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1.
Transplantation ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39020464

RESUMEN

BACKGROUND: Coronary allograft vasculopathy (CAV) remains a significant cause of morbidity and mortality after heart transplantation. The use of aspirin for CAV prophylaxis has recently garnered interest as a possible therapeutic adjunct in this setting. METHODS: This 2-center retrospective cohort study included 372 patients who underwent heart transplantation between January 2009 and March 2018 and were stratified according to the commencement of aspirin during their index transplant admission. The primary outcome was the development of moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) at surveillance coronary angiography. Secondary endpoints included mortality at follow-up. RESULTS: There were no differences in age, sex, and cause of heart failure. In the early aspirin group, the preponderant risk factors included use of ventricular assist devices, pretransplant smoking, and mild or moderate rejection. Multivariable analyses to assess for independent predictors of CAV development and mortality demonstrated that aspirin was associated with reduced mortality (adjusted hazard ratio = 0.19; 95% confidence interval, 0.08-0.47, P < 0.01) and a trend toward a protective effect against the development of moderate or severe CAV (adjusted hazard ratio = 0.24; 95% confidence interval, 0.54-1.19; P = 0.08). CONCLUSIONS: In this retrospective risk-adjusted 2-center cohort study, early aspirin administration was associated with reduced risk of death and a trend toward a protective effect against CAV development. These findings warrant validation in prospective randomized trials.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38826135

RESUMEN

Extranuclear localization of long non-coding RNAs (lncRNAs) is poorly understood. Based on machine learning evaluations, we propose a lncRNA-mitochondrial interaction pathway where Polynucleotide Phosphorylase (PNPase), through domains that provide specificity for primary sequence and secondary structure, binds nuclear-encoded lncRNAs to facilitate mitochondrial import. Using FVB/NJ mouse and human cardiac tissues, RNA from isolated subcellular compartments (cytoplasmic and mitochondrial) and crosslinked immunoprecipitate (CLIP) with PNPase within the mitochondrion were sequenced on the Illumina HiSeq and MiSeq, respectively. LncRNA sequence and structure were evaluated through supervised (Classification and Regression Trees (CART) and Support Vector Machines, (SVM)) machine learning algorithms. In HL-1 cells, qPCR of PNPase CLIP knockout mutants (KH and S1) were performed. In vitro fluorescence assays assessed PNPase RNA binding capacity and verified with PNPase CLIP. 112 (mouse) and 1,548 (human) lncRNAs were identified in the mitochondrion with Malat1 being the most highly expressed. Most non-coding RNAs binding PNPase were lncRNAs, including Malat1. LncRNA fragments bound to PNPase compared against randomly generated sequences of similar length showed stratification with SVM and CART algorithms. The lncRNAs bound to PNPase were used to create a criterion for binding, with experimental validation revealing increased binding affinity of RNA designed to bind PNPase compared to control RNA. Binding of lncRNAs to PNPase was decreased through knockout of RNA binding domains KH and S1. In conclusion, sequence and secondary structural features identified by machine learning enhance the likelihood of nuclear-encoded lncRNAs to bind to PNPase and undergo import into the mitochondrion.

3.
Protein Sci ; 33(7): e5083, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38924211

RESUMEN

The effect of population bottlenecks and genome reduction on enzyme function is poorly understood. Candidatus Liberibacter solanacearum is a bacterium with a reduced genome that is transmitted vertically to the egg of an infected psyllid-a population bottleneck that imposes genetic drift and is predicted to affect protein structure and function. Here, we define the function of Ca. L. solanacearum dihydrodipicolinate synthase (CLsoDHDPS), which catalyzes the committed branchpoint reaction in diaminopimelate and lysine biosynthesis. We demonstrate that CLsoDHDPS is expressed in Ca. L. solanacearum and expression is increased ~2-fold in the insect host compared to in planta. CLsoDHDPS has decreased thermal stability and increased aggregation propensity, implying mutations have destabilized the enzyme but are compensated for through elevated chaperone expression and a stabilized oligomeric state. CLsoDHDPS uses a ternary-complex kinetic mechanism, which is to date unique among DHDPS enzymes, has unusually low catalytic ability, but an unusually high substrate affinity. Structural studies demonstrate that the active site is more open, and the structure of CLsoDHDPS with both pyruvate and the substrate analogue succinic-semialdehyde reveals that the product is both structurally and energetically different and therefore evolution has in this case fashioned a new enzyme. Our study suggests the effects of genome reduction and genetic drift on the function of essential enzymes and provides insights on bacteria-host co-evolutionary associations. We propose that bacteria with endosymbiotic lifestyles present a rich vein of interesting enzymes useful for understanding enzyme function and/or informing protein engineering efforts.


