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Δευτέρα 29 Μαρτίου 2021

Quality of Life during Treatment with Lenvatinib for Thyroid Cancer: The Patients' Perspective beyond the Medical Evaluation

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Eur Thyroid J. 2021 Mar;10(1):65-71. doi: 10.1159/000508186. Epub 2020 Jul 13.

ABSTRACT

BACKGROUND: Lenvatinib (LEN) has shown great efficacy but important toxicity in patients with advanced radioactive iodine-refractory (RAI-R) thyroid cancer (TC); a focused evaluation of its impact on patients' quality of life (QoL) is still lacking. Our prospective study investigated the impact of this drug on QoL in a group of RAI-R TC patients treated at our centre.

METHODS: All patients filled in two questionnaires before and during treatment: (1) the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events adapted questionnaire, assessing prevalence, severity, and/or interference on daily activities of the most frequent symptomatic adverse events (AEs) reported in previous clinical trials during therapy with LEN, and (2) the European Quality of Life 5 Dimensions 3 Levels (EQ-5D-3L) questionnaire, providing the EQ-5D index and the EQ visual analogue scale (EQ-VAS). Data from baseline questionnaires were compared with those obtained 3, 6, and 12 months after the start of treatment.

RESULTS: In our population (n = 20), an overall increased perception of symptomatic AEs emerged during treatment (statistically significant for abdominal pain, asthenia/fatigue, decreased appetite, and xerostomia). The median EQ-5D index and EQ-VAS scores after 3 months of treatment were lower than at baseline, almost returning to initial value s after 12 months.

CONCLUSION: RAI-R TC patients reported a general increase in prevalence and interference on daily activities of symptomatic AEs during therapy with LEN. Self-perceived QoL initially decreased during therapy. However, our data suggest that QoL could be restored after 12 months; this trend might partly reflect the impact of therapy optimisation.

PMID:33777821 | PMC:PMC7983562 | DOI:10.1159/000508186

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microRNA-23 inhibits inflammation to alleviate rheumatoid arthritis via regulating CXCL12

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Exp Ther Med. 2021 May;21(5):459. doi: 10.3892/etm.2021.9890. Epub 2021 Mar 3.

ABSTRACT

Rheumatoid arthritis (RA) is a common systemic, inflammatory and autoimmune disorder. MicroRNAs (miRs) are strongly associated with the initiation and progression of RA. However, the functions and mechanisms underlying miR-23 in RA are not completely understood. Therefore, the present study aimed to investigate the molecular mechanisms underlying miR-23 in RA. A bioinformatics tool (StarBase) and a wide range of experimental assays, including reverse transcription-quantitative PCR, western blotting, luciferase reporter assays and ELISAs, were performed to investigate the biological role of miR-23 in RA. The results indicated that miR-23 was downregulated and chemokine C-X-C motif ligand 12 (CXCL12) was upregulated in RA samples compared with healthy samples. Furthermore, miR-23 overexpression suppressed inflammation via reducing TNF-α, IL-1β and I L-8 expression levels compared with the NC mimic group. Regarding the underlying mechanism, compared with NC mimic, miR-23 mimic decreased CXCL12 mRNA expression by binding to its 3'-untranslated region. Additionally, CXCL12 overexpression reversed miR-23 mimic-mediated effects on inflammation. NF-κB signaling is associated with inflammation. Therefore, the present study indicated that CXCL12 promoted inflammation by activating NF-κB signaling. In conclusion, miR-23 inhibited inflammation to alleviate RA by regulating CXCL12 via the NF-κB signaling pathway, which may serve as a potential target for the diagnosis and treatment of RA.

PMID:33777193 | PMC:PMC7967800 | DOI:10.3892/etm.2021.9890

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Distinctive gut microbial dysbiosis between chronic alcoholic fatty liver disease and metabolic-associated fatty liver disease in mice

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Exp Ther Med. 2021 May;21(5):418. doi: 10.3892/etm.2021.9862. Epub 2021 Feb 25.

