The relationship between patients' kidney stone type and demographics in Israel: analysis of 10 K patients.

PURPOSE: To analyze urinary stone composition in Israel and assess the effects of key demographic parameters (gender, age, socioeconomic status, ethnicity, medical history and geographic region) on stone composition. METHODS: A retrospective review was conducted of stone analysis of 10,633 patients from an HMO Israeli database analyzed by a central laboratory from 2014 to 2019 and subjected to Fourier-transform infrared spectroscopy. Associations between stone composition and different demographic parameters were determined using the Chi-square test. RESULTS: Calcium oxalate (CaOx) monohydrate accounted for 51.9% of the stones. Of the total sample, 5776 stones had one single component (54%), whereas 4857 (46%) had mixed components. Men had a higher frequency of CaOx stones (89.6% vs. 85.6%), whereas women had a higher frequency of calcium phosphate, infection, and cystine stones (27.2%, 17.7%, and 0.9% vs. 17.2%, 7.5%, and 0.5%, respectively). Cystine stones were more abundant in Arabs (1.2% vs. 0.5% in the Jewish population). Lower socioeconomic status was associated with a higher prevalence of calcium phosphate, uric acid, and infection stones and a lower prevalence of CaOx stones. Uric acid stones were associated with medical conditions such as diabetes, hypertension, ischemic heart disease, and obesity (28.3%, 24.9%, 25.7%, and 22.6% vs. 9.6%, 8.4%, 12.3%, and 10.3%, respectively). CONCLUSIONS: Stone types were highly influenced by patients' demographics. COM was the most common stone component in either pure or complex form. UA stone prevalence was found to increase with age and was associated with medical conditions such as diabetes, hypertension, ischemic heart disease, and obesity.

The effect of calcium phosphate ion clusters in enhancing enamel conditions versus Duraphat and Icon.

This study aimed to evaluate and compare the remineralisation, mechanical, anti-aging, acid resistance and antibacterial properties of calcium phosphate ion clusters (CPICs) materials with those of Duraphat and Icon. The remineralisation and mechanical properties were investigated using scanning electron microscopy, Fourier-transform infrared (FTIR) spectroscopy and nanoindentation. CPICs induced epitaxial crystal growth on the enamel surface, where the regrown enamel-like apatite layers had a similar hardness and elastic modulus to natural enamel (p > 0.05). Acid resistance and anti-aging properties were tested based on ion dissolution and surface roughness. CPICs exhibited similar calcium and phosphate ion dissolution to the control (p > 0.05), and its roughness decreased after thermocycling (p < 0.05), thereby decreasing the risk of enamel surface demineralisation. The minimum inhibitory concentration was 0.1 mg/ml, and the minimum bactericidal concentration ranged from 0.05 to 0.1 mg/ml. Overall, this biomimetic CPICs is a promising alternative to dental demineralisation.

UROLITHIASIS IN FOXES: ASSESSMENT OF 65 UROLITH SUBMISSIONS TO THE MINNESOTA UROLITH CENTER FROM 1981 TO 2021.

This article summarizes urinary stone submissions from foxes in human care to the Minnesota Urolith Center over 40 years. A previous report documented the analysis of uroliths from foxes that were submitted between 1981 and 2007.13 New data compiled from 2008 to 2021 included an additional 38 stones submitted from foxes, totaling 65 fox urolith submissions from 1981 to 2021. Struvite and cystine uroliths were most common, with the remainder comprised of calcium phosphate, calcium oxalate, compound, mixed, or miscellaneous material. Most stones were submitted from male foxes. Seventy-two percent of the stones were urocystoliths, and from 2010 to 2021, most stones were diagnosed antemortem and removed surgically. More than half of the stones were submitted from red foxes (Vulpes vulpes) and fennec foxes (Vulpes zerda). Urolithiasis in foxes may be an underrecognized condition, and data from this study suggest that clinicians should consider routine urinalysis and diagnostic imaging as part of the preventive medicine program for fox species, especially red foxes and fennec foxes.

Velvet antler polypeptide combined with calcium phosphate coating to protect peripheral nerve cells from oxidative stress.

