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PURPOSE: Interferon-stimulated gene 15 (ISG15) deficiency, a rare human inborn error of immunity characterized by susceptibility to Bacillus Calmette-Guerin (BCG) diseases, neuropathic and dermatological manifestations. METHODS: The clinical and immunological features of two siblings with ISG15 deficiency combined with asymptomatic myeloperoxidase (MPO) mutations were analyzed, and their pathogenesis, as well as target therapeutic candidates, were explored. RESULTS: The manifestation in patient 2 was skin lesions, while those in patient 1 were intracranial calcification and recurrent pneumonia. Whole-exome identified novel, dual mutations in ISG15 and MPO. PBMCs and B cell lines derived from the patients showed hyper-activated JAK/STAT signaling. Normal neutrophil function excluded pathogenicity caused by the MPO mutation. RNA sequencing identified baricitinib as therapeutic candidate. CONCLUSIONS: We report two sibling patients harboring the same novel ISG15 mutation showing diverse clinical features, and one harbored a rare phenotype of pneumonia. These findings expand the clinical spectrum of ISG15 deficiency and identify baricitinib as therapeutic candidate.
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Interferones , Neumonía , Humanos , Citocinas/genética , Citocinas/metabolismo , Interferones/genética , Mutación , Hermanos , Ubiquitinas/genética , Ubiquitinas/metabolismoRESUMEN
BACH2-related immunodeficiency and autoimmunity (BRIDA) is an inborn error of immunity, newly reported in 2017, presenting with symptoms of immunoglobulin deficiency and ongoing colitis. Studies using a mouse model have demonstrated that BACH2 deficiency predisposes individuals to systemic lupus erythematosus (SLE); however, no BACH2 deficiency has been reported in SLE patients. Here we describe a patient with BRIDA presenting with early-onset SLE, juvenile dermatomyositis, and IgA deficiency. Whole exome sequencing analysis of the patient and her parents revealed a novel heterozygous point mutation in BACH2, c.G1727T, resulting in substitution of a highly conserved arginine with leucine (R576L), which is predicted to be deleterious, in the patient and her father. Reduced BACH2 expression and deficient transcriptional repression of the BACH2 target, BLIMP1, were detected in PBMCs or lymphoblastoid cell lines of our patient. Notably, extreme reduction of memory B cells was detected in the patient's father, although he had no obvious symptoms. SLE symptoms and recurrent fever were relieved by treatment with prednisone combined with tofacitinib. Thus, we present the second report of BRIDA and demonstrate that BACH2 may be a monogenic cause of SLE.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Síndromes de Inmunodeficiencia , Lupus Eritematoso Sistémico , Femenino , Humanos , Masculino , Autoinmunidad , Mutación de Línea Germinal , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genéticaRESUMEN
Primordial germ cell (PGC) migration in zebrafish is directed by the chemokine SDF-1a that activates its receptor CXCR4b. Little is known about the molecular mechanisms controlling the distribution of this chemoattractant in vivo. We demonstrate that the activity of a second SDF-1/CXCL12 receptor, CXCR7, is crucial for proper migration of PGCs toward their targets. We show that CXCR7 functions primarily in the somatic environment rather than within the migrating cells. In CXCR7 knocked-down embryos, the PGCs exhibit a phenotype that signifies defects in SDF-1a gradient formation as the cells fail to polarize effectively and to migrate toward their targets. Indeed, somatic cells expressing CXCR7 show enhanced internalization of the chemokine suggesting that CXCR7 acts as a sink for SDF-1a, thus allowing the dynamic changes in the transcription of sdf-1a to be mirrored by similar dynamics at the protein level.
