Jasmine Ion Titapiccolo | Politecnico di Milano (original) (raw)

Papers by Jasmine Ion Titapiccolo

Nefrología, Sep 1, 2018

Introduction: Anaemia is common in haemodialysis patients and treating it with erythropoiesis-sti... more Introduction: Anaemia is common in haemodialysis patients and treating it with erythropoiesis-stimulating agents (ESAs) is complex due to many factors. Objectives: To assess the usefulness of the anaemia control model (ACM) in the treatment of anaemia in haemodialysis. Methods: ACM is a software that predicts the optimal dose of darbepoetin and iron sucrose to achieve target haemoglobin (Hb) and ferritin levels, and makes prescription suggestions. Study conducted in dialysis clinics lasting 18 months with two intervention phases (IPs) with ACM (IP1, n: 213; IP2, n: 218) separated by a control phase (CP, n: 219). The primary outcome was the percentage of Hb in range and the median dose of ESAs, and the secondary outcomes were transfusion, hospitalisation and cardiovascular events. Clinical and patient analyses were performed. Hb variability was assessed by the standard deviation (SD) of the Hb. We also analysed the patients with most of the suggestions confirmed (ACM compliant group). Results: ACM increased the percentage of Hb in range: 80.9% in IP2, compared with 72.7% in the CP and reduced the intake of darbepoetin (IP1: 20 [70]; CP 30 [80] g, p = 0.032) with less Hb fluctuation (0.91 ± 0.49 in the CP to 0.82 ± 0.37 g/dl in IP2, p < 0.05), improving in the ACM compliant group. The secondary outcomes decreased with the use of ACM. Conclusions: ACM helps to obtain better anaemia results in haemodialysis patients, minimising the risks of treatment with ESAs and reducing costs.

Nephrology Dialysis Transplantation, May 1, 2021

Springer eBooks, 2010

Abstract—Ca2+ is an intracellular signal that can regulate many cellular functions. It is at the ... more Abstract—Ca2+ is an intracellular signal that can regulate many cellular functions. It is at the basis of the communication of different cellular populations, as astrocytes. Astrocytes are cells of the brain endowed with supportive functions towards neurons. They also regulate and ...

IEEE Transactions on Biomedical Engineering, Sep 1, 2011

Calcium (Ca 2+) waves and Ca 2+ oscillations within cells initiate a wide range of physiological ... more Calcium (Ca 2+) waves and Ca 2+ oscillations within cells initiate a wide range of physiological processes including control of cell signaling, gene expression, secretion, and cell migration. A thorough analysis of Ca 2+ waves in glial cells provides information not only about the subcellular location of signaling processing events but also about nonneuronal or intercellular signaling pathways, their timing, routes, spatial domains, and coordination. In this study, three novel image processing methods have been applied to the study of Ca 2+ dynamics in cells. These bring additional information to the methods already available in the literature, providing insight into the analysis of calcium dynamics in fluorescence recordings and defining bidimensional maps that give a complete and detailed description of calcium intracellular behavior. The application of these processing methods to glial cells highlighted the complex 2-D Ca 2+ dynamics phenomena, the location of calcium uptake and release microdomains on the endoplasmic reticulum, and the correlation between different calcium signals inside the cell. A perinuclear zone acting as a filter and regulator of intracellular calcium waves was detected: it acts as a controller of calcium fluxes between the cytoplasm and the nucleus. Index Terms-Biomedical image processing, calcium signaling, cell signaling, molecular biology, signal processing. I. INTRODUCTION C a 2+ SIGNALING has a fundamental role in the central nervous system (CNS): it plays an important role in synaptic communication among neurons and between neurons and glial cells [1]. It also participates in different forms of intercellular communication among astrocytes and between astrocytes and other cell types such as neurons [2] and smooth muscle cells around brain blood vessels [3], [4]. The flexibility of calcium signaling is due to the ability of intracellular organelles to control calcium uptake and release into the cytoplasm, in particular the endoplasmic reticulum (ER) stores. When calcium is released, [Ca 2+ ] i rises but then rapidly