Functionalizing biomaterial substrates with biological signals shows promise in regulating cell behaviors through mimicking cellular microenvironment. Calcium phosphate (CaP) coating is an excellent carrier for immobilizing biological molecules due to its non-toxicity, good biocompatibility, biodegradability, and favorable affinity to plenty of molecules. In this study, we reported the adhesion, the viability and proliferation behaviors after oxidative stress injury of Schwann cells RSC96 on CaP immobilized with the Velvet Antler Peptide (VAP) isolated from velvet antler through coprecipitation process in modified Dulbecco's phosphate-buffered saline (DPBS) containing VAP. This approach provided well retention of functional molecules up to 28 days, and supported the adhesion and proliferation of RSC96 after oxidative stress injury without cytotoxicity. The simple and reproducible method of coprecipitation suggests that CaP is an ideal carrier to functionalize materials with biological molecules for peripheral nerve repair-related applications.

Micro-elemental analysis and characterization of major heavy metals and trace elements in the urinary stones collected from patients living in diverse geographical regions.

In the process of urinary stone formation, several heavy metals and trace elements (HMTE) have been identified among the major constituents of the calculi. The micro-elements within the stones cannot be identified by ordinary laboratory analytical techniques, the latter can only detect the major crystalline component. The objective of the present study was to evaluate the different types of HMTE (no. 22) and their concentrations within the urinary stones. The stone samples were obtained from patients living in different geographical locations (10 countries: 5 Western and 5 non-Western). The number of retrieved stones after open or endoscopic procedures was 1177. The concentrations of the 22 HMTE in the stones were assessed by inductively coupled plasma optical emission spectrometry (ICP-OES). The statistical data were analyzed using Kruskal-Wallis, one-way ANOVA, and SPSS software (version 20). The biochemical stone analysis showed that calcium oxalate was present as a major component in 650 patients (55.2%), calcium phosphate in 317 (26.9%), and uric acid and cystine stones in 210 (17.8%). The analyzed stones showed the presence of HMTE in different concentrations. Significantly higher concentrations of 17 elements (Al, As, Ba, B, Ca, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, S, Se, Sr, and Zn) were noted in all stones. Seven elements (Al, As, Se, Sr, Fe, Zn, and Ni) were present in higher concentrations in calcium-based stones. In comparison, eight elements (Mg, B, Ba, Cd, Se, Pb, Sr, and Zn) in higher concentrations were associated with phosphate-based stones. Both uric acid and cystine stones had a higher concentration of sulfur. The concentrations of HMTE in calcium phosphate stones were higher than in calcium oxalate and uric acid stones. Calculi obtained from patients living in western countries contained higher levels of 13 HMTE (B, Ba, Ca, Cd, Co, Cu, Fe, K, Mg, Mo, P, Pb, and Se) than those in non-western countries. The age of calculi-forming patients from non-western countries was younger than those living in western countries. These results may indicate the role of many significant heavy metals and trace elements in the pathogenesis of urinary stone formation. The types and contents of HMTE within urinary stones differ from one country to another. The conventional stone analysis techniques cannot either identify the stone micro-elements or the concentrations of HMTE, so a specific and additional instrument such as the ICP-OES is necessary. Further research work on the urinary stone micro-elemental structure could lead to a new strategy for the prevention of stone formation and recurrence.

Differential biomolecular recognition by synthetic vs. biologically-derived components in the stone-forming process using 3D microfluidics.