Asunto(s)
Flujo Genético , Genoma Bacteriano , Lisina , Simbiosis , Lisina/biosíntesis , Lisina/metabolismo , Lisina/genética , Hidroliasas/genética , Hidroliasas/química , Hidroliasas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Animales
4.
Chem Commun (Camb) ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38920113

RESUMEN

Two novel aza-BODIPY based anion sensors, decorated with halogen bonding recognition sites, are capable of detecting halide anions at biologically-relevant near-IR wavelengths. With potential application for improving the selectivity of photodynamic therapy agents, unprecedented supramolecular host-guest anion binding-modulated singlet oxygen generation is demonstrated.

5.
Ecol Evol ; 14(6): e11538, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38859887

RESUMEN

Understanding the factors that drive spatial synchrony among populations or species is important for management and recovery of populations. The range-wide declines in Atlantic salmon (Salmo salar) populations may be the result of broad-scale changes in the marine environment. Salmon undergo rapid growth in the ocean; therefore changing marine conditions may affect body size and fecundity estimates used to evaluate whether stock reference points are met. Using a dataset that spanned five decades, 172,268 individuals, and 19 rivers throughout Eastern Canada, we investigated the occurrence of spatial synchrony in changes in the body size of returning wild adult Atlantic salmon. Body size was then related to conditions in the marine environment (i.e., climate indices, thermal habitat availability, food availability, density-dependence, and fisheries exploitation rates) that may act on all populations during the ocean feeding phase of their life cycle. Body size increased during the 1980s and 1990s for salmon that returned to rivers after one (1SW) or two winters at sea (2SW); however, significant changes were only observed for 1SW and/or 2SW in some mid-latitude and northern rivers (10/13 rivers with 10 of more years of data during these decades) and not in southern rivers (0/2), suggesting weak spatial synchrony across Eastern Canada. For 1SW salmon in nine rivers, body size was longer when fisheries exploitation rates were lower. For 2SW salmon, body size was longer when suitable thermal habitat was more abundant (significant for 3/8 rivers) and the Atlantic Multidecadal Oscillation was higher (i.e., warmer sea surface temperatures; significant for 4/8 rivers). Overall, the weak spatial synchrony and variable effects of covariates on body size across rivers suggest that changes in Atlantic salmon body size may not be solely driven by shared conditions in the marine environment. Regardless, body size changes may have consequences for population management and recovery through the relationship between size and fecundity.

6.
Heart Lung Circ ; 33(6): 773-827, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38749800

RESUMEN

Transthoracic echocardiography (TTE) is the most widely available and utilised imaging modality for the screening, diagnosis, and serial monitoring of all abnormalities related to cardiac structure or function. The primary objectives of this document are to provide (1) a guiding framework for treating clinicians of the acceptable indications for the initial and serial TTE assessments of the commonly encountered cardiovascular conditions in adults, and (2) the minimum required standard for TTE examinations and reporting for imaging service providers. The main areas covered within this Position Statement pertain to the TTE assessment of the left and right ventricles, valvular heart diseases, pericardial diseases, aortic diseases, infective endocarditis, cardiac masses, pulmonary hypertension, and cardiovascular diseases associated with cancer treatments or cardio-oncology. Facilitating the optimal use and performance of high quality TTEs will prevent the over or under-utilisation of this resource and unnecessary downstream testing due to suboptimal or incomplete studies.


