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1.
J Pharm Bioallied Sci ; 16(Suppl 3): S2676-S2678, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39346387

RESUMEN

Background: Tele-orthodontics, the application of telecommunications technology in orthodontic care, has emerged as a promising tool to enhance patient compliance and facilitate treatment monitoring. In traditional orthodontic practice, patient compliance and monitoring are pivotal but often challenging aspects. Tele-orthodontics offers a solution by providing remote communication and monitoring capabilities, potentially improving patient engagement and treatment outcomes. Materials and Methods: This study conducted a retrospective analysis of orthodontic patients who utilized tele-orthodontics as part of their treatment plan. A total of 100 patients were included in the study, with ages ranging from 12 to 40 years old. Patients were provided with mobile applications or web-based platforms enabling them to communicate with their orthodontists, submit progress images, and receive feedback remotely. Treatment compliance was assessed based on adherence to scheduled appointments, wearing of orthodontic appliances, and completion of prescribed exercises. Results: The analysis revealed a significant improvement in patient compliance with the implementation of tele-orthodontics. Adherence to scheduled appointments increased by 30%, with patients attending 95% of their appointments compared to 65% before the introduction of tele-orthodontics. Moreover, compliance with wearing orthodontic appliances showed a remarkable rise, with patients consistently wearing their appliances for an average of 22 h per day, up from 14 h per day previously. Additionally, the completion rate of prescribed exercises saw a notable enhancement, with 80% of patients completing their exercises as instructed, compared to 50% previously. Conclusion: Tele-orthodontics plays a significant role in enhancing patient compliance and treatment monitoring in orthodontic care. The remote communication and monitoring capabilities provided by tele-orthodontic platforms empower patients to actively participate in their treatment process, leading to improved adherence to appointments, better compliance with wearing orthodontic appliances, and increased completion of prescribed exercises. These findings underscore the importance of integrating tele-orthodontics into orthodontic practice to optimize patient outcomes and satisfaction.

2.
Tomography ; 10(9): 1397-1410, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39330751

RESUMEN

The Brain Tumor Segmentation (BraTS) Challenge has been a main driver of the development of deep learning (DL) algorithms and provides by far the largest publicly available expert-annotated brain tumour dataset but contains solely preoperative examinations. The aim of our study was to facilitate the use of the BraTS dataset for training DL brain tumour segmentation algorithms for a postoperative setting. To this end, we introduced an automatic conversion of the three-label BraTS annotation protocol to a two-label annotation protocol suitable for postoperative brain tumour segmentation. To assess the viability of the label conversion, we trained a DL algorithm using both the three-label and the two-label annotation protocols. We assessed the models pre- and postoperatively and compared the performance with a state-of-the-art DL method. The DL algorithm trained using the BraTS three-label annotation misclassified parts of 10 out of 41 fluid-filled resection cavities in 72 postoperative glioblastoma MRIs, whereas the two-label model showed no such inaccuracies. The tumour segmentation performance of the two-label model both pre- and postoperatively was comparable to that of a state-of-the-art algorithm for tumour volumes larger than 1 cm3. Our study enables using the BraTS dataset as a basis for the training of DL algorithms for postoperative tumour segmentation.


Asunto(s)
Algoritmos , Neoplasias Encefálicas , Imagen por Resonancia Magnética , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Imagen por Resonancia Magnética/métodos , Aprendizaje Profundo , Glioblastoma/diagnóstico por imagen , Glioblastoma/cirugía , Glioblastoma/patología , Conjuntos de Datos como Asunto
3.
Discov Oncol ; 15(1): 485, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39331166

