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1.
Neurosurg Focus ; 56(5): E14, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38691865

RESUMO

OBJECTIVE: Chordomas are locally aggressive neoplasms of the spine or skull base that arise from embryonic remnants of the notochord. Intradural chordomas represent a rare subset of these neoplasms, and few studies have described intradural chordomas in the spine. This review evaluates the presentation, management, and outcomes of intradural spinal chordomas. METHODS: A systematic review of PubMed/MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science was performed. Studies describing at least 1 case of intradural chordomas anywhere in the spine were included. Extracted details included presenting symptoms, radiological findings, treatment course, follow-up, and disease progression. RESULTS: Thirty-one studies, with a total of 41 patients, were included in this review. Seventy-six percent (31/41) of patients had primary intradural tumors, whereas 24% (10/41) presented with metastasis. The most common signs and symptoms were pain (n = 27, 66%); motor deficits (n = 20, 49%); sensory deficits (n = 17, 42%); and gait disturbance (n = 10, 24%). The most common treatment for intradural chordoma was resection and postoperative radiotherapy. Sixty-six percent (19/29) of patients reported improvement or complete resolution of symptoms after surgery. The recurrence rate was 37% (10/27), and the complication rate was 25% (6/24). The median progression-free survival was 24 months (range 4-72 months). Four patient deaths were reported. The median follow-up time was 12 months (range 13 days-84 months). CONCLUSIONS: Treatment of intradural spinal chordomas primarily involves resection and radiotherapy. A significant challenge and complication in management is spinal tumor seeding after resection, with 9 studies proposing seeding as a mechanism of tumor metastasis in 11 cases. Factors such as tumor size, Ki-67 positivity, and distant metastasis may correlate with worse outcomes and demonstrate potential as prognostic indicators for intradural spinal chordomas. Further research is needed to improve understanding of this tumor and develop optimal treatment paradigms for these patients.


Assuntos
Cordoma , Neoplasias da Medula Espinal , Humanos , Cordoma/cirurgia , Cordoma/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/terapia , Resultado do Tratamento , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Gerenciamento Clínico
2.
Plant Cell Environ ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780063

RESUMO

Plasmodesmata (PDs) are intercellular organelles carrying multiple membranous nanochannels that allow the trafficking of cellular signalling molecules. The channel regulation of PDs occurs dynamically and is required in various developmental and physiological processes. It is well known that callose is a critical component in regulating PD permeability or symplasmic connectivity, but the understanding of the signalling pathways and mechanisms of its regulation is limited. Here, we used the reverse genetic approach to investigate the role of C-type lectin receptor-like kinase 1 (CLRLK1) in the aspect of PD callose-modulated symplasmic continuity. Here, we found that loss-of-function mutations in CLRLK1 resulted in excessive PD callose deposits and reduced symplasmic continuity, resulting in an accelerated gravitropic response. The protein interactome study also found that CLRLK1 interacted with actin depolymerizing factor 3 (ADF3) in vitro and in plants. Moreover, mutations in ADF3 result in elevated PD callose deposits and faster gravitropic response. Our results indicate that CLRLK1 and ADF3 negatively regulate PD callose accumulation, contributing to fine-tuning symplasmic opening apertures. Overall, our studies identified two key components involved in the deposits of PD callose and provided new insights into how symplasmic connectivity is maintained by the control of PD callose homoeostasis.

3.
Nurs Outlook ; 72(3): 102145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38442465

RESUMO

BACKGROUND: As the disabled population ages and the demand for care increases, Socially, the need for care robots is emerging but, perceptions of care robots among care recipients is unknown. PURPOSE: To determine the level of intention to use care robots among care recipients and identify predictors of intention to use care robots. METHODS: A cross-sectional survey was conducted using a convenience sample of 163 persons with disabilities from January to March 2022 at the Veterans Health Service Medical Center. DISCUSSION: Overall, 64.42% of respondents intended to use care robots. Predictors included perceived behavioral control, participants' perceptions of the caregiver's burden, attitude toward robot use, subjective norms, and age. CONCLUSION: These findings suggest that individuals who are community-dwelling desire the use care robots to maintain their independence and may provide useful insignt for the introduction various care robots in acute care and long-term care settings.


