To investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history ...of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment.
A phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity.
Of the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement.
Efgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG.
This study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.
La fragilidad presente al ingreso hospitalario y los estresores a los que son sometidos los pacientes durante su estancia, pueden incrementar la dependencia al alta del hospital.
Evaluar la validez ...predictiva de la Clinical Frailty Scale-España (CFS-España) sobre el incremento de la dependencia a 3 y 12 meses (m) del alta hospitalaria.
Estudio de cohorte multicéntrico en 2020-2022. Incluidos pacientes con estancia >48h en unidades de cuidados intensivos (UCI) y no COVID-19. Variables: fragilidad previa al ingreso (CFS-España). Sexo, edad, días de estancia (UCI y hospital), dependencia al ingreso y a 3m y 12m del alta (Índice de Barthel), debilidad muscular (Medical Research Council Scale sum score <48), reingresos hospitalarios. Estadística: descriptiva y análisis multivariante.
Se incluyeron 254 casos. El 39% fueron mujeres y la mediana Q1-Q3 de edad fue de 67 56-77 años. SAPS 3 al ingreso (medianaQ1-Q3): 6251-71 puntos.
Pacientes frágiles al ingreso (CFS-España 5-9): 58 (23%). Dependencia al ingreso (n=254) vs. 3m del alta hospitalaria (n=171) vs. 12m del alta hospitalaria (n=118): 1) Barthel 90-100: 82% vs. 68% vs. 65%. 2) Barthel 60-85: 15% vs. 15% vs. 20%. 3) Barthel 0-55: 3% vs. 17% vs. 15%.
En el análisis multivariante, ajustado por las variables registradas, observamos que los pacientes frágiles al ingreso (CFS-España 5-9) tienen 2,8 veces (IC95%: 1,03-7,58; p=0,043) más posibilidades de incrementar la dependencia (Barthel 90-100 a <90 o Barthel 85-60 a <60) a 3m del alta (respecto al ingreso) y 3,5 veces (IC95%: 1,18-10,30; p=0,024) más posibilidades de incrementar dependencia a 12m del alta. Además, por cada punto adicional de CFS-España se multiplica por 1,6 (IC95%: 1,01-2,23; p=0,016) la posibilidad de incrementar la dependencia en los 12m siguientes al alta.
La CFS-España al ingreso puede predecir un incremento de la dependencia a los 3m y 12m del alta del hospital.
The frailty present at hospital admission and the stressors to which patients are subjected during their stay may increase dependency at hospital discharge.
To assess the predictive validity of the Clinical Frailty Scale-Spain (CFS-Spain) on increased dependency at 3 and 12 months (m) after hospital discharge.
Multicentre cohort study in 2020-2022. Including patients with >48h stay in intensive care units (ICU) and non-COVID-19. Variables: pre-admission frailty (CFS-Spain). Sex, age, days of stay (ICU and hospital), dependency on admission and at 3m and 12m after discharge (Barthel Index), muscle weakness (Medical Research Council Scale sum score <48), hospital readmissions. Statistics: descriptive and multivariate analysis.
254 cases were included. Thirty-nine per cent were women and the median Q1-Q3 age was 67 56-77 years. SAPS 3 on admission (median Q1-Q3): 62 51-71 points.
Frail patients on admission (CFS-SAPS 5-9): 58 (23%). Dependency on admission (n=254) vs. 3m after hospital discharge (n=171) vs. 12m after hospital discharge (n=118): 1) Barthel 90-100: 82% vs. 68% vs. 65%. 2) Barthel 60-85: 15% vs. 15% vs. 20%. 3) Barthel 0-55: 3% vs. 17% vs 15%.
In the multivariate analysis, adjusted for the variables recorded, we observed that frail patients on admission (CFS-Spain 5-9) are 2.8 times (95%CI: 1.03-7.58; p=0.043) more likely to increase dependency (Barthel 90-100 to <90 or Barthel 85-60 to <60) at 3m post-discharge (with respect to admission) and 3.5 times (95%CI: 1.18-10.30; p=0.024) more likely to increase dependency at 12m post-discharge. Furthermore, for each additional CFS-Spain point there is a 1.6-fold (95%CI: 1.01-2.23; p=0.016) greater chance of increased dependency in the 12m following discharge.
CFS-Spain at admission can predict increased dependency at 3m and 12m after hospital discharge.
Community-acquired (CA) and healthcare-associated (HCA) infections caused by carbapenemase-producing Enterobacterales (CPE) are not well characterized. The objective was to provide detailed ...information about the clinical and molecular epidemiological features of nosocomial, HCA and CA infections caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp) and Escherichia coli (CP-Ec).
