Bosnian Journal of Basic Medical Sciences (BJBMS)
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Thiersch graft follow-up with narrow band imaging for acquired atresia of the external auditory canal: Canaloplasty with Thiersch graft versus vascularization evaluated with narrow band imaging
Get PDFAcquired atresia of the external ear canal is a narrowing of the external ear canal (EAC) that appears obstructed by fibrous tissue or bone tissue. Acquired atresia has two different phases: wet and dry stage. Computed tomography (CT) scan may show a scan where soft tissue fills EAC. Treatment may be medical and/or surgical. The surgical treatment of choice is represented by canaloplasty with a skin-free flap. To our knowledge, no article has reported data on the analysis of vascularization of acquired atresia of the external ear canal and vascularization of skin flap during follow-up with narrow-band imaging. This study evaluated patients suffering from acquired atresia of the external auditory duct, treated surgically in our Department of Organi di Senso of Sapienza University, from 2017 to 2020. All patients underwent: anamnestic collection, physical examination, CT. Preoperative and postoperative otoendoscopic evaluation (1,3,6 and12 months) was performed with both cold white light endoscopic vision (CWL) and narrowband imaging (NBI). 17 patients were enrolled in the study. Preoperative otoendoscopic examination of WL showed stenosis with a diameter <75% and a tympanic membrane not viewable in all patients. At 12 months of follow-up, 94% of patients had no recurrence of external ear canal stenosis. 88% of patients had normal NBI light vascularization. Our study evaluated how NBI can be a superior method, compared to CWL, to assess the state of the flap and can be relevant in the decision-making process of a re-intervention
Regulatory aspects of biological medicines in Bosnia and Herzegovina
Get PDFThe use of the biological medicines, also called “biologics,” has contributed to the progress of the treatment of many chronic diseases, such as cancer, rheumatoid arthritis, Crohn’s disease, multiple sclerosis, and psoriasis. However, biologicals are expensive for healthcare systems in several countries. Their availability has been a global issue, which has affected many patients that suffer from various diseases. A biosimilar medicine, also called “biosimilar,” is a medicine with similar characteristics in terms of quality, biological activity, safety, and efficacy as the approved original biological medicine, known as “originator biologic.” Biosimilars generate competition within the market because they lower the prices of biologics and thus allow for an increase in patient access. However, there are barriers when it comes to the acceptability rate of biosimilars and how interchangeable they are with the originator biologic. In this review, we present a national regulatory framework for biologics along with its limitations, a system of monitoring the safety profile of biologics, the guideline for interchangeability, and a list of approved and available biologics in Bosnia and Herzegovina. Additionally, recommendations were made here in order to provide opportunities for greater acceptance of biosimilars and better access to biologics. These recommendations include, but are not limited to, strengthening the national regulatory framework for biologics, capacity building, increasing awareness among healthcare providers for reporting adverse drug events and active pharmacovigilance, and better definitions of interchangeability. Finally, awareness among healthcare providers regarding biosimilars and biologics should be raised through continuous education and workshops, and by including this important topic in the graduate and postgraduate curriculum programs in the country
Acceptance, effects, and tolerability in the vaccination process against SARS-CoV-2 among cancer patients in Bosnia and Herzegovina: A single-center cross-sectional study
