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.

Combined miRNA and SERS urine liquid biopsy for the point-of-care diagnosis and molecular stratification of bladder cancer.

BACKGROUND: Bladder cancer (BC) has the highest per-patient cost of all cancer types. Hence, we aim to develop a non-invasive, point-of-care tool for the diagnostic and molecular stratification of patients with BC based on combined microRNAs (miRNAs) and surface-enhanced Raman spectroscopy (SERS) profiling of urine. METHODS: Next-generation sequencing of the whole miRNome and SERS profiling were performed on urine samples collected from 15 patients with BC and 16 control subjects (CTRLs). A retrospective cohort (BC = 66 and CTRL = 50) and RT-qPCR were used to confirm the selected differently expressed miRNAs. Diagnostic accuracy was assessed using machine learning algorithms (logistic regression, naïve Bayes, and random forest), which were trained to discriminate between BC and CTRL, using as input either miRNAs, SERS, or both. The molecular stratification of BC based on miRNA and SERS profiling was performed to discriminate between high-grade and low-grade tumors and between luminal and basal types. RESULTS: Combining SERS data with three differentially expressed miRNAs (miR-34a-5p, miR-205-3p, miR-210-3p) yielded an Area Under the Curve (AUC) of 0.92 ± 0.06 in discriminating between BC and CTRL, an accuracy which was superior either to miRNAs (AUC = 0.84 ± 0.03) or SERS data (AUC = 0.84 ± 0.05) individually. When evaluating the classification accuracy for luminal and basal BC, the combination of miRNAs and SERS profiling averaged an AUC of 0.95 ± 0.03 across the three machine learning algorithms, again better than miRNA (AUC = 0.89 ± 0.04) or SERS (AUC = 0.92 ± 0.05) individually, although SERS alone performed better in terms of classification accuracy. CONCLUSION: miRNA profiling synergizes with SERS profiling for point-of-care diagnostic and molecular stratification of BC. By combining the two liquid biopsy methods, a clinically relevant tool that can aid BC patients is envisaged.

SERS Liquid Biopsy Profiling of Serum for the Diagnosis of Kidney Cancer.

Renal cancer (RC) represents 3% of all cancers, with a 2% annual increase in incidence worldwide, opening the discussion about the need for screening. However, no established screening tool currently exists for RC. To tackle this issue, we assessed surface-enhanced Raman scattering (SERS) profiling of serum as a liquid biopsy strategy to detect renal cell carcinoma (RCC), the most prevalent histologic subtype of RC. Thus, serum samples were collected from 23 patients with RCC and 27 controls (CTRL) presenting with a benign urological pathology such as lithiasis or benign prostatic hypertrophy. SERS profiling of deproteinized serum yielded SERS band spectra attributed mainly to purine metabolites, which exhibited higher intensities in the RCC group, and Raman bands of carotenoids, which exhibited lower intensities in the RCC group. Principal component analysis (PCA) of the SERS spectra showed a tendency for the unsupervised clustering of the two groups. Next, three machine learning algorithms (random forest, kNN, naïve Bayes) were implemented as supervised classification algorithms for achieving discrimination between the RCC and CTRL groups, yielding an AUC of 0.78 for random forest, 0.78 for kNN, and 0.76 for naïve Bayes (average AUC 0.77 ± 0.01). The present study highlights the potential of SERS liquid biopsy as a diagnostic and screening strategy for RCC. Further studies involving large cohorts and other urologic malignancies as controls are needed to validate the proposed SERS approach.

Renal Tumors in Young Adults: Is Preoperative Computer Tomography Imaging Suggestive for the Nature of the Tumors?

Renal cell carcinoma (RCC) accounts for 2-3% of all adult malignant neoplasms and is even rarer in patients under 45 years old. Clear-cell carcinoma represents most of the pathological subtypes. Our study aimed to investigate the association between preoperative computer tomography imagistic evaluation and histopathological diagnosis of renal tumors in young adults. Patients younger than 45 years old with renal tumors who were referred for medical treatment at the Clinical Institute of Urology and Renal Transplantation Cluj-Napoca from 2012 to 2019 were considered eligible for the study. Medical charts were retrospectively reviewed, and patients with complete data regarding preoperative diagnostic, histopathological evaluation, and follow-up data, regardless of gender, were included in the study. Sixteen patients younger than 45 years fulfilled all the inclusion criteria and were evaluated. With two exceptions, the evaluated patients were in a T1 and T2 stage, with no vascular invasion or of the adjacent organs. Two-thirds of our patients had a clear-cell renal cell carcinoma. None of our patients fitted in the low complexity surgery category of the R.E.N.A.L. Nephrometry Score and 37.5% of them benefited from partial nephrectomy. Half of the suppositions made based on imaging were concordant with the histopathology report. Fifteen of the patients showed no recurrence during the respective follow-up interval. Computer tomography imaging reports showed on our sample a higher concordance with the histopathological report in the more common subtypes (namely Renal Clear Cell RCC), with typical appearances.

Angle grinder as surgical tool for incarcerated penoscrotal steel ring.

Penile strangulation with concomitant scrotal entrapment by a steel ring is an extremely rare urological emergency that requires immediate intervention. Any delay may lead to irreversible complications. Metal rings increase penile engorgement and are usually associated with an attempt to improve sexual pleasure or to maintain a prolonged erection. The removal of steel rings can be challenging and may require a multidisciplinary approach. We present a unique case report of an 18-year-old male with a penoscrotal steel ring retained for 24 hours that was safely removed using an angle grinder as a surgical tool.

Imaging appearance and role of CEUS of high flow priapism. A case report.

High flow priapism caused by perineal trauma is a relatively rare disorder. Early diagnosis represents a mandatory condition for the therapeutic resolution. Ultrasound examination is affordable and a within reach method for diagnosis also in an emergency context. We present the case of a 56-year-old male patient with traumatic priapism which was subsequently investigated by contrast-enhanced ultrasound and shear wave elastography. This may be one of the first cases presented in the literature.