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Movimiento Celular , Quimiocina CXCL12/metabolismo , Células Germinativas/citología , Receptores CXCR/metabolismo , Proteínas de Pez Cebra/metabolismo , Pez Cebra/embriología , Animales , Animales Modificados Genéticamente , Polaridad Celular , Embrión no Mamífero/citología , Regulación del Desarrollo de la Expresión Génica , Receptores CXCR/genética , Proteínas de Pez Cebra/genéticaRESUMEN
BACKGROUND: The implementation of the NVBP policy has generated considerable reductions in drug procurement prices and an increase in the market share of the NVBP drugs.This study aimed to investigate patients' attitudes towards switching to drugs of national volume-based procurement (NVBP) and identify their underlying influencing factors in Wuhan, China. METHODS: A total of 21 eligible patients from the Wuhan Union Hospital who were switched to NVBP drugs between January 2022 and May 2022 were included in our study. Semi-structured face-to-face interviews were conducted to collect interview information and the interview data was analyzed by the Colaizzi seven-step method. RESULTS: Twenty-one semi-structured face-to-face interviews were conducted. The duration of each interview was 25-35 min and three themes related to patients' attitudes and their influencing factors were extracted, including (1) Patients' perception of the NVBP drugs; (2) Family and social influence to patients; (3) Medication habits of patients. This study found: 1) 71.4% patients (15/21) showed a positive attitude towards switching to NVBP medicines; 2)80.9% patients (17/21) have felt a significant reduction in their medication cost after the implementation of the NVBP policy; 3)Advices from healthcare professionals and health insurance reimbursement policies showed great impacts on patients' attitude towards switching to NVBP drugs; 4)Attitudes towards switching to NVBP drugs varied considerably among patients with different severities of disease. CONCLUSION: The implementation of the NVBP policy has significantly reduced the cost of healthcare for patients and has been supported by71.4% (15 of 21) patients. However, some issues have been identified in the implementation of the policy in this study. Health professionals in general need to contribute more efforts to improve patients' preconceptions about the NVBP drugs and boost their confidence in the NVBP drugs.
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Actitud , Pacientes , Humanos , Reembolso de Seguro de Salud , Costos de los Medicamentos , China , Investigación CualitativaRESUMEN
PURPOSE: China is currently one of the countries with the largest increased number of new cancer cases in the world, but cancer pain management (CPM) is still inadequate. This study uses a questionnaire to demonstrate the status and differences in knowledge, attitude and practice (KAP) of CPM among healthcare workers (HCWs) in developed regions of China, to find deficiencies and priorities for improvement, from which areas and advantages of the role of pharmacists and mobile devices can be explored. METHODS: This study used data from a questionnaire on CPM from March to June 2019. The study population consisted of a total of 515 HCWs in four first-tier developed cities in China. The questionnaire has four major components, analysis of differences in KAP of different occupations through one-way analysis of variance (ANOVA). RESULTS: Among the respondents, the physicians had the highest knowledge scores toward CPM, pharmacists had the lowest practice scores. Around half of the respondents indicated that their hospital or department have a pharmacist participating in CPM. Physicians and nurses were more likely to expect pharmacists to provide drug counseling. The HCWs interviewed most expect that the mobile-based pain management system can automatically screen and mark patients with pain. CONCLUSION: From this study, it can be suggested that pharmacists and nurses in the CPM team should actively promote relevant knowledge. Besides, pharmacists should focus on improving practical ability such as increasing the frequency of pain assessment. Multidisciplinary collaboration and the introduction of mobile devices can improve and refine the CPM.
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Neoplasias , Médicos , Actitud del Personal de Salud , Ciudades , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , Manejo del Dolor/psicología , Farmacéuticos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To produce high concentrations of hyperoside from quercetin using recombinant Escherichia coli with in situ regeneration of UDP-galactose. RESULTS: Sucrose synthase from Glycine max (GmSUS) was co-expressed with UDP-glucose epimerase from E. coli (GalE) in E. coli for regenerating UDP-galactose from UDP and sucrose. Glycosyltransferase from Petunia hybrida (PhUGT) was introduced to synthesize hyperoside from quercetin through the regeneration system of UDP-galactose. Co-expressing with molecular chaperones GroEL/ES successfully enhanced the catalytic efficiency of the recombinant strain, which assisted the soluble expression of PhUGT. By using a fed-batch approach, the production of hyperoside reached 863.7 mg L-1 with a corresponding molar conversion of 93.6% and a specific productivity of 72.5 mg L-1 h-1. CONCLUSION: The method described herein for hyperoside production can be widely applied for the synthesis of isorhamnetin-3-O-galactoside, kaempferol-3-O-galactoside and other flavonoids.