Assuntos
Pessoas com Deficiência , Intenção , Robótica , Humanos , Masculino , Estudos Transversais , Feminino , Robótica/estatística & dados numéricos , Pessoa de Meia-Idade , Pessoas com Deficiência/psicologia , Pessoas com Deficiência/estatística & dados numéricos , Adulto , Idoso , Inquéritos e Questionários , Estados Unidos , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Idoso de 80 Anos ou mais
4.
Adv Radiat Oncol ; 9(1): 101327, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38260225

RESUMO

Purpose: Although surgical decompression is the gold standard for metastatic epidural spinal cord compression (MESCC) from solid tumors, not all patients are candidates or undergo successful surgical Bilsky downgrading. We report oncologic and functional outcomes for patients treated with stereotactic body radiation therapy (SBRT) to high-grade MESCC. Methods and Materials: Patients with Bilsky grade 2 to 3 MESCC from solid tumor metastases treated with SBRT at a single institution from 2009 to 2020 were retrospectively reviewed. Patients who received upfront surgery before SBRT were included only if postsurgical Bilsky grade remained ≥2. Neurologic examinations, magnetic resonance imaging, pain assessments, and analgesic usage were assessed every 3 to 4 months post-SBRT. Cumulative incidence of local recurrence was calculated with death as a competing risk, and overall survival was estimated by Kaplan-Meier. Results: One hundred forty-three patients were included. The cumulative incidence of local recurrence was 5.1%, 7.5%, and 14.1% at 6, 12, and 24 months, respectively. At first post-SBRT imaging, 16.2% of patients with initial Bilsky grade 2 improved to grade 1, and 53.8% of patients were stable. Five of 13 patients (38.4%) with initial Bilsky grade 3 improved to grade 1 to 2. Pain response at 3 and 6 months post-SBRT was complete in 45.4% and 55.7%, partial in 26.9% and 13.1%, stable in 24.1% and 27.9%, and worse in 3.7% and 3.3% of patients, respectively. At 3 and 6 months after SBRT, 17.8% and 25.0% of patients had improved ambulatory status and 79.7% and 72.4% had stable status. Conclusions: We report the largest series to date of patients with high-grade MESCC treated with SBRT. The excellent local control and functional outcomes suggest SBRT is a reasonable approach in inoperable patients or cases unable to be successfully surgically downgraded.

7.
Nat Commun ; 14(1): 7600, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37990009

RESUMO

Subcutaneous patient-derived xenografts (PDXs) are an important tool for childhood cancer research. Here, we describe a resource of 68 early passage PDXs established from 65 pediatric solid tumor patients. Through genomic profiling of paired PDXs and patient tumors (PTs), we observe low mutational similarity in about 30% of the PT/PDX pairs. Clonal analysis in these pairs show an aggressive PT minor subclone seeds the major clone in the PDX. We show evidence that this subclone is more immunogenic and is likely suppressed by immune responses in the PT. These results suggest interplay between intratumoral heterogeneity and antitumor immunity may underlie the genetic disparity between PTs and PDXs. We further show that PDXs generally recapitulate PTs in copy number and transcriptomic profiles. Finally, we report a gene fusion LRPAP1-PDGFRA. In summary, we report a childhood cancer PDX resource and our study highlights the role of immune constraints on tumor evolution.