Physiological Measurement, Mar 23, 2012

Methods: Total 327 patients were enrolled from 2008 to 2011 in the Korean registry program. They ... more Methods: Total 327 patients were enrolled from 2008 to 2011 in the Korean registry program. They met the criteria of PAH and we investigated the clinical data, the medication prescribed and survival status et al. Results: Their mean age was 40.8 AE 15.8years with female /male patient ratio of 2.7:1. The patients in WHO I/II were 32.4% and WHO III/IV were 67.6%. The peak/mean pulmonary arterial pressure was 86.3/ 56.6 mmHg. Idiopathic PAH (22%), connective tissue disease (24%) and congenital heart disease (46%) were predominant. Small number of patients with familial PAH, portal hypertension, HIV infection, pulmonary capillary hemangiomatosis (PCH) existed. The patients described bosentan were 107, sildenafil 50, iloprost 31, and veraprost 49. After follow-up for mean (AE SD) duration of 37.2 AE 18.1 months of idiopathic PAH, the survival rates at 1, 2, and 3 years were 70.0%, 64%, and 55% respectively. The survival rates of patients with non-idiopathic PAH were better than that of idiopathic PAH patients. Conclusions: The baseline characteristics and survival rates of our cohort study are close to those of the National Institutes of Health Registry of other countries, and the survival rates of patients with idiopathic PAH were worse than that of non-idiopathic PAH patients. Therefore, the target related therapy should be more popular for the improvement of survival rate of idiopathic PAH patients.

Kidney International, Aug 1, 2016

Managing anemia in hemodialysis patients can be challenging because of competing therapeutic targ... more Managing anemia in hemodialysis patients can be challenging because of competing therapeutic targets and individual variability. Because therapy recommendations provided by a decision support system can benefit both patients and doctors, we evaluated the impact of an artificial intelligence decision support system, the Anemia Control Model (ACM), on anemia outcomes. Based on patient profiles, the ACM was built to recommend suitable erythropoietic-stimulating agent doses. Our retrospective study consisted of a 12-month control phase (standard anemia care), followed by a 12-month observation phase (ACM-guided care) encompassing 752 patients undergoing hemodialysis therapy in 3 NephroCare clinics located in separate countries. The percentage of hemoglobin values on target, the median darbepoetin dose, and individual hemoglobin fluctuation (estimated from the intrapatient hemoglobin standard deviation) were deemed primary outcomes. In the observation phase, median darbepoetin consumption significantly decreased from 0.63 to 0.46 mg/kg/month, whereas on-target hemoglobin values significantly increased from 70.6% to 76.6%, reaching 83.2% when the ACM suggestions were implemented. Moreover, ACM introduction led to a significant decrease in hemoglobin fluctuation (intrapatient standard deviation decreased from 0.95 g/dl to 0.83 g/dl). Thus, ACM support helped improve anemia outcomes of hemodialysis patients, minimizing erythropoietic-stimulating agent use with the potential to reduce the cost of treatment.

Frontiers in nephrology, Jul 12, 2022

Background and Objectives: Cardiovascular (CV) disease is the main cause of morbidity and mortali... more Background and Objectives: Cardiovascular (CV) disease is the main cause of morbidity and mortality in patients suffering from chronic kidney disease (CKD). Although it is widely recognized that CV risk assessment represents an essential prerequisite for clinical management, existing prognostic models appear not to be entirely adequate for CKD patients. We derived a literature-based, naïve-bayes model predicting the yearly risk of CV hospitalizations among patients suffering from CKD, referred as the CArdiovascular, LIterature-Based, Risk Algorithm (CALIBRA). Methods: CALIBRA incorporates 31 variables including traditional and CKD-specific risk factors. It was validated in two independent CKD populations: the FMC NephroCare cohort (European Clinical Database, EuCliD ®) and the German Chronic Kidney Disease (GCKD) study prospective cohort. CALIBRA performance was evaluated by c-statistics and calibration charts. In addition, CALIBRA discrimination was compared with that of three validated tools currently used for CV prediction in CKD, namely the Framingham Heart Study (FHS) risk score, the atherosclerotic cardiovascular disease risk score (ASCVD), and the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) calculator. Superiority was defined as a DAUC>0.05. Results: CALIBRA showed good discrimination in both the EuCliD ® medical registry (AUC 0.79, 95%CI 0.76-0.81) and the GCKD cohort (AUC 0.73, 95%CI 0.70-0.76). CALIBRA demonstrated improved accuracy compared to the benchmark models in EuCliD ®

Nephrology Dialysis Transplantation, May 1, 2022

Blood pressure (BP) response to volume depletion induced by hemodialysis (HD) treatment may be im... more Blood pressure (BP) response to volume depletion induced by hemodialysis (HD) treatment may be important to understand the pathophysiology of the increased mortality in HD patients with vascular calcification. In the present study a comparison between end stage renal disease (ESRD) patients affected by peripheral vascular disease (PVD) and ESRD patients without PVD was performed. Continuous blood pressure was recorded at the beginning and at the end of HD. BP and heart rate variability (HRV) were analyzed to quantify the autonomic nervous system regulation of heart beat and peripheral resistance. PVD patients showed an increase of pulse pressure (PP) during HD, an altered autonomic peripheral control, a lower sympathetic activity, with respect to ESRD patients without PVD.

