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1.
BMC Urol ; 24(1): 30, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310269

RESUMEN

Kidney stones, a persistent urological condition, continue to affect people globally. In this critical review, we examine the work of Borghi et al. who evaluated patients with idiopathic stone formation and randomised 99 patients to increased water intake (≥ 2 L/day) and 100 patients to usual care in a 5-year randomized controlled trial. The study examined baseline urine volume in individuals with idiopathic calcium stones, recurrence rates, and relevant biochemical factors. The study found reduced recurrence rate (12.1% vs. 27% (p = 0.008)), and time to recurrence with increased water intake (38.7 ± 13.2 months) vs. (25 ± 16.4 months) (p = 0.016). These findings inform clinical practice, contributing to the guideline recommendations that kidney stone patients should aim for fluid intake of at least 2.5 L per day to prevent stone recurrence.


Asunto(s)
Cálculos Renales , Nefrolitiasis , Urología , Humanos , Calcio , Estudios Prospectivos , Agua , Recurrencia , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
HLA ; 103(2): e15364, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38312022

RESUMEN

Transplantation of HLA and/or KIR mismatched allogeneic hematopoietic stem cells can lead NK cells to different states of activation/inhibition or education/resetting and change anti-tumor immunosurveillance. In this study, we used molecular relapse monitoring to investigate a correlation between either missing ligand recognition or variation of the cognate iKIR-HLA pairs with clinical outcomes in patients with hematological malignancies requiring allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients (N = 418) with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), or lymphoma receiving T-cell repleted graft from HLA-matched or partly mismatched unrelated donors between 2012 and 2020 in our center were included in this study. Missing-ligand recognition was assessed through the presence or absence of recipients' HLA ligand for a particular inhibitory KIR (iKIR) exhibited by the donor. Inhibitory KIR-HLA pair number variation was defined by loss or gain of a new cognate pair of HLA-KIR within the new HLA environment of the recipient, compared with the donor's one. Considering the results of our research, we drew the following conclusions: (i) loss of iKIR-HLA cognate pair for C1, C2, and/or Bw4 groups led to significant deterioration of disease-free survival (DFS), molecular relapse, overall survival (OS) and non-relapse mortality (NRM) for patients undergoing allo-HSCT in the standard phase of the disease. This phenomenon was not observed in patients who underwent transplantation in advanced hematological cancer. (ii) The missing ligand recognition had no impact if the proportion of HLA mismatches was not considered; however, adjustments of HLA mismatch level in the compared groups highlighted the adverse effect of the missing ligand constellation. (iii) The adverse effect of adjusted missing ligand suggests a predominance of lost NK cell education over lost NK cell inhibition in posttransplant recipients' new HLA environment. Our results suggested that donors with the loss of an iKIR-HLA cognate pair after transplantation should be avoided, and donors who provided an additional iKIR-HLA cognate pair should be preferred in the allo-HSCT donor selection process.


Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Ligandos , Alelos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Células Asesinas Naturales , Neoplasias Hematológicas/genética , Receptores KIR/genética , Enfermedad Crónica , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Recurrencia
3.
Riv Psichiatr ; 59(1): 20-27, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38362785

RESUMEN

AIM: To evaluate the effectiveness of the Falloon Psychoeducational Family Intervention (PFI), originally developed for the management of schizophrenia, afterwards adapted for early psychosis, in terms of adherence to the treatment, low relapse rate, improvement social functioning and stress management. METHODS: This is a one-year, pragmatic, real-world observational study with subjects consecutively recruited at the Campobasso psychiatry ward (SPDC) or Mental Health Center (MHC) starting in November 2020 over an 18 month period. Patients recruited were asked for consent for family members' participation. The effectiveness of the intervention was evaluated in terms of treatment adherence, discontinuity, relapse rates, clinical symptoms assessed by BPRS and PANSS, improvement in social functioning and stress management. RESULTS: 13 subjects were recruited; 10 males and 3 females, all singles, with a DUP inferior to one year. At the end of the intervention, significant improvements in treatment adherence, absence of drop-outs and relapses, statistically significant improvements in clinical symptoms, social functioning and stress management were found. DISCUSSION AND CONCLUSIONS: The results clearly show that family psychoeducational intervention according to the adapted Falloon model, specifically focused on crisis and early stress management, is effective in improving treatment adherence, clinical outcome and social life of first-episode psychotic patients. The limit is the lack of a control and randomization.


