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Our laboratory recently developed [ 11 C]PS13 as a PET radioligand to selectively measure cyclooxygenase-1 (COX-1). The cyclooxygenase enzyme family converts arachidonic acid into prostaglandins and thromboxanes, which mediate inflammation. The total brain uptake of [ 11 C]PS13, which is composed of both specific binding and background uptake, can be accurately quantified with gold standard methods of compartmental modeling. This study sought to quantify the specific binding of [ 11 C]PS13 to COX-1 in healthy human brain using scans performed with arterial input function at baseline and after blockade by the COX-1-selective inhibitor ketoprofen. Methods: Eight healthy volunteers underwent two 90-min [ 11 C]PS13 PET scans with radiometabolite-corrected arterial input function, at baseline and about 2 h after oral administration of ketoprofen (75 mg). Results: Two-tissue compartment modeling effectively identified the total uptake of radioactivity in the brain (as distribution volume), showing the highest densities in the hippocampus, the occipital cortex, and the banks of the central sulcus. All brain regions exhibited displaceable and specific binding, and thus none could be used as a reference region. Ketoprofen blocked approximately 84% of the binding sites on COX-1 in the whole brain. After full occupancy was extrapolated, the average whole-brain values of [ 11 C]PS13 were 1.6 ± 0.8 mL·cm -3 for specific uptake, 1.7 ± 0.6 mL·cm -3 for background uptake, and 1.1 ± 0.5 for the specific-to-background ratio. The hippocampus had the highest specific-to-background ratio value of 2.7 ± 0.9. Conclusion: [ 11 C]PS13 exhibited high specific binding to COX-1 in the human brain, but its quantification requires arterial blood sampling., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: Infectious catheter-related right atrial thrombus (CRAT) is a potentially fatal but often underestimated contingency associated with central venous catheter (CVC) in patients on hemodialysis. Management guidelines for CRAT are lacking, and its occurrence poses clinical challenges. Here, we describe the case of an infectious CRAT in a young patient on hemodialysis with peculiar clinical complications and perform a literature review. Case presentation and literature review: A 30-year-old man on hemodialysis after bilateral nephrectomy due to polycystic disease presented with hyperpyrexia resistant to broad-spectrum antibiotics. A pleural empyema caused by methicillin-resistant Staphylococcus aureus (MRSA) was diagnosed. Since fever persisted despite targeted antibiotic therapy, a transthoracic echocardiogram to exclude infective endocarditis was performed, showing a right atrial thrombus. CVC was promptly removed and the thrombus was aspirated through a percutaneous retrieval system. The thrombus cultural exam resulted positive for MRSA. After performing an extensive literature review, we could not find another case reporting the concomitance of these two rare complications. Conclusions: CRAT is a life-threatening complication in hemodialysis patients. While various treatment options exist, evidence-based guidelines are lacking, leading to individualized management strategies. Minimizing CVC use remains the best option for preventing such a complication.

"Palliative dialysis" is defined as the renal replacement therapy directed to patients living the most critical phases of illness and the end-of-life stage. Offering targeted dialysis prescriptions becomes imperative when health conditions, along with comorbidities, unfavorable prognosis and complications, do not allow standard dialysis to be started or continued. Management should also integrate adequate supportive care measures in both incident and prevalent patients. This document summarizes nephrological recommendations and scientifical evidence regarding the palliative approach to dialysis, and proposes operative tools for a good clinical practice. After planning and sharing the route of care ("shared-decision-making"), which includes multidimensional evaluation of the patient, a pathway of treatment should be started, focusing on combining the therapeutical available options, adequacy and proportionality of care and patients' preferences. We propose a framework of indications that could help the nephrologist in practicing appropriate measures of treatment in patients' frailest conditions, with the aim of reducing the burden of dialysis, improving quality of life, providing a better control of symptoms, decreasing the hospitalization rates in the end-of-life stage and promoting a home-centered form of care. Such a decisional pathway is nowadays increasingly needed in nephrology practice, but not standardized yet., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS., Competing Interests: Gaia Rizzo is an employee of Invicro. No other authors have competing interests to declare., (© 2024 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Data standardization promotes a common framework through which researchers can utilize others' data and is one of the leading methods neuroimaging researchers use to share and replicate findings. As of today, standardizing datasets requires technical expertise such as coding and knowledge of file formats. We present ezBIDS, a tool for converting neuroimaging data and associated metadata to the Brain Imaging Data Structure (BIDS) standard. ezBIDS contains four major features: (1) No installation or programming requirements. (2) Handling of both imaging and task events data and metadata. (3) Semi-automated inference and guidance for adherence to BIDS. (4) Multiple data management options: download BIDS data to local system, or transfer to OpenNeuro.org or to brainlife.io. In sum, ezBIDS requires neither coding proficiency nor knowledge of BIDS, and is the first BIDS tool to offer guided standardization, support for task events conversion, and interoperability with OpenNeuro.org and brainlife.io., (© 2024. The Author(s).)

