Bosnian Journal of Basic Medical Sciences (BJBMS)
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Risk factors for recurrent IgA nephropathy after renal transplantation: A meta-analysis
Get PDFRecurrent glomerulonephritis after renal transplantation is the third most common cause of allograft loss, the most frequent of which is associated with IgA nephropathy (IgAN). This study aims to provide a systematic review of the risk factors associated with recurrent IgAN after renal transplantation. We searched English and Chinese databases, including PubMed, Embase, Web of Science, CNKI, and others, and included all case-control studies involving risk factors for recurrent IgAN after renal transplantation from the databases’ establishment to March 2022. Data were analyzed using the Stata 12.0. A total of 20 case–control studies were included in the meta-analysis, with 542 patients with recurrent IgAN and 1385 patients without recurrent IgAN. The results showed that donor age (standardized mean difference [SMD] -0.13 [95% CI -0.26, -0.001]; P = 0.048), patient age at transplantation (SMD -0.41 [95% CI -0.53, -0.29]; P < 0.001), time from diagnosis to end-stage renal disease (SMD -0.42 [95% CI -0.74, -0.10]; P = 0.010), previous transplantation (odds ratio [OR] 1.73 [95% CI 1.06, 2.81]; P = 0.027), living donor (OR 1.86 [95% CI 1.34, 2.58]; P < 0.001), related donor (OR 2.64, [95% CI 1.84, 3.79]; P < 0.001), tacrolimus use (OR 0.71 [95% CI 0.52, 0.98]; P = 0.035), basiliximab use (OR 0.39 [95% CI 0.27, 0.55]; P < 0.001), proteinuria (SMD 0.42 [95% CI 0.13, 0.71]; P = 0.005) and serum IgA level (SMD 0.48 [95% CI 0.27, 0.69]; P < 0.001) were associated with recurrent IgAN after renal transplantation. In general, tacrolimus and basiliximab use were protective factors against recurrent IgAN after renal transplantation, whereas donor age, patient age at transplantation, time from diagnosis to end-stage renal disease, previous transplantation, living donor, related donor, proteinuria, and serum IgA level were risk factors for recurrent IgAN after renal transplantation. Clinical decision making should warrant further consideration of these risk factors
Electrodermal activity and heart rate variability for detection of peripheral abnormalities in type 2 diabetes: A review
Get PDFModern medicine exhibits an upward trend towards non-invasive methods for early detection of disease and long-term monitoring of patients’ health. Diabetes mellitus and its complications are a promising area for implementation of new medical diagnostic devices. One of the most serious complications of diabetes is diabetic foot ulcer. The main causes responsible for diabetic foot ulcer are ischemia caused by peripheral artery disease and diabetic neuropathy caused by polyol pathway-induced oxidative stress. Autonomic neuropathy impairs function of sweat glands, which can be measured by electrodermal activity. On the other hand, autonomic neuropathy leads to changes in heart rate variability, which is used to assess autonomic regulation of the sinoatrial node. Both methods are enough sensitive to detect pathological changes caused by autonomic neuropathy and are promising screening methods for early diagnosis of diabetic neuropathy, which could prevent the onset of diabetic ulcer
Molecular basis and therapeutic targets in prostate cancer: A comprehensive review
Get PDFProstate cancer is one of the most significant causes of morbidity and mortality in male patients. The incidence increases with age, and it is higher among African Americans. The occurrence of prostate cancer is associated with many risk factors, including genetic and hereditary predisposition. The most common genetic syndromes associated with prostate cancer risk are BRCA-associated hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. Local-regional therapy, i.e., surgery is beneficial in early-stage prostate cancer management. Advanced and metastatic prostate cancers require systemic therapies, including hormonal inhibition, chemotherapy, and targeted agents. Most prostate cancers can be treated by targeting the androgen-receptor pathway and decreasing androgen production or binding to androgen receptors (AR). Castration-resistant prostate cancer (CRPC) usually involves the PI3K/AKT/mTOR pathway and requires targeted therapy. Specific molecular therapy can target mutated cell lines in which DNA defect repair is altered, caused by mutations of BRCA2, partner and localizer of BRCA2 (PALB2), and phosphatase and tensin homolog (PTEN) or the transmembrane protease serine 2-ERG (TMPRSS2-ERG) fusion. Most benefits were demonstrated in cyclin dependent-kinase 12 (CDK12) mutated cell lines when treated with anti-programmed cell death protein 1 (PD1) therapy. Therapies targeting p53 and AKT are the subject of ongoing clinical trials. Many genetic defects are listed as diagnostic, prognostic, and clinically actionable markers in prostate cancer. Androgen receptor splice variant 7 (AR-V7) is an important oncogenic driver and an early diagnostic and prognostic marker, as well as a therapeutic target in hormone-resistant CRPC. This review summarizes the pathophysiological mechanisms and available targeted therapies for prostate cancer
Sacituzumab govitecan expands its therapeutic spectrum among breast cancer subtypes
Get PDFAntibody-drug conjugates (ADCs) are novel, highly potent drugs composed of a small molecule of an anticancer drug (payload)attached to humanized antibody recognizing an epitope on the surface of cancer cells. ADCs are rapidly expanding in the oncology field. By 2022, >180 ADC-based clinical trials have been conducted [1]. Most of these clinical trials are in phases I or II [1]. Several ADCs have been approved and used for the treatment of various malignancies (e.g., brentuximab vedotin (BV) for the treatment of CD30+ lymphomas, trastuzumab emtansine (T-DM1) for advanced/metastatic/or early-stage high-risk HER2-positive breast cancer with residual disease after neoadjuvant treatment) [2].
