Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 781
Filtrar
1.
Artículo en Inglés | MEDLINE | ID: mdl-35654719

RESUMEN

Cardiac computed tomography (CCT) has increasingly been used in the assessment of both children and adults with congenital heart disease (CHD), in part due to advances in CCT technology and an increased prevalence of adults with palliated CHD. It serves as a complimentary modality to echocardiography, cardiac magnetic resonance imaging and cardiac catheterization. CCT can provide unique diagnostic information, is less invasive and less likely to require sedation compared to other modalities. Detailed knowledge of individual patient cardiac anatomy, physiology, surgical repair and possible residual lesions are paramount to optimal CCT imaging. This comprehensive review details the use of CCT both pre- and postoperatively for the most common CHD diagnoses. We also aim to highlight some new and innovative technologies that have become available and can further optimize CCT imaging for CHD patients.

2.
Artículo en Chino | MEDLINE | ID: mdl-35527449

RESUMEN

Objective: To assess the incidence of symptomatic torus tubarius hypertrophy (TTH) in recurred OSA in children, and to explore the preliminary experience of partial resection of TTH assisted with radiofrequency ablation. Methods: From January 2004 to February 2020, 4 922 children, who diagnosed as OSA and received adenotonsillectomy at the Department of Otolaryngology, The 4th Medical Center of the PLA General Hospital, were retrospectively reviewed. There were 3 266 males and 1 656 females, the age ranged from 1 to 14 years old(median age of 5.0 years). Twenty-two cases were identified with recurrence of OSA syndrome, and the clinical data, including sex, age of primary operation, age of recurrence and presentation, and opertation methods were analyzed. Follow-up was carried out by outpatient visit or telephone. Graphpad prism 5.0 software was used for statistical analysis. Results: Twenty-two cases were identified as recurred OSA and received revised surgery in 4 922 cases. Among these 22 cases, 11 cases were diagnosed as TTH resulting in an incidence of 2.23‰(11/4 922), 1 case was cicatricial adhesion on tubal torus (0.20‰, 1/4 922), 10 cases were residual adenoid combined with tubal tonsil hypertrophy (2.03‰, 10/4 922). Median age of primary operation was 3.0 years (range:2.4 to 6.0 years) in 11 TTH cases. Recurrent interval varied from 2 months to 5.5 years (2.4±1.9 years) after first operation. Age of revised partial resection of TTH was 7.0±2.7 years (range: 4.0 to 12.0 years). Average time interval between primary operation and revised operation was 3.5±2.1 years (range: 0.5 to 6.0 years). Individualized treatments were carried out based on partial resection of TTH assisted with radiofrequency ablation. All of 11 cases received satisfied therapeutic results without nasopharyngeal stenosis occured. Twenty-two cases were followed up for 1.6 to 13 years (median follow-up time was 6.2 years). Conclusions: TTH contributed to recurred OSA in child. TTH might be misdiagnosed as tubal tonsil hypertrophy. Partial resection of TTH assisted with radiofrequency ablation was a safty and effective treatment.


Asunto(s)
Tonsila Faríngea , Apnea Obstructiva del Sueño , Adenoidectomía , Tonsila Faríngea/cirugía , Adolescente , Niño , Preescolar , Femenino , Humanos , Hipertrofia/cirugía , Lactante , Masculino , Estudios Retrospectivos , Apnea Obstructiva del Sueño/cirugía
3.
Niger J Clin Pract ; 25(5): 664-669, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35593610

RESUMEN

Background: Anchorage control is one of the components in the treatment of extraction cases. However, what determines more or less anchorage loss is still an unanswered question. Aim: The purpose of this study was to investigate the most important factors contributing to the anchorage loss of maxillary first molars in premolar extraction cases. Materials and Methods: The study included 726 upper premolar extraction cases, including 214 male patients and 512 female patients, and the mean age was 14.4 ± 4.5 years old (range: 9-45). Factors including physiological characteristics, treatment mechanics, and cephalometric variables were collected and their influences on the angulation changes of maxillary first molars were analyzed. Results: The mean angulation change of maxillary first molar after treatment was 2.81°(mesial tipping). The change of UM/PP showed a statistically significant difference in different sex (male 3.84° ± 5.26° vs female 2.38° ± 5.10°), age (adult -0.05° ± 4.73° vs teenager 3.46° ± 5.07°), and molar relationship (Class II 3.28° ± 5.15° vs Class I 2.36° ± 5.19°). There are six variables accounted in the regression analysis (R = 0.608, R2 = 37.0%). Among them, the pre-treatment molar tipping (Standardized Coefficients: -0.65) and the pre-treatment incisor/molar height ratio (Standardized Coefficients: -0.27) were the most important factors influencing anchorage loss during treatment. Conclusion: Compared with treatment-related factors, the patient's physiological characteristics play a more important role in anchorage loss. The pre-treatment angulation of the maxillary first molar is the most influential factor in changes to maxillary molar angulation, which are often predisposing anchorage loss.