Introduction: Cardiovascular disease (CVD) is one of the global leading causes of morbidity and mortality in chronic kidney disease (CKD) patients. Vascular calcification (VC) is a major cause of CVD in this population and is the consequence of complex interactions between inhibitor and promoter factors leading to pathological deposition of calcium and phosphate in soft tissues. Different pathological landscapes are associated with the development of VC, such as endothelial dysfunction, oxidative stress, chronic inflammation, loss of mineralization inhibitors, release of calcifying extracellular vesicles (cEVs) and circulating calcifying cells., Areas Covered: In this review, we examined the literature and summarized the pathophysiology, biomarkers and focused on the treatments of VC., Expert Opinion: Even though there is no consensus regarding specific treatment options, we provide the currently available treatment strategies that focus on phosphate balance, correction of vitamin D and vitamin K deficiencies, avoidance of both extremes of bone turnover, normalizing calcium levels and reduction of inflammatory response and the potential and promising therapeutic approaches liketargeting cellular mechanisms of calcification (e.g. SNF472, TNAP inhibitors).Creating novel scores to detect in advance VC and implementing targeted therapies is crucial to treat them and improve the future management of these patients.

Hospitalizations for heart failure exceed 1 million per year in both the United States and Europe and more than 90% are due to symptoms and signs of fluid overload. Rates of rehospitalizations or emergency department visit at 60 days are remarkable regardless of whether loop diuretics were administered at low vs high doses or by bolus injection vs continuous infusion. Ultrafiltration (UF) has been considered a promising alternative to stepped diuretic therapy and it consists in the mechanical, adjustable removal of iso-tonic plasma water across a semipermeable membrane with the application of hydrostatic pressure gradient generated by a pump. Fluid removal with ultrafiltration presents several advantages such as elimination of higher amount of sodium with less neurohormonal activation. However, the conflicting results from UF studies highlight that patient selection and fluid removal targets are not completely understood. The best way to assess fluid status and therefore establish the fluid removal target is also still a matter of debate. Herein, we provide an up-to-date systematic review about the role of ultrafiltration among patients with fluid overload and its gaps in daily practice., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest regarding this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Oncology nursing requires specialized education and clinical training. It is not possible to deliver safe cancer nursing care across the cancer continuum with only a general nursing education and experience. Complex cancer therapies, e.g., immunotherapies, and technologies, e.g., radiotherapy, and advanced surgeries, demand nursing support delivered by knowledgeable and skilled professionals. To achieve this required workforce, necessitates cancer education that begins at pre-licensure, strong onboarding training, competency standards, continuing education and oncology nursing leadership across cancer control activities, e.g., national cancer control planning. Nevertheless, current nursing shortages, the lack of qualified oncology nursing faculty and adequate nursing schools, as well as government accreditation of oncology nursing specialties threaten appropriate cancer nursing care in the future. Given the exponential growth of the public health burden of cancer everywhere, prompt attention to the single largest workforce to support this patient population is urgent. Guidance from international authorities such as the World Health Organization, International Council of Nurses, and oncology nursing associations/societies allows governments to appropriately scale up their oncology nursing workforce to improve survival. We present the challenges in oncology nursing education and successful interventions to address those challenges to provide an overview of the current status of oncology nursing education from around the world.

Aging is the progressive decline of body functions and a number of chronic conditions can lead to premature aging characterized by frailty, a diseased vasculature, osteoporosis, and muscle wasting. One of the major conditions associated with premature and accelerated aging is chronic kidney disease (CKD), which can also result in early vascular aging and the stiffening of the arteries. Premature vascular aging in CKD patients has been considered as a marker of prognosis of mortality and cardiovascular morbidity and therefore requires further attention. Oxidative stress, inflammation, advanced glycation end products, fructose, and an aberrant gut microbiota can contribute to the development of early aging in CKD patients. There are several key molecular pathways and molecules which play a role in aging and vascular aging including nuclear factor erythroid 2-related factor 2 (Nrf-2), AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and klotho. Potential therapeutic strategies can target these pathways. Future studies are needed to better understand the importance of premature aging and early vascular aging and to develop therapeutic alternatives for these conditions., Competing Interests: M.C. is the Ad Interim Editor-in-Chief of CKJ. M.K. is member of the CKJ editorial board., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Introduction: Secondary hyperparathyroidism (SHPT) is a common and major complication of chronic kidney disease (CKD) among patients on dialysis and in patients with CKD stage G3 to G5. SHPT in CKD is caused by disturbances in metabolic parameters. Paricalcitol (PCT), other active vitamin D analogous (doxercalciferol and alfacalcidol), and active vitamin D (calcitriol) have been commonly used to treat SHPT in non-dialysis CKD (ND-CKD) for several years. However, recent studies indicate that these therapies adversely increase serum calcium, phosphate, and fibroblast growth factor 23 (FGF-23) levels. Extended release calcifediol (ERC) has been developed as an alternative treatment for SHPT in ND-CKD. The present meta-analysis compares the effect of ERC against PCT in the control of PTH and calcium levels. Methods: A systematic literature review was conducted, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to identify studies for inclusion in the Network Meta-Analysis (NMA). Results: 18 publications were eligible for inclusion in the network meta-analysis and 9 articles were included in the final NMA. The estimated PTH reduction from PCT (-59.5 pg/ml) was larger than the PTH reduction from ERC (-45.3 pg/ml), but the difference in treatment effects did not show statistical significance. Treatment with PCT caused statistically significant increases in calcium vs. placebo (increase: 0.31 mg/dl), while the marginal increase in calcium from treatment with ERC (increase: 0.10 mg/dl) did not reach statistical significance. Conclusions: The evidence suggests that both PCT and ERC are effective in reducing levels of PTH, whereas calcium levels tended to increase from treatment with PCT. Therefore, ERC may be an equally effective, but more tolerable treatment alternative to PCT., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Introduction: Vascular calcification (VC) which is the pathological mineral deposition in the vascular system, predominantly at the intimal and medial layer of the vessel wall, is an important comorbidity in patients with chronic kidney disease (CKD) leading to significant morbidity and mortality while necessitating appropriate treatment. Our review aims to provide an in-depth analysis of the current understanding of VC., Areas Covered: In this review, we first discuss the pathophysiology of VC in CKD patients, then we explain the methods to predict and assess VC. Afterwards, we provide the currently available as well as the potential therapeutic approaches of VC. We finally discuss our understanding regarding the current situation surrounding VC in our expert opinion section., Expert Opinion: Predicting, assessing and treating VC is crucial and the future advances in the field of research surrounding VC will potentially occur in one or more of these three areas of clinical management. There is a current lack of evidence and consensus regarding specific therapeutic options for alleviating VC and this situation may not necessitate VC to be determined, detected, and documented before the available options are implemented. Regardless, the prediction and assessment of VC is still important and requires further improvement together with the developments in therapeutic alternatives. The future has the potential to bring better research which would guide and improve the management of this patient group. A more specialized approach consisting of targeted therapies and more tailored management plans for patients with CKD and VC is on the horizon.

