Papel del radiofarmacéutico clínico en la seguridad del paciente durante los estudios de perfusión miocárdica de esfuerzo con vasodilatadores / Role of the clinical radiopharmacist in patient safety during myocardial perfusion imaging with vasodilator stress agents

Objetivos: Evaluar el papel del radiofarmacéutico en un equipo multidisciplinar en la detección de contraindicaciones del regadenosón para su uso seguro en pacientes a los que se solicitó una SPECT de perfusión miocárdica. Métodos: Se estudió ambispectivamente su uso seguro en 1.905 pacientes (54,1% mujeres, edad media: 66,6±11,7 años, rango: 20-95años). Se registraron datos relativos al sexo, a la edad, al historial médico, a la medicación, a las alergias medicamentosas y a las contraindicaciones para el estrés farmacológico, así como las recomendaciones realizadas al médico nuclear responsable. Resultados: Las contraindicaciones detectadas y las correspondientes recomendaciones fueron las siguientes: riesgo de prolongación del intervalo QTc (7,5%): comprobación previa del intervalo QTc y monitorización del ECG; ictus o AIT previo (4,2%): evaluación de estenosis carotídea; alergia a salicilatos y/o sulfamidas (3,1%): empleo de [99mTc]Tc-MIBI; epilepsia o riesgo de convulsiones (2,4%): uso de adenosina o reconsiderar su indicación; tratamiento con corticosteroides sistémicos en EPOC severa (1,3%): reevaluar las condiciones del paciente; EPOC reagudizada (0,8%): posponer hasta la resolución del episodio agudo; asma grave (0,4%): no realizar la prueba; toma de metilxantinas (0,3%): evitar su consumo previo; otras (6,1%): evaluación de cada contraindicación. No se observaron contraindicaciones en el 73,6% de los pacientes. Se anularon el 2,9% de las peticiones debido a contraindicaciones absolutas. Conclusiones: Empleando una metodología de trabajo sistemática, el radiofarmacéutico detectó un elevado número de incidencias, presentando uno de cada cuatro pacientes alguna contraindicación clínica. Las recomendaciones emitidas fueron aceptadas por los médicos nucleares, que modificaron su enfoque, incrementando así la seguridad de estos pacientes.(AU)

Aim: To assess the radiopharmacist's role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. Methods: We ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20-95years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. Results: Detected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% — measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% — consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% — use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% — use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% — reassessment of patient's condition; acute exacerbation of COPD 0.8% — defer test until acute episode is over; severe asthma 0.4% — do not perform test; methylxanthine ingestion 0.3% — avoid consumption previously; other 6.1% — evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was cancelled due to absolute contraindications in 2.9% of the requests. Conclusions: Working in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.(AU)

Role of the clinical radiopharmacist in patient safety during myocardial perfusion imaging with vasodilator stress agents.

AIM: To assess the radiopharmacist's role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. METHODS: We ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20-95 years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. RESULTS: Detected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% - measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% - consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% - use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% - use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% - reassessment of patient's condition; acute exacerbation of COPD 0.8% - defer test until acute episode is over; severe asthma 0.4% - do not perform test; methylxanthine ingestion 0.3% - avoid consumption previously; other 6.1% - evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was canceled due to absolute contraindications in 2.9% of the requests. CONCLUSIONS: Working in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.

Appropriateness of antibiotic prescribing for patients with sepsis in rural hospital emergency departments.