Calcium phosphate (CaP) biomineralization is the hallmark of extra-skeletal tissue calcification and renal calcium stones. Although such a multistep process starts with CaP crystal formation, the mechanism is still poorly understood due to the complexity of the in vivo system and the lack of a suitable approach to simulate a truly in vivo-like environment. Although endogenous proteins and lipids are engaged with CaP crystals in such a biological process of stone formation, most in vitro studies use synthetic materials that can display differential bioreactivity and molecular recognition by the cellular component. Here, we used our in vitro microfluidic (MF) tubular structure, which is the first completely cylindrical platform, with renal tubular cellular microenvironments closest to the functional human kidney tubule, to understand the precise role of biological components in this process. We systematically evaluated the contribution of synthetic and biological components in the stone-forming process in the presence of dynamic microenvironmental cues that originated due to cellular pathophysiology, which are critical for the nucleation, aggregation, and growth of CaP crystals. Our results show that crystal aggregation and growth were enhanced by immunoglobulin G (IgG), which was further inhibited by etidronic acid due to the chelation of extracellular Ca2+. Interestingly, biogenic CaP crystals from mice urine, when applied with cell debris and non-specific protein (bovine serum albumin), exhibited a more discrete crystal growth pattern, compared to exposure to synthetic CaP crystals under similar conditions. Furthermore, proteins found on those calcium crystals from mice urine produced discriminatory effects on crystal-protein attachment. Specifically, such biogenic crystals exhibited enhanced affinity to the proteins inherent to those crystals. More importantly, a physiological comparison of crystal induction in renal tubular cells revealed that biogenic crystals are less effective at producing a sustained rise in cytosolic Ca2+ compared to synthetic crystals, suggesting a milder detrimental effect to downstream signaling. Finally, synthetic crystal-internalized cells induced more oxidative stress, inflammation, and cellular damage compared to the biogenic crystal-internalized cells. Together, these results suggest that the intrinsic nature of biogenically derived components are appropriate to generate the molecular recognition needed for spatiotemporal effects and are critical towards understanding the process of kidney stone formation.

Dietary calcium phosphate strongly impacts gut microbiome changes elicited by inulin and galacto-oligosaccharides consumption.

BACKGROUND: Fructo-oligosaccharides (FOS), inulin, and galacto-oligosaccharides (GOS) are widely recognized prebiotics that profoundly affect the intestinal microbiota, including stimulation of bifidobacteria and lactobacilli, and are reported to elicit several health benefits. The combination of dietary FOS and inulin with calcium phosphate was reported to stimulate commensal Lactobacillus populations and protect the host against pathogenic Enterobacteriaceae, but little is known about the effects of GOS in diets with a different level of calcium phosphate. METHODS: We investigated the microbiome changes elicited by dietary supplementation with GOS or inulin using diets with high (100 mmol/kg) and low (30 mmol/kg) calcium phosphate levels in adult Wistar rats. Rats were acclimatized to the respective experimental diets for 14 days, after which fecal material was collected, DNA was extracted from fecal material, and the V3­V4 region of the bacterial 16S rRNA gene was amplified with PCR, followed by microbial composition analysis. In tandem, the organic acid profiles of the fecal material were analyzed. RESULTS: Feeding rats non-supplemented (no prebiotic-added) diets revealed that diets rich in calcium phosphate favored members of the Firmicutes and increased fecal lactic, succinic, acetic, propionic, and butyric acid levels. In contrast, relatively low dietary calcium phosphate levels promoted the abundance of mucin degrading genera like Akkermansia and Bacteroides, and resulted in increased fecal propionic acid levels and modest increases in lactic and butyric acid levels. Irrespective of the calcium phosphate levels, supplementation with GOS or inulin strongly stimulated Bifidobacterium, while only high calcium phosphate diets increased the endogenous Faecalibaculum populations. CONCLUSIONS: Despite the prebiotic's substantial difference in chemical structure, sugar composition, oligomer size, and the microbial degradation pathway involved in their utilization, inulin and GOS modulated the gut microbiota very similarly, in a manner that strongly depended on the dietary calcium phosphate level. Therefore, our study implies that the collection of detailed diet information including micronutrient balance is necessary to correctly assess diet-driven microbiota analysis. Video Abstract.

Large database study of urinary stone composition in South Korea: Korean Society of Endourology and Robotics (KSER) research series.

PURPOSE: To evaluate the characteristics of urinary stone composition in a Korean population using a large database of stone composition. MATERIALS AND METHODS: From January 1, 2014, to June 30, 2019, a total of 33,078 urinary stone composition data were analyzed. Stone composition was classified into four main groups: calcium oxalate (CaOx), struvite, uric acid (UA), and calcium phosphate (CaP). We examined the relationship between stone composition and sex, age, geographic region, calendar month, and season. RESULTS: The CaOx group (46.41%) was the largest, followed by the struvite group (29.66%), UA group (19.61%), and CaP group (4.32%). The CaOx group tended to decrease with age, but the UA group increased with age. Also, the CaOx group had the highest percentage in summer and the lowest in spring (p<0.001). The struvite and CaP groups had higher percentages of females than males (struvite: 36.6% vs. 25.7%, p<0.001; CaP: 6.2% vs. 3.3%, p<0.001). Conversely, the UA stones were more common in males than in females (24.5% vs. 11.0%, p<0.001). The UA group had the lowest percentage in the capital region (p<0.001). The total male-to-female ratio decreased over time from 1.95:1 in 2014 to 1.67:1 in 2018 (p<0.001). CONCLUSIONS: There were differences for each stone composition in the percentages according to sex, age, geographic region, month, and season. Identifying these differences based on the stone composition is vital for the treatment and prevention of urinary stones.

