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1.
Neuropsychiatr Dis Treat ; 20: 1465-1473, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100573

RESUMEN

Purpose: To validate the efficacy of enhanced measurement-based care against standard measurement-based care in patients with major depressive disorder. Patients and Methods: In this pilot study of an ongoing multicenter cluster randomized controlled trails, 160 patients diagnosed with major depressive disorder were enrolled from 2 mental health centers, with a plan to include 12 centers in total. One hundred patients engaged in a six-month evaluation using a technology-enhanced measurement-based care tool, including assessments of clinical symptoms, side effects, and functionality at baseline, two months, four months and six months. Simultaneously, the remaining 60 patients underwent standard paper-based measurement-based care, utilizing the same set of scales over the same six-month period, with assessments at the same time points. Results: Patients utilizing the enhanced measurement-based care tool demonstrated a significantly higher reduction rate in PHQ-9 scores compared to those using standard paper-based measurement-based care during the two-month follow-up. Additionally, a notable positive correlation was observed between the frequency of enhanced measurement-based care tool usage and the quality of life during the two-month follow-up. Conclusion: Enhanced measurement-based care has the effect of reducing depressive symptoms. Our study emphasized that using enhanced measurement-based care via smartphones is a feasible tool for patients with major depressive disorder. Our future study, including results from additional research centers, may further validate the effectiveness of enhanced measurement-based care.

2.
J Biomech Eng ; : 1-50, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196594

RESUMEN

This study proposes a numerical approach for simulating bone remodeling in lumbar interbody fusion (LIF). It employs a topology optimization method to drive the remodeling process and uses a pixel function to describe the structural topology and bone density distribution. Unlike traditional approaches based on strain energy density or compliance, this study adopts von Mises stress to guide the remodeling of LIF. A novel pixel interpolation scheme associated with stress criteria is applied to the physical properties of the bone, directly addressing the stress shielding effect caused by the implanted cage, which significantly influences the bone remodeling outcome in LIF. Additionally, a boundary inverse approach is utilized to reconstruct a simplified analysis model. To reduce computational cost while maintaining high structural resolution and accuracy, the Scaled Boundary Finite Element Method (SBFEM) is introduced. The proposed numerical approach successfully generates results that closely resemble human lumbar interbody fusion.

3.
BMC Psychiatry ; 24(1): 529, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39048972

RESUMEN

BACKGROUND: Schizophrenia (SCZ) patients undergoing antipsychotic treatment demonstrated a high prevalence and harmful effects of metabolic syndrome (MetS), which acted as the major cause of cardiovascular disease. The major clinical challenge is the lack of biomarkers to identify MetS episodes and prevent further damage, while the mechanisms underlying these drug-induced MetS remain unknown. METHODS: This study divided 173 participants with SCZ into 3 groups (None, High risk, and MetS, consisting of 22, 88, and 63 participants, respectively). The potential biomarkers were searched based on 16S rRNA gene sequence together with metabolism analysis. Logistic regression was used to test the effects of the genus-metabolites panel on early MetS diagnoses. RESULTS: A genus-metabolites panel, consisting of Senegalimassilia, sphinganine, dihomo-gamma-linolenoylcholine, isodeoxycholic acid, and MG (0:0/22:5/0:0), which involved in sphigolipid metabolism, fatty acid metabolism, secondary bile acid biosynthesis and glycerolipid metabolism, has a great discrimination efficiency to MetS with an area under the curve (AUC) value of 0.911 compared to the None MetS group (P = 1.08E-8). Besides, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) distinguished between subgroups robustly and exhibited a potential correlation with the severity of MetS in patients with SCZ, and may act as the biomarkers for early MetS diagnosis. CONCLUSIONS: Our multi-omics study showed that one bacterial genus-five lipid metabolites panel is the potential risk factor for MetS in SCZ. Furthermore, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) could serve as novel diagnostic markers in the early stage. So, it is obvious that the combination of bacterial genus and metabolites yields excellent discriminatory power, and the lipid metabolism provide new understanding to the pathogenesis, prevention, and therapy for MetS in SCZ.