Asunto(s)
Trastornos Psicóticos , Esquizofrenia , Masculino , Femenino , Humanos , Estudios de Seguimiento , Trastornos Psicóticos/psicología , Esquizofrenia/tratamiento farmacológico , Psicoterapia , Recurrencia
4.
PLoS One ; 19(2): e0297929, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38363769

RESUMEN

BACKGROUND: Poor management of mental illnesses is associated with lower treatment adherence, chronification, avoidable re-hospitalisations, and high costs. Remote measurement based care (RMBC) interventions have gained increasing relevance due to its potential in providing a comprehensive and patient-centric approach to mental health management. OBJECTIVES: The systematic review and meta-analysis aims to provide a comprehensive overview and analysis of existing evidence on the use of RMBC for patients with mental illness and to examine the effectiveness of RMBC interventions in alleviating disorder-specific symptoms, reducing relapse and improving recovery-oriented outcomes, global functioning, and quality of life. METHODS AND ANALYSIS: Our multidisciplinary research team will develop a comprehensive search strategy, adapted to each electronic database (PubMed, Medline, Embase, and PsychINFO) to be examined systematically. Studies with patients formally diagnosed by the International Classification of Diseases or the Diagnostic and Statistical Manual of Mental Disorders which include assessment of self-reported psychiatric symptoms will be included. Publications will be reviewed by teams of independent researchers. Quality of studies will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. Outcomes cover symptom-focused or disease-specific outcomes, relapse, recovery-focused outcomes, global functioning, quality of life and acceptability of the intervention. Further data that will be extracted includes study characteristics, target population, intervention, and tracking characteristics. Data will be synthesised qualitatively, summarising findings of the systematic review. Randomised controlled trials (RCTs) will be considered for meta-analysis if data is found comparable in terms of mental illness, study design and outcomes. Cumulative evidence will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation framework. TRIAL REGISTRATION: Trial registration number: PROSPERO CRD42022356176.


Asunto(s)
Trastornos Mentales , Salud Mental , Humanos , Revisiones Sistemáticas como Asunto , Trastornos Mentales/terapia , Enfermedad Crónica , Recurrencia , Metaanálisis como Asunto
5.
PLoS One ; 19(2): e0297805, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38363781

RESUMEN

BACKGROUND: Leukemia cutis (LC) is an extramedullary acute myeloid leukemia (AML) infiltrate. No previous study has described the clinical characteristics and outcomes of Thai patients diagnosed with AML with LC. MATERIALS AND METHODS: We conducted a 7-year retrospective case-control study on Thai AML patients at Siriraj Hospital from November 2013 to July 2020. Patients were divided into LC and non-LC groups. Initial clinical presentations and laboratory findings were examined to identify LC-associated factors. Overall survival (OS) and relapse-free survival (RFS) were assessed. Pathological tissues underwent re-evaluation to validate the LC diagnoses. RESULTS: The study included 159 patients in a 2:1 ratio (106 non-LC and 53 LC). The LC group had a mean ± SD age of 54.3 ± 15.5 years; females were predominant. Three-fifths of the LC patients had intermediate-risk cytogenetics; 20.4% had an adverse risk, and 10.2% had a favorable risk. Most were classified as AML-M4 and AML-M5. Leukemic nodules were the primary finding in 58.5% of the cases, mainly on the legs. In the multivariate analysis of predictive factors associated with LC, organomegalies, specifically hepatomegaly, and lymphadenopathy, remained significant factors associated with LC [OR 4.45 (95%CI 1.20, 16.50); p = 0.026 and OR 5.48 (95%CI 1.65, 18.20); p = 0.005], respectively. The LC group demonstrated a significantly reduced OS (log-rank test p = 0.002) (median OS of 8.6 months vs. 32.4 months). RFS was considerably lower in the LC group (log-rank test p = 0.001) (median duration of 10.3 months vs. 24.4 months in the non-LC). CONCLUSIONS: AML patients who developed LC tended to experience notably poorer prognoses. Therefore, it is imperative to consider aggressive treatment options for such individuals. The presence of organomegalies in AML patients serves as a strong predictor of the possible occurrence of LC when accompanied by skin lesions.


