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.

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)

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.

Neurocognitive correlates of the varied domains of outcomes at 20 year follow-up of first-episode psychosis.

Little is known about long-term outcomes of the first episode of psychosis (FEP) other than in the symptomatic domain. We hypothesised that cognitive impairment is associated with poorer multi-domain outcomes at a long-term follow-up of FEP patients. We followed-up 172 FEP patients for a mean of 20.3 years. Ten outcome dimensions were assessed (symptomatic, functional and personal recovery, social disadvantage, physical health, suicide attempts, number of episodes, current drug use, chlorpromazine equivalent doses (CPZ), and schizophrenia/schizoaffective disorder final diagnosis). Cognition was assessed at follow-up. Processing speed and verbal memory deficits showed significant associations with poor outcomes on symptomatic, social functioning, social disadvantage, higher number of episodes, and higher CPZ. Significant associations were found between visual memory impairments were significantly associated with low symptomatic and functional recovery, between attentional deficits and a final diagnosis of schizophrenia/schizoaffective disorder, and between social cognition deficits and poor personal recovery.Lower cognitive global scores were significantly associated with all outcome dimensions except for drug abuse and physical status. Using multiple outcome dimensions allowed for the inclusion of the patients' perspective and other commonly neglected outcome measures. Taken together, cognitive impairment in FEP patients is strongly related to poor performance on several outcome dimensions beyond symptomatic remission.

Particle release from refit operations in shipyards: Exposure, toxicity and environmental implications.

European harbours are known to contribute to air quality degradation. While most of the literature focuses on emissions from stacks or logistics operations, ship refit and repair activities are also relevant aerosol sources in EU harbour areas. Main activities include abrasive removal of filler and spray painting with antifouling coatings/primers/topcoats. This work aimed to assess ultrafine particle (UFP) emissions from ship maintenance activities and their links with exposure, toxicity and health risks for humans and the aquatic environment. Aerosol emissions were monitored during mechanical abrasion of surface coatings under real-world operating conditions in two scenarios in the Mallorca harbour (Spain). Different types of UFPs were observed: (1) highly regular (triangular, hexagonal) engineered nanoparticles (Ti-, Zr-, Fe-based), embedded as nano-additives in the coatings, and (2) irregular, incidental particles emitted directly or formed during abrasion. Particle number concentrations monitored were in the range of industrial activities such as drilling or welding (up to 5 ∗ 105/cm3, mean diameters <30 nm). The chemical composition of PM4 aerosols was dominated by metallic tracers in the coatings (Ti, Al, Ba, Zn). In vitro toxicity of PM2 aerosols evidenced reduced cell viability and a moderate potential for cytotoxic effects. While best practices (exhaust ventilation, personal protective equipment, dust removal) were in place, it is unlikely that exposures and environmental release can be fully avoided at all times. Thus, it is advisable that health and safety protocols should be comprehensive to minimise exposures in all types of locations (near- and far-field) and periods (activity and non-activity). Potential release to coastal surface waters of metallic engineered and incidental nanomaterials, as well as fine and coarse particles (in the case of settled dust), should be assessed and avoided.

Breast cancer PAM50 signature: correlation and concordance between RNA-Seq and digital multiplexed gene expression technologies in a triple negative breast cancer series.

BACKGROUND: Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular. RESULTS: The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80. CONCLUSIONS: In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method.

Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients.

BACKGROUND: Cancer immune therapy has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish whether the incidence of irAEs after the use of anti-PD-1 antibodies nivolumab or pembrolizumab in advanced malignancies is associated with anti-PD-1 treatment efficacy. PATIENTS AND METHODS: We studied patients treated with single-agent nivolumab or pembrolizumab for advanced cancer. irAEs (immune-related adverse events) were identified clinically and graded as per the Common Terminology Criteria for Adverse Events version 4.0. Efficacy was evaluated with objective response rate (ORR, immune-Response Evaluation Criteria in Solid Tumours [RECIST] criteria) progression-free survival (PFS) and overall survival (OS). Tests were performed to determine the association between irAEs and ORR, PFS or OS. RESULTS: We identified 106 patients. Primary diagnoses were lung cancer (n = 77), melanoma (n = 8), head and neck carcinoma (n = 7), renal carcinoma (n = 5), Hodgkin's lymphoma (n = 3), urothelial carcinoma (n = 3) and gallbladder adenocarcinoma, hepatocellular carcinoma and Merkel cell carcinoma (n = 1 each). IrAEs were observed in 40 patients (37.7%). The most frequent irAEs were hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4). Objective response was observed in 44 patients (41.5%), and median PFS was 5.5 months (0.5-31 months). Thirty-three of the 40 patients with irAEs had objective response (82.5%) in contrast with 11 of the 66 cases without irAEs (16.6%) (OR 23.5, P < 0.000001). PFS in patients with irAEs was 10 months and 3 months in those without irAEs (HR 2.2, P = 0.016). OS in patients with irAEs was 32 months and 22 in those without irAEs, without statistically significant differences. CONCLUSION: In advanced cancer treated with single-agent anti-PD-1 antibodies, patients with irAEs showed a markedly improved efficacy over patients without irAEs (ORR of 82.5% and PFS of 10 months vs ORR of 16.6% and PFS of 3 months). Future studies of anti-PD-1 immune-therapy should address this association to explore the underlying biological mechanisms of efficacy.