Asunto(s)
Maloclusión Clase II de Angle , Técnicas de Movimiento Dental , Adolescente , Adulto , Diente Premolar/cirugía , Cefalometría , Niño , Femenino , Humanos , Incisivo , Masculino , Maloclusión Clase II de Angle/terapia , Maxilar/cirugía , Diente Molar/cirugía , Estudios Retrospectivos
4.
ESMO Open ; 7(3): 100473, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35526510

RESUMEN

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance frequently occurs in patients with non-small-cell lung cancer (NSCLC). EGFR Thr790Met mutation (T790M+) is seen in ∼50% of patients. We assessed the safety, tolerability, and pharmacokinetics (PK) of BPI-15086, a novel, ATP-competitive, irreversible, third-generation, mutation-selective EGFR-TKI in patients with EGFR T790M-mutated NSCLC. PATIENTS AND METHODS: This two-center, phase I, dose-escalation study included patients who were 18-65 years old, with an Eastern Cooperative Oncology Group performance status of 0-2, with histologically or cytologically confirmed locally advanced or metastatic T790M+ NSCLC who were not surgical or radiotherapy candidates, and had imaging-identified disease progression after prior EGFR-TKIs. This dose-escalation study enrolled patients using a 3 + 3 study design. Patients received 25, 50, 100, 200, and 300 mg/day orally in 21-day cycles. The primary endpoints were safety, tolerability, and PK. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR). The dose-expansion study was not conducted. RESULTS: We enrolled 17 patients from 29 December 2016 to 16 May 2018, in the safety and full analysis sets. All patients completed a single dosing trial, and no adverse events (AEs) causing drug discontinuation were seen. Grade 1-2 nausea, hypoalbuminemia, and decreased appetite were the most common treatment-related AEs. Grade 3 hyperglycemia was seen in one patient dosed at 300 mg/day. The ORR and DCR were 17.7% [95% confidence interval (CI) 3.8% to 43.4%] and 47.1% (95% CI 23.0% to 72.2%), respectively. CONCLUSION: BPI-15086 is a safe and tolerable third-generation EGFR-TKI with a rationale for further clinical studies.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adolescente , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos , Adulto Joven
5.
Zhonghua Gan Zang Bing Za Zhi ; 30(4): 407-412, 2022 Apr 20.
Artículo en Chino | MEDLINE | ID: mdl-35545566