A prospective cohort study was performed in 59 Spanish hospitals from February to March 2019, including the first 10 consecutive patients from whom CP-Kp or CP-Ec were isolated. Patients were stratified according to acquisition type. A multivariate analysis was performed to identify the impact of acquisition type in 30-day mortality.
Overall, 386 patients were included (363 94% with CP-Kp and 23 6% CP-Ec); in 296 patients (76.3%), the CPE was causing an infection. Acquisition was CA in 31 (8.0%) patients, HCA in 183 (47.4%) and nosocomial in 172 (48.3%). Among patients with a HCA acquisition, 100 (54.6%) had been previously admitted to hospital and 71 (38.8%) were nursing home residents. Urinary tract infections accounted for 19/23 (82.6%), 89/130 (68.5%) and 42/143 (29.4%) of CA, HCA and nosocomial infections, respectively. Overall, 68 infections (23%) were bacteremia (8.7%, 17.7% and 30.1% of CA, HCA and nosocomial, respectively). Mortality in infections was 28% (13%, 14.6% and 42.7% of CA, HCA and nosocomial, respectively). Nosocomial bloodstream infections were associated with increased odds for mortality (adjusted OR, 4.00; 95%CI 1.21-13.19).
HCA and CA infections caused by CPE are frequent and clinically significant. This information may be useful for a better understanding of the epidemiology of CPE.
The widespread distribution of heteroreceptor complexes with allosteric receptor-receptor interactions in the CNS represents a novel integrative molecular mechanism in the plasma membrane of neurons ...and glial cells. It was proposed that they form the molecular basis for learning and short-and long-term memories. This is also true for drug memories formed during the development of substance use disorders like morphine and cocaine use disorders. In cocaine use disorder it was found that irreversible A2AR-D2R complexes with an allosteric brake on D2R recognition and signaling are formed in increased densities in the ventral enkephalin positive striatal-pallidal GABA antireward neurons. In this perspective article we discuss and propose how an increase in opioid heteroreceptor complexes, containing MOR-DOR, MOR-MOR and MOR-D2R, and their balance with each other and A2AR-D2R complexes in the striatal-pallidal enkephalin positive GABA antireward neurons, may represent markers for development of morphine use disorders. We suggest that increased formation of MOR-DOR complexes takes place in the striatal-pallidal enkephalin positive GABA antireward neurons after chronic morphine treatment in part through recruitment of MOR from the MOR-D2R complexes due to the possibility that MOR upon morphine treatment can develop a higher affinity for DOR. As a result, increased numbers of D2R monomers/homomers in these neurons become free to interact with the A2A receptors found in high densities within such neurons. Increased numbers of A2AR-D2R heteroreceptor complexes are formed and contribute to enhanced firing of these antireward neurons due to loss of inhibitory D2R protomer signaling which finally leads to the development of morphine use disorder. Development of cocaine use disorder may instead be reduced through enkephalin induced activation of the MOR-DOR complex inhibiting the activity of the enkephalin positive GABA antireward neurons. Altogether, we propose that these altered complexes could be pharmacological targets to modulate the reward and the development of substance use disorders.
Objectives
CARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing
K. pneumoniae
(CP-Kpn) and
E. coli
...(CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.
Methods
In total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.
Results
In total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were
bla
OXA–48
(263/377),
bla
KPC–3
(62/377),
bla
VIM–1
(28/377), and
bla
NDM–1
(12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).
Conclusion
This study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3.
OBJECTIVETo adapt the ICU Mobility Scale (IMS) to the area of intensive care units (ICU) in Spain and to evaluate the metric properties of the Spanish version of the IMS (IMS-Es). METHODDescriptive ...metric study developed in two phases. Phase 1, adaptation to Spanish of the IMS by a team of nurses and physiotherapists (translation, pilot, backtranslation and agreement). Phase 2, analysis of metric properties (convergent, divergent and predictive validity, interobserver reliability, sensitivity and minimum important difference) of the IMS-Es. Patient characteristics (Barthel, Charlson, BMI, sex), sedation/agitation level (RASS), ICU and hospital stays, survival, quality of life (SF-12), muscle weakness (MRC-SS) and mobility (IMS-Es) were recorded in the patients of the MOviPre national multicentre study. RESULTSAfter obtaining the IMS-Es, it was implemented in 645 patients from 80 Spanish ICUs between April and June 2017. Convergent validity: moderate correlation between IMS-Es and MRC-SS (r=.389; P<.001) and significant comparison between groups with and without ICU-acquired weakness (P<.001). Divergent validity: no correlation between IMS-Es and BMI r (95%CI): -.112 (-.232 to .011), weight r (95%CI): -.098 (-.219 to .026), Charlson r (95%CI): -.122 (-.242 to .001) and Barthel r(95%CI): -.037 (-.160 to .087) and no differences between sexes (P=.587) or BMI categories (P=.412). Predictive validity: moderate and significant correlations with post-ICU hospital stay r (95%CI): -.442 (-.502 to -.377) and physical component of SF-12 (PCS) r (95%CI): .318 (.063 to .534); patients without active mobilisation in ICU increased risk of hospital mortality OR (95%CI): 3.769 (1.428 to 9.947). Interobserver reliability: very good concordance between nurses CCI (95%CI): .987 (.983 to .990) and nurse-physiotherapist CCI (95%CI): .963 (.948 to .974). Sensitivity to change: small effect on discharge from ICU (d=.273) and moderate effect at 3months after hospital discharge (d=.709). Minimal important difference: 2-point difference cut-off point, 91.1% sensitivity and 100.0% specificity. CONCLUSIONSThe IMS-Es is useful, valid and reliable for implementation by ICU nurses and physiotherapists in assessing the mobility of critical patients.
Patient dosimetry in neurointerventional procedures Rivera-Montalvo, T.; Ugalde-Valdés, M.A.; Uruchurtu-Chavarín, E.S. ...
Radiation physics and chemistry (Oxford, England : 1993),
September 2020, 2020-09-00, 20200901, Letnik:
174
Journal Article
Recenzirano
Neurointerventional radiology (NIR) procedures often require an extended long time to perform. Patient radiation dose is an important issue due to hazards of X-ray radiation. The aim of this work was ...to measure the entrance surface dose (ESD) on the patient's head during interventional neurologic procedure. A batch of solid-state dosimeters were used by mean of thermally stimulated luminescence (TSL) phenomena. Thermoluminescent dosimeters (TLDs) were placed around the head patient during interventional procedures. The ESD on the surface of the head patient was measured. The monitoring of patient's ESDs varied from 5.91 mGy up to 67.44 mGy for arteriovenous fistula (AVF) classified as diagnostic interventional radiology procedures. The highest ESD was determined for 180° with 67.44 mGy. Meanwhile, for therapeutic interventional procedures named arteriovenous malformation (AVM), the ESD measurements revealed a variation from 65.91 mGy and 600.73 mGy. The highest ESD values is attributed acquisition imaging mode during AVM therapeutic procedures. The results suggest the requirements of adopting strategies for radiation dose optimization during neurologic interventional procedures.
•Entrance surface dose (ESD) in the AVM interventional procedure are reported.•Thermoluminescent dosimeters were used for ESD determination.•ESD highest was estimated in AVM interventional procedures.•Corrective action for high dose in AVM procedures was implemented.
Although new digital pathology tools have improved the positive cell quantification, there is a heterogeneity of the quantification methods in the literature. The aim of this study was to evaluate ...and propose a novel dendritic cells quantification method in squamous cell carcinoma comparing it with a conventional quantification method.
Twenty-six squamous cell carcinomas HIV-positive cases affecting the oropharynx, lips and oral cavity were selected. Immunohistochemistry for CD1a, CD83, and CD207 was performed. The immunohistochemical stains were evaluated by automated examination using a positive pixel count algorithm. A conventional quantification method (unspecific area method; UA) and a novel method (specific area method; SA) were performed obtaining the corresponding density of positive dendritic cells for the intratumoral and peritumoral regions. The Mann-Whitney U test was used to verify the influence of the quantification methods on the positive cell counting according to the evaluated regions. Data were subjected to the ANOVA and Student's t-test to verify the influence of the tumour location, stage, histological grade, and amount of inflammation on the dendritic cells density counting.
The cell quantification method affected the dendritic cells counting independently of the evaluated region (P-value <0.05). Significant differences between methods were also observed according to the tumour features evaluations.
The positive cell quantification method influences the dendritic cells density results. Unlike the conventional method (UA method), the novel SA method avoids non-target areas included in the hotspots improving the reliability and reproducibility of the density cell quantification.
To adapt the ICU Mobility Scale (IMS) to the area of intensive care units (ICU) in Spain and to evaluate the metric properties of the Spanish version of the IMS (IMS-Es).
Descriptive metric study ...developed in two phases. Phase 1, adaptation to Spanish of the IMS by a team of nurses and physiotherapists (translation, pilot, backtranslation and agreement). Phase 2, analysis of metric properties (convergent, divergent and predictive validity, interobserver reliability, sensitivity and minimum important difference) of the IMS-Es. Patient characteristics (Barthel, Charlson, BMI, sex), sedation/agitation level (RASS), ICU and hospital stays, survival, quality of life (SF-12), muscle weakness (MRC-SS) and mobility (IMS-Es) were recorded in the patients of the MOviPre national multicentre study.
After obtaining the IMS-Es, it was implemented in 645 patients from 80 Spanish ICUs between April and June 2017. Convergent validity: moderate correlation between IMS-Es and MRC-SS (r = .389; p < .001) and significant comparison between groups with and without ICU-acquired weakness (p < .001). Divergent validity: no correlation between IMS-Es and BMI r(95%CI)=-.112((-.232)-(.011)), weight r(95%CI)=-.098((-.219)-(.026)), Charlson r(95%CI)=-.122((-.242)-(.001)) and Barthel r95%CI=-.037((-.160)-(.087)) and no differences between sexes (p = .587) or BMI categories (p = .412). Predictive validity: moderate and significant correlations with post-ICU hospital stay r(95%CI)=-.442((-.502)-(-.377)) and physical component of SF-12 (PCS) r(95%CI) = .318(.063-.534); patients without active mobilisation in ICU increased risk of hospital mortality OR(95%CI) = 3.769(1.428-9.947). Interobserver reliability: very good concordance between nurses CCI (95%CI) = .987(.983-.990) and nurse-physiotherapist CCI (95%CI) = .963(.948-.974). Sensitivity to change: small effect on discharge from ICU (d = .273) and moderate effect at 3 months after hospital discharge (d = .709). Minimal difference: 2-point difference cut-off point, 91.1% sensitivity and 100.0% specificity.
The IMS-Es is useful, valid and reliable for implementation by ICU nurses and physiotherapists in assessing the mobility of critical patients.
Adaptar la ICU Mobility Scale (IMS) al ámbito de las unidades de cuidados intensivos (UCI) de España y evaluar las propiedades métricas de la IMS versión española (IMS-Es).
Estudio descriptivo de carácter métrico desarrollado en dos fases. Fase 1, adaptación al español de la IMS mediante equipo de enfermeras y fisioterapeutas (traducción, piloto, retrotraducción y acuerdo). Fase 2, análisis de propiedades métricas (validez convergente, divergente y predictiva, fiabilidad interobservador, sensibilidad y diferencia mínima importante) de la IMS-Es. Se registraron características de los pacientes (Barthel, Charlson, IMC, sexo), nivel de sedación/agitación (RASS), estancias en UCI y hospital, supervivencia, calidad de vida (SF-12), debilidad muscular (MRC-SS) y movilidad (IMS-Es) en los pacientes del estudio multicéntrico nacional MOviPre.
Tras obtener la IMS-Es, se implementó en 645 pacientes de 80 UCI españolas entre abril y junio de 2017. Validez convergente: moderada correlación entre IMS-Es y MRC-SS (r = 0,389; p < 0,001) y comparación significativa entre grupos con y sin debilidad adquirida en la UCI (p < 0,001). Validez divergente: no correlación entre IMS-Es e IMC r(IC95%)=-0,112((-0,232)–(0,011)), peso r(IC95%)=-0,098((-0,219)–(0,026)), Charlson r(IC95%)=-0,122((-0,242)–(0,001)) y Barthel rIC95%=-0,037((-0,160)–(0,087)) y sin diferencias entre sexos (p = 0,587) ni categorías de IMC (p = 0,412). Validez predictiva: moderadas y significativas correlaciones con estancia en hospital post-UCI r(IC95%)=-0,442((-0,502)–(-0,377)) y componente físico del SF-12 (PCS) r(IC95%) = 0,318(0,063–0,534); pacientes sin movilización activa en UCI mayor riesgo de mortalidad hospitalaria OR(IC95%) = 3,769(1,428–9,947). Fiabilidad interobservador: muy buena concordancia entre enfermeras CCI(IC95%) = 0,987(0,983–0,990) y entre enfermera-fisioterapeuta CCI(IC95%) = 0,963(0,948–0,974). Sensibilidad al cambio: efecto pequeño al alta de UCI (d = 0,273) y moderado a los 3 meses del alta hospitalaria (d = 0,709). Diferencia mínima importante: punto de corte de la diferencia de 2 puntos, sensibilidad 91,1% y especificidad 100,0%.
La IMS-Es es útil, válida y fiable para ser implementada, por enfermeras de UCI y fisioterapeutas, al valorar la movilidad de los pacientes críticos.
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