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PURPOSE: To compare T1 and T2 measurements across commercial and prototype 0.55T MRI systems in both phantom and healthy participants using the same vendor-neutral pulse sequences, reconstruction, and analysis methods. METHODS: Standard spin echo measurements and abbreviated protocol measurements of T1, B1, and T2 were made on two prototype 0.55 T systems and two commercial 0.55T systems using an ISMRM/NIST system phantom. Additionally, five healthy participants were imaged at each system using the abbreviated protocol for T1, B1, and T2 measurement. The phantom measurements were compared to NMR-based reference measurements to determine accuracy, and both phantom and in vivo measurements were compared to assess reproducibility and differences between the prototype and commercial systems. RESULTS: Vendor-neutral sequences were implemented across all four systems, and the code for pulse sequences and reconstruction is freely available. For participants, there was no difference in the mean T1 and T2 relaxation times between the prototype and commercial systems. In the phantom, there were no significant differences between the prototype and commercial systems for T1 and T2 measurements using the abbreviated protocol. CONCLUSION: Quantitative T1 and T2 measurements at 0.55T in phantom and healthy participants are not statistically different across the prototype and commercial systems.
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Substaging of T1 urothelial cancer is associated with tumor progression and its reporting is recommended by international guidelines. However, it has not been integrated in risk stratification tools and there is no agreement on the best method to use for its reporting. We aimed to investigate the applicability, interobserver variability, and prognostic value of histological landmark based and micrometric (aggregate linear length of invasive carcinoma (ALLICA), microscopic vs. extensive system, Rete Oncologica Lombarda (ROL) system) substaging methods. A total of 79 patients with the primary diagnosis of T1 urothelial cancer treated with conventional transurethral resection and adjuvant BCG therapy between 2000 and 2020 at the Medical University of Vienna were included. The anatomical and metrical substaging systems were evaluated using agreement rate, Cohen's kappa, Kendall's tau, and Spearman rank correlation. Prognostic value for high-grade recurrence or T2 progression was evaluated in uni- and multivariable analysis. Applicability and reproducibility were good to moderate and varied between substaging methods. Obstacles are mainly due to fragmentation of samples. Anatomical substaging was associated with progression in univariable and multivariable analysis. In our cohort, we could only identify anatomical landmark-based substaging to be prognostic for T2 progression. A major obstacle for proper pathological assessment is fragmentation of samples due to operational procedure. Avoiding such fragmentation might improve reproducibility and significance of pathological T1 substaging of urothelial cancer.
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BACKGROUND: Neoadjuvant chemotherapy can cause hepatic sinusoidal obstruction syndrome (SOS) in patients with colorectal cancer liver metastases and increases postoperative morbidity and mortality. AIM: To evaluate T1 mapping based on gadoxetic acid-enhanced magnetic resonance imaging (MRI) for diagnosis of hepatic SOS induced by monocrotaline. METHODS: Twenty-four mice were divided into control (n = 10) and experimental (n = 14) groups. The experimental groups were injected with monocrotaline 2 or 6 days before MRI. MRI parameters were: T1 relaxation time before enhancement; T1 relaxation time 20 minutes after enhancement (T1post); a reduction in T1 relaxation time (â³T1%); and first enhancement slope percentage of the liver parenchyma (ESP). Albumin and bilirubin score was determined. Histological results served as a reference. Liver parenchyma samples from the control and experimental groups were analyzed by western blotting, and organic anion transporter polypeptide 1 (OATP1) was measured. RESULTS: T1post, â³T1%, and ESP of the liver parenchyma were significantly different between two groups (all P < 0.001) and significantly correlated with the total histological score of hepatic SOS (r = -0.70, 0.68 and 0.79; P < 0.001). â³T1% and ESP were positively correlated with OATP1 levels (r = 0.82, 0.85; P < 0.001), whereas T1post had a negative correlation with OATP1 levels (r = -0.83; P < 0.001). CONCLUSION: T1 mapping based on gadoxetic acid-enhanced MRI may be useful for diagnosis of hepatic SOS, and MRI parameters were associated with OATP1 levels.