Identificación endoscópica de la composición de los cálculos urinarios: un estudio del Southeastern Group for Lithiasis Research (SEGUR 2) / Endoscopic identification of urinary stone composition: A study of South Eastern Group for Urolithiasis Research (SEGUR 2)

INTRODUCCIÓN Y OBJETIVOS: Evaluar la capacidad del endourólogo para evaluar la composición del cálculo mediante la observación de imágenes endoscópicas. MATERIALES Y MÉTODOS: Una serie de 20 videoclips de tratamientos endoscópicos de cálculos urinarios que también estaba disponible el resultado de la espectroscopia infrarroja se cargó en un sitio de YouTube accesible solo a miembros del South Eastern Group for Urolithiasis Research (SEGUR), a quienes se les preguntó para identificar la composición de los cálculos. RESULTADOS: Un total de 32 endourólogos de 9 países diferentes participaron en el estudio. El número promedio de detecciones correctas de participantes fue de 7,81 ± 2,68 (1-12). La precisión general fue del 39% (250 de 640 predicciones). Cálculos de dihidrato de oxalato de calcio se han detectado correctamente en el 69,8%, monohidrato de oxalato de calcio en el 41,8%, ácido úrico en el 33,3%, oxalato de calcio/ácido úrico en el 34,3% y cistina en el 78,1%. Las tasas de precisión para estruvita (15,6%), fosfato de calcio (0%) y oxalato de calcio/fosfato de calcio (9,3%) fueron bastante bajas. CONCLUSIONES: La observación del cálculo durante el procedimiento endoscópico no fue confiable para identificar la composición de la mayoría de los cálculos, aunque los cálculos de oxalato de calcio dihidrato y cistina pueden identificarse con buena precisión. Sin embargo, se debe alentar la presentación de fotos o videos de cálculo intacto y su estructura interna para implementar los resultados del análisis de cálculo después de la cirugía. Los endourólogos deben mejorar su capacidad de identificación visual de los diferentes tipos de cálculos

INTRODUCTION AND OBJECTIVES: To assess the surgeon's ability to evaluate the composition of the stone by observation of endoscopic images. MATERIALS AND METHODS: A series of 20 video clips of endoscopic treatments of urinary stones of which was also available the result of infrared spectroscopy was uploaded to a YouTube site accessible only to members of the South Eastern Group for Urolithiasis Research (SEGUR) who were asked to identify the composition of the stones. RESULTS: A total of 32 clinicians from 9 different countries participated in the study. The average number of correct detections of participants was 7.81 ± 2.68 (range 1-12). Overall accuracy was 39% (250 out of 640 predictions). Calcium oxalate dihydrate stones have been correctly detected in 69.8%, calcium oxalate monohydrate in 41.8%, uric acid in 33.3%, calcium oxalate/uric acid in 34.3% and cystine in 78.1%. Precision rates for struvite (15.6%), calcium phosphate (0%) and mixed calcium oxalate/calcium phosphate (9.3%) were quite low. CONCLUSIONS: Observation of the stone during the endoscopic procedure was not reliable to identify the composition of most stones although it gave some information allowing to identify with a good sensitivity calcium oxalate dihydrate and cystine stones. Nevertheless, photo or video reporting of the intact stone and its internal structure could should be encouraged to implement results of still mandatory post-operative stone analysis. Endourologists should improve their ability of visual identification of the different types of stones

Effectiveness of a toothpaste and a serum containing calcium silicate on protecting the enamel after interproximal reduction against demineralization.