Asunto(s)
Ecocardiografía , Enfermedades de las Válvulas Cardíacas , Adulto , Humanos , Cardiología/métodos , Cardiología/normas , Ecocardiografía/métodos , Ecocardiografía/normas , Enfermedades de las Válvulas Cardíacas/diagnóstico , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Sociedades Médicas , Guías de Práctica Clínica como Asunto
7.
Biomolecules ; 14(5)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38785932

RESUMEN

Augmenting the natural melanocortin pathway in mouse eyes with uveitis or diabetes protects the retinas from degeneration. The retinal cells are protected from oxidative and apoptotic signals of death. Therefore, we investigated the effects of a therapeutic application of the melanocortin alpha-melanocyte-stimulating hormone (α-MSH) on an ischemia and reperfusion (I/R) model of retinal degenerative disease. Eyes were subjected to an I/R procedure and were treated with α-MSH. Retinal sections were histopathologically scored. Also, the retinal sections were immunostained for viable ganglion cells, activated Muller cells, microglial cells, and apoptosis. The I/R caused retinal deformation and ganglion cell loss that was significantly reduced in I/R eyes treated with α-MSH. While α-MSH treatment marginally reduced the number of GFAP-positive Muller cells, it significantly suppressed the density of Iba1-positive microglial cells in the I/R retinas. Within one hour after I/R, there was apoptosis in the ganglion cell layer, and by 48 h, there was apoptosis in all layers of the neuroretina. The α-MSH treatment significantly reduced and delayed the onset of apoptosis in the retinas of I/R eyes. The results demonstrate that therapeutically augmenting the melanocortin pathways preserves retinal structure and cell survival in eyes with progressive neuroretinal degenerative disease.


Asunto(s)
Apoptosis , Homeostasis , Daño por Reperfusión , Retina , Células Ganglionares de la Retina , alfa-MSH , Animales , alfa-MSH/farmacología , alfa-MSH/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Ratones , Apoptosis/efectos de los fármacos , Retina/metabolismo , Retina/efectos de los fármacos , Retina/patología , Homeostasis/efectos de los fármacos , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología , Ratones Endogámicos C57BL , Microglía/metabolismo , Microglía/efectos de los fármacos , Masculino , Células Ependimogliales/metabolismo , Células Ependimogliales/efectos de los fármacos , Células Ependimogliales/patología , Modelos Animales de Enfermedad , Degeneración Retiniana/metabolismo , Degeneración Retiniana/patología , Degeneración Retiniana/tratamiento farmacológico
8.
JMIR Med Inform ; 12: e55499, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38607672

RESUMEN

The cognitive load theory suggests that completing a task relies on the interplay between sensory input, working memory, and long-term memory. Cognitive overload occurs when the working memory's limited capacity is exceeded due to excessive information processing. In health care, clinicians face increasing cognitive load as the complexity of patient care has risen, leading to potential burnout. Electronic health records (EHRs) have become a common feature in modern health care, offering improved access to data and the ability to provide better patient care. They have been added to the electronic ecosystem alongside emails and other resources, such as guidelines and literature searches. Concerns have arisen in recent years that despite many benefits, the use of EHRs may lead to cognitive overload, which can impact the performance and well-being of clinicians. We aimed to review the impact of EHR use on cognitive load and how it correlates with physician burnout. Additionally, we wanted to identify potential strategies recommended in the literature that could be implemented to decrease the cognitive burden associated with the use of EHRs, with the goal of reducing clinician burnout. Using a comprehensive literature review on the topic, we have explored the link between EHR use, cognitive load, and burnout among health care professionals. We have also noted key factors that can help reduce EHR-related cognitive load, which may help reduce clinician burnout. The research findings suggest that inadequate efforts to present large amounts of clinical data to users in a manner that allows the user to control the cognitive burden in the EHR and the complexity of the user interfaces, thus adding more "work" to tasks, can lead to cognitive overload and burnout; this calls for strategies to mitigate these effects. Several factors, such as the presentation of information in the EHR, the specialty, the health care setting, and the time spent completing documentation and navigating systems, can contribute to this excess cognitive load and result in burnout. Potential strategies to mitigate this might include improving user interfaces, streamlining information, and reducing documentation burden requirements for clinicians. New technologies may facilitate these strategies. The review highlights the importance of addressing cognitive overload as one of the unintended consequences of EHR adoption and potential strategies for mitigation, identifying gaps in the current literature that require further exploration.