Assuntos
Neoplasias , Animais , Criança , Humanos , Xenoenxertos , Neoplasias/genética , Neoplasias/patologia , Transcriptoma/genética , Mutação , Modelos Animais de Doenças , Genômica/métodos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Spine (Phila Pa 1976) ; 48(18): 1272-1281, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37417689

RESUMO

STUDY DESIGN: A retrospective analysis. OBJECTIVE: The aim of our study was to analyze the association of Area Deprivation Index (ADI) with the utilization and costs of elective anterior cervical discectomy and fusion (ACDF) surgery. SUMMARY OF BACKGROUND DATA: ADI, a comprehensive neighborhood-level measure of socioeconomic disadvantage, has been shown to be associated with worse perioperative outcomes in a variety of surgical settings. MATERIALS AND METHODS: The Maryland Health Services Cost Review Commission Database was queried to identify patients who underwent primary elective ACDF between 2013 and 2020 in the state. Patients were stratified into tertiles by ADI, from least disadvantaged (ADI1) to most disadvantaged (ADI3). The primary endpoints were ACDF utilization rates per 100,000 adults and episode-of-care total costs. Univariable and multivariable regression analyses were performed. RESULTS: A total of 13,362 patients (4984 inpatient and 8378 outpatient) underwent primary ACDF during the study period. In our study, there were 2,401 (17.97%) patients residing in ADI1 neighborhoods (least deprived), 5974 (44.71%) in ADI2, and 4987 (37.32%) in ADI3 (most deprived). Factors associated with increased surgical utilization were increasing ADI, outpatient surgical setting, non-Hispanic ethnicity, current tobacco use, and diagnoses of obesity and gastroesophageal reflux disease. Factors associated with lower surgical utilization were: non-white race, rurality, Medicare/Medicaid insurance status, and diagnoses of cervical disk herniation or myelopathy. Factors associated with higher costs of care were increasing ADI, older age, Black/African American race, Medicare or Medicaid insurance, former tobacco use, and diagnoses of ischemic heart disease and cervical myelopathy. Factors associated with lower costs of care were outpatient surgical setting, female sex, and diagnoses of gastroesophageal reflux disease and cervical disk herniation. CONCLUSIONS: Neighborhood socioeconomic deprivation is associated with increased episode-of-care costs in patients undergoing ACDF surgery. Interestingly, we found greater utilization of ACDF surgery among patients with higher ADI. LEVEL OF EVIDENCE: 3.


Assuntos
Refluxo Gastroesofágico , Deslocamento do Disco Intervertebral , Doenças da Medula Espinal , Fusão Vertebral , Adulto , Humanos , Feminino , Idoso , Estados Unidos/epidemiologia , Estudos Retrospectivos , Deslocamento do Disco Intervertebral/cirurgia , Medicare , Doenças da Medula Espinal/cirurgia , Discotomia , Fatores Socioeconômicos , Vértebras Cervicais/cirurgia
9.
Compr Physiol ; 13(3): 4833-4850, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37358511

RESUMO

Most cells in our body release membrane-bound, nano-sized particles into the extracellular milieu through cellular metabolic processes. Various types of macromolecules, reflecting the physiological and pathological status of the producing cells, are packaged into such so-called extracellular vesicles (EVs), which can travel over a distance to target cells, thereby transmitting donor cell information. The short, noncoding ribonucleic acid (RNA) called microRNA (miRNA) takes a crucial part in EV-resident macromolecules. Notably, EVs transferring miRNAs can induce alterations in the gene expression profiles of the recipient cells, through genetically instructed, base-pairing interaction between the miRNAs and their target cell messenger RNAs (mRNAs), resulting in either nucleolytic decay or translational halt of the engaged mRNAs. As in other body fluids, EVs released in urine, termed urinary EVs (uEVs), carry specific sets of miRNA molecules, which indicate either normal or diseased states of the kidney, the principal source of uEVs. Studies have therefore been directed to elucidate the contents and biological roles of miRNAs in uEVs and moreover to utilize the gene regulatory properties of miRNA cargos in ameliorating kidney diseases through their delivery via engineered EVs. We here review the fundamental principles of the biology of EVs and miRNA as well as our current understanding of the biological roles and applications of EV-loaded miRNAs in the kidney. We further discuss the limitations of contemporary research approaches, suggesting future directions to overcome the difficulties to advance both the basic biological understanding of miRNAs in EVs and their clinical applications in treating kidney diseases. © 2023 American Physiological Society. Compr Physiol 13:4833-4850, 2023.