To evaluate the effectiveness of a calcium silicate/phosphate fluoridated tooth paste and a serum compared with a toothpaste containing hydroxyapatite on protecting the enamel after interproximal reduction against demineralization. 3 sets of eleven incisors were created. The teeth underwent interproximal enamel reduction (IER) of 0.5 mm. Each set was allocated to one of three groups: (1) Brushing without toothpaste (control group); (2) Vitis toothpaste + Remin Pro; (3) Regenerate toothpaste + Regenerate Serum. The agents were applied three times a day and specimens subjected to demineralization cycles for 30 days. The weight percentages of calcium (Ca) and phosphorous (P) were quantified by X-ray microfluorescence spectroscopy. Surface microhardness measurements and electron scanning microscopy (SEM) observations were made. Ca data and the Ca/P ratio were significantly higher in Group 3 than the other groups (p < 0.017), while P was significantly lower in Group 3 (p < 0.017). No significant differences were found between Groups 1 and 2 (p > 0.017). Group 3 showed significantly higher microhardness values (p < 0.05) than Group 1. No significant differences were found for other comparisons between groups (p < 0.05). SEM images showed less demineralization in Group 3. The application of a calcium silicate/phosphate fluoridated tooth paste (Regenerate advance) and a dual serum (Regenerate advance enamel serum) protect the enamel with interproximal reduction against demineralization. Therefore, this treatment could be used to prevent the dissolution of hydroxyapatite after IER.

Metabolic effects of cholecalciferol supplementation in patients with calcium nephrolithiasis and vitamin D deficiency.

INTRODUCTION: In this paper, we investigated whether cholecalciferol supplementation may increase the risk of stone recurrence in patients with calcium nephrolithiasis and Vitamin D deficiency. METHODS: Thirty-three stone formers (56 ± 17 years old, 12 males) with 25(OH)D < 20 ng/mL were considered. Calcium excretion and urine supersaturation with calcium oxalate (ßCaOx) and brushite (ßbsh) were evaluated, both before and after cholecalciferol supplementation. Values of ß > 1 mean supersaturation. Cholecalciferol was prescribed as oral bolus of 100,000-200,000 IU, followed by weekly (5000-10,000 IU) or monthly (25,000-50,000 IU) doses. Calcium intake varied between 800 and 1000 mg/day. In urine, total nitrogen (TNE) was taken as an index of protein intake, sodium as a marker of dietary intake, and net acid excretion (NAE) as an index of acid-base balance. RESULTS: TNE, sodium, and NAE did not change during the study (p = ns). Compared to baseline values, after cholecalciferol, both serum calcium and phosphate did not vary (p = ns); 25(OH)D increased from 11.8 ± 5.5 to 40.2 ± 12.2 ng/mL (p < 0.01); 1.25(OH)2D increased from 41.6 ± 17.6 to 54 ± 16 pg/mL (p < 0.01); PTH decreased from 75 ± 27.2 to 56.7 ± 21.1 pg/mL (p < 0.01); urinary calcium increased from 2.7 ± 1.5 to 3.6 ± 1.6 mg/Kg b.w. (p < 0.01); ßbsh increased from 0.9 ± 0.7 to 1.3 ± 1.3 (p = 0.02); whereas ßCaOx varied but not significantly. Before cholecalciferol supplementation, 6/33 patients were hypercalciuric (i.e., urine Ca ≥ 4 mg/Kg b.w.) and increased to 13/33 after cholecalciferol supplementation (pX2 = 0.03). CONCLUSIONS: Cholecalciferol supplementation may increase calcium excretion, or reveal an underlying condition of absorptive hypercalciuria. This may increase both urine supersaturation with calcium salts and stone-forming risk.

Assessing the Onset of Calcium Phosphate Nucleation by Hyperpolarized Real-Time NMR.