High sperm DNA fragmentation delays human embryo kinetics when oocytes from young and healthy donors are microinjected.

BACKGROUND: Time-lapse monitoring (TLM) technology has been implemented in the clinical setting for the culture and selection of human embryos. Many studies have assessed the association between sperm DNA fragmentation (sDNAf) and clinical outcomes after ART, but little is known about the influence of sDNA on embryo morphokinetics. OBJECTIVES: The objective of this retrospective study, which includes 971 embryos from 135 consecutive ICSI cycles (56 cases with own oocytes, 79 with oocytes from young and healthy donors), was to assess if sDNAf has an impact on embryo morphokinetics. MATERIALS AND METHODS: Samples used to perform ICSI were analyzed by the flow cytometry TUNEL assay, and embryo development was assessed through an EmbyoScope® system. The association between sDNAf and the timings of cell cleavage was analyzed by categorizing the first variable into quartiles: ≤6.50%; 6.51-10.70%; 10.71-20.15%; >20.15%. RESULTS: In cases where sDNAf was above 20.15% (the upper quartile), embryos derived from donated oocytes (n = 644) showed significantly slower divisions. Such association was not observed in embryos obtained from the patients' own oocytes (n = 327). The embryo cleavage pattern (either normal, direct from 1 to 3 blastomeres, direct from 1 to 4 blastomeres, incomplete, reversed or asynchronous) was independent of the sDNAf level. Blastocyst arrival rate was 63.0% and the rate of good quality embryos (transferred and frozen embryos divided by the number of zygotes) was 45.49%. Neither parameter was related to the levels of sDNAf. DISCUSSION: According to our results, the association between high sDNAf and donated oocytes led to delayed cell division. To our knowledge, this is the first study suggesting that sDNAf can delay human embryo cleavage timings when oocytes from donors are inseminated. CONCLUSIONS: This finding may indicate that, in the presence of increased DNA damage, time is needed before the first embryonic cell division for the activation of the optimal DNA repairing machinery in higher quality oocytes.

Predicted environmental concentration of engineering nanomaterials as emerging pollutants: baseline scenario / Predicción de la concentración ambiental de los nanomateriales de ingeniería como contaminantes emergentes: escenario de referencia

Nanotechnology is one of the fastest growing and most promising technologies in our society. Due to its potential to develop new added value products, a growing number of engineered nanomaterials (ENMs) are already available on the market. However, in contrast to their benefits, there is an on-going debate about their potential adverse effects on human health and the environment. Such rapid proliferation however entails a crucial environmental problem due to an expected increase of the concentration of ENMs in the environment. The current concentration of ENMs remains unknown and poorly researched. In addition, toxicological studies pointed out adverse effects on key species and communities. Activities supporting the characterization of the concentration of ENMs in the environment will improve the protection of the environment. This paper conducte a thorough review of current data on the concentration of ENMs in the environment, demonstrating the presence of ENMs in freshwater, where quantities above 76 µg/L were estimated in peer reviewed publications

La nanotecnología es una de las tecnologías de más rápido crecimiento y más prometedoras de nuestra sociedad. Debido a su potencial para desarrollar nuevos productos de valor agregado, un número creciente de nanomateriales de ingeniería (ENM) ya están disponibles en el mercado. No obstante, a diferencia de sus beneficios, hay un debate en curso sobre sus posibles efectos adversos en la salud humana y el medio ambiente. Esta rápida proliferación, sin embargo, conlleva un crucial problema ambiental debido al aumento esperado de la concentración de ENMs en el medio ambiente. La concentración actual de ENMs sigue siendo desconocida y poco investigada. Además, los estudios toxicológicos señalaron efectos adversos en especies clave y comunidades. Las actividades que apoyan la caracterización de la concentración de ENMs en el medio ambiente mejorarán la protección del medio ambiente. Este artículo realizó una revisión exhaustiva de los datos actuales sobre la concentración de ENMs en el medio ambiente, demostrando la presencia de ENMs en agua dulce,donde se estimaron cantidades superiores a 76 µg/L en publicaciones revisadas por pares