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Aims: Recent studies have shown that extracellular volume (ECV) can also be obtained without blood sampling by the linear relationship between haematocrit (HCT) and blood pool R1 (1/T1). However, whether this relationship holds for patients with myocardial infarction is still unclear. This study established and validated an ECV model without blood sampling in ST-segment elevation myocardial infarction (STEMI) patients. Methods and results: A total of 398 STEMI patients who underwent cardiac magnetic resonance (CMR) examination with T1 mapping and venous HCT within 24â h were retrospectively analysed. All patients were randomly divided into a derivation group and a validation group. The mean CMR scan time was 3â days after primary percutaneous coronary intervention. In the derivation group, a synthetic HCT formula was obtained by the linear regression between HCT and blood pool R1 (R 2 = 0.45, P < 0.001). The formula was used in the validation group; the results showed high concordance and correlation between synthetic ECV and conventional ECV in integral (bias = -0.12; R 2 = 0.92, P < 0.001), myocardial infarction site (bias = -0.23; R 2 = 0.93, P < 0.001), and non-myocardial infarction sites (bias = -0.09; R 2 = 0.94, P < 0.001). Conclusion: In STEMI patients, synthetic ECV without blood sampling had good consistency and correlation with conventional ECV. This study might provide a convenient and accurate method to obtain the ECV from CMR to identify myocardial fibrosis.
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T1 ρ and Quantitative Susceptibility Mapping (QSM) are evolving as substrates for quantifying the progressive nature of knee osteoarthritis. Objective: To evaluate the effects of spin lock time combinations on depth-dependent T1 ρ estimation, in adjunct to QSM, and characterize the degree of shared variance in QSM and T1 ρ for the quantitative measurement of articular cartilage. Design: Twenty healthy participants (10 âM/10F, 22.2 â± â3.4 years) underwent bilateral knee MRI using T1 ρ MAPPS sequences with varying TSLs ([0-120] ms), along with a 3D spoiled gradient echo for QSM. Five total TSL combinations were used for T1 ρ computation, and direct depth-based comparison. Depth-wide variance was assessed in comparison to QSM as a basis to assess for depth-specific variation in T1 ρ computations across healthy cartilage. Results: Longer T1 ρ relaxation times were observed for TSL combinations with higher spin lock times. Depth-specific differences were documented for both QSM and T1 ρ , with most change found at â¼60% depth of the cartilage, relative to the surface. Direct squared linear correlation revealed that most T1 ρ TSL combinations can explain over 30% of the variability in QSM, suggesting inherent shared sensitivity to cartilage microstructure. Conclusions: T1 ρ mapping is subjective to the spin lock time combinations used for computation of relaxation times. When paired with QSM, both similarities and differences in signal sensitivity may be complementary to capture depth-wide changes in articular cartilage.
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Background: Determining brain atrophy is crucial for the diagnosis of neurodegenerative diseases. Despite detailed brain atrophy assessments using three-dimensional (3D) T1-weighted magnetic resonance imaging, their practical utility is limited by cost and time. This study introduces deep learning algorithms for quantifying brain atrophy using a more accessible two-dimensional (2D) T1, aiming to achieve cost-effective differentiation of dementia of the Alzheimer's type (DAT) from cognitively unimpaired (CU), while maintaining or exceeding the performance obtained with T1-3D individuals and to accurately predict AD-specific atrophy similarity and atrophic changes [W-scores and Brain Age Index (BAI)]. Methods: Involving 924 participants (478 CU and 446 DAT), our deep learning models were trained on cerebrospinal fluid (CSF) volumes from 2D T1 images and compared with 3D T1 images. The performance of the models in differentiating DAT from CU was assessed using receiver operating characteristic analysis. Pearson's correlation analyses were used to evaluate the relations between 3D T1 and 2D T1 measurements of cortical thickness and CSF volumes, AD-specific atrophy similarity, W-scores, and BAIs. Results: Our deep learning models demonstrated strong correlations between 2D and 3D T1-derived CSF volumes, with correlation coefficients r ranging from 0.805 to 0.971. The algorithms based on 2D T1 accurately distinguished DAT from CU with high accuracy (area under the curve values of 0.873), which were comparable to those of algorithms based on 3D T1. Algorithms based on 2D T1 image-derived CSF volumes showed high correlations in AD-specific atrophy similarity (r = 0.915), W-scores for brain atrophy (0.732 ≤ r ≤ 0.976), and BAIs (r = 0.821) compared with those based on 3D T1 images. Conclusion: Deep learning-based analysis of 2D T1 images is a feasible and accurate alternative for assessing brain atrophy, offering diagnostic precision comparable to that of 3D T1 imaging. This approach offers the advantage of the availability of T1-2D imaging, as well as reduced time and cost, while maintaining diagnostic precision comparable to T1-3D.
