pH changes in radicular dentine associated with calcium hydroxide and corticosteroid/antibiotic pastes.

The aim was to compare hydroxyl ion diffusion through dentine following placement of calcium hydroxide and Ledermix paste. Thirty-six teeth were divided into one control (n = 6) and three experimental (n = 10) groups - (i) Pulpdent paste; (ii) Pulpdent/Ledermix pastes; (iii) Ledermix paste and (iv) Saline. pH was measured in inner and outer dentine cavities over 12 months. Inner dentine time to maximum pH (Tmax ) was 1 week for Pulpdent and 2 weeks for Pulpdent/Ledermix. Pulpdent's outer dentine Tmax was 4 weeks and Pulpdent/Ledermix was 10 weeks. After day 1, Pulpdent pH was higher and this continued for 12 months. Pulpdent's outer dentine pH was higher than Ledermix and controls, but not significantly different from Pulpdent/Ledermix. Pulpdent/Ledermix had significantly higher pH than controls and Ledermix from day 5 until 10 months when Pulpdent/Ledermix outer dentine pH decreased and became similar. In all groups, pH reduced after 3 months.

ATM-TCR: TCR-Epitope Binding Affinity Prediction Using a Multi-Head Self-Attention Model.

TCR-epitope pair binding is the key component for T cell regulation. The ability to predict whether a given pair binds is fundamental to understanding the underlying biology of the binding mechanism as well as developing T-cell mediated immunotherapy approaches. The advent of large-scale public databases containing TCR-epitope binding pairs enabled the recent development of computational prediction methods for TCR-epitope binding. However, the number of epitopes reported along with binding TCRs is far too small, resulting in poor out-of-sample performance for unseen epitopes. In order to address this issue, we present our model ATM-TCR which uses a multi-head self-attention mechanism to capture biological contextual information and improve generalization performance. Additionally, we present a novel application of the attention map from our model to improve out-of-sample performance by demonstrating on recent SARS-CoV-2 data.

Effect of nutritional calcium and phosphate loading on calciprotein particle kinetics in adults with normal and impaired kidney function.

Plasma approaches metastability with respect to its calcium and phosphate content, with only minor perturbations in ionic activity needed to sustain crystal growth once nucleated. Physiologically, calcium and phosphate are intermittently absorbed from the diet each day, yet plasma concentrations of these ions deviate minimally post-prandially. This implies the existence of a blood-borne mineral buffer system to sequester calcium phosphates and minimise the risk of deposition in the soft tissues. Calciprotein particles (CPP), endogenous mineral-protein colloids containing the plasma protein fetuin-A, may fulfill this function but definitive evidence linking dietary mineral loading with their formation is lacking. Here we demonstrate that CPP are formed as a normal physiological response to feeding in healthy adults and that this occurs despite minimal change in conventional serum mineral markers. Further, in individuals with Chronic Kidney Disease (CKD), in whom mineral handling is impaired, we show that both fasting and post-prandial levels of CPP precursors are markedly augmented and strongly inversely correlated with kidney function. This study highlights the important, but often neglected, contribution of colloidal biochemistry to mineral homeostasis and provides novel insight into the dysregulation of mineral metabolism in CKD.

Automated deep-neural-network surveillance of cranial images for acute neurologic events.

Rapid diagnosis and treatment of acute neurological illnesses such as stroke, hemorrhage, and hydrocephalus are critical to achieving positive outcomes and preserving neurologic function-'time is brain'1-5. Although these disorders are often recognizable by their symptoms, the critical means of their diagnosis is rapid imaging6-10. Computer-aided surveillance of acute neurologic events in cranial imaging has the potential to triage radiology workflow, thus decreasing time to treatment and improving outcomes. Substantial clinical work has focused on computer-assisted diagnosis (CAD), whereas technical work in volumetric image analysis has focused primarily on segmentation. 3D convolutional neural networks (3D-CNNs) have primarily been used for supervised classification on 3D modeling and light detection and ranging (LiDAR) data11-15. Here, we demonstrate a 3D-CNN architecture that performs weakly supervised classification to screen head CT images for acute neurologic events. Features were automatically learned from a clinical radiology dataset comprising 37,236 head CTs and were annotated with a semisupervised natural-language processing (NLP) framework16. We demonstrate the effectiveness of our approach to triage radiology workflow and accelerate the time to diagnosis from minutes to seconds through a randomized, double-blinded, prospective trial in a simulated clinical environment.

