BACKGROUND: The use of lutetium-177 (177Lu)-based radiopharmaceuticals in peptide receptor nuclear therapy is increasing, but so is the number of nuclear medicine workers exposed to higher levels of radiation. In recent years, [177Lu]Lu-DOTA-TATE has begun to be widely used for the treatment of neuroendocrine tumours. However, there are few studies evaluating the occupational radiation exposure during its administration, and there are still some challenges that can result in higher doses to the staff, such as a lack of trained personnel or fully standardised procedures. In response, this study aims to provide a comprehensive analysis of occupational doses to the staff involved in the administration of [177Lu]Lu-DOTA-TATE. RESULTS: A total of 32 administrations of [177Lu]Lu-DOTA-TATE (7.4 GBq/session) carried out by a physician and a nurse, were studied. In total, two physicians and four nurses were independently monitored with cumulative (passive) and/or real-time (active) dosemeters. Extremity, eye lens and whole-body doses were evaluated in terms of the dosimetric quantities Hp(0.07), Hp(3) and Hp(10), respectively. It was obtained that lead aprons reduced dose rates and whole-body doses by 71% and 69% for the physicians, respectively, and by 56% and 68% for the nurses. On average, normalised Hp(10) values of 0.65 ± 0.18 µSv/GBq were obtained with active dosimetry, which is generally consistent with passive dosemeters. For physicians, the median of the maximum normalised Hp(0.07) values was 41.5 µSv/GBq on the non-dominant hand and 45.2 µSv/GBq on the dominant hand. For nurses 15.4 µSv/GBq on the non-dominant and 13.9 µSv/GBq on the dominant hand. The ratio or correction factor between the maximum dose measured on the hand and the dose measured on the base of the middle/ring finger of the non-dominant hand resulted in a factor of 5/6 for the physicians and 3/4 for the nurses. Finally, maximum normalised Hp(3) doses resulted in 2.02 µSv/GBq for physicians and 1.76 µSv/GBq for nurses. CONCLUSIONS: If appropriate safety measures are taken, the administration of [177Lu]Lu-DOTA-TATE is a safe procedure for workers. However, regular monitoring is recommended to ensure that the annual dose limits are not exceeded.
Introduction Response to ADP P2Y 12 receptor inhibition by clopidogrel can be evaluated by various techniques. Here, we compared a functional rapid point-of-care technique (PFA-P2Y) with the degree of biochemical inhibition assessed by the VASP/P2Y 12 assay. Methods Platelet response to clopidogrel was investigated in 173 patients undergoing elective intracerebral stenting (derivation cohort n = 117; validation cohort n = 56). High platelet reactivity (HPR) was defined as PFA-P2Y occlusion time <106 seconds or VASP/P2Y 12 platelet reactivity index (PRI) >50%. Results In the derivation cohort, receiver operator characteristics analysis for the ability of PFA-P2Y to detect biochemical HPR showed high specificity (98.4%) but poor sensitivity (20.0%) and a very low area under the curve (0.59). The VASP/P2Y 12 assay revealed two coexisting platelet populations with different levels of vasodilator-stimulated phosphoprotein (VASP) phosphorylation: a fraction of highly phosphorylated, inhibited platelets and another of poorly phosphorylated, reactive platelets. Analysis of the PFA-P2Y curve shape revealed different types, categorized by time of occlusion (<106 seconds, 106 to 300 seconds, >300 seconds), and pattern (regular, irregular, and atypical). Noteworthy, curves with late occlusion and permeable curves with an irregular or atypical pattern correlated with VASP-PRI >50% and smaller sizes of the inhibited platelet subpopulation. Considering the PFA-P2Y shape of the curve for the detection of HPR improved sensitivity (72.7%) and preserved specificity (91.9%), with a rather high AUC (0.823). The validation cohort confirmed the VASP/P2Y 12 assay data and the usefulness of considering the PFA-P2Y curve shape. Conclusion In patients treated with acetylsalicylic acid and clopidogrel for 7-10 days, the VASP/P2Y 12 assay reveals two coexisting subpopulations of differentially inhibited platelets, whose relative sizes predict global PRI and distinct PFA-P2Y curve patterns, indicating incomplete clopidogrel efficacy. The detailed analysis of both VASP/P2Y 12 and PFA-P2Y is necessary for optimal detection of HPR.