ABSTRACT

The gut microbiota, which may affect normal physiological and biochemical functions, has an important role in the development of human liver diseases. The aim of the present study was to investigate differences in the gut microbiota between chronic alcoholic fatty liver disease (AFLD) and metabolic-associated fatty liver disease (MAFLD). AFLD was induced by chronic alcohol administration and MAFLD was induced by a Western-style diet in C57BL/6 mice. After 8 weeks, the levels of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-10 were assessed and H&E staining of mouse liver tissue was performed. High-throughput sequencing of 16S ribosomal DNA from the intestinal contents was used to analy ze the different effects of AFLD and MAFLD on the gut microbiota. Differences in the gut microbiota composition were assessed by the t-test. The results revealed increases in LPS, ALT, AST, TG, IL-1β and TNF-α in the AFLD group. Compared with those in the MAFLD control group, the MAFLD group exhibited increased plasma ALT, TG, TC, IL-6, IL-1β and TNF-α levels and decreased plasma IL-10 levels. In addition, the α- and β-diversities revealed that the AFLD and MAFLD groups exhibited obvious changes in the gut structure (with an increase in abundance in the AFLD group and a decrease in abundance in the MAFLD group). In comparison to the AFLD control group, Enterococcaceae were the most abundant bacteria at the family level and Enterococcus and Streptococcus were the most abundant bacteria at the genus level in the AFLD group. However, in the MAFLD group, Lachnospiraceae was the most abundant at the family level, with increases in Erysipelatoclostridium, Gor donibacter and Streptococcus at the genus level and a decrease in the genus Bifidobacterium. In conclusion, the present study confirmed that the AFLD and MAFLD groups harbored differences in the gut microbiota. The marked differences in the gut microbiota at the family and genus levels may contribute to the development process of FLD.

PMID:33777186 | PMC:PMC7967804 | DOI:10.3892/etm.2021.9862

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Protein tyrosine phosphatase receptor-type O expression as a prognostic marker in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A prospective study

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Exp Ther Med. 2021 May;21(5):435. doi: 10.3892/etm.2021.9852. Epub 2021 Feb 26.

ABSTRACT

Optimal clinical indicators are crucial for evaluating the prognosis of patients with acute coronary syndrome (ACS). In the present study, the potential prognostic value of protein tyrosine phosphatase receptor-type O (PTPRO) expression in the peripheral blood mononuclear cells of patients with ACS undergoing percutaneous coronary intervention (PCI) was investigated. Patients diagnosed with ACS were prospectively recruited, and PTPRO expression in mononuclear cells separated from peripheral blood was assessed by western blotting. The prognosis was judged by the occurrence of major adverse cardiovascular events. Cox regression analyses were performed to assess the association between PTPRO expression and prognosis. In the enrolled 185 patients with ACS, PTPRO expression was lower after PCI compared with that before PCI (P<0.05). Although the pre- PCI PTPRO expression did not differ significantly between the good and poor prognosis groups, PTPRO expression after PCI was significantly lower in the good prognosis group compared with the poor prognosis group (P<0.05). The area under the receiver operating characteristic curve for the prognostic value of post-PCI PTPRO expression was significantly greater than that for pre-PCI PTPRO expression (P<0.05). Cox regression analysis identified high post-PCI PTPRO expression as an independent risk factor for poor prognosis in patients with ACS (P<0.05), and further analysis indicated that the post-PCI PTPRO expression level was associated with the prognosis of patients with ACS (P<0.05). PTPRO expression in peripheral blood mononuclear cells after PCI is associated with the prognosis of patients with ACS, with high PTPRO expression indicating a high risk of poor prognosis in patients with ACS.

PMID:33777188 | PMC:PMC7967798 | DOI:10.3892/etm.2021.9852

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Recent advances of glucocorticoids in the treatment of Duchenne muscular dystrophy (Review)

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Exp Ther Med. 2021 May;21(5):447. doi: 10.3892/etm.2021.9875. Epub 2021 Mar 1.

ABSTRACT

Duchenne muscular dystrophy (DMD) is the most common degenerative neuromuscular disease. The incidence of DMD in live births is 1/3,600-1/6,000. Although glucocorticoid-dependent medication is the mainstay treatment option for DMD, a standard treatment regimen has yet to be determined. The present review discusses the literature on the timing, methods and courses of glucocorticoid treatment for DMD. The review highlights the importance of the immediate commencement of glucocorticoid treatment following the diagnosis of DMD, with weekend-only administration being advantageous. Adherence to long-term single-glucocorticoid therapy can delay the loss of ambulation ability, and the side effects of the treatment are controllable. However, the standard medication for patients of different ages and stages of disease development, and the use of combination t herapy require further investigation.

PMID:33777191 | PMC:PMC7967797 | DOI:10.3892/etm.2021.9875

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Clinical application of liver stiffness measurement in patients with cavernous transformation of portal vein

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Exp Ther Med. 2021 May;21(5):442. doi: 10.3892/etm.2021.9881. Epub 2021 Feb 28.