RESUMEN

Objective: To investigate the effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors. Methods: 127 cases with liver cirrhosis accompanied with esophageal and gastric varices without bleeding history were included in the endoscopic and non-endoscopic treatment group, respectively. Informed consent was obtained from both groups. Gastric varices (Lgf) and esophageal varices (Leg) were diagnosed according to LDRf classification criteria, and the corresponding treatment scheme was selected according to the recommended principle of this method.The incidence rate of bleeding from ruptured esophageal varices were observed at 3, 6 months, and 1, and 2 years in the treated and the untreated group, and the patients with different Child-Pugh scores were followed-up for 2 years. Gender, age, etiology, varicose degree, Child-Pugh grade, platelet count, prothrombin activity, portal vein thrombosis, collateral circulation, portal vein width and other factors affecting the bleeding rate were assessed. Measurement data were described as mean ± standard deviation (x¯±s), and qualitative data of categorical variables were expressed as percentage (%), and χ2 test was used. Results: 127 cases were followed up for 2 years. There were 55 cases in the endoscopic treatment group (18 cases underwent band ligation, 2 cases underwent band ligation combined with tissue adhesive embolization, 28 cases underwent sclerotherapy, and 7 cases underwent sclerotherapy combined with tissue adhesive embolization). Recurrent bleeding and hemorrhage was occurred in 5 (9.1%) and 28 cases (38.9%), respectively (P<0.05). In addition, there were 72 cases in the untreated group (P<0.05). Severe varicose veins proportions in treated and untreated group were 91.1% and 85.1%, respectively (P>0.05). There was no statistically significant difference in liver cirrhosis-related medication and ß-blocker therapy between the treated and untreated group (P>0.05). There was no statistically significant difference in the bleeding rate between the different treated groups (P>0.05). The bleeding rates at 3, 6 months, 1, and 2 years in endoscopic treated and untreated group were 2.00% vs. 2.59% (P>0.05), 2.30% vs. 5.88% (P>0.05), 3.10% vs. 7.55% (P>0.05) and 4.00% vs. 21.62% (P<0.05), respectively. All patients with Child-Pugh grade A, B and C in the treated and the untreated group were followed-up for 2 years, and the bleeding rates were 1.8% vs. 8.1% (P<0.05), 1.1% vs. 9.4% (P<0.05) and 9.1% vs. 10.1% (P>0.05), respectively. There were statistically significant differences in the rupture and bleeding of esophageal and gastric varices, varices degree, Child-Pugh grade and presence or absence of thrombosis formation in portal vein (P<0.05); however, no statistically significant differences in gender, age, etiology, platelet count, prothrombin activity, collateral circulation and portal vein width (P>0.05). There was no intraoperative bleeding and postoperative related serious complications in the treated group. Conclusion: The risk of initial episodes of bleeding from esophageal and gastric varices is significantly correlated with the varices degree, Child-Pugh grade, and portal vein thrombosis. Primary preventive treatment under endoscope is safe and effective for reducing the long-term variceal bleeding risk from esophageal and gastric varices.


Asunto(s)
Várices Esofágicas y Gástricas , Hipertensión Portal , Adhesivos Tisulares , Várices , Trombosis de la Vena , Endoscopios , Várices Esofágicas y Gástricas/complicaciones , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Hemorragia Gastrointestinal/cirugía , Humanos , Hipertensión Portal/complicaciones , Ligadura , Cirrosis Hepática/complicaciones , Protrombina , Escleroterapia , Trombosis de la Vena/complicaciones
6.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(2): 340-345, 2022 Apr 18.
Artículo en Chino | MEDLINE | ID: mdl-35435202

RESUMEN

OBJECTIVE: To investigate the efficacy of vertical control by using conventional mini-implant anchorage in maxillary posterior buccal area for Angle class Ⅱ extraction patients. METHODS: Twenty-eight Angle class Ⅱ patients [9 males, 19 females, and age (22.6±2.8) years] were selected in this study. All of these patients were treated by using straight wire appliance with 4 premolars extraction and 2 mini-implant anchorage in maxillary posterior buccal area. In this study, the self-control method was used to measure and analyze the lateral radiographs taken before and after orthodontic treatment in each case, the main cephalometric analysis items were related to vertical changes. The digitized lateral radiographs were imported into Dolphin Imaging Software (version 11.5: Dolphin Imaging and Management Solutions, Chatsworth, California, USA), and marked points were traced. Each marked point was confirmed by two orthodontists. The same orthodontist performed measurement on the lateral radiographs over a period of time. All measurement items were required to be measured 3 times, and the average value was taken as the final measurement result. RESULTS: Analysis of the cephalometric radiographs showed that, for vertical measurements after treatment, the differences of the following measurements were highly statistically significant (P < 0.001): SN-MP decreased by (1.40±1.45) degrees on average, FMA decreased by (1.58±1.32) degrees on average, the back-to-front height ratio (S-Go/N-Me) decreased by 1.42%±1.43% on average, Y-axis angle decreased by (1.03±0.99) degrees on average, face angle increases by (1.37±1.05) degree on average; The following measurements were statistically significant (P < 0.05): the average depression of the upper molars was (0.68±1.40) mm, and the average depression of the upper anterior teeth was (1.07±1.55) mm. The outcomes indicated that there was a certain degree of upper molar depression after the treatment, which produced a certain degree of counterclockwise rotation of the mandibular plane, resulting in a positive effect on the improvement of the profile. CONCLUSION: The conventional micro-implant anchorage in maxillary posterior buccal area has a certain vertical control ability, and can give rise to a certain counterclockwise rotation of the mandible, which would improve the profile of Angle Class Ⅱ patients.