RESUMEN

BACKGROUND: Small Cell Lung Cancer (SCLC) presents a significant clinical challenge due to its aggressive nature and the need for effective biomarkers for treatment monitoring. This study aimed to compare ProGRP and CEA as serological markers in the monitoring of SCLC treatment. METHODS: We retrospectively analyzed data from 80 SCLC patients and 80 matched controls. ProGRP and CEA levels were measured, and their associations with clinical parameters, including tumor stage and treatment response, were assessed using Spearman's rank correlation coefficient. Multivariate logistic regression models were employed to identify independent predictors of treatment response and disease progression. RESULTS: ProGRP and CEA levels were considerably higher in cases than controls, with median ProGRP levels at 198.5 pg/mL versus 48.7 pg/mL and median CEA levels at 5.2 ng/mL versus 2.9 ng/mL (both p < 0.001). ProGRP levels correlated positively with tumor stage (ρ = 0.58, p < 0.001) and negatively with treatment response (ρ = - 0.45, p = 0.001). CEA levels also showed positive correlation with tumor stage (ρ = 0.48, p = 0.002) and negative correlation with treatment response (ρ = - 0.35, p = 0.005). Multivariate analysis revealed that ProGRP was an independent predictor for treatment response (OR 1.25 per 100 pg/mL increase, p = 0.001) and disease progression (OR 1.25 per 50 pg/mL increase, p = 0.012), while CEA was a marginal predictor for treatment response (OR 0.95 per 1 ng/mL increase, p = 0.045). CONCLUSION: Both ProGRP and CEA are significant serological markers in SCLC patients, with ProGRP showing a stronger correlation with tumor stage and treatment response. ProGRP may serve as a superior independent predictor of treatment response and disease progression compared to CEA. These findings support the incorporation of ProGRP in SCLC treatment monitoring protocols.

4.
Colloids Surf B Biointerfaces ; 245: 114265, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39321721

RESUMEN

Anticancer therapies with cisplatin and volasertib (BI-6727) were monitored by fluorescence lifetime imaging microscopy (FLIM) in live SK-Mel-2 melanoma cells. A CdSe/ZnS quantum dot functionalized with a peptide containing D-penicillamine and histidine (CdSe/ZnS-PH) was used as intracellular pH fluorescent probe. A faster cytosol acidification was observed for cells treated with cisplatin when compared to volasertib. The first changes in the intracellular pH were found after 2 hours of treatment with cisplatin and 8 hours with volasertib. Additionally, the relationship between cytosol acidification and apoptosis was investigated using an innovative methodology based on time-resolved fluorescence measurements. Similar low percentages of apoptotic cells were observed after short incubation periods (2 - 8 hours) with both drugs. In contrast, late apoptosis and death were found for a large fraction of cells during 24-hour incubation with cisplatin but not volasertib. Thus, the early acidification observed in cisplatin treatment could accelerate apoptosis and cell death. Despite volasertib treatment shows slower mechanism of action than cisplatin, similar inhibitory effects were found for both drugs at longer incubation periods (72 hours). This study proves the potential of CdSe/ZnS-PH nanoparticle as a fluorescence lifetime probe in the study of the mechanism of action of antitumor drugs.

5.
Diagnostics (Basel) ; 14(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39202212

RESUMEN

BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Due to its high prevalence, considerable morbidity, and chronicity, there is a need for the accurate in vivo evaluation of treatment efficacy. Line-field confocal optical coherence tomography (LC-OCT) is a new emerging imaging technique able to perform a non-invasive, real-time examination of the epidermis and the upper dermis. LC-OCT may represent a promising tool in the diagnosis and treatment follow-up of chronic eczematous skin diseases with barrier defects. OBJECTIVES: We aimed to investigate the role of LC-OCT in the non-invasive monitoring of the treatment effect on five patients with severe atopic dermatitis during dupilumab treatment. MATERIALS AND METHODS: LC-OCT imaging was performed on five patients (three women and two men) aged between 14 and 85 years old at the baseline and at 2, 4, and 6 weeks of treatment with dupilumab. The LC-OCT scans were performed at two sites, the lesional skin in the antecubital fossa and the extensor part of the arm, considered a control site on each patient for comparison. The captured images were later evaluated. Descriptive statistics and a t-test were used to compare the analyzed parameters over time and between involved atopic skin and clinically healthy skin. RESULTS: The LC-OCT imaging was able to detect the difference in stratum corneum (SC) thickness and quality and epidermal thickness (ET) and the changes before and after treatment with high accuracy. The main findings include a significant reduction in the epidermal and stratum corneum thickness and decreased epidermal spongiosis and inflammation, with better quality of the stratum corneum indicating restoration of its tightness at both lesional and control sites. CONCLUSIONS: This study demonstrates that clinical improvement of affected and unaffected atopic skin under dupilumab treatment correlates with the LC-OCT findings. LC-OCT represents a novel, non-invasive tool examining the in vivo skin barrier and inflammation and can help to monitor the treatment efficacy among patients with atopic dermatitis in daily practice.