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Escherichia coli , Quercetina , Escherichia coli/genética , Escherichia coli/metabolismo , Galactosa/metabolismo , Quercetina/análogos & derivados , Quercetina/metabolismo , Uridina Difosfato/metabolismoRESUMEN
PURPOSE: Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that mediates cellular responses to interferons (IFNs) and other cytokines and growth factors in diverse cell types. STAT1 gain-of-function (GOF) mutations result in an unexpectedly wide range of clinical features. It remains unclear why STAT1 GOF mutations result in such a broad spectrum of phenotypes. METHODS: We analyzed the clinical, molecular, and phenotypic characteristics of nine Chinese patients with STAT1 GOF mutations. RESULTS: This study enrolled nine patients with STAT1 GOF mutations including five novel mutations. We discuss the molecular and phenotypic characterization such as unique Penicillium marneffei lymphadenitis. Patients with STAT1 GOF mutations had defects in both innate and adaptive immunity, including impaired T cell receptor (TCR) diversity; reduced numbers of naïve and effector memory CD4+ T cells, memory B cells, and NK cells; and defects in the production of IL-17A and IFN-γ. In addition, experiments with primary immune cells revealed that enhanced STAT1 phosphorylation resulted from not only lower rates of STAT1 dephosphorylation but also increased total STAT1 expression. CONCLUSIONS: Our report provides the first comprehensive overview of the molecular genetics, clinical heterogeneity, and underlying immunological abnormalities of patients with STAT1 GOF mutations in China. In further study, to find the relationship between different STAT1 GOF mutations and clinical phenotype as well as the mechanism of increased total STAT1 expression will be needed.
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Mutación con Ganancia de Función/genética , Factor de Transcripción STAT1/genética , Linfocitos T CD4-Positivos/inmunología , Células Cultivadas , China , Femenino , Mutación con Ganancia de Función/inmunología , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/inmunología , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-17/genética , Interleucina-17/inmunología , Células Asesinas Naturales/inmunología , Linfadenitis/genética , Linfadenitis/inmunología , Masculino , Penicillium/inmunología , Fenotipo , Fosforilación/genética , Fosforilación/inmunología , Factor de Transcripción STAT1/inmunologíaRESUMEN
Eph receptor and ephrin signaling has a major role in segregating distinct cell populations to form sharp borders. Expression of interacting Ephs and ephrins typically occurs in complementary regions, such that polarised activation of both components occurs at the interface. Forward signaling through Eph receptors can drive cell segregation, but it is unclear whether reverse signaling through ephrins can also contribute. We have tested the role of reverse signaling, and of polarised versus non-polarised activation, in assays in which contact repulsion drives cell segregation and border sharpening. We find that polarised forward signaling drives stronger segregation than polarised reverse signaling. Nevertheless, reverse signaling contributes since bidirectional Eph and ephrin activation drives stronger segregation than unidirectional forward signaling alone. In contrast, non-polarised Eph activation drives little segregation. We propose that although polarised forward signaling is the principal driver of segregation, reverse signaling enables bidirectional repulsion which prevents mingling of each population into the other.
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Efrinas/fisiología , Receptores de la Familia Eph/fisiología , Transducción de Señal , Movimiento Celular , Polaridad Celular , Efrinas/genética , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Transducción de Señal/genéticaRESUMEN
Neuronal differentiation is regulated by proneural genes that promote neurogenesis and inhibitory mechanisms that maintain progenitors. This raises the question of how the up-regulation of proneural genes required to initiate neurogenesis occurs in the presence of such inhibition. We carried out loss and gain of gene function, an interaction screen for binding partners, and biochemical analyses to uncover the regulation, developmental role, and mechanism of action of a ubiquitination adaptor protein, Btbd6a (BTB domain containing 6a). We find that the proneural gene neurog1 up-regulates btbd6a, which in turn is required for up-regulation of neurog1. Btbd6a is an adaptor for the Cul3 ubiquitin ligase complex, and we find that it binds to the transcriptional repressor Plzf (promyelocytic leukemia zinc finger). Btbd6a promotes the relocation of Plzf from nucleus to cytoplasm and targets Plzf for ubiquitination and degradation. plzfa is expressed widely in the neural epithelium; when overexpressed, it inhibits neurogenesis, and this inhibition is reversed by btbd6a. The antagonism of endogenous plzfa by btbd6a is required for neurogenesis, since the block in neuronal differentiation caused by btbd6a knockdown is alleviated by plzfa knockdown. These findings reveal a feedback loop mediated by degradation of an inhibitor that is essential for progenitors to undergo the transition to neuronal differentiation.
