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1.
Cells ; 13(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39273069

RESUMEN

Multiple sclerosis (MS) is a chronic autoimmune disease with an unknown etiology. The purpose of this research was to assess miR-223, miR-146a, and miR-193a in acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) mice to consider the possible role of these genes in the pathogenesis of MS. EAE induction was given by myelin oligodendrocyte glycoprotein peptide on female C57BL/6 mice. Clinical scores and other criteria were followed daily until day 21 for the acute group and day 77 for the chronic group. At the end of the course, inflammation and demyelination of the central nervous system (CNS) were assessed by histological analysis. MicroRNA expression levels were assessed by real-time PCR. EAE development attenuated in the chronic group, and histological analysis showed less infiltration and demyelination in the chronic group compared to the acute group. The upper expression of miR-223 is demonstrated in the acute phase of EAE. Moreover, the expression levels of miR-146a and miR-193a decreased in the chronic phase of EAE. MiR-223 showed a highly coordinated elevation in the acute phase both in vivo and in vitro. MiR-146a shares a pathway with miR-223 through effecting IL-6 expression. Further studies are needed to reveal their impact on EAE and possible applications as drug targets and biomarkers.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Ratones Endogámicos C57BL , MicroARNs , Animales , MicroARNs/genética , MicroARNs/metabolismo , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/metabolismo , Ratones , Femenino , Enfermedad Crónica , Regulación de la Expresión Génica , Enfermedad Aguda , Esclerosis Múltiple/genética , Esclerosis Múltiple/patología , Esclerosis Múltiple/metabolismo
2.
Brain Behav Immun ; 123: 64-80, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39242055

RESUMEN

Traumatic brain injury (TBI) is a disabling neurotraumatic condition and the leading cause of injury-related deaths and disability in the United States. Attenuation of neuroinflammation early after TBI is considered an important treatment target; however, while these inflammatory responses can induce secondary brain injury, they are also involved in the repair of the nervous system. Pioglitazone, which activates peroxisome proliferator-activated receptor gamma, has been shown to decrease inflammation acutely after TBI, but the long-term consequences of its use remain unknown. For this reason, the impacts of treatment with pioglitazone during the acute/subacute phase (30 min after injury and each subsequent 24 h for 5 days) after TBI were interrogated during the chronic phase (30- and 274-days post-injury (DPI)) in mice using the controlled cortical impact model of experimental TBI. Acute/subacute pioglitazone treatment after TBI results in long-term deleterious consequences, including disruption of tau homeostasis, chronic glial cell activation, neuronal pathology, and worsened injury severity particularly at 274 DPI, with male mice being more susceptible than female mice. Further, male pioglitazone-treated TBI mice exhibited increased dominant and offensive-like behavior while having a decreased non-social exploring behavior at 274 DPI. After TBI, both sexes exhibited glial activation at 30 DPI when treated with pioglitazone; however, while injury severity was increased in females it was not impacted in male mice. This work reveals that although pioglitazone has been shown to lead to attenuated TBI outcomes acutely, sex-based differences, timing and long-term consequences of treatment with glitazones must be considered and further studied prior to their clinical use for TBI therapy.

3.
Cureus ; 16(7): e64149, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39119419

RESUMEN

Although the treatment strategy for febrile infection-related epilepsy syndrome (FIRES) is improving, current research focuses on acute management. Evidence for the management of the chronic phase is limited. We present the case of a 19-year-old woman with FIRES who showed excellent response to a ketogenic diet (KD) administered in the chronic phase. At the age of four years, she presented with new-onset super-refractory status epilepticus after a febrile episode. She was diagnosed with FIRES and had profound motor and cognitive deterioration and drug-resistant epilepsy. From the age of 17, she experienced numerous seizures that often led to status epilepticus with respiratory failure, necessitating laryngotracheal separation and nocturnal mechanical ventilation. To improve seizure control, we planned a KD for the first time 15 years after the onset of FIRES. We introduced a classic KD (ketogenic ratio, 3:1) using blended meals through gastrotomy. Two months after starting the KD, she experienced a decrease in seizure frequency and duration. Moreover, as unexpected stabilization of respiration was achieved, mechanical ventilation was stopped. Our case implies that KD may be a promising treatment option for patients with FIRES in the chronic phase, as is believed to be the case in the acute phase.