9.
Pest Manag Sci ; 80(8): 3861-3872, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38511652

RESUMEN

BACKGROUND: Grapevine downy mildew, caused by Plasmopara viticola, is an economically important disease in Australia and worldwide. The application of fungicides is the main tool to control this disease. Frequent fungicide applications can lead to the selection of resistant P. viticola populations, which has negative impacts on the management of the disease. Identification of resistance and its prevalence is necessary to inform resistance management strategies. RESULTS: A total of 86 P. viticola isolates were collected between 2017 and 2022 from vineyards in 15 growing regions across Australia for four fungicide groups; phenylamide (PA, group 4), carboxylic acid amide (CAA, group 40), quinone outside inhibitor (QoI, group 11) and quinone outside inhibitor stigmatellin binding type (QoSI, group 45). Decreased phenotypic sensitivity was detected for all four groups, and resistance to metalaxyl-M (PA) and pyraclostrobin (QoI), was detected. Genetic analysis to detect the G143A (QoI) and G1105S (CAA) mutations using amplicon-based sequencing was performed for 239 and 65 isolates collected in 2014-2017 and 2017-2022, respectively. G143A was detected in 8% and 52% of isolates, respectively, with strong association to phenotypic resistance. However, G1105S was not detected in any isolates. CONCLUSION: Plasmopara viticola isolates in Australia with resistance to at least two fungicide groups have been detected, therefore it is necessary to adopt resistance management strategies where resistance has been detected. Vineyards should continue to be monitored to improve management strategies for downy mildew. © 2024 Society of Chemical Industry.


Asunto(s)
Fungicidas Industriales , Oomicetos , Enfermedades de las Plantas , Vitis , Fungicidas Industriales/farmacología , Vitis/microbiología , Australia , Enfermedades de las Plantas/microbiología , Oomicetos/genética , Oomicetos/efectos de los fármacos , Farmacorresistencia Fúngica/genética , Mutación
10.
Chemistry ; 30(30): e202400952, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38536767

RESUMEN

The first example of a [2]rotaxane shuttle capable of selective optical sensing of chloride anions over other halides is reported. The rotaxane was synthesised via a chloride ion template-directed cyclisation of an isophthalamide macrocycle around a multi-station axle containing peripheral naphthalene diimide (NDI) stations and a halogen bonding (XB) bis(iodotriazole) based station. Proton NMR studies indicate the macrocycle resides preferentially at the NDI stations in the free rotaxane, where it is stabilised by aromatic donor-acceptor charge transfer interactions between the axle NDI and macrocycle hydroquinone moieties. Addition of chloride ions in an aqueous-acetone solvent mixture induces macrocycle translocation to the XB anion binding station to facilitate the formation of convergent XB⋅⋅⋅Cl- and hydrogen bonding HB⋅⋅⋅Cl- interactions, which is accompanied by a reduction of the charge-transfer absorption band. Importantly, little to no optical response was induced by addition of bromide or iodide to the rotaxane, indicative of the size discriminative steric inaccessibility of the interlocked cavity to the larger halides, demonstrating the potential of using the mechanical bond effect as a potent strategy and tool in chloride-selective chemo-sensing applications in aqueous containing solvent environments.

11.
Artif Organs ; 48(6): 655-664, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38459775

RESUMEN

OBJECTIVES: Right ventricular failure following implantation of a durable left ventricular assist device (LVAD) is a major driver of mortality. Reported survival following biventricular (BiVAD) or total artificial heart (TAH) implantation remains substantially inferior to LVAD alone. We report our outcomes with LVAD and BiVAD HeartMate 3 (HM3). METHODS: Consecutive patients undergoing implantation of an HM3 LVAD between November 2014 and December 2021, at The Alfred, Australia were included in the study. Comparison was made between the BiVAD and LVAD alone groups. RESULTS: A total of 86 patients, 65 patients with LVAD alone and 21 in a BiVAD configuration underwent implantation. The median age of the LVAD and BiVAD groups was 56 years (Interquartile range 46-62) and 49 years (Interquartile range 37-55), respectively. By 4 years after implantation, 54% of LVAD patients and 43% of BiVAD patients had undergone cardiac transplantation. The incidence of stroke in the entire experience was 3.5% and pump thrombosis 5% (all in the RVAD). There were 14 deaths in the LVAD group and 1 in the BiVAD group. The actuarial survival for LVAD patients at 1 year was 85% and BiVAD patients at 1 year was 95%. CONCLUSIONS: The application of HM 3 BiVAD support in selected patients appears to offer a satisfactory solution to patients requiring biventricular support.


