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1.
Diagnosis (Berl) ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38721721

RESUMEN

OBJECTIVES: Analytical interferences, caused by antibodies, often go unnoticed and require a deep understanding of analyzer principles in the correct clinical context. METHODS: A case report details a 56-year-old man with symptoms of hyperviscosity syndrome (HVS) due to multiple myeloma. RESULTS: The DxH 900 analyzer revealed abnormalities in the nucleated red blood cell (nRBC) graph, attributed to a high concentration of IgA kappa. Immediate plasmapheresis successfully treated HVS, reducing the monoclonal component and eliminating the aberrant green signal. CONCLUSIONS: In the appropriate clinical context, the recognition of analytical interferences is necessary for accurate clinical interpretation, and it is only possible with knowledge of the analytical principles of the instruments. In this case, the high concentration of IgA kappa generated an aberrant green signal in the VCSm.

2.
Foods ; 13(7)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38611342

RESUMEN

Lyophilized plant-origin extracts are rich in highly potent antioxidant polyphenols. In order to incorporate them into food products, it is necessary to protect these phytochemicals from atmospheric factors such as heat, light, moisture, or pH, and to enhance their bioavailability due to their low solubility. To address these challenges, recent studies have focused on the development of encapsulation techniques for antioxidant compounds within polymeric structures. In this study, lyophilized olive leaf extracts were microencapsulated with the aim of overcoming the aforementioned challenges. The method used for the preparation of the studied microparticles involves external ionic gelation carried out within a water-oil (W/O) emulsion at room temperature. HPLC analysis demonstrates a high content of polyphenols, with 90% of the bioactive compounds encapsulated. Meanwhile, quantification by inductively coupled plasma optical emission spectroscopy (ICP-OES) reveals that the dried leaves, lyophilized extract, and microencapsulated form contain satisfactory levels of macro- and micro-minerals (calcium, potassium, sodium). The microencapsulation technique could be a novel strategy to harness the polyphenols and minerals of olive leaves, thus enriching food products and leveraging the antioxidant properties of the polyphenolic compounds found in the lyophilized extract.

3.
Rev. colomb. cir ; 39(2): 326-331, 20240220. fig
Artículo en Español | LILACS | ID: biblio-1532721

RESUMEN

Introducción. La hidatidosis o equinococosis es una zoonosis parasitaria que se adquiere al ingerir huevos de cestodos del género Echinococcus. El diagnóstico clínico raramente se hace en sitios no endémicos. La mayoría de los pacientes se encuentran asintomáticos y los hallazgos incidentales en los estudios de imágenes o en procedimientos quirúrgicos permiten la sospecha diagnóstica. Caso clínico. Paciente masculino de 70 años, residente en área rural del municipio de Puerto Libertador, departamento de Córdoba, Colombia, quien consultó por masa abdominal en epigastrio y mesogastrio, parcialmente móvil e indolora. Resultados. En cirugía se identificaron lesiones quísticas mesentérica y hepática. Después de la cirugía y mediante estudios de inmunohistoquímica, se confirmó el diagnóstico de quiste hidatídico. El paciente tuvo una evolución satisfactoria. Conclusión. La hidatidosis quística mesentérica y hepática sintomática es una enfermedad rara en sitios no endémicos, donde la cirugía constituye un pilar fundamental en el diagnóstico y tratamiento, sumado al manejo médico farmacológico.


Introduction. Hydatidosis or echinococcosis is a parasitic zoonosis that is acquired by ingesting eggs of cestodes of the genus Echinococcus. Clinical diagnosis is rarely made in non-endemic sites. Most patients are asymptomatic and incidental findings on imaging studies or surgical procedures allow for diagnostic suspicion. Clinical case. A 70-year-old male patient, resident in a rural area of the municipality of Puerto Libertador, department of Córdoba, Colombia, who consulted for an abdominal mass in the epigastrium and mesogastrium, partially mobile and painless. Results. In surgery, mesenteric and hepatic cystic lesions were identified. After surgery and through immunohistochemistry studies, the diagnosis of hydatid cyst was confirmed. The patient had a satisfactory evolution. Conclusion. Symptomatic mesenteric and hepatic cystic hydatidosis is a rare disease in non-endemic sites, where surgery constitutes a fundamental pillar in the diagnosis and treatment in addition to pharmacological medical management.