4.
EJHaem ; 5(4): 859-862, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39157620

RESUMEN

Chronic myeloid leukaemia (CML) has been classically described as a disease restricted to the bone marrow with very few reports of extramedullary involvement. CNS involvement with CML has been described in the literature as an aggressive disease in the leukaemic phase either preceding or coexisting with medullary blast crisis or seen in patients with long-term Imatinib therapy. No treatment consensus exists for this patient group and outcomes remain poor. We hereby present a very rare report of CNS involvement with chronic phase CML at diagnosis in a patient who presented with raised intracranial pressure and cranial nerve palsies.

5.
Pediatr Neurol ; 160: 18-25, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39173307

RESUMEN

BACKGROUND: To investigate the long-term outcome of pediatric mild traumatic brain injury (mTBI) in terms of neurocognitive, behavioral, and school functioning and to identify clinical risk factors for adverse outcomes. METHODS: This study describes the follow-up of a prospective multicenter sample of 89 children with mTBI 3.6 years postinjury and 89 neurologically healthy children matched for sex, age, and socioeconomic status. Neurodevelopmental outcomes were assessed using an intelligence test, behavioral questionnaires, computerized neurocognitive tests, and longitudinal (pre- and postinjury) standardized school performance data. RESULTS: Children with mTBI exhibited intelligence in the average range but had more behavioral problems related to inattentiveness (P = 0.004, d = 0.47) and hyperactive impulsivity (P = 0.01, d = 0.40) and showed poorer neurocognitive performance in information processing stability (P = 0.003, d = -0.55) and Visual Working Memory (P = 0.04, d = -0.39) compared with matched peers. Longitudinal school performance data revealed poorer performance in Technical Reading up to two years postinjury (P = 0.005, d = -0.42) when compared with normative data. Clinical risk factors did not reveal predictive value for adverse outcomes in children with mTBI. CONCLUSIONS: This study indicates that children with mTBI are at risk of long-term deficits in neurocognitive and behavioral functioning, with longitudinal evidence suggesting shortfalls in school performance up to two years postinjury. Clinical risk factors do not provide a solid basis for long-term neurodevelopmental prognosis. Findings emphasize the importance of, and challenges for, early identification of children at risk for adverse neurodevelopmental outcome after mTBI.


Asunto(s)
Conmoción Encefálica , Pruebas Neuropsicológicas , Humanos , Niño , Masculino , Femenino , Conmoción Encefálica/complicaciones , Conmoción Encefálica/fisiopatología , Adolescente , Estudios de Seguimiento , Estudios Prospectivos , Rendimiento Académico , Estudios Longitudinales , Trastornos del Neurodesarrollo/etiología , Preescolar
6.
Front Oncol ; 14: 1369246, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011484

RESUMEN

The introduction of tyrosine kinase inhibitors (TKIs) has transformed the treatment of chronic myeloid leukemia (CML). Each approved TKI has its own risk-benefit profile, and patients have choices across lines of therapy. Identifying the initial and subsequent treatment that will lead to the best possible outcome for individual patients is challenging. In this review, we summarize data for each approved TKI across lines of therapy in patients with CML in chronic phase, highlighting elements of each agent's safety and efficacy profile that may impact patient selection, and provide insights into individualized treatment sequencing decision-making aimed at optimizing patient outcomes.