Asunto(s)
Insuficiencia Cardíaca , Corazón Auxiliar , Humanos , Persona de Mediana Edad , Masculino , Femenino , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Adulto , Estudios Retrospectivos , Resultado del Tratamiento , Trasplante de Corazón/métodos , Australia/epidemiología , Implantación de Prótesis/instrumentación , Implantación de Prótesis/efectos adversos , Implantación de Prótesis/métodos
13.
Open Heart ; 11(1)2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38458771

RESUMEN

OBJECTIVE: Coronary CT angiography (CCTA) permits both qualitative and quantitative analysis of atherosclerotic plaque and may be a suitable risk modifier in assessing patients at intermediate risk of atherosclerotic cardiovascular disease. We sought to determine the association of plaque components with long-term major adverse cardiovascular events (MACEs) in asymptomatic intermediate-risk patients, compared with conventional coronary artery calcium (CAC) score. METHODS: 100 intermediate-risk patients underwent double-blinded CCTA. Follow-up was conducted at 10 years and data were cross-referenced with the National Death Index. The primary outcome was MACE, which was a composite of death, acute coronary syndrome (ACS), revascularisation and stroke. RESULTS: The median time from CCTA to follow-up was 9.5 years. 83 patients completed follow-up interview and mortality data were available on all 100 patients. MACE occurred in 17 (20.5%) patients, which included 2 (2%) deaths, 8 (10%) ACS, 3 (4%) strokes and 5 (6%) revascularisation procedures. 47 (57%) patients had mixed plaque, which was predictive of MACE (OR 4.68 (95% CI 1.19 to 18.5) p=0.028). The burden of non-calcified and mixed plaque, defined by non-calcified plaque segment stenosis score, was also a predictor of long-term MACE (OR 1.59 (95% CI 1.18 to 2.13) p=0.002). Neither calcified plaque (OR 3.92 (95% CI 0.80 to 19.3)) nor CAC score (OR 1.01 (95% CI 0.999 to 1.02)) was associated with long-term MACE. CONCLUSION: The presence and burden of mixed plaque on CCTA is associated with an increased risk of long-term MACE among asymptomatic intermediate-risk patients and is a superior predictor to CAC score.


Asunto(s)
Síndrome Coronario Agudo , Aterosclerosis , Placa Aterosclerótica , Humanos , Angiografía por Tomografía Computarizada/métodos , Pronóstico , Angiografía Coronaria/métodos , Tomografía Computarizada por Rayos X/métodos , Síndrome Coronario Agudo/diagnóstico por imagen
14.
Circ Cardiovasc Interv ; 17(4): e013738, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38487882

RESUMEN

BACKGROUND: Suboptimal coronary reperfusion (no reflow) is common in acute coronary syndrome percutaneous coronary intervention (PCI) and is associated with poor outcomes. We aimed to develop and externally validate a clinical risk score for angiographic no reflow for use following angiography and before PCI. METHODS: We developed and externally validated a logistic regression model for prediction of no reflow among adult patients undergoing PCI for acute coronary syndrome using data from the Melbourne Interventional Group PCI registry (2005-2020; development cohort) and the British Cardiovascular Interventional Society PCI registry (2006-2020; external validation cohort). RESULTS: A total of 30 561 patients (mean age, 64.1 years; 24% women) were included in the Melbourne Interventional Group development cohort and 440 256 patients (mean age, 64.9 years; 27% women) in the British Cardiovascular Interventional Society external validation cohort. The primary outcome (no reflow) occurred in 4.1% (1249 patients) and 9.4% (41 222 patients) of the development and validation cohorts, respectively. From 33 candidate predictor variables, 6 final variables were selected by an adaptive least absolute shrinkage and selection operator regression model for inclusion (cardiogenic shock, ST-segment-elevation myocardial infarction with symptom onset >195 minutes pre-PCI, estimated stent length ≥20 mm, vessel diameter <2.5 mm, pre-PCI Thrombolysis in Myocardial Infarction flow <3, and lesion location). Model discrimination was very good (development C statistic, 0.808; validation C statistic, 0.741) with excellent calibration. Patients with a score of ≥8 points had a 22% and 27% risk of no reflow in the development and validation cohorts, respectively. CONCLUSIONS: The no-reflow prediction in acute coronary syndrome risk score is a simple count-based scoring system based on 6 parameters available before PCI to predict the risk of no reflow. This score could be useful in guiding preventative treatment and future trials.