Get PDFThe SARS-CoV-2 pandemic has been the main public health issue since the end of 2019. The vaccination campaign in Bosnia and Herzegovina started in April 2021, with several vaccines available. Our study aimed to evaluate the acceptance, effects, and tolerability of vaccines against SARS-COV-2 among cancer patients. We conducted a cross-sectional, observational study between 22 October and 30 November 2021, at the Clinic of Oncology, Clinical Center University of Sarajevo. Patients were enrolled during their regular visit to the Clinic of Oncology by agreeing to completean individual paper questionnaire. The study included 1063 patients with malignant diseases, of whom 681 (64.1%) were adequately vaccinated patients. In the study population, 76.9% of patients reported that they did not experience any side effects due to vaccination, while only 0.5% had side effects, causing a delay in their treatment. Among adequately vaccinated patients, there were 40 patients (3.8%) who were infected with SARS-CoV-2 after the second or booster dose of the vaccine. Five patients (0.5%) were hospitalized due to COVID-19 after being adequately vaccinated. The findings of our study suggest that cancer patients have a higher acceptance of vaccines against SARS-CoV-2 than the general population in Bosnia and Herzegovina. Vaccination side effects are tolerable and do not cause major delays in specific cancer treatment. The protective effects of COVID-19 vaccines in the cancer patients presented in our study are comparable to available results of similar studies, which included the general population
Role and significance of c-KIT receptor tyrosine kinase in cancer: A review
Get PDFc-kit is a classical proto-oncogene that encodes a receptor tyrosine kinase (RTK) that responds to stem cell factor (SCF). C-KIT signaling is a critical regulator of cell proliferation, survival, and migration and is implicated in several physiological processes, including pigmentation, hematopoiesis and gut movement. Accumulating evidence suggests that dysregulated c-KIT function, caused by either overexpression or mutations in c-kit, promotes tumor development and progression in various human cancers. In this review, we discuss the most important structural and biological features of c-KIT, as well as insights into the activation of intracellular signaling pathways following SCF binding to this RTK. We then illustrate how different c-kit alterations are associated with specific human cancers and describe recent studies that highlight the contribution of c-KIT to cancer stemness, epithelial-mesenchymal transition and progression to metastatic disease in different experimental models. The impact of tyrosine kinase inhibitors in treating c-KIT-positive tumors and limitations due to their propensity to develop drug resistance are summarized. Finally, we appraise the potential of novel therapeutic approaches targeting c-KIT more selectively while minimizing toxicity to normal tissue
Neural stem cell-conditioned medium ameliorates Aβ25–35-induced damage in SH-SY5Y cells by protecting mitochondrial function
Get PDFInhibition of amyloid β (Aβ)-induced mitochondrial damage is considered crucial for reducing the pathological damage in Alzheimer’s disease (AD). We evaluated the effect of neural stem cell-conditioned medium (NSC-CDM) on Aβ25–35-induced damage in SH-SY5Y cells. An in vitro model of AD was established by treating SH-SY5Y cells with 40 µM Aβ25–35 for 24 h. SH-SY5Y cells were divided into control, Aβ25–35 (40 µM), Aβ25–35 (40 µM) + NSC-CDM, and Aβ25–35 (40 µM) + neural stem cell-complete medium (NSC-CPM) groups. Cell viability was detected by CCK-8 assay. Apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) were detected by flow cytometry. Malondialdehyde content was detected by ELISA assay. Western blot analysis was used to detect cytochrome c release and apoptosis-related proteins. Transmission electron microscopy was used to observe mitochondrial morphology. Cell viability significantly decreased and apoptosis significantly increased in SH-SY5Y cells treated with Aβ25–35, and both effects were rescued by NSC-CDM. In addition, NSC-CDM reduced ROS production and significantly inhibited the reduction of MMP caused by Aβ25–35. Furthermore, NSC-CDM ameliorated Aβ25–35-induced reduction in Bcl-2 expression levels and increased the expression levels of cytochrome c, caspase-9, caspase-3, and Bax. Moreover, Aβ25–35 induced the destruction of mitochondrial ultrastructure and this effect was reversed by NSC-CDM. Collectively, our findings demonstrated the protective effect of NCS-CDM against Aβ25–35-induced SH-SY5Y cell damage and clarified the mechanism of action of Aβ25–35 in terms of mitochondrial maintenance and mitochondria-associated apoptosis signaling pathways, thus providing a theoretical basis for the development of novel anti-AD treatments
