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1.
Sensors (Basel) ; 21(3)2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33498590

RESUMEN

Wandering is a common behavioral disorder in the community-dwelling elderly. More than two-thirds of caregivers believe that wandering would cause falls. While physical restraint is a common measure to address wandering, it could trigger challenging behavior in approximately 80% of the elderly with dementia. This study aims to develop a virtual restraint using a night monitoring system (eNightLog) to provide a safe environment for the elderly and mitigate the caregiver burden. The eNightLog system consisted of remote sensors, including a near infra-red 3D time-of-flight sensor and ultrawideband sensors. An alarm system was controlled by customized software and algorithm based on the respiration rate and body posture of the elderly. The performance of the eNightLog system was evaluated in both single and double bed settings by comparing to that of a pressure mat and an infrared fence system, under simulated bed-exiting scenarios. The accuracy and precision for the three systems were 99.0%, 98.8%, 85.9% and 99.2%, 97.8%, 78.6%, respectively. With higher accuracy, precision, and a lower false alarm rate, eNightLog demonstrated its potential as an alternative to physical restraint to remedy the workload of the caregivers and the psychological impact of the elderly.


Asunto(s)
Monitoreo Fisiológico , Conducta Errante , Accidentes por Caídas , Anciano , Cuidadores , Humanos , Vida Independiente
2.
Hemoglobin ; 43(1): 1-3, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30879337

RESUMEN

Purulent pericarditis is a localized infection with a thick, fibrinous hypercellular exudate and is historically associated with a high mortality. We describe a case of purulent pericarditis due to Streptococcus agalactiae (S. agalactiae) in a 30-year-old woman with sickle cell disease who presented with fever, dyspnea, and S. agalactiae septicemia. Despite timely initiation of antibiotics, she developed a large purulent pericardial effusion requiring surgical pericardiocentesis followed by a pericardial window. At 14 months follow-up, she has remained asymptomatic without sequelae. A review of the literature contained only four patients with purulent pericarditis in sickle cell patients. We discuss the unique aspects of this case in the context of purulent pericarditis in the age of modern antibiotics and hypothesize on the pathogenesis of delayed pericardial effusion after pericarditis.


Asunto(s)
Anemia de Células Falciformes/complicaciones , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/etiología , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae , Adulto , Animales , Biomarcadores , Terapia Combinada , Ecocardiografía , Femenino , Humanos , Derrame Pericárdico/terapia , Pericardiocentesis , Radiografía Torácica , Evaluación de Síntomas , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
3.
Biomed Eng Online ; 17(1): 91, 2018 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-29941043

RESUMEN

BACKGROUND: Rehabilitation robots can provide intensive physical training after stroke. However, variations of the rehabilitation effects in translation from well-controlled research studies to clinical services have not been well evaluated yet. This study aims to compare the rehabilitation effects of the upper limb training by an electromyography (EMG)-driven robotic hand achieved in a well-controlled research environment and in a practical clinical service. METHODS: It was a non-randomized controlled trial, and thirty-two participants with chronic stroke were recruited either in the clinical service (n = 16, clinic group), or in the research setting (n = 16, lab group). Each participant received 20-session EMG-driven robotic hand assisted upper limb training. The training frequency (4 sessions/week) and the pace in a session were fixed for the lab group, while they were flexible (1-3 sessions/week) and adaptive for the clinic group. The training effects were evaluated before and after the treatment with clinical scores of the Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), Functional Independence Measure (FIM), and Modified Ashworth Scale (MAS). RESULTS: Significant improvements in the FMA full score, shoulder/elbow and wrist/hand (P < 0.001), ARAT (P < 0.001), and MAS elbow (P < 0.05) were observed after the training for both groups. Significant improvements in the FIM (P < 0.05), MAS wrist (P < 0.001) and MAS hand (P < 0.05) were only obtained after the training in the clinic group. Compared with the lab group, higher FIM improvement in the clinic group was observed (P < 0.05). CONCLUSIONS: The functional improvements after the robotic hand training in the clinical service were comparable to the effectiveness achieved in the research setting, through flexible training schedules even with a lower training frequency every week. Higher independence in the daily living and a more effective release in muscle tones were achieved in the clinic group than the lab group.