Asunto(s)
Biomarcadores , Microbioma Gastrointestinal , Síndrome Metabólico , Esquizofrenia , Humanos , Esquizofrenia/metabolismo , Esquizofrenia/microbiología , Síndrome Metabólico/metabolismo , Síndrome Metabólico/microbiología , Microbioma Gastrointestinal/fisiología , Masculino , Femenino , Adulto , Biomarcadores/metabolismo , Persona de Mediana Edad , Antipsicóticos/uso terapéutico , ARN Ribosómico 16S/genética
4.
Proc Natl Acad Sci U S A ; 121(16): e2320331121, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38593071

RESUMEN

Smart polymer materials that are nonliving yet exhibit complex "life-like" or biomimetic behaviors have been the focus of intensive research over the past decades, in the quest to broaden our understanding of how living systems function under nonequilibrium conditions. Identification of how chemical and mechanical coupling can generate resonance and entrainment with other cells or external environment is an important research question. We prepared Belousov-Zhabotinsky (BZ) self-oscillating hydrogels which convert chemical energy to mechanical oscillation. By cyclically applying external mechanical stimulation to the BZ hydrogels, we found that when the oscillation of a gel sample entered into harmonic resonance with the applied oscillation during stimulation, the system kept a "memory" of the resonant oscillation period and maintained it post stimulation, demonstrating an entrainment effect. More surprisingly, by systematically varying the cycle length of the external stimulation, we revealed the discrete nature of the stimulation-induced resonance and entrainment behaviors in chemical oscillations of BZ hydrogels, i.e., the hydrogels slow down their oscillation periods to the harmonics of the cycle length of the external mechanical stimulation. Our theoretical model calculations suggest the important roles of the delayed mechanical response caused by reactant diffusion and solvent migration in affecting the chemomechanical coupling in active hydrogels and consequently synchronizing their chemical oscillations with external mechanical oscillations.

5.
J Psychiatr Res ; 174: 297-303, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38678687

RESUMEN

BACKGROUND: Biological rhythms denote the cyclical patterns of life activities anchored to a 24-hour cycle. Research shows that depression exhibits disturbances in biological rhythms. Yet, the relationship between these biological rhythms and concomitant anxiety symptoms is insufficiently investigated in structured clinical assessments. METHODS: This multicenter study, carried out in four Chinese hospitals, comprehensively examined the relationship between anxiety and disruptions in biological rhythms among patients with depression. The study encompassed 218 patients diagnosed with depression and 205 matched healthy controls. The Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry was utilized to evaluate the participants' biological rhythms, focusing on four dimensions: sleep, activity, social, and diet. RESULTS: In patients with depression, there is a significant positive correlation between the severity of anxiety symptoms and the disturbances in biological rhythms. The severity of anxiety and depression, along with the quality of life, are independently associated with disruptions in biological rhythms. The mediation model reveals that anxiety symptoms mediate the relationship between depressive symptoms and biological rhythms. CONCLUSION: This research highlights the role of anxiety within the spectrum of depressive disorders and the associated disturbances in biological rhythms. Our findings shed light on potential pathways towards more targeted preventive strategies and therapeutic interventions for individuals battling depression and anxiety.


Asunto(s)
Ansiedad , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Ansiedad/fisiopatología , Depresión/fisiopatología , Ritmo Circadiano/fisiología , Trastorno Depresivo/fisiopatología , Adulto Joven , Trastornos Cronobiológicos/fisiopatología
6.
J Affect Disord ; 356: 1-12, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38548210

RESUMEN

BACKGROUND: Major depressive disorder (MDD) and bipolar disorder (BD) are psychiatric disorders with overlapping symptoms, leading to high rates of misdiagnosis due to the lack of biomarkers for differentiation. This study aimed to identify metabolic biomarkers in urine samples for diagnosing MDD and BD, as well as to establish unbiased differential diagnostic models. METHODS: We utilized a metabolomics approach employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) to analyze the metabolic profiles of urine samples from individuals with MDD (n = 50), BD (n = 12), and healthy controls (n = 50). The identification of urine metabolites was verified using MS data analysis tools and online metabolite databases. RESULTS: Two diagnostic panels consisting of a combination of metabolites and clinical indicators were identified-one for MDD and another for BD. The discriminative capacity of these panels was assessed using the area under the receiver operating characteristic (ROC) curve, yielding an area under the curve (AUC) of 0.9084 for MDD and an AUC value of 0.9017 for BD. CONCLUSIONS: High-resolution mass spectrometry-based assays show promise in identifying urinary biomarkers for depressive disorders. The combination of urine metabolites and clinical indicators is effective in differentiating healthy controls from individuals with MDD and BD. The metabolic pathway indicating oxidative stress is seen to significantly contribute to depressive disorders.