Asunto(s)
Leucemia Monocítica Aguda , Leucemia Mieloide Aguda , Neoplasias Cutáneas , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Estudios de Casos y Controles , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Neoplasias Cutáneas/complicaciones , Recurrencia , Pronóstico
6.
BMC Cardiovasc Disord ; 24(1): 111, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365602

RESUMEN

OBJECTIVES: The study aims to assess the effect of baseline glycated hemoglobin (HbA1c) levels on atrial fibrillation (AF) recurrence following cryoballoon ablation in patients with and without diabetes. METHODS: Consecutive AF patients receiving first cryoballoon ablation between April 2018 and April 2021 were included. AF recurrence and other clinical outcomes were recorded for a minimum of 12 months post-ablation, with regular assessments at 3, 6, and 12 months, followed by annual check-ups. The primary outcome was AF recurrence after ablation at longest follow-up. Multivariate Cox proportional hazards regression models were utilized to calculate the hazard ratio (HR) and 95% CI per standard deviation (SD) increase of baseline HbA1c level. RESULTS: 335 patients were included in the analysis. The mean age was 61.7 years, 61.8% were male. 12.8% had type 2 diabetes, and 81.7% of patients had paroxysmal AF. The median level of HbA1c was 5.3%, and the mean CHA2DS2-VASc score was 1.8. All cryoballoon ablation procedures, utilizing a 28-mm balloon, achieved successful pulmonary vein isolation. Over a median follow-up of 18 months, 105 patients (31.3%) experienced AF recurrence. In multivariate Cox proportional hazards analysis, a higher HbA1c level, persistent AF (HR 1.91, 95% CI 1.08 to 3.39, P = 0.026), alcohol consumption (HR 2.67, 95% CI 1.33 to 5.37, P = 0.006), and Nadir RSPV (HR 1.04, 95% CI 1.00 to 1.08, P = 0.005) were significant predictors of AF recurrence. Per-SD increase of HbA1c was associated with a 1.75-fold increase risk of AF recurrence (HR 1.75, 95% CI 1.39 to 2.21, P < 0.001). Subgroup analysis revealed that a higher HbA1c level was associated with a higher risk of AF recurrence in patients with and without diabetes, and in patients with paroxysmal and persistent AF. CONCLUSION: Baseline HbA1c level was an independent predictor of AF recurrence following cryoablation, both in patients with and without diabetes.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Criocirugía , Diabetes Mellitus Tipo 2 , Venas Pulmonares , Humanos , Masculino , Persona de Mediana Edad , Femenino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Hemoglobina Glucada , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Resultado del Tratamiento , Factores de Riesgo , Criocirugía/efectos adversos , Recurrencia , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Venas Pulmonares/cirugía
7.
J Neuroinflammation ; 21(1): 52, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38368354

RESUMEN

Establishing biomarkers to predict multiple sclerosis diagnosis and prognosis has been challenging using a single biomarker approach. We hypothesised that a combination of biomarkers would increase the accuracy of prediction models to differentiate multiple sclerosis from other neurological disorders and enhance prognostication for people with multiple sclerosis. We measured 24 fluid biomarkers in the blood and cerebrospinal fluid of 77 people with multiple sclerosis and 80 people with other neurological disorders, using ELISA or Single Molecule Array assays. Primary outcomes were multiple sclerosis versus any other diagnosis, time to first relapse, and time to disability milestone (Expanded Disability Status Scale 6), adjusted for age and sex. Multivariate prediction models were calculated using the area under the curve value for diagnostic prediction, and concordance statistics (the percentage of each pair of events that are correctly ordered in time for each of the Cox regression models) for prognostic predictions. Predictions using combinations of biomarkers were considerably better than single biomarker predictions. The combination of cerebrospinal fluid [chitinase-3-like-1 + TNF-receptor-1 + CD27] and serum [osteopontin + MCP-1] had an area under the curve of 0.97 for diagnosis of multiple sclerosis, compared to the best discriminative single marker in blood (osteopontin: area under the curve 0.84) and in cerebrospinal fluid (chitinase-3-like-1 area under the curve 0.84). Prediction for time to next relapse was optimal with a combination of cerebrospinal fluid[vitamin D binding protein + Factor I + C1inhibitor] + serum[Factor B + Interleukin-4 + C1inhibitor] (concordance 0.80), and time to Expanded Disability Status Scale 6 with cerebrospinal fluid [C9 + Neurofilament-light] + serum[chitinase-3-like-1 + CCL27 + vitamin D binding protein + C1inhibitor] (concordance 0.98). A combination of fluid biomarkers has a higher accuracy to differentiate multiple sclerosis from other neurological disorders and significantly improved the prediction of the development of sustained disability in multiple sclerosis. Serum models rivalled those of cerebrospinal fluid, holding promise for a non-invasive approach. The utility of our biomarker models can only be established by robust validation in different and varied cohorts.