DESIGN/PARTICIPANTS: This was a multicentre retrospective cohort study of adult patients (≥18 years) presenting with a process associated International Classification of Diseases code (ICD-AM-10) pertaining to sepsis between January 2017 and July 2020 to rural Emergency Departments. MAIN OUTCOME MEASURES: Our primary outcome was antibiotic appropriateness as defined by the Australian Therapeutic Guidelines (for antibiotic selection relative to infecting source) and the National Antimicrobial Prescribing Survey tool. Our secondary outcome was in-hospital mortality. METHODS: Relevant clinical and non-clinical, physiological and laboratory data were collected retrospectively. Multivariate logistic regression was used to estimate the odds of both inappropriate antibiotic prescribing and in-hospital mortality based on clinical and non-clinical factors. RESULTS: A total of 378 patients were included who primarily presented with sepsis of unknown origin (36.8%), a genitourinary (22.22%) or respiratory (18.78%) source. Antibiotics were appropriately prescribed in 59% of patients. A positive Quick Sequential Organ Failure Assessment score (qSOFA) (odds ratio [OR] = 0.49; 95% confidence interval [CI], 0.29-0.83), a respiratory infection source (OR = 0.5; 95% CI, 0.29-0.86) and documented allergy (OR = 0.42; 95% CI, 0.25-0.72) were associated with a lower risk of appropriate prescribing in multivariate analysis. Forty-one percent of patients received antibiotics within 1 h of presentation. Inappropriate antibiotic prescribing was not associated with in-hospital mortality. CONCLUSION: The rates of appropriate antibiotic prescribing in rural Emergency Departments for patients presenting with sepsis is low, but comparable to other referral metropolitan centres.

Valoración del tromboembolismo pulmonar relacionado con infección SARS-CoV-2 activa en pacientes embarazadas / Assessment of pulmonary embolism related to active SARS-CoV-2 infection in pregnant women

Objetivo Analizar la muestra de pacientes embarazadas a las que se les realizó una gammagrafía de perfusión pulmonar para descartar la sospecha de tromboembolismo pulmonar (TEP) durante el ingreso en nuestro centro por infección aguda por COVID-19. Material y métodos A todas las pacientes (n=5) se les realizó una gammagrafía SPECT con dosis reducida (111MBq) de 99mTc-macroagregados de albúmina. Las imágenes obtenidas se interpretaron comparando los hallazgos con la imagen radiológica según criterios PISAPED. Resultados De las 5 pacientes, tan solo en una se diagnosticó TEP. En 2 pacientes los hallazgos patológicos de la gammagrafía fueron atribuibles a alteraciones radiológicas por neumonía COVID-19, y otras 2 mostraron una perfusión pulmonar normal. Conclusión Dado lo inespecífico de las manifestaciones clínicas y los valores del dímero D dentro de la COVID-19, así como su similitud con los de TEP, la gammagrafía de perfusión pulmonar, por su alta sensibilidad y menor irradiación que la TC, tiene un papel crucial en el despistaje de TEP en estas pacientes. Los resultados obtenidos son de especial relevancia, a pesar del número limitado de pacientes, dada la ausencia de publicaciones científicas en este grupo de pacientes dentro de la situación excepcional por la pandemia de COVID-19 (AU)

Aim To analyze the sample of pregnant patients who underwent pulmonary perfusion scintigraphy to rule out the pulmonary embolism (PE) suspicion during the acute COVID-19 infection hospitalization period in our hospital. Material and methods SPECT scintigraphy with a reduced dose (111MBq) of 99mTc-macroaggregated albumin was performed in all of the patients (n=5). The obtained images were interpreted by comparing the findings with the radiological images according to the PISAPED criteria. Results Only one of the 5 patients was diagnosed with PE. Two patients obtained pathological findings of the scintigraphy attributable to radiological alterations due to COVID-19 pneumonia, and the other 2 had normal pulmonary perfussion. Conclusion Given the non-specific features of the clinical manifestations and D-dimer values in COVID-19, as well as their similarity to those of PE, the pulmonary perfusion scintigraphy plays a crucial role in the screening of PE in these patients due to its high sensitivity and lower irradiation compared to CT. Despite the limited number of patients, the results obtained have special relevance related to the absence of scientific publications on this group of patients within the context of COVID-19 pandemic exceptional situation (AU)

La cardiología nuclear en la pandemia COVID-19 / Nuclear Cardiology in the COVID-19 pandemic