Asunto(s)
Electromiografía , Laboratorios , Robótica , Rehabilitación de Accidente Cerebrovascular/métodos , Extremidad Superior , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
4.
J Interprof Care ; 32(2): 203-210, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29182406

RESUMEN

Student-run free clinics (SRFCs) have become important contributors not only to improve access to primary-care services for homeless and uninsured populations but also to enhance health sciences student education. In order for SRFCs to reliably provide high quality healthcare services and educationally benefit students, it is imperative to assess client perceptions of the quality of care provided. The objective of this study was to evaluate the delivery of healthcare services through a client satisfaction questionnaire at the University of California, Los Angeles Mobile Clinic Project (UCLA MCP). From 2012 to 2015, 194 questionnaires that addressed demographic information, satisfaction with services and client outcomes were analysed. Satisfaction scores were evaluated on a four-point scale and differences in the composite satisfaction scores were assessed using Mann-Whitney U-tests. Half (50%) of the client respondents report that UCLA MCP is their primary source of health care (MCP primary care clients), while 81.3% reported that the clinic improved access to other healthcare resources. Overall, clients are highly satisfied with their experiences (Range: 3.5-3.9) and 62% have recommended our services to others. While MCP primary-care clients report significantly higher satisfaction scores than non-primary-care clients on average (p < 0.01), the mean composite scores for all subgroups are consistently high. The UCLA MCP clients perceive the clinic to provide high-quality healthcare services. This article presents a framework that may help other SRFCs evaluate clients' perception of the quality of their care, an essential building block for effective physician-client relationships.


Asunto(s)
Satisfacción del Paciente , Calidad de la Atención de Salud/organización & administración , Clínica Administrada por Estudiantes/organización & administración , Actitud del Personal de Salud , Femenino , Humanos , Los Angeles , Masculino , Seguridad del Paciente , Calidad de la Atención de Salud/normas , Clínica Administrada por Estudiantes/normas , Factores de Tiempo , Confianza
5.
Inorg Chem ; 56(5): 3087-3094, 2017 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-28211684

RESUMEN

The reactivity of germanium phosphanido complexes with elemental chalcogens is reported. Addition of sulfur to [(BDI)GePCy2] (BDI = CH{(CH3)CN-2,6-iPr2C6H3}2) results in oxidation at germanium to form germanium(IV) sulfide [(BDI)Ge(S)PCy2] and oxidation at both germanium and phosphorus to form germanium(IV) sulfide dicylohexylphosphinodithioate complex [(BDI)Ge(S)SP(S)Cy2], whereas addition of tellurium to [(BDI)GePCy2] only gives the chalcogen inserted product, [(BDI)GeTePCy2]. This reactivity is different from that observed between [(BDI)GePCy2] and selenium. Addition of selenium to the diphenylphosphanido germanium complex, [(BDI)GePPh2], results in insertion of selenium into the Ge-P bond to form [(BDI)GeSePCy2] as well as the oxidation at phosphorus to give [(BDI)GeSeP(Se)Ph2]. In contrast, addition of selenium to the bis(trimethylsilyl)phosphanido germanium complex, [(BDI)GeP(SiMe3)2], yields the germanium(IV) selenide [(BDI)Ge(Se)P(SiMe3)2].

6.
Inorg Chem ; 56(24): 14831-14841, 2017 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-29189007

RESUMEN

The reactivity of tin and lead phosphanido complexes with chalogens is reported. The addition of sulfur to [(BDI)MPCy2] (M = Sn, Pb; BDI = CH{(CH3)CN-2,6-iPr2C6H3}2) results in the formation of phosphinodithioates [(BDI)MSP(S)Cy2] regardless of the conditions; however, when selenium is added to [(BDI)MPCy2], a selenium insertion product, phosphinoselenoite [(BDI)MSePCy2], can be isolated. This compound readily reacts with additional selenium to form the phosphinodiselenoate complex [(BDI)MSeP(Se)Cy2]. In contrast, the addition of selenium to [(BDI)SnP(SiMe3)2] results in the formation of the heavy ether [(BDI)SnSeSiMe3]. Differences in the solution and solid-state molecular species of tin phosphinoselenoite and phosphinodiselenoate complexes were probed using multinuclear solution and solid-state NMR spectroscopy.