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S1P/S1PR signaling pathway advancements in autoimmune diseases
Get PDFSphingosine-1-phosphate (S1P) is a versatile sphingolipid that is generated through the phosphorylation of sphingosine by sphingosine kinase (SPHK). S1P exerts its functional effects by binding to the G protein-coupled S1P receptor (S1PR). This lipid mediator plays a pivotal role in various cellular activities. The S1P/S1PR signaling pathway is implicated in the pathogenesis of immune-mediated diseases, significantly contributing to the functioning of the immune system. It plays a crucial role in diverse physiological and pathophysiological processes, including cell survival, proliferation, migration, immune cell recruitment, synthesis of inflammatory mediators, and the formation of lymphatic and blood vessels. However, the full extent of the involvement of this signaling pathway in the development of autoimmune diseases remains to be fully elucidated. Therefore, this study aims to comprehensively review recent research on the S1P/S1PR axis in diseases related to autoimmunity
Videolaryngoscopy as a primary intubation modality in obstetrics: A narrative review of current evidence
Get PDFPregnancy-related physiologic and anatomic changes affect oxygenation and airway management, and it is widely believed that airway difficulty may be more common in obstetric patients as a result. In addition, most obstetric intubations are performed under emergency conditions, and preoperative airway assessment poorly predicts airway management outcomes. These considerations necessitate special protocols for airway care in the obstetric population, and the evolution of the videolaryngoscope represents one of the most important milestones in recent decades. However, recommendations for the use of videolaryngoscopy in obstetrics remain unclear. A considerable body of evidence affirms that videolaryngoscopy improves laryngeal visualisation, increases first-attempt and overall intubation success rates, shortens intubation time, and facilitates team communication and education. In contrast, a significant number of studies have also reported conflicting results regarding comparative clinical outcomes and have highlighted other limitations regarding the adoption of videolaryngoscopy in routine obstetric care. Nevertheless, considering the peculiarities of obstetric intubation, the Macintosh-style videolaryngoscope can be suggested as the primary intubation device as it offers the benefits of both videolaryngoscopy and direct laryngoscopy. However, more rigorous evidence is needed to clarify the current blind spots and controversies regarding the role of videolaryngoscopy in obstetrics
Comparison of the clinical features and long-term prognosis of gallbladder neuroendocrine carcinoma versus gallbladder adenocarcinoma: A propensity score-matched analysis
Get PDFGallbladder neuroendocrine carcinoma (GBNEC) is rare and characterized by a low degree of tumor differentiation. The clinical features of GBNEC versus gallbladder adenocarcinoma (GBADC) remain a subject of debate. A total of 201 GBADC and 36 GBNEC cases that underwent surgery resection between January 2010 and 2022 at the Department of Biliary Surgery, West China Hospital, Sichuan University were included. A 1:1 propensity score matching (PSM) was performed based on seven predefined variables: age, sex, the American Joint Committee on Cancer (AJCC) stage, resection status, perineural invasion (PNI), lymphovascular invasion (LVI), and degree of tumor differentiation. Compared with GBADC, GBNEC patients were younger (median age 56.0 vs 64.0 years; P = 0.001), and more patients presented with advanced stages of tumor (P = 0.003). Patients with GBNEC also had a higher rate of PNI (55.6% vs 22.4%; P < 0.001), and LVI (63.9% vs 45.80%; P = 0.658). Before PSM, GBNEC patients had inferior prognoses compared with GBADC patients with a shorter median overall survival (mOS) (15.02 vs 20.11 months; P = 0.0028) and a shorter median recurrence-free survival (mRFS) (10.30 vs 15.17 months; P = 0.0028). However, after PSM analyses, there were no differences in OS (mOS 18.6 vs 18.0 months; P=0.24) or RFS (mRFS 10.98 vs 12.02 months; P = 0.39) between the GBNEC and GBADC cases. After multivariate analysis, tumor diagnosis (GBNEC vs GBADC) was not identified as an independent risk factor for shorter RFS (P = 0.506) or OS (P = 0.731). Unfavorable pathological features, including advanced AJCC tumor stages, poor differentiation, presence of LVI, and positive resection margins (all P < 0.05), were independent risk factors for inferior OS and RFS. GBNEC is difficult to diagnose early and has a prognosis comparable to stage-matched poorly differentiated GBADC. Tumor diagnosis (either GBADC or GBNEC) was not an independent risk factor for the patient’s OS. Unfavorable pathological features of the neoplasm are the main determinants