Asunto(s)
Síndrome Coronario Agudo , Infarto del Miocardio , Fenómeno de no Reflujo , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Intervención Coronaria Percutánea/efectos adversos , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/terapia , Angiografía Coronaria , Resultado del Tratamiento , Factores de Riesgo , Infarto del Miocardio/etiología , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/etiología , Fenómeno de no Reflujo/diagnóstico por imagen , Fenómeno de no Reflujo/etiología
15.
Angew Chem Int Ed Engl ; 63(6): e202315959, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38063409

RESUMEN

Anion sensing via either optical or electrochemical readouts has separately received enormous attention, however, a judicious combination of the advantages of both modalities remains unexplored. Toward this goal, we herein disclose a series of novel, redox-active, fluorescent, halogen bonding (XB) and hydrogen bonding (HB) BODIPY-based anion sensors, wherein the introduction of a ferrocene motif induces remarkable changes in the fluorescence response. Extensive fluorescence anion titration, lifetime and electrochemical studies reveal anion binding-induced emission modulation through intramolecular photoinduced electron transfer (PET), the magnitude of which is dependent on the nature of both the XB/HB donor and anion. Impressively, the XB sensor outperformed its HB congener in terms of anion binding strength and fluorescence switching magnitude, displaying significant fluorescence turn-OFF upon anion binding. In contrast, redox-inactive control receptors display a turn-ON response, highlighting the pronounced impact of the introduction of the redox-active ferrocene on the optical sensing performance. Additionally, the redox-active ferrocene motif also serves as an electrochemical reporter group, enabling voltammetric anion sensing in competitive solvents. The combined advantages of both sensing modalities were further exploited in a novel, proof-of-principle, fluorescence spectroelectrochemical anion sensing approach, enabling simultaneous and sensitive read out of optical and electrochemical responses in multiple oxidation states and at very low receptor concentration.

16.
Clin Infect Dis ; 78(2): 445-452, 2024 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-38019958

RESUMEN

BACKGROUND: Recent cases of clinical failure in malaria patients in the United Kingdom (UK) treated with artemether-lumefantrine have implications for malaria chemotherapy worldwide. METHODS: Parasites were isolated from an index case of confirmed Plasmodium falciparum treatment failure after standard treatment, and from comparable travel-acquired UK malaria cases. Drug susceptibility in vitro and genotypes at 6 resistance-associated loci were determined for all parasite isolates and compared with clinical outcomes for each parasite donor. RESULTS: A traveler, who returned to the UK from Uganda in 2022 with Plasmodium falciparum malaria, twice failed treatment with full courses of artemether-lumefantrine. Parasites from the patient exhibited significantly reduced susceptibility to artemisinin (ring-stage survival, 17.3% [95% confidence interval {CI}, 13.6%-21.1%]; P < .0001) and lumefantrine (effective concentration preventing 50% of growth = 259.4 nM [95% CI, 130.6-388.2 nM]; P = .001). Parasite genotyping identified an allele of pfk13 encoding both the A675V variant in the Pfk13 propeller domain and a novel L145V nonpropeller variant. In vitro susceptibility testing of 6 other P. falciparum lines of Ugandan origin identified reduced susceptibility to artemisinin and lumefantrine in 1 additional line, also from a 2022 treatment failure case. These parasites did not harbor a pfk13 propeller domain variant but rather the novel nonpropeller variant T349I. Variant alleles of pfubp1, pfap2mu, and pfcoronin were also identified among the 7 parasite lines. CONCLUSIONS: We confirm, in a documented case of artemether-lumefantrine treatment failure imported from Uganda, the presence of pfk13 mutations encoding L145V and A675V. Parasites with reduced susceptibility to both artemisinin and lumefantrine may be emerging in Uganda.