ABSTRACT

The clinical outcomes differ between patients with cavernous transformation of the portal vein (CTPV) with and without cirrhosis. Therefore, invasive liver biopsy may be needed for the differential diagnosis of patients with CTPV with or without cirrhosis. The present study aimed to investigate the diagnostic efficacy of liver stiffness measurements (LSM) for the prediction of cirrhosis in patients with CTPV. A total of 20 patients with CTPV, 34 with chronic hepatitis B (CHB)-related cirrhosis and 20 healthy volunteers, were retrospectively recruited in the study. CTPV was diagnosed with contrast-enhanced computed tomography (CT) and ultrasound for the abdomen. LSM values were detected for each patient, while liver biopsy was performed in each patient in the CTPV and cirrhosis groups. The results demonstrated that LSM values were significantly lowe r in the CTPV group (12.5 kPa; range, 6.8-21.5 kPa) compared with the CHB-related cirrhosis group (21.0 kPa; range, 15.5-27.2 kPa; P=0.017). However, this was still higher compared with healthy volunteers (4.9 kPa; range 4.0-5.8 kPa; P<0.001). In addition, CTPV patients with cirrhosis (17.7 kPa; range, 13.9-30.8 kPa) exhibited significantly increased LSM values compared with those without cirrhosis (6.4 kPa; range, 5.7-7.8 kPa; P<0.001). Furthermore, LSM values in CTPV patients without cirrhosis were slightly higher compared with those of healthy volunteers (P=0.003), while no statistically significant difference was observed in LSM between CTPV patients with cirrhosis and CHB-related cirrhosis group. These findings indicated that LSM values could be used for the differential diagnosis of CTPV patients with or without cirrhosis. However, further validation studies are needed.

PMID:33777190 | PMC:PMC7967803 | DOI:10.3892/etm.2021.9881

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Congenital dyserythropoietic anemia and drug-induced liver injury present as bland cholestasis: A case report

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Exp Ther Med. 2021 May;21(5):456. doi: 10.3892/etm.2021.9887. Epub 2021 Mar 2.

ABSTRACT

Anemias and drug-induced liver injury(DILI) are separate disorders, which are difficult to diagnose. The clinical effects of DILI vary among individuals. However, the outcome determinants remain to be fully established. To the best of our knowledge, the role of anemia in DILI has yet to be reported. The present study reported on the case of one Chinese patient (male; age, 21 years) who experienced obvious drug-induced cholestasis. Of note, the hepatocyte injury was minimal compared with that in previously reported cases treated with the same drug. In addition, the patient suffered from mild hemolytic anemia with no obvious cause. A genetic pedigree analysis revealed compound heterozygous mutations in the congenital anemia-associated gene codanin 1, including the novel rare p.R1067H mutation. Treatment with ursodeoxycholic acid alone sufficed and the outcome was good. Therefore, whilst chronic hemolysis predisposed the liver to cholestasis, it could have shielded the liver from further injuries, since bilirubin, a by-product of hemolysis, is a known antioxidant. The results of the present study indicated that genetic screening may be used for the diagnosis of liver injury concurring with undiagnosed anemia.

PMID:33777192 | PMC:PMC7967802 | DOI:10.3892/etm.2021.9887

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miR-23a-3p regulates the proliferation and apoptosis of human lens epithelial cells by targeting Bcl-2 in an in vitro model of cataracts

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Exp Ther Med. 2021 May;21(5):436. doi: 10.3892/etm.2021.9853. Epub 2021 Feb 26.

ABSTRACT

Cataracts account for ~50% of the cases of blindness in individuals worldwide. The apoptosis of lens epithelial cells (LECs) occurs during the formation of cataracts, which is a non-congenital condition. Numerous microRNAs (miRs) have been reported to regulate apoptosis in LECs. For instance, miR-23a expression levels were shown to be upregulated in cataractous lenses; however, the function of miR-23a in cataracts remains undetermined. To establish an in vitro model of cataracts, human LECs, HLE-B3 cells, were induced with 200 µmol/l H2O2 for 24 h. HLE-B3 cells were transfected with the miR-negative control (NC) mimic, miR-23a-3p mimic, miR-NC inhibitor, miR-23a-3p inhibitor, small interfering RNA (siRNA) targeting BCL2 (siRNA-BCL2) and siRNA-NC. The expression levels of miR-23a-3p were detected using reverse transcrip tion-quantitative PCR. The interaction between miR-23a-3p and the 3'-untranslated region (UTR) of the target mRNA BCL2 was predicted by TargetScan 7.1, and further validated using a dual luciferase reporter assay. The BCL2 protein expression levels were analyzed using western blotting, cell proliferation was determined using a CCK-8 assay and the levels of cell apoptosis were analyzed using flow cytometric analysis. The results of the present study revealed that the expression levels of miR-23a-3p were significantly upregulated, while the expression levels of BCL2 were significantly downregulated in H2O2-induced HLE-B3 cells compared to untreated control cells. BCL2 was shown to be a target of miR-23a-3p. The miR-23a-3p inhibitor subsequently attenuated H2O2-induced apoptosis and increased the proliferation of HLE-B3 cells, which was partially reversed by siRNA-BCL2. In conclusion, the findings of the current study suggested that the inhib ition of miR-23a-3p may attenuate H2O2-induced cataract formation by targeting BCL2, thus providing a novel therapeutic target for the treatment of patients with cataracts in the clinic.

