The Use of Machine Learning Algorithms and the Mass Spectrometry Lipidomic Profile of Serum for the Evaluation of Tacrolimus Exposure and Toxicity in Kidney Transplant Recipients.

Tacrolimus has a narrow therapeutic window; a whole-blood trough target concentration of between 5 and 8 ng/mL is considered a safe level for stable kidney transplant recipients. Tacrolimus serum levels must be closely monitored to obtain a balance between maximizing efficacy and minimizing dose-related toxic effects. Currently, there is no specific tacrolimus toxicity biomarker except a graft biopsy. Our study aimed to identify specific serum metabolites correlated with tacrolinemia levels using serum high-precision liquid chromatography-mass spectrometry and standard laboratory evaluation. Three machine learning algorithms were used (Naïve Bayes, logistic regression, and Random Forest) in 19 patients with high tacrolinemia (8 ng/mL) and 23 patients with low tacrolinemia (5 ng/mL). Using a selected panel of five lipid metabolites (phosphatidylserine, phosphatidylglycerol, phosphatidylethanolamine, arachidyl palmitoleate, and ceramide), Mg2+, and uric acid, all three machine learning algorithms yielded excellent classification accuracies between the two groups. The highest classification accuracy was obtained by Naïve Bayes, with an area under the curve of 0.799 and a classification accuracy of 0.756. Our results show that using our identified five lipid metabolites combined with Mg2+ and uric acid serum levels may provide a novel tool for diagnosing tacrolimus toxicity in kidney transplant recipients. Further validation with targeted MS and biopsy-proven TAC toxicity is needed.

Clinical impact of echocardiography parameters and molecular biomarkers in heart failure: Correlation of ACE2 and MCP-1 polymorphisms with echocardiography parameters: A comparative study.

Heart failure is still the leading cause of hospitalization in patients over 65 years of age and is defined as a multifactorial pathology which involves environmental factors and also genetic predispositions. The aim of the present study was to evaluate a possible correlation between single nucleotide polymorphisms (SNPs) of angiotensin converting enzyme 2 (ACE2) and monocyte chemoattractant protein-1 (MCP-1) genes and cardiac remodeling in Caucasian patients diagnosed with heart failure. Our comparative translational research study included 116 patients diagnosed with heart failure and was carried out in Cluj-Napoca, Romania between September 2017 and March 2019. Three SNPs, namely rs4646156, rs4646174 and rs1024611, were genotyped using a Taqman real-time PCR technique. Our results showed that carriers of the AA genotype for ACE2 rs4646156 had a significant dilatation of the left ventricle (LV) with signs of LV hypertrophy (LVH), while TT carriers had a significant left atrial dilatation. For ACE2 rs4646174, homozygotes for the C allele presented a dilated LV with signs of LVH with statistical significance and had a tendency towards a lower ejection fraction. MCP-1 rs1024611 AA variant carriers had a significant LVH in the dominant model. In conclusion, our study showed a strong association between echocardiographic parameters of cardiac remodeling and SNPs rs4646156, rs4646174 of ACE2 and rs1024611 of MCP-1.

Health Related Quality of life in bladder cancer. Current approach and future perspectives.

Bladder cancer is a real health problem due to its increased incidence, high recurrence rate and the fact that usually it is detected in advanced stages with limited number of diagnostic tools and different therapy response rates to current therapeutic strategies. Because of these issues we must develop screening programs and sensitive diagnostic strategies capable of detecting the disease during its early stages but also for characterizing evolution, prognosis and therapeutic response. Issues of great importance are those related to health quality of life of patients from the moment of diagnosis till the use of existing therapeutic approaches. This paper reviews some facets of life quality in patients diagnosed with bladder cancer stressing upon some proposed questionnaires and some new cell and molecular biology and genomic acquisitions (molecular biomarkers) that may become indicators of prognosis, therapeutic response and life quality but also essential tools in guiding therapeutic strategies.

Novel non invasive diagnostic strategies in bladder cancer.

Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, -145, -222, -210, -10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population.

Clinical and pathological implications of miRNA in bladder cancer.

MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20-22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer.

Hyperechogenic liver lesion.

Current paper focuses on an ultrasonography image representing a hyperechogenic liver lesion that appeared in less than a year time in a patient with clinical alarm signs. There are also described the steps for the final diagnosis, that proved to be geographical map steatosis and possible differential diagnoses together with brief literature correlations.