Nephrology Dialysis Transplantation, Apr 21, 2021

Background. Treatment of end-stage kidney disease patients is extremely challenging given the int... more Background. Treatment of end-stage kidney disease patients is extremely challenging given the interconnected functional derangements and comorbidities characterizing the disease. Continuous quality improvement (CQI) in healthcare is a structured clinical governance process helping physicians adhere to best clinical practices. The digitization of patient medical records and data warehousing technologies has standardized and enhanced the efficiency of the CQI's evidence generation process. There is limited evidence that ameliorating intermediate outcomes would translate into better patient-centred outcomes. We sought to evaluate the relationship between Fresenius Medical Care medical patient review CQI (MPR-CQI) implementation and patients' survival in a large historical cohort study. Methods. We included all incident adult patients with 6-months survival on chronic dialysis registered in the Europe, Middle East and Africa region between 2011 and 2018. We compared medical key performance indicator (KPI) target achievements and 2-year mortality for patients enrolled prior to and after MPR-CQI policy onset (Cohorts A and B). We adopted a structural equation model where MPR-CQI policy was the exogenous explanatory variable, KPI target achievements was the mediator variable and survival was the outcome of interest. Results. About 4270 patients (Cohort A: 2397; Cohort B: 1873) met the inclusion criteria. We observed an increase in KPI target achievements after MPR-CQI policy implementation. Mediation analysis demonstrated a significant reduction in mortality due to an indirect effect of MPR-CQI implementation through improvement in KPI target achievement occurring in the post-implementation era [odds ratio 0.70 (95% confidence interval 0.65-0.76); P < 0.0001]. Conclusions. Our study suggests that MPR-CQI achieved by standardized clinical practice and periodic structured MPR may improve patients' survival through improvement in medical KPIs.

Nefrologia, Sep 1, 2018

Resumen Introduccion La anemia es frecuente en los pacientes en hemodialisis, y su tratamiento co... more Resumen Introduccion La anemia es frecuente en los pacientes en hemodialisis, y su tratamiento con estimulantes de la eritropoyesis (AEE) resulta complejo debido a multiples factores. Objetivos Valorar la utilidad del modelo de control de anemia (MCA) en el tratamiento de la anemia en hemodialisis. Metodos El MCA es un software que predice la dosis optima de darbepoetina y hierro sacarosa para alcanzar niveles de hemoglobina (Hb) y ferritina deseados, emitiendo sugerencias de prescripcion. Estudio realizado en clinicas de dialisis de 18 meses de duracion en dos fases de intervencion (FI) con MCA (FI1, n: 213; FI2, n: 218) separadas por una fase de control (FC, n: 219). El resultado primario fue el porcentaje de Hb en rango y la mediana de dosis de AEE y los resultados secundarios fueron las transfusiones, las hospitalizaciones o los acontecimientos cardiovasculares. Analisis a nivel de clinica y de pacientes valorando la variabilidad de la Hb mediante la desviacion estandar (DE) de esta. Tambien se analizaron pacientes con la mayoria de sugerencias confirmadas (grupo MCA cumplidores) Resultados El MCA aumento el porcentaje de Hb en rango: 80,9% FI2 frente a 72,7% en FC, y redujo el consumo de darbepoetina (FI1: 20 [70]; FC 30 [80] μg, p = 0,032) con menor fluctuacion de la Hb (0,91 ± 0,49 en FC a 0,82 ± 0,37 g/dl en FI2; p Conclusiones El MCA ayuda a obtener mejores resultados de anemia en los pacientes en hemodialisis, minimizando los riesgos del tratamiento con AEE y reduciendo costes.

Springer eBooks, 2014

Chronic renal failure (CRF) patients experience a 30% higher risk of cardiovascular (CV) death co... more Chronic renal failure (CRF) patients experience a 30% higher risk of cardiovascular (CV) death compared to the general population. In this study data of 3581 incident hemodialysis (HD) patients were considered, i.e. patients who started for the first time the HD treatment. In this work supervised SOM were used with an innovative strategy to built a predictive model to estimate the probability that incident CRF patients experience a CV event in the second semester after a semester of HD treatment. A feature selection approach based on the minimum redundancy maximum relevance (mRMR) algorithm, was wrapped on the self-organizing maps (SOMs) model and a subset of 17 physiological variables with higher performance capability than the complete set of 39 variables was identified. AUC of the ROC curve of the shrunk model was 67±4%. The obtained model permits to investigate non-linear relationships among features related to an increased CV risk condition.

A crucial point in the haemodialysis (HD) treatment is the reliable assessment of hydration statu... more A crucial point in the haemodialysis (HD) treatment is the reliable assessment of hydration status. An inadequate removed volume may lead to chronic fluid overload which can lead to hypertension, left ventricular hypertrophy and heart failure. Therefore, the estimation of the hydration state and the management of a well-tolerated water removal is an important challenge. This exploratory study aims at identifying new parameters obtained from continuous Blood Volume Monitoring (BVM) allowing a qualitative evaluation of hydration status for verifying the adequacy of HD setting parameters (e.g UFR, target dry weight). The percentage of blood volume reduction (BVR%) during HD was compared against a gold standard method for hydration status assessment. The slope of the first 30 minute of blood volume reduction (BVR) was proposed as a useful parameter to identify overhydrated patients.