7.
Front Oncol ; 14: 1418417, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38978732

RESUMEN

Background: Imatinib is the most widely used tyrosine kinase inhibitor (TKI) in patients with newly diagnosed chronic-phase chronic myeloid leukemia(CML-CP). However, failure to achieve optimal response after imatinib administration, and subsequent switch to second-generation TKI therapy results in poor efficacy and induces drug resistance. In the present study, we developed and validated a nomogram to predict the efficacy of imatinib in the treatment of patients newly diagnosed with CML-CP in order to help clinicians truly select patients who need 2nd generation TKI during initial therapy and to supplement the risk score system. Methods: We retrospectively analyzed 156 patients newly diagnosed with CML-CP who met the inclusion criteria and were treated with imatinib at the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2012 to June 2022. The patients were divided into a poor-response cohort (N = 60)and an optimal-response cohort (N = 43) based on whether they achieved major molecular remission (MMR) after 12 months of imatinib treatment. Using univariate and multivariate logistic regression analyses, we developed a chronic myeloid leukemia imatinib-poor treatment (CML-IMP) prognostic model using a nomogram considering characteristics like age, sex, HBG, splenic size, and ALP. The CML-IMP model was internally validated and compared with Sokal, Euro, EUTOS, and ELTS scores. Results: The area under the curve of the receiver operator characteristic curve (AUC)of 0.851 (95% CI 0.778-0.925) indicated satisfactory discriminatory ability of the nomogram. The calibration plot shows good consistency between the predicted and actual observations. The net reclassification index (NRI), continuous NRI value, and the integrated discrimination improvement (IDI) showed that the nomogram exhibited superior predictive performance compared to the Sokal, EUTOS, Euro, and ELTS scores (P < 0.05). In addition, the clinical decision curve analysis (DCA) showed that the nomogram was useful for clinical decision-making. In predicting treatment response, only Sokal and CML-IMP risk stratification can effectively predict the cumulative acquisition rates of CCyR, MMR, and DMR (P<0.05). Conclusion: We constructed a nomogram that can be effectively used to predict the efficacy of imatinib in patients with newly diagnosed CML-CP based on a single center, 10-year retrospective cohort study.

8.
Cureus ; 16(5): e60525, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38887352

RESUMEN

Febrile infection-related epilepsy syndrome (FIRES) is a rare epileptic encephalopathy that occurs in children or adolescents. To date, evidence for the management of the post-acute phase of FIRES is focused on drug-resistant epilepsy that continues from the acute phase. Information on involuntary movements, which are newly developed in the chronic phase, is limited. We report a 13-year-old boy, who had a history of FIRES at nine years of age and experienced worsening seizure control that was accompanied by unremitting involuntary movements after two years of a fairly controlled period. The involuntary movements resulted in motor deterioration and forced him to be bedridden. Although no neuronal autoantibodies were detected, we hypothesized that the boy's neurological deterioration was triggered by an autoimmune response based on the elevation of serum anti-glutamic acid decarboxylase and serum anti-thyroid peroxidase antibodies and hypermetabolism of bilateral lenticular nuclei on 18-fluorodeoxyglucose positron emission tomography that resembled those reported in patients with other types of autoimmune encephalitis. Serial methylprednisolone pulse therapy and intravenous immunoglobulin therapy ameliorated involuntary movements and improved his activities of daily living. Late-onset involuntary movements, along with seizure exacerbation, may appear in the chronic phase of FIRES. Immunotherapy could be effective in treating these symptoms.

9.
J Stroke Cerebrovasc Dis ; 33(8): 107777, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38795794

RESUMEN

OBJECTIVE: To identify acute predictors of generic and specific health-related quality of life (HRQoL) six and 12 months after stroke in individuals from a middle-income country. MATERIAL AND METHODS: This was a prospective study. The dependent outcomes assessed during six and 12 months after stroke included both generic and specific HRQoL (Short Form Health Survey-36 [SF-36] and stroke-specific quality of life [SSQOL]). The predictors were age, sex, education level, length of hospital stay, current living arrangement, stroke severity, functional independence, and motor impairment. RESULTS: 122 (59.9±14 years) and 103 (59.8±14.71 years) individuals were evaluated six and 12 months after stroke, respectively. Functional independence and sex were significant acute predictors of both generic and specific HRQoL. Functional independence was the strongest predictor (0.149≤R2≤0.262; 20.01≤F≤43.96, p<0.001), except for generic HRQoL at 12 months, where sex was the strongest predictor (R2=0.14; F=17.97, p<0.001). CONCLUSION: Generic and specific HRQoL in chronic individuals six and 12 months after stroke, from a middle-income country, can be predicted based on functional independence, the strongest predictor, assessed in the acute phase, except for generic HRQoL at 12 months. Functional independence can be modified by rehabilitation strategies and thus should be considered for HRQoL prognoses at chronic phase.


