Urinary peptidomic liquid biopsy for non-invasive differential diagnosis of chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Specific urinary peptides hold information on disease pathophysiology, which, in combination with artificial intelligence, could enable non-invasive assessment of chronic kidney disease (CKD) aetiology. Existing approaches are generally specific for the diagnosis of single aetiologies. We present the development of models able to simultaneously distinguish and spatially visualize multiple CKD aetiologies. METHODS: The urinary peptide data of 1850 healthy control (HC) and CKD [diabetic kidney disease (DKD), immunoglobulin A nephropathy (IgAN) and vasculitis] participants were extracted from the Human Urinary Proteome Database. Uniform manifold approximation and projection (UMAP) coupled to a support vector machine algorithm was used to generate multi-peptide models to perform binary (DKD, HC) and multiclass (DKD, HC, IgAN, vasculitis) classifications. This pipeline was compared with the current state-of-the-art single-aetiology CKD urinary peptide models. RESULTS: In an independent test set, the developed models achieved 90.35% and 70.13% overall predictive accuracies, respectively, for the binary and the multiclass classifications. Omitting the UMAP step led to improved predictive accuracies (96.14% and 85.06%, respectively). As expected, the HC class was distinguished with the highest accuracy. The different classes displayed a tendency to form distinct clusters in the 3D space based on their disease state. CONCLUSION: Urinary peptide data present an effective basis for CKD aetiology differentiation using machine learning models. Although adding the UMAP step to the models did not improve prediction accuracy, it may provide a unique visualization advantage. Additional studies are warranted to further validate the pipeline's clinical potential as well as to expand it to other CKD aetiologies and also other diseases.

A novel microneedle device for controlled and reliable liquid biopsy of the human inner ear.

Sensorineural hearing loss is the most common sensory deficit worldwide, yet our understanding of the underlying pathophysiology is limited by the challenges of access to the inner ear in a safe and reliable manner. We present a novel microneedle device for trans-round window membrane liquid biopsy, which utilizes controlled depth of perforation and microliter aspiration control to safely biopsy fluids of the inner ear. Of eleven devices tested in fresh frozen human temporal bones, seven demonstrated alignment between electrical, visual and tactile detection of round window membrane perforation, and nine were successful in aspiration of meaningful diagnostic samples from the perilymphatic space. Purity of the average perilymph sample was 69% for a 5 µL sample volume, equivalent to 3.5 µL attributable to perilymph. Diagnostic success was shown both by transmastoid facial recess and transcanal tympanotomy approach. This device can enable new advances in the understanding of inner ear pathology, and brings us one step closer to liquid biopsy of the inner ear becoming a routine part of clinical care.

Comparison of cytological adequacy and pain scale score in ultrasound-guided fine-needle aspiration of solid thyroid nodules for liquid-based cytology with with 23- and 25-gauge needles: a single-center prospective study.

In ultrasound (US)-guided fine-needle aspiration (FNA) of solid thyroid nodules (STN) using liquid-based cytology (LBC), the most appropriate needle size for LBC remains unclear. This study compared the cytological adequacy and complications associated with using 23- and 25-gauge needles in US-guided FNA of STNs using LBC. US-guided FNA was performed in consecutive patients by one radiologist to diagnose STNs ≥ 5 mm in the largest diameter. The one-sampling technique through a single needle puncture and multiple to-and-fro needle motions was used in each patient. The 23- and 25-guage needles were used consecutively each day. After FNA, the pain and complications experienced by each patient were investigated by a nurse, who was blinded to the information of needle gauge used. A cytopathologist retrospectively analyzed the cytological adequacy and cellularity of the cases. Of the 99 STNs, eight (8.1%) exhibited inadequate cytology (4 each with 23- and 25-gauge needles). The rate of cytological adequacy was not statistically different between the groups (p = 0.631). The mean pain scale values with 23- and 25-gauge needles were 2.1 ± 1.3 and 1.6 ± 1.3, respectively (p = 0.135). There were no significant complications in either group. In conclusion, both 23- and 25-gauge needles are useful in LBC because cytological adequacy and complications were not statistically different with both sizes of the needles.