Results from recent randomized controlled trials on inhibitors of the sodium-glucose cotransporter 2 (SGLT2) have determined a paradigm shift in the treatment of patients with type 2 diabetes mellitus. These agents have been shown not only to ameliorate metabolic control, but also to independently protect from cardiovascular events and to reduce the progression of chronic kidney disease (CKD) in these patients. The magnitude of the nephroprotective effect observed in these studies is likely to make SGLT2 inhibitors the most impactful drug class for the treatment of diabetic patients with CKD since the discovery of renin-angiotensin system inhibitors. Even more surprisingly, SGLT2 inhibitors have also been shown to slow CKD progression in non-diabetic individuals with varying degrees of proteinuria, suggesting that activation of SGLT2 is involved in the pathogenesis of CKD independent of its etiology. As indications continue to expand, it is still unclear whether the observed benefits of SGLT2 inhibitors may extend to CKD patients at lower risk of progression and if their association with other agents may confer additional protection.

Introduction: In chronic kidney disease (CKD), the high morbidity and mortality risk for cardiovascular disease (CVD) are not easily explained only on the basis of traditional factors. Among nontraditional ones involved in CKD, malnutrition, inflammation, and atherosclerosis/calcification have been described as the "MIA syndrome.", Methods: In this pilot study, we evaluated the association between the variation in serum levels of 27 uremic retention solutes plus 6 indexes related to the MIA syndrome processes in a population of dialysis patients., Results: As expected, we found a direct correlation between serum albumin and both phosphate and total cholesterol (r = 0.54 and 0.37, respectively; p < 0.05). Moreover, total cholesterol and phosphate directly correlate (r = 0.40, p < 0.05). The relationship between malnutrition and inflammation is highlighted by the correlation of serum cholesterol levels with serum alpha-1 acid glycoprotein and IL-6 levels (r = -0.56, r = -0.39, respectively; p < 0.05). Moreover, the relation between inflammation and atherosclerosis/calcification is supported by the correlation of IL-6 with VEGF levels and vascular smooth muscle cell high-Pi in vitro calcification (r = 0.81, r = 0.66, respectively; p < 0.01)., Conclusion: We found significant correlations between several uremic retention solutes and malnutrition, inflammation, and atherosclerosis/calcification. Our findings support the hypothesis of a central role of the uremic milieu in the MIA syndrome and ultimately in the pathogenesis of CKD-specific CVD risk factors., (© 2022 S. Karger AG, Basel.)

Tools supporting the teaching and learning of programming may help professors in correcting assignments and students in receiving immediate feedback, thus improving the solution before the final submission. This paper describes the rDSA tool, which was designed, developed, and evaluated to support students in completing assignments concerning (i) the execution of statistical analyses in the R language and (ii) commenting on the results in natural language. The paper focuses on the feedback provided by the tool to students and how it was designed/evaluated/improved over the years. The paper also presents the results of two studies that indicate the advantages of using the tool in terms of engagement and learning outcomes. To conclude, we provide a discussion on the characteristics of the tool, its use in similar courses, and the scope for future work., Competing Interests: Conflicts of interests/Competing interestsThe authors declare that they did not receive support from any organisation for the submitted work., (© The Author(s) 2022.)