La infección por SARS-CoV-2 tiene una relación muy importante con la patología cardiovascular. Desde el inicio de la pandemia se objetivó una relación estrecha entre la comorbilidad cardiovascular y un peor pronóstico de los pacientes COVID-19. El estudio de la fisiopatología de la infección por SARS-CoV-2 y la enfermedad cardiovascular sugieren varias hipótesis concomitantes: el daño miocárdico directo por el virus, la hipoxemia secundaria a la insuficiencia respiratoria, la respuesta inflamatoria a la infección y/o los fenómenos tromboembólicos. El daño cardiovascular se puede manifestar en la fase aguda de la infección con cuadros de infarto agudo de miocardio, miocarditis, arritmias…, durante esta fase los procedimientos de Cardiología Nuclear no han tenido un papel determinante en el diagnóstico y manejo de estos pacientes. En cambio, en la fase subaguda de la infección y en el síndrome del COVID post-agudo la Cardiología Nuclear parece ofrecer luz a lo que sucede en el sistema cardiovascular en esta fase de la enfermedad. La pandemia de la COVID-19 ha representado un gran reto para los sistemas de salud constatándose una reducción importante de pruebas diagnósticas no urgentes con el objetivo de disminuir el riesgo de transmisión a pacientes y personal sanitario. La Cardiología Nuclear no ha sido una excepción. Además de la priorización de pruebas urgentes/preferentes y las medidas generales de screening, higiene y distancia, los principales organismos y sociedades científicas de Medicina Nuclear y Cardiología Nuclear han elaborado recomendaciones y guías para su práctica segura introduciendo notables cambios en los protocolos SPECT de perfusión miocárdica (AU)

SARS-CoV-2 infection has a very important relationship with cardiovascular disease. Since the beginning of the pandemic, a close relationship has been observed between cardiovascular comorbidity and a worse prognosis in COVID-19 patients. The study of the pathophysiology of SARS-CoV-2 infection and cardiovascular disease suggests several concomitant hypotheses: direct myocardial damage by the virus, hypoxemia secondary to respiratory failure, inflammatory response to infection and/or thromboembolic phenomena. Cardiovascular damage can manifest in the acute phase of infection with acute myocardial infarction, myocarditis, arrhythmias..., during this phase Nuclear Cardiology procedures have not played a determining role in the diagnosis and management of these patients. On the other hand, in the subacute phase of the infection and in the post-acute COVID syndrome, Nuclear Cardiology seems to shed light on what happens in the cardiovascular system in this phase of the disease. The COVID-19 pandemic has represented a great challenge for health systems, with a significant reduction in non-urgent diagnostic procedures with the aim of reducing the risk of transmission to patients and health personnel. Nuclear Cardiology has not been an exception. In addition to the prioritization of urgent/non-deferrable procedures and general screening, hygiene and distance measures, the main organizations and scientific societies of Nuclear Medicine and Nuclear Cardiology released recommendations and guidelines for safe practice, introducing significant changes in myocardial perfusion SPECT protocol (AU)

Assessment of pulmonary embolism related to active SARS-CoV-2 infection in pregnant women.

AIM: To analyze a sample of pregnant patients who underwent pulmonary perfusion scintigraphy to rule out suspicion of pulmonary embolism (PE) during the acute COVID-19 infection hospitalization period in our hospital. MATERIAL AND METHODS: SPECT scintigraphy with a reduced dose (111MBq) of 99mTc-macroaggregated albumin was performed in all the patients (n=5). The images obtained were interpreted by comparing the findings with the radiological images according to the PISAPED criteria. RESULTS: Only one of the 5 patients was diagnosed with PE. Two patients showed pathological scintigraphy findings attributable to radiological alterations due to COVID-19 pneumonia, and the other two had normal pulmonary perfusion. CONCLUSION: Given the non-specific features of the clinical manifestations and d-dimer values ​​in COVID-19, as well as their similarity to those of PE, pulmonary perfusion scintigraphy plays a crucial role in the screening of PE in these patients due to its high sensitivity and lower irradiation compared to CT. Despite the limited number of patients, the results obtained have special relevance due to the absence of scientific publications in this group of patients within the exceptional context of the COVID-19 pandemic.

[Nuclear Cardiology in the COVID-19 pandemic]. / La cardiología nuclear en la pandemia COVID-19.