Asunto(s)
Antimaláricos , Artemisininas , Malaria Falciparum , Malaria , Humanos , Lumefantrina/farmacología , Lumefantrina/uso terapéutico , Plasmodium falciparum , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Combinación Arteméter y Lumefantrina/farmacología , Combinación Arteméter y Lumefantrina/uso terapéutico , Uganda , Resistencia a Medicamentos , Arteméter/farmacología , Arteméter/uso terapéutico , Artemisininas/farmacología , Artemisininas/uso terapéutico , Malaria/tratamiento farmacológico , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Insuficiencia del Tratamiento , Reino Unido , Proteínas Protozoarias/genética
17.
Int J Cardiol ; 395: 131416, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-37802298

RESUMEN

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the commonest genetic cardiomyopathy and may result in sudden cardiac death (SCD). Clinical risk stratification scores are utilised to estimate SCD risk and determine potential utility of a primary prevention implantable cardioverter defibrillator (ICD). METHODS: Patients with a confirmed diagnosis of HCM from a quaternary HCM service were defined according to clinical characteristics, genetic profiles and cardiac imaging results. European Risk-SCD score and American Heart Association / American College of Cardiology (AHA/ACC) Score were calculated. The primary outcome was cardiac arrest. RESULTS: 380 patients with HCM were followed up for a median of 6.4 years. 18 patients (4.7%) experienced cardiac arrest, with predictive factors being younger age (37.2 vs 54.4 years, p = 0.0041), unexplained syncope (33.3% vs 9.4%, p = 0.007), non-sustained ventricular tachycardia (50.0% vs 12.7%, p < 0.0001), increased septal thickness (21.5 vs 17.5 mm, p = 0.0003), and presence of a sarcomeric gene mutation (100.0% vs 65.8%, p = 0.038). The Risk-SCD and AHA/ACC scores had poor agreement (kappa coefficient 0.38). Risk-SCD score had poor sensitivity (44.4%), classifying 55.6% of patients with cardiac arrest as low-risk but was highly specific (93.7%). AHA/ACC risk score did not discriminate between groups significantly. 20 patients (5.3%) died, with most >60-year-olds having a non-cardiac cause of death (p = 0.0223). CONCLUSION: This study highlights limited (38%) agreement between the Risk-SCD and AHA/ACC scores. Most cardiac arrests occurred in ostensibly low or medium-risk patients under both scores. Appropriate ICD selection remains challenging. Incorporating newer risk markers such as HCM genotyping and myocardial fibrosis quantification by cardiac MRI may assist future risk refinement.


Asunto(s)
Cardiomiopatía Hipertrófica , Desfibriladores Implantables , Humanos , Persona de Mediana Edad , Medición de Riesgo/métodos , Factores de Riesgo , Desfibriladores Implantables/efectos adversos , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/genética
18.
Vaccine ; 42(3): 522-528, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38154991

RESUMEN

BACKGROUND: Myocarditis and myopericarditis are well described adverse events of special interest (AESI) following COVID-19 vaccinations. Although reports are reassuring regarding initial clinical outcomes, information about longer term outcomes remains limited. We aimed to further this knowledge and report outcomes to 6 months post diagnosis from a single population cohort. METHODS: Reports of myocarditis following COVID-19 vaccination were followed up by SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community), the state-wide vaccine safety service for Victoria, Australia. Confirmed myocarditis cases (Brighton Collaboration Criteria levels 1-3) were followed up via surveys at 1, 3 and 6 months post symptom onset. Responses received between 22 February 2021 and 30 September 2022 were analysed. RESULTS: 87.5 % (N = 182) of eligible participants completed at least 1 survey report. 377 reports were analysed. 76.9 % of completed reports were from male patients. The median age of patients was 21 years [IQR: 16 to 32]. 54.8 % (n = 74) of survey reports at 6 months, reported ongoing symptoms. At all follow-up time points, females were significantly more likely to have ongoing symptoms. At 6 months, 51.9 % of male respondents reported symptom resolution compared to 22.6 % of female patients (p = 0.002). Females were also more likely to continue medication and have ongoing exercise restrictions. However, males were significantly more likely to have higher initial peak troponin results and abnormal initial cardiac imaging investigations. CONCLUSIONS: There appears to be a significant proportion of patients who experience ongoing symptoms to 6 months post onset amongst patients that experience these AESI. Male patients were more likely to report earlier and more complete symptom recovery, despite significantly higher average initial peak troponin. This difference in phenotypic presentation in females compared to males warrants further investigation and there is a need for longer term follow up data.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Miocarditis , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Estudios de Seguimiento , Miocarditis/inducido químicamente , Miocarditis/epidemiología , Troponina , Vacunación/efectos adversos , Victoria/epidemiología
19.
Endosc Int Open ; 11(12): E1161-E1167, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38094028