6.
Heliyon ; 10(15): e35670, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170565

RESUMEN

Objective: This study aimed to investigate the impact of diabetes mellitus (DM) on tuberculosis (TB) treatment response using bacterial clearance as a surrogate marker. Method: We compared smear microscopy, culture, and tuberculosis molecular bacterial load assay (TB-MBLA) for treatment monitoring. Following that, bacterial clearance was longitudinally monitored among TB-only (TB without DM) and TB-diabetes (TBDM) patients using TB-MBLA. Results: Ninety-three participants, including 59 TB-only and 34 TBDM patients, were enrolled. TB-only patients exhibited higher upper zone infiltrations (32/35 vs 16/22, p = 0.059) suggesting a trend towards significance, and significantly more cavitation in the same zone (16/18 vs 7/13, p = 0.028). There was a high proportion of Mycobacterium africanum (Maf) among the TBDM cohort (p = 0.0044).At baseline, TB-only patients exhibited a higher average bacterial burden (4.49 logeCFU/mL) compared to the TBDM group (3.91 logeCFU/mL) (p = 0.042). The bacterial load in the TB-only group decreased significantly during treatment but the TBDM group experienced delayed clearance throughout the intensive phase of anti-TB treatment even at day 56 (p = 0.028). The TB-only group demonstrated a shorter median time to TB-MBLA conversion to negative (57 days) compared to the TBDM group (62 days) (p = 0.022). Conclusion: These findings underscore the urgent call for understanding the interplay between diabetes and TB, emphasizing the need for tailored interventions in optimizing TB care for individuals comorbid with diabetes.

7.
BMC Pulm Med ; 24(1): 406, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39180021

RESUMEN

BACKGROUND: Tuberculosis (TB) remains a global health challenge, with India bearing a significant burden. Despite advancements in TB diagnosis and treatment, monitoring TB treatment is challenging, particularly in resource-limited settings. This study aimed to explore the mean platelet volume (MPV) as a potential surrogate marker for monitoring TB treatment and assessing if the neutrophil-to-albumin ratio (NAR) enhances treatment monitoring. METHODS: Patients diagnosed with TB following NTEP guidelines were recruited. Participants underwent routine blood tests during the six-month Anti-Tubercular therapy course at the start, end of the intensive phase, and end of the continuous phase. Statistical analyses included Spearman correlation, Friedman test, linear mixed effects (LME) models, and multiple linear regression. RESULTS: 150 individuals were included for analysis. Deviations from normality were noted. Significant associations were found between CRP and sputum grade. MPV mediated between CRP and sputum grade. Significant differences were observed across the three-time points. LME models showed changes in MPV and CRP levels over time. Including NAR enhanced predictive capability. CONCLUSIONS: MPV may serve as a promising surrogate marker for monitoring ATT. Personalized approaches are crucial in TB treatment monitoring. LME models revealed MPV and CRP level trends. Future research should explore MPV's treatment response mechanisms and cost-effectiveness.


Asunto(s)
Antituberculosos , Biomarcadores , Volúmen Plaquetario Medio , Neutrófilos , Humanos , Masculino , Femenino , Biomarcadores/sangre , Adulto , Estudios Prospectivos , Antituberculosos/uso terapéutico , Persona de Mediana Edad , Estudios Longitudinales , India , Esputo/microbiología , Tuberculosis/diagnóstico , Tuberculosis/sangre , Tuberculosis/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/diagnóstico , Proteína C-Reactiva/análisis , Albúminas/análisis , Adulto Joven , Modelos Lineales
8.
Ann Med ; 56(1): 2386030, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39097795

RESUMEN

Tuberculosis (TB) continues to pose a significant health challenge worldwide, emphasizing the importance of prompt diagnosis and efficient monitoring of treatment outcomes for effective disease control. Biomarkers have become increasingly important in the realm of TB diagnoses and treatment. The objective of this comprehensive review is to examine the present state of biomarkers employed in the diagnosis of TB, monitoring the response to treatment, and predicting treatment outcomes. In this study, we undertake a comprehensive examination of the diverse biomarkers utilized in TB diagnoses, spanning molecular, immunological, and other novel methodologies. Furthermore, we examine the potential of biomarkers in the context of therapeutic monitoring, assessment of treatment effectiveness, and anticipation of drug resistance. Additionally, this paper presents future prospects regarding the utilization of biomarkers in the therapy of tuberculosis.