Asunto(s)
Maloclusión Clase II de Angle , Métodos de Anclaje en Ortodoncia , Diente Premolar , Cefalometría/métodos , Femenino , Humanos , Masculino , Maloclusión Clase II de Angle/diagnóstico por imagen , Maloclusión Clase II de Angle/terapia , Mandíbula , Maxilar/diagnóstico por imagen , Técnicas de Movimiento Dental , Dimensión Vertical
9.
Neurocrit Care ; 37(Suppl 2): 259-266, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35314969

RESUMEN

Heterogeneity is recognized as a major barrier in efforts to improve the care and outcomes of patients with traumatic brain injury (TBI). Even within the narrower stratum of moderate and severe TBI, current management approaches do not capture the complexity of this condition characterized by manifold clinical, anatomical, and pathophysiologic features. One approach to heterogeneity may be to resolve undifferentiated TBI populations into endotypes, subclasses that are distinguished by shared biological characteristics. The endotype paradigm has been explored in a range of medical domains, including psychiatry, oncology, immunology, and pulmonology. In intensive care, endotypes are being investigated for syndromes such as sepsis and acute respiratory distress syndrome. This review provides an overview of the endotype paradigm as well as some of its methods and use cases. A conceptual framework is proposed for endotype research in moderate and severe TBI, together with a scientific road map for endotype discovery and validation in this population.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Síndrome de Dificultad Respiratoria , Sepsis , Lesiones Traumáticas del Encéfalo/terapia , Humanos
10.
PLoS Pathog ; 18(2): e1010364, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35202447

RESUMEN

Leishmaniasis is an infectious disease caused by protozoan parasites belonging to the genus Leishmania for which there are no approved human vaccines. Infections localise to different tissues in a species-specific manner with the visceral form of the disease caused by Leishmania donovani and L. infantum being the most deadly in humans. Although Leishmania spp. parasites are predominantly intracellular, the visceral disease can be prevented in dogs by vaccinating with a complex mixture of secreted products from cultures of L. infantum promastigotes. With the logic that extracellular parasite proteins make good subunit vaccine candidates because they are directly accessible to vaccine-elicited host antibodies, here we attempt to discover proteins that are essential for in vitro growth and host infection with the goal of identifying subunit vaccine candidates. Using an in silico analysis of the Leishmania donovani genome, we identified 92 genes encoding proteins that are predicted to be secreted or externally anchored to the parasite membrane by a single transmembrane region or a GPI anchor. By selecting a transgenic L. donovani parasite that expresses both luciferase and the Cas9 nuclease, we systematically attempted to target all 92 genes by CRISPR genome editing and identified four that were required for in vitro growth. For fifty-five genes, we infected cohorts of mice with each mutant parasite and by longitudinally quantifying parasitaemia with bioluminescent imaging, showed that nine genes had evidence of an attenuated infection although all ultimately established an infection. Finally, we expressed two genes as full-length soluble recombinant proteins and tested them as subunit vaccine candidates in a murine preclinical infection model. Both proteins elicited significant levels of protection against the uncontrolled development of a splenic infection warranting further investigation as subunit vaccine candidates against this deadly infectious tropical disease.


Asunto(s)
Leishmania donovani , Leishmania infantum , Leishmaniasis Visceral , Leishmaniasis , Parásitos , Animales , Perros , Leishmania donovani/genética , Ratones
11.
ESMO Open ; 7(1): 100395, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35149428

RESUMEN

Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. Its alterations, including mutation, amplification and overexpression, could result in oncogenic potential and have been detected in many cancers such as non-small-cell lung cancer (NSCLC). Such alterations are, in general, considered markers of poor prognosis. Anti-HER2 antibody-drug conjugates, e.g. trastuzumab deruxtecan (T-DXd, DS-8201) and disitamab vedotin (RC48), were recently approved for HER2-positive breast and gastric cancers. Meanwhile, several HER2-targeted drugs, such as T-DXd, neratinib, afatinib, poziotinib and pyrotinib, have been evaluated in patients with advanced NSCLC, with several of them demonstrating clinical benefit. Therefore, identifying HER2 alterations is pivotal for NSCLC patients to benefit from these targeted therapies. Recent guidelines on HER2 testing were developed for breast and gastric cancer, however, and have not been fully established for NSCLC. The expert group here reached a consensus on HER2 alteration testing in NSCLC with the focus on clinicopathologic characteristics, therapies, detection methods and diagnostic criteria for HER2-altered NSCLC patients. We hope this consensus could improve the clinical management of NSCLC patients with HER2 alterations.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Consenso , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapéutico
13.
Pediatr Cardiol ; 43(3): 497-507, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34812909