High-intensity physical exercise increases serum α-klotho levels in healthy volunteers.

The recently discovered klotho proteins have roles in a diverse range of metabolic processes with the oldest protein, α-klotho, implicated in various cellular pathways in energy, glucose, and phosphate metabolism. Circulating soluble klotho (sKl), derived from membrane α-klotho cleavage, not only has effects on ion channels and insulin signaling pathways, but is inversely associated with mortality. Effects of physical exercise on sKl have not been well studied. The effect of a single high-intensity standardized exercise on sKl and serum phosphate (sPi) levels in healthy adults was investigated. A standard Bruce protocol treadmill exercise was undertaken by 10 fasting healthy volunteers. sKl, sPi, and blood glucose levels were measured in samples collected 1-week prior, immediately pre (Tpre), 0 (Tpost), 30 (T30), 240 (T240) min, and 1-week after exercise. Median (interquartile range) age of participants was 47.5 (44-51) years; five (50%) were male. All study participants achieved at least 90% predicted maximum heart rate (MHR). sKl increased acutely after exercise (Tpre median 448 pg/mL vs. Tpost median 576 pg/mL; p < 0.01). There was a nonsignificant sPi decline at T30 (Tpre 0.94 ± 0.12 mmol/L vs. T30 0.83 ± 0.22 mmol/L). Exercise led to a reduction in blood glucose by T240 with median glucose levels at Tpre, Tpost, T30, and T240 of 6.0, 6.5, 6.3, and 5.7 mmol/L, respectively. In conclusion, a single high-intensity exercise session is associated with a transient increase in sKl, a delayed reduction in blood glucose, and a nonsignificant decrease in sPi levels in healthy adults. The evaluation of long-term effects of cardiovascular fitness programs on sKl and sPi in healthy individuals and disease cohorts are required to identify potential lifestyle modifications to help improve chronic disease management and long-term outcomes.

Calciprotein Particle Formation in Peritoneal Dialysis Effluent Is Dependent on Dialysate Calcium Concentration.

BACKGROUND: The accumulation of fetuin-A-containing calciprotein particles (CPP) in the serum of patients with renal disease and those with chronic inflammation may be involved in driving sterile inflammation and extraosseous mineral deposition. We previously showed that both fetuin-A and CPP were present in the peritoneal dialysis (PD) effluent of stable PD patients. It is unknown whether different PD fluids might affect the formation of CPP in vivo. METHOD: Peritoneal effluent from 12 patients was collected after a 6-hour dwell with 7 different commercial PD fluids. Calciprotein particles and inflammatory cytokines were measured by flow cytometry. RESULTS: High inter-subject variability in CPP concentration was observed. Peritoneal dialysis fluids containing 1.75 mmol/L calcium were associated with enhanced formation of CPP in vivo, compared with fluids containing 1.25 mmol/L calcium. Osmotic agent, fluid pH, and glucose concentration did not affect CPP formation. Peritoneal dialysis effluent CPP levels were not associated with changes in inflammatory cytokines. CONCLUSION: High calcium-containing PD fluids favor intraperitoneal CPP formation. This finding may have relevance for future PD fluid design.

Hydroxyl Ion Diffusion through Radicular Dentine When Calcium Hydroxide Is Used under Different Conditions.

Calcium hydroxide's anti-bacterial action relies on high pH. The aim here was to investigate hydroxyl ion diffusion through dentine under different conditions. Teeth were divided into control (n = 4) and four experimental groups (n = 10): Group 1-no medicament; Group 2-Calmix; Group 3-Calmix/Ledermix; Group 4-Calasept Plus/Ledermix; Group 5-Pulpdent/smear layer. Deep (inner dentine) and shallow (outer dentine) cavities were cut into each root. pH was measured in these cavities for 12 weeks. The inner and outer dentine pH in Group 2 was significantly higher than all groups. Inner dentine pH in Group 3 was slightly higher than that in Group 4 initially but subsequently comparable. After Day 2, Group 5 had significantly lower pH than Groups 3 and 4. The outer dentine pH in Group 3 started higher than that in Groups 4 and 5, but by Day 28 the difference was insignificant. The time for the inner dentine to reach maximum pH was one week for Group 2 and four weeks for Groups 3 and 4. The time for the outer dentine to reach maximum pH was eight weeks for all experimental groups. Mixing different Ca(OH)2 formulations with Ledermix gave similar hydroxyl ion release but pH and total diffusion was lower than Ca(OH)2 alone. The smear layer inhibited diffusion.