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AIMS: Human recombinant insulin is currently the only therapy for children and adolescents with type 1 diabetes (T1D), although not always efficient for the glycemic control of these individuals. The interrelation between the gut microbiome and the glycemic control of apparently healthy populations, as well as various populations with diabetes, is undeniable. Probiotics are biotherapeutics that deliver active components to various targets, primarily the gastrointestinal tract. This systematic review and meta-analysis examined the effect of the administration of probiotics on the glycemic control of pediatric and adolescent individuals with T1D. MATERIALS AND METHODS: Randomized controlled trials employing the administration of probiotics in children and adolescents with T1D (with ≥10 individuals per treatment arm), written in English, providing parameters of glycemic control, such as mean glucose concentrations and glycosylated hemoglobin (HbA1c), were deemed eligible. RESULTS: The search strategy resulted in six papers with contradictory findings. Ultimately, five studies of acceptable quality, comprising 388 children and adolescents with T1D, were included in the meta-analysis. Employing a random and fixed effects model revealed statistically significant negative effect sizes of probiotics on the glycemic control of those individuals, i.e., higher concentrations of glucose and HbA1c than controls. CONCLUSIONS: Children and adolescents with T1D who received probiotics demonstrated worse glycemic control than controls after the intervention. Adequately powered studies, with extended follow-up periods, along with monitoring of compliance and employing the proper strains, are required to unravel the mechanisms of action and the relative effects of probiotics, particularly concerning diabetes-related complications and metabolic outcomes.
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Glucemia , Diabetes Mellitus Tipo 1 , Hemoglobina Glucada , Control Glucémico , Probióticos , Humanos , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Adolescente , Niño , Control Glucémico/métodos , Glucemia/metabolismo , Hemoglobina Glucada/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Microbioma Gastrointestinal , Femenino , MasculinoRESUMEN
The different susceptibility to HIV-1 infection in U937 cells-permissive (Plus) or nonpermissive (Minus)-is linked to the expression in Minus cells of interferon (IFN)-γ inducible antiviral factors such as tripartite motif-containing protein 22 (TRIM22) and class II transactivator (CIITA). CIITA interacts with Cyclin T1, a key component of the Positive-Transcription Elongation Factor b (P-TEFb) complex needed for the efficient transcription of HIV-1 upon interaction with the viral transactivator Tat. TRIM22 interacts with CIITA, recruiting it into nuclear bodies together with Cyclin T1. A 50 kDa Cyclin T1 was found only in Minus cells, alongside the canonical 80 kDa protein. The expression of this truncated form remained unaffected by proteasome inhibitors but was reduced by IFNγ treatment. Unlike the nuclear full-length protein, truncated Cyclin T1 was also present in the cytoplasm, and this subcellular localization correlated with its capacity to inhibit Tat-mediated HIV-1 transcription. The 50 kDa Cyclin T1 in Minus cells likely contributes to their non-permissive phenotype by acting as a dominant negative factor, disrupting P-TEFb complex formation and function. Its reduction upon IFNγ treatment suggests a regulatory loop by which its inhibitory role on HIV-1 replication is then exerted by the IFNγ-induced CIITA, which binds to the canonical Cyclin T1, displacing it from the P-TEFb complex.