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Proteínas Portadoras/metabolismo , Diferenciación Celular , Retroalimentación Fisiológica/fisiología , Neurogénesis/fisiología , Neuronas/citología , Proteínas de Pez Cebra/metabolismo , Animales , Proteínas Portadoras/genética , Línea Celular , Embrión de Pollo , Pollos , Secuencia Conservada , Regulación del Desarrollo de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Factores de Transcripción de Tipo Kruppel/antagonistas & inhibidores , Factores de Transcripción de Tipo Kruppel/metabolismo , Proteínas del Tejido Nervioso/genética , Neuronas/fisiología , Transporte de Proteínas , Ubiquitinación , Pez Cebra/embriología , Proteínas de Pez Cebra/genéticaRESUMEN
The formation of sharp borders, across which cell intermingling is restricted, has a crucial role in the establishment and maintenance of organized tissues. Signaling of Eph receptors and ephrins underlies formation of a number of boundaries between and within tissues during vertebrate development. Eph-ephrin signaling can regulate several types of cell response-adhesion, repulsion and tension-that can in principle underlie the segregation of cells and formation of sharp borders. Recent studies have implicated each of these cell responses as having important roles at different boundaries: repulsion at the mesoderm-ectoderm border, decreased adhesion at the notochord-presomitic mesoderm border, and tension at boundaries within the hindbrain and forebrain. These distinct responses to Eph receptor and ephrin activation may in part be due to the adhesive properties of the tissue.
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Adhesión Celular/fisiología , Efrinas/metabolismo , Organogénesis/fisiología , Receptor EphA1/metabolismo , Transducción de Señal/fisiología , Vertebrados/embriología , Animales , Transducción de Señal/genéticaRESUMEN
We have generated an inducible system to control the timing of transgene expression in zebrafish and chick. An estrogen receptor variant (ERT2) fused to the GAL4 transcriptional activator rapidly and robustly activates transcription within 3 hours of treatment with the drug 4-hydroxy-tamoxifen (4-OHT) in tissue culture and transgenic zebrafish. We have generated a broadly expressed inducible ERT2-GAL4 zebrafish line using the ubiquitin (ubi) enhancer. In addition, use of ERT2-GAL4 in conjunction with tissue-specific enhancers enables the control of transgene expression in both space and time. This spatial restriction and the ability to sustain forced expression are important advantages over the currently used heat-shock promoters. Moreover, in contrast to currently available TET and LexA systems, which require separate constructs with their own unique recognition sequences, ERT2-GAL4 is compatible with the growing stock of UAS lines being generated in the community. We also applied the same inducible system to the chick embryo and find that it is fully functional, suggesting that this strategy is generally applicable.
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Biología Evolutiva/métodos , Regulación del Desarrollo de la Expresión Génica , Receptores de Estrógenos/genética , Transgenes , Animales , Animales Modificados Genéticamente , Embrión de Pollo , Cruzamientos Genéticos , Células HEK293 , Humanos , Inmunohistoquímica , Hibridación in Situ , Fenotipo , Receptores de Estrógenos/metabolismo , Tamoxifeno/análogos & derivados , Tamoxifeno/farmacología , Pez Cebra , Proteínas de Pez Cebra/metabolismoRESUMEN
The posterior lateral line primordium in zebrafish provides an amenable model to study mechanisms of collective cell migration. The directed migration of the cell cluster along the path of Sdf1a chemokine requires two receptors, Cxcr4b and Cxcr7b, which are expressed in the leading and trailing part of the primordium, respectively. The polarized expression of receptors is regulated by Wnt signaling, but downstream players mediating this control remain to be found. Here, we show that the Hox homeobox gene Hoxb8a is a critical component that acts downstream of the Wnt pathway to coordinate the expression of both chemokine receptors. We find that Hoxb8a is expressed in the leading part of the primordium and is required for the correct speed and extent of migration. Hoxb8a expression is dependent upon Wnt activity and needed both for cxcr4b expression and to repress and thus restrict cxcr7b expression to the trailing zone of the primordium. In the absence of Wnt activity, overexpressed Hoxb8a is able to repress cxcr7b but not up-regulate cxcr4b expression. Together with results from expressing dominant activator and repressor constructs, these findings suggest that Hoxb8a is induced by and cooperates with Wnt signaling to up-regulate cxcr4b, and acts through multiple mechanisms to repress cxcr7b expression.