Cell division cycle 42 effector protein 4 inhibits prostate cancer progression by suppressing ERK signaling pathway
Get PDFProstate cancer (PCa) is the most common malignancy among men worldwide. The cell division cycle 42 effector protein 4 (CDC42EP4) functions downstream of CDC42, yet its role and molecular mechanisms in PCa remain unexplored. This study aimed to elucidate the role of CDC42EP4 in the progression of PCa and its underlying mechanisms. Bioinformatical analysis indicated that CDC42EP4 expression was significantly lower in PCa tissue compared to normal prostate tissue. Cellular phenotyping analysis suggested that CDC42EP4 markedly inhibited the proliferation, migration, and invasion of PCa cells. Xenograft tumor assays further demonstrated that CDC42EP4 suppressed the growth of PCa cells in vivo. Mechanistically, the study established that CDC42EP4 inhibited the ERK pathway in PCa cells. Additionally, the ERK pathway inhibitor PD0325901 was employed, revealing that PD0325901 significantly nullified the effects of CDC42EP4 on PCa cell proliferation, migration, and invasion. Collectively, our findings demonstrate that CDC42EP4 acts as a critical tumor suppressor gene, inhibiting PCa cell proliferation, migration, and invasion through the ERK pathway, thereby presenting potential targets for PCa therapy
Methylation pattern of caveolin-1 in prostate cancer as potential cfDNA biomarker
Get PDFHigh prevalence and mortality of prostate cancer (PCa) are well known global health issues. Novel biomarkers for better identifying patients with PCa are the subject of extensive research. Prostate specific antigen (PSA) shows low specificity in screening and diagnostics, leading to unnecessary biopsies and health costs. Eighty patients with PCa and benign prostate hyperplasia (BPH) were included in the study. We analyzed CAV1 gene expression and methylation in tissue. CAV1 cfDNA methylation from blood and seminal plasma was accessed as a potential PCa biomarker. Although methylation in blood plasma did not differ between PCa and BPH patients, methylation in seminal plasma showed better PCa biomarker performances than tPSA (AUC 0.63 vs. AUC 0.52). Discrimination of BPH and Gleason grade group 1 PCa patients from patients with higher Gleason grade groups revealed very good performance as well (AUC 0.72). CAV1 methylation is useful biomarker with potential for further seminal plasma cfDNA research, but its diagnostic accuracy should be improved, as well as general knowledge about cfDNA in seminal plasma
Prognostic and predictive significance of VEGF, CD31, and Ang-1 in patients with metastatic clear cell renal cell carcinoma treated with first-line sunitinib
Get PDFThe most common type of renal cell carcinoma (RCC) is clear cell renal cell carcinoma (ccRCC), which has a high metastatic potential. Even though the International Metastatic RCC Database Consortium (IMDC) risk model is conventionally utilized for selection and stratification of patients with metastatic RCC (mRCC), there remains an unmet demand for novel prognostic and predictive markers. The goal of this study was to analyze the expression of Vascular endothelial growth factor (VEGF), Cluster of Differentiation 31 (CD31) to determine microvessel density, and Angiopoietin-1 (Ang-1) in primary kidney tumors, as well as their predictive and prognostic value in patients with metastatic ccRCC (mccRCC) who were treated with first-line sunitinib. The study included 35 mccRCC patients who were treated with first-line sunitinib in period between 2009 and 2019. Immunofluorescence was used to examine biomarker expression in tissue specimens of the primary tumor and surrounding normal kidney tissue. Median disease-free survival (DFS) was longer in patients with negative and low tumor VEGF score than in patients with medium tumor VEGF score (p=0.02). Those with low tumor CD31 expression had a longer median DFS than patients with high tumor CD31 expression (p=0.019). There was no correlation between Ang-1 expression and DFS. The expression of biomarkers in normal kidney tissue was significantly lower than in tumor tissue (p<0.001). In conclusion, higher VEGF scores and greater CD31 expression were associated with longer DFS, but neither of these biomarkers correlated with progression-free survival or overall survival