settings. Multi-year monitoring showed that across all water bodies temperature and pCO2 covaried, suggesting that pCO2 variability was governed, in part, by seasonal temperature changes with average pCO2 being lower in cooler, winter months and higher in warmer, summer months. Furthermore, the timing of seasonal shifts towards increasing (or decreasing) pCO2 varied by location and appears to be related to regional climate conditions. Specifically, pCO2 increases began earlier in the year in warmer water, lower latitude water bodies in the GOM (Tampa Bay; Mission-Aransas Estuary) as compared with cooler water, higher latitude water bodies in the northeast (Barnegat Bay; Casco Bay), and upwelling-influenced West Coast water bodies (Tillamook Bay; Santa Monica Bay; San Francisco Bay). Results suggest that both thermal and non-thermal influences are important drivers of pCO2 in Tampa Bay oxygen, National Estuary Program and Mission-Aransas Estuary. Conversely, non-thermal processes, most notably the biogeochemical structure of coastal upwelling, appear to be largely responsible for the observed pCO2 values in West Coast water bodies. The co-occurrence of high salinity, high pCO2, low DO, and low temperature water in Santa Monica Bay and San Francisco Bay characterize the coastal upwelling paradigm that is also evident in Tillamook Bay when upwelling dominates freshwater runoff and local processes. These data demonstrate that high-quality carbonate chemistry observations can be recorded from estuarine environments using autonomous sensors originally designed for open-ocean settings.
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BACKGROUND: Patients with signs and symptoms of myocardial ischemia and non-obstructive coronary artery disease (CAD) frequently have coronary functional abnormalities, including coronary microvascular dysfunction. Those with the latter are grouped under the term "microvascular angina" (MVA). Although diagnostic criteria exist for MVA, as recently proposed by our COVADIS (COronary VAsomotor Disorders International Study) group and the condition has been increasingly recognized in clinical practice, the clinical characteristics and long-term prognosis of MVA patients in the current era remain to be fully elucidated. AIMS: In the present study, we aimed to prospectively assess the clinical characteristics and long-term prognosis of MVA subjects in the current era in an international, multicenter, observational, and prospective registry study. METHODS: A total of 15 medical centers across 7 countries (USA, UK, Germany, Spain, Italy, Australia, and Japan) enrolled subjects fulfilling the COVADIS diagnostic criteria for MVA as follows; (1) signs and/or symptoms of myocardial ischemia, (2) absence of obstructive CAD, and (3) objective evidence of myocardial ischemia and/or coronary microvascular dysfunction. The primary endpoint was the composite of major cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to heart failure or unstable angina. Between July 2015 and December 2018, a total of 706 subjects with MVA (M/F 256/450, 61.1 ± 11.8 [SD] yrs.) were registered. Subjects will be followed for at least 1 year. SUMMARY: The present study will provide important information regarding the clinical characteristics, management, and long-term prognosis of MVA patients in the current era.
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RTS,S/AS01E has been tested in a phase 3 malaria vaccine study with partial efficacy in African children and infants. In a cohort of 1028 subjects from one low (Bagomoyo) and two high (Nanoro, Kintampo) malaria transmission sites, we analysed IgG plasma/serum concentration and avidity to CSP (NANP-repeat and C-terminal domains) after a 3-dose vaccination against time to clinical malaria events during 12-months. Here we report that RTS,S/AS01E induces substantial increases in IgG levels from pre- to post-vaccination (p < 0.001), higher in NANP than C-terminus (2855 vs 1297 proportional change between means), and higher concentrations and avidities in children than infants (p < 0.001). Baseline CSP IgG levels are elevated in malaria cases than controls (p < 0.001). Both, IgG magnitude to NANP (hazard ratio [95% confidence interval] 0.61 [0.48-0.76]) and avidity to C-terminus (0.07 [0.05-0.90]) post-vaccination are significantly associated with vaccine efficacy. IgG avidity to the C-terminus emerges as a significant contributor to RTS,S/AS01E-mediated protection.
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Antígenos de Protozoos/inmunología , Vacunas contra la Malaria/inmunología , Malaria Falciparum/prevención & control , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología , África del Sur del Sahara , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/inmunología , Anticuerpos Antiprotozoarios/aislamiento & purificación , Afinidad de Anticuerpos/inmunología , Epítopos/inmunología , Femenino , Humanos , Inmunogenicidad Vacunal , Lactante , Vacunas contra la Malaria/uso terapéutico , Malaria Falciparum/sangre , Malaria Falciparum/inmunología , Malaria Falciparum/parasitología , Masculino , Resultado del TratamientoRESUMEN
Ex vivo functional immunoassays such as ELISpot and intracellular cytokine staining (ICS) by flow cytometry are crucial tools in vaccine development both in the identification of novel immunogenic targets and in the immunological assessment of samples from clinical trials. Cryopreservation and subsequent thawing of PBMCs via validated processes has become a mainstay of clinical trials due to processing restrictions inherent in the disparate location and capacity of trial centres, and also in the need to standardize biological assays at central testing facilities. Logistical and financial requirement to batch process samples from multiple study timepoints are also key. We used ELISpot and ICS assays to assess antigen-specific immunogenicity in blood samples taken from subjects enrolled in a phase II malaria heterologous prime-boost vaccine trial and showed that the freeze thaw process can result in a 3-5-fold reduction of malaria antigen-specific IFNγ-producing CD3+CD4+ effector populations from PBMC samples taken post vaccination. We have also demonstrated that peptide responsive CD8+ T cells are relatively unaffected, as well as CD4+ T cell populations that do not produce IFNγ. These findings contribute to a growing body of data that could be consolidated and synthesised as guidelines for clinical trials with the aim of increasing the efficiency of vaccine development pipelines.
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Linfocitos T CD4-Positivos/inmunología , Ensayos Clínicos Fase II como Asunto/métodos , Criopreservación , Evaluación Preclínica de Medicamentos/métodos , Interferón gamma/análisis , Vacunas contra la Malaria/inmunología , Manejo de Especímenes/métodos , Linfocitos T CD4-Positivos/efectos de la radiación , Ensayo de Immunospot Ligado a Enzimas , Citometría de Flujo , Humanos , Vacunas contra la Malaria/administración & dosificación , Coloración y EtiquetadoRESUMEN
Objectives The aim of this study was to quantify the radiation dose reduction during coronary angiography and percutaneous coronary intervention (PCI) through removal of the anti-scatter grid (ASG), and to assess its impact on image quality in adult patients with a low body mass index (BMI). Methods A phantom with different thicknesses of acrylic was used with a Westmead Test Object to simulate patient sizes and assess image quality. 129 low BMI patients underwent coronary angiography or PCI with or without the ASG in situ. Radiation dose was compared between both patient groups. Results With the same imaging system and a comparable patient population, ASG removal was associated with a 47% reduction in total dose-area product (DAP) (p < 0.001). Peak skin dose was reduced by 54% (p < 0.001). Operator scatter was reduced to a similar degree and was significantly reduced through removal of the ASG. Using an image quality phantom it was demonstrated that image quality remained satisfactory. Conclusions Removal of the ASG is a simple and effective method to significantly reduce radiation dose in coronary angiography and PCI. This was achieved while maintaining adequate diagnostic image quality. Selective removal of the ASG is likely to improve the radiation safety of cardiac angiography and interventions.