We report an experimental approach for high-resolution real-time monitoring of transiently formed species occurring during the onset of precipitation of ionic solids from solution. This is made possible by real-time nuclear magnetic resonance (NMR) monitoring using dissolution dynamic nuclear polarization (D-DNP) to amplify signals of functional intermediates and is supported by turbidimetry, cryogenic electron microscopy, and solid-state NMR measurements. D-DNP can provide drastic signal improvements in NMR signal amplitudes, permitting dramatic reductions in acquisition times and thereby enabling us to probe fast interaction kinetics such as those underlying formation of prenucleation species (PNS) that precede solid-liquid phase separation. This experimental strategy allows for investigation of the formation of calcium phosphate (CaP)-based minerals by 31P NMR-a process of substantial industrial, geological, and biological interest. Thus far, many aspects of the mechanisms of CaP nucleation remain unclear due to the absence of experimental methods capable of accessing such processes on sufficiently short time scales. The approach reported here aims to address this by an improved characterization of the initial steps of CaP precipitation, permitting detection of PNS by NMR and determination of their formation rates, exchange dynamics, and sizes. Using D-DNP monitoring, we find that under our conditions (i) in the first 2 s after preparation of oversaturated calcium phosphate solutions, PNS with a hydrodynamic radius of Rh ≈ 1 nm is formed and (ii) following this rapid initial formation, the entire crystallization processes proceed on considerably longer time scales, requiring >20 s to form the final crystal phase.

Association of Impaired Renal Function With Changes in Urinary Mineral Excretion and Stone Composition.

OBJECTIVE: To investigate the effect of kidney function on stone composition and urinary mineral excretion in patients undergoing surgical intervention for nephrolithiasis. METHODS: Using our institutional kidney stone database, we performed a retrospective review of stone patients who underwent surgical intervention between 2004 and 2015. Patients' demographic information, 24-hour urinary mineral excretion, and stone characteristics were reported. The patients' estimated glomerular filtration rates (eGFR) were compared with their stone compositions and 24-hour urine mineral excretions. RESULTS: A statistically significant difference was noted between the groups, with uric acid stones being associated with lower eGFR and calcium phosphate stones associated with higher eGFR. No relationship could be demonstrated between eGFR and calcium oxalate or struvite stones. Patients with lower eGFR also demonstrated a statistically significant association with lower urinary pH as well as lower urinary excretion of calcium and citrate. CONCLUSION: While various factors have been found to play significant roles in kidney stone formation and composition, our findings demonstrate a definite relationship between these and renal function. This paper highlights the fact that renal function evaluation should be considered an important component in the evaluation, counseling, and management of patients with nephrolithiasis.

Selected DNA aptamers as hydroxyapatite affinity reagents.

DNA aptamers were selected for their ability to bind specifically and quickly to crystalline hydroxyapatite (Ca10(PO4)6(OH)2; HAP), the primary mineral component of enamel and bone. Aptamers were found to have an enhanced percent of G-nucleotides and a propensity for forming a G-quadruplex secondary structure. One aptamer was studied in comparison to control sequences and was found to bind with high affinity and at high loading capacity, with enhanced binding kinetics, and with specificity for crystalline HAP material over amorphous calcium phosphate (ACP) and ß-tricalcium phosphate (TCP). The fluorescently-functionalized aptamer was demonstrated to specifically label HAP in a surface binding experiment and suggests the usefulness of this selected aptamer in biomedical or biotechnology fields where the labeling of specific calcium phosphate materials is required.

Relationship of endoscopic lesions of the renal papilla with type of renal stone and 24 h urine analysis.

BACKGROUND: Our purpose was to study the relationship of the 3 different types of endoscopic calcifications of the renal papilla (Randall's plaque, intratubular calcification, papillary crater) with the type of stone and urine analysis. METHODS: This prospective study examined 41 patients (age range: 18 to 80 years) who received retrograde intrarenal surgery (RIRS) for renal lithiasis (mean stone size: 15.3 ± 7.2 mm). The renal papilla injuries were endoscopically classified as Randall's plaque, intratubular calcification, or papillary crater. Calculi were classified as uric acid, calcium oxalate monohydrate (COM; papillary and cavity), calcium oxalate dihydrate (COD), or calcium phosphate (CP). A 24 h urine analysis of calcium, oxalate, citrate, phosphate, and pH was performed in all patients. The relationship of each type of papillary injury with type of stone and urine chemistry was determined. Fisher's exact test and Student's t-test were used to determine the significance of relationships, and a p value below 0.05 was considered significant. RESULTS: The most common injury was tubular calcification (78%), followed by Randall's plaque (58%), and papillary crater (39%). There was no significant relationship of Randall's plaque with type of stone. However, endoscopic intratubular calcification (p = 0.025) and papillary crater (p = 0.041) were more common in patients with COD and CP stones. There were also significant relationships of papillary crater with hypercalciuria (p = 0.036) and hyperoxaluria (p = 0.024), and of Randall's plaque with hypocitraturia (p = 0.005). CONCLUSIONS: There are certain specific relationships between the different types of papillary calcifications that were endoscopically detected with stone chemistry and urine analysis. COD and CP stones were associated with endoscopic tubular calcifications and papillary craters. Hypercalciuria was associated with tubular calcification, and hypocitraturia was associated with Randall's plaque.