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Ciclina T , VIH-1 , Humanos , Ciclina T/metabolismo , VIH-1/fisiología , Células U937 , Infecciones por VIH/virología , Infecciones por VIH/metabolismo , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/genética , Replicación Viral , Fenotipo , Interferón gamma/farmacología , Interferón gamma/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Antígenos de Histocompatibilidad MenorRESUMEN
PURPOSE: Myocardial T1ρ mapping techniques commonly acquire multiple images in one breathhold to calculate a single-slice T1ρ map. Recently, non-selective adiabatic pulses have been used for robust spin-lock preparation (T1ρ,adiab). The objective of this study was to develop a fast multi-slice myocardial T1ρ,adiab mapping approach. METHODS: The proposed-sequence reduces the number of breathholds required for whole-heart 2D T1ρ,adiab mapping by acquiring multiple interleaved slices in each breathhold using slice-selective T1ρ,adiab preparation pulses. The proposed-sequence was implemented with two interleaved slices per breathhold scan and was quantitatively evaluated in phantom experiments and 10 healthy-volunteers against a single-slice T1ρ,adiab mapping sequence. The sequence was demonstrated in two patients with myocardial scar. RESULTS: The phantom experiments showed the proposed-sequence had slice-to-slice variation of 1.62% ± 1.05% and precision of 4.51 ± 0.68 ms. The healthy volunteer cohort subject-wise mean relaxation time was lower for the proposed-sequence than the single-slice sequence (137.7 ± 5.3 ms vs. 148.4 ± 8.3 ms, p < 0.001), and spatial-standard-deviation was better (18.7 ± 1.8 ms vs. 21.8 ± 3.4 ms, p < 0.018). The mean within-subject, coefficient of variation was 5.93% ± 1.57% for the proposed-sequence and 6.31% ± 1.92% for the single-slice sequence (p = 0.35) and the effect of slice variation (0.81 ± 4.87 ms) was not significantly different to zero (p = 0.61). In both patient examples increased T1ρ,adiab (maximum American Heart Association-segment mean = 174 and 197 ms) was measured within the myocardial scar. CONCLUSION: The proposed sequence provides a twofold acceleration for myocardial T1ρ,adiab mapping using a multi-slice approach. It has no significant difference in within-subject variability, and significantly better precision, compared to a 2D T1ρ,adiab mapping sequence based on non-selective adiabatic spin-lock preparations.
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Cathepsin G (CTSG) plays an important role in the regulation of immune processes. Accumulated studies show that CTSG is involved in the onset and development of type 1 diabetes mellitus (T1DM). As the genetic background of T1DM varies widely among populations, we aimed to study the relationship between genetic polymorphisms in CTSG and T1DM susceptibility in Chinese populations. A total of 141 patients with T1DM and 200 healthy controls were enrolled in the study. Serum CTSG expression was detected using enzyme-linked immunosorbent assay (ELISA). Genotyping of two selected single nucleotide polymorphisms (SNPs) (rs2236742 and rs2070697) of CTSG was performed using PCR and Sanger sequencing. CTSG expression in patients with T1DM was significantly higher than in the control group. Alleles C and T of CTSG SNP rs2236742 were increased in T1DM. No significant associations were found for the SNP rs2070697. Our results indicate that the CTSG rs2236742 allele (C/T) is associated with T1DM in Chinese children and may serve as a new biomarker for predicting T1DM susceptibility.
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Alelos , Pueblo Asiatico , Diabetes Mellitus Tipo 1 , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo de Nucleótido Simple , Humanos , Diabetes Mellitus Tipo 1/genética , Femenino , Masculino , Niño , Estudios de Casos y Controles , Pueblo Asiatico/genética , China/epidemiología , Preescolar , Frecuencia de los Genes , Ensayo de Inmunoadsorción Enzimática , Adolescente , Reacción en Cadena de la Polimerasa , Biomarcadores/sangre , Pueblos del Este de AsiaRESUMEN
Obesity among adolescents poses a significant global health concern with profound short- and long-term impact on physical and mental well-being. The intricate relationship between obesity and the onset of diabetes remains ambiguous, particularly in cases where the manifestation may differ from that observed in individuals with uncomplicated obesity. Herein, we present the case of a 14-year-old male adolescent with Prader-Willi phenotype and subsequent obesity, exhibiting symptoms of polyuria and polydipsia over a 10-day period, indicative of potential diabetes mellitus (DM). Laboratory assessments revealed a hemoglobin A1c level of 10%, confirming the suspected diagnosis. Notably, despite the absence of ketosis, elevated C-peptide levels and the presence of slightly positive islet-cell antibodies warranted further investigation. While the presence of antibodies typically aligns with a diagnosis of type 1 DM, recent research has highlighted the occurrence of anti-insulin pancreatic cell antibodies in type 2 DM cases. This article aims to delve into the multifaceted issues surrounding adolescent obesity, atypical presentations of DM with positive antibodies, and the long-term management of patients with genetic syndromes.