The Role of Secondary Calciprotein Particles in the Mineralisation Paradox of Chronic Kidney Disease.

Mineralisation paradox is prevalent in chronic kidney disease and ageing where increased vascular calcification is accompanied by reduced bone mineralisation and osteopenia. Secondary calciprotein particles (CPP2), colloidal nanoparticles containing hydroxyapatite crystal stabilised by a protein shell, have been implicated in vascular calcification in chronic kidney disease. Here, we describe the effect of CPP2 on osteoblasts and vascular smooth muscle cells (VSMC) mineralisation in an in vitro model system. The mineralisation paradox can be simulated in vitro by the addition of phosphate ions (Pi, 3 mM) and CPP2 (10 µg/ml of Ca equivalent). Pi alone induced osteoblast mineralisation but had no effect on VSMC mineralisation. CPP2 alone had no effect on mineralisation in either cell line, but when combined with elevated Pi, reduced osteoblast-like mineralisation (P < 0.001) whilst induced VSMC mineralisation (P < 0.001). These results suggest that in an in vitro system the synergistic interaction between Pi and CPP2 could mimic the mineralisation paradox, and may provide a potential mechanistic link to explain these clinical observations.

A novel fluorescent probe-based flow cytometric assay for mineral-containing nanoparticles in serum.

Calciprotein particles, nanoscale aggregates of insoluble mineral and binding proteins, have emerged as potential mediators of phosphate toxicity in patients with Chronic Kidney Disease. Although existing immunochemical methods for their detection have provided compelling data, these approaches are indirect, lack specificity and are subject to a number of other technical and theoretical shortcomings. Here we have developed a rapid homogeneous fluorescent probe-based flow cytometric method for the detection and quantitation of individual mineral-containing nanoparticles in human and animal serum. This method allows the discrimination of membrane-bound from membrane-free particles and different mineral phases (amorphous vs. crystalline). Critically, the method has been optimised for use on a conventional instrument, without the need for manual hardware adjustments. Using this method, we demonstrate a consistency in findings across studies of Chronic Kidney Disease patients and commonly used uraemic animal models. These studies demonstrate that renal dysfunction is associated with the ripening of calciprotein particles to the crystalline state and reveal bone metabolism and dietary mineral as important modulators of circulating levels. Flow cytometric analysis of calciprotein particles may enhance our understanding of mineral handling in kidney disease and provide a novel indicator of therapeutic efficacy for interventions targeting Chronic Kidney Disease-Mineral Bone Disorder.

Is there a role for newer biomarkers in chronic kidney disease-mineral and bone disorder management?

The current management of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) relies largely on clinical judgement and assessment of biochemical parameters including serum calcium, phosphate and intact parathyroid hormone concentrations. In the past two decades, there has been a leap in the understanding of the pathophysiology of CKD-MBD, leading to the discovery of novel biomarkers. The potential utility of these markers in this clinical setting is an area of intense investigation. In the absence of any guidelines aiding the clinician's understanding and application of these markers, we summarise the current available literature surrounding fibroblast growth factor-23, α-Klotho, sclerostin and serum calcification propensity testing and their respective assays in the context of CKD-MBD management.

Relationship between timed and spot urine collections for measuring phosphate excretion.