RESUMEN

Background and study aims Foreign body ingestion is a common cause for Emergency Department presentation. In adults, foreign body ingestion is more common in patients with underlying psychiatric comorbidity, the elderly, alcohol intoxication, and in prisoners. This study reviewed the management of patients presenting to a tertiary hospital with foreign body ingestion. Patients and methods A retrospective review of patients presenting with foreign body ingestion to a tertiary hospital in Melbourne, Victoria, was undertaken from January 2017 to December 2021. Data collected included patient demographics, type of foreign body, length of stay, imaging modalities, management strategies, and complications. High-risk ingestion was defined as sharp objects, length >5 cm, diameter >2.5 cm, button battery and/or magnet ingestion or esophageal as per international guidelines. Results A total of 157 presentations by 63 patients with foreign body ingestion occurred between 2017 and 2021 (50% male; median age 30 years). Of the patients, 56% had underlying psychiatric comorbidities. The majority of presentations occurred in prisoners (65%). The most commonly ingested objects were batteries (23%), alleged drug-containing balloons (17%), razor blades (16%), and miscellaneous (40%). High-risk ingestion occurred in approximately two-thirds of presentations. Conservative management was the most common approach in 55% of patients. Complications, defined as perforation, bowel obstruction or fistula formation, did not occur in this cohort despite more than half presenting with high-risk ingestions. Thirty-day re-presentation rates were high (31%) and that was most common in patients with intentional ingestion, underlying mental health disorders, and a documented history of self-harm. Conclusions Conservative management for patients presenting with recurrent high-risk foreign body ingestion was safe in appropriately selected cases. Re-presentation is common and poses significant challenges for health care providers.

20.
Lancet Reg Health West Pac ; 38: 100839, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37790074

RESUMEN

Background: This study examined chest pain epidemiology and care quality for Aboriginal and Torres Strait Islander ('Indigenous') patients presenting to hospital via emergency medical services (EMS) with chest pain. Methods: State-wide population-based cohort study of consecutive patients attended by ambulance for acute chest pain with individual linkage to emergency, hospital admission and mortality data in the state of Victoria, Australia from January 2015 to June 2019. Multivariable models were used to assess for differences in pre-hospital and hospital adherence to care quality, process measures and clinical outcomes. Findings: From 204,969 EMS attendances for chest pain, 3890 attendances (1.9%) identified as Aboriginal or Torres Strait Islander. Age-standardized incidence rates were higher overall for Indigenous people (3128 vs. 1147 per 100,000 person-years, incidence rate ratio 2.73, 95% CI 2.72-2.74), this difference being particularly striking for younger patients, women, and those residing in outer regional areas. In multivariable models, adherence to care quality and process measures was lower for attendances involving Indigenous people. In the pre-hospital setting, Indigenous people were less likely to be provided intravenous access or analgesia. In the hospital setting, Indigenous people were less likely to be seen by emergency clinicians within target time and less likely to transferred following myocardial infarction to a revascularization capable centre. Interpretation: Incidence of acute chest pain presentations is high among Indigenous people in Victoria, Australia. Opportunities to improve the quality of care for Indigenous Australians presenting with acute chest pain are identified. Funding: National Health and Medical Research Council, National Heart Foundation.

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