Assuntos
Vesículas Extracelulares , MicroRNAs , Humanos , MicroRNAs/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Rim/metabolismo , RNA Mensageiro/metabolismo
10.
Front Mol Neurosci ; 16: 1187300, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37181650

RESUMO

Conventional inter-neuronal communication conceptualizes the wired method of chemical synapses that physically connect pre-and post-synaptic neurons. In contrast, recent studies indicate that neurons also utilize synapse-independent, hence "wireless" broadcasting-type communications via small extracellular vesicles (EVs). Small EVs including exosomes are secreted vesicles released by cells and contain a variety of signaling molecules including mRNAs, miRNAs, lipids, and proteins. Small EVs are subsequently absorbed by local recipient cells via either membrane fusion or endocytic processes. Therefore, small EVs enable cells to exchange a "packet" of active biomolecules for communication purposes. It is now well established that central neurons also secrete and uptake small EVs, especially exosomes, a type of small EVs that are derived from the intraluminal vesicles of multivesicular bodies. Specific molecules carried by neuronal small EVs are shown to affect a variety of neuronal functions including axon guidance, synapse formation, synapse elimination, neuronal firing, and potentiation. Therefore, this type of volume transmission mediated by small EVs is thought to play important roles not only in activity-dependent changes in neuronal function but also in the maintenance and homeostatic control of local circuitry. In this review, we summarize recent discoveries, catalog neuronal small EV-specific biomolecules, and discuss the potential scope of small EV-mediated inter-neuronal signaling.

11.
Eur Spine J ; 32(7): 2513-2520, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37186159

RESUMO

PURPOSE: Scoring systems for metastatic spine disease focus on predicting long- to medium-term mortality or a combination of perioperative morbidity and mortality. However, accurate prediction of perioperative mortality alone may be the most important factor when considering surgical intervention. We aimed to develop and evaluate a new tool, the H2-FAILS score, to predict 30-day mortality after surgery for metastatic spine disease. METHODS: Using the National Surgical Quality Improvement Program database, we identified 1195 adults who underwent surgery for metastatic spine disease from 2010 to 2018. Incidence of 30-day mortality was 8.7% (n = 104). Independent predictors of 30-day mortality were used to derive the H2-FAILS score. H2-FAILS is an acronym for: Heart failure (2 points), Functional dependence, Albumin deficiency, International normalized ratio elevation, Leukocytosis, and Smoking (1 point each). Discrimination was assessed using area under the receiver operating characteristic curve (AUC). The H2-FAILS score was compared with the American Society of Anesthesiologists Physical Status Classification (ASA Class), the 5-item modified Frailty Index (mFI-5), and the New England Spinal Metastasis Score (NESMS). Internal validation was performed using bootstrapping. Alpha = 0.05. RESULTS: Predicted 30-day mortality was 1.8% for an H2-FAILS score of 0 and 78% for a score of 6. AUC of the H2-FAILS was 0.77 (95% confidence interval: 0.72-0.81), which was higher than the mFI-5 (AUC 0.58, p < 0.001), ASA Class (AUC 0.63, p < 0.001), and NESMS (AUC 0.70, p = 0.004). Internal validation showed an optimism-corrected AUC of 0.76. CONCLUSIONS: The H2-FAILS score accurately predicts 30-day mortality after surgery for spinal metastasis. LEVEL OF EVIDENCE: Prognostic level III.