Asunto(s)
Humanos , Zoonosis , Equinococosis Hepática , Equinococosis , Laparotomía , Mesenterio
4.
Foods ; 13(2)2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38254490

RESUMEN

Around two million tons of olive oil are produced in Europe annually, with Portugal being among the top five European olive oil-producing countries. Olive oil production results in a substantial amount of waste in the form of olive leaves. These discarded olive leaves contain valuable phenolic compounds with antioxidant, anti-inflammatory, hypoglycaemic, neuroprotective, and antiproliferative properties. Due to their richness in polyphenols with health-promoting properties, olive leaves can be considered a potential functional food ingredient. Thus, sustainable practices for reusing olive leaf waste are in demand. In this study, the polyphenolic content in olive leaves from different Portuguese locations was determined using HPLC-UV-Vis after defining the best fit-for-purpose liquid extraction strategy. The differences in the in vitro antioxidant activity in these samples were determined by several methodologies based on radical scavenging (against 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-2-picrylhydrazyl (DPPH), and peroxyl radical (ORAC)) and on reducing properties (cupric-reducing antioxidant capacity (CUPRAC), and Folin-Ciocalteu assay (FC)), to unveil the relationship between the profile and quantity of polyphenols with antioxidant mechanisms and their capacity. At last, the stability of extracted compounds upon lyophilization and exposition to surrogate biological fluids was assessed, envisioning the future incorporation of olive leaves extracted compounds in food products.

5.
Blood ; 143(7): 597-603, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38048552

RESUMEN

ABSTRACT: The role of measurable residual disease (MRD) negativity as a biomarker to stop treatment is being investigated in transplant-eligible patients with multiple myeloma (MM). Thus, it is important to identify risk factors of MRD resurgence and/or progressive disease (PD) among patients achieving undetectable MRD to avoid undertreating them. Here, we studied 267 newly diagnosed transplant-eligible patients with MM enrolled in the GEM2012MENOS65 and GEM2014MAIN clinical trials who achieved MRD negativity by next-generation flow cytometry. After a median follow-up of 73 months since the first MRD negative assessment, 111 of the 267 (42%) patients showed MRD resurgence and/or PD. The only prognostic factors at diagnosis that predicted MRD resurgence and/or PD were an International Staging System (ISS) 3 and the presence of ≥0.01% circulating tumor cells (CTCs). Failure to achieve MRD negativity after induction also predicted higher risk of MRD resurgence and/or PD. Patients having 0 vs 1 vs ≥2 risk factors (ISS 3, ≥0.01% CTCs, and late MRD negativity) showed 5-year rates of MRD resurgence and/or PD of 16%, 33%, and 57%, respectively (P < .001). Thus, these easily measurable risk factors could help refine the selection of patients for whom treatment cessation after MRD negativity is being investigated in clinical trials. This trial was registered at www.clinicaltrials.gov as NCT01916252 and NCT02406144.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Resultado del Tratamiento , Factores de Riesgo , Neoplasia Residual/diagnóstico
6.
EJIFCC ; 34(1): 76-80, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37124659

RESUMEN

Dasatinib is a tyrosine kinase inhibitor drug used for chronic myeloid leukaemia (CML) treatment. Chylothorax has been rarely reported as a secondary effect of dasatinib occurring especially in long-term treated patients, although its pathophysiology is not yet fully understood. Laboratory analysis of the pleural effusion is crucial for chylothorax diagnosis. We report a case of a 53-year-old male patient presenting a chylothorax after 14 years of dasatinib therapy where the clinical laboratory was key in the diagnosis.

7.
Cancers (Basel) ; 15(5)2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36900296

RESUMEN

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February-June 2020; n = 769 (66%)) and later (July 2020-February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11-0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01-3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22-0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81-1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

8.
J Clin Oncol ; 41(16): 3019-3031, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36930848

RESUMEN

PURPOSE: The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)-like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated. PATIENTS AND METHODS: An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis. RESULTS: Patients with smoldering MM with MGUS-like phenotype showed significantly lower rates of disease progression (4.5% and 0% at 2 years in two independent series). There were no statistically significant differences in time to progression between treatment versus observation in these patients. In active newly diagnosed MM, MGUS-like phenotype retained independent prognostic value in multivariate analyses of progression-free survival (PFS; hazard ratio [HR], 0.49; P = .001) and overall survival (OS; HR, 0.56; P = .039), together with International Staging System, lactate dehydrogenase, cytogenetic risk, transplant eligibility, and complete remission status. Transplant-eligible patients with active MM with MGUS-like phenotype showed PFS and OS rates at 5 years of 79% and 96%, respectively. In this subgroup, there were no differences in PFS and OS according to complete remission and measurable residual disease status. Application of the algorithm in two independent series of patients with AL predicted for different survival. CONCLUSION: We developed an open-access algorithm for the identification of MGUS-like patients with distinct clinical outcomes. This phenotypic classification could become part of the diagnostic workup of MM and AL amyloidosis.