SARS-CoV-2 infection has a very important relationship with cardiovascular disease. Since the beginning of the pandemic, a close relationship has been observed between cardiovascular comorbidity and a worse prognosis in COVID-19 patients. The study of the pathophysiology of SARS-CoV-2 infection and cardiovascular disease suggests several concomitant hypotheses: direct myocardial damage by the virus, hypoxemia secondary to respiratory failure, inflammatory response to infection and/or thromboembolic phenomena. Cardiovascular damage can manifest in the acute phase of infection with acute myocardial infarction, myocarditis, arrhythmias..., during this phase Nuclear Cardiology procedures have not played a determining role in the diagnosis and management of these patients. On the other hand, in the subacute phase of the infection and in the post-acute COVID syndrome, Nuclear Cardiology seems to shed light on what happens in the cardiovascular system in this phase of the disease.The COVID-19 pandemic has represented a great challenge for health systems, with a significant reduction in non-urgent diagnostic procedures with the aim of reducing the risk of transmission to patients and health personnel. Nuclear Cardiology has not been an exception. In addition to the prioritization of urgent/non-deferrable procedures and general screening, hygiene and distance measures, the main organizations and scientific societies of Nuclear Medicine and Nuclear Cardiology released recommendations and guidelines for safe practice, introducing significant changes in myocardial perfusion SPECT protocols.

Semi-mechanistic PK/PD modelling of fosfomycin and sulbactam combination against carbapenem-resistant Acinetobacter baumannii.

Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are now considered potential treatments for CR-AB. This study aimed to explore the utility of fosfomycin-sulbactam combination (FOS/SUL) therapy against CR-AB isolates.Synergism of FOS/SUL against 50 clinical CR-AB isolates were screened using the checkerboard method. Thereafter, time-kill studies against two CR-AB isolates were performed. The time-kill data were described using a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Monte Carlo simulations were then performed to estimate the probability of stasis, 1-log kill and 2-log kill after 24-hours with combination therapy.The FOS/SUL combination demonstrated a synergistic effect against 74% of isolates. No antagonism was observed. The MIC50 and MIC90 of FOS/SUL were decreased four- to eight-fold, compared to the monotherapy MIC50 and MIC90 In the time-kill studies, the combination displayed bactericidal activity against both isolates and synergistic activity against one isolate, at the highest clinically achievable concentrations. Our PK/PD model was able to describe the interaction between fosfomycin and sulbactam in vitro Bacterial kill was mainly driven by sulbactam, with fosfomycin augmentation. FOS/SUL regimens that included sulbactam 4 g every 8 hours, demonstrated a probability of target attainment of 1-log10 kill at 24 h of ∼69-76%, as compared to ∼15-30% with monotherapy regimens at the highest doses.The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that FOS/SUL may potentially be effective against some CR-AB infections.

Pharmacodynamics of ceftriaxone for the treatment of methicillin-susceptible Staphylococcus aureus: is it a viable treatment option?

Ceftriaxone is a broad-spectrum cephalosporin that may be one option to treat methicillin-susceptible Staphylococcus aureus (MSSA). Although MSSA may be susceptible to ceftriaxone, the minimum inhibitory concentration (MIC) is generally two- to four-fold higher than other susceptible bacterial pathogens. This study aimed to explore the pharmacodynamics of ceftriaxone against MSSA and to determine the likely optimal dose. A hollow-fibre infection model was used with one clinical MSSA isolate (MIC = 4 mg/L) at an initial inoculum of 1 × 106 CFU/mL. Ceftriaxone dosing regimens of 1 g once and twice daily and 2 g once and twice daily were simulated. Ceftriaxone 1 g dosing regimens did not substantially impact bacterial killing within the first 12 h. Conversely, when administered as a 2 g dose either once or twice daily, an approximate 1-log10 bacterial reduction was observed where it plateaued for up to 96 h. No resistance was identified. Only a high ceftriaxone dose of 2 g twice daily achieves bacterial killing and sustained inhibition of bacterial growth. Ceftriaxone at routinely used doses is unsuitable for the treatment of MSSA infections and alternative agents should be preferentially used.