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Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas de Homeodominio/metabolismo , Receptores CXCR4/biosíntesis , Receptores CXCR/biosíntesis , Vía de Señalización Wnt/fisiología , Proteínas de Pez Cebra/biosíntesis , Pez Cebra/embriología , Animales , Proteínas de Homeodominio/genética , Receptores CXCR/genética , Receptores CXCR4/genética , Regulación hacia Arriba/fisiología , Pez Cebra/genética , Proteínas de Pez Cebra/genéticaRESUMEN
The directional migration of many cell populations occurs as a coherent group. An amenable model is provided by the posterior lateral line in zebrafish, which is formed by a cohesive primordium that migrates from head to tail and deposits future neuromasts at intervals. We found that prior to the onset of migration, the compact state of the primordium is not fully established, as isolated cells with lateral line identity are present caudal to the main primordium. These isolated cells are retained in position such that they fuse with the migrating primordium as it advances, and later contribute to the leading zone and terminal neuromasts. We found that the isolated lateral line cells are positioned by two antagonistic cues: Fgf signalling attracts them towards the primordium, which counteracts Sdf1α/Cxcr4b-mediated caudal attraction. These findings reveal a novel chemotactic role for Fgf signalling in which it enables the coalescence of the lateral line primordium from an initial fuzzy pattern into a compact group of migrating cells.
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Quimiocinas/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Sistema de la Línea Lateral/embriología , Sistema de la Línea Lateral/metabolismo , Transducción de Señal , Pez Cebra/embriología , Pez Cebra/metabolismo , Animales , Fusión Celular , Movimiento Celular , Separación Celular , Sistema de la Línea Lateral/citología , Modelos Biológicos , Receptores CXCR/metabolismo , Receptores CXCR4/metabolismo , Proteínas de Pez Cebra/metabolismoRESUMEN
The complex physiology of the gastrointestinal tract is regulated by intricate neural networks embedded within the gut wall. How neural crest cells colonize the intestine to form the enteric nervous system is of great interest to developmental biologists, but also highly relevant for understanding gastrointestinal disorders. A recent paper in BMC Biology addresses this issue with live imaging of gut explants from mouse embryos.
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Movimiento Celular , Sistema Nervioso Entérico/citología , Cresta Neural/citología , AnimalesRESUMEN
BACKGROUND: A range of studies concerning the effects of breathing exercises on chronic low back pain (CLBP) have been proven inconclusive. OBJECTIVE: The study aimed to evaluate the effectiveness of breathing exercises for the treatment of CLBP. METHODS: We considered randomized controlled trials in English or Chinese that used breathing exercises for the treatment of CLBP. An electronic search was performed in the MEDLINE, EMBASE, Web of Science, Cochrane Library, CNKI, Wan Fang, and CBM databases for articles published up to November 2022. Two reviewers independently screened the articles, assessed the risk of bias using the Cochrane risk of bias tool, and extracted the data. The outcomes included pain, lumbar function and pulmonary function post-intervention. RESULTS: A total of thirteen studies (n= 677) satisfied the inclusion criteria. The meta-analysis results demonstrated a significant effect of breathing exercises on the Visual Analog Scale (VAS) score (SMD =-0.84, 95% CI: -1.24 to -0.45, P< 0.0001), the Oswestry Disability Index (ODI) score (SMD =-0.74, 95% CI: -0.95 to -0.54, P< 0.00001), Forced Vital Capacity (FVC) score (MD = 0.24, 95% CI: 0.10 to 0.37, P= 0.0006), Forced Expiratory Volume in 1 second /Forced Vital Capacity (FEV1/FVC) (MD = 1.90, 95% CI: 0.73 to 3.07, P= 0.001), although there was no significant difference between the breathing exercises and control interventions for Forced Expiratory Volume in the first second (FEV1) score (MD = 0.22, 95% CI = [0.00, 0.43], P= 0.05), and Maximal Voluntary Ventilation (MVV) score (MD = 8.22, 95% CI = [-4.02, 20.45], P= 0.19). CONCLUSION: Breathing exercises can reduce pain, assist people with lumbar disabilities, and improve pulmonary function, and could be considered as a potential alternative treatment for CLBP.