AIM: To evaluate the effect of the historic Spanish heatwave (9th-26th July 2022) over glycemic control in adults with type 1 diabetes (T1D). METHODS: Cross-sectional retrospective analysis of adult patients with T1D in Castilla-La Mancha (south-central Spanish region) using intermittently scanned continuous glucose monitoring (isCGM) during and after the heatwave. Primary outcome was change in time in range (TIR) 3.0-10 mmol/L (70-180 mg/dL) of interstitial glucose in the two weeks following the heatwave. RESULTS: A total of 2701 T1D patients were analyzed. We detected a TIR reduction of 4.0 % (95 % CI -3.4, -4.6; P < 0.001) in the two weeks following the heatwave. Patients in the highest daily scan frequency quartile (>13 scans/day) during the heatwave showed the greatest deterioration in TIR after it concluded (-5.4 % [95 % CI -6.5, -4.3; P < 0.001]). The percentage of patients meeting all the recommendations of the International Consensus of Time in Range was greater during the heatwave than after it ended (10.6 % vs. 8.4 %, P < 0.001). CONCLUSIONS: Adults with T1D had better glycemic control during the historic Spanish heatwave compared to the following period.
Blood Glucose , Diabetes Mellitus, Type 1 , Humans , Adult , Blood Glucose Self-Monitoring , Cross-Sectional Studies , Diabetes Mellitus, Type 1/drug therapy , Glycemic Control , Retrospective Studies , Glucose
Deficiency in DNA MMR activity results in tumors with a hypermutator phenotype, termed microsatellite instability (MSI). Beyond its utility in Lynch syndrome screening algorithms, today MSI has gained importance as predictive biomarker for various anti-PD-1 therapies across many different tumor types. Over the past years, many computational methods have emerged to infer MSI using either DNA- or RNA-based approaches. Considering this together with the fact that MSI-high tumors frequently exhibit a hypermethylated phenotype, herein we developed and validated MSIMEP, a computational tool for predicting MSI status from microarray DNA methylation tumor profiles of colorectal cancer samples. We demonstrated that MSIMEP optimized and reduced models have high performance in predicting MSI in different colorectal cancer cohorts. Moreover, we tested its consistency in other tumor types with high prevalence of MSI such as gastric and endometrial cancers. Finally, we demonstrated better performance of both MSIMEP models vis-à-vis a MLH1 promoter methylation-based one in colorectal cancer.
El cuidado perdido tiene un impacto negativo en los resultados en salud, los cuales son reconocidos como eventos adversos por los participantes de la investigación.
Missed care has a negative impact on health outcomes, which are recognized as adverse events by research participants.
A falta de cuidados tem um impacto negativo nos resultados da saúde, que são reconhecidos como eventos adversos pelos participantes da pesquisa.
Kummel's disease is a crush fracture of a vertebral body caused by a minor trauma, with the most accepted etiology being avascular necrosis. It is more frequent in individuals with risk factors such as osteoporosis or prolonged treatment with corticosteroids. Initially, it usually has normal radiological tests and an asymptomatic period, followed by a progressive onset of pain along with probable kyphosis and a sign of void or fluid abscess on radiological tests, which may create nerve/spinal involvement. The case is presented of a 76-year-old man, who was admitted to this center for the differential diagnosis of a single vertebral lesion. After imaging tests and biopsy, the definitive diagnosis of Kummel's disease was reached. The confirmatory diagnosis was reached by vertebral biopsy, but given its invasive nature, imaging techniques can play a significant role. As regards metabolic imaging tests, bone scintigraphy has shown to be one of the most sensitive tools to detect ischemia in earlier stages or to determine if it affects other locations. The whole body scan with diphosphonates shows an increase in activity in relation to bone remodeling activity in this condition. The 3-phase study makes it possible to differentiate whether it is an acute/subacute or chronic process, and can influence the therapeutic decision. Knowledge of this disease is important to make a differential diagnosis with tumour or infectious pathology, with emphasis on performing imaging tests in the event of persistent pain with a normal initial plaque.