Assuntos
Neoplasias da Coluna Vertebral , Adulto , Humanos , Neoplasias da Coluna Vertebral/secundário , Prognóstico , Curva ROC , Coluna Vertebral/cirurgia
12.
Blood Adv ; 7(16): 4233-4246, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-36930803

RESUMO

Platelets use signal transduction pathways facilitated by class I phosphatidylinositol transfer proteins (PITPs). The 2 mammalian class I PITPs, PITPα and PITPß, are single PITP domain soluble proteins that are encoded by different genes and share 77% sequence identity, although their individual roles in mammalian biology remain uncharacterized. These proteins are believed to shuttle phosphatidylinositol and phosphatidylcholine between separate intracellular membrane compartments, thereby regulating phosphoinositide synthesis and second messenger formation. Previously, we observed that platelet-specific deletion of PITPα, the predominantly expressed murine PITP isoform, had no effect on hemostasis but impaired tumor metastasis formation and disrupted phosphoinositide signaling. Here, we found that mice lacking the less expressed PITPß in their platelets exhibited a similar phenotype. However, in contrast to PITPα-null platelet lysates, which have impaired lipid transfer activity, PITPß-null platelet lysates have essentially normal lipid transfer activity, although both isoforms contribute to phosphoinositide synthesis in vitro. Moreover, we found that platelet-specific deletion of both PITPs led to ex vivo platelet aggregation/secretion and spreading defects, impaired tail bleeding, and profound tumor dissemination. Our study also demonstrated that PITP isoforms are required to maintain endogenous phosphoinositide PtdInsP2 levels and agonist-stimulated second messenger formation. The data shown here demonstrate that the 2 isoforms are functionally overlapping and that a single isoform is able to maintain the homeostasis of platelets. However, both class I PITP isoforms contribute to phosphoinositide signaling in platelets through distinct biochemical mechanisms or different subcellular domains.


Assuntos
Plaquetas , Proteínas de Transferência de Fosfolipídeos , Animais , Camundongos , Tempo de Sangramento , Plaquetas/metabolismo , Deleção de Genes , Homeostase/genética , Camundongos Endogâmicos C57BL , Neoplasias/genética , Fosfatidilinositóis/biossíntese , Fosfatidilinositóis/metabolismo , Proteínas de Transferência de Fosfolipídeos/genética , Proteínas de Transferência de Fosfolipídeos/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transdução de Sinais/genética , Trombose/genética
13.
Neurotherapeutics ; 20(3): 853-869, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36976493

RESUMO

We investigated whether pharmacological increase of "M-type" (KCNQ, Kv7) K + channel currents by the M-channel opener, retigabine (RTG), acutely after repetitive traumatic brain injuries (rTBIs), prevents or reduces their long-term detrimental effects. rTBIs were studied using a blast shock air wave mouse model. Animals were monitored by video and electroencephalogram (EEG) records for nine months after the last injury to assess the occurrence of post-traumatic seizures (PTS), post-traumatic epilepsy (PTE), sleep-wake cycle architecture alterations, and the power of the EEG signals. We evaluated the development of long-term changes in the brain associated with various neurodegenerative diseases in mice by examining transactive response DNA-binding protein 43 (TDP-43) expression and nerve fiber damage ~ 2 years after the rTBIs. We observed acute RTG treatment to reduce the duration of PTS and impair the development of PTE. Acute RTG treatment also prevented post-injury hypersomnia, nerve fiber damage, and cortical TDP-43 accumulation and translocation from the nucleus to the cytoplasm. Mice that developed PTE displayed impaired rapid eye movement (REM) sleep, and there were significant correlations between seizure duration and time spent in the different stages of the sleep-wake cycle. We observed acute RTG treatment to impair injury-induced reduction of age-related increase in gamma frequency power of the EGG, which has been suggested to be necessary for a healthy aged brain. The data show that RTG, administered acutely post-TBI, is a promising, novel therapeutic option to blunt/prevent several long-term effects of rTBIs. Furthermore, our results show a direct relationship between sleep architecture and PTE.


