Clinical Role
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Yongji Li ◽  
Wendi Yang ◽  
Feng Wang

Abstract Background Cell division control protein 42 (CDC42) is reported to be involved in multiple inflammation processes by regulating T cell differentiation, maintaining immune cell homeostasis, and altering their function, while no relevant studies explored its clinical role in patients with rheumatoid arthritis (RA). Therefore, this study aimed to explore the correlation of CDC42 with Th1 and Th17 cells and its association with disease risk, activity, and treatment outcomes of RA. Methods After the enrollment of 95 active RA patients and 50 healthy subjects (HC), their CDC42, Th1 cells, and Th17 cells were assayed by RT-qPCR and flow cytometry, accordingly. For RA patients only, CDC42 was also detected at W6, and W12 after treatment. The treatment response and remission status were evaluated at W12. Results Compared to HC, CDC42 was reduced (P < 0.001), while Th1 cells (P = 0.021) and Th17 cells (P < 0.001) were increased in RA patients. Besides, CDC42 was negatively correlated with Th17 cells (P < 0.001), erythrocyte sedimentation rate (ESR) (P = 0.012), C-reactive protein (P = 0.002), and disease activity score in 28 joints (DAS28) (P = 0.007), but did not relate to Th1 cells or other disease features (all P > 0.05) in RA patients. Furthermore, CDC42 was elevated during treatment in RA patients (P < 0.001). Moreover, CDC42 increment at W12 correlated with treatment response (P = 0.004). Besides, CDC42 elevation at W0 (P = 0.038), W6 (P = 0.001), and W12 (P < 0.001) also linked with treatment remission. Conclusion CDC42 has the potential to serve as a biomarker to monitor disease activity and treatment efficacy in patients with RA.

2021 ◽  
Vol 11 ◽  
Wen-Long Guan ◽  
Yue Ma ◽  
Yue-Hong Cui ◽  
Tian-Shu Liu ◽  
Yan-Qiao Zhang ◽  

BackgroundThe clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival.MethodsPatients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathological data were collected from the medical record system.ResultsA total of 196 patients with dMMR/MSI-H status were enrolled for analysis. The prevalence of MSI-H/dMMR in GC was 6.6%. Another 694 proficient MMR (pMMR) GC patients were enrolled for comparison. Compared with pMMR patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status. The median overall survival (OS) of the dMMR/MSI-H group was better than that of the pMMR/microsatellite stability (MSS) group (not reached vs. 53.9 months, p = 0.014). Adjuvant chemotherapy had no impact in both disease-free survival (DFS) and OS of dMMR/MSI-H patients (p = 0.135 and 0.818, respectively). dMMR/MSI-H patients had poorer response and progression-free survival (PFS) of first-line chemotherapy, though they were statistically significant (p = 0.361 and 0.124, respectively).ConclusionsdMMR/MSI-H GC patients have specific clinicopathological characteristics and better prognosis than pMMR patients.

2021 ◽  
Vol 8 ◽  
Jiahui Liu ◽  
Fangfang Fan ◽  
Xingyu Luo ◽  
Wenjun Ji ◽  
Yaokun Liu ◽  

Background: A large amount of evidence suggests that proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors have clinical benefits in patients with cardiovascular disease (CVD). However, whether PCSK9 concentrations predict future cardiovascular (CV) events remains unclear.Methods: We conducted a meta-analysis to investigate the ability of PCSK9 concentrations to predict future CV events in patients with established CVD. A comprehensive search of electronic databases was conducted in June 2021. We included relative risk (RR) estimates with 95% CI or events of interest.Results: Eleven cohort studies including 8,471 patients with CVD were enrolled. The pooled RR of CV events for the increase in the circulating baseline PCSK9 concentrations by 1 SD showed a positive association in a random-effect model (RR 1.226, 95% CI: 1.055–1.423, P = 0.008). Similarly, the risk of the total CV events increased by 52% in the patients in the highest tertile compared with those in the lowest tertile of circulating PCSK9 concentrations (RR 1.523, 95% CI: 1.098–2.112, P = 0.012). The association between PCSK9 and CV events was stronger in stable patients with CVD, patients treated with statins, and Asian patients.Conclusions: High PCSK9 concentrations are significantly related to the increased risk of future CV events. These results enrich the knowledge of PCSK9 function and suggest the further possible clinical role of PCSK9 inhibitors.