RESUMEN

Single ventricle patients typically undergo some form of advanced diagnostic imaging prior to superior cavopulmonary connection (SCPC). We sought to evaluate variability of diagnostic practice and associated comprehensive risk. A retrospective evaluation across 4 institutions was performed (1/1/2010-9/30/2016) comparing the primary modalities of cardiac catheterization (CC), cardiac magnetic resonance (CMR), and cardiac computed tomography (CT). Associated risks included anesthesia/sedation, vascular access, total room time, contrast agent usage, radiation exposure, and adverse events (AEs). Of 617 patients undergoing SCPC, 409 (66%) underwent at least one advanced diagnostic imaging study in the 60 days prior to surgery. Seventy-eight of these patients (13%) were analyzed separately because of a concomitant cardiac intervention during CC. Of 331 (54%) with advanced imaging and without catheterization intervention, diagnostic CC was most common (59%), followed by CT (27%) and CMR (14%). Primary modality varied significantly by institution (p < 0.001). Median time between imaging and SCPC was 13 days (IQR 3-33). Anesthesia/sedation varied significantly (p < 0.001). Pre-procedural vascular access did not vary significantly across modalities (p = 0.111); procedural access varied between CMR/CT and CC, in which central access was used in all procedures. Effective radiation dose was significantly higher for CC than CT (p < 0.001). AE rate varied significantly, with 12% CC, 6% CMR, and 1% CT (p = 0.004). There is significant practice variability in the use of advanced diagnostic imaging prior to SCPC, with important differences in associated procedural risk. Future studies to identify differences in diagnostic accuracy and long-term outcomes are warranted to optimize diagnostic protocols.


Asunto(s)
Procedimiento de Fontan , Cardiopatías Congénitas , Corazón Univentricular , Diagnóstico por Imagen , Procedimiento de Fontan/efectos adversos , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , Humanos , Lactante , Estudios Retrospectivos
14.
Anaesth Crit Care Pain Med ; 41(1): 101015, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34968747

RESUMEN

BACKGROUND: There is an unmet need for timely and reliable prediction of post-cardiac arrest (CA) clinical trajectories. We hypothesized that physiological time series (PTS) data recorded on the first day of intensive care would contribute significantly to discrimination of outcomes at discharge. PATIENTS AND METHODS: Adult patients in the multicenter eICU database who were mechanically ventilated after resuscitation from out-of-hospital CA were included. Outcomes of interest were survival, neurological status based on Glasgow motor subscore (mGCS) and surrogate functional status based on discharge location (DL), at hospital discharge. Three machine learning predictive models were trained, one with features from the electronic health records (EHR), the second using features derived from PTS collected in the first 24 h after ICU admission (PTS24), and the third combining PTS24 and EHR. Model performances were compared, and the best performing model was externally validated in the MIMIC-III dataset. RESULTS: Data from 2216 admissions were included in the analysis. Discrimination of prediction models combining EHR and PTS24 features was higher than models using either EHR or PTS24 for prediction of survival (AUROC 0.83, 0.82 and 0.79 respectively), neurological outcome (0.87, 0.86 and 0.79 respectively), and DL (0.80, 0.78 and 0.76 respectively). External validation in MIMIC-III (n = 86) produced similar model performance. Feature analysis suggested prognostic significance of previously unknown EHR and PTS24 variables. CONCLUSION: These results indicate that physiological data recorded in the early phase after CA resuscitation contain signatures that are linked to post-CA outcome. Additionally, they attest to the effectiveness of ML for post-CA predictive modeling.