Gammagrafía cardíaca con 99mTc-difosfonatos en la amiloidosis cardíaca / Cardiac scintigraphy with 99mTc-diphosphonates in cardiac amyloidosis

La amiloidosis cardíaca relacionada con el depósito de transtirretina (ATTR) ha sido tradicionalmente considerada como una enfermedad rara, de difícil diagnóstico y sin tratamiento. Sin embargo, en la actualidad sabemos que su prevalencia es mayor de la considerada, disponemos de métodos diagnósticos no invasivos y están apareciendo tratamientos eficaces. En este contexto, la gammagrafía cardíaca (GC) con difosfonatos marcados con 99mTc ha alcanzado un inusitado interés al mostrar alta sensibilidad y especificidad para el diagnóstico no invasivo y fiable de la ATTR. Este artículo, a modo de guía, pretende identificar los componentes críticos en la realización de la GC que resulten de utilidad en la práctica clínica diaria y, así, ayudar a los especialistas a utilizar los radiofármacos idóneos, obtener las imágenes más adecuadas, interpretar los resultados de estas y conocer los escenarios clínicos en los que resulta apropiado realizar la GC

Transthyretin cardiac amyloidosis (ATTR) has traditionally been considered a rare, difficult-to-diagnose and untreatable disease. However, its prevalence is known to be greater than what was previously thought, non-invasive diagnostic methods are available, and that effective treatments are emerging. In this context, cardiac scintigraphy (CS) with 99mTc-labelled diphosphonates has aroused a noticeable surge in interest by demonstrating high sensitivity and specificity for the reliable, non-invasive diagnosis of ATTR. By way of a guide, this article aims to identify the critical components in the performance of CS that are useful in everyday clinical practice and, thus, help specialists use optimal radiopharmaceuticals, obtain the most appropriate images, interpret the results thereof, and acquaint themselves with those clinical scenarios in which it is convenient to perform CS

Cardiac scintigraphy with 99mTc-diphosphonates in cardiac amyloidosis. / Gammagrafía cardíaca con 99mTc-difosfonatos en la amiloidosis cardíaca.

Transthyretin cardiac amyloidosis (ATTR) has traditionally been considered a rare, difficult-to-diagnose and untreatable disease. However, its prevalence is known to be greater than what was previously thought, non-invasive diagnostic methods are available, and that effective treatments are emerging. In this context, cardiac scintigraphy (CS) with 99mTc-labelled diphosphonates has aroused a noticeable surge in interest by demonstrating high sensitivity and specificity for the reliable, non-invasive diagnosis of ATTR. By way of a guide, this article aims to identify the critical components in the performance of CS that are useful in everyday clinical practice and, thus, help specialists use optimal radiopharmaceuticals, obtain the most appropriate images, interpret the results thereof, and acquaint themselves with those clinical scenarios in which it is convenient to perform CS.

Harmonizing analytical chemistry and clinical epidemiology for human biomonitoring studies. A case-study of plastic product chemicals in urine.

There is an interdisciplinary interface between analytical chemistry and epidemiology studies with respect to the design, execution, and analysis of environmental epidemiology cohorts and studies. Extracting meaningful results linking chemical exposure to human health outcomes begins at study design and spans the entire workflow. Here we discuss analytical experimental design from an exposure science perspective, and propose a reporting checklist for the design of human biomonitoring studies. We explain key analytical chemistry concepts of blanks and limits of reporting and present a case series of plastic product chemical exposure in prenatal urine specimens from the Barwon Infant Study.

Effect of cardiac resynchronization therapy on septal perfusion and septal thickening: Association with left ventricular function, reverse remodelling and dyssynchrony.