A cytokine storm drives the pathogenesis of severe COVID-19 infection and several biomarkers have been linked to mortality. Chronic kidney disease (CKD) emerged as a risk factor for severe COVID-19. We investigated the association between selected biomarkers and mortality in 77 patients hospitalized for COVID-19, and whether they differ in patients with eGFR higher and lower than 45 mL/min. The association between patients’ characteristics, plasma biomarkers and mortality was conducted by univariate logistic regression models and independent predictors of mortality were then used to create a multivariate prediction model through Cox regression. Patients with lower eGFR had a significant increase of GDF-15, CD-25 and RAGE, with higher plasma levels in non-survivors and in patients who needed ventilation. At univariate analysis, low and mid-low GDF-15 quartiles (<4.45 ng/mL) were associated with lower mortality risk, while mid-high and high quartiles (>4.45 ng/mL) were associated with higher mortality risk. Independent association between GDF-15 quartiles and mortality risk was confirmed in the Cox model and adjusted for eGFR, age, fever and dyspnea (HR 2.28, CI 1.53−3.39, p < 0.0001). The strength of the association between GDF-15 quartiles and mortality risk increased in patients with lower compared to higher eGFR (HR 2.53, CI 1.34−4.79 versus HR 1.99, CI 1.17−3.39). Our findings may suggest a further investigation of the effect of GDF-15 signaling pathway inhibition in CKD.

Antibacterial activity of atmosferic pressure non-thermal plasma (APNTP) was assessed for bacterial, yeast and mold strains. This investigation is to be considered preliminary: a second step is envisaged in which the efficacy of the technique and the device will be assessed directly on food of animal and plant origin. The strains (ATCC or wild type) of Listeria innocua , Escherichia coli , Salmonella thyphimurium , Pseudomonas aeruginosa , Staphylococcus aureus , Enterococcus faecalis , Proteus mirabilis (bacteria); Alternaria alternata , Aspergillus flavus , Cladosporium herbarum , Fusarium graminearum , Geotrichum candidum , Penicillium roqueforti , Rhizopus nigricans (moulds); Candida parapsilosis and Candida albicans (yeasts) were subjected to plasma plume generated by the action of electric fields with a gas mixture (oxygen and helium) delivered for 5 min at a distance of 2 cm. Types of experiments were listed as following: microorganism at concentration 1×10^8 and 1×10 4 cfu on PCA (Plate Count Agar); Listeria innocua and Salmonella thiphymurium at concentration 1×10^4 cfu on semi-synthetic and synthetic medium; mycetes (moulds and yeasts) at concentration 1×10^8 and 1×10^4 cfu on SDA (Sabouraud Dextrose Agar). The results obtained on the bacteria subjected to atmospheric cold plasma were evident on all the strains tested except for Proteus mirabilis (1×10^8 cfu), most evident at a concentration of 1×10^4 cfu, not only on culture media PCA but also on semi-synthetic medium and jelly meat-PCA medium. In spite of bacterial results, treatment with plasma plume did not decrease or inhibit of fungal growth. That means plasma plume was neither fungicidal nor fungistatic activities., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Chronic kidney disease (CKD) patients are more susceptible to infections compared to the general population. SARS-CoV-2 virus pathology is characterized by a cytokine storm responsible for the systemic inflammation typical of the COVID-19 disease. Since CKD patients have a reduced renal clearance, we decided to investigate whether they accumulate harmful mediators during the COVID-19 disease. We conducted a retrospective study on 77 COVID-19 hospitalized subjects in the acute phase of the illness. Thirteen different cytokines were assessed in plasma collected upon hospitalization. The patients were divided into three groups according to their estimated glomerular filtration rate, eGFR &lt; 30 (n = 23), 30 &lt; eGFR &lt; 60 (n = 33), eGFR &gt; 60 mL/min (n = 21). We found that Tumor Necrosis Factor α and its receptors I and II, Interleukin-7, Leukemia Inhibitory Factor, FAS receptor, Chitinase 3-like I, and the Vascular Endothelial Growth Factor showed an increased accumulation that negatively correlate with eGFR. Moreover, non-survivor patients with an impaired kidney function have significantly more elevated levels of the same mediators. In conclusion, there is a tendency in COVID-19 ESRD patients to accumulate harmful cytokines. The accumulation seems to associate with mortality outcomes and may be due to reduced clearance but also to increased biosynthesis in most severe cases., Competing Interests: The authors declare no conflict of interest.

Patients with CKD on RRT are at high risk for severe disease and mortality in COVID-19 disease. We decided to conduct an observational prospective study to evaluate antibody response after vaccination for COVID-19 in a cohort of 210 adult patients on RRT (148 on HD; 20 on PD; and 42 kidney transplant recipients). Blood samples were taken before and 4 weeks after vaccination. Antibody levels were evaluated with CLIA immunoassay testing for IgG anti-trimeric spike protein of SARS-CoV-2. A positive antibody titer was present in 89.9% of HD patients, 90% of PD patients, and 52.4% of kidney transplant recipients. Non-responders were more frequent among patients on immunosuppressive therapy. Mycophenolate use in kidney transplant patients was associated with lower antibody response. The median antibody titer was 626 (228-1480) BAU/mL; higher in younger patients and those previously exposed to the virus and lower in HD patients with neoplasms and/or on immunosuppressive therapy. Only two patients developed COVID-19 in the observation period: they both had mild disease and antibody titers lower than 1000 BAU/mL. Our data show a valid response to COVID-19 mRNA vaccination in HD and PD patients and a reduced response in kidney transplant recipients. Mycophenolate was the most relevant factor associated with low response.