Asunto(s)
Antituberculosos , Biomarcadores , Tuberculosis , Humanos , Biomarcadores/sangre , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Antituberculosos/uso terapéutico , Resultado del Tratamiento , Mycobacterium tuberculosis/aislamiento & purificación , Monitoreo de Drogas/métodos
9.
Med Phys ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39092910

RESUMEN

BACKGROUND: Although B-mode imaging has been widely used in ultrasound-guided high-intensity focused ultrasound (HIFU) treatment, challenges remain in improving its quality and sensitivity for monitoring the thermal dose. Recently, quantitative ultrasound (QUS) imaging has been recognized with the potential to better sense the changes in the microstructure of ablated tissues. PURPOSE: This study proposed to use a QUS method called weighted ultrasound entropy (WUE) imaging to monitor the HIFU ablation. METHODS: Based on ex-vivo and in-vivo experiments, WUE images reflecting tissue changes during HIFU treatment under different acoustic power levels (174-308 W) were reconstructed with a newly established imaging framework. The performance of the proposed WUE imaging in the monitoring of HIFU treatment was compared with the corresponding B-mode images in terms of their contrast-to-noise ratios (CNRs) between the focal region and the background. RESULTS: It was found that HIFU irradiation with higher power generated larger WUE values in the focal region, and the bright spots grew in size as the acoustic sonication proceeded. Compared with the in-situ B-mode images, the WUE images had higher image quality in indicating lesion formation, with a 39.2%-53.4% improvement in the CNR at different stages. Meanwhile, a correlation (R = 0.84) between the damage area estimated in WUE images and that measured from the dissected ex-vivo tissue samples was found. CONCLUSIONS: WUE imaging is more sensitive and accurate than B-mode imaging in monitoring HIFU therapy. These findings suggest that WUE imaging could be a promising technique for assisting ultrasound-guided HIFU ablation.

10.
Sci Rep ; 14(1): 15121, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956402

RESUMEN

Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1-4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient's response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP's response to biological therapy.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Interleucina-17 , Microscopía Confocal , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/diagnóstico por imagen , Psoriasis/patología , Interleucina-17/antagonistas & inhibidores , Microscopía Confocal/métodos , Femenino , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Persona de Mediana Edad , Adulto , Proyectos Piloto , Estudios de Seguimiento , Anciano , Piel/patología , Piel/diagnóstico por imagen , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Anticuerpos Monoclonales/uso terapéutico
11.
Behav Anal Pract ; 17(2): 643-655, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38966272

RESUMEN

Ensuring high levels of procedural fidelity during behavior-analytic interventions is a crucial component of providing effective behavior-analytic services. However, few resources are available to help guide practitioners through measuring procedural fidelity. In fact, most published behavior-analytic research on procedural fidelity analyzes a single treatment procedure, which might not completely reflect the process of monitoring and addressing the procedural fidelity of a robust treatment package that might be necessary in clinical settings. The purpose of this article is to guide behavior analysts through the process of creating and using procedural fidelity measurement systems, with a focus on direct observation of implementation as a means of fidelity data collection. This process consists of six steps: (1) task analyze treatment procedures into measurable units; (2) assign measures to each treatment component; (3) plan the direct observation; (4) collect procedural fidelity data; (5) analyze and interpret procedural fidelity data; and (6) take action to improve procedural fidelity. Each step is described and discussed in the article.

12.
Ophthalmologie ; 121(8): 616-622, 2024 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-39083094

RESUMEN

The first regulatory approval of treatment for geographic atrophy (GA) secondary to age-related macular degeneration in the USA constitutes an important milestone; however, due to the nature of GA as a non-acute, insidiously progressing pathology, the ophthalmologist faces specific challenges concerning risk stratification, making treatment decisions, monitoring of treatment and patient education. Innovative retinal imaging modalities, such as fundus autofluorescence (FAF) and optical coherence tomography (OCT) have enabled identification of typical morphological alterations in relation to GA, which are also suitable for the quantitative characterization of GA. Solutions based on artificial intelligence (AI) enable automated detection and quantification of GA-specific biomarkers on retinal imaging data, also retrospectively and over time. Moreover, AI solutions can be used for the diagnosis and segmentation of GA as well as the prediction of structure and function without and under GA treatment, thereby making a valuable contribution to treatment monitoring and the identification of high-risk patients and patient education. The integration of AI solutions into existing clinical processes and software systems enables the broad implementation of informed and personalized treatment of GA secondary to AMD.