Asunto(s)
Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Paraproteinemias , Humanos , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Gammopatía Monoclonal de Relevancia Indeterminada/terapia , Relevancia Clínica , Progresión de la Enfermedad , Paraproteinemias/diagnóstico , Paraproteinemias/terapia , Mieloma Múltiple/diagnóstico , Fenotipo
9.
JCO Precis Oncol ; 7: e2200546, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36862967

RESUMEN

PURPOSE: The aim of this study was to assess the cost-effectiveness of using next-generation sequencing (NGS) versus single-gene testing (SgT) for the detection of genetic molecular subtypes and oncogenic markers in patients with advanced non-small-cell lung cancer (NSCLC) in the setting of Spanish reference centers. METHODS: A joint model combining decision tree with partitioned survival models was developed. A two-round consensus panel was performed to describe clinical practice of Spanish reference centers, providing data on testing rate, prevalence of alterations, turnaround times, and treatment pathways. Treatment efficacy data and utility values were obtained from the literature. Only direct costs (euros, 2022), obtained from Spanish databases, were included. A lifetime horizon was considered, so a 3% discount rate for future costs and outcomes was considered. Both deterministic and probabilistic sensitivity analyses were performed to assess uncertainty. RESULTS: A target population of 9,734 patients with advanced NSCLC was estimated. If NGS was used instead of SgT, 1,873 more alterations would be detected and 82 more patients could potentially be enrolled in clinical trials. In the long term, using NGS would provide 1,188 additional quality-adjusted life-years (QALYs) in the target population compared with SgT. On the other hand, the incremental cost of NGS versus SgT in the target population was €21,048,580 euros for a lifetime horizon (€1,333,288 for diagnosis phase only). The obtained incremental cost-utility ratios were €25,895 per QALY gained, below the standard cost-effectiveness thresholds. CONCLUSION: Using NGS in Spanish reference centers for the molecular diagnosis of patients with metastatic NSCLC would be a cost-effective strategy over SgT.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Análisis Costo-Beneficio , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Pruebas Genéticas
10.
Sci Rep ; 12(1): 21897, 2022 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-36536019

RESUMEN

The diagnosis of non-alcoholic steatohepatitis (NASH) requires liver biopsy. Patients with NASH are at risk of progression to advanced fibrosis and hepatocellular carcinoma. A reliable non-invasive tool for the detection of NASH is needed. We aimed at developing a tool to diagnose NASH based on a predictive model including routine clinical and transient hepatic elastography (TE) data. All subjects undergoing elective cholecystectomy in our center were invited to participate, if alcohol intake was < 30 g/d for men and < 15 g/d for women. TE with controlled attenuation parameter (CAP) was obtained before surgery. A liver biopsy was taken during surgery. Multivariate logistic regression models to predict NASH were constructed with the first 100 patients, the elaboration group, and the results were validated in the next pre-planned 50 patients. Overall, 155 patients underwent liver biopsy. In the elaboration group, independent predictors of NASH were CAP value [adjusted OR (AOR) 1.024, 95% confidence interval (95% CI) 1.002-1.046, p = 0.030] and HOMA value (AOR 1.847, 95% CI 1.203-2.835, p < 0.001). An index derived from the logistic regression equation to identify NASH was designated as the CAP-insulin resistance (CIR) score. The area under the receiver operating characteristic curve (95%CI) of the CIR score was 0.93 (0.87-0.99). Positive (PPV) and negative predictive values (NPV) of the CIR score were 82% and 91%, respectively. In the validation set, PPV was 83% and NPV was 88%. In conclusion, the CIR score, a simple index based on CAP and HOMA, can reliably identify patients with and without NASH.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Resistencia a la Insulina , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Masculino , Humanos , Femenino , Enfermedad del Hígado Graso no Alcohólico/patología , Diagnóstico por Imagen de Elasticidad/métodos , Hígado/patología , Curva ROC , Biopsia , Neoplasias Hepáticas/patología , Cirrosis Hepática/patología
11.
Sensors (Basel) ; 22(13)2022 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-35808407