Computational fluid dynamics simulation from microCT stacks of commercial biomaterials usable for bone grafting.

Granules of calcium/phosphate biomaterials are used to fill small bone defects in oral and maxilla-facial surgery. Granules of natural (e.g., trabecular bone, coral) or synthetic biomaterials are provided by industry. Small granules can also form of putty. The 3D geometry of granules creates a macroporosity allowing invasion of vascular and bone cells when pores are larger than 300 µm. We analyzed the 3D-porosity of 11 different stacks of biomaterials: Osteopure®, CopiOs®, Bio-Oss®, TCP Dental HP®, KeraOs®, TCH®, Biocoral®, EthOss® and Nanostim®. For each granular biomaterial, two sizes of granules were analyzed: small and large. Microcomputed tomography (microCT) determined porosity and microarchitectural characteristics of the biomaterials stacks. Computational fluid dynamics (CFD), a simulation method, was used on the stacks of microCT images. Stacks of small granules had a much lower permeation and fluid velocity than large granules and the hydraulic tortuosity was increased. Significant correlations were observed between microarchitecture parameters (porosity, mean pore diameter and specific surface) and fluid dynamic parameters. The two putties were associated with low (or absence of) porosity and permeation study revealed a very low (or absence) of flow rate. Stacks of granules represent 3D scaffolds resembling trabecular bone with an interconnected porous microarchitecture. Small granules create pores less than 300 µm in diameter; this induces a low fluid flow rate. CFD simulates the accessibility of body fluids and progenitor cells and confirms that it is depending on the shape and 3D arrangements of granules within a stack. Large granules must be preferred to putties and small granules.

Raman Spectroscopy Reveals That Biochemical Composition of Breast Microcalcifications Correlates with Histopathologic Features.

Breast microcalcifications are a common mammographic finding. Microcalcifications are considered suspicious signs of breast cancer and a breast biopsy is required, however, cancer is diagnosed in only a few patients. Reducing unnecessary biopsies and rapid characterization of breast microcalcifications are unmet clinical needs. In this study, 473 microcalcifications detected on breast biopsy specimens from 56 patients were characterized entirely by Raman mapping and confirmed by X-ray scattering. Microcalcifications from malignant samples were generally more homogeneous, more crystalline, and characterized by a less substituted crystal lattice compared with benign samples. There were significant differences in Raman features corresponding to the phosphate and carbonate bands between the benign and malignant groups. In addition to the heterogeneous composition, the presence of whitlockite specifically emerged as marker of benignity in benign microcalcifications. The whole Raman signature of each microcalcification was then used to build a classification model that distinguishes microcalcifications according to their overall biochemical composition. After validation, microcalcifications found in benign and malignant samples were correctly recognized with 93.5% sensitivity and 80.6% specificity. Finally, microcalcifications identified in malignant biopsies, but located outside the lesion, reported malignant features in 65% of in situ and 98% of invasive cancer cases, respectively, suggesting that the local microenvironment influences microcalcification features. This study confirms that the composition and structural features of microcalcifications correlate with breast pathology and indicates new diagnostic potentialities based on microcalcifications assessment. SIGNIFICANCE: Raman spectroscopy could be a quick and accurate diagnostic tool to precisely characterize and distinguish benign from malignant breast microcalcifications detected on mammography.

Deep learning computer vision algorithm for detecting kidney stone composition.