Asunto(s)
Aprendizaje Automático , Paro Cardíaco Extrahospitalario , Adulto , Hospitalización , Humanos , Pronóstico , Factores de Tiempo
15.
ESMO Open ; 7(1): 100334, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34959168

RESUMEN

BACKGROUND: Our prospective, open-label, single-arm phase II study investigated the safety and efficacy of DCVAC/LuCa (dendritic cell vaccines for lung cancer) combined with standard carboplatin/pemetrexed in advanced non-squamous (nsq) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients had stage IV nsq NSCLC without oncogenic drivers and had not received prior systemic cancer therapy. Treatment consisted of carboplatin/pemetrexed for up to 6 cycles followed by 21 cycles of pemetrexed maintenance or until progression or intolerance. Non-progression patients after two cycles of chemotherapy started to receive DCVAC/LuCa subcutaneously (s.c.) on day 15 of cycle 3, and thereafter q3w (day 15 of chemotherapy cycles) for up to 15 doses. Dosing of DCVAC/LuCa s.c. varied among patients depending on the baseline number of leucocytes but remained constant for each single patient. Safety was assessed by adverse events (AEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). Efficacy was measured by overall survival (OS), progression-free survival (PFS), time to progression (TTP), and objective response rate (ORR). RESULTS: Sixty-one patients were enrolled. In the safety population (n = 60), eight patients (13.33%) had grade 3 or greater TRAEs, and six patients (10.0%) showed SAEs which were not related to leukapheresis or DC vaccination. Six grade 1 AEs were considered to be related to leukapheresis. No AESIs or DCVAC/LuCa-induced AEs were observed. The 2-year survival rate in the modified intention-to-treat population (n = 44) was 52.57%. Median OS was not reached. Median PFS was 8.0 months, median TTP was 10.2 months, and the ORR was 31.82%. CONCLUSION: In treatment-naïve stage IV nsq NSCLC patients without oncogenic drivers, the combination of carboplatin/pemetrexed and DCVAC/LuCa was well tolerated and showed promising efficacy. Therefore, a study to prove our immunotherapeutic concept in a randomized phase III trial is planned.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Acetilcisteína/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/farmacología , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Células Dendríticas , Humanos , Inmunoterapia/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Pemetrexed/farmacología , Pemetrexed/uso terapéutico , Estudios Prospectivos
16.
CRISPR J ; 5(1): 40-52, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34935462

RESUMEN

Nearly 90% of human pathogenic mutations are caused by small genetic variations, and methods to correct these errors efficiently are critically important. One way to make small DNA changes is providing a single-stranded oligo deoxynucleotide (ssODN) containing an alteration coupled with a targeted double-strand break (DSB) at the target locus in the genome. Coupling an ssODN donor with a CRISPR-Cas9-mediated DSB is one of the most streamlined approaches to introduce small changes. However, in many systems, this approach is inefficient and introduces imprecise repair at the genetic junctions. We herein report a technology that uses spatiotemporal localization of an ssODN with CRISPR-Cas9 to improve gene alteration. We show that by fusing an ssODN template to the trans-activating RNA (tracrRNA), we recover precise genetic alterations, with increased integration and precision in vitro and in vivo. Finally, we show that this technology can be used to enhance gene conversion with other gene editing tools such as transcription activator like effector nucleases.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Sistemas CRISPR-Cas/genética , ADN , Roturas del ADN de Doble Cadena , Humanos , ARN/genética
17.
Sci Rep ; 11(1): 23654, 2021 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-34880296

RESUMEN

Our goal is to explore quantitative motor features in critically ill patients with severe brain injury (SBI). We hypothesized that computational decoding of these features would yield information on underlying neurological states and outcomes. Using wearable microsensors placed on all extremities, we recorded a median 24.1 (IQR: 22.8-25.1) hours of high-frequency accelerometry data per patient from a prospective cohort (n = 69) admitted to the ICU with SBI. Models were trained using time-, frequency-, and wavelet-domain features and levels of responsiveness and outcome as labels. The two primary tasks were detection of levels of responsiveness, assessed by motor sub-score of the Glasgow Coma Scale (GCSm), and prediction of functional outcome at discharge, measured with the Glasgow Outcome Scale-Extended (GOSE). Detection models achieved significant (AUC: 0.70 [95% CI: 0.53-0.85]) and consistent (observation windows: 12 min-9 h) discrimination of SBI patients capable of purposeful movement (GCSm > 4). Prediction models accurately discriminated patients of upper moderate disability or better (GOSE > 5) with 2-6 h of observation (AUC: 0.82 [95% CI: 0.75-0.90]). Results suggest that time series analysis of motor activity yields clinically relevant insights on underlying functional states and short-term outcomes in patients with SBI.