Asunto(s)
Estado Funcional , Calidad de Vida , Recuperación de la Función , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo , Rehabilitación de Accidente Cerebrovascular , Evaluación de la Discapacidad , Resultado del Tratamiento , Factores Sexuales , Adulto , Estado de Salud , Índice de Severidad de la Enfermedad
10.
Int J Cardiol ; 410: 132216, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38821121

RESUMEN

BACKGROUND: Tyrosine kinase inhibitors (TKI), such as Dasatinib, are effective in the treatment of chronic myeloid leukemia (CML) but associated with development of pleural effusions (PE). The relationship between haemodynamic parameters identified on transthoracic echocardiogram (TTE) such as elevated estimated left atrial pressure (LAP), and PE development is unknown. This study aims to describe associations between Dasatinib, elevated LAP and PE. METHODS: This was a retrospective study of 71 CML patients who underwent TTE during treatment with various TKIs. Descriptive analysis was performed to identify associations between TKI use, PE and elevated LAP on TTE. Multivariate logistic regression was performed to identify predictors of elevated LAP. RESULTS: There were 36 patients treated with Dasatinib, 15 Nilotinib, and 20 Imatinib. Those treated with Dasatinib had higher rates of elevated LAP (44% vs 7% Nilotinib vs 10% Imatinib, p < 0.01) and PE (39% vs 7% vs 0%, p < 0.01). In the 15 patients who developed PE, 14 (93%) patients were treated with Dasatinib. Patients with PE had higher rates of elevated LAP (67% vs 16%, p < 0.01). Nineteen (26.8%) patients in the entire cohort had elevated LAP. After multivariate adjustment, Dasatinib (OR 33.50, 95% CI = 4.99-224.73, p < 0.01) and age (OR 1.12, 95% CI = 1.04-1.20, p < 0.01) were associated with elevated LAP. CONCLUSIONS: Among patients with CML, there was an association between Dasatinib use, PE and elevated LAP on TTE. These findings are hypothesis generating and further studies are required to evaluate the utility of elevated LAP on TTE as a novel marker for prediction and surveillance of PE.


Asunto(s)
Dasatinib , Leucemia Mielógena Crónica BCR-ABL Positiva , Derrame Pleural , Inhibidores de Proteínas Quinasas , Humanos , Dasatinib/efectos adversos , Dasatinib/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Derrame Pleural/epidemiología , Derrame Pleural/inducido químicamente , Anciano , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Presión Atrial/fisiología , Presión Atrial/efectos de los fármacos , Ecocardiografía/métodos
11.
Pleura Peritoneum ; 9(1): 39-43, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38558869

RESUMEN

Objectives: Pleural effusion (PE) is the most frequent pulmonary complication of dasatinib, a tyrosine kinase inhibitor (TKI). Concurrent pericardial effusions have been reported in about one-third of the cases. In this study, we aimed to investigate ascites generation in chronic-phase chronic myeloid leukemia (CML-CP) patients developing PE under dasatinib. Methods: We conducted a cross-sectional study to evaluate whether pericardial effusion and ascites accompany PE in CML-CP patients treated with dasatinib. For this purpose, consecutive patients with CML-CP who developed PE under dasatinib therapy have been evaluated with chest X-ray, transthoracic echocardiography, and abdominal ultrasonography. Results: There were seven patients, and the median age was 50 years (range, 31-73 years). Most of patients were male (n=5). All patients received imatinib as first-line TKI. Six patients received dasatinib following imatinib failure in second line. The median duration from dasatinib initiation to PE generation was 58 months (range, 8-135 months). Consequently, four patients had grade 1 pericardial effusion, and no patient had ascites. Conclusions: In our small study, dasatinib-related PE was associated with low-grade pericardial effusion but no ascites. There are hypothetical explanations of this phenomenon including the simultaneous activation/inhibition of kinases; however, more research needs to be performed on this topic.