Background: The COVID-19 pandemic prompted the scientific community to share timely evidence, also in the form of pre-printed papers, not peer reviewed yet., Purpose: To develop an artificial intelligence system for the analysis of the scientific literature by leveraging on recent developments in the field of Argument Mining., Methodology: Scientific quality criteria were borrowed from two selected Cochrane systematic reviews. Four independent reviewers gave a blind evaluation on a 1-5 scale to 40 papers for each review. These scores were matched with the automatic analysis performed by an AM system named MARGOT, which detected claims and supporting evidence for the cited papers. Outcomes were evaluated with inter-rater indices (Cohen's Kappa, Krippendorff's Alpha, s * statistics)., Results: MARGOT performs differently on the two selected Cochrane reviews: the inter-rater indices show a fair-to-moderate agreement of the most relevant MARGOT metrics both with Cochrane and the skilled interval scores, with larger values for one of the two reviews., Discussion and Conclusions: The noted discrepancy could rely on a limitation of the MARGOT system that can be improved; yet, the level of agreement between human reviewers also suggests a different complexity between the two reviews in debating controversial arguments. These preliminary results encourage to expand and deepen the investigation to other topics and a larger number of highly specialized reviewers, to reduce uncertainty in the evaluation process, thus supporting the retraining of AM systems., (Copyright © 2022 Brambilla, Rosi, Antici, Galassi, Giansanti, Magurano, Ruggeri, Torroni, Cisbani and Lippi.)

Background: Heterogeneous progression of chronic kidney disease (CKD) toward dialysis advocates improving in renal care management. Diagnosis and staging of CKD relies on estimated glomerular filtration rate (eGFR) and albuminuria. Tubular biomarkers emerged as new predictors of worsening renal function (WRF), due to partial inaccuracy of eGFR and existing WRF in non-proteinuric patients. Active vitamin D is synthesized in renal tubules and participates to mineral adaptation in CKD. Circulating 1,25-dihydroxyvitamin D [1,25(OH) 2 D] was poorly investigated as a biomarker of endocrine tubular function and predictor of WRF., Objective: Investigate capability of 1,25(OH) 2 D to predict parathormone (PTH) increase and WRF in CKD stage 3-4., Methods: PASCaL-1,25D was an observational, prospective, monocentric study. Primary outcomes were absolute and 20% increase in PTH, and WRF defined as 20% reduction in eGFR or dialysis initiation at 6 months., Results: Seventy-one patients completed follow up. Absolute increase in PTH (1-84) was independently predicted by lower 1,25(OH) 2 D levels ( p = 0.0134). No association was detected between 1,25(OH) 2 D and iPTH increase. Higher 1,25(OH) 2 D was associated with reduced risk of WRF at univariate analysis [OR 0.89 (95% CI 0.86-0.93), p = 0.006]. The 1,25(OH) 2 D/PTH (1-84) ratio was associated with non-significant 84% risk reduction for WRF [OR 0.16 (95% CI 0.06-0.41), p = 0.05]. Low 1,25(OH) 2 D reached 100% sensitivity in predicting WRF in CKD stage 3 (AUC 9.909, p < 0.0001) and non-elderly patients (AUC 0.883, p < 0.0001). Machine learning models retained 1,25(OH) 2 D/PTH (1-84) as relevant predictor of WRF together with eGFR and albuminuria. Age influenced interaction between renal and mineral biomarkers., Conclusion: 1,25(OH) 2 D deserves attention as biomarker of tubular health, and sensible predictor of WRF on the short run among non-elderly patients affected by stage 3 CKD. The 1,25(OH) 2 D/PTH (1-84) ratio may represent a composite biomarker of tubular reserve/endocrine response to the transition from adaptive to maladaptive equilibrium in CKD-MBD., Competing Interests: FB, MC, and FAB are employees of DiaSorin the manufacturer of the LIAISON® bone and mineral tests. CZ is an independent consultant to DiaSorin. MGC has received consulting fees from DiaSorin in the past for advisory board membership. AG and MGC have received speaking honoraria from Abbvie, Amgen, Shire, and Vifor Fresenius. CM and MAP are employed by Reply Data. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Galassi, Fasulo, Ciceri, Casazza, Bonelli, Zierold, Calleri, Blocki, Palmieri, Mastronardo and Cozzolino.)