Asunto(s)
Lesiones Encefálicas/clasificación , Enfermedad Crítica , Acelerometría , Anciano , Lesiones Encefálicas/patología , Femenino , Escala de Consecuencias de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Índice de Severidad de la Enfermedad
18.
Eur Rev Med Pharmacol Sci ; 25(22): 6826, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34859841

RESUMEN

The article "MiR-155-5p affects Wilms' tumor cell proliferation and apoptosis via targeting CREB1", by X.-S. Zhao, B. Han, J.-X. Zhao, N. Tao, C.-Y. Dong, published in Eur Rev Med Pharmacol Sci 2019; 23 (3): 1030-1037-DOI: 10.26355/eurrev_201902_16990-PMID: 30779069, has been retracted by the authors due to a slight deviation in the data. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16990.

19.
Zhonghua Yi Xue Za Zhi ; 101(45): 3718-3723, 2021 Dec 07.
Artículo en Chino | MEDLINE | ID: mdl-34856699

RESUMEN

Objective: To verify the safety and feasibility of sacral alar screw fixation and fusion surgery in lumbosacral area. Methods: The clinical and radiological data of patients receiving L5/S1 single-level cortical bone trajectory screw combined with sacral alar screw decompression fixation and fusion in Beijing Chaoyang Hospital due to lumbar spinal stenosis from January 2019 to January 2020 were retrospectively analyzed. The clinical data included operation duration, intraoperative blood loss, postoperative drainage, pain and function scores during follow-up. The radiological data included preoperative and postoperative follow-up X-rays and three-dimensional reconstruction of lumbar spine CT. The fusion status and complication of internal fixation, such as screw loosening and fixation failure were evaluated by the radiological examination. Results: According to the inclusion and exclusion criteria, a total of 16 patients (7 males and 9 females) were included, with an average age of (69.6±5.2) years. The patients were followed-up for (16.2±1.7) months. The average operation duration was (144±21) min, the intraoperative blood loss was (103±20) ml, and the postoperative drainage was (80±34) ml. The patient's low back pain visual analogue scale (VAS) score was 6.8±1.0 before surgery, and it was improved to 0.9±0.7 at the last follow-up; leg pain VAS score was 6.1±0.9 before the operation and it improved to 0.9±0.7 at the last follow-up; Oswestry disability index (ODI) function score was 66.2%±8.0% before the surgery and it decreased to 26.6%±7.2% at the last follow-up. No neurological complications, surgical site infection, screw loosening, internal fixation failure or cage displacement were observed during the follow-up. The fusion rate was 68.8% (11/16) at 6 months post operation. Conclusion: It is safe, feasible and effective to apply cortical screws combined with sacral alar screws in short-segment decompression, fixation and fusion surgery on the lumbosacral region to treat lumbosacral spinal stenosis.


Asunto(s)
Fusión Vertebral , Anciano , Tornillos Óseos , Femenino , Humanos , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sacro/cirugía , Resultado del Tratamiento
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(5): 948-954, 2021 May 10.
Artículo en Chino | MEDLINE | ID: mdl-34814494

RESUMEN

Combined vaccines contain two or more antigens. Research suggested that combined vaccines could prevent multi diseases and reduce the frequency of vaccination. This article focus on combined vaccines for children used both at home and abroad, such as diphtheria-pertussis-tetanus vaccine (DTaP), measles-rubella-mumps vaccine (MMR), etc. and summarizes their immunogenicity, safety and social values, including benefits to families, vaccination workers and health services, to provide evidence for promoting the research, development and use of combined vaccines in China. We found that combined vaccines can not only ensure the immunogenicity and safety, but also give convenient and lower cost vaccination to families, and using combined vaccines can improve the work efficiency of vaccination workers, reduce the impact of the epidemic on immunization services and improve vaccination coverage and timeliness. At present, the promotion of combined vaccines in China is restricted by many technical bottlenecks, high prices, and low awareness among people. It is recommended that research on the safety, effectiveness and health economics of combined vaccines should be strengthened, and the value of combined vaccines should be scientifically evaluated; the public's awareness and trust in combined vaccines should be enhanced, as well as the development and application of multi-linked multivalent vaccines should be promoted. The government should improve regulations to assist the development and application of combined vaccines.


Asunto(s)
Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Valores Sociales , Niño , Humanos , Lactante , Vacuna contra el Sarampión-Parotiditis-Rubéola , Vacuna Antipolio de Virus Inactivados , Vacunación , Vacunas Combinadas
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...