8.
Arch Phys Med Rehabil ; 97(4): 536-544, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26694578

RESUMEN

OBJECTIVES: To investigate (1) the intrarater, interrater, and test-retest reliability of the timed 360° turn test in subjects with stroke; (2) the concurrent validity of the timed 360° turn test by exploring its correlation with other measures of stroke-specific impairments; and (3) the cutoff times that best discriminate individuals with stroke from healthy older adults. DESIGN: Cross-sectional study. SETTING: University-based rehabilitation center. PARTICIPANTS: Individuals with chronic stroke (n=72) and healthy individuals (n=35) of similar age (N=107). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The timed 360° turn test was administered along with the Fugl-Meyer assessment of the lower extremity, measurement of muscle strength of ankle dorsiflexors and plantarflexors using a handheld dynamometer, Berg Balance Scale, limit of stability test, five times sit-to-stand (FTSTS) test, 10-m walk test, and timed Up and Go (TUG) test. RESULTS: The 360° turn times showed excellent intrarater, interrater, and test-retest reliability in individuals with stroke. A minimal detectable change of .76 seconds was found for subjects turning toward the affected side and 1.22 seconds for subjects turning toward the unaffected side. The 360° turn times were found to correlate significantly with Fugl-Meyer assessment of the lower extremity scores, dosiflexor strength of the affected ankle, plantarflexor strength of both ankles, FTSTS test times, balance performance, gait speed, and TUG test times. The 360° turn times of 3.43 to 3.49 seconds were shown to discriminate reliably between individuals with stroke and healthy older adults. CONCLUSIONS: The timed 360° turn test is a reliable and an easily administered clinical tool to assess the turning ability of subjects with chronic stroke.


Asunto(s)
Evaluación de la Discapacidad , Prueba de Esfuerzo/métodos , Accidente Cerebrovascular/fisiopatología , Anciano , Articulación del Tobillo , Estudios de Casos y Controles , Enfermedad Crónica , Estudios Transversales , Femenino , Marcha/fisiología , Voluntarios Sanos , Humanos , Extremidad Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Dinamómetro de Fuerza Muscular , Músculo Esquelético/fisiopatología , Variaciones Dependientes del Observador , Paresia/etiología , Paresia/fisiopatología , Reproducibilidad de los Resultados , Accidente Cerebrovascular/complicaciones , Factores de Tiempo , Caminata/fisiología
9.
J Phys Ther Sci ; 27(6): 1839-45, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26180332

RESUMEN

[Purpose] This study investigated the intra-rater, inter-rater and test-retest reliability of the sideways step test (SST), its correlation with other indicators of stroke-specific impairment, and the cut-off count best discriminating subjects with stroke from their healthy counterparts. [Subjects and Methods] Forty-three subjects with chronic stroke and 41 healthy subjects older than 50 years participated in this study. The SST was administered along with the Fugl-Meyer motor assessment for the lower extremities (FMA-LE), the five-times sit to stand (5TSTS) test, the Berg Balance Scale (BBS), the movement velocity (MVL) by the limits of stability (LOS) test, the ten-metre walk (10mW) test, the timed "Up and Go" (TUG) test and the Activities-specific Balance Confidence (ABC) scale. [Results] The SST showed good to excellent intra-rater, inter-rater and test-retest reliability. The SST counts correlated with 5TSTS times, 10mW times, TUG times, and the FMA-LE and BBS scores. SST counts of 11 for the paretic leg and 14 for the non-paretic leg were found to distinguish the healthy adults from subjects with stroke. [Conclusion] The sideways step test is a reliable clinical test, which correlates with the functional strength, gait speed, and functional balance of people with chronic stroke.

10.
Nat Cell Biol ; 9(8): 893-904, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17618273

RESUMEN

Invasive cell migration through tissue barriers requires pericellular remodelling of extracellular matrix (ECM) executed by cell-surface proteases, particularly membrane-type-1 matrix metalloproteinase (MT1-MMP/MMP-14). Using time-resolved multimodal microscopy, we show how invasive HT-1080 fibrosarcoma and MDA-MB-231 breast cancer cells coordinate mechanotransduction and fibrillar collagen remodelling by segregating the anterior force-generating leading edge containing beta1 integrin, MT1-MMP and F-actin from a posterior proteolytic zone executing fibre breakdown. During forward movement, sterically impeding fibres are selectively realigned into microtracks of single-cell calibre. Microtracks become expanded by multiple following cells by means of the large-scale degradation of lateral ECM interfaces, ultimately prompting transition towards collective invasion similar to that in vivo. Both ECM track widening and transition to multicellular invasion are dependent on MT1-MMP-mediated collagenolysis, shown by broad-spectrum protease inhibition and RNA interference. Thus, invasive migration and proteolytic ECM remodelling are interdependent processes that control tissue micropatterning and macropatterning and, consequently, individual and collective cell migration.