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Dolor de la Región Lumbar , Humanos , Ejercicios Respiratorios/métodos , Volumen Espiratorio Forzado , Dolor de la Región Lumbar/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Capacidad VitalRESUMEN
CONTEXT: Various non-pharmacological therapies (NPTs) have been found to be helpful for depression in women with breast cancer (BC). However, the relative efficacy of different NPTs in women with BC at different treatment phases is unclear. OBJECTIVES: To conduct a systematic review and network meta-analysis (NMA) to compare the relative efficacy of various NPTs for improving depression in women with BC during the inter-/post-treatment periods. METHODS: We searched eight databases (Embase, PubMed, PsycINFO, The Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, and WanFang Database) to identify relevant randomized controlled trials published in English and Chinese from their inception to January 31, 2024. We assessed the methodological quality of the included studies using the Cochrane Collaboration Risk of Bias Tool. NMA was conducted using a frequentist approach. Surface under the cumulative ranking (SUCRA) probabilities were used to rank the NPTs. RESULTS: A total of 41 articles involving 5408 participants studied 18 NPTs. Based on NMA, in the inter-treatment phase, mindfulness-based cognitive therapy (MBCT), psychological education, virtual reality (VR) and yoga significantly improved depression in women with BC. MBCT, psychological education, and VR were the three most effective NPTs in this period. In the post-treatment phase, mindfulness-based stress reduction significantly improved depression in women with BC, which was the most effective NPTs in this period. Based on the GRADE framework, most results were rated as "high" to "very low" for the confidence of evidence. CONCLUSIONS: Our study confirmed the efficacy of several NPTs for depression in women with BC during inter-/post-treatment phases. These results should inform future clinical decisions and guidelines for depression in women with BC.
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OBJECTIVES: To evaluate the therapeutic regimen, efficacy and safety of intrathecal or intraventricular (ITH/IVT) administration of polymyxin B for hospital-acquired central nervous system (CNS) infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: A retrospective study was performed on patients with CNS infections caused by CRAB treated with ITH/IVT combination therapy. The primary study outcome was the clinical efficacy after treatment. Secondary outcomes were bacterial clearance rate and safety of therapy. RESULTS: In total, 35 patients who received ITH (13[37.1%]) or IVT (22[62.9%]) polymyxin B as combination therapy were included. The median duration of ITH/IVT polymyxin B therapy was 9 days (interquartile ranges, 7-11). The overall clinical cure and bacterial clearance rate was 77.1% and 85.7%, respectively. No adverse effects deemed related with ITH/IVT polymyxin B were recorded. Clinical failure was independently associated with the initial Acute Physiology and Chronic Health Evaluation II (≥ 15) (odds ratio [OR], 1.24; 95% confidence interval [CI]: 1.05-1.42; Pâ¯=â¯0.038) and Glasgow Coma Scale scores (≤ 8) (OR, 0.69; 95% CI: 0.49-0.88; Pâ¯=â¯0.029). Early administration (within 4 days) of ITH/IVT polymyxin B therapy can support significantly higher clinical cure rate (OR, 0.65; 95% CI: 0.49-1.12; P < 0.001), and potentially reduce the length of treatment and the adverse effects. CONCLUSIONS: ITH/IVT administration of polymyxin B is a valid alternative for the treatment of CNS infections caused by CRAB. Early use of ITH/IVT polymyxin B can lead to higher clinical success.
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OBJECTIVES: This retrospective study aimed to identify the effectiveness of ceftazidime/avibactam (CAZ/AVI) and its optimisation programs for severe hospital-acquired pulmonary infections (sHAPi) caused by carbapenem-resistant and difficult-to-treat Pseudomonas aeruginosa (CRPA and DTR-P. aeruginosa). METHODS: We retrospectively analysed observational data on treatment and outcomes of CAZ/AVI for sHAPi caused by CRPA or DTR-P. aeruginosa. The primary study outcomes were to evaluate the clinical and microbiology efficacy of CAZ/AVI. RESULTS: The cohort consisted of 84 in-patients with sHAPi caused by CRPA (n = 39) and DTR-P. aeruginosa (n = 45) who received at least 72 h of CAZ/AVI therapy. The clinical cure rate was 63.1% in total. There was no significant difference in study outcomes between patients treated with CAZ/AVI monotherapy and those managed with combination regimens. CAZ/AVI as first-line therapy possessed prominent clinical benefits regarding infections caused by DTR-P. aeruginosa. The clinical cure rate was positively relevant with loading dose for CAZ/AVI (odds ratio [OR] 0.03; 95% confidence interval [CI] 0.004-0.19; P < 0.001) and with CAZ/AVI administration by prolonged infusion (odds ratio 0.15; 95% confidence interval 0.03-0.77; P = 0.002). APACHE II score>15 (P = 0.013), septic shock at infection onset (P = 0.001), and CAZ/AVI dose adjustment for renal dysfunction (P = 0.003) were negative predictors of clinical cure. CONCLUSION: CAZ/AVI is a valid alternative for sHAPi caused by CPRA and DTR-P. aeruginosa, even when used alone. Optimisations of the treatment with CAZ/AVI in critically ill patients, including loading dose, adequate maintenance dose and prolonged infusion, were positively associated with potential clinical benefits.