PMID:33777189 | PMC:PMC7967796 | DOI:10.3892/etm.2021.9853

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Dysregulation of lncRNA SNHG1/miR-145 axis affects the biological function of human carotid artery smooth muscle cells as a mechanism of carotid artery restenosis

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Exp Ther Med. 2021 May;21(5):423. doi: 10.3892/etm.2021.9867. Epub 2021 Feb 25.

ABSTRACT

Carotid angioplasty and stenting have developed into reliable options for patients with carotid stenosis. However, postoperative restenosis remains a serious and unresolved problem. Restenosis is partly caused by the proliferation of vascular smooth muscle cells. As certain long non-coding RNAs (lncRNAs) affect cell proliferation and migration, the present study aimed to investigate them as novel biomarkers for restenosis development and to further reveal the potential underlying mechanisms. The expression of lncRNA small nucleolar RNA host gene 1 (SNHG1) and microRNA145 (miR-145) in human carotid artery smooth muscle cells (hHCtASMCs) was analyzed using reverse transcription-quantitative PCR. In addition, a luciferase reporter assay was performed to investigate the interaction between SNHG1 and miR-145. The effects of the SNHG1/miR-145 axis on the proliferation and migration of hHCtASMCs were evaluated by Cell Counting Kit-8 and Transwell assays. Serum SNHG1 and miR-145 expression levels were increased and decreased, respectively, in patients with restenosis (all P<0.001). High SNHG1 and low miR-145 were identified as risk factors for restenosis onset (all P<0.01). Furthermore, decreasing SNHG1 expression levels in hHCtASMCs inhibited cell proliferation and migration. The luciferase reporter assay and expression results demonstrated that miR-145 may be a target of SNHG1 and mediated the effects of SNHG1 on hHCtASMC proliferation and migration. The results obtained suggested that abnormal expression of SNHG1 and miR-145 may be risk factors for restenosis. The present study revealed that the SNHG1/miR-145 axis regulates hHCtASMC proliferation and migration, indicating its potential for restenosis prevention and treatment.

PMID:33777187 | PMC:PMC7967805 | DOI:10.3892/etm.2021.9867

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The Endonasal Endoscopic Management of Cerebrospinal Fluid Rhinorrhea

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Cureus. 2021 Feb 20;13(2):e13457. doi: 10.7759/cureus.13457.

ABSTRACT

Introduction Cerebrospinal fluid (CSF) rhinorrhea is the result of a bony defect at the skull base with disruption of the arachnoid, dura mater, and sinonasal mucosa that leads to an active CSF leak and flow of clear fluid from the nose. The endoscopic repair of CSF leaks and skull defects have been used by an increasing number of surgeons and is the standard of care for repairing CSF leaks. Materials and methods We conducted a retrospective study of all cases of CSF leaks managed via the endonasal endoscopic approach from 2010 to 2020 at a tertiary referral hospital of King Fahad Specialist Hospital, Dammam (KFSH-D). Results Over 10 years, 61 procedures were performed on a total of 56 patients (average age, 39.9 years) with 26 spontaneous CSF leaks and 30 traumatic CSF leaks. The leak sites were frontal bone in 14% of the cases, the roof of the ethmoid in 25%, the cribrifo rm plate of ethmoid in 39%, and the walls of sphenoid sinus in 21%; multiple site defects were found in eight patients. The defect was localized by high-resolution computed tomography (CT) of the paranasal sinuses and skull base and magnetic resonance imaging (MRI) in all patients. CT cisternography, intrathecal fluorescein injection, and topical application of fluorescein dye were used in patients as required. A combination of free grafts and flaps materials were used in most patients. A middle and inferior turbinate graft was used in 12 patients, a septal cartilage graft in 18 patients, and a pedicled nasoseptal flap in 12 patients. The success rate was 92% after the first closure attempt. A recurrence of CSF leaks was observed in four patients. The mean hospitalization time was 6.5 days. The postoperative follow-up period ranged from one year to 10 years with a mean postoperative follow-up time of three years. Conclusions The endonasal endoscopic approach is the current standard of care for repairing most CSF leaks and skull base defects. We have had an excellent experience with endonasal endoscopic CSF leak repair, with high success rates and low morbidity. Our results support the effectiveness and safety of this technique and should encourage otolaryngologists to apply the procedure in cases of CSF leak.

PMID:33777546 | PMC:PMC7984942 | DOI:10.7759/cureus.13457

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