Asunto(s)
Movimiento Celular/fisiología , Matriz Extracelular/metabolismo , Metaloproteinasa 14 de la Matriz/metabolismo , Invasividad Neoplásica , Actinas/metabolismo , Animales , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Forma de la Célula , Colágeno/metabolismo , Femenino , Fibrosarcoma/metabolismo , Fibrosarcoma/patología , Humanos , Integrina beta1/metabolismo , Metaloproteinasa 14 de la Matriz/genética , Microscopía/métodos , Inhibidores de Proteasas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo
11.
J Org Chem ; 79(17): 8059-66, 2014 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-25122518

RESUMEN

The key cyclopentenyl intermediate 11b was synthesized in 4 steps from d-ribose in 41% overall yield via an efficient intramolecular Baylis-Hillman reaction. This novel key intermediate can be modified easily and transformed to neplanocin A (1a) and its 3'-epimer (1b).


Asunto(s)
Adenosina/análogos & derivados , Ciclopentanos/química , Adenosina/síntesis química , Adenosina/química , Catálisis , Técnicas Químicas Combinatorias , Estructura Molecular , Estereoisomerismo
12.
Jpn J Clin Oncol ; 49(7): 691-692, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31135905
13.
Clin Ophthalmol ; 18: 1295-1312, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38751993

RESUMEN

Purpose: To investigate the safety and effectiveness of micropulse transscleral cyclophotocoagulation (MPTSCPC) in non-incisional eyes with ocular hypertension (OHT) and early, moderate, and severe primary open-angle glaucoma (POAG). Methods: Retrospective cohort study of eyes that underwent MPTSCPC from 2016 to 2019 at an outpatient clinic in Canada. Eyes were excluded if any incisional procedures, except cataract surgery, were performed prior to MPTSCPC treatment. Laser power ranged from 900 to 2500mW. Results: A total of 153 eyes from 93 patients were included (OHT n=22; early POAG n=46; moderate POAG n=35; severe POAG n=50). The baseline IOP was 18.37 ± 4.76mmHg in the total cohort. All cohorts experienced a significant mean IOP reduction by final follow-up (total p<0.001; OHT p=0.003; early POAG p<0.001; moderate POAG p=0.022; severe POAG p=0.015). Overall, 52.9% of eyes achieved an IOP reduction of ≥20% from baseline to final follow-up (OHT 59.1%; early POAG 58.7%; moderate POAG 45.7%; severe POAG 50.0%). There was worsening in best-corrected visual acuity in the total cohort (mean difference=0.11 ± 0.36 logMAR, p=0.11), mostly attributable to cataract progression (34.1% of phakic eyes) and ocular surface disease (7.2%). The number of topical medications and drug classes remained unchanged in the total cohort (p=0.425 and p=0.791, respectively). Twenty-two eyes (14.4%) required retreatment, which provided an additional IOP reduction of 1.26mmHg (p=0.344). By final follow-up, 8 eyes (5.2%) required escalation to incisional procedures. Conclusion: MPTSCPC is a safe and effective adjunct IOP-lowering treatment in non-incisional eyes with OHT and POAG.