RESUMEN

This work analyzed the use of Microsoft HoloLens 2 in orthopedic oncological surgeries and compares it to its predecessor (Microsoft HoloLens 1). Specifically, we developed two equivalent applications, one for each device, and evaluated the augmented reality (AR) projection accuracy in an experimental scenario using phantoms based on two patients. We achieved automatic registration between virtual and real worlds using patient-specific surgical guides on each phantom. They contained a small adaptor for a 3D-printed AR marker, the characteristic patterns of which were easily recognized using both Microsoft HoloLens devices. The newest model improved the AR projection accuracy by almost 25%, and both of them yielded an RMSE below 3 mm. After ascertaining the enhancement of the second model in this aspect, we went a step further with Microsoft HoloLens 2 and tested it during the surgical intervention of one of the patients. During this experience, we collected the surgeons' feedback in terms of comfortability, usability, and ergonomics. Our goal was to estimate whether the improved technical features of the newest model facilitate its implementation in actual surgical scenarios. All of the results point to Microsoft HoloLens 2 being better in all the aspects affecting surgical interventions and support its use in future experiences.


Asunto(s)
Realidad Aumentada , Procedimientos Ortopédicos , Cirugía Asistida por Computador , Ergonomía , Humanos , Fantasmas de Imagen , Programas Informáticos , Cirugía Asistida por Computador/métodos
12.
Comput Methods Programs Biomed ; 224: 106991, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35810510

RESUMEN

BACKGROUND AND OBJECTIVE: Sacral nerve stimulation (SNS) is a minimally invasive procedure where an electrode lead is implanted through the sacral foramina to stimulate the nerve modulating colonic and urinary functions. One of the most crucial steps in SNS procedures is the placement of the tined lead close to the sacral nerve. However, needle insertion is very challenging for surgeons. Several x-ray projections are required to interpret the needle position correctly. In many cases, multiple punctures are needed, causing an increase in surgical time and patient's discomfort and pain. In this work we propose and evaluate two different navigation systems to guide electrode placement in SNS surgeries designed to reduce surgical time, minimize patient discomfort and improve surgical outcomes. METHODS: We developed, for the first alternative, an open-source navigation software to guide electrode placement by real-time needle tracking with an optical tracking system (OTS). In the second method, we present a smartphone-based AR application that displays virtual guidance elements directly on the affected area, using a 3D printed reference marker placed on the patient. This guidance facilitates needle insertion with a predefined trajectory. Both techniques were evaluated to determine which one obtained better results than the current surgical procedure. To compare the proposals with the clinical method, we developed an x-ray software tool that calculates a digitally reconstructed radiograph, simulating the fluoroscopy acquisitions during the procedure. Twelve physicians (inexperienced and experienced users) performed needle insertions through several specific targets to evaluate the alternative SNS guidance methods on a realistic patient-based phantom. RESULTS: With each navigation solution, we observed that users took less average time to complete each insertion (36.83 s and 44.43 s for the OTS and AR methods, respectively) and needed fewer average punctures to reach the target (1.23 and 1.96 for the OTS and AR methods respectively) than following the standard clinical method (189.28 s and 3.65 punctures). CONCLUSIONS: To conclude, we have shown two navigation alternatives that could improve surgical outcome by significantly reducing needle insertions, surgical time and patient's pain in SNS procedures. We believe that these solutions are feasible to train surgeons and even replace current SNS clinical procedures.


Asunto(s)
Realidad Aumentada , Cirugía Asistida por Computador , Humanos , Agujas , Dolor , Fantasmas de Imagen , Cirugía Asistida por Computador/métodos , Tomografía Computarizada por Rayos X
13.
Int J Comput Assist Radiol Surg ; 17(11): 2081-2091, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35776399