2021 ◽  
Vol 11 ◽  
Hua Yang ◽  
Mu-Zi-he Zhang ◽  
Hui-wei Sun ◽  
Yan-tao Chai ◽  
Xiaojuan Li ◽  

BAY-876 is an effective antagonist of the Glucose transporter type 1 (GLUT1) receptor, a mediator of aerobic glycolysis, a biological process considered a hallmark of hepatocellular carcinoma (HCC) together with cell proliferation, drug-resistance, and metastasis. However, the clinical application of BAY-876 has faced many challenges. In the presence study, we describe the formulation of a novel microcrystalline BAY-876 formulation. A series of HCC tumor models were established to determine not only the sustained release of microcrystalline BAY-876, but also its long-acting antitumor activity. The clinical role of BAY-876 was confirmed by the increased expression of GLUT1, which was associated with the worse prognosis among advanced HCC patients. A single dose of injection of microcrystalline BAY-876 directly in the HCC tissue achieved sustained localized levels of Bay-876. Moreover, the single injection of microcrystalline BAY-876 in HCC tissues not only inhibited glucose uptake and prolonged proliferation of HCC cells, but also inhibited the expression of epithelial-mesenchymal transition (EMT)-related factors. Thus, the microcrystalline BAY-876 described in this study can directly achieve promising localized effects, given its limited diffusion to other tissues, thereby reducing the occurrence of potential side effects, and providing an additional option for advanced HCC treatment.

2021 ◽  
Vol 22 (22) ◽  
pp. 12364
Jörg Kumbrink ◽  
Pan Li ◽  
Agnes Pók-Udvari ◽  
Frederick Klauschen ◽  
Thomas Kirchner ◽  

p130 Crk-associated substrate (p130Cas) is associated with poor prognosis and treatment resistance in breast and lung cancers. To elucidate p130Cas functional and clinical role in colorectal cancer (CRC) progression/therapy resistance, we performed cell culture experiments and bioinformatic/statistical analyses of clinical data sets. p130Cas expression was associated with poor survival in the cancer genome atlas (TCGA) data set. Knockdown/reconstitution experiments showed that p130Cas drives migration but, unexpectedly, inhibits proliferation in CRC cells. TCGA data analyses identified the growth factor epiregulin (EREG) as inversely correlated with p130Cas. p130Cas knockdown and simultaneous EREG treatment further enhanced proliferation. RNA interference and EREG treatment experiments suggested that p130Cas/EREG limit each other’s expression/activity. Inverse p130Cas/EREG Spearman correlations were prominent in right-sided and earlier stage CRC. p130Cas was inducible by 5-fluorouracil (5-FU) and FOLFIRI (folinic acid, 5-FU, irinotecan), and p130Cas and EREG were upregulated in distant metastases (GSE121418). Positive p130Cas/EREG correlations were observed in metastases, preferentially in post-treatment samples (especially pulmonary metastases). p130Cas knockdown sensitized CRC cells to FOLFIRI independent of EREG treatment. RNA sequencing and gene ontology analyses revealed that p130Cas is involved in cytochrome P450 drug metabolism and epithelial-mesenchymal transition. p130Cas expression was associated with poor survival in right-sided, stage I/II, MSS (microsatellite stable), or BRAF-mutated CRC. In summary, p130Cas represents a prognostic factor and potential therapeutic target in CRC.

2021 ◽  
Vol 11 ◽  
Serkan Kuyumcu ◽  
Yasemin Sanli ◽  
Rathan M. Subramaniam

Fibroblast activation protein (FAP), overexpressed on cancer-associated fibroblasts (CAFs), is a novel target for molecular imaging of various tumors. Recently, the development of several small-molecule FAP inhibitors for radiolabeling with 68Ga has resulted in the emergence of studies evaluating its clinical role in cancer imaging. Preliminary findings have demonstrated that, in contrast to radiotracers taking advantage of cancer-specific targets such as PSMA and DOTATATE, FAPs as a target are the most promising that can compete with 18FDG in terms of widespread indications. They also have the potential to overcome the shortcomings of 18FDG, particularly false-positive uptake due to inflammatory or infectious processes, low sensitivity in certain cancer types, and radiotherapy planning. In addition, the attractive theranostic properties may facilitate the treatment of many refractory cancers. This review summarizes the current FAP variants and related clinical studies, focusing on radiopharmacy, dosimetry, and diagnostic and theranostic applications.