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Ceftazidima , Infecciones por Pseudomonas , Humanos , Ceftazidima/uso terapéutico , Pseudomonas aeruginosa , Antibacterianos/uso terapéutico , Carbapenémicos/uso terapéutico , Estudios Retrospectivos , Compuestos de Azabiciclo/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Combinación de Medicamentos , Resultado del Tratamiento , Hospitales , Pruebas de Sensibilidad MicrobianaRESUMEN
INTRODUCTION: Up to 78% of patients who had a stroke develop post-stroke dysphagia (PSD), a significant consequence. Life-threatening aspiration pneumonia, starvation, and water and electrolyte abnormalities can result. Several meta-analyses have shown that repeated transcranial magnetic stimulation (rTMS) improves swallowing in patients who had a stroke; however, the optimum model is unknown. This study will be the first Bayesian network meta-analysis (NMA) to determine the best rTMS modalities for swallowing of patients who had a stroke. METHODS AND ANALYSIS: PubMed, Web of Science, Embase, Google Scholar, Cochrane, the Chinese National Knowledge Infrastructure, the Chongqing VIP Database and WanFang Data will be searched from their creation to 2 September 2023. All randomised controlled trials associated with rTMS for PSD will be included. Only Chinese or English results will be studied. Two researchers will independently review the literature and extract data, then use the Cochrane Collaboration's Risk of Bias 2.0 tool to assess the included studies' methodological quality. The primary outcome is swallowing function improvement, whereas secondary outcomes include side effects (eg, paraesthesia, vertigo, seizures) and quality of life. A pairwise meta-analysis and NMA based on a Bayesian framework will be conducted using Stata and R statistical software. The Grading of Recommendations Assessment, Development, and Evaluation system will assess outcome indicator evidence quality. ETHICS AND DISSEMINATION: As all data in this study will be taken from the literature, ethical approval is not needed. We will publish our work in peer-reviewed publications and present it at academic conferences. PROSPERO REGISTRATION NUMBER: CRD42023456386.
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Teorema de Bayes , Trastornos de Deglución , Metaanálisis en Red , Accidente Cerebrovascular , Revisiones Sistemáticas como Asunto , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Accidente Cerebrovascular/complicaciones , Metaanálisis como Asunto , Rehabilitación de Accidente Cerebrovascular/métodos , Proyectos de Investigación , Resultado del TratamientoRESUMEN
INTRODUCTION: Breast cancer has become the most common cancer worldwide. Various types of mindfulness-based interventions (e.g., mindfulness-based cognitive therapy, mindfulness-based stress reduction) have been conducted in different delivery methods (including face to face and internet delivered) to help patients with breast cancer mitigate their depression. However, at present, there are no studies that compare the effectiveness of all these types and deliveries of mindfulness-based interventions. Therefore, this protocol aims to conduct a systematic review and network meta-analysis to assess the effectiveness of various types and deliveries of mindfulness-based interventions in mitigating depression in patients with breast cancer. METHODS: This protocol is according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The electronic databases, including PubMed, Web of Science, the Cochrane Library, Embase, Google Scholar, The China National Knowledge Infrastructure and OpenGrey, will be comprehensively retrieved for related randomised controlled trials (RCTs) from inception to December 2023. Two reviewers will independently assess the risk of bias using the Cochrane Risk of Bias Tool for Randomised Trials 2.0 (RoB 2.0). The network meta-analysis will be performed using the STATA V.16.0, and the assessment of heterogeneity, inconsistency, publication bias, evidence quality, subgroup analyses and sensitivity analyses will be conducted. ETHICS AND DISSEMINATION: This protocol does not require approval from an ethics committee as it is based on previous research findings. The results will be disseminated via peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42024495996.