12.
Neuropharmacology ; 251: 109931, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38570067

RESUMEN

The prospective involvement of the Wnt/ß-catenin signaling pathway in epilepsy, with the proposed therapeutic uses of its modulators, has been suggested; however, comprehensive knowledge in this regard is currently limited. Despite postulations about the pathway's significance and treatment potential, a systematic investigation is required to better understand its implications in chronic epilepsy. We investigated the role of key proteins like ß-catenin, GSK-3ß, and their modulators sulindac and 6-BIO, in Wnt/ß-catenin pathway during chronic phase of temporal lobe epilepsy. We also evaluated the role of modulators in seizure score, seizure frequency and neurobehavioral parameters in temporal lobe epilepsy. We developed status epilepticus model using lithium-pilocarpine. The assessment of neurobehavioral parameters was done followed by histopathological examination and immunohistochemistry staining of hippocampus as well as RT-qPCR and western blotting to analyse gene and protein expression. In SE rats, seizure score and frequency were significantly high compared to control rats, with notable changes in neurobehavioral parameters and neuronal damage observed in hippocampus. Our study also revealed a substantial upregulation of the Wnt/ß-catenin pathway in chronic epilepsy, as evidenced by gene and protein expression studies. Sulindac emerged as a potent modulator, reducing seizure score, frequency, neuronal damage, apoptosis, and downregulating the Wnt/ß-catenin pathway when compared to 6-BIO. Our findings emphasize the potential of GSK-3ß and ß-catenin as promising drug targets for chronic temporal lobe epilepsy, offering valuable treatment options for chronic epilepsy. The promising outcomes with sulindac encourages further exploration in clinical trials to assess its therapeutic potential.


Asunto(s)
Epilepsia del Lóbulo Temporal , Estado Epiléptico , Ratas , Animales , Vía de Señalización Wnt , Sulindac/farmacología , Sulindac/uso terapéutico , beta Catenina/metabolismo , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/patología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Estudios Prospectivos
13.
Arch. argent. pediatr ; 122(2): e202310068, abr. 2024. tab, ilus
Artículo en Inglés, Español | LILACS, BINACIS | ID: biblio-1537959

RESUMEN

El priapismo es una erección dolorosa y persistente acompañada o no de estímulo sexual. Una causa poco frecuente de esta anormalidad es la leucemia mieloide crónica. Se han reportado pocos casos de priapismo como manifestación inicial de una leucemia de este tipo en pacientes adolescentes. A continuación, se informa el caso de un paciente de 16 años de edad que presentó priapismo como manifestación inicial de una leucemia mieloide crónica. Durante su evolución, no se realizó aspiración de los cuerpos cavernosos. Se inició tratamiento hematológico específico y, ante la persistencia del priapismo, fue necesario realizar un shunt de cuerpos cavernosos en dos ocasiones, tratamiento a pesar del cual existen altas probabilidades de secuelas.


Priapism is a painful and persistent erection, with or without sexual stimulation. A rare cause of such abnormality is chronic myeloid leukemia. Few cases of priapism as an initial manifestation of this type of leukemia have been reported in adolescent patients. Here we describe the case of a 16-year-old patient who presented with priapism as the initial manifestation of chronic myeloid leukemia. No cavernosal aspiration was performed. A specific hematological treatment was started and, given the persistence of priapism, the patient required 2 corpora cavernosa shunt procedures; despite this treatment, there is a high probability of sequelae.


Asunto(s)
Humanos , Masculino , Adolescente , Priapismo/complicaciones , Priapismo/etiología , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Enfermedad Crónica
14.
World J Urol ; 42(1): 124, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38453751

RESUMEN

BACKGROUND: Extracorporeal shock wave lithotripsy represents one option for the non-surgical management of Peyronie's disease. Despite promising results, several questions are still pending. We want to present the long-term results of a retrospective study using high-energy extracorporeal shock wave lithotripsy. MATERIAL AND METHODS: We evaluated retrospectively 110 patients treated between 1996 and 2020 at the Department of Urology, SLK Kliniken Heilbronn for chronic phase Peyronie's disease using two electromagnetic lithotripters (Siemens Lithostar Plus Overhead Module, Siemens Lithoskop) applying high-energy shock waves under local anesthesia and sonographic or fluoroscopic control. A standardized questionnaire focused on the change in pain, curvature, sexual function and the need of penile surgery. RESULTS: In 85 of the 110 patients (mean age 54 years) we had sufficient data for evaluation. The median follow-up was 228 (6-288) months. There were no significant complications. Pain reduction was achieved in all patients, 65 (76%) patients were free of pain. Improvement of penile curvature was achieved in 43 patients (51%) ranging from 25% improvement (deflected angle < 30°) to 95% (angle 30-60°). 59 patients (69%) reported problems with sexual intercourse, 40 of those (68%) reported improvement. Only 9 (10.5%) patients underwent surgical correction. We did not observe any significant differences between both electromagnetic devices with stable long-term results. CONCLUSIONS: High-energy shock wave therapy delivered by two standard electromagnetic lithotripters is safe and efficient providing stable long-term results. In cases with significant plaque formation, the concept of high-energy ESWT should be considered in future studies.