Asunto(s)
Quitinasas , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/líquido cefalorraquídeo , Osteopontina , Proteína de Unión a Vitamina D , Biomarcadores/líquido cefalorraquídeo , Recurrencia
9.
BMJ Open Gastroenterol ; 11(1)2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38341192

RESUMEN

Inflammatory bowel disease (IBD) treatment was revolutionised with the arrival of biological therapy two decades ago. There are now multiple biologics and increasingly novel small molecules licensed for the treatment of IBD. Treatment guidelines highlight the need for effective control of inflammation and early escalation to advanced therapies to avoid long-term complications. Consequently, a large proportion of patients with IBD receive advanced therapies for a long time. Despite their beneficial risk-benefit profile, these treatments are not without risk of side effects, are costly to healthcare providers and pose a burden to the patient. It is, therefore, paramount to examine in which circumstances a temporary cessation of therapy can be attempted without undue clinical risk. Some patients may benefit from cyclical rather than continuous treatment. This review examines the risk of relapse after discontinuation of advanced therapies, how to identify patients at the lowest risk of relapse and the chance of recapturing response when flaring after discontinuation.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Terapia Biológica , Recurrencia
10.
Sci Rep ; 14(1): 2634, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38302547

RESUMEN

Identifying patients who would benefit from extensive catheter ablation along with pulmonary vein isolation (PVI) among those with persistent atrial fibrillation (AF) has been a subject of controversy. The objective of this study was to apply uplift modeling, a machine learning method for analyzing individual causal effect, to identify such patients in the EARNEST-PVI trial, a randomized trial in patients with persistent AF. We developed 16 uplift models using different machine learning algorithms, and determined that the best performing model was adaptive boosting using Qini coefficients. The optimal uplift score threshold was 0.0124. Among patients with an uplift score ≥ 0.0124, those who underwent extensive catheter ablation (PVI-plus) showed a significantly lower recurrence rate of AF compared to those who received only PVI (PVI-alone) (HR 0.40; 95% CI 0.19-0.84; P-value = 0.015). In contrast, among patients with an uplift score < 0.0124, recurrence of AF did not significantly differ between PVI-plus and PVI-alone (HR 1.17; 95% CI 0.57-2.39; P-value = 0.661). By employing uplift modeling, we could effectively identify a subset of patients with persistent AF who would benefit from PVI-plus. This model could be valuable in stratifying patients with persistent AF who need extensive catheter ablation before the procedure.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Humanos , Resultado del Tratamiento , Recurrencia , Venas Pulmonares/cirugía , Ablación por Catéter/métodos
11.
Sci Rep ; 14(1): 3503, 2024 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347079

RESUMEN

In Thailand, resource limitations lead many multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients to use off-label immunosuppressants. This study assesses the efficacy and safety of rituximab (RTX) with a CD19-based reinfusion regimen among Thai MS and NMOSD patients. A retrospective review of patients at the Faculty of Medicine Siriraj Hospital from January 1994 to April 2023 was conducted. The primary outcome assessed was the change in annualized relapse rate (ARR) for patients using RTX for over a year. Secondary outcomes included changes in the Expanded Disability Status Scale (EDSS) scores, time to the first relapse after RTX initiation for patients using RTX for over a year, and an evaluation of the safety of RTX. The study encompassed 36 MS and 39 NMOSD patients. A majority of patients (91.7% of MS and 79.5% of NMOSD) experienced no relapses during a median follow-up of 30 months (Interquartile range [IQR] 20-46) and 31 months (IQR 23-41), respectively. The median ARR significantly decreased in both MS (from 0.77 [IQR 0.42-1.83] to 0 [IQR 0-0], p < 0.001) and NMOSD (from 0.92 [IQR 0.68-1.78] to 0 [IQR 0-0.17], p < 0.001) patients after switching to RTX, with no difference between those following a fixed 6-month time point regimen and a CD19-based reinfusion regimen. Median EDSS scores improved significantly at the last follow-up visit in both groups. The mean time to the first subsequent relapse was 8.3 ± 3.0 months in MS and 6.8 ± 1.7 months in NMOSD. Mild adverse drug reactions occurred in 44% of patients. RTX effectively prevents relapses in Thai MS and NMOSD patients, with no observed serious adverse drug reactions.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Rituximab/efectos adversos , Neuromielitis Óptica/tratamiento farmacológico , Factores Inmunológicos/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Antígenos CD19 , Recurrencia
12.
Neurol Neuroimmunol Neuroinflamm ; 11(2): e200206, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38350043