Asunto(s)
Biomarcadores , Trastorno Bipolar , Trastorno Depresivo Mayor , Espectrometría de Masas , Metabolómica , Humanos , Trastorno Bipolar/orina , Trastorno Bipolar/diagnóstico , Trastorno Depresivo Mayor/orina , Trastorno Depresivo Mayor/diagnóstico , Biomarcadores/orina , Femenino , Masculino , Adulto , Diagnóstico Diferencial , Persona de Mediana Edad , Cromatografía Líquida de Alta Presión , Curva ROC , Estudios de Casos y Controles
7.
Biomed Chromatogr ; 38(6): e5864, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38551083

RESUMEN

As one of the most common antipsychotics, olanzapine may cause metabolic-related adverse effects, but it is still unknown how olanzapine alters lipid metabolism. In this study, we found that olanzapine-treated mice showed varying degrees of dyslipidemia, which was particularly pronounced in female mice. Based on ultra-performance liquid chromatography-quadrupole time-of-flight-MS (UPLC-Q-TOF-MS) technology and lipid metabolomics, we mapped the changes in lipid metabolism in olanzapine-treated mice and then compared the changes in lipid metabolism between male and female mice. There were 98 metabolic differentiators between the olanzapine-treated and control groups in females and 79 in males. These metabolites were glycerolipids, glycerophospholipids, fatty amides, and sphingolipids, which are involved in glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. These results suggest that olanzapine-induced changes in the levels of lipid metabolites are closely associated with disturbances in lipid metabolic pathways, which may underlie lipemia. This lipidome profiling study not only visualizes changes in lipid metabolism in liver tissue but also provides a foundation for understanding the regulatory pathways and mechanisms involved in olanzapine-induced lipid metabolism disorders. Furthermore, this study demonstrates differences in lipid metabolism between males and females, providing a reference for clinical treatment regimen selection.


Asunto(s)
Metabolismo de los Lípidos , Olanzapina , Aumento de Peso , Animales , Femenino , Masculino , Ratones , Metabolismo de los Lípidos/efectos de los fármacos , Aumento de Peso/efectos de los fármacos , Cromatografía Líquida de Alta Presión/métodos , Lipidómica/métodos , Ratones Endogámicos C57BL , Hígado/efectos de los fármacos , Hígado/metabolismo , Factores Sexuales , Benzodiazepinas/farmacología , Espectrometría de Masas/métodos , Dislipidemias/inducido químicamente , Dislipidemias/metabolismo , Antipsicóticos , Lípidos/sangre , Lípidos/química
8.
Neurospine ; 21(1): 212-222, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38317552

RESUMEN

OBJECTIVE: Surgical procedures for patients with posttraumatic syringomyelia (PTS) remain controversial. Until now, there have been no effective quantitative evaluation methods to assist in selecting appropriate surgical plans before surgery. METHODS: We consecutively enrolled PTS patients (arachnoid lysis group, n = 42; shunting group, n = 14) from 2003 to 2023. Additionally, 19 intrathecal anesthesia patients were included in the control group. All patients with PTS underwent physical and neurological examinations and spinal magnetic resonance imaging preoperatively, 3-12 months postoperatively and during the last follow-up. Preoperative lumbar puncture was performed and blood-spinal cord barrier disruption was detected by quotient of albumin (Qalb, cerebrospinal fluid/serum). RESULTS: The ages (p = 0.324) and sex (p = 0.065) of the PTS and control groups did not differ significantly. There were also no significant differences in age (p = 0.216), routine blood data and prognosis (p = 0.399) between the arachnoid lysis and shunting groups. But the QAlb level of PTS patients was significantly higher than that of the control group (p < 0.001), and the shunting group had a significantly higher QAlb (p < 0.001) than the arachnoid lysis group. A high preoperative QAlb (odds ratio, 1.091; 95% confidence interval, 1.004-1.187; p = 0.041) was identified as the predictive factor for the shunting procedure, with the receiver operating characteristic curve showing 100% specificity and 80.95% sensitivity for patients with a QAlb > 12.67. CONCLUSION: Preoperative QAlb is a significant predictive factor for the types of surgery. For PTS patients with a QAlb > 12.67, shunting represents the final recourse, necessitating the exploration and development of novel treatments for these patients.