Asunto(s)
Inteligencia Artificial , Atrofia Geográfica , Degeneración Macular , Tomografía de Coherencia Óptica , Humanos , Atrofia Geográfica/diagnóstico , Degeneración Macular/diagnóstico , Degeneración Macular/patología , Angiografía con Fluoresceína , Sensibilidad y Especificidad
13.
Adv Sci (Weinh) ; 11(30): e2404172, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38874481

RESUMEN

Smart drug platforms based on spatiotemporally controlled release and integration of tumor imaging are expected to overcome the inefficiency and uncertainty of traditional theranostic modes. In this study, a composite consisting of a thermosensitive hydrogel (polyvinyl alcohol-carboxylic acid hydrogel (PCF)) and a multifunctional nanoparticle (Fe3O4@Au/Mn(Zn)-4-carboxyphenyl porphyrin/polydopamine (FAMxP)) is developed to combine tumor immunogenic cell death (ICD)/immune checkpoint blockade (ICB) therapy under the guidance of magnetic resonance imaging (MRI) and fluorescence imaging (FI). It can not only further recognize the target cells through the folate receptor of tumor cells, but also produce thermal dissolution after exposure to near-infrared light to slowly release FAMxP in situ, thereby prolonging the treatment time and avoiding tumor recurrence. As FAMxP entered the tumor cells, it released FAMx in a pH-dependent manner. Chemodynamic, photothermal and photodynamic therapy can cause significant ICD in cancer cells. ICB can thus be further enhanced by injecting anti-programmed cell death ligand 1, improving the effectiveness of tumor treatment. The developed PCF-FAMxP composite hydrogel may represent an updated drug design approach with simple compositions for cooperative MRI/FI-guided targeted therapeutic pathways for tumors.


Asunto(s)
Hidrogeles , Hidrogeles/química , Animales , Ratones , Humanos , Imagen por Resonancia Magnética/métodos , Modelos Animales de Enfermedad , Nanopartículas Multifuncionales/química , Línea Celular Tumoral , Indoles/química , Indoles/farmacología , Sistemas de Liberación de Medicamentos/métodos , Polímeros/química , Imagen Óptica/métodos
14.
J Neurooncol ; 169(2): 241-245, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38842696

RESUMEN

PURPOSE: This study aimed to evaluate the prognostic performance of amino-acid PET in high-grade gliomas (HGG) patients at the time of temozolomide (TMZ) treatment discontinuation, after the Stupp protocol. METHODS: The analysis included consecutive HGG patients with dynamic [18F]FDOPA PET imaging within 3 months of the end of TMZ therapy, post-Stupp protocol. Static and dynamic PET parameters, responses to RANO criteria for MRI and clinical and histo-molecular factors were correlated to progression-free (PFS). RESULTS: Thirty-two patients (59.4 [54.0;67.6] years old, 13 (41%) women) were included. Static PET parameters peak tumor-to-background ratio and metabolic tumor volume (respective thresholds of 1.9 and 1.5 mL) showed the best 84% accuracies for predicting PFS at 6 months (p = 0.02). These static PET parameters were also independent predictor of PFS in multivariate analysis (p ≤ 0.05). CONCLUSION: In HGG patients having undergone a Stupp protocol, the absence of significant PET uptake after TMZ constitutes a favorable prognostic factor.


Asunto(s)
Antineoplásicos Alquilantes , Neoplasias Encefálicas , Glioma , Tomografía de Emisión de Positrones , Temozolomida , Humanos , Temozolomida/uso terapéutico , Femenino , Masculino , Glioma/tratamiento farmacológico , Glioma/diagnóstico por imagen , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Pronóstico , Anciano , Antineoplásicos Alquilantes/uso terapéutico , Aminoácidos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Clasificación del Tumor , Dihidroxifenilalanina/análogos & derivados , Estudios de Seguimiento
15.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38931393