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BACKGROUND: Type 1 diabetes mellitus (T1DM) is well-known to trigger a disruption of lipid metabolism. This study aimed to compare lipid profile changes in T1DM patients after achieving glucose control and explore the underlying mechanisms. In addition, we seek to identify novel lipid biomarkers associated with T1DM under conditions of glycemic control. METHODS: A total of 27 adults with T1DM (age: 34.3 ± 11.2 yrs) who had maintained glucose control for over a year, and 24 healthy controls (age: 35.1 + 5.56 yrs) were recruited. Clinical characteristics of all participants were analyzed and plasma samples were collected for untargeted lipidomic analysis using mass spectrometry. RESULTS: We identified 594 lipid species from 13 major classes. Differential analysis of plasma lipid profiles revealed a general decline in lipid levels in T1DM patients with controlled glycemic levels, including a notable decrease in triglycerides (TAGs) and diglycerides (DAGs). Moreover, these T1DM patients exhibited lower levels of six phosphatidylcholines (PCs) and three phosphatidylethanolamines (PEs). Random forest analysis determined DAG(14:0/20:0) and PC(18:0/20:3) to be the most prominent plasma markers of T1DM under glycemic control (AUC = 0.966). CONCLUSIONS: The levels of all metabolites from the 13 lipid classes were changed in T1DM patients under glycemic control, with TAGs, DAGs, PCs, PEs, and FFAs demonstrating the most significant decrease. This research identified DAG(14:0/20:0) and PC(18:0/20:3) as effective plasma biomarkers in T1DM patients with controled glycemic levels.
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Biomarcadores , Glucemia , Diabetes Mellitus Tipo 1 , Control Glucémico , Lípidos , Humanos , Diabetes Mellitus Tipo 1/sangre , Masculino , Femenino , Biomarcadores/sangre , Adulto , Lípidos/sangre , Glucemia/análisis , Glucemia/metabolismo , Estudios de Casos y Controles , Persona de Mediana Edad , Metabolismo de los Lípidos , Lipidómica/métodos , PronósticoRESUMEN
Coronary artery disease (CAD) is the leading cause of death in India. Many genetic polymorphisms play a role in regulating oxidative stress, blood pressure and lipid metabolism, contributing to the pathophysiology of CAD. This study examined the association between ten polymorphisms and CAD in the Jat Sikh population from Northern India, also considering polygenic risk scores. This study included 177 CAD cases and 175 healthy controls. The genetic information of GSTM1 (rs366631), GSTT1 (rs17856199), ACE (rs4646994), AGT M235T (rs699), AGT T174M (rs4762), AGTR1 A1166C (rs5186), APOA5 (rs3135506), APOC3 (rs5128), APOE (rs7412) and APOE (rs429358) and clinical information was collated. Statistical analyses were performed using SPSS version 27.0 and SNPstats. Significant independent associations were found for GST*M1, GST*T1, ACE, AGT M235T, AGT T174M, AGTR1 A1166C and APOA5 polymorphisms and CAD risk (all p < 0.05). The AGT CT haplotype was significantly associated with a higher CAD risk, even after controlling for covariates (adjusted OR = 3.93, 95% CI [2.39-6.48], p < 0.0001). The APOA5/C3 CC haplotype was also significantly associated with CAD (adjusted OR = 1.86, 95% CI [1.14-3.03], p < 0.05). A higher polygenic risk score was associated with increased CAD risk (adjusted OR = 1.98, 95% CI [1.68-2.34], p < 0.001). Seven polymorphisms were independently associated with an increase in the risk of CAD in this North Indian population. A considerable risk association of AGT, APOA5/C3 haplotypes and higher genetic risk scores is documented, which may have implications for clinical and public health applications.
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Angiotensinógeno , Apolipoproteína A-V , Apolipoproteínas E , Enfermedad de la Arteria Coronaria , Puntuación de Riesgo Genético , Glutatión Transferasa , Polimorfismo de Nucleótido Simple , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Angiotensinógeno/genética , Apolipoproteína A-V/genética , Apolipoproteína C-III , Apolipoproteínas E/genética , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/epidemiología , Frecuencia de los Genes , Estudios de Asociación Genética , Glutatión Transferasa/genética , Haplotipos , India/epidemiología , Peptidil-Dipeptidasa A/genética , Receptor de Angiotensina Tipo 1/genética , Factores de RiesgoRESUMEN
OBJECTIVE: The purpose of this study was to investigate an approach for motion-corrected T1 mapping of the abdomen that allows for free breathing data acquisition with 100% scan efficiency. MATERIALS AND METHODS: Data were acquired using a continuous golden radial trajectory and multiple inversion pulses. For the correction of respiratory motion, motion estimation based on a surrogate was performed from the same data used for T1 mapping. Image-based self-navigation allowed for binning and reconstruction of respiratory-resolved images, which were used for the estimation of respiratory motion fields. Finally, motion-corrected T1 maps were calculated from the data applying the estimated motion fields. The method was evaluated in five healthy volunteers. For the assessment of the image-based navigator, we compared it to a simultaneously acquired ultrawide band radar signal. Motion-corrected T1 maps were evaluated qualitatively and quantitatively for different scan times. RESULTS: For all volunteers, the motion-corrected T1 maps showed fewer motion artifacts in the liver as well as sharper kidney structures and blood vessels compared to uncorrected T1 maps. Moreover, the relative error to the reference breathhold T1 maps could be reduced from up to 25% for the uncorrected T1 maps to below 10% for the motion-corrected maps for the average value of a region of interest, while the scan time could be reduced to 6-8 s. DISCUSSION: The proposed approach allows for respiratory motion-corrected T1 mapping in the abdomen and ensures accurate T1 maps without the need for any breathholds.