14.
J Cataract Refract Surg ; 50(2): 160-166, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37847109

RESUMEN

PURPOSE: To evaluate the effect of femtosecond laser-assisted cataract surgery (FLACS) and manual cataract surgery (MCS) on proinflammatory cytokine expression in patients with diabetes vs nondiabetic patients. SETTING: Outpatient surgical center in Vaughan, Ontario, Canada. DESIGN: Prospective cohort study. METHODS: Patients with diabetes and nondiabetic patients undergoing noncomplicated MCS or FLACS were assigned into 4 cohorts: MCS nondiabetic (n = 30), FLACS nondiabetic (n = 42), MCS diabetic (n = 40), and FLACS diabetic (n = 40). Aqueous humor inflammatory mediator concentrations were evaluated at MCS onset and after femtosecond laser treatment. The presence of cystoid macular edema, anterior chamber (AC) inflammation, central retinal thickness, macular volume, and retinal microvascular changes (through optical coherence tomography angiography) were evaluated preoperatively and on postoperative day 1, week 1, month 1 (POM1), and month 3 (POM3). RESULTS: Patients with diabetes receiving FLACS had a higher concentration of interleukin (IL)-7, IL-13, and interferon-induced protein-10 than MCS diabetic patients; they also demonstrated higher levels of vascular endothelial growth factor and lower levels of interferon (IFN)-γ, granulocyte colony-stimulating factor, and IFN-α2 compared with MCS nondiabetic patients. Macular volume appeared to be significantly higher in MCS diabetic vs MCS non-diabetic patients at POM1 and between FLACS diabetic vs FLACS nondiabetic patients at POM3. There were no other significant differences between the cohorts for any parameter. CONCLUSIONS: FLACS use in patients with diabetes demonstrated some differences in AC cytokine expression compared with non-diabetic FLACS or diabetic patients undergoing MCS; however, there was no increase in clinical inflammatory biomarkers. FLACS seems to be a safe technique to use in patients with diabetes.


Asunto(s)
Extracción de Catarata , Catarata , Diabetes Mellitus , Terapia por Láser , Edema Macular , Facoemulsificación , Humanos , Edema Macular/etiología , Facoemulsificación/métodos , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Terapia por Láser/métodos , Extracción de Catarata/métodos , Cámara Anterior , Citocinas , Rayos Láser , Interferones , Ontario
15.
BMJ Open Ophthalmol ; 9(1)2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38199790

RESUMEN

INTRODUCTION: Artificial intelligence (AI) development has led to improvements in many areas of medicine. Canada has workforce pressures in delivering cataract care. A potential solution is using AI technology that can automate care delivery, increase effectiveness and decrease burdens placed on patients and the healthcare system. This study assesses the use of 'Dora', an example of an AI assistant that is able to deliver a regulated autonomous, voice-based, natural-language consultation with patients over the telephone. Dora is used in routine practice in the UK, but this study seeks to assess the safety, usability, acceptability and cost-effectiveness of using the technology in Canada. METHODS AND ANALYSIS: This is a two-phase prospective single-centred trial. An expected 250 patients will be recruited for each phase of the study. For Phase I of the study, Dora will phone patients at postoperative week 1 and for Phase II of the study, Dora will phone patients within 24hours of their cataract surgery and again at postoperative week 1. We will evaluate the agreement between Dora and a supervising clinician regarding the need for further review based on the patients' symptoms. A random sample of patients will undergo the System Usability Scale followed by an extended semi-structured interview. The primary outcome of agreement between Dora and the supervisor will be assessed using the kappa statistic. Qualitative data from the interviews will further gauge patient opinions about Dora's usability, appropriateness and level of satisfaction. ETHICS AND DISSEMINATION: Research Ethics Board William Osler Health System (ID: 22-0044) has approved this study and will be conducted by guidelines of Declaration of Helsinki. Master-linking sheet will contain the patient chart identification (ID), full name, date of birth and study ID. Results will be shared through peer-reviewed journals and presentations at conferences.


Asunto(s)
Inteligencia Artificial , Catarata , Humanos , Estudios Prospectivos , Cuidados Posoperatorios , Estudios de Factibilidad
16.
Front Oncol ; 14: 1329893, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410106

RESUMEN

Graft-versus-host disease (GVHD) is a common complication in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized as either acute or chronic based on symptomatology and histopathological findings. Despite advancements in disease-targeting therapeutics, steroid-refractory GVHD remains a significant contributor to mortality in HSCT recipients, highlighting the gaps in our understanding of its pathophysiology and treatment strategies. We present the case of a 46-year-old woman diagnosed with acute undifferentiated leukemia, who exhibited persistently elevated levels of serum total bilirubin (T.Bili), alkaline phosphatase (ALP), and liver function tests (LFTs) beginning on [day +201] post-haploidentical peripheral blood stem cell (PBSC) transplantation. The patient received fludarabine/total body irradiation (Flu/TBI) as a myeloablative conditioning regimen and post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) as GVHD prophylaxis. A liver biopsy confirmed the diagnosis of GVHD, while other possible etiologies were excluded by corresponding tests. Initial treatment with prednisone and tacrolimus, and the later addition of ruxolitinib, all showed poor response indicated by worsening T.Bili, ALP, and LFTs at the same time. Based on a multidisciplinary comprehensive assessment, we decided to administer 1,000 mg/m2 (1,600 mg) of cyclophosphamide ("pulse Cy"), which resulted in a dramatic improvement in T.Bili and transaminases starting from the very next day. A durable response to pulse cyclophosphamide was observed, as all indicators normalized ("complete response") within 55 days without relapses. The patient remains in good health with no recurrence of hepatic GVHD. To our knowledge, this is the first case in which Grade IV hepatic GVHD, refractory to multiple agents including steroids, tacrolimus, and ruxolitinib, demonstrated a complete response to pulse cyclophosphamide. The success highlights the potential therapeutic role of cyclophosphamide, a potent and cost-effective chemotherapy agent, in treating multi-agent-refractory GVHD. Large-scale clinical trials are warranted to validate its efficacy in this setting.