11.
Spine (Phila Pa 1976) ; 49(6): E62-E71, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38014747

RESUMEN

STUDY DESIGN: Cohort study. OBJECTIVE: The aim of this study was to explore the association between blood-spinal cord barrier (BSCB) markers and other factors associated with an unfavorable outcome among patients with post-traumatic syringomyelia (PTS) who achieved successful intradural adhesion lysis (IAL). SUMMARY OF BACKGROUND DATA: Only approximately half of PTS patients receiving IAL have a favorable outcome. PATIENTS AND METHODS: Forty-six consecutive patients with PTS and 19 controls (CTRL) were enrolled. All PTS patients underwent physical and neurological examinations and spinal magnetic resonance imaging before and 3 to 12 months after IAL. All patients underwent myelography before surgery. BSCB disruption was detected by increased intrathecal and serum concentrations of albumin, immunoglobulin (Ig)G, IgA, and IgM. A multivariable analysis was performed with a logistic regression model to identify factors associated with unfavorable outcomes. Receiver operating characteristic curves were calculated to investigate the diagnostic value of biomarkers. RESULTS: The ages and general health of the PTS and CTRL groups did not differ significantly. QAlb, IGAQ, IGGQ, and IGMQ was significantly higher in PTS patients than in controls ( P =<0.001). The degree of intradural adhesion was significantly higher in the unfavorable outcome group than in the favorable outcome group ( P <0.0001). QAlb, immunoglobulin (Ig)AQ, IGGQ, and IGMQ was significantly correlated with clinical status ( R =-0.38, P <0.01; R =-0.47, P =0.03; R =-0.56, P =0.01; R =-0.43, P =0.05, respectively). Higher QAlb before surgery (odds ratio=2.66; 95% CI: 1.134-6.248) was significantly associated with an unfavorable outcome. The receiver operating characteristic curve analysis demonstrated a cutoff for QAlb higher than 10.62 with a specificity of 100% and sensitivity of 96.3%. CONCLUSION: This study is the first to detect increased permeability and BSCB disruption in PTS patients. QAlb>10.62 was significantly associated with unfavorable clinical outcomes following intradural decompression. LEVEL OF EVIDENCE: Level III-prognostic.


Asunto(s)
Traumatismos de la Médula Espinal , Siringomielia , Humanos , Siringomielia/diagnóstico por imagen , Siringomielia/etiología , Siringomielia/cirugía , Estudios de Cohortes , Traumatismos de la Médula Espinal/complicaciones , Pronóstico , Inmunoglobulinas
12.
PLoS Pathog ; 19(12): e1011856, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38048356

RESUMEN

The rapid emergence of SARS-CoV-2 variants of concern (VOCs) calls for efforts to study broadly neutralizing antibodies elicited by infection or vaccination so as to inform the development of vaccines and antibody therapeutics with broad protection. Here, we identified two convalescents of breakthrough infection with relatively high neutralizing titers against all tested viruses. Among 50 spike-specific monoclonal antibodies (mAbs) cloned from their B cells, the top 6 neutralizing mAbs (KXD01-06) belong to previously defined IGHV3-53/3-66 public antibodies. Although most antibodies in this class are dramatically escaped by VOCs, KXD01-06 all exhibit broad neutralizing capacity, particularly KXD01-03, which neutralize SARS-CoV-2 from prototype to the emerging EG.5.1 and FL.1.5.1. Deep mutational scanning reveals that KXD01-06 can be escaped by current and prospective variants with mutations on D420, Y421, L455, F456, N460, A475 and N487. Genetic and functional analysis further indicates that the extent of somatic hypermutation is critical for the breadth of KXD01-06 and other IGHV3-53/3-66 public antibodies. Overall, the prevalence of broadly neutralizing IGHV3-53/3-66 public antibodies in these two convalescents provides rationale for novel vaccines based on this class of antibodies. Meanwhile, KXD01-06 can be developed as candidates of therapeutics against SARS-CoV-2 through further affinity maturation.