BACKGROUND: Twenty-four hour urinary phosphate excretion (UPE) reflects intestinal phosphate absorption in steady state and may be more informative than serum phosphate (sPi) when assessing phosphate homoeostasis clinically. Timed urine collections are cumbersome and prone to collection errors. Spot urine phosphate/creatinine ratio (uPiCr) may be a useful, simple surrogate for 24-h UPE, but requires further validation. This study aimed to determine the relationship between uPiCr and 24-h UPE. METHODS: This single-centre cross-sectional study examined contemporaneous serum, spot urine and 24-h urine. Serum biochemistry was analysed. Urine phosphate concentration (uPi) and creatinine concentration (uCr) were measured in spot and 24-h urine collections. Spearman's rank correlation coefficients and Bland-Altman plots were used to assess agreement between spot uPiCr and UPE. Backward multivariate analysis was undertaken for UPE prediction. RESULTS: One hundred and sixteen participants (77 with kidney disease and 39 healthy volunteers) were studied. Seventy-four (63.8 %) were male. Median (IQR) age was 61(49-71) years. Median (IQR) spot uPiCr and total UPE were 1.7 (1.3-2.2) mmol/mmol and 25.8 (19.9-35.0) mmol/d, respectively. There was no correlation between spot uPiCr and 24-h UPE (R = 0.064, P = 0.51) but spot uPi significantly correlated with 24-h UPE (R = 0.385, P < 0.001). Although spot and 24-h measures of phosphate handling correlated (all P < 0.001), Bland-Altman analysis revealed bias between collection techniques. UPE prediction model using the independent variables of eGFR, sPi, albumin and spot uPi provided R (2) = 0.443. CONCLUSION: No direct correlation was noted between spot uPiCr and 24-h UPE. Normalization of uPi to uCr on spot urine samples may be inappropriate when evaluating urinary phosphate excretion in adults and thus, a spot uPiCr is not a suitable surrogate for measuring UPE. A UPE prediction model utilising spot urine biochemistry cannot be advocated at present.

No apparent transmission of transgenic α-synuclein into nigrostriatal dopaminergic neurons in multiple mouse models.

BACKGROUND: α-synuclein (α-syn) is the main component of intracytoplasmic inclusions deposited in the brains of patients with Parkinson's disease (PD) and certain other neurodegenerative disorders. Recent studies have explored the ability of α-syn to propagate between or across neighboring neurons and supposedly "infect" them with a prion-like mechanism. However, much of this research has used stereotaxic injections of heterologous α-syn fibrils to induce the spreading of inclusions in the rodent brains. Whether α-syn is able to transmit from the host cells to their neighboring cells in vivo is unclear. METHODS: Using immunestaining, we examined the potential propagation of α-syn into nigrostriatal dopaminergic (DA) neurons in three lines of transgenic mice that overexpress human wild-type α-syn (hα-syn) in different neuron populations. RESULTS: After testing for three different routes by which hα-syn propagation might occur, we were unable to find any evidence that hα-syn behaved like a prion and could be transmitted overtime into the DA neurons initially lack of hα-syn expression. CONCLUSIONS: In transgenic mice hα-syn does not have the ability to propagate at pathologically significant levels between or across neurons. It must be noted that these observations do not disprove the studies that show its prion-like qualities, but rather that propagation is not detectable in transgenic models that do not use any injections of heterologous proteins or viral vectors to induce a spreading state.

The role of fetuin-A in mineral trafficking and deposition.

Calcium and phosphate are the principle ions involved in the deposition of mineral in the human body. Inhibitors of mineralisation are essential for the prevention of ectopic mineral precipitation and deposition. In the past decade, through in vitro, in vivo and clinical observation studies, we have come to appreciate the importance of fetuin-A (Fet-A), a circulating glycoprotein, in preventing ectopic calcium phosphate mineralisation. Moreover, the detection of Fet-A-containing mineral complex, termed calciprotein particles (CPPs), has provided new ways to assess an individual's calcific risk. The pathophysiological significance of CPPs in disease states is yet to be defined, but it provides an exciting avenue to further our understanding of the development of ectopic mineralisation.

Relative abundance of fetuin- A in peritoneal dialysis effluent and its association with in situ formation of calciprotein particles: an observational pilot study.

AIM: In patients with renal failure or chronic inflammation, the accumulation of fetuin-A-containing calciprotein particles (CPP) in the extracellular fluid has been implicated in driving inflammatory pathways and extraosseous mineral deposition. We aimed to discover whether CPP are present in the peritoneal dialysis fluid effluent (PDF) of stable peritoneal dialysis (PD) patients, and if so, how these particles might be formed. METHODS: Serum and PDF were sampled from 20 stable PD patients. CPP were quantified by the reduction in fetuin-A concentration after high speed centrifugation. 8-iso-PGF2α in PDF was measured as a marker of oxidative stress. Fetuin-A and phosphate were added to commercially available dialysis fluids to assess their ability to support CPP formation ex vivo. RESULTS: We report that the major protein component of these mineral-containing nanoparticles, fetuin-A, is relatively abundant in PDF and that CPP were present in the PDF of 17/20 PD patients. PDF CPP levels were strongly correlated with 8-iso-PGF2α concentrations. In vitro experiments suggested that commonly used peritoneal dialysate fluids, irrespective of composition, could not sustain appreciable de novo CPP formation ex vivo. CONCLUSION: Fetuin-A is either actively transported or locally produced by the peritoneal membrane in PD patients. The association between fetuin-A-containing CPP and markers of oxidative stress warrants further mechanistic studies.