RESUMEN

PURPOSE: Augmented Reality (AR) has the potential to simplify ultrasound (US) examinations which usually require a skilled and experienced sonographer to mentally align narrow 2D cross-sectional US images in the 3D anatomy of the patient. This work describes and evaluates a novel approach to track retroreflective spheres attached to the US probe using an inside-out technique with the AR glasses HoloLens 2. Finally, live US images are displayed in situ on the imaged anatomy. METHODS: The Unity application UltrARsound performs spatial tracking of the US probe and attached retroreflective markers using the depth camera integrated into the AR glasses-thus eliminating the need for an external tracking system. Additionally, a Kalman filter is implemented to improve the noisy measurements of the camera. US images are streamed wirelessly via the PLUS toolkit to HoloLens 2. The technical evaluation comprises static and dynamic tracking accuracy, frequency and latency of displayed images. RESULTS: Tracking is performed with a median accuracy of 1.98 mm/1.81[Formula: see text] for the static setting when using the Kalman filter. In a dynamic scenario, the median error was 2.81 mm/1.70[Formula: see text]. The tracking frequency is currently limited to 20 Hz. 83% of the displayed US images had a latency lower than 16 ms. CONCLUSIONS: In this work, we showed that spatial tracking of retroreflective spheres with the depth camera of HoloLens 2 is feasible, achieving a promising accuracy for in situ visualization of live US images. For tracking, no additional hardware nor modifications to HoloLens 2 are required making it a cheap and easy-to-use approach. Moreover, a minimal latency of displayed images enables a real-time perception for the sonographer.


Asunto(s)
Estudios Transversales , Humanos , Ultrasonografía
14.
J Clin Oncol ; 40(27): 3151-3161, 2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-35666958

RESUMEN

PURPOSE: Patients with multiple myeloma (MM) may show patchy bone marrow (BM) infiltration and extramedullary disease. Notwithstanding, quantification of plasma cells (PCs) continues to be performed in BM since the clinical translation of circulating tumor cells (CTCs) remains undefined. PATIENTS AND METHODS: CTCs were measured in peripheral blood (PB) of 374 patients with newly diagnosed MM enrolled in the GEM2012MENOS65 and GEM2014MAIN trials. Treatment included bortezomib, lenalidomide, and dexamethasone induction followed by autologous transplant, consolidation, and maintenance. Next-generation flow cytometry was used to evaluate CTCs in PB at diagnosis and measurable residual disease (MRD) in BM throughout treatment. RESULTS: CTCs were detected in 92% (344 of 374) of patients with newly diagnosed MM. The correlation between the percentages of CTCs and BM PCs was modest. Increasing logarithmic percentages of CTCs were associated with inferior progression-free survival (PFS). A cutoff of 0.01% CTCs showed an independent prognostic value (hazard ratio: 2.02; 95% CI, 1.3 to 3.1; P = .001) in multivariable PFS analysis including the International Staging System, lactate dehydrogenase levels, and cytogenetics. The combination of the four prognostic factors significantly improved risk stratification. Outcomes according to the percentage of CTCs and depth of response to treatment showed that patients with undetectable CTCs had exceptional PFS regardless of complete remission and MRD status. In all other cases with detectable CTCs, only achieving MRD negativity (and not complete remission) demonstrated a statistically significant increase in PFS. CONCLUSION: Evaluation of CTCs in PB outperformed quantification of BM PCs. The detection of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible MM.


Asunto(s)
Mieloma Múltiple , Células Neoplásicas Circulantes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Humanos , Lactato Deshidrogenasas , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Neoplasia Residual/tratamiento farmacológico , Células Neoplásicas Circulantes/patología
15.
Clin Cancer Res ; 28(12): 2598-2609, 2022 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-35063966

RESUMEN

PURPOSE: Undetectable measurable residual disease (MRD) is a surrogate of prolonged survival in multiple myeloma. Thus, treatment individualization based on the probability of a patient achieving undetectable MRD with a singular regimen could represent a new concept toward personalized treatment, with fast assessment of its success. This has never been investigated; therefore, we sought to define a machine learning model to predict undetectable MRD at the onset of multiple myeloma. EXPERIMENTAL DESIGN: This study included 487 newly diagnosed patients with multiple myeloma. The training (n = 152) and internal validation cohorts (n = 149) consisted of 301 transplant-eligible patients with active multiple myeloma enrolled in the GEM2012MENOS65 trial. Two external validation cohorts were defined by 76 high-risk transplant-eligible patients with smoldering multiple myeloma enrolled in the Grupo Español de Mieloma(GEM)-CESAR trial, and 110 transplant-ineligible elderly patients enrolled in the GEM-CLARIDEX trial. RESULTS: The most effective model to predict MRD status resulted from integrating cytogenetic [t(4;14) and/or del(17p13)], tumor burden (bone marrow plasma cell clonality and circulating tumor cells), and immune-related biomarkers. Accurate predictions of MRD outcomes were achieved in 71% of cases in the GEM2012MENOS65 trial (n = 214/301) and 72% in the external validation cohorts (n = 134/186). The model also predicted sustained MRD negativity from consolidation onto 2 years maintenance (GEM2014MAIN). High-confidence prediction of undetectable MRD at diagnosis identified a subgroup of patients with active multiple myeloma with 80% and 93% progression-free and overall survival rates at 5 years. CONCLUSIONS: It is possible to accurately predict MRD outcomes using an integrative, weighted model defined by machine learning algorithms. This is a new concept toward individualized treatment in multiple myeloma. See related commentary by Pawlyn and Davies, p. 2482.