Asunto(s)
COVID-19 , Vacunas , Humanos , SARS-CoV-2/genética , Infección Irruptiva , Estudios Prospectivos , Anticuerpos Monoclonales , Anticuerpos Monoclonales Humanizados , Anticuerpos Antivirales , Anticuerpos Neutralizantes , Glicoproteína de la Espiga del Coronavirus/genética
13.
Sci Rep ; 13(1): 21764, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38065966

RESUMEN

The reliable joint connection between precast members is vital to resisting earthquake loads in precast concrete structures. To further improve the convenience of precast construction, this paper presents a new horizontal joint of precast concrete panels with castellated keys supports pillar connections based on the stable mechanical properties of the wet concrete joint. To examine the seismic response of this connection type, a series of in-plane cyclic loading tests were carried out using six full-size precast specimens and one cast-in-place specimen for comparison. The influences of axial compression ratio, joint width, and joint concrete strength on the seismic indicators of the precast concrete panel were considered in the design of specimens. The test results showed all specimens had the same damage process, and the ultimate failure modes combined compression and bending. The precast specimens exhibited similar seismic performance to the cast-in-place specimen, especially whose joint concrete strength is higher than the precast concrete panel. Based on the load-displacement test curve, a hysteretic curve model that included both the envelope curve and the stiffness degradation law was proposed. The predictions from the model showed good compatibility with the experimental results, and the model can be used as a reference for analyzing the elastic-plastic response of the precast concrete panels with castellated keys supporting pillar connections.

14.
Heliyon ; 9(11): e20951, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37920522

RESUMEN

Background: This research was designed to investigate Algorithm Guided Treatment (AGT) and clinical traits for the prediction of antidepressant treatment outcomes in Chinese patients with major depressive disorder (MDD). Methods: This study included 581 patients who had reached treatment response and 406 patients remained non-responded observed after three months of treatment. Sociodemographic factors, clinical traits, and psychiatric rating scales for evaluating therapeutic responses between the two groups were compared. Logistic regression analysis was adopted to determine the risk factors of unresponsive to antidepressant (URA) in MDD. Kaplan-Meier survival analysis was utilized to compare the therapeutic response between AGT and treatment as usual (TAU). Results: Compared to the MDD responsive to antidepressant (RA) group, the URA group had significantly lower rates of the following clinical traits: married status, anxious distress, moderate to severe depressive symptoms, and higher rates of comorbidity (p-value < 0.05). Logistic Regression Analysis showed that eight clinical traits from psychiatric rating scales, such as anxious characteristics, were correlated positively with URA, while the other eight symptoms, such as autonomic symptoms, were negatively correlated. Time to symptomatic remission was longer in TAU without statistically significant (p-value = 0.11) by log-rank testing. Conclusions: The factors may affect the therapeutic responses and compliance of patients, increasing the non-response risk for antidepressants. Therapeutic responses might be improved by increasing the clarification and elucidation of different symptom clusters of patients. Benefits on treatment response to AGT were not found in our study, indicating a one-size-fits-all approach may not work.Trial Registration: We registered as a clinical trial at the International Clinical Trials Registry Platform (No. NCT01764867) and obtained ethical approval 2012-42 from SMHC.

15.
J Neuroimmunol ; 383: 578191, 2023 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-37660537

RESUMEN

Hypertrophic pachymeningitis (HP) is a relatively rare disease of the central nervous system characterized by local or diffuse fibrous thickening of the dura mater. At present, there is still insufficient research on the pathogenesis and treatment strategies of this disease. We reported a continuous case series of seven patients with idiopathic HP (IHP), and also details one case of immunoglobulin G4-related HP requiring surgical intervention. Early diagnosis and appropriate surgical intervention for IHP could prevent the progression of permanent neurological damage and spinal cord paraplegia.


Asunto(s)
Meningitis , Humanos , Duramadre/diagnóstico por imagen , Duramadre/cirugía , Duramadre/patología , Hipertrofia , Meningitis/complicaciones , Meningitis/diagnóstico por imagen , Médula Espinal/patología
16.
Neurospine ; 20(2): 498-506, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37401068

RESUMEN

OBJECTIVE: The surgical management of basilar invagination without atlantoaxial dislocation (type B basilar invagination) remains controversial. Hence, we have reported the use of posterior intra-articular C1-2 facet distraction, fixation, and cantilever technique versus foramen magnum decompression in treating type B basilar invagination as well as the results and surgical indications for this procedure. METHODS: This was a single-center retrospective cohort study. Fifty-four patients who underwent intra-articular distraction, fixation, and cantilever reduction (experimental group) and foramen magnum decompression (control group) were enrolled in this study. Distance from odontoid tip to Chamberlain's line, clivus-canal angle, cervicomedullary angle, craniovertebral junction (CVJ) triangle area, width of subarachnoid space and syrinx were used for radiographic assessment. Japanese Orthopedic Association (JOA) scores and 12-item Short Form health survey (SF-12) scores were used for clinical assessment. RESULTS: All patients in the experimental group had a better reduction of basilar invagination and better relief of pressure on nerves. JOA scores and SF-12 scores also had better improvements in the experimental group postoperation. SF-12 score improvement was associated with preoperative CVJ triangle area (Pearson index, 0.515; p = 0.004), cutoff value of 2.00 cm2 indicating the surgical indication of our technique. No severe complications or infections occurred. CONCLUSION: Posterior intra-articular C1-2 facet distraction, fixation, and cantilever reduction technique is an effective treatment for type B basilar invagination. As various factors involved, other treatment strategies should also be investigated.