In search of an effective treatment for recurrent mesangiocapillary glomerulonephritis in the renal allograft.

In patients with end-stage kidney disease (ESKD) secondary to mesangiocapillary glomerulonephritis (MCGN), recurrent disease post transplantation is a common cause of graft loss. We report a case of a 33-year-old female with ESKD due to idiopathic MCGN who developed recurrent disease in two consecutive renal allografts. Recurrent disease was diagnosed two months after receiving her primary transplant from a live related donor. Oral cyclophosphamide was initiated but discontinued after 10 months due to cystitis. This was followed by rapid deterioration in her renal function. Despite salvage therapy with rituximab, the graft was lost 2 years post transplantation. After 7 years on haemodialysis, the patient received a second graft from a deceased donor. Recurrent MCGN was once again diagnosed one year post transplantation. She was treated with plasma exchange and rituximab. Despite ongoing nephrotic range proteinuria, her graft function remained stable 2 years post transplantation. The optimal therapy for recurrent MCGN is unknown at this stage. It is hoped that a better understanding of its pathogenesis will enable the development of more effective and targeted therapies.

Protection provided by a herpes simplex virus 2 (HSV-2) glycoprotein C and D subunit antigen vaccine against genital HSV-2 infection in HSV-1-seropositive guinea pigs.

A prophylactic vaccine for genital herpes disease remains an elusive goal. We report the results of two studies performed collaboratively in different laboratories that assessed immunogenicity and vaccine efficacy in herpes simplex virus 1 (HSV-1)-seropositive guinea pigs immunized and subsequently challenged intravaginally with HSV-2. In study 1, HSV-2 glycoproteins C (gC2) and D (gD2) were produced in baculovirus and administered intramuscularly as monovalent or bivalent vaccines with CpG and alum. In study 2, gD2 was produced in CHO cells and given intramuscularly with monophosphoryl lipid A (MPL) and alum, or gC2 and gD2 were produced in glycoengineered Pichia pastoris and administered intramuscularly as a bivalent vaccine with Iscomatrix and alum to HSV-1-naive or -seropositive guinea pigs. In both studies, immunization boosted neutralizing antibody responses to HSV-1 and HSV-2. In study 1, immunization with gC2, gD2, or both immunogens significantly reduced the frequency of genital lesions, with the bivalent vaccine showing the greatest protection. In study 2, both vaccines were highly protective against genital disease in naive and HSV-1-seropositive animals. Comparisons between gD2 and gC2/gD2 in study 2 must be interpreted cautiously, because different adjuvants, gD2 doses, and antigen production methods were used; however, significant differences invariably favored the bivalent vaccine. Immunization of naive animals with gC2/gD2 significantly reduced the number of days of vaginal shedding of HSV-2 DNA compared with that for mock-immunized animals. Surprisingly, in both studies, immunization of HSV-1-seropositive animals had little effect on recurrent vaginal shedding of HSV-2 DNA, despite significantly reducing genital disease.

Urinary neutrophil gelatinase-associated lipocalin may aid prediction of renal decline in patients with non-proteinuric Stages 3 and 4 chronic kidney disease (CKD).