Asunto(s)
Ondas de Choque de Alta Energía , Litotricia , Induración Peniana , Masculino , Humanos , Persona de Mediana Edad , Induración Peniana/terapia , Estudios Retrospectivos , Pene , Dolor , Fenómenos Electromagnéticos , Resultado del Tratamiento
15.
Leuk Lymphoma ; 65(6): 705-714, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38335007

RESUMEN

Due to the remarkable success of tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML), allogeneic stem cell transplantation (alloSCT) is not first-line treatment for delivering durable, long-term survival. Consequently, alloSCT is reserved for patients with TKI-resistant or TKI-intolerant chronic phase CML (CP-CML) and advanced phase CML (AP-CML). Advances in transplant technology, such as high-resolution HLA typing, introduction of reduced intensity conditioning and increased alternative donor availability, coupled with improved supportive care, have significantly reduced transplant-related mortality and expanded the pool of transplant-eligible patients. Refinement of conditioning regimens, innovative use of post-transplant cellular and pharmacological therapies, and judicious post-transplant monitoring are important strategies for reducing risk of relapse. Given its potential to cure, alloSCT will invariably remain a key part of the treatment algorithm. This article reviews the data underpinning the role and outcomes of alloSCT and provides an update on current recommendations.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva , Inhibidores de Proteínas Quinasas , Acondicionamiento Pretrasplante , Trasplante Homólogo , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Resistencia a Antineoplásicos
16.
Neurol Res Pract ; 6(1): 7, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38326907

RESUMEN

BACKGROUND: Acquired brain injuries are among the most common causes of disability in adulthood. An intensive rehabilitation phase is crucial for recovery. However, there is a lack of concepts to further expand the therapeutic success after the standard rehabilitation period. Hereafter, the characteristics of a transsectoral, multiprofessional long-term neurorehabilitation concept and its effects on outcome at different ICF levels are described. METHODS: The P.A.N. Center for Post-Acute Neurorehabilitation combines living with 24/7 support of pedagogical staff with on-site outpatient therapy and medical care. A secondary data analysis was conducted on the records of all patients with completeted P.A.N. treatment between 01.01.2015 and 09.04.2022. Outcome parameters included demographic characteristics, diagnostics, Barthel Index (BI), the German scale "Hilfebedarf von Menschen mit Behinderung für den Lebensbereich Wohnen " (HMBW), the Canadian Occupational Performance Measure (COPM) and the destination after discharge. For BI and discharge destination, potential determinants of therapy success are evaluated. RESULTS: 168 patients were enrolled in the analyses. Significant improvements were observed in the BI (p < .001), with median values increasing from 55 to 80 points. The HMBW showed a significant decrease in the need for assistance in everyday living (p < .001), individual basic care (p < .001), shaping social relationship (p = .003) and communication (p < .001). Significant improvements were reported in the COPM total score for performance (p < .001) and satisfaction (p < .001). 72% of the patients were able to move in a community living arrangement with moderate need for support. Main predictive factor for discharge destination was the initial cognitive deficit. The comparison of the third-person scales BI and HMBW with the self-reported COPM showed that individually formulated patient goals are only insufficiently reflected in these global scales. DISCUSSION: The data show that a highly coordinated, trans-sectoral 24/7 approach of goal-oriented practice as pursued at P.A.N. is feasible and effective. We assume that the success of the intervention is due to the high intensity of therapies delivered over a long time and its interlink with real world practice. For a comprehensive analysis of rehabilitation success, it is necessary to record and evaluate individual patient goals, as these are not always reflected in the commonly used global scales.