Excimer Laser Coronary Atherectomy (ELCA) is a well-established therapy that emerged for the treatment of peripheral vascular atherosclerosis in the late 1980s, at a time when catheters and materials were rudimentary and associated with the most serious complications. Refinements in catheter technology and the introduction of improved laser techniques have led to their effective use for the treatment of a wide spectrum of complex coronary lesions, such as thrombotic lesions, severe calcific lesions, non-crossable or non-expandable lesions, chronic occlusions, and stent under-expansion. The gradual introduction of high-energy strategies combined with the contrast infusion technique has enabled us to treat an increasing number of complex cases with a low rate of periprocedural complications. Currently, the use of the ELCA has also been demonstrated to be effective in acute coronary syndrome (ACS), especially in the context of large thrombotic lesions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Chronic kidney disease mineral and bone disorder may persist after successful kidney transplantation. Persistent hyperparathyroidism has been identified in up to 80% of patients throughout the first year after kidney transplantation. International guidelines lack strict recommendations about the management of persistent hyperparathyroidism. However, it is associated with adverse graft and patient outcomes, including higher fracture risk and an increased risk of all-cause mortality and allograft loss. Secondary hyperparathyroidism may be treated medically (vitamin D, phosphate binders and calcimimetics) or surgically (parathyroidectomy). Guideline recommendations suggest medical therapy first but do not clarify optimal parathyroid hormone targets or indications and timing of parathyroidectomy. There are no clear guidelines or long-term studies about the impact of hyperparathyroidism therapy. Parathyroidectomy is more effective than medical treatment, although it is associated with increased short-term risks. Ideally parathyroidectomy should be performed before kidney transplantation to prevent persistent hyperparathyroidism and improve graft outcomes. We now propose a roadmap for the management of secondary hyperparathyroidism in patients eligible for kidney transplantation that includes the indications and timing (pre- or post-kidney transplantation) of parathyroidectomy, the evaluation of parathyroid gland size and the integration of parathyroid gland size in the decision-making process by a multidisciplinary team of nephrologists, radiologists and surgeons., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Hyperphosphatemia is a common feature in patients with chronic kidney disease (CKD), especially in those with end-stage renal disease (ESRD). Commonly, high serum phosphate levels are observed only in later stages of CKD. The control of hyperphosphatemia plays a key role in the management of CKD patients. However, the optimal range for serum phosphate levels in CKD patients is still controversial. Currently, phosphate binders are the only medications available to reduce elevated serum phosphate levels in patients with ESRD receiving hemodialysis. Tenapanor, an inhibitor of gastrointestinal sodium/hydrogen exchanger 3 (NHE3), acts via a non-phosphate-binding mechanism, reducing paracellular phosphate transport in the intestine. Has tenapanor the potential to improve management of mineral bone disorder in CKD?, (Copyright 2022 Clarivate Analytics.)

Introduction: Secondary hyperparathyroidism (SHPT) represents a complication of chronic kidney disease (CKD). Vitamin D system is altered since early CKD, and vitamin D deficiency is an established trigger of SHPT. Although untreated SHPT may degenerate into tertiary hyperparathyroidism with detrimental consequences in advanced CKD, best treatments for counteracting SHPT from stage 3 CKD are still debated. Enthusiasm on prescription of vitamin D receptor activators (VDRA) in non-dialysis renal patients, has been mitigated by the risk of low bone turnover and positive calcium-phosphate balance. Nutritional vitamin D is now suggested as first-line therapy to treat SHPT with low 25(OH)D insufficiency. However, no high-grade evidence supports the best choice between ergocalciferol, cholecalciferol, and calcifediol (in its immediate or extended-release formulation). Areas covered: The review discusses available data on safety and efficacy of nutritional vitamin D, VDRA and nutritional therapy in replenishing 25(OH)D deficiency and counteracting SHPT in non-dialysis CKD patients. Expert opinion: Best treatment for low 25(OH)D and SHPT remains unknown, due to incomplete understanding of the best homeostatic, as mutable, adaptation of mineral metabolism to CKD progression. Nutritional vitamin D and nutritional therapy appear safest interventions, whenever contextualized with single-patient characteristics. VDRA should be restricted to uncontrolled SHPT by first-line therapy.

Attention is an increasingly popular mechanism used in a wide range of neural architectures. The mechanism itself has been realized in a variety of formats. However, because of the fast-paced advances in this domain, a systematic overview of attention is still missing. In this article, we define a unified model for attention architectures in natural language processing, with a focus on those designed to work with vector representations of the textual data. We propose a taxonomy of attention models according to four dimensions: the representation of the input, the compatibility function, the distribution function, and the multiplicity of the input and/or output. We present the examples of how prior information can be exploited in attention models and discuss ongoing research efforts and open challenges in the area, providing the first extensive categorization of the vast body of literature in this exciting domain.