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PURPOSE: Calculation of extracellular volume fraction (ECV), a marker of myocardial fibrosis in cardiac magnetic resonance imaging (CMR), requires hematocrit (Hct). We aimed to correlate Hct levels with native blood T1 times, to derive a formula for estimating synthetic Hct (Hctsyn) and synthetic ECV (ECVsyn), to assess accuracy of ECVsyn and to compare our model with published formulas. METHOD: In this retrospective study, a cohort of 250 CMR scans with T1 mapping (3T, MOLLI 5(3)3, endsystolic aquisition), was divided into a derivation and validation cohort. Native T1 times of the left ventricular blood pool (T1native,midLV) were correlated with Hct levels from blood sampling within 24 h (Hct24h) and a formula for calculation of Hctsyn was derived by linear regression. RESULTS: In the derivation cohort (n = 167), Hct24h showed a good association with T1native,midLV (r = -0.711, p < 0.001). The resulting regression equation was Hctsyn = 1/T1native,midLV * 1355.52-0.310. In the validation cohort (n = 83), Hctsyn and Hct24h showed good correlation (r = 0.726, p < 0.001), while ECVsyn, and ECV24h demonstrated excellent correlation (r = 0.940, p < 0.001). ECVsyn had a minimal bias of 0.28 % and the misclassification rate (8.8 %) was comparable to the variability introduced by repeated Hct measurements (misclassification in 7.5 %). Applying published formulas in our cohort resulted in incorrect classification in up to 60 %. CONCLUSION: We provide a formula for estimating Hctsyn from native blood T1 on a 3T scanner. The measurement error of ECVsyn is low and comparable to the error due to retest variability of conventional Hct. Scanner- and sequence-specific formulas should be used.
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Imagen por Resonancia Magnética , Humanos , Hematócrito , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Interpretación de Imagen Asistida por Computador/métodos , Sensibilidad y Especificidad , AlgoritmosRESUMEN
Replacement of beta cells through transplantation is a potential therapeutic approach for individuals with pancreas removal or poorly controllable type 1 diabetes. However, stress and death of beta cells pose significant challenges. Circulating miRNA has emerged as potential biomarkers reflecting early beta cell stress and death, allowing for timely intervention. The aim of this study was to identify miRNAs as potential biomarkers for beta cell health. Literature review combined with small RNA sequencing was employed to select islet-enriched miRNA. The release of those miRNA was assessed by RT-qPCR in vivo, using a streptozotocin induced diabetes mouse model and in vitro, through mouse and human islets exposed to varying degrees of hypoxic and cytokine stressors. Utilizing the streptozotocin induced model, we identified 18 miRNAs out of 39 candidate islet-enriched miRNA to be released upon islet stress in vivo. In vitro analysis of culture supernatants from cytokine and/or hypoxia stressed islets identified the release of 45 miRNAs from mouse and 8 miRNAs from human islets. Investigation into the biological pathways targeted by the cytokine- and/or hypoxia-induced miRNA suggested the involvement of MAPK and PI3K-Akt signaling pathways in both mouse and human islets. We have identified miRNAs associated with beta cell health and stress. The findings allowed us to propose a panel of 47 islet-related human miRNA that is potentially valuable for application in clinical contexts of beta cell transplantation and presymptomatic early-stage type 1 diabetes.