RESUMEN

PURPOSE: This study aimed to evaluate the feasibility of using [68Ga]-fibroblast-activating protein inhibitor (FAPI) positron emission tomography (PET) imaging for diagnosing pulmonary fibrosis in a mouse model. We also examined its value in monitoring treatment response and compared it with traditional [18F]-fluorodeoxyglucose (FDG) PET and computed tomography (CT) imaging. METHODS: A model of idiopathic pulmonary fibrosis was established using intratracheal injection of bleomycin (BLM, 2 mg/kg) into C57BL/6 male mice. For the treatment of IPF, a daily oral dose of 400 mg/kg/day of pirfenidone was administered from 9 to 28 days after the establishment of the model. Disease progression and treatment efficacy were assessed at different stages of the disease every week for four weeks using CT, [18F]FDG PET, and [68Ga]FAPI PET (baseline imaging performed at week 0). Mice were sacrificed and lung tissues were harvested for hematoxylin-eosin staining, picrosirius red staining, and immunohistochemical staining for glucose transporter 1 (GLUT1) and FAP. Expression levels of GLUT1 and FAP in pathological sections were quantified. Correlations between imaging parameters and pathological quantitative values were analyzed. RESULTS: CT, [18F]FDG PET and [68Ga]FAPI PET revealed anatomical and functional changes in the lung that reflected progression of pulmonary fibrosis. In untreated mice with pulmonary fibrosis, lung uptake of [18F]FDG peaked on day 14, while [68Ga]FAPI uptake and mean lung density peaked on day 21. In mice treated with pirfenidone, mean lung density and lung uptake of both PET tracers decreased. Mean lung density, [18F]FDG uptake, and [68Ga]FAPI uptake correlated well with quantitative values of picrosirius red staining, GLUT1 expression, and FAP expression, respectively. Conclusions: Although traditional CT and [18F]FDG PET reflect anatomical and metabolic status in fibrotic lung, [68Ga]FAPI PET provides a means of evaluating fibrosis progression and monitoring treatment response.

16.
Biomedicines ; 12(6)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38927360

RESUMEN

INTRODUCTION: After receiving different lines of treatment, multiple myeloma patients tend to present with less secretory and more frequent extramedullary disease. These features make treatment monitoring and follow-up very complex since they have to be based on the use of imaging methods and/or bone marrow aspirations or biopsies. OBJECTIVE: To present the case of a patient with myeloma progressing with non-secretory bone disease and to discuss the potential impact of mass spectrometry as a new highly sensitive method able to identify the monoclonal protein (MP) in the serum of these types of patients. MATERIALS AND METHODS: Informed consent was signed by the patient prior to receiving each line of treatment. The clinical information and images were obtained from anonymized electronic files. The mass spectrometry was performed with the Immunoglobulin Isotypes (GAM) assay for the mass spectrometry EXENT® Analyser Technology from Binding Site, part of Thermofisher. RESULTS: A 73-year-old male with IgG kappa multiple myeloma progressing with a new lytic lesion after receiving 14 cycles of Talquetamab as a third line of therapy who, due to the non-secretory nature of the disease at this point, could not be enrolled in a clinical trial, thus limiting his therapeutic options. The mass spectrometry was able to identify and quantify the presence of the patient's MP when the serum protein electrophoresis and immunofixation were still negative and therefore could have been used to confirm the progression, to permit the inclusion of the patient in a clinical trial and to further monitor the disease response. CONCLUSIONS: The higher sensitivity of the mass spectrometry methods to detect the MP in patients with myeloma and other monoclonal gammopathies translates into better identification of the disease progression, permits the inclusion of more patients in clinical trials and facilitates treatment monitoring.

17.
Int J Mol Sci ; 25(11)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38891959

RESUMEN

The tyrosine kinase domain of the FMS-Like tyrosine kinase 3 (FLT3-TKD) is recurrently mutated in acute myeloid leukemia (AML). Common molecular techniques used in its detection include PCR and capillary electrophoresis, Sanger sequencing and next-generation sequencing with recognized sensitivity limitations. This study aims to validate the use of droplet digital PCR (ddPCR) in the detection of measurable residual disease (MRD) involving the common FLT3-TKD mutations (D835Y, D835H, D835V, D835E). Twenty-two diagnostic samples, six donor controls, and a commercial D835Y positive control were tested using a commercial Bio-rad® ddPCR assay. All known variants were identified, and no false positives were detected in the wild-type control (100% specificity and sensitivity). The assays achieved a limit of detection suitable for MRD testing at 0.01% variant allelic fraction. Serial samples from seven intensively-treated patients with FLT3-TKD variants at diagnosis were tested. Five patients demonstrated clearance of FLT3-TKD clones, but two patients had FLT3-TKD persistence in the context of primary refractory disease. In conclusion, ddPCR is suitable for the detection and quantification of FLT3-TKD mutations in the MRD setting; however, the clinical significance and optimal management of MRD positivity require further exploration.