Progress in research on childhood T-cell acute lymphocytic leukemia, Notch1 signaling pathway, and its inhibitors: A review
Get PDFChildhood leukemia is cancer that seriously threatens the life of children in China. Poor sensitivity to chemotherapy and susceptibility to drug resistance are the reasons for the treatment of T-cell acute lymphocytic leukemia (T-ALL) being extremely difficult. Moreover, traditional intensive chemotherapy regimens cause great damage to children. Therefore, it is highly important to search for targeted drugs and develop a precise individualized treatment for child patients. There are activating mutations in the NOTCH1 gene in more than 50% of human T-ALLs and the Notch signaling pathway is involved in the pathogenesis of T-ALL. In this review, we summarize the progress in research on T-ALL and Notch1 signaling pathway inhibitors to provide a theoretical basis for the clinical treatment of T-ALL
Safety and effectiveness of new embolization microspheres SCBRM for intermediate-stage hepatocellular carcinoma: A feasibility study
Get PDFTransarterial chemoembolization (TACE) is, currently, the recommended treatment for hepatocellular carcinoma (HCC). However, long-term chemoembolization triggers the inflammatory response and may lead to postembolization syndrome (PES). Although several types of degradable microspheres have been developed to reduce drug toxicity and PES incidence, the clinical outcomes remain unsatisfactory. Previously, we have developed a new type of spherical, calibrated, biodegradable, radiopaque microspheres (SCBRM) and demonstrated their safety and efficacy in a pig model. Thus, the goal of this feasibility study was to determine the clinical safety and efficacy of the new SCBRM in intermediate-stage HCC patients. In this study, 12 intermediate-stage HCC patients underwent TACE using SCBRM with a calibrated size of 100–250 μm. The disease control rates at 1 month and 3 months after TACE-SCBRM treatment were 100% and 75.0%, respectively. The objective response rates at 1 month and 3 months after treatment were 66.7% and 58.3%, respectively. Very few adverse events were observed with one patient developing nausea. One day after the treatment, alanine aminotransferase, alanine aminotransferase, and total bilirubin levels were slightly elevated in the patients, but all returned to baseline on day 7. The median and mean overall survival times were 33 months (interquartile range, 12.8–42.0) and 29.2 ± 14.3 months, respectively. The 1-year and 2-year survival rates were 91.7% and 58.3%, respectively. In conclusion, TACE with the new SCBRM microspheres is clinically safe and effective, and it represents a promising approach in the management of intermediate-stage HCC
Pharmacogenomics biomarkers for personalized methadone maintenance treatment: The mechanism and its potential use
Get PDFMethadone has a wide pharmacokinetic interindividual variability, resulting in unpredicted treatment response. Pharmacogenomic biomarkers seem promising for personalized methadone maintenance treatment. The evidence supports the use of ABCB1 single-nucleotide polymorphism (SNP) 1236C>T with genotypes C/T or C/C (Jewish) and haplotypes AGCTT carrier, AGCGC heterozygote, or non-carrier (Caucasian), which have a predicted lower methadone dose requirement. In contrast, ABCB1 SNP 1236C>T with genotype T/T (Jewish); haplotypes AGCGC homozygote, AGCTT non-carrier (Caucasian), and ABCB1 3435C>T variant carrier; and haplotypes CGT, TTC, and TGT (Han Chinese) have a predicted higher methadone dose. For methadone plasma levels, ABCB1 diplotype non-CGC/TTT (Malay) predicted lower, and diplotype CGC/TTT (Malay), 3435C>T allelic carrier, haplotypes (CGT, TTC, TGT) (Han Chinese) predicted higher methadone levels. In terms of metabolism biomarkers, a lower