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Diabetes Mellitus Experimental , Islotes Pancreáticos , MicroARNs , Animales , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Ratones , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Islotes Pancreáticos/metabolismo , Células Secretoras de Insulina/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estrés Fisiológico/genética , Masculino , RNA-Seq/métodos , Ratones Endogámicos C57BL , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismoRESUMEN
BACKGROUND: Blast transformation is a rare but well-recognized event in Philadelphia-negative myeloproliferative neoplasms associated with a poor prognosis. Secondary acute myeloid leukemias evolving from myeloproliferative neoplasms are characterized by a unique set of cytogenetic and molecular features distinct from de novo disease. t(8;21) (q22;q22.1); RUNX1::RUNX1T1, one of the most frequent cytogenetic abnormalities in de novo acute myeloid leukemia, is rarely observed in post-myeloproliferative neoplasm acute myeloid leukemia. Here we report a case of secondary acute myeloid leukemia with t(8;21) evolving from JAK2-mutated essential thrombocythemia. CASE PRESENTATION: The patient was a 74-year-old Japanese woman who was referred because of thrombocytosis (platelets 1046 × 109/L). Bone marrow was hypercellular with increase of megakaryocytes. Chromosomal analysis presented normal karyotype and genetic test revealed JAK2 V617F mutation. She was diagnosed with essential thrombocythemia. Thrombocytosis had been well controlled by oral administration of hydroxyurea; 2 years after the initial diagnosis with ET, she presented with leukocytosis (white blood cells 14.0 × 109/L with 82% of blasts), anemia (hemoglobin 91 g/L), and thrombocytopenia (platelets 24 × 109/L). Bone marrow was hypercellular and filled with 80% of myeloperoxidase-positive blasts bearing Auer rods. Chromosomal analysis revealed t(8;21) (q22;q22.1) and flow cytometry presented positivity of CD 13, 19, 34, and 56. Molecular analysis showed the coexistence of RUNX1::RUNX1T1 chimeric transcript and heterozygous JAK2 V617F mutation in leukemic blasts. She was diagnosed with secondary acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 evolving from essential thrombocythemia. She was treated with combination chemotherapy with venetoclax and azacytidine. After the first cycle of the therapy, blasts disappeared from peripheral blood and decreased to 1.4% in bone marrow. After the chemotherapy, RUNX1::RUNX1T1 chimeric transcript disappeared, whereas mutation of JAK2 V617F was still present in peripheral leukocytes. CONCLUSIONS: To our best knowledge, the present case is the first one with JAK2 mutation preceding the acquisition of t(8;21). Our result suggests that t(8;21); RUNX1::RUNX1T1 can be generated as a late event in the progression of JAK2-mutated myeloproliferative neoplasms. The case presented typical morphological and immunophenotypic features associated with t(8;21) acute myeloid leukemia.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal , Janus Quinasa 2 , Leucemia Mieloide Aguda , Trombocitemia Esencial , Translocación Genética , Humanos , Femenino , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Anciano , Janus Quinasa 2/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Trombocitemia Esencial/genética , Trombocitemia Esencial/tratamiento farmacológico , Proteína 1 Compañera de Translocación de RUNX1/genética , Cromosomas Humanos Par 8/genética , Cromosomas Humanos Par 21/genética , MutaciónRESUMEN
Introduction: Differentiating hypertensive heart disease (HHD) from hypertrophic cardiomyopathy (HCM) is crucial yet challenging due to overlapping clinical and morphological features. Recent studies have explored the use of various cardiac magnetic resonance (CMR) parameters to distinguish between these conditions, but findings have remained inconclusive. This study aims to identify which CMR parameters effectively discriminate between HHD and HCM and to investigate their underlying pathophysiological mechanisms through a meta-analysis. Methods: The researchers conducted a systematic and comprehensive search for all studies that used CMR to discriminate between HHD and HCM and calculated the Hedges'g effect size for each of the included studies, which were then pooled using a random-effects model and tested for the effects of potential influencing variables through subgroup and regression analyses. Results: In this review, 26 studies encompassing 1,349 HHD and 1,581 HCM cases were included for meta-analysis. Analysis revealed that HHD showed a significant lower in T1 mapping (g = -0.469, P < 0.001), extracellular volume (g = -0.417, P = 0.024), left ventricular mass index (g = -0.437, P < 0.001), and maximal left ventricular wall thickness (g = -2.076, P < 0.001), alongside a significant higher in end-systolic volume index (g = 0.993, P < 0.001) and end-diastolic volume index (g = 0.553, P < 0.001), compared to HCM. Conclusion: This study clearly demonstrates that CMR parameters can effectively differentiate between HHD and HCM. HHD is characterized by significantly lower diffuse interstitial fibrosis and myocardial hypertrophy, along with better-preserved diastolic function but lower systolic function, compared to HCM. The findings highlight the need for standardized CMR protocols, considering the significant influence of MRI machine vendors, post-processing software, and study regions on diagnostic parameters. These insights are crucial for improving diagnostic accuracy and optimizing treatment strategies for patients with HHD and HCM. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023470557, PROSPERO (CRD42023470557).