17.
Clin Lymphoma Myeloma Leuk ; 24(3): e59-e66.e2, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38061959

RESUMEN

INTRODUCTION: Detection of measurable residual disease (MRD) in adults with acute lymphoblastic leukemia (ALL) is a vital biomarker in risk prediction and treatment selection. Next-generation sequencing (NGS) offers greater sensitivity relative to multiparametric flow cytometry (MFC) and may be a better predictive tool for identifying ALL patients at risk of relapse. PATIENTS AND METHODS: This single-center retrospective study compares MRD detection by NGS versus MFC in 52 adult B- and T-ALL patients treated at our institution between 2018 and 2023. Pretreatment bone marrow samples were used for assay calibration, while post-treatment MRD assessment was completed up to 4.5 months after the first complete remission (CR1) using an MRD cutoff of 10-6 for distinguishing relapse risk. RESULTS: The 2-year cumulative incidence of relapse (CIR) among patients who were MRD positive using MFC and NGS was 39.5% and 46.2%, respectively. Unlike MFC, post-CR1 MRD positivity with NGS significantly predicted CIR (HR = 9.47, P = .028). In patients who were MRD negative by MFC, low levels of MRD detected by NGS distinguished patients at high risk of relapse (HR 10.3, P = .026, 2-year CIR 51.6%). CONCLUSION: Our data suggests that assessment of post-CR1 MRD using a highly sensitive NGS assay can identify ALL patients undergoing frontline therapy at increased risk of relapse and guide the use of adjuvant therapy.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Estudios Retrospectivos , Citometría de Flujo , Enfermedad Aguda , Recurrencia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Neoplasia Residual/diagnóstico , Neoplasia Residual/terapia , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Trasplante de Células Madre Hematopoyéticas/métodos
18.
Leuk Res ; 141: 107501, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38631149

RESUMEN

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a pivotal treatment for high-risk acute lymphocytic leukemia (ALL), although limited by suitable human leukocyte antigen (HLA)-matched sibling donors (MSD). This study evaluates the impact of donor selection on outcomes in post-HSCT Hispanic B-cell ALL patients. METHODOLOGY: This single-center retrospective study evaluates outcomes in 88 adult Hispanic B-cell ALL patients who underwent haploidentical, MSD, or MUD myeloablative HSCT between 2013 and 2023. RESULTS: Compared to Haploidentical transplants, MSD exhibited worse cumulative incidence of relapse (CIR) (HR = 3.39; P = 0.014) and disease-free survival (DFS) (HR = 2.44; P = 0.048) whereas MUD outcomes did not differ. This effect persisted even when controlling for pre-HSCT stage and Minimal residual disease (MRD) status. In addition, Ph-like was a significant predictor of worse DFS (HR = 3.60; P=0.014) and CIR (HR = 2.97; P=0.035) on multivariate analysis. Older donor age correlated with worse GVHD-free, relapse-free survival (GRFS) in haploidentical transplants (HR = 1.05; P=0.036). CONCLUSION: Our data highlights improved outcomes with younger, haploidentical donors among Hispanic B-cell ALL patients undergoing myeloablative HSCT. This underscores the importance of donor selection in optimizing outcomes for ALL patients.