2021 ◽  
pp. 473-513
Elena Locci ◽  
Silvia Raymond

According to the results of a global phase 2 clinical trial, the new drug sotorasib reduces tumor size and promises to improve and increase survival in patients with lung tumors caused by specific DNA mutations. It is designed to counteract the effects of mutations that are seen in about 13% of patients with non-small cell lung adenocarcinoma (a common type of lung cancer). The Food and Drug Administration (FDA) on May 28 approved the drug as a targeted treatment for patients with small cell lung cancer whose tumors express a specific mutation called G12C in the KRAS gene. Small cell lung cancer accounts for more than 80% of lung cancers. More than 200,000 new cases of nonsmall cell lung cancer are diagnosed in the United States each year. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

2021 ◽  
Vol 8 (11) ◽  
pp. 17-22
Prof. U. Bhagyalakshmi

The nursing profession has the widest range of opportunities, but the unawareness and ignorance of nurses are making them be at a dependent level only rather than independent. In most of the scenarios, administrative nurses, health care policymakers, and administrators of institutions and agencies, make and implement roles and activities for nurses to fulfill the aims of medicine and institutional bureaucracy. This problem 'forces' nursing to travel a dependent path. A view is set forth that the problem stems from the collective failure of nursing to articulate and implement a function and product distinct from that of medicine and other professions. Making this distinction is critical to the charting of an independent path. Nursing's past and present are examined in terms of the service nursing does provide for society. This paper deals with the various emerging job opportunities for nurses and ways to choose the best working environment for career advancement. Keywords: Teaching Role, Clinical Role, Research Role, Entrepreneur Role, Indian Nursing Council, Migration.

2021 ◽  
Vol 25 (1) ◽  
Alexander G.G. Doruyter ◽  
Jeannette Parkes ◽  
Jonathan Carr ◽  
James M. Warwick

Positron emission tomography combined with X-ray computed tomography (PET-CT) has an established role in the management of brain disorders, but may be underutilised in South Africa. Possible barriers to access include the limited number of PET-CT facilities and the lack of contemporary guidelines for the use of brain PET-CT in South Africa. The current review aims to highlight the evidence-based usage of brain Positron emission tomography (PET) in dementia, movement disorders, brain tumours, epilepsy, neuropsychiatric lupus, immune-mediated encephalitides, and brain infections. While being areas of research, there is currently no clinical role for the use of PET-CT in traumatic brain injury or in psychiatric or neurodevelopmental disorders. Strategies to expand the appropriate use of PET-CT in brain disorders are discussed in this article.

2021 ◽  
Vol 12 (3) ◽  
pp. 47
Phil Coleman

This study, underpinned by Critical Realism, explores the use of block and integrated placement frameworks within employer-sponsored pre-registration nursing programmes at a United Kingdom university. Digitally recorded, commercially transcribed semi-structured interviews involving four stakeholder groups (employers, students, mentors, and practice tutors), were exposed to qualitative content analysis, and yielded four common themes; connectedness, role transition, carer work and difference. Most respondents perceived the block model as being more effective in promoting connectedness, facilitating role transition, and mitigating against perceived difference; although use of the integrated model was considered more desirable for services having to release these students from carer work. Results also highlight various factors which may influence the most appropriate choice of practicum model, including individual student characteristics, the service in which learners undertake their non-registrant care work, the nature of the placement and mentor autonomy within their clinical role. Congruent with the principles of Critical Realism, efforts to establish potential underlying causative mechanisms associated with practicum experiences are underway and currently involves scrutiny of these results against key features of the Theory of Human Relatedness. Furthermore, a regression analysis to identify the statistical relationship between the placement model completed by two national cohorts and retention rates/degree classifications is in progress. This combined work contributes to the extremely limited body of knowledge in an important area of curriculum design within nurse education.

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