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OBJECTIVES: There is currently no evidence documenting the clinical characteristics and prognosis of non-high-risk patients with incidental stage T1 lung cancer (LC). The aim of this study was to investigate the clinical characteristics and prognosis of non-high-risk patients with incidental stage T1 LC. METHODS: This prospective cohort study included patients with incidental stage T1 LC who were diagnosed pathologically at the First Affiliated Hospital of Chongqing Medical University between 1st Jan 2019 and 31st Dec 2023. The follow-up time for all participants concluded on 31st Jan 2024, or upon death. All included patients were divided into non-high-risk (observation) and high-risk (control) groups based on the 2021 US preventative services task force recommendations. The primary outcomes were overall survival probability and LC-specific survival probability. The secondary outcomes were clinical characteristics, including demographic variables, histological types and TNM staging. RESULTS: We studied 1876 patients with incidental stage T1 LC. Of these, 1491 (79.48%) non-high-risk patients were included in the observation group, and the remaining 385 (20.52%) high-risk patients composed the control group. The follow-up interval was between 0 and 248 months for all participants, with a median time of 41.64 ± 23.85 months. The patients in the observation group were younger and had smaller tumors, more adenocarcinomas, and earlier disease stages than those in the control group (p ≤ 0.001). The overall survival probability (HR = 0.23, [95% CI: 0.18, 0.31], p < 0.001) and the LC-specific survival probability (HR = 0.23, [95% CI: 0.17, 0.31], p < 0.001) for the patients in the observation group were also both higher than those in the control group. The results appeared to be consistent across important subgroups. CONCLUSION: In this study, non-high-risk patients with incidental stage T1 LC were younger, had smaller tumors, had more adenocarcinomas, had a lower probability of metastasis, and had longer survival than did high-risk patients.
Asunto(s)
Neoplasias Pulmonares , Estadificación de Neoplasias , Humanos , Masculino , Femenino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Pronóstico , Hallazgos Incidentales , Análisis de Supervivencia , Adulto , Anciano de 80 o más Años , Factores de RiesgoRESUMEN
BACKGROUND: Psychological resilience is defined as the process and outcome of individuals' successful adaptation to challenging life experiences. The Habenula (Hb) is known to be involved in the stress response; however, the relationship between Hb volume and resilience in humans remains unclear. This study investigated the correlation among resilience, Hb volume, and depressive tendencies in adults. METHODS: Hb volumes were assessed using deep learning techniques applied to 110 healthy participants. Resilience and depression were evaluated using the Connor-Davidson Resilience Scale and Beck Depression Inventory-II, respectively. We examined the relationship between Hb volume and resilience and assessed the mediating effects of resilience on the relationship between Hb volume and depressive tendencies. RESULTS: Correlation analysis revealed a positive correlation between resilience and Hb volume (partial r = 0.176, p = 0.001), which was more pronounced in women (partial r = 0.353, p = 0.003). Hb volumes on the left and right sides exhibited significant lateralization (LI = 0.031, 95 % CI = [0.016, 0.046]). Despite Hb asymmetry, lateralization was not significantly associated with resilience. The mediation analysis shows significant indirect effect of resilience on the relationship between Hb volume and depressive tendencies (ß = -0.093, 95%CI = [-0.189, -0.019]). CONCLUSION: This study found that populations with lower resilience have smaller Hb volume. Previous research has shown that Hb volume decreased with the increasing severity of depression symptoms in patients. Our findings support this view and extend it to a population that has not been clinically diagnosed with depression. Additionally, we found that psychological resilience can be predicted by Hb volume and may serve as a mediating factor indirectly affecting depressive tendencies, even in healthy individuals. LIMITATIONS: Due to its cross-sectional design, this study was unable to analyze dynamic changes in Hb volume during the process of resilience adaptation.