methadone requirement was related to carriers of CYP2B6 genotypes *4(G/G) and *9(T/T) among Jewish patients, CYP2B6*9 genotype (T/T) and haplotypes (TA/TG); and CYP2C19 (*2/*2,*2/*3, and *3/*3; Han Chinese). Higher methadone dose was observed in CYP2C19*1 allelic carriers (Han Chinese) and CYP2D6 ultrarapid metabolizer (Caucasian). Lower methadone levels were reported in CYP2B6 SNPs, haplotypes TTT, and AGATAA (Han Chinese), CYP2C19 genotype *1/*1 (Han Chinese), allelic carrier *1xN (Caucasian), and CYP3A4 genotype *1/*1 (Caucasian). Carriers of CYP2B6 genotype *6/*6 (Caucasian), CYP2B6 haplotypes ATGCAG and ATGCTG (Han Chinese), and CYP3A4 genotype *1/*1B (Caucasian) had predicted higher methadone plasma levels. Specific pharmacokinetics biomarkers have potential uses for personalized methadone treatment in specific populations
Tranexamic acid is associated with decreased transfusion, hospital length of stay, and hospital cost in simultaneous bilateral total knee arthroplasty
Get PDFTranexamic acid (TXA) reduces blood loss and transfusion rates in unilateral total knee arthroplasty (TKA), but there is limited data regarding its efficacy in bilateral TKA. This study reports the impact TXA has on clinical outcomes and hospital cost of care in simultaneous, primary bilateral TKA. The 449 patients were retrospectively reviewed. Primary outcomes included the rates of allogeneic and autologous blood transfusion. Secondary outcomes included hospital length of stay (HLOS), post-hospital discharge disposition, 30-day thromboembolic events (TEE), and mean hospital cost of care. Total direct medical costs were obtained from an institutional research database and adjusted to nationally representative unit costs in 2013 inflation-adjusted dollars. Our study revealed that in patients undergoing simultaneous bilateral TKA, TXA use was associated with reduced allogeneic (OR 0.181, 95% CI 0.090-0.366, p < 0.001) and combined allogeneic and autologous transfusion rates (OR 0.451, 95% CI 0.235-0.865, p = 0.017). TXA was associated with a HLOS reduction of 0.9 days (β-coefficient −0.582, 95% CI −1.008-−0.156, p = 0.008), an increased likelihood of hospital discharge over skilled nursing facility (SNF) (OR 2.25, 95% CI 1.117-4.531, p = 0.023) and reduced total hospital cost of care by 6.45% (p < 0.001), room and board costs by 11.76% (p < 0.001), and transfusion costs by 81.65% (p < 0.001). In conclusion, TXA use in bilateral TKA is associated with lower blood transfusion rates, reduced hospital length of stay, reduced cost of hospital care and skilled nursing facility avoidance
Development and validation of prognostic nomogram for lung cancer patients below the age of 45 years
Get PDFThis study aimed to establish a nomogram for the prognostic prediction of patients with early-onset lung cancer (EOLC) in both overall survival (OS) and cancer-specific survival (CSS). EOLC patients diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and further divided into training and validation sets randomly. The prognostic nomogram for predicting 3-, 5- and 10-years OS and CSS was established based on the relative clinical variables determined by the multivariate Cox analysis results. Furthermore, the predictive performance of nomogram was assessed by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve. A total of 1,822 EOLC patients were selected and randomized into a training cohort (1,275, 70%) and a validation cohort (547, 30%). The nomograms were established based on the statistical results of Cox analysis. In training set, the C-indexes for OS and CSS prediction were 0.797 (95% confidence interval [CI]: 0.773-0.818) and 0.794 (95%CI:0.771-0.816). Significant agreement in the calibration curves was noticed in the nomogram models. The results of ROC and DCA indicated nomograms possessed better predict performance compared with TNM-stage and SEER-stage. And the area under the curve (AUC) of the nomogram for OS and CSS prediction in ROC analysis were 0.766 (95%CI:0.745-0.787) and 0.782 (95%CI:0.760-0.804) respectively. The prognostic nomogram provided an accurate prediction of 3-, 5-, and 10-year OS and CSS of EOLC patients which contributed clinicians to optimize individualized treatment plans.