OBJECTIVES: To assess the recall of a deep learning (DL) method to automatically detect kidney stones composition from digital photographs of stones. MATERIALS AND METHODS: A total of 63 human kidney stones of varied compositions were obtained from a stone laboratory including calcium oxalate monohydrate (COM), uric acid (UA), magnesium ammonium phosphate hexahydrate (MAPH/struvite), calcium hydrogen phosphate dihydrate (CHPD/brushite), and cystine stones. At least two images of the stones, both surface and inner core, were captured on a digital camera for all stones. A deep convolutional neural network (CNN), ResNet-101 (ResNet, Microsoft), was applied as a multi-class classification model, to each image. This model was assessed using leave-one-out cross-validation with the primary outcome being network prediction recall. RESULTS: The composition prediction recall for each composition was as follows: UA 94% (n = 17), COM 90% (n = 21), MAPH/struvite 86% (n = 7), cystine 75% (n = 4), CHPD/brushite 71% (n = 14). The overall weighted recall of the CNNs composition analysis was 85% for the entire cohort. Specificity and precision for each stone type were as follows: UA (97.83%, 94.12%), COM (97.62%, 95%), struvite (91.84%, 71.43%), cystine (98.31%, 75%), and brushite (96.43%, 75%). CONCLUSION: Deep CNNs can be used to identify kidney stone composition from digital photographs with good recall. Future work is needed to see if DL can be used for detecting stone composition during digital endoscopy. This technology may enable integrated endoscopic and laser systems that automatically provide laser settings based on stone composition recognition with the goal to improve surgical efficiency.

Upper urinary tract stone compositions: the role of age and gender

ABSTRACT Objective: To analyze the compositions of upper urinary tract stones and investigate their distributions in different gender and age groups. Materials and Methods: Patients diagnosed with upper urinary tract stone disease between December 2014 and March 2018 were retrospectively reviewed. Patient's age, gender, BMI, comorbidities, stone event characteristics, and compositions were collected, and proportions of stone components in different gender and age groups were analyzed. Results: A total of 1532 stone analyses were performed (992 from males and 540 from females). The mean age was younger in males (p <0.001). Males included more cases with larger BMI, hyperuricemia, and obesity, while females had more urinary tract infections. Multiple components were present in 61.8% of stones. Calcium oxalate (CaOx) (67.0%) was the most common component, followed by uric acid (UA) (11.8%), infection stone (11.4%), calcium phosphate (CaP) (8.0%), cystine (1.1%), brushite (0.4%), and 2, 8-dihydroxyadenine (0.2%). Men contributed with more CaOx stones than women at age 30-49 years (all p <0.01) and more UA stones at 30-59 years (all p <0.05). Women contributed with more infection stones than men in age groups 30-49 and 60-69 years (all p <0.05), and more CaP stones at 30-49 years. The prevalence peak was 50-59 years in men and 60-69 years in women. Both genders had the lowest prevalence in adolescence. Prevalence of UA stones increased while that of infection stones decreased with aging in both genders. Conclusions: Age and sex had a strong association with distribution of stone compositions in this Chinese cohort.

Nanoscale Analysis of Randall's Plaques by Electron Energy Loss Spectromicroscopy: Insight in Early Biomineral Formation in Human Kidney.

Idiopathic kidney stones originate mainly from calcium phosphate deposits at the tip of renal papillae, known as Randall's plaques (RPs), also detected in most human kidneys without stones. However, little is known about the mechanisms involved in RP formation. The localization and characterization of such nanosized objects in the kidney remain a real challenge, making their study arduous. This study provides a nanoscale analysis of the chemical composition and morphology of incipient RPs, characterizing in particular the interface between the mineral and the surrounding organic compounds. Relying on data gathered from a calculi collection, the morphology and chemical composition of incipient calcifications in renal tissue were determined using spatially resolved electron energy-loss spectroscopy. We detected microcalcifications and individual nanocalcifications found at some distance from the larger ones. Strikingly, concerning the smaller ones, we show that two types of nanocalcifications coexist: calcified organic vesicles and nanometric mineral granules mainly composed of calcium phosphate with carbonate in their core. Interestingly, some of these nanocalcifications present similarities with those reported in physiological bone or pathological cardiovascular biominerals, suggesting possible common formation mechanisms. However, the high diversity of these nanocalcifications suggests that several mechanisms may be involved (nucleation on a carbonate core or on organic compounds). In addition, incipient RPs also appear to present specific features at larger scales, revealing secondary calcified structures embedded in a fibrillar organic material. Our study proves that analogies exist between physiological and pathological biominerals and provides information to understand the physicochemical processes involved in pathological calcification formation.