Asunto(s)
Selección de Donante , Trasplante de Células Madre Hematopoyéticas , Hispánicos o Latinos , Acondicionamiento Pretrasplante , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Femenino , Masculino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Acondicionamiento Pretrasplante/métodos , Adulto Joven , Adolescente , Donantes de Tejidos , Enfermedad Injerto contra Huésped/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Supervivencia sin Enfermedad , Resultado del Tratamiento , Hermanos , Tasa de Supervivencia
19.
Pflugers Arch ; 465(2): 295-317, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23322113

RESUMEN

The molecular mechanisms that contribute to the pathogenesis of pressure-induced deep tissue injury are largely unknown. This study tested the hypothesis that oxidative stress and DNA damage signalling mechanism in skeletal muscle are involved in deep tissue injury. Adult Sprague Dawley rats were subject to an experimental protocol to induce deep tissue injury. Two compression cycles with a static pressure of 100 mmHg was applied to an area of 1.5 cm(2) over the mid-tibialis region of right limb of the rats. The left uncompressed limb served as intra-animal control. Muscle tissues underneath compression region were collected for examination. Our analyses indicated that pathohistological characteristics including rounding contour of myofibres and extensive nuclei accumulation were apparently shown in compressed muscles. The elevation of 8OHdG immunopositively stained nuclei indicated the presence of oxidative DNA damage. Increase in oxidative stress was revealed by showing significant elevation of 4HNE and decreases in mRNA abundance of SOD1, catalase and GPx, and protein content of SOD2 in compressed muscles relative to control muscles. Increase in nitrosative stress was demonstrated by significant elevation of nitrotyrosine and NOS2 mRNA content. The activation of tumor suppressor p53 signalling was indicated by the remarkable increases in protein contents of total p53 and serine-15 phosphorylated p53. The transcript expression of the DNA-repairing enzyme, Rad23A, was significantly suppressed in compressed muscles. Our time-course study indicated that increased oxidative/nitrosative stress and proapoptotic signalling were maintained in muscles receiving increasing amount of compression cycles and post-compression time. Furthermore, resveratrol was found to attenuate the histological damage, oxidative/nitrosative stress and proapoptotic signalling in response to prolonged moderate compression. In conclusion, our findings are consistent with the hypothesis that oxidative stress and DNA damage signalling in skeletal muscle are involved in the underlying mechanisms responsible for the pathogenesis of pressure-induced deep tissue injury.


Asunto(s)
Daño del ADN , Músculo Esquelético/lesiones , Músculo Esquelético/metabolismo , Estrés Oxidativo , Presión , Animales , Apoptosis/efectos de los fármacos , Catalasa/genética , Catalasa/metabolismo , Núcleo Celular/patología , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Femenino , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Miembro Posterior/lesiones , Músculo Esquelético/patología , Miofibrillas/patología , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosforilación , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Resveratrol , Transducción de Señal , Estilbenos/farmacología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1 , Transcripción Genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
20.
J Appl Clin Med Phys ; 14(5): 140-52, 2013 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-24036866

RESUMEN

In lung stereotactic body radiotherapy (SBRT), variability of intrafractional target motion can negate the potential benefits of four-dimensional (4D) treatment planning that aims to account for the dosimetric impacts of organ motion. This study used tumor motion data obtained from CyberKnife SBRT treatments to quantify the reproducibility of probability motion function (pmf) of 37 lung tumors. The reproducibility of pmf was analyzed with and without subtracting the intrafractional baseline drift from the original motion data. Statistics of intrafractional tumor motion including baseline drift, target motion amplitude and period, were also calculated. The target motion amplitude significantly correlates with variations (1SD) of motion amplitude and baseline drift. Significant correlation between treatment time and variations (1 SD) of motion amplitude was observed in anterior-posterior (AP) motion, but not in craniocaudal (CC) and left-right (LR) motion. The magnitude of AP and LR baseline drifts significantly depend on the treatment time, while the CC baseline drift does not. The reproducibility of pmf as a function of time can be well described by a two-exponential function with a fast and slow component. The reproducibility of pmf is over 60% for the CC motion and over 50% for the AP and LR motions when baseline variations were subtracted from the original motion data. It decreases to just over 30% for the CC motion and about 20% for the AP and LR motion, otherwise. 4D planning has obvious limitations due to variability of intrafractional target motion. To account for potential risks of overdosing critical organs, it is important to simulate the dosimetric impacts of intra- and interfractional baseline drift using population statistics obtained from SBRT treatments.


Asunto(s)
Algoritmos , Tomografía Computarizada Cuatridimensional , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Radiocirugia , Planificación de la Radioterapia Asistida por Computador , Humanos , Movimiento , Órganos en Riesgo/efectos de la radiación , Dosificación Radioterapéutica , Carga Tumoral
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