17.
Neurospine ; 20(2): 701-708, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37401089

RESUMEN

OBJECTIVE: Although cerebrospinal fluid (CSF)-based liquid biopsy was proved to be practical in molecular analysis of intracranial gliomas, liquid biopsy of primary intramedullary astrocytoma was rarely reported. Given the distinct genomic profiles between primary intramedullary glioma and intracranial astrocytoma, whether the feasibility of CSF-based molecular analysis of intracranial gliomas can be replicated in primary spinal cord astrocytoma needs to be investigated. The aim of this pilot study is to evaluate the feasibility of molecular analysis of primary intramedullary astrocytoma through sequencing CSF-derived circulating tumor DNA (ctDNA). METHODS: Two grade IV diffuse midline gliomas, 1 grade II, and 1 grade I astrocytoma were included. Intraoperative collection of peripheral blood and CSF samples was conducted, along with postoperative collection of matched tumor tissues. A panel covering the 1,021 most common driver genes of solid tumors was used for targeted DNA sequencing. RESULTS: CSF-derived ctDNA was detected in 3 CSF samples (2 grade IV diffuse midline gliomas and 1 grade I astrocytoma), 5 mutations were found in both tumor tissues and CSF samples, while 11 mutations and 20 mutations were detected exclusively in tumor tissues and CSF samples, respectively. Importantly, hotspot genetic alterations, including H3F3A K28M, TP53, and ATRX, were identified in CSF and the average mutant allele frequency was often higher in CSF than in tumor tissues. CONCLUSION: CSF-based liquid biopsy showed potential feasibility for molecular analysis of primary intramedullary astrocytoma through sequencing of ctDNA. This approach may assist in diagnosis and prognostic evaluation of this rare spinal cord tumor.

18.
Eur J Pharmacol ; 952: 175752, 2023 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-37164118

RESUMEN

Although rat sarcoma viral oncogene homolog (RAS) mutations occur in about 30% of solid tumors, targeting RAS mutations other than KRAS-G12C is still challenging. As an alternative approach, developing inhibitors targeting RAF, the downstream effector of RAS signaling, is currently one of the main strategies for cancer therapy. Selective v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-V600E inhibitors Vemurafenib, Encorafenib, and Dabrafenib have been approved by FDA and received remarkable clinical responses, but these drugs are ineffective against RAS mutant tumors due to limited inhibition on dimerized RAF. In this study, we developed a highly potent pan-RAF inhibitor, IHMT-RAF-128, which exhibited similarly high efficacies in inhibiting both partners of the RAF dimer, and showed potent anti-tumor efficacy against a variety of cancer cells harboring either RAF or RAS mutations, especially Adagrasib and Sotorasib (AMG510) resistant-KRAS-G12C secondary mutations, such as KRAS-G12C-Y96C and KRAS-G12C-H95Q. In addition, IHMT-RAF-128 showed excellent pharmacokinetic profile (PK), and the bioavailability in mice and rats were 63.9%, and 144.1%, respectively. Furthermore, IHMT-RAF-128 exhibited potent anti-tumor efficacy on xenograft mouse tumor models in a dose-dependent manner without any obvious toxicities. Together, these results support further investigation of IHMT-RAF-128 as a potential clinical drug candidate for the treatment of cancer patients with RAF or RAS mutations.