Assuntos
Lesões Encefálicas Traumáticas , Epilepsia Pós-Traumática , Camundongos , Animais , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Convulsões/tratamento farmacológico , Convulsões/etiologia , Carbamatos/farmacologia , Carbamatos/uso terapêutico
14.
Parasite Immunol ; 45(5): e12979, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36971331

RESUMO

We demonstrate that CD193, the eotaxin receptor, is highly expressed on circulating B cells in paediatric schistosomiasis mansoni. CD193 plays a role in directing granulocytes into sites of allergic-like inflammation in the mucosa, but little is known about its functional significance on human B cells. We sought to characterize CD193 expression and its relationship with S. mansoni infection. We found that CD193+ B cells increased with the intensity of schistosome infection. In addition, a significant negative association was observed between CD193 expression by B cells and IgE production. Decreased IgE levels are generally associated with susceptibility to re-infection. B cell stimulation with eotaxin-1 increased CD193 levels whereas IL-4 led to a reduction. This was supported by plasma levels of eotaxin-1 correlating with CD193 levels on B cells and other cells. In contrast, CD193 expression was induced on naive B cells with a combination of IL-10 and schistosome antigens. Whereas T cells had a modest increase in CD193 expression, only B cell CD193 appeared functionally chemotactic to eotaxin-1. Thus, CD193+ B cells, which co-express CXCR5, may be enroute to sites with allergic-like inflammation, such as gastrointestinal follicles, or even to Th2 granulomas, which develop around parasite eggs. Overall, our results suggest that schistosome infection may promote CD193 expression and suppress IgE via IL-10 and other undefined mechanisms related to B cell trafficking. This study adds to our understanding of why young children may have poor immunity. Nonetheless, praziquantel treatment was shown to reduce percentages of circulating CD193+ B cells lending hope for future vaccine efforts.


Assuntos
Interleucina-10 , Esquistossomose mansoni , Animais , Criança , Pré-Escolar , Humanos , Quimiocina CCL11 , Imunoglobulina E , Inflamação , Receptores CCR3 , Schistosoma mansoni , Linfócitos B/imunologia
15.
J Alzheimers Dis ; 91(4): 1313-1322, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36617780

RESUMO

BACKGROUND: Lower cerebral blood flow (CBF) and excessive brain atrophy are linked to Alzheimer's disease (AD). It is still undetermined whether reduced CBF precedes or follows brain tissue loss. OBJECTIVE: We compared total CBF (tCBF), global cerebral perfusion (GCP), and volumes of AD-prone regions between cognitively normal (CN) and early amnestic mild cognitive impairment (aMCI) and tested their associations with cognitive performance to assess their predictive value for differentiation between CN and early aMCI. METHODS: A total of 74 participants (mean age 69.9±6.2 years, 47 females) were classified into two groups: 50 CN and 24 aMCI, of whom 88% were early aMCI. tCBF, GCP, and global and regional brain volumetry were measured using phase-contrast and T1-weighted MRI. Neuropsychological tests tapping global cognition and four cognitive domains (memory, executive function, language, and visuospatial) were administered. Comparisons and associations were investigated using analyses of covariance (ANCOVA) and linear regression analyses, respectively. RESULTS: Women had significantly higher GCP than men. Both, tCBF and GCP were significantly reduced in aMCI compared with CN, while differences in volumes of cerebral gray matter, white matter, and AD-prone regions were not significant. tCBF and GCP were significantly associated with global cognition (standardized beta (stß) = 0.324 and stß= 0.326) and with memory scores (stß≥0.297 and stß≥0.264) across all participants. Associations of tCBF and GCP with memory scores were also significant in CN (stß= 0.327 and stß= 0.284) and in aMCI (stß= 0.627 and stß= 0.485). CONCLUSION: Reduced tCBF and GCP are sensitive biomarkers of early aMCI that likely precede brain tissue loss.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Masculino , Humanos , Feminino , Idoso , Encéfalo , Cognição , Testes Neuropsicológicos , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética
16.
Adv Ther ; 40(3): 1047-1061, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36624354