La enfermedad de Kummel es una fractura-aplastamiento de un cuerpo vertebral precedida por un traumatismo menor, cuya etiología más aceptada es la necrosis avascular. Es más frecuente en individuos con factores de riesgo como osteoporosis o tratamiento prolongado con corticoides. Inicialmente, suele presentar pruebas radiológicas normales y un periodo asintomático, con aparición progresiva del dolor junto a probable cifosis y signo del vacío o absceso líquido en las pruebas radiológicas, pudiendo llegar a crear compromiso nervioso/medular. Presentamos el caso de un varón de 76 arios que ingresa en nuestro centro para el diagnóstico diferencial de una lesión única vertebral; tras la realización de las pruebas de imagen y biopsia se llega al diagnóstico definitivo de enfermedad de Kummel. El diagnóstico de confirmación de esta enfermedad se alcanza mediante la biopsia vertebral, pero dada su naturaleza invasiva, las técnicas de imagen toman un papel relevante. En relación con las pruebas de imagen metabólicas, la gammagrafía ósea ha demostrado ser una de las herramientas más sensibles para detectar isquemia en fases más tempranas o para conocer si afecta a otras localizaciones. El rastreo corporal de cuerpo completo con difosfonatos muestra un aumento de actividad en relación con la actividad ósea remodelativa en este cuadro. El estudio de tres fases permite diferenciar si se trata de un proceso agudo/subagudo o crónico, lo que influye en la decisión terapéutica. Es importante el conocimiento de esta enfermedad para realizar diagnóstico diferencial con patología tumoral o infecciosa e insistir en la realización de pruebas de imagen ante la persistencia del dolor con una placa inicial normal.
Humans , Male , Aged , Bone Diseases , Radionuclide Imaging , Musculoskeletal Diseases , Embryophyta , Diagnostic Techniques and Procedures , Carum , Diagnosis , Eukaryota , Femur Head Necrosis
BACKGROUND: Since it was first approved in Europe in 2016, the gallium-68 (68Ga) radiopharmaceutical [68Ga]Ga-DOTA-TOC has been widely used for imaging of somatostatin receptor (SSTR) positive tumours using positron emission tomography-computed tomography (PET/CT). Significant patient benefits have been reported, so its use is rapidly increasing. However, few studies have been published regarding occupational doses to nuclear medicine personnel handling this radiopharmaceutical, despite its manual usage at low distances from the skin and the beta-emission decay scheme, which may result in an increased absorbed dose to their hands. In this context, this study aims to analyse the occupational exposure during the administration of [68Ga]Ga-DOTA-TOC for PET/CT imaging. For this purpose, extremity, eye lens and whole-body dosimetry in terms of Hp(0.07), Hp(3) and Hp(10), respectively, was conducted on six workers with both thermoluminescent dosimeters, and personal electronic dosimeters. RESULTS: The non-dominant hand is more exposed to radiation than the dominant hand, with the thumb and the index fingertip being the most exposed sites on this hand. Qualitative analysis showed that when no shielding is used during injection, doses increase significantly more in the dominant than in the non-dominant hand, so the use of shielding is strongly recommended. While wrist dosimeters may significantly underestimate doses to the hands, placing a ring dosimeter at the base of the ring or middle finger of the non-dominant hand may give a valuable estimation of maximum doses to the hands if at least a correction factor of 5 is applied. Personal equivalent doses for the eyes did not result in measurable values (i.e., above the lowest detection limit) for almost all workers. The extrapolated annual dose estimations showed that there is compliance with the annual dose limits during management of [68Ga]Ga-DOTA-TOC for diagnostics with PET in the hospital included in this study. CONCLUSIONS: Imaging with [68Ga]Ga-DOTA-TOC is a safe process for the workers performing the administration of the radiopharmaceutical, including intravenous injection to the patient and the pre- and post-activity control, as it is highly unlikely that annual dose limits will be exceeded if good working practices and shielding are used.