Chronic kidney disease-mineral bone disorder (CKD-MBD) plays a pivotal role in the excess of cardiovascular morbidity and mortality associated with CKD. There is now a growing awareness that pathways involved in CKD-MBD, like canonical Wnt signalling, are activated from the earliest stages of CKD, playing a role in the development of adynamic bone disease with unknown consequences on vasculature. These changes occur before the classic changes in mineral metabolism: secondary hyperparathyroidism, calcitriol deficiency and hyperphosphataemia. Furthermore, vascular calcification is frequently associated and evolves with decreased bone mineral density and deranged bone turnover, while bone and arterial mineralization share common pathways. Therefore, results of clinical trials focused on mineral bone disorder, aimed at preserving bone and cardiovascular health, are considered unsatisfactory. In order to identify more effective therapeutic strategies, it is necessary to clarify the pathways modulating the cross-talk between bone and vasculature and identify new mediators involved in the pathogenesis of CKD-MBD. Much attention has been paid recently to the role of the transforming growth factor-beta superfamily members in renal disease, and in particular of activin A (ActA). Preclinical studies demonstrate an upgrade of ActA signalling in kidney, skeleton, vasculature and heart during CKD. This supports the idea that an endocrine factor produced in the kidney during renal disease, in addition to promoting the progression of kidney damage, deranges other organs' homoeostasis and participates in CKD-MBD. In this review, we analyse the contribution of ActA to kidney fibrosis and inflammation as well as its role in the development of CKD-MBD., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in March 2020 by the World Health Organization. Older individuals and patients with comorbid conditions such as hypertension, heart disease, diabetes, lung disease, chronic kidney disease (CKD) and immunologic diseases are at higher risk of contracting this severe infection. In particular, patients with advanced CKD constitute a vulnerable population and a challenge in the prevention and control of the disease. Home-based renal replacement therapies offer an opportunity to manage patients remotely, thus reducing the likelihood of infection due to direct human interaction. Patients are seen less frequently, limiting the close interaction between patients and healthcare workers who may contract and spread the disease. However, while home dialysis is a reasonable choice at this time due to the advantage of isolation of patients, measures must be assured to implement the program. Despite its logistical benefits, outpatient haemodialysis also presents certain challenges during times of crises such as the coronavirus disease 2019 (COVID-19) pandemic and potentially future ones., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Cardiovascular disease is a frequent complication and the most common cause of death in patients with CKD. Despite landmark medical advancements, mortality due to cardiovascular disease is still 20 times higher in CKD patients than in the general population, which is mainly due to the high prevalence of risk factors in this group. Indeed, in addition to traditional cardiovascular risk factors, CKD patients are exposed to nontraditional ones, which include metabolic, hormonal, and inflammatory alterations. The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought novel challenges for both cardiologists and nephrologists alike. Emerging evidence indicates that coronavirus disease 2019 (COVID-19) increases the risk of cardiovascular events and that several aspects of the disease may synergize with pre-existing cardiovascular risk factors in CKD patients. A better understanding of these mechanisms is pivotal for the prevention and treatment of cardiovascular events in this context, and we believe that additional clinical and experimental studies are needed to improve cardiovascular outcomes in CKD patients with COVID-19. In this review, we provide a summary of traditional and nontraditional cardiovascular risk factors in CKD patients, discussing their interaction with SARS-CoV-2 infection and focusing on CO-VID-19-related cardiovascular complications that may severely affect short- and long-term outcomes in this high-risk population., (© 2021 S. Karger AG, Basel.)

Identifying patients with high risk of hip fracture is a great challenge in osteoporosis clinical assessment. Bone Mineral Density (BMD) measured by Dual-Energy X-Ray Absorptiometry (DXA) is the current gold standard in osteoporosis clinical assessment. However, its classification accuracy is only around 65%. In order to improve this accuracy, this paper proposes the use of Machine Learning (ML) models trained with data from a biomechanical model that simulates a sideways-fall. Machine Learning (ML) models are models able to learn and to make predictions from data. During a training process, ML models learn a function that maps inputs and outputs without previous knowledge of the problem. The main advantage of ML models is that once the mapping function is constructed, they can make predictions for complex biomechanical behaviours in real time. However, despite the increasing popularity of Machine Learning (ML) models and their wide application to many fields of medicine, their use as hip fracture predictors is still limited. This paper proposes the use of ML models to assess and predict hip fracture risk. Clinical, geometric, and biomechanical variables from the finite element simulation of a side fall are used as independent variables to train the models. Among the different tested models, Random Forest stands out, showing its capability to outperform BMD-DXA, achieving an accuracy over 87%, with specificity over 92% and sensitivity over 83%., Competing Interests: All authors state that they have no conflicts of interest., (Copyright © 2020 Alessio Galassi et al.)

Introduction: The most accurate way of assessing kidney function is the measurement of the glomerular filtration rate (GFR). Since, we do not have good formulae to estimate GFR in elderly, in this study we  evaluate the accuracy of the most commonly used formulas for the estimation of GFR in comparison with direct measurement in elderly., Materials and Methods: 85 patients (51 males and 34 females), with an average age of 76.2 ± 4.4 years, 42% already diagnosed with chronic kidney disease (CKD) were investigated. Two plasma samples were collected between  60-90 and 165-195 minutes after injection of 99mTc-DTPA, and the GFR was calculated applying Charles D. Russell's two-sample method., Results: When comparing the GFR values obtained from the various formulae by creatinine levels with the GFR values obtained by measuring 99mTc-DTPA residue, the following concordance values emerged: (1) MDRD: 57.5 ± 9.59 %; (2) Cockroft-Gault: 48.33 ± 24.93; (3) CKD-EPI: 49.40 ± 26.30; (4) BIS1: 58 ± 6.79., Conclusion: Our data shows a greater concordance between the GFR values calculated with the Russell's method and the estimated values of GFR when the latter are calculated using the MDRD or BIS1 formulae.