RESUMO

INTRODUCTION: SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications. METHODS: This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]. RESULTS: In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1 weeks. CONCLUSION: This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Medicamentos Biossimilares , Espondilite Anquilosante , Criança , Humanos , Adulto , Infliximab/efeitos adversos , Espondilite Anquilosante/tratamento farmacológico , Medicamentos Biossimilares/efeitos adversos , Estudos Prospectivos , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Resultado do Tratamento , República da Coreia , Vigilância de Produtos Comercializados
17.
Saudi J Gastroenterol ; 29(1): 53-58, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36571385

RESUMO

Background: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity. Methods: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm2) and MB. Cytotoxicity was evaluated using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. In vivo toxicity was evaluated in the stomach of beagles using the same dose of fiber-optic LED via gastroscopy, after spraying 0.1% and 0.5% MB solutions. Stomach tissue was also evaluated using the TUNEL assay. Results: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P < 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P < 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10. Conclusions: : Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period.


Assuntos
Azul de Metileno , Fotoquimioterapia , Cães , Animais , Humanos , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/toxicidade , Fármacos Fotossensibilizantes/uso terapêutico , Linhagem Celular , Mucosa Gástrica
18.
Biol Imaging ; 3: e23, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38510173

RESUMO

Spatially resolved transcriptomics (SRT) is a growing field that links gene expression to anatomical context. SRT approaches that use next-generation sequencing (NGS) combine RNA sequencing with histological or fluorescent imaging to generate spatial maps of gene expression in intact tissue sections. These technologies directly couple gene expression measurements with high-resolution histological or immunofluorescent images that contain rich morphological information about the tissue under study. While broad access to NGS-based spatial transcriptomic technology is now commercially available through the Visium platform from the vendor 10× Genomics, computational tools for extracting image-derived metrics for integration with gene expression data remain limited. We developed VistoSeg as a MATLAB pipeline to process, analyze and interactively visualize the high-resolution images generated in the Visium platform. VistoSeg outputs can be easily integrated with accompanying transcriptomic data to facilitate downstream analyses in common programing languages including R and Python. VistoSeg provides user-friendly tools for integrating image-derived metrics from histological and immunofluorescent images with spatially resolved gene expression data. Integration of this data enhances the ability to understand the transcriptional landscape within tissue architecture. VistoSeg is freely available at http://research.libd.org/VistoSeg/.

19.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(8): 1182-1190, 2022 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-36073217

RESUMO

OBJECTIVE: To explore the expression of fibronectin type Ⅲ domain containing 1(FNDC1) protein in lung adenocarcinoma and its prognostic significance. METHODS: The expression of FNDC1 in lung adenocarcinoma was predicted by analysis of data from GEO database and GEPIA, and the results were verified by immunohistochemical staining in 92 pairs of clinical specimens of lung adenocarcinoma and adjacent tissues.We further analyzed the correlation of FNDC1 expression with the clinicopathological features of the patients, and evaluated its prognostic value using Cox survival analysis. RESULTS: Analysis of the data form GEO database and GEPIA showed a significantly higher expression level of FNDC1 in lung adenocarcinoma than in matched normal tissues (P < 0.05).Kaplan-Meier survival analysis suggested that a high expression of FNDC1 protein was associated with a significantly shorter overall survival time of the patients (P < 0.05).Immunohistochemistry of the clinical specimens also showed a significantly higher protein expression of FNDC1 in lung adenocarcinoma tissues than in paired adjacent tissues (P < 0.001).A high expression of FNDC1 protein was significantly correlated with advanced clinical stage, T stage and N stage (P < 0.05).Cox univariate and multivariate regression survival analysis indicated that an increased expression of FNDC1 was an independent risk factor for poor prognosis of the patients with lung adenocarcinoma (P < 0.05). CONCLUSION: FNDC1 protein is highly expressed in patients with lung adenocarcinoma and in closely related with the occurrence, progression and prognosis of the tumor, suggesting the value of FNDC1 protein as a potential biomarker for assessment of the survival and prognosis of patients with lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas de Neoplasias , Adenocarcinoma de Pulmão/metabolismo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/genética , Prognóstico , Proteínas
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