Asunto(s)
Leucemia Mieloide Aguda , Mutación , Neoplasia Residual , Reacción en Cadena de la Polimerasa , Tirosina Quinasa 3 Similar a fms , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
18.
Cancers (Basel) ; 16(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38730633

RESUMEN

Liquid biopsy involves the utilization of minimally invasive or noninvasive techniques to detect biomarkers in biofluids for disease diagnosis, monitoring, or guiding treatments. This approach is promising for the early diagnosis of childhood cancer, especially for brain tumors, where tissue biopsies are more challenging and cause late detection. Extracellular vesicles offer several characteristics that make them ideal resources for childhood cancer liquid biopsy. Extracellular vesicles are nanosized particles, primarily secreted by all cell types into body fluids such as blood and urine, and contain molecular cargos, i.e., lipids, proteins, and nucleic acids of original cells. Notably, the lipid bilayer-enclosed structure of extracellular vesicles protects their cargos from enzymatic degradation in the extracellular milieu. Proteins and nucleic acids of extracellular vesicles represent genetic alterations and molecular profiles of childhood cancer, thus serving as promising resources for precision medicine in cancer diagnosis, treatment monitoring, and prognosis prediction. This review evaluates the recent progress of extracellular vesicles as a liquid biopsy platform for various types of childhood cancer, discusses the mechanistic roles of molecular cargos in carcinogenesis and metastasis, and provides perspectives on extracellular vesicle-guided therapeutic intervention. Extracellular vesicle-based liquid biopsy for childhood cancer may ultimately contribute to improving patient outcomes.

19.
Inn Med (Heidelb) ; 65(6): 566-575, 2024 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-38743073

RESUMEN

Outpatient parenteral anti-infective therapy (OPAT) involves the administration of intravenous anti-infectives outside a hospital setting. This shortens the inpatient stay and leads to a reduction in treatment costs, fewer instances of nosocomial infections and enhanced quality of life for the patient.


Asunto(s)
Antiinfecciosos , Humanos , Antiinfecciosos/administración & dosificación , Antiinfecciosos/uso terapéutico , Infección Hospitalaria/prevención & control , Infección Hospitalaria/tratamiento farmacológico , Atención Ambulatoria , Calidad de Vida , Infusiones Intravenosas , Infusiones Parenterales
20.
Int J Mol Sci ; 25(7)2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38612833

RESUMEN

Angiosarcoma is a rare and aggressive type of soft-tissue sarcoma with high propensity to metastasize. For patients with metastatic angiosarcoma, prognosis is dismal and treatment options are limited. To improve the outcomes, identifying patients with poor treatment response at an earlier stage is imperative, enabling alternative therapy. Consequently, there is a need for improved methods and biomarkers for treatment monitoring. Quantification of circulating tumor-DNA (ctDNA) is a promising approach for patient-specific monitoring of treatment response. In this case report, we demonstrate that quantification of ctDNA using SiMSen-Seq was successfully utilized to monitor a patient with metastatic angiosarcoma. By quantifying ctDNA levels using 25 patient-specific mutations in blood plasma throughout surgery and palliative chemotherapy, we predicted the outcome and monitored the clinical response to treatment. This was accomplished despite the additional complexity of the patient having a synchronous breast cancer. The levels of ctDNA showed a superior correlation to the clinical outcome compared with the radiological evaluations. Our data propose a promising approach for personalized biomarker analysis to monitor treatment in angiosarcomas, with potential applicability to other cancers and for patients with synchronous malignancies.


Asunto(s)
Neoplasias de la Mama , Hemangiosarcoma , Neoplasias Primarias Secundarias , Sarcoma , Humanos , Femenino , Hemangiosarcoma/genética , Hemangiosarcoma/terapia , Neoplasias de la Mama/genética
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