Asunto(s)
Neoplasias , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Animales , Ratones , Proteínas Proto-Oncogénicas p21(ras)/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Vemurafenib/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/genética
19.
Int J Surg ; 109(8): 2276-2285, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37204435

RESUMEN

BACKGROUND: To develop a practical prediction model to predict the risk of deep surgical site infection (SSI) in patients receiving open posterior instrumented thoracolumbar surgery. METHODS: Data of 3419 patients in four hospitals from 1 January 2012 to 30 December 2021 were evaluated. The authors used clinical knowledge-driven, data-driven, and decision tree model to identify predictive variables of deep SSI. Forty-three candidate variables were collected, including 5 demographics, 29 preoperative, 5 intraoperative, and 4 postoperative variables. According to model performance and clinical practicability, the best model was chosen to develop a risk score. Internal validation was performed by using bootstrapping methods. RESULTS: After open posterior instrumented thoracolumbar surgery, 158 patients (4.6%) developed deep SSI. The clinical knowledge-driven model yielded 12 predictors of deep SSI, while the data-driven and decision tree model produced 11 and 6 predictors, respectively. A knowledge-driven model, which had the best C-statistics [0.81 (95% CI: 0.78-0.85)] and superior calibration, was chosen due to its favorable model performance and clinical practicality. Moreover, 12 variables were identified in the clinical knowledge-driven model, including age, BMI, diabetes, steroid use, albumin, duration of operation, blood loss, instrumented segments, powdered vancomycin administration, duration of drainage, postoperative cerebrospinal fluid leakage, and early postoperative activities. In bootstrap internal validation, the knowledge-driven model still showed optimal C-statistics (0.79, 95% CI: 0.75-0.83) and calibration. Based on these identified predictors, a risk score for deep SSI incidence was created: the A-DOUBLE-SSI (Age, D [Diabetes, Drainage], O [duration of Operation, vancOmycin], albUmin, B [BMI, Blood loss], cerebrospinal fluid Leakage, Early activities, Steroid use, and Segmental Instrumentation) risk score. Based on the A-DOUBLE-SSI score system, the incidence of deep SSI increased in a graded fashion from 1.06% (A-DOUBLE-SSIs score ≤8) to 40.6% (A-DOUBLE-SSIs score>15). CONCLUSIONS: The authors developed a novel and practical model, the A-DOUBLE-SSIs risk score, that integrated easily accessible demographics, preoperative, intraoperative, and postoperative variables and could be used to predict individual risk of deep SSI in patients receiving open posterior instrumented thoracolumbar surgery.


Asunto(s)
Infección de la Herida Quirúrgica , Vancomicina , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Estudios de Cohortes , Factores de Riesgo , Albúminas , Esteroides , Estudios Retrospectivos
20.
Acta Neurol Belg ; 123(3): 807-814, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37046133

RESUMEN

BACKGROUND: A specific scoring system for syringomyelia is lacking. Our objective was to investigate the value of a novel scoring system (Syringomyelia Outcome Scale of Xuanwu hospital, SOS-XW) in assessing surgical outcomes in the treatment of syringomyelia (SM) associated with Chiari malformation type I (CM I). METHODS: A quantitative evaluation system (SOS-XW) of SM includes 4 parameters: pain (P), sensation (S), movement (M), and syringomyelia tension index (STI). The clinical data of 88 patients with CM I-related syringomyelia treated by foramen magnum and Magendie dredging (FMMD) from January 2018 to January 2019 were retrospectively analysed with a mean follow-up of 14.3 months, and the SOS-XW score was used to assess the efficacy. RESULTS: The higher the SOS-XW score, the more severe was the SM and related symptoms. The mean preoperative score was 5.97, and the postoperative score was 2.66. The symptom improvement rates were 77.78% for P, 69.01% for S, 31.82% for M, and 95.06% for the syringomyelia tension index (STI). The symptom improvement rate of the PSM score was weakly correlated with the improvement rate of STI, R2 = 0.0016. The percentage of PSM (P + S + M) improvement was lower in patients with an STI of 0. The postoperative SOS-XW score was positively correlated with the postoperative JOA score, R2 = 0.8314. The positive detection rate of SOS-XW was higher than that of the JOA score. CONCLUSIONS: To evaluate the surgical procedure efficacy in the treatment of syringomyelia, the SOS-XW score can provide a more objective, detailed, and comprehensive analysis, especially STI. A reduction in STI is the practical standard for assessing the effectiveness of surgery.


Asunto(s)
Malformación de Arnold-Chiari , Siringomielia , Humanos , Adulto , Malformación de Arnold-Chiari/complicaciones , Malformación de Arnold-Chiari/cirugía , Siringomielia/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Descompresión Quirúrgica/métodos , Foramen Magno , Imagen por Resonancia Magnética
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