Italy was hit hard by the World Wars, still today the discovery of human remains dating back to 20th century is a common phenomenon, in particular on Alpine glaciers, due to climate changes. The authors will describe the Italian scenario in terms of legislation, scientific procedures and related disciplines involved, then the difficulties in the identification of human remains of soldiers, but also potential issues related to uncontrolled "scavenging" activities and consequent ethical aspects. The interdisciplinarity, used as systematic approach to deal with complex cases, allowed the presumptive identification of a WWI soldier recovered after one century from the glaciers of the Adamello mountain, as described. Putting aside the national perspective, the authors endorse and encourage the establishment of an international working group in order to share common issues, to exchange experience and to build global best-practices., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The retention of a large number of solutes that are normally excreted or metabolized by the kidney is responsible for the symptoms typical in uraemic patients. These molecules are defined as uraemic toxins and can be classified into three groups: small water-soluble molecules, middle molecules and protein-bound toxins. Recently, efforts were put towards developing dialysis membranes that allow the removal of large middle molecules without clinically relevant albumin loss. These membranes are the medium cut-off (MCO) membranes that allow the removal of middle molecules up to ∼50 000 Da., Methods: We performed a prospective, open-label, controlled, cross-over pilot study comparing expanded haemodialysis (HDx) (novel MCO membrane Theranova 400) and conventional haemodialysis (HD) in 20 prevalent HD patients. Ten patients used conventional HD high-flux dialyser and 10 patients used HDx for 3 months; later the patients switched and received the other treatment for a further 3 months. We then analysed the pro-calcifying effect of uraemic serum in a model of high phosphate(Pi)-induced calcification in vascular smooth muscle cells (VSMCs)., Results: In this study, every patient was the control of himself and, interestingly, we found a tendency of less pro-calcifying potential from HDx-treated patients' serum compared with HD. Studying pathogenetic processes involved in high Pi-induced calcium deposition, we found that uraemic serum of HDx-treated patients induced less VSMC necrosis compared with uraemic serum of HD patients. Nevertheless, no differences were found between the different dialytic treatments in the serum potential to induce apoptosis and to modulate the expression of a panel of genes involved in VSMC simil-osteoblastic differentiation such as bone morphogenetic protein 2, runt-related transcription factor 2, osteocalcin, matrix Gla protein, osteopontin, elastin and collagen I α1. In an effort to characterize the difference in uraemic toxin profile during the two different dialytic treatments, we measured a panel of 10 uraemic toxins and 3 precursors, finding a significant increased removal during HDx of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, tryptophane and some of its metabolites, such as 3-indoxyl sulphate, indole 3-acetic acid and kynurenine., Conclusions: These preliminary data are promising, although larger patients' groups are needed to better understand the effects of HDx on vascular calcification., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

As the coronavirus spread from Asia to Western Europe and North America, healthcare institutions in the Middle East, Africa, South Asia, and Latin America prepared for the COVID-19 pandemic. Interprofessional task forces were established to coordinate institutions' responses, inventory supplies of personal protective equipment, educate staff and patients, develop procedures for triaging patients and prioritizing care, and provide support to nurses to mitigate their stress. Despite challenges, nurses continued to deliver quality care to patients with cancer.

Chronic kidney disease (CKD) patients have a higher risk of cardiovascular (CVD) morbidity and mortality compared to the general population. The links between CKD and CVD are not fully elucidated but encompass both traditional and uremic-related risk factors. The term CKD-mineral and bone disorder (CKD-MBD) indicates a systemic disorder characterized by abnormal levels of calcium, phosphate, PTH and FGF-23, along with vitamin D deficiency, decreased bone mineral density or altered bone turnover and vascular calcification. A growing body of evidence shows that CKD patients can be affected by subclinical vitamin K deficiency; this has led to identifying such a condition as a potential therapeutic target given the specific role of Vitamin K in metabolism of several proteins involved in bone and vascular health. In other words, we can hypothesize that vitamin K deficiency is the common pathogenetic link between impaired bone mineralization and vascular calcification. However, some of the most common approaches to CKD, such as (1) low vitamin K intake due to nutritional restrictions, (2) warfarin treatment, (3) VDRA and calcimimetics, and (4) phosphate binders, may instead have the opposite effects on vitamin K metabolism and storage in CKD patients.

Vitamin Ddeficiency is frequently present in patients affected by chronic kidney disease (CKD). Experimental studies demonstrated that Vitamin D may play a role in the pathophysiology of diseases beyond mineral bone disorders in CKD (CKD-MBD). Unfortunately, the lack of large and interventional studies focused on the so called "non-classic" effects of 25(OH) Vitamin D supplementation in CKD patients, doesn't permit to conclude definitely about the beneficial effects of this supplementation in clinical practice. In conclusion, treatment of nutritional vitamin D deficiency in CKD may play a central role in both bone homeostasis and cardiovascular outcomes, but there is not clear evidence to support one formulation of nutritional vitamin D over another in CKD., (Copyright © 2019 Elsevier B.V. All rights reserved.)