RESUMEN

BACKGROUND AND OBJECTIVES: Neuromyelitis optica (NMO) is an autoimmune astrocytopathy mediated by anti-AQP4 antibody-producing B cells. Recently, a B-cell subset highly expressing CD11c and T-bet, originally identified as age-associated B cells, has been shown to be involved in the pathogenesis of various autoimmune diseases. The objective of this study was to determine the relationship between the frequency of CD11chigh B cells per CD19+ B cells in the peripheral blood of patients with NMO and the clinical profiles including the brain volume. METHODS: In this observational study, 45 patients with anti-AQP4 antibody-positive NMO in remission and 30 healthy control subjects (HCs) were enrolled. Freshly isolated peripheral blood mononuclear cells were analyzed for immune cell phenotypes. The frequency of CD11chigh B cells per CD19+ B cells was assessed by flow cytometry and was evaluated in association with the clinical profiles of patients. Brain MRI data from 26 patients were included in the study for the analysis on the correlation between CD11chigh B-cell frequency and brain atrophy. RESULTS: We found that the frequency of CD11chigh B cells in CD19+ B cells was significantly increased in patients with NMO compared with HCs. The expansion of CD11chigh B cells significantly correlated with EDSS, past relapse numbers, and disease duration. In addition, a higher frequency of CD11chigh B cells negatively correlated with total brain, white matter, and gray matter volumes and positively correlated with T2/FLAIR high lesion volumes. When the past clinical relapse episodes of patients with or without the expansion of CD11chigh B cells were compared, relapses in the brain occurred more frequently in patients with CD11chigh B-cell expansion. CD11chigh B cells had distinct features including expression of chemokine receptors associated with migration into peripheral inflammatory tissues and antigen presentation. CD11chigh B-cell frequency was positively correlated with T peripheral helper-1 (Tph-1) cell frequency. DISCUSSION: Even during the relapse-free period, CD11chigh B cells could expand in the long disease context, possibly through the interaction with Tph-1 cells. The increased frequency of CD11chigh B cells associated with brain atrophy and disease severity, indicating that this cell population could be involved in chronic neuroinflammation in NMO.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Neuromielitis Óptica , Sustancia Blanca , Humanos , Acuaporina 4 , Leucocitos Mononucleares/metabolismo , Sustancia Blanca/patología , Enfermedades del Sistema Nervioso Central/complicaciones , Recurrencia
13.
J Immunother Cancer ; 12(2)2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38350684

RESUMEN

BACKGROUND: Chimeric antigen receptor (CAR)-T cells are approved for use in the treatment of hematological malignancies. Axicabtagene ciloleucel (YESCARTA) and brexucabtagene autoleucel (TECARTUS) genetically modified autologous T cells expressing an anti-CD19 scFv based on the FMC63 clone have shown impressive response rates for the treatment of CD19+B cell malignancies, but there remain challenges in monitoring long-term persistence as well as the functional characterization of low-level persisting CAR-T cells in patients. Furthermore, due to CD19-negative driven relapse, having the capability to monitor patients with simultaneous detection of the B cell malignancy and persisting CAR-T cells in patient peripheral blood is important for ensuring timely treatment optionality and understanding relapse. METHODS: This study demonstrates the development and technical validation of a comprehensive liquid biopsy, high-definition single cell assay (HDSCA)-HemeCAR for (1) KTE-X19 CAR-T cell identification and analysis and (2) simultaneously monitoring the CD19-epitope landscape on neoplastic B cells in cryopreserved or fresh peripheral blood. Proprietary anti-CD19 CAR reagents, healthy donor transduced CAR-T cells, and patient samples consisting of malignant B cell fractions from manufacturing were used for assay development. RESULTS: The CAR-T assay showed an approximate limit of detection at 1 cell in 3 million with a sensitivity of 91%. Genomic analysis was additionally used to confirm the presence of the CAR transgene. This study additionally reports the successful completion of two B cell assays with multiple CD19 variants (FMC63 and LE-CD19) and a unique fourth channel biomarker (CD20 or CD22). In patient samples, we observed that CD19 isoforms were highly heterogeneous both intrapatient and interpatient. CONCLUSIONS: With the simultaneous detection of the CAR-T cells and the B cell malignancy in patient peripheral blood, the HDSCA-HemeCAR workflow may be considered for risk monitoring and patient management.