Abstract The main objective of this work is to develop and apply data mining methods for the pred... more Abstract The main objective of this work is to develop and apply data mining methods for the prediction of patient outcome in nephrology care. Cardiovascular events have an incidence of 20% in the first year of hemodialysis (HD). Real data routinely collected during HD administration were extracted from the Fresenius Medical Care database EuCliD (39 independent variables) and used to develop a random forest predictive model for the forecast of cardiovascular events in the first year of HD treatment. Two feature selection ...

Expert Systems With Applications, Sep 1, 2013

End stage renal disease condition increases the risk of cardiovascular disease. The mortality rat... more End stage renal disease condition increases the risk of cardiovascular disease. The mortality rates among hemodialysis patients are 20% higher than the general population, thus in recent years the preservation of the cardiovascular system has become a major point of focus for nephrology care in patients. Cardiovascular events jeopardize the life of a dialysis patient and must therefore be prevented. The aim of this study is to develop forecast models that can predict the cardiovascular outcome of incident hemodialysis (HD) patients. Data relating to the treatment methods and the physiological condition of patients was collected during the first 18 months of renal replacement therapy and then used to predict the insurgence of cardiovascular events within a 6-month time window. Information regarding 4246 incident hemodialysis patients was collected. A Lasso logistic regression model and a random forest model were developed and used for predictive comparison. Every forecast model was tested on 20% of the data and a 5-fold cross validation approach was used to validate the random forest model. Random forest showed higher performance with AUC of the ROC curve and sensitivity higher than 70% in both the temporal windows models, proving that random forests are able to exploit non-linear patterns retrieved in the feature space. Out of bag estimates of variable importance and regression coefficients were used to gain insight into the models implemented. We found out that malnutrition and an inflammatory condition strongly influence cardiovascular outcome in incident HD patients. Indeed the most important variables in the model were blood test variables such as the total protein content, percentage value of albumin, total protein content, creatinine and C reactive protein. Age of patients and weight loss in the first six months of renal replacement therapy were also highly involved in the prediction. A greater understanding of the mechanisms involved in the insurgence of cardiovascular events in dialysis patients can ensure physicians to intervene in the appropriate manner when a high-risk cardiovascular condition is identified.

Springer eBooks, 2010

... Abstract— Astrocytes perinuclear zone is an intracellular region of great interest for its ro... more ... Abstract— Astrocytes perinuclear zone is an intracellular region of great interest for its role in calcium intracellular dynamics regulation. ... Keywords— Astrocytes, fluorescence,calcium dynamics, IP3 receptors, SERCA pumps. I. INTRODUCTION ...

Nephrology Dialysis Transplantation, Jun 1, 2020

Nephrology Dialysis Transplantation, May 1, 2022

BACKGROUND AND AIMS: Low muscle strength is associated with adverse clinical outcomes in patients... more BACKGROUND AND AIMS: Low muscle strength is associated with adverse clinical outcomes in patients on hemodialysis (HD). However, the association between dynapenia, characterized by both low handgrip strength (HGS) and leg strength (LS) and long-term clinical outcomes in patients on HD has not yet been reported. Therefore, this study investigated whether dynapenia was associated with higher cardiovascular (CV) hospitalization risk and all-cause mortality in patients on HD. METHOD: This retrospective study used the data of outpatients on HD from two dialysis facilities between October 2002 and March 2020. This study was approved by the Institutional Review Board/Ethics Committee of Kitasato University of Allied Health Sciences and was conducted in accordance with the principles of the Declaration of Helsinki. All participants provided written informed consent before inclusion in the study. Low muscle strength was defined as an HGS of < 28 kg for men and < 18 kg for women and an LS of < 40% dry weight. Furthermore, dynapenia was categorized into three groups: robust ('high HGS and high LS'), either low HGS or low LS ('low HGS only' or 'low LS only') and dynapenia ('low HGS and low LS'). The outcomes were all-cause mortality and a composite of CV hospitalizations and mortality. These associations were examined using Cox proportional hazards and negative binomial models. RESULTS: Data from 616 patients (mean age, 65.4 ± 12.2 years; men, 61%) were analyzed. During the follow-up (median, 3.0 years), 163 deaths and 288 CV hospitalizations occurred. Figure 1 shows the results of the Kaplan-Meier survival analyses of the robust, either low HGS or low LS, and dynapenia groups. The logrