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1.
Trials ; 22(1): 595, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488845

RESUMO

BACKGROUND: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. METHODS: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. DISCUSSION: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Noma , Tecido Adiposo , Animais , Ensaios Clínicos Fase II como Assunto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Método Duplo-Cego , Humanos , Isquemia/diagnóstico , Isquemia/terapia , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Resultado do Tratamento
2.
Artigo em Espanhol | PAHO-IRIS | ID: phr-54642

RESUMO

[RESUMEN]. Desde 1948, la Organización Mundial de la Salud ha venido publicando un sistema codificado de causas de enfermedad y muerte bajo el nombre genérico de Clasificación Estadística Internacional de Enfermedades (CIE), con revisiones en profundidad cada 10-15 años. En su última versión, CIE-11, se utiliza una terminolo-gía para caracterizar la vejez como “períodos geriátricos inicial y final”, lo que implica una medicalización de esta etapa de la vida que ha generado confusión y polémica. En este trabajo se discute la nueva terminología propuesta a la luz del conocimiento actual en torno a la vejez y el proceso de envejecimiento, y su definición más aceptada. La CIE no solo clasifica las enfermedades sino también los períodos de la vida y los “proble-mas relacionados con la salud”, y la vejez por sí sola no representa un problema relacionado con la salud para muchos de quienes se encuentran en esta etapa de la vida. Desde esta perspectiva, es imprescindible cambiar o matizar el epígrafe “vejez” de la CIE-11 para que no se perciba como síntoma, signo o resultado clínico anómalo, e introducir términos que reflejen mucho mejor el estado de envejecimiento patológico. Entre los términos que gozan de un creciente soporte experimental y bibliográfico están “fragilidad” y “pérdida de la capacidad intrínseca”, que aportan mucha mayor precisión a la hora de definir la condición de la persona que no goza de un envejecimiento saludable.


[ABSTRACT]. Since 1948, the World Health Organization has been publishing the International Statistical Classification of Diseases and Related Health Problems (ICD), a coded system of causes of disease and death with an in-depth revision every 10-15 years. In its latest revision, the ICD-11 uses nomenclature characterizing old age as “initial and final geriatric periods,” implying the medicalization of this stage of life, which has created confusion and sparked controversy. This article discusses the new nomenclature proposed, given the current knowledge about old age and the aging process and its most accepted definition. The ICD not only classifies diseases but periods of life and “health-related problems,” and old age per se is not a health-related problem for many people at this stage of life. It is therefore essential to change or provide a more nuanced definition of the term “old age” in the ICD-11, so it is not perceived as a symptom, sign, or anomalous clinical outcome, and to introduce nomenclature that more accurately reflects pathological aging. Two terms that are enjoying growing experimental and bibliographic support are “fragility” and “loss of intrinsic capacity,” which offer grea-ter precision when defining the condition of a person who is not experiencing healthy aging.


[RESUMO]. Desde 1948, a Organização Mundial da Saúde publica um sistema codificado de causas de doença e morte sob o nome de Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde (CID), com revisões profundas a cada 10-15 anos. Sua última versão, a CID-11, utiliza determinada terminologia para caracterizar a velhice como “períodos geriátricos iniciais e finais”, o que implica uma medicalização dessa fase da vida que tem gerado confusão e polêmica. Este artigo discute a nova terminologia proposta à luz dos conhecimentos atuais sobre a velhice e o processo de envelhecimento, e sua definição mais aceita. A CID não classifica apenas as doenças, mas também períodos da vida e “problemas de saúde”, sendo que a velhice por si só não representa um problema de saúde para muitos que se encontram nesta fase da vida. A partir dessa perspectiva, é imprescindível alterar ou qualificar o verbete “velhice” da CID-11 para que não seja percebido como sintoma, sinal ou resultado clínico anormal, e em seu lugar introduzir termos que melhor reflitam o estado de envelhecimento patológico. Entre os termos que têm crescente suporte experimental e bibliográfico estão “fragilidade” e “perda de capacidade intrínseca”, que proporcionam uma precisão muito maior na definição da condição de quem não goza de um envelhecimento saudável.


Assuntos
Classificação Internacional de Doenças , Envelhecimento , Envelhecimento Saudável , Classificação Internacional de Doenças , Envelhecimento , Envelhecimento Saudável , Classificação Internacional de Doenças , Envelhecimento , Envelhecimento Saudável
3.
Biomed Chromatogr ; 35(10): e5188, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34081795

RESUMO

Cefuroxime (CFX) is a broad-spectrum second-generation cephalosporin and one of the best choices for antibiotic prophylaxis. However, when used in critically ill patients, it may present changes in its pharmacokinetic properties. Therefore, therapeutic drug monitoring of CFX is necessary for effective dosing strategies. A simple, rapid and sensitive liquid chromatographic method with UV detection was developed and validated for the quantification of CFX in plasma. The method involved a single-step precipitation of proteins with methanol and trifluoroacetic acid. Cefuroxime was analyzed on a Brisa LC2 C18 column in isocratic mode consisting of 0.1% trifluoroacetic acid in water and acetonitrile (75:25) with UV detection at a wavelength of 280 nm. The retention times of CFX and cephazolin (internal standard) were 9.8 and 7.4 min, respectively. The calibration curve was linear over a concentration range of 0.25-50 µg/ml. The limits of detection and quantification were 0.1 µg/ml and 0.25 µg/ml, respectively. The accuracy and precision were always <10%. The mean recovery was 93.52%. This fast and simple method could be applied in routine analysis and pharmacokinetic studies.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34067492

RESUMO

Core stability (CS) deficits can have a significant impact on lower limb function. The aim of this study was to investigate the relationship between two dynamic core exercise assessments and dynamic knee valgus during single-leg squats. In total, 20 physically active female students participated in this study. The OCTOcore smartphone application assesses CS during two dynamic exercise tests, the partial range single-leg deadlift (SLD) test and the bird-dog (BD) test. A two-dimensional assessment of a single-leg squat test was used to quantify participants' hip frontal angle (HFASLS) and knee frontal plane projection angle (FPPASLS). Ankle dorsiflexion was evaluated through the weight-bearing dorsiflexion test. The correlational analyses indicated that the HFASLS was significantly related to the partial range single-leg deadlift test (r = 0.314, p < 0.05) and ankle dorsiflexion (r = 0.322, p < 0.05). The results showed a significant difference (p < 0.05) in the CS test between cases categorised as dynamic knee valgus (>10°) and normal (≤10°). The CS deficit may influence the neuromuscular control of the lumbopelvic-hip complex during single-leg movements. The link between CS and kinematic factors related to knee injuries was only observed when CS was measured in the SLD test but not in the BD test.


Assuntos
Perna (Membro) , Postura , Animais , Fenômenos Biomecânicos , Cães , Feminino , Humanos , Joelho , Articulação do Joelho , Extremidade Inferior , Amplitude de Movimento Articular
5.
J Musculoskelet Neuronal Interact ; 21(1): 59-67, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657755

RESUMO

OBJECTIVES: The purpose of the current study was to firstly examine the effects of different whole-body vibration (WBV) frequencies in the lower-body muscles when applied simultaneously during a bridge exercise. Secondly, determine if there were any sex differences in the lower-body muscles of WBV during the bridge. METHODS: Seven females and 7 males completed 2 familiarization and 1 test sessions. In the test session participants were randomized to complete one 30 s bout of a bridge exercise for 3 separate conditions followed by 3-min of rest. The 3 conditions (a) No-WBV (without WBV); (b) WBV-30 (30 Hz, low amplitude); (c) WBV-50 (50 Hz, low amplitude) were performed on a WBV platform. Muscle activity of the biceps femoris (BF), semitendinosus (ST), gluteus maximus (Gmax), multifidus muscle (MF) muscles were measured. RESULTS: Muscle activity was increased with WBV in the BF and ST muscles at WBV-30 and WBV-50 conditions (p<0.05) vs. no-WBV. During No-WBV and WBV-50 conditions, males had a higher biceps femoris activity compared to females for (p<0.05) 45 and 27 %, respectively; however, during all conditions females had a high level of Gmax activity (57%) than males (p<0.05). CONCLUSION: Additional vibration at 30 and 50 Hz during the bridge exercise could be a useful method to enhance hamstring muscle activity.

6.
Transfus Apher Sci ; 60(2): 103052, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33483284

RESUMO

Plerixafor (Mozobil, Sanofi) is approved for using in patients with lymphoma and multiple myeloma when steady-state mobilization strategies fail. Although off-label use of plerixafor in healthy related donors (HRD) is known, limited data are available and no recommendations exist to guide its use in this setting. With the aim of collecting data from HRDs who received plerixafor in our country, we designed an observational case series study within the Spanish Group of Hematopoietic Transplant and Cell Therapy (GETH). Plerixafor was administered subcutaneously to 30 HRDs at a median dose of 0.24 mg/Kg (interquartile range (IQR): 0.23-0.25) because mobilization failure after using mobilization with G-CSF (mobilization failure was defined as collection of <4.0 × 106 CD34+ cells/Kg recipient). All HRDs received G-CSF at a median dose of 11 µg/Kg/day (IQR: 10-12) for 4-5 days. Leukocytapheresis after G-CSF mobilization was performed in 23 (77 %) HRDs collecting a median of 1.6 × 106 CD34+ cells/Kg recipient weight (IQR: 0.9-2.5). Addition of plerixafor allowed the collection of a higher median number of CD34 cells (4.98 × 106 CD34+ cells/Kg recipient weight (IQR: 3.5-5.8)) when compared with the collection of CD34+ cells with G-CSF alone (p < 0.01). The final median total number of CD34+ cells collected was 6.1 × 106/Kg recipient weight (IQR: 4.8-7.3). Mild adverse events related with plerixafor administration were reported in 8 (27 %) donors. In conclusion, addition of plerixafor after G-CSF mobilization failure in HRDs allowed collecting higher number of CD34+ cells in comparison with steady-state mobilization.

7.
Prev Vet Med ; 186: 105222, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33316583

RESUMO

Antimicrobial Resistance (AMR) is a global threat for human and animal health. Few studies have been carried out on laying hens. The aim of this work was to evaluate the antimicrobial susceptibility of commensal Campylobacter spp., E. coli, and Enterococcus spp. isolates in Spanish laying hens in 2018. Samples were collected from 39 laying hen farms. The microorganisms of interest were isolated and confirmed by PCR. The Minimum Inhibitory Concentration (MIC) to antimicrobials of C and D categories were determined. 195 E. coli, 195 Enterococcus spp. and 25 Campylobacter spp. isolates were obtained. E. coli isolates showed high resistance to D category antimicrobials (sulfamethoxazole 76.41 %, tetracycline 62.05 %, trimethoprim 50.77 %, ampicillin 30.77 %) and lower resistance to C category (azithromycin 30.26 %, gentamicin 12.31 %, chloramphenicol 4.62 %). A 10.26 % of E. coli isolates were susceptible to all antimicrobials tested, Multi Drug Resistance (MDR) to 3 antimicrobial families was found in 23.08 % of the isolates and 13.85 % were MDR to 4 families, being Erythromycin-Sulfamethoxazole-Tetracycline the most common resistance profile (10.77 %). Enterococcus spp. showed very high resistance to D category tetracycline (78.47 %) and C category erythromycin (76.42 %). The 11.79 % of Enterococcus spp. isolates were susceptible to all antimicrobials and 53.33 % were resistant to 2 families, being Erythromycin-Tetracycline the most common AMR profile (51.79 %). Regarding Campylobacter spp., resistance to tetracycline (48 %) was higher than resistance to C category antimicrobials (erythromycin 28 %, streptomycin 24 %, gentamicin 16 %). There was a 52 % sensitivity to all tested antimicrobials and 24 % showed MDR to aminoglycosides, macrolides and tetracyclines (Gentamicin-Streptomycin-Erythromycin-Tetracycline MDR profile). Novel data on AMR in laying hen commensal isolates in Spain was provided. High resistance to several antimicrobials was found, especially to key drugs for the treatment of zoonosis, which represents a public health risk. Better surveillance and careful regulation of antimicrobial use is required in laying hen production.


Assuntos
Antibacterianos/farmacologia , Campylobacter/efeitos dos fármacos , Galinhas/microbiologia , Farmacorresistência Bacteriana Múltipla , Enterococcus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Animais , Feminino , Espanha
9.
PLoS One ; 15(11): e0241778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33147257

RESUMO

BACKGROUND: Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT. METHODS: Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT. RESULTS: The incidence of NF among the groups was reduced (64%, 44%, and 24%; P<0.001), with a non-significant decrease in hospital readmissions as well (12%, 6%, and 2%; P = 0.07). The most important variables identified for NF were: HCT-CI >2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P<0.001); and for hospital readmission: age ≥60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05). CONCLUSIONS: G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial.


Assuntos
Corticosteroides/uso terapêutico , Febre/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mieloma Múltiplo/terapia , Readmissão do Paciente/estatística & dados numéricos , Transplante de Células-Tronco , Adulto , Fatores Etários , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Feminino , Febre/epidemiologia , Humanos , Incidência , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Razão de Chances , Intervalo Livre de Progressão , Fatores de Risco , Transplante de Células-Tronco/efeitos adversos , Transplante Autólogo
10.
J Vet Pharmacol Ther ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33107624

RESUMO

The present study aimed to assess the pharmacokinetic features of enrofloxacin (ENR) and its major metabolite, ciprofloxacin (CIP) in green sea turtles (Chelonia mydas) after single intravenous (i.v.) and intramuscular (i.m.) administration at two dosages of 5 and 7.5 mg/kg body weight (b.w.). The study used 10 animals randomly divided into equal groups. Blood samples were collected at assigned times up to 168 hr. The concentrations of ENR and CIP in turtle plasma were quantified by a validated high-performance liquid chromatography equipped with fluorescence detector (HPLC-FLD). The concentration of ENR in the experimental turtles with respect to time was pharmacokinetically analyzed using a noncompartment model. The concentrations of ENR in the plasma were quantified up to 144 hr after i.v. and i.m. administrations at dosages of 5 and 7.5 mg/kg b.w., whereas CIP was quantified up to 96 and 144 hr, respectively. The elimination half-life values of ENR were 38.7 and 50.4 hr at dose rates of 5 and 7.5 mg/kg b.w. after i.v. administration, whereas CIP was 33.6 and 22.6 hr, respectively. The maximum concentration (Cmax ) values of ENR were 2.07 and 2.59 µg/ml at dose rates of 5 and 7.5 mg/kg b.w., respectively. The value of area under the curve from 0 to 24 hr (AUC0-24 )/minimum inhibitory concentration (MIC) ratio of ENR was >125 for bacteria with MIC of 0.12 and 0.13 µg/ml after the administration of 5 mg/kg by i.m. and i.v. administration, respectively. Based on the pharmacokinetic data, susceptibility break-point and pharmacokinetic (PK)/pharmacodynamic (PD) indices, i.m. single administration of ENR at a dosage of 5 mg/kg b.w. might be clinically appropriate for treatment of susceptible bacteria in green sea turtles (Chelonia mydas).

11.
Animals (Basel) ; 10(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32752202

RESUMO

A single-dose disposition kinetics for tildipirosin was evaluated in clinically healthy ewes (n = 6) after intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration of a commercial formulation. Tildipirosin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Plasma concentration-time data was calculated by non-compartmental pharmacokinetic methods. The apparent volume of distribution (Vz) of tildipirosin after IV administration was 5.36 ± 0.57 L/kg suggesting a wide distribution in tissues and inside the cells. The elimination half-life (t½λz) was 17.16 ± 2.25, 23.90 ± 6.99 and 43.19 ± 5.17 h after IV, IM and SC administration, respectively. Following IM administration, tildipirosin was rapidly absorbed (tmax = 0.62 ± 0.10 h) even to a greater extent than after SC administration. Time to reach peak concentration (tmax) and peak plasma concentrations (Cmax) differed significantly, but both parameters showed a more significant variability after SC than after IM administration. Bioavailabilities after extravascular administration were high (>70%). Therefore, given general adverse reactions that were not observed in any ewe and favourable pharmacokinetics, tildipirosin could be effective in treating bacterial infections in sheep.

12.
J Strength Cond Res ; 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32732776

RESUMO

Soriano, MA, García-Ramos, A, Calderbank, J, Marín, PJ, Sainz de Baranda, P, and Comfort, P. Does sex impact the differences and relationships in the one repetition maximum performance across weightlifting overhead pressing exercises? J Strength Cond XX(X): 000-000, 2020-This study aimed to determine the impact of sex on the differences and relationships of the one repetition maximum (1RM) performance between 3 overhead pressing exercises (push press [PP], push jerk [PJ] and split jerk [SJ]). 15 men (body mass [BM]: 82.3 ± 9.9 kg; weightlifting training experience: 2.6 ± 1.6 years) and 15 women (BM: 64.4 ± 7.0 kg; weightlifting training experience: 2.2 ± 1.4 years) participated in this study. A ratio-scaled (1RM·BM) was used for the comparison between them. The 1RM of the 3 exercises were evaluated within the same testing session using a combined 1RM assessment method. The interaction effect of exercise and sex did not reach statistical significance (p = 0.671; η = 0.001). In contrast, there were significant main effects of exercise (p ≤ 0.01) and sex (p < 0.001) with medium (η = 0.096) and large effect sizes (η = 0.306), respectively. A similar main effect of exercise was reported for both men (PP [1.0 ± 0.1 kg·kg] < PJ [1.1 ± 0.2 kg·kg] ∼ SJ [1.2 ± 0.2 kg·kg]) and women (PP [0.8 ± 0.1 kg·kg] < PJ [0.9 ± 0.2 kg·kg] ∼ SJ [0.9 ± 0.2 kg·kg]). The 1RM performance of the 3 exercises was significantly correlated for men (r [range] = 0.856-0.963) and women (r [range] = 0.636-0.925). Sex does not affect the differences in the 1RM performance across weightlifting overhead pressing exercises. However, stronger correlations and lower variation in the 1RM performance during the PP, PJ, and SJ are expected for men compared with women.

13.
PLoS One ; 15(7): e0235905, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697809

RESUMO

BACKGROUND: Whole-body vibration (WBV) is a method utilizing vibrating platforms to expose individuals to mechanical vibration. In its various applications, it has been linked to improved muscular, skeletal, metabolic, or cognitive functioning, quality of life, and physiological parameters such as blood pressure. Most evidence concerning WBV is inconclusive and meta-analytical reviews may not readily produce insights since the research has a risk of misunderstandings of vibration parameters and incomplete reporting occurs. This study aims at laying an empirical foundation for reporting guidelines for human WBV studies to improve the quality of reporting and the currently limited comparability between studies. METHOD: The Delphi methodology is employed to exploit the integrated knowledge of WBV experts to distil the specific aspects of WBV methodology that should be included in such guidelines. Over three rounds of completing online questionnaires, the expert panel (round 1/2/3: 51/40/37 experts respectively from 17 countries with an average of 19.4 years of WBV research experience) rated candidate items. RESULTS: A 40-item list was established based on the ratings of the individual items from the expert panel with a large final consensus (94.6%). CONCLUSION: The final consensus indicates comprehensiveness and valuableness of the list. The results are in line with previous guidelines but expand these extensively. The present results may therefore serve as a foundation for updated guidelines for reporting human WBV studies in order to improve the quality of reporting of WBV studies, improve comparability of studies and facilitate the development of WBV study designs.


Assuntos
Modalidades de Fisioterapia , Vibração/uso terapêutico , Adulto , Idoso , Técnica Delfos , Prova Pericial , Feminino , Corpo Humano , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa , Inquéritos e Questionários
14.
J Immunother Cancer ; 8(1)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32527933

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a hematopoietic malignancy which is biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies for patients with refractory or relapse (R/R) AML are challenging because of the absence of a universal pan-AML target antigen and the shared expression of target antigens with normal hematopoietic stem/progenitor cells (HSPCs), which may lead to life-threating on-target/off-tumor cytotoxicity. CD33-redirected and CD123-redirected CARTs for AML are in advanced preclinical and clinical development, and they exhibit robust antileukemic activity. However, preclinical and clinical controversy exists on whether such CARTs are myeloablative. METHODS: We set out to comparatively characterize in vitro and in vivo the efficacy and safety of 41BB-based and CD28-based CARCD123. We analyzed 97 diagnostic and relapse AML primary samples to investigate whether CD123 is a suitable immunotherapeutic target, and we used several xenograft models and in vitro assays to assess the myeloablative potential of our second-generation CD123 CARTs. RESULTS: Here, we show that CD123 represents a bona fide target for AML and show that both 41BB-based and CD28-based CD123 CARTs are very efficient in eliminating both AML cell lines and primary cells in vitro and in vivo. However, both 41BB-based and CD28-based CD123 CARTs ablate normal human hematopoiesis and prevent the establishment of de novo hematopoietic reconstitution by targeting both immature and myeloid HSPCs. CONCLUSIONS: This study calls for caution when clinically implementing CD123 CARTs, encouraging its preferential use as a bridge to allo-HSCT in patients with R/R AML.

15.
Sports Biomech ; : 1-27, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32336212

RESUMO

The assessment of the mechanical power production is of great importance for researchers and practitioners. The purpose of this review was to compare the differences in ground reaction force (GRF), kinematic, and combined (bar velocity x GRF) methods to assess mechanical power production during weightlifting exercises. A search of electronic databases was conducted to identify all publications up to 31 May 2019. The peak power output (PPO) was selected as the key variable. The exercises included in this review were clean variations, which includes the hang power clean (HPC), power clean (PC) and clean. A total of 26 articles met the inclusion criteria with 53.9% using the GRF, 38.5% combined, and 30.8% the kinematic method. Articles were evaluated and descriptively analysed to enable comparison between methods. The three methods have inherent methodological differences in the data analysis and measurement systems, which suggests that these methods should not be used interchangeably to assess PPO in Watts during weightlifting exercises. In addition, this review provides evidence and rationale for the use of the GRF to assess power production applied to the system mass while the kinematic method may be more appropriate when looking to assess only the power applied to the barbell.

17.
Leuk Lymphoma ; 61(7): 1565-1574, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32208787

RESUMO

Despite the use of fluoroquinolone (FQ) prophylaxis, neutropenic fever (NF) is the most frequent cause of hospital readmission in ambulatory care programs for patients treated with autologous stem cell transplantation (ASCT). We analyzed the impact of intensifying primary prophylaxis with the addition of piperacillin/tazobactam (PT) to FQ. Between January 2002 and August 2018, 154 lymphoma patients conditioned with BEAM were included (40% received ceftriaxone (Ct) plus FQ and 60% PT plus FQ). NF and hospital readmission were required in 84 vs. 41% (p < .0001) and 12 vs. 1% (p = .007) of patients within the Ct and PT groups, respectively. The multivariate analysis showed that PT plus FQ retained its independent protective factor for NF (odds ratio (OR): 0.13; p < .001) and for hospital readmission (OR: 0.07; p = .01). The use of PT and FQ prophylaxis may effectively prevent episodes of NF and hospitalizations in lymphoma patients managed in our at-home ASCT care model.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfoma/tratamento farmacológico , Transplante Autólogo
18.
Sensors (Basel) ; 20(5)2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32110939

RESUMO

The aim of this study was to evaluate changes in electromyographic activity with the use of gradual compression stockings (GCSs) on middle-distance endurance athletes' performance, based on surface electromyography measurement techniques. Sixteen well-trained athletes were recruited (mean ± SD: age 33.4 ± 6.3 years, VO2max 63.7 ± 6.3 mL·kg-1·min-1, maximal aerobic speed 19.7 ± 1.5 km·h). The athletes were divided into two groups and were assigned in a randomized order to their respective groups according to their experience with the use of GCSs. Initially, a maximum oxygen consumption (VO2max) test was performed to standardize the athletes' running speeds for subsequent tests. Afterward, electromyographic activity, metabolic, and performance variables for each group were measured with surface electromyography. In addition, blood lactate concentration was measured, both with and without GCSs, during 10 min at 3% above VT2 (second ventilatory threshold), all of which were performed on the track. Next, surface electromyography activity was measured during a 1 km run at maximum speed. No significant changes were found in electromyography activity, metabolic and performance variables with GCSs use (p > 0.164) in any of the variables measured. Overall, there were no performance benefits when using compression garments against a control condition.


Assuntos
Atletas , Músculos/fisiologia , Corrida/fisiologia , Meias de Compressão , Adulto , Eletromiografia , Feminino , Humanos , Perna (Membro)/fisiologia , Masculino
19.
Int J Sports Physiol Perform ; 15(6): 862-867, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32150725

RESUMO

OBJECTIVE: To (1) compare the 1-repetition-maximum (1RM) performance between the push press, push jerk, and split jerk and (2) explore these differences between weightlifters, CrossFit athletes, and a mixed group of athletes. METHODS: Forty-six resistance-trained males (age 28.8 [6.4] y; height 180.0 [6.0] cm; body mass 84.1 [10.2] kg; weightlifting training experience 3.64 [3.14] y) participated in this study. The 1RM performance of the push press, push jerk, and split jerk was assessed during the same session in a sequential order (ie, combined 1RM assessment method). Thirty-six participants were retested to determine between-sessions reliability of the 1RM values. RESULTS: Intraclass correlation coefficients (ICCs) and associated 95% confidence intervals (CIs) showed a high between-sessions reliability for the push press (ICC = .98; 95% CI, .95-.99), push jerk (ICC = .99; 95% CI, .98-1.00), and split jerk (ICC = .99; 95% CI, .98-1.00). There was a significant main effect of exercise (η2 = .101) and exercise × group interaction (η2 = .012) on 1RM performance (P < .001), whereas the main effect of group did not reach statistical significance (P = .175). CONCLUSIONS: This study provides evidence that the weightlifting overhead press derivatives affect 1RM performance. In addition, the interaction of exercise and sport group was caused by the higher differences in 1RM performance between exercises for weightlifters compared with CrossFit and a mixed group of athletes. Therefore, strength and conditioning professionals should be aware that the differences in 1RM performance between weightlifting overhead-press derivatives may be affected by sport group.


Assuntos
Teste de Esforço/métodos , Treinamento de Força/classificação , Treinamento de Força/métodos , Levantamento de Peso/fisiologia , Adulto , Humanos , Masculino , Força Muscular/fisiologia , Reprodutibilidade dos Testes , Adulto Jovem
20.
Transfusion ; 60(4): 779-785, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32064638

RESUMO

BACKGROUND: Plerixafor should be administered 6 to 11 hours before starting leukocytapheresis. However, we have been using plerixafor followed by leukocytapheresis according to different time schedules since 2007. Our objective was to compare the CD34+ cell collection efficiency (CE1) of the first leukocytapheresis performed after using plerixafor at different time intervals. STUDY DESIGN AND METHODS: Same-day schedule refers to the administration of plerixafor at 10:00 AM and starting the leukocytapheresis on the same day at 4:00 PM (6 hours interval). Next-day schedule refers to the administration of plerixafor at 8:00 PM and starting the leukocytapheresis on the next day (10:00 AM or 4:00 PM; either a 14- or 20-hr interval). Variables that might influence the CE1 of CD34+ cells were analyzed by longitudinal linear regression with a random effects model derived by generalized estimating equations. RESULTS: The median CE1 of CD34+ cells was higher in the group of 30 patients who underwent leukocytapheresis on the same day when compared with the group of 62 patients who underwent leukocytapheresis on the next day (65.8% vs. 56.7%; p < 0.01). In the longitudinal linear regression analysis, only the time from plerixafor administration to leukocytapheresis start was associated with a statistically significant decrease in the CE1 of CD34+ cells (CE1 change -0.034%; p < 0.01). CONCLUSION: Higher CE1 of CD34+ cells was observed when patients underwent leukocytapheresis on the same day after receiving plerixafor in comparison with administering plerixafor and underwent leukocytapheresis on the next day. Larger studies are necessary to confirm present results.


Assuntos
Antígenos CD34/análise , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Leucaférese/métodos , Fatores de Tempo , Esquema de Medicação , Compostos Heterocíclicos/farmacologia , Humanos
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