Asunto(s)
Mieloma Múltiple , Anciano , Biomarcadores , Humanos , Aprendizaje Automático , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Neoplasia Residual/diagnóstico , Tasa de Supervivencia
16.
Chest ; 161(4): 960-970, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34785234

RESUMEN

BACKGROUND: Body composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined. RESEARCH QUESTION: Is the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics? STUDY DESIGN AND METHODS: Participants with complete data for at least one visit in the COPDGene study (n = 9,268) and the ECLIPSE study (n = 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation. RESULTS: Both cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1% (95% CI, 2.4%-3.7%; P < .001) in COPDGene, and 2.4% (95% CI, 0.9%-4.0%; P < .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA. INTERPRETATION: Longitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Fumadores , Composición Corporal , Índice de Masa Corporal , Humanos , Estudios Longitudinales , Pulmón , Músculos Pectorales , Enfermedad Pulmonar Obstructiva Crónica/complicaciones
17.
Rev. bras. oftalmol ; 81: e0012, 2022. graf
Artículo en Inglés | LILACS | ID: biblio-1360916

RESUMEN

ABSTRACT Objective: A unusual case of ocular toxoplasmosis with significant vitreomacular traction is reported. The patient improved significantly following pars plana vitrectomy combined with visual stimulation and occlusion therapy. Methods: The case of a 5-year-old girl with significant unilateral vision loss associated with vitreous condensation and macular traction is described. Results: Pars plana vitrectomy was carried out for vitreomacular traction release. This was followed by visual stimulation and occlusion therapy. Significant improvement was observed. Conclusion: Despite structural damage, the combination of properly indicated surgery and amblyopia management strategies allowed the achievement of maximum vision goals in this case, suggesting structural damage may be associated with functional amblyopia.


RESUMO Objetivo: Relata-se um caso de apresentação atípica de toxoplasmose ocular, com importante tração vitreomacular. A paciente apresentou melhora significativa após vitrectomia via pars plana, com estimulação visual e oclusão. Métodos: Descreve-se o caso de uma menina de 5 anos, com importante perda de visão unilateral associada à condensação vítrea e à tração macular. Resultados: Foi realizada vitrectomia via pars plana para alívio da tração vitreomacular, seguida de estimulação visual e oclusão. Foi observada melhora significativa. Conclusão: Apesar dos danos estruturais, a combinação de cirurgia bem indicada com estratégias de tratamento da ambliopia permitiu alcançar o máximo do potencial visual nesta paciente, sugerindo que os danos estruturais podem estar associados à ambliopia funcional.


Asunto(s)
Humanos , Femenino , Preescolar , Estimulación Luminosa , Vitrectomía/métodos , Adherencias Tisulares/cirugía , Toxoplasmosis Ocular/complicaciones , Coriorretinitis/etiología , Membrana Epirretinal/cirugía , Membrana Epirretinal/etiología , Tracción , Coriorretinitis/complicaciones , Desprendimiento del Vítreo/terapia , Cirugía Vitreorretiniana
18.
Sensors (Basel) ; 21(23)2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34883825