BACKGROUND: Chronic kidney disease (CKD) is an increasing public health issue. It is therefore potentially highly advantageous to identify patients at risk of accelerated renal progression and death. Neutrophil gelatinase-associated lipocalin (NGAL) is an established urinary biomarker for acute kidney injury, but it is not known whether adding urinary NGAL (uNGAL) measurements to conventional risk factors will improve risk assessment in the setting of chronic disease. METHODS: This is a prospective observational cohort study of 158 patients with Stage 3 or 4 CKD. The ability of baseline uNGAL to improve prediction of outcome was assessed by multivariate modelling and a number of metrics including net reclassification analysis. A primary composite endpoint of all-cause mortality or progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT) at 2 years and a secondary endpoint of ≥5 mL/min/1.73 m(2) decline in the estimated glomerular filtration rate (eGFR) after 1 year were considered. RESULTS: Forty patients (25%) reached the primary composite endpoint, 20 of whom died. Twenty-seven patients (19%) reached the secondary endpoint of a ≥5 mL/min/1.73 m(2) decline in the eGFR. The baseline uNGAL-to-creatinine ratio (uNCR) was associated with the combined endpoint of death or initiation of RRT (HR per 5 µg/mmol increase 1.27, 95% CI: 1.01-1.60, P = 0.036) independent of conventional cardiovascular and renal risk factors, including proteinuria. In separate analysis of these two competing endpoints, however, uNCR only remained associated with increased risk of progression to ESRD requiring RRT. Higher baseline uNCR was also independently predictive of rapid renal decline over 1 year (HR per 5 µg/mmol increase 1.47, 95% CI: 1.06-2.06, P = 0.022). Addition of uNCR to the base model resulted in a significant increase in discrimination for the secondary (C-statistic 0.76-0.85, P = 0.001) but not the primary endpoint (P = 0.276). Reclassification analysis on the other hand, demonstrated an improvement in risk predication of both primary and secondary endpoints by incorporating uNCR into the base model, but only in those with low-level urine protein excretion (<28 mg/mmol), with category-free net reclassification improvement (NRI) scores of 64% (95% CI: 8-70; P = 0.019) and 79% (95% CI: 12-83; P = 0.009), respectively. CONCLUSION: The utilization of uNCR in addition to conventional established cardiovascular and renal risk factors may improve the prediction of disease progression in elderly Caucasian pre-dialysis CKD patients with low-grade proteinuria.

Serum fetuin-A concentration and fetuin-A-containing calciprotein particles in patients with chronic inflammatory disease and renal failure.

AIM: Fetuin-A (Fet-A) is an important regulator of extracellular matrix mineralization. Fet-A plays a critical role in the formation and stabilization of high molecular weight colloidal protein-mineral complexes known as calciprotein particles (CPP). The aim of this study was to examine the effects of inflammation, renal function and dialysis modality on serum Fet-A and CPP. METHODS: This is an observational study of patients with chronic kidney disease (CKD) and those with chronic inflammatory disease (CID) but normal renal function. Serum CPP were quantified indirectly by analysing the apparent reduction in serum Fet-A concentration (reduction ratio, RR) after high-speed centrifugation. RESULTS: Serum total Fet-A concentrations are reduced in renal disease and in patients with CID. CPP were not detectable in the serum of normal individuals. CPP represent an increasing percentage of total circulating Fet-A concentrations in patients with CID (RR, 13.3 ± 8.5%), as well as in patients with pre-dialysis CKD (12.4 ± 7.3%) and those undergoing peritoneal dialysis (RR, 22.8 ± 6.0%) or haemodialysis (RR, 38.1 ± 12.8%). The highest Fet-A RR were found in patients with calcific uraemic arteriolopathy (CUA) on haemodialysis (73.9 ± 15.6%). Serum total Fet-A concentrations and Fet-A reduction ratios decreased during a single haemodialysis session, by 24% (P < 0.001) and 34% (P < 0.001), respectively. CONCLUSION: Inflammation appears to be associated with mineral stress even in the absence of renal dysfunction. Patients with CUA on haemodialysis have very high serum Fet-A reduction ratios, suggesting that this measurement may have a prognostic/diagnostic role in this condition.

Fetuin-A-containing calciprotein particle levels can be reduced by dialysis, sodium thiosulphate and plasma exchange. Potential therapeutic implications for calciphylaxis?

Calciprotein particles (CPP) are a novel marker of mineral stress. High levels of CPP are found in patients with calciphylaxis, a condition associated with marked vascular calcification and a poor prognosis. We report substantial reductions in CPP levels in a dialysis patient having combined haemodialysis (HD) and plasma exchange (PEx) prior to an ABO-incompatible kidney transplant. We also report the effects of the same treatments combined with sodium thiosulphate (STS) in a patient newly diagnosed with calciphylaxis. Combining HD with intra-dialytic STS and PEx we achieved a significant reduction in CCP with the least rebound between treatment sessions. After 6 weeks of treatment, the CPP reduction was paralleled by clinical improvement. Measurement of CPP may be an attractive marker for monitoring the effectiveness of calciphylaxis therapy.