The purpose of this work is to present useful recommendations for the use of [18F]FDG-PET/CT imaging in radiotherapy planning and monitoring under different versions of EARL accreditation for harmonization of PET devices. A proof-of-concept experiment designed on an anthropomorphic phantom was carried out to establish the most suitable interpolation methods of the PET images in the different steps of the planning procedure. Based on PET/CT images obtained by using these optimal interpolations for the old EARL accreditation (EARL1) and for the new one (EARL2), the treatment plannings of representative actual clinical cases were calculated, and the clinical implications of the resulting differences were analyzed. As expected, EARL2 provided smaller volumes with higher resolution than EARL1. The increase in the size of the reconstructed volumes with EARL1 accreditation caused high doses in the organs at risk and in the regions adjacent to the target volumes. EARL2 accreditation allowed an improvement in the accuracy of the PET imaging precision, allowing more personalized radiotherapy. This work provides recommendations for those centers that intend to benefit from the new accreditation, EARL2, and can help build confidence of those that must continue working under the EARL1 accreditation.
Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Phantoms, Imaging , Positron-Emission Tomography/methods
The corrosion inhibition of 5-O-ß-D-glucopyranosyl-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin (4-PC) in AISI 1018 steel immersed in 3% NaCl + CO2 was studied by electrochemical impedance spectroscopy (EIS). The results showed that, at just 10 ppm, 4-PC exerted protection against corrosion with Õ² = 90% and 97% at 100 rpm. At static conditions, the polarization curves indicated that, at 5 ppm, the inhibitor presented anodic behavior, while at 10 and 50 ppm, there was a cathodic-type inhibitor. The inhibitor adsorption was demonstrated to be chemisorption, according to the Langmuir isotherm for 100 and 500 rpm. By means of SEM-EDS, the corrosion inhibition was demonstrated, as well as the fact that the organic compound was effective for up to 72 h of immersion. At static conditions, dispersion-corrected density functional theory results reveal that the chemical bonds established by the phenyl group of 4-PC are responsible of the chemisorption on the steel surface. According with Fukui reactivity indices, the molecules adsorbed on the metal surface provide a protective cover against nucleophilic and electrophilic attacks, pointing to the corrosion inhibition properties of 4-PC.
Sodium Chloride , Steel , Carbon Dioxide , Corrosion , Coumarins , Glucosides , Models, Theoretical , Sodium Chloride/chemistry , Sodium Chloride/pharmacology , Steel/chemistry
Multidrug-resistant Gram-negative bacteria (MDR-GNB) are microorganisms that have acquired resistance to extended-spectrum antibacterials and constitute an emerging threat to public health. Although carriers are an important source of transmission in healthcare settings, data about risk factors for MDR-GNB carriage are limited. Therefore, we aimed to identify risk factors for MDR-GNB carriage upon intensive care unit (ICU) admission and to optimise screening strategies. We conducted a case-control study. Admissions of adult patients to the ICU of a 1000-bed hospital during a year were included. We collected sociodemographic, clinical and microbiological data and performed a multivariate logistic regression model. A total of 1342 patients resulted in 1476 episodes of ICU admission, 91 (6.2%) of whom harboured MDR-GNB (38.5% women; median age 63.9 years). The most frequently isolated pathogens were Escherichia coli (57%) and Klebsiella pneumoniae (16%). The most frequent resistance mechanism was production of extended-spectrum beta lactamases. MDR-GNB carriage was associated to liver cirrhosis (OR 6.54, 95% CI 2.17-19.17), previous MDR-GNB carriage (OR 5.34, 1.55-16.60), digestive surgery (OR 2.83, 1.29-5.89) and length of hospital stay (OR 1.01 per day, 1.00-1.03). Several risk factors for MDR-GNB carriage upon admission to a high-risk setting were identified; the main comorbidity was liver cirrhosis.