Asunto(s)
Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/genética , Receptores de Antígenos de Linfocitos T/genética , Recurrencia , Antígenos CD19 , Tratamiento Basado en Trasplante de Células y Tejidos
14.
Zhonghua Gan Zang Bing Za Zhi ; 32(1): 22-28, 2024 Jan 20.
Artículo en Chino | MEDLINE | ID: mdl-38320787

RESUMEN

Objective: To observe the recurrence condition of hepatitis B in different risk groups after liver transplantation in an attempt to provide useful information on whether to discontinue hepatitis B immunoglobulin (HBIG) in the future at an early stage. Methods: The patient population was divided into high, low-risk, and special groups [especially primary hepatocellular carcinoma (HCC)] according to the guidelines for the prevention and treatment of hepatitis B recurrence after liver transplantation. The recurrence condition and risk factors in this population were observed for hepatitis B. Measurement data were analyzed using a t-test and a rank-sum test. Count data were compared using a χ(2) test between groups. Results: This study finally included 532 hepatitis B-related liver transplant cases. A total of 35 cases had HBV recurrence after liver transplantation, including 34 cases that were HBsAg positive, one case that was HBsAg negative, and 10 cases that were hepatitis B virus (HBV) DNA positive. The overall HBV recurrence rate was 6.6%. The recurrence rate of HBV was 9.2% and 4.8% in the high- and low-risk HBV DNA positive and negative groups before surgery (P = 0.057). Among the 293 cases diagnosed with HCC before liver transplantation, 30 had hepatitis B recurrence after surgery, with a recurrence rate of 10.2%. The independent related factors for the recurrence of hepatitis B in patients with HCC after liver transplantation were HCC recurrence (HR =181.92, 95%CI 15.99~2 069.96, P < 0.001), a high postoperative dose of mycophenolate mofetil dispersible tablets (MMF) ( HR =5.190, 95%CI 1.289~20.889, P = 0.020), and a high dosage of HBIG (HR = 1.012, 95%CI 1.001~1.023, P = 0.035). Among the 239 cases who were non-HCC before liver transplantation, five cases (recurrence rate of 2.1%) arouse postoperative hepatitis B recurrence. Lamivudine was used in all cases, combined with on-demand HBIG prophylaxis after surgery. There was no hepatitis B recurrence in non-HCC patients who treated with entecavir combined with HBIG after surgery. Conclusion: High-barrier-to-resistance nucleotide analogues combined with long-term HBIG have a good effect on preventing the recurrence of hepatitis B after liver transplantation. The discontinuation of HBIG may be considered at an early stage after administration of a high-barrier-to-resistance nucleotide analogue in low-risk patients. Domestically, the HBV infection rate is high, so further research is still required to explore the timing of HBIG discontinuation for high-risk patients, especially those with HCC.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/tratamiento farmacológico , Antivirales/efectos adversos , Antígenos de Superficie de la Hepatitis B , Resultado del Tratamiento , Neoplasias Hepáticas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Hepatitis B/tratamiento farmacológico , Virus de la Hepatitis B/genética , Factores de Riesgo , Inmunoglobulinas/uso terapéutico , Lamivudine/uso terapéutico , Nucleótidos/uso terapéutico , Recurrencia
15.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38338760

RESUMEN

Tobacco smoking is the leading cause of preventable death and disease. Although there are some FAD-approved medicines for controlling smoking, the relapse rate remains very high. Among the factors that could induce nicotine relapse, stress might be the most important one. In the last decades, preclinical studies have generated many new findings that lead to a better understanding of stress-induced relapse of nicotine-seeking. Several molecules such as α3ß4 nicotinic acetylcholine receptor, α2-adrenergic receptors, cannabinoid receptor 1, trace amine-associated receptor 1, and neuropeptide systems (corticotropin-releasing factor and its receptors, dynorphine and kappa opioid receptor) have been linked to stress-induced nicotine relapse. In this review, we discuss recent advances in the neurobiology, treatment targets, and potential therapeutics of stress-induced nicotine relapse. We also discuss some factors that may influence stress-induced nicotine relapse and that should be considered in future studies. In the final section, a perspective on some research directions is provided. Further investigation on the neurobiology of stress-induced nicotine relapse will shed light on the development of new medicines for controlling smoking and will help us understand the interactions between the stress and reward systems in the brain.