BACKGROUND: We evaluated the effect of cardiac resynchronization therapy (CRT) on septal perfusion and thickening at 6 months post implantation assessed on Tc99m-MIBI Gated myocardial perfusion SPECT (GMPS).We also studied the association of change in septal perfusion and thickening with primary outcome defined as at least one [improvement in ≥1NYHA class, left ventricular ejection fraction (LVEF) by ≥ 5%, reduction of end-systolic volume (ESV) by ≥ 15%, and improvement ≥ 5 points in Minnesota living with heart failure questionnaire (MLHFQ)]. METHOD: One hundred and five patients underwent clinical and GMPS evaluation before and at 6 months post CRT. RESULT: Post CRT there was significant improvement in mean normalized septal perfusion uptake and in septal thickening (P value = 0.001, both). There was no significant relation between improvement in septal perfusion and primary outcome. However, improvement in septal thickening was statistically significant with favorable primary outcome (P = 0.001).There was no significant correlation between improvement of septal perfusion and improvement in LVEF, reduction in End diastolic volume (EDV), ESV, and Left ventricular Dyssynchrony (LVD). But, there was significant correlation between improvement of septal thickening and these parameters. CONCLUSION: Improvement in septal thickening was associated with reverse remodeling, improvement in LVEF, and reduction of LVD.

Saturable elimination of piperacillin in critically ill patients: implications for continuous infusion.

The study aimed to evaluate saturation of piperacillin elimination in critically ill adult patients. Seventeen critically ill adult patients received continuous and intermittent infusion of piperacillin/tazobactam. Piperacillin plasma concentrations (n = 217) were analysed using population pharmacokinetic (PopPK) modelling. Post-hoc simulations were performed to evaluate the type I error rate associated with the study. Unseen data were used to validate the final model. The mean error (ME) and root mean square error (RMSE) were calculated as a measure of bias and imprecision, respectively. A PopPK model with parallel linear and non-linear elimination best fitted the data. The median and 95% confidence interval (CI) for the model parameters drug clearance (CL), volume of central compartment (V), volume of peripheral compartment (Vp) and intercompartmental clearance (Q) were 9 (7.69-11) L/h, 6.18 (4.93-11.2) L, 11.17 (7.26-12) L and 15.61 (12.66-23.8) L/h, respectively. The Michaelis-Menten constant (Km) and the maximum elimination rate for Michaelis-Menten elimination (Vmax) were estimated without population variability in the model to avoid overfitting and inflation of the type I error rate. The population estimates for Km and Vmax were 37.09 mg/L and 353.57 mg/h, respectively. The bias (ME) was -20.8 (95% CI -26.2 to -15.4) mg/L, whilst imprecision (RMSE) was 49.2 (95% CI 41.2-56) mg/L. In conclusion, piperacillin elimination is (partially) saturable. Moreover, the population estimate for Km lies within the therapeutic window and therefore saturation of elimination should be accounted for when defining optimum dosing regimens for piperacillin in critically ill patients.

Gammagrafía de inervación simpática cardiaca con 123I-metayodobencilguanidina. Fundamento, protocolos y aplicaciones clínicas en Cardiología / Cardiac sympathetic innervation scintigraphy with 123I-meta-iodobenzylguanidine. Basis, protocols and clinical applications in Cardiology

La obtención de imágenes de la inervación simpática cardiaca solo es posible mediante técnicas de cardiología nuclear, y su valoración es de importancia decisiva en la evaluación y en la toma de decisiones en pacientes en los que exista deterioro de inervación simpática. Se revisa el fundamento de la gammagrafía de inervación simpática cardiaca con 123I-metayodobencilguanidina (123I-MIBG), los protocolos recomendados para su realización, incluyendo preparación del paciente, técnicas de obtención y cuantificación de imágenes, reproducibilidad, consideraciones dosimétricas, etc. , analizando las indicaciones clínicas de esta exploración en pacientes cardiológicos, principalmente en insuficiencia cardiaca, arritmias, coronariopatía, cardiotoxicidad, contribución a la indicación y seguimiento de respuesta a dispositivos de estimulación cardiaca, tratamiento farmacológico, trasplante cardiaco y otros

Imaging of cardiac sympathetic innervation is only possible by nuclear cardiology techniques and its assessment is key in the evaluation of and decision-making for patients with cardiac sympathetic impairment. This review includes the basis of cardiac sympathetic scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG), recommended protocols, patient preparation, image acquisition and quantification, reproducibility, dosimetry, etc. , and also the clinical indications for cardiac patients, mainly with regard to heart failure, arrhythmia, coronary artery disease, cardiotoxicity, including its contribution to establishing the indication for and monitoring the response to implantable cardiac devices, pharmacological treatment, heart transplantation and other

Vancomycin population pharmacokinetics for adult patients with sepsis or septic shock: are current dosing regimens sufficient?