Cross Infection , Gram-Negative Bacterial Infections , Adult , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Case-Control Studies , Cross Infection/microbiology , Drug Resistance, Multiple, Bacterial , Female , Gram-Negative Bacteria , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/microbiology , Humans , Intensive Care Units , Male , Middle Aged , Risk Factors
BACKGROUND: Functional tests for the diagnosis of heparin-induced thrombocytopenia (HIT) exhibit variable performance. OBJECTIVES: We evaluated in a multicenter study whether 5B9, a monoclonal anti-PF4/heparin IgG mimicking human HIT antibodies, could be used as an internal quality control. METHODS: 5B9 was sent to 11 laboratories in seven countries, and six initial concentrations ranging from 10 to 400 µg/mL were tested by heparin-induced platelet activation assay (HIPA), serotonin release assay (SRA), platelet aggregation test (PAT), flow cytometry (FC), or heparin-induced multiple-electrode aggregometry (HIMEA). Each method was evaluated in three different laboratories using experimental procedures identical to those usually applied for the diagnosis of HIT by testing platelets from 10 different healthy donors. RESULTS: The procedures used varied among the laboratories, particularly when platelet-rich plasma and whole blood were used. Nevertheless, positive results were obtained with at least 100 µg/ml of 5B9 for most donors tested by all centers (except one) performing HIPA, SRA, or HIMEA. FC and PAT results were more heterogeneous. FC results from one center that used washed platelets preincubated with PF4 were positive with all donors at 50 µg/ml 5B9, but at least 200 µg/ml of 5B9 were required to activate cells with most donors tested using PAT. CONCLUSION: This study confirms that HIT functional tests are not well standardized and exhibit variable sensitivity for the detection of platelet-activating antibodies. However, 5B9 is a potentially useful tool to standardize functional tests, to select responding platelet donors, and consequently to improve the performance of these assays and comparability between laboratories.
Platelet Factor 4 , Thrombocytopenia , Antibodies, Monoclonal , Anticoagulants/adverse effects , Blood Platelets , Communication , Heparin/adverse effects , Humans , Immunoglobulin G , Platelet Activation , Quality Control , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis
ABSTRACT A case is presented of an atypical manifestation of localized scleroderma. The patient is a 30-year-old Caucasian women with localized facial scleroderma "coup de sabre", with clinical stability foryears. She was seen in the Emergency Department due to a sudden lack of sensitivity in her left side, and was treated as a stroke. Complementary tests showed intracranial parenchymal images that were finally attributed to the localized scleroderma. After a comprehensive literature review, this presentation was more frequent than expected. This is why neurological symptoms should be carefully evaluated in these patients. This is the first stroke-mimic case reported.
RESUMEN A continuación, presentamos el caso de una paciente con una manifestación atípica para esclerodermia localizada. Mujer de 30 an˜ os con esclerodermia localizada facial en sabré¼, con estabilidad clínica de las lesiones durante an˜ os. En el 2017 acude al servicio de urgencias por un cuadro de alteración sensitiva en hemicuerpo izquierdo que fue tratada como un ictus. En los estudios complementarios se objetivaron lesiones parenquimatosas finalmente atribuibles a la esclerodermia localizada. Tras revisar la literatura, este tipo de lesiones es más frecuente de lo esperado, por lo que parece obligatorio dedicar más atención a los síntomas neurológicos en los pacientes con esclerodermia localizada. Este es el primer caso de stroke-mimic reportado.
Humans , Female , Adult , Scleroderma, Localized , Skin and Connective Tissue Diseases , Connective Tissue Diseases