RESUMEN

Patient-specific instruments (PSIs) have become a valuable tool for osteotomy guidance in complex surgical scenarios such as pelvic tumor resection. They provide similar accuracy to surgical navigation systems but are generally more convenient and faster. However, their correct placement can become challenging in some anatomical regions, and it cannot be verified objectively during the intervention. Incorrect installations can result in high deviations from the planned osteotomy, increasing the risk of positive resection margins. In this work, we propose to use augmented reality (AR) to guide and verify PSIs placement. We designed an experiment to assess the accuracy provided by the system using a smartphone and the HoloLens 2 and compared the results with the conventional freehand method. The results showed significant differences, where AR guidance prevented high osteotomy deviations, reducing maximal deviation of 54.03 mm for freehand placements to less than 5 mm with AR guidance. The experiment was performed in two versions of a plastic three-dimensional (3D) printed phantom, one including a silicone layer to simulate tissue, providing more realism. We also studied how differences in shape and location of PSIs affect their accuracy, concluding that those with smaller sizes and a homogeneous target surface are more prone to errors. Our study presents promising results that prove AR's potential to overcome the present limitations of PSIs conveniently and effectively.


Asunto(s)
Realidad Aumentada , Neoplasias Pélvicas , Cirugía Asistida por Computador , Humanos , Imagenología Tridimensional , Pelvis/cirugía , Fantasmas de Imagen
19.
Endocrinol Diabetes Nutr (Engl Ed) ; 68(6): 372-380, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34742470

RESUMEN

INTRODUCTION: Bariatric surgery aims to reduce weight and resolve the comorbidities associated with obesity. Few studies have assessed mid/long-term changes in lipid profile with sleeve gastrectomy versus gastric bypass. This study was conducted to assess and compare changes in lipid profile with each procedure after 60 months. METHODS: This was an observational, retrospective study of analytical cohorts enrolling 100 patients distributed into two groups: 50 had undergone gastric bypass (GBP) surgery and 50 sleeve gastrectomy (SG) surgery. Total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured before surgery and at 1, 6, 12, 24, 36, 48, and 60 months. Weight loss and the resolution of dyslipidemia with each of the procedures were also assessed. RESULTS: Ninety-five of the 100 patients completed follow-up. At 60 months, TC and LDL levels had significantly decreased in the BPG group (167.42 ±â€¯31.22 mg/dl and 88.06 ±â€¯31.37 mg/dl, respectively), while there were no differences in the SG group. Increased HDL levels were seen with both procedures (BPG: 62.69 ±â€¯16.3 mg/dl vs. SG: 60.64 ±â€¯18.73 mg/dl), with no difference between the procedures. TG levels decreased in both groups (BPG: 86.06 ±â€¯56.57 mg/dl vs. SG: 111.09 ±â€¯53.08 mg/dl), but values were higher in the BPG group (P < .05). The percentage of overweight lost (PSP) was higher in the BPG group: 75.65 ±â€¯22.98 mg/dl vs. the GV group: 57.83 ±â€¯27.95 mg/dl. CONCLUSION: Gastric bypass achieved better mid/long-term results in terms of weight reduction and the resolution of hypercholesterolemia as compared to sleeve gastrectomy. While gastric bypass improved all lipid profile parameters, sleeve gastrectomy only improved HDL and triglyceride levels.


Asunto(s)
Cirugía Bariátrica , Derivación Gástrica , Lípidos/sangre , Obesidad Mórbida , Gastrectomía , Humanos , Lipoproteínas HDL/sangre , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Triglicéridos/sangre , Pérdida de Peso
20.
Nat Chem Biol ; 17(9): 989-997, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34341587

RESUMEN

The cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is essential to maintain fluid homeostasis in key organs. Functional impairment of CFTR due to mutations in the cftr gene leads to cystic fibrosis. Here, we show that the first nucleotide-binding domain (NBD1) of CFTR can spontaneously adopt an alternate conformation that departs from the canonical NBD fold previously observed. Crystallography reveals that this conformation involves a topological reorganization of NBD1. Single-molecule fluorescence resonance energy transfer microscopy shows that the equilibrium between the conformations is regulated by adenosine triphosphate binding. However, under destabilizing conditions, such as the disease-causing mutation F508del, this conformational flexibility enables unfolding of the ß-subdomain. Our data indicate that, in wild-type CFTR, this conformational transition of NBD1 regulates channel function, but, in the presence of the F508del mutation, it allows domain misfolding and subsequent protein degradation. Our work provides a framework to design conformation-specific therapeutics to prevent noxious transitions.


Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/química , Regulador de Conductancia de Transmembrana de Fibrosis Quística/aislamiento & purificación , Transferencia Resonante de Energía de Fluorescencia , Células HEK293 , Humanos , Modelos Moleculares , Conformación Proteica , Desplegamiento Proteico
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