Asunto(s)
Receptores Nicotínicos , Tabaquismo , Humanos , Nicotina/uso terapéutico , Tabaquismo/tratamiento farmacológico , Recompensa , Hormona Liberadora de Corticotropina/farmacología , Recurrencia
16.
Int J Mol Sci ; 25(3)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38339034

RESUMEN

Acute lymphoblastic leukemia (ALL) represents around 25% of adult acute leukemias. Despite the increasing improvement in the survival rate of ALL patients during the last decade, the heterogeneous clinical and molecular features of this malignancy still represent a major challenge for treatment and achieving better outcomes. To identify aberrantly expressed genes in bone marrow (BM) samples from adults with ALL, transcriptomic analysis was performed using Affymetrix Human Transcriptome Array 2.0 (HTA 2.0). Differentially expressed genes (DEGs) (±2-fold change, p-value < 0.05, and FDR < 0.05) were detected using the Transcriptome Analysis Console. Gene Ontology (GO), Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA) were employed to identify gene function and define the enriched pathways of DEGs. The protein-protein interactions (PPIs) of DEGs were constructed. A total of 871 genes were differentially expressed, and DNTT, MYB, EBF1, SOX4, and ERG were the top five up-regulated genes. Meanwhile, the top five down-regulated genes were PTGS2, PPBP, ADGRE3, LUCAT1, and VCAN. An association between ERG, CDK6, and SOX4 expression levels and the probability of relapse and death was observed. Regulation of the immune system, immune response, cellular response to stimulus, as well as apoptosis signaling, inflammation mediated by chemokines and cytokines, and T cell activation were among the most altered biological processes and pathways, respectively. Transcriptome analysis of ALL in adults reveals a group of genes consistently associated with hematological malignancies and underscores their relevance in the development of ALL in adults.


Asunto(s)
Perfilación de la Expresión Génica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Transcriptoma , Biomarcadores , Recurrencia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Biología Computacional , Factores de Transcripción SOXC
17.
Pediatr Allergy Immunol ; 35(2): e14078, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38339981

RESUMEN

Preschool children with wheezing disorders pose diagnostic and therapeutic challenges and consume substantial healthcare resources. Peripheral eosinophil blood count (EBC) has been proposed as a potential indicator for future asthma development. This review by the European Academy of Allergy and Clinical Immunology (EAACI) Preschool Wheeze Task Force aimed to provide systematic evidence for the association between increased EBC and the risk of future asthma, as well as to identify potential cutoff values. In February 2023, a search of PubMed, EMBASE, and Cochrane Library databases was conducted to identify studies comparing EBCs in preschool children with wheezing who continued to wheeze later in life and those who did not. Included observational studies focused on children aged <6 years with a wheezing disorder, assessment of their EBCs, and subsequent asthma status. No language or publication date restrictions were applied. Among the initial 3394 studies screened, 10 were included in the final analysis, involving 1225 patients. The data from these studies demonstrated that high EBC in preschool children with wheezing is associated with future asthma development, with odds ratios of 1.90 (95% CI: 0.45-7.98, p = .38), 2.87 (95% CI: 1.38-5.95, p < .05), and 3.38 (95% CI: 1.72-6.64, p < .05) for cutoff values in the <300, 300-449, and ≥450 cells/µL ranges, respectively. Defining a specific cutoff point for an elevated EBC lacks consistency, but children with EBC >300 cells/µL are at increased risk of asthma. However, further research is needed due to the limitations of the included studies. Future investigations are necessary to fully elucidate the discussed association.


Asunto(s)
Asma , Eosinófilos , Humanos , Preescolar , Ruidos Respiratorios/etiología , Asma/diagnóstico , Asma/epidemiología , Asma/complicaciones , Recurrencia
18.
BMC Pulm Med ; 24(1): 74, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38331769