17.
eNeuro ; 11(2)2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38262737

RESUMEN

Spinal cord injury (SCI) often results in various long-term sequelae, and chronically injured spinal cords exhibit a refractory feature, showing a limited response to cell transplantation therapies. To our knowledge, no preclinical studies have reported a treatment approach with results surpassing those of treatment comprising rehabilitation alone. In this study of rats with SCI, we propose a novel combined therapy involving a semaphorin 3A inhibitor (Sema3Ai), which enhances axonal regeneration, as the third treatment element in combination with neural stem/progenitor cell transplantation and rehabilitation. This comprehensive therapeutic strategy achieved significant improvements in host-derived neuronal and oligodendrocyte differentiation at the SCI epicenter and promoted axonal regeneration even in the chronically injured spinal cord. The elongated axons established functional electrical connections, contributing to significant enhancements in locomotor mobility when compared with animals treated with transplantation and rehabilitation. As a result, our combined transplantation, Sema3Ai, and rehabilitation treatment have the potential to serve as a critical step forward for chronic SCI patients, improving their ability to regain motor function.


Asunto(s)
Células-Madre Neurales , Traumatismos de la Médula Espinal , Humanos , Ratas , Animales , Semaforina-3A , Traumatismos de la Médula Espinal/terapia , Trasplante de Células Madre/métodos , Neuronas , Células-Madre Neurales/trasplante , Axones , Médula Espinal , Regeneración Nerviosa/fisiología , Recuperación de la Función/fisiología
18.
Arch Argent Pediatr ; 122(2): e202310068, 2024 04 01.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37871128

RESUMEN

Priapism is a painful and persistent erection, with or without sexual stimulation. A rare cause of such abnormality is chronic myeloid leukemia. Few cases of priapism as an initial manifestation of this type of leukemia have been reported in adolescent patients. Here we describe the case of a 16-year-old patient who presented with priapism as the initial manifestation of chronic myeloid leukemia. No cavernosal aspiration was performed. A specific hematological treatment was started and, given the persistence of priapism, the patient required 2 corpora cavernosa shunt procedures; despite this treatment, there is a high probability of sequelae.


El priapismo es una erección dolorosa y persistente acompañada o no de estímulo sexual. Una causa poco frecuente de esta anormalidad es la leucemia mieloide crónica. Se han reportado pocos casos de priapismo como manifestación inicial de una leucemia de este tipo en pacientes adolescentes. A continuación, se informa el caso de un paciente de 16 años de edad que presentó priapismo como manifestación inicial de una leucemia mieloide crónica. Durante su evolución, no se realizó aspiración de los cuerpos cavernosos. Se inició tratamiento hematológico específico y, ante la persistencia del priapismo, fue necesario realizar un shunt de cuerpos cavernosos en dos ocasiones, tratamiento a pesar del cual existen altas probabilidades de secuelas.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Priapismo , Masculino , Humanos , Adolescente , Priapismo/etiología , Priapismo/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Enfermedad Crónica
19.
Mod Pathol ; 37(2): 100406, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38104892

RESUMEN

Chronic myeloid leukemia (CML) is characterized by leukocytosis with left-shifted neutrophilia, basophilia, eosinophilia, and variable thrombocytosis. However, extremely rare cases of patients with CML without significant leukocytosis and thrombocytosis (aleukemic phase [ALP] CML, or CML-ALP) have been reported. Due to its rarity and limited awareness, there remains a significant knowledge gap concerning the pathologic diagnosis, disease progression, and optimal patient management and outcomes. In this multi-institutional study, we investigated 31 patients with CML-ALP. Over half (54.8%) of patients had a history of or concurrent hematopoietic or nonhematopoietic malignancies. At time of diagnosis of CML-ALP, approximately 26.7% of patients exhibited neutrophilia, 56.7% had basophilia, and 13.3% showed eosinophilia. The median number of metaphases positive for t(9;22)(q34;q11.2) was 15, with a median of 38.5% of interphase nuclei positive for BCR::ABL1 by fluorescence in situ hybridization. The median BCR::ABL1 level was 26.14%. Remarkably, 14 (45.2%) patients were initially misdiagnosed or not diagnosed before karyotype or fluorescence in situ hybridization information for BCR::ABL1 became available. Twenty-five patients received tyrosine kinase inhibitors (TKIs). One patient developed blast crisis while on TKI treatment 8 months after initial diagnosis. With a median follow-up time of 46.1 months, 20 of 22 patients who received TKI therapy and had detailed follow-up information achieved complete cytogenetic remission or deeper, 15 achieved major molecular remission or deeper, and 10 achieved molecularly undetectable leukemia. In conclusion, given the frequent occurrence of prior or concurrent malignancies, aleukemic presentation, and low level of t(9;22)(q34;q11.2)/BCR::ABL1, misdiagnosis or delayed diagnosis is common among these patients. While these patients generally respond well to TKIs, rare patients may develop blastic transformation. It is therefore important for pathologists and hematologists to be aware of this highly unusual presentation of CML to ensure timely diagnosis and appropriate management.