PURPOSE: Vancomycin is commonly used for the management of severe infections; however, vancomycin dosing may be challenging in critically ill patients. This observational study aims to describe the population pharmacokinetics of vancomycin in adult patients with sepsis or septic shock. METHODS: A single-centre retrospective review of adult patients with sepsis or septic shock receiving vancomycin with therapeutic drug monitoring was undertaken. Blood samples taken 1 h after the vancomycin infusion cessation and 30 min prior to the next dose were assayed using the Vitros Crea Slide method. Vancomycin concentrations determined on different days were included. A pharmacokinetic model was developed using Pmetrics for R. Monte Carlo dosing simulations were performed using the final model. RESULTS: Vancomycin concentrations were available for 27 adult patients admitted to the intensive care unit with sepsis or septic shock. A one-compartment pharmacokinetic model with inter-occasion variability of clearance and volume of distribution before and after 72 h adequately described the data. Creatinine clearance normalized to body surface area was included as a covariate on vancomycin clearance. The clearance and volume of distribution within 72 h of admission were 7.29 L/h and 54.20 L, respectively. Monte Carlo simulations suggested that for patients with a creatinine clearance of ≥ 80 mL/min/1.73 m2, vancomycin doses of ≥ 2 g every 8 h are required to consistently achieve key therapeutic targets. CONCLUSIONS: Vancomycin doses ≥ 2 g every 8 h in adult patients with sepsis or septic shock with a creatinine clearance ≥ 80 mL/min/1.73 m2 are likely needed to achieve an optimal therapeutic exposure.

Cardiac sympathetic innervation scintigraphy with 123I-meta-iodobenzylguanidine. Basis, protocols and clinical applications in Cardiology. / Gammagrafía de inervación simpática cardiaca con 123I-metayodobencilguanidina. Fundamento, protocolos y aplicaciones clínicas en Cardiología.

Imaging of cardiac sympathetic innervation is only possible by nuclear cardiology techniques and its assessment is key in the evaluation of and decision-making for patients with cardiac sympathetic impairment. This review includes the basis of cardiac sympathetic scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG), recommended protocols, patient preparation, image acquisition and quantification, reproducibility, dosimetry, etc., and also the clinical indications for cardiac patients, mainly with regard to heart failure, arrhythmia, coronary artery disease, cardiotoxicity, including its contribution to establishing the indication for and monitoring the response to implantable cardiac devices, pharmacological treatment, heart transplantation and other.

Integrated chemical exposure assessment of coastal green turtle foraging grounds on the Great Barrier Reef.

The Great Barrier Reef receives run-off from 424,000 km2 catchment area across coastal Queensland, incorporating diffuse agricultural run-off, and run-off point sources of land-based chemical pollutants from urban and industrial development. Marine biota, such as green turtles (Chelonia mydas), are exposed to these diverse chemical mixtures in their natural environments, and the long term effects on turtle and ecosystem health remain unknown. This study was part of a larger multi-disciplinary project characterising anthropogenic chemical exposures from the marine environment and turtle health. The aim of this study was to screen for a wide range of anthropogenic chemical pollutants present in the external and internal environment of green turtles, using a combination of traditional targeted chemical analyses, non-target suspect screening, and effect-based bioassay methods, while employing a case-control study design. A combination of passive (water) and grab (water, sediment) samples were investigated. Three known green turtle foraging sites were selected for sampling: two coastal 'case' sites influenced primarily by urban/industrial and agricultural activities, respectively; and a remote, offshore 'control' site. Water and sediment samples from each of the three sampling locations showed differences in chemical pollutant profiles that reflected the dominant land uses in the adjacent catchment. Targeted mass spectrometric analysis for a range of pesticides, industrial chemicals, pharmaceuticals and personal care products found the greatest detection frequency and highest concentrations in coastal samples, compared to the control. Non-target screening analysis of water showed clear differentiation in chemical profile of the urban/industrial site. In-vitro assays of sediment samples from the control site had lowest induction, compared to coastal locations, as expected. Here we present evidence that turtles foraging in coastal areas are exposed to a range of anthropogenic pollutants derived from the adjacent coastal catchment areas.