RESUMEN

BACKGROUND: Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare disease characterized by pulmonary radiological alterations, peripheral eosinophilia, and demonstrated pulmonary eosinophilia. Oral steroids (OSs) are the standard management, but relapses occur in up to 50% of patients during the decrease or suspension of steroids, usually requiring reinitiation of treatment, exposing patients to secondary events derived from the management. Management with monoclonal antibodies has been proposed in these cases to control the disease and limit the secondary effects. The objective is to describe the extent and type of evidence regarding the use of monoclonal antibodies for ICEP. METHODS: A panoramic review of the literature was performed. Observational and experimental studies of pediatric and adult populations that managed recurrent ICEP with monoclonal antibodies were included. Data search, selection, and extraction were performed by two independent reviewers. RESULTS: 937 studies were found. After applying the inclusion and exclusion criteria, 37 titles remained for the final analysis: a retrospective, observational, real-life study, two case series publications, and 34 case reports published in academic poster sessions and letters to the editor. In general, the use of monoclonal antibodies approved for severe asthma could be useful for the control of ICEP, since most of the results show a good response for clinical and radiological outcomes. Biological drugs seem to be a safer option for controlling relapses in ICEP, allowing lowering/suspension of OSs, and sometimes replacing them in patients intolerant to them, patients with significant comorbidities, and patients who have already developed adverse events. CONCLUSION: The extent of the evidence supporting management of ICEP with monoclonal antibodies against IL-5 and IgE (omalizumab) is limited, but it could be promising in patients who present frequent relapses, in cortico-dependent individuals, or in patients in whom the use of steroids is contraindicated. The extent of the evidence for management with dupilumab is more limited. Studies with better design and structure are needed to evaluate quality of life and outcomes during a clear follow-up period. To our knowledge, this is the first scoping review of the literature showing the extent of the evidence for the management of ICEP with monoclonal antibodies.


Asunto(s)
Asma , Eosinofilia Pulmonar , Adulto , Humanos , Niño , Eosinofilia Pulmonar/tratamiento farmacológico , Eosinofilia Pulmonar/complicaciones , Anticuerpos Monoclonales/uso terapéutico , Calidad de Vida , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Asma/complicaciones , Esteroides/uso terapéutico , Recurrencia
19.
Hematology ; 29(1): 2313357, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38332700

RESUMEN

Haploidentical hematopoietic can be conducted on an outpatient basis but the two main reasons to accept into the hospital a patient in this setting are complications of the hematological toxicity and/or the cytokine-release syndrome. With the aim of reducing the post-transplant cyclophosphamide-dependent toxicity without compromising its effectivity, attempts to reduce the dose of post-transplant cyclophosphamide have been made: Decreases from the conventional total dose of post-transplant cyclophosphamide (100 mg/Kg) have been explored worldwide, showing that decreasing the total dose to even 50 mg/Kg significantly decreases the toxicity of the procedure without compromising its efficacy, safety and results. We present here the salient data of the attempts to diminish the doses of post-transplant cyclophosphamide which have been done and published worldwide, information that suggests that the conventional doses of post-transplant cyclophosphamide can be significantly reduced thus decreasing the toxicity, without compromising the effectiveness of the procedure, mainly the development of graft versus host disease.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Ciclofosfamida/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Recurrencia , Acondicionamiento Pretrasplante/efectos adversos
20.
Cells ; 13(3)2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38334635

RESUMEN

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic malignancy with poor outcomes. The World Health Organization (WHO) redefined BDCN as a distinct disease entity in 2016. BPDCN arises from plasmacytoid dendritic cells, manifesting primarily in the skin, bone marrow, and lymph nodes, occasionally involving the central nervous system (CNS). This presents challenges in diagnosis and treatment, with CNS involvement often overlooked in standard diagnostic workups due to BPDCN's rarity and patients often being neurologically asymptomatic at diagnosis. CNS involvement typically emerges during relapse, yet clinical trials often exclude such cases, limiting our understanding of its development and treatment. Treatment options for CNS involvement include intrathecal (IT) chemotherapies like methotrexate and cytarabine, often in combination with systemic agents. Tagraxofusp and traditional regimens for acute myeloid leukemia show limited success at preventing CNS relapse, prompting exploration of combined therapies like hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HyperCVAD) with venetoclax and adding IT chemotherapy to other backbones. Ongoing clinical trials investigating emerging therapies offer hope despite limited focus on CNS implications. Trials incorporating CNS-involved patients aim to pioneer novel treatment approaches, potentially reshaping BPDCN management. Understanding CNS involvement's complexities in BPDCN remains crucial for tailored treatments and better patient outcomes.


Asunto(s)
Trastornos Mieloproliferativos , Neoplasias Cutáneas , Humanos , Sistema Nervioso Central/patología , Neoplasias Cutáneas/patología , Trastornos Mieloproliferativos/patología , Células Dendríticas/patología , Recurrencia
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