Asunto(s)
Eosinofilia , Leucemia Mielógena Crónica BCR-ABL Positiva , Trombocitosis , Humanos , Hibridación Fluorescente in Situ , Leucocitosis , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Trombocitosis/genética , Inhibidores de Proteínas Quinasas/uso terapéutico
20.
Rev. neurol. (Ed. impr.) ; 77(6): 133-140, Juli-Dic. 2023.
Artículo en Español | IBECS | ID: ibc-225557

RESUMEN

Introducción: La cefalea es un síntoma frecuente tras el ictus isquémico agudo. Su identificación y diagnóstico constituyen un reto por el perfil de paciente y los criterios diagnósticos actuales de esta entidad. Los objetivos del estudio fueron determinar la prevalencia de cefalea atribuida a ictus isquémico y su forma persistente, y analizar las variables clinicodemográficas y el grado de cumplimiento de los criterios de la Clasificación Internacional de Cefaleas (ICHD-III). Pacientes y métodos: Es un estudio observacional analítico de cohortes prospectivo de pacientes ingresados con ictus isquémico agudo en la unidad de ictus de un hospital de tercer nivel en un período de 12 meses. Resultados: Se incluyó a 244 pacientes con ictus isquémico agudo (el 59,8%, varones; edad media: 71 ± 12,8 años). El 23,2% presentó cefalea en el momento del ingreso o bien en las primeras 72 horas y el 12,5% de ellos presentó cefalea persistente atribuida a ictus isquémico. El 62,5% cumplió los criterios diagnósticos de acuerdo con la ICHD-III. Conclusión: La cefalea tras el ictus isquémico es un síntoma frecuente. Su aparición se asoció al sexo femenino, al ictus de territorio vertebrobasilar y a puntuaciones bajas en la National Institutes of Health Stroke Scale. Sería recomendable revisar los criterios diagnósticos actuales.(AU)


Introduction: Headache is a common symptom in acute ischemic stroke which is often overlooked and undertreated because of focus in neurologic function, communication difficulties in stroke patients and the current diagnostic criteria of this type of headache. The present study aimed to determine the prevalence of Acute and Persistent Headache Attributed to Ischemic Stroke and to analyze the fulfillment of the criteria of the International Classification of Headaches (ICHD-IID). Patients and methods: Prospective observational analytical cohort study. The study population consisted of patients with acute ischemic stroke admitted to the Stroke Unit of a tertiary care hospital over a period of 12 months. Results: Two hundred and forty-four patients with acute ischemic stroke (59.8% males, mean age 71+12.8 years) were included. Headache at onset or at the first 72 hours was present in 23.2% and 12.5% of them presented persistent headache attributed to ischemic stroke. Only 62.5% of the headaches at stroke onset fulfilled the diagnostic criteria of ICHD-III. Conclusion: Headache after ischemic stroke is a common symptom. It was associated with female sex, posterior circulation stroke and low scores on the National Institutes of Health Stroke Scale (NIHSS). The current diagnostic criteria should be reviewed.


Asunto(s)
Humanos , Masculino , Femenino , Anciano , Cefalea/diagnóstico , Accidente Cerebrovascular/complicaciones , Cefalea/clasificación , Cefalalgias Vasculares , Trastornos Migrañosos , Prevalencia , Neurología , Enfermedades del Sistema Nervioso , Dolor , Dolor/diagnóstico , Estudios Prospectivos , Estudios de Cohortes
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