Perfluorinated alkyl acids in the serum and follicular fluid of UK women with and without polycystic ovarian syndrome undergoing fertility treatment and associations with hormonal and metabolic parameters.

Women with polycystic ovarian syndrome (PCOS) undergoing treatment for infertility could be a sensitive subpopulation for endocrine effects of exposure to perfluorinated alkyl acids (PFAAs), persistent organic pollutants with potential endocrine activity. Women with, PCOS (n = 30) and age- and BMI-matched controls (n = 29) were recruited from a UK fertility clinic in 2015. Paired serum and follicular fluid samples were collected and analysed for 13 PFAAs. Sex steroid and thyroid hormones, and metabolic markers were measured and assessed for associations with serum PFAAs. Four PFAAs were detected in all serum and follicular fluid samples and concentrations in the two matrices were highly correlated (R2 > 0.95): perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). Serum PFOS was positively associated with age (1 ng/mL per yr, p < 0.05) and was higher in PCOS cases than controls (geometric mean [GM] 3.9 vs. 3.1 ng/mL, p < 0.05) and in women with irregular vs. regular menstrual cycles (GM 3.9 vs. 3.0 ng/mL, p = 0.01). After adjustment for confounders, serum testosterone was significantly associated with PFOA, PFHxS, PFNA, and the molar sum of the four frequently detected serum PFAAs (approximately 50 percent increase per ln-unit) among controls but not PCOS cases. HbA1c in PCOS cases was inversely associated with serum PFOA, PFHxs, and sum of PFAAs (2-3 mmol/mol per ln-unit). In controls, fasting glucose was positively associated with serum PFOA and sum of PFAAs (0.25 nmol/L per ln-unit increase in PFAAs). Few other associations were observed. The analyses and findings here should be considered exploratory in light of the relatively small sample sizes and large number of statistical comparisons conducted. However, the data do not suggest increased sensitivity to potential endocrine effects of PFAAs in PCOS patients.

Individualising Therapy to Minimize Bacterial Multidrug Resistance.

The scourge of antibiotic resistance threatens modern healthcare delivery. A contributing factor to this significant issue may be antibiotic dosing, whereby standard antibiotic regimens are unable to suppress the emergence of antibiotic resistance. This article aims to review the role of pharmacokinetic and pharmacodynamic (PK/PD) measures for optimising antibiotic therapy to minimise resistance emergence. It also seeks to describe the utility of combination antibiotic therapy for suppression of resistance and summarise the role of biomarkers in individualising antibiotic therapy. Scientific journals indexed in PubMed and Web of Science were searched to identify relevant articles and summarise existing evidence. Studies suggest that optimising antibiotic dosing to attain defined PK/PD ratios may limit the emergence of resistance. A maximum aminoglycoside concentration to minimum inhibitory concentration (MIC) ratio of > 20, a fluoroquinolone area under the concentration-time curve to MIC ratio of > 285 and a ß-lactam trough concentration of > 6 × MIC are likely required for resistance suppression. In vitro studies demonstrate a clear advantage for some antibiotic combinations. However, clinical evidence is limited, suggesting that the use of combination regimens should be assessed on an individual patient basis. Biomarkers, such as procalcitonin, may help to individualise and reduce the duration of antibiotic treatment, which may minimise antibiotic resistance emergence during therapy. Future studies should translate laboratory-based studies into clinical trials and validate the appropriate clinical PK/PD predictors required for resistance suppression in vivo. Other adjunct strategies, such as biomarker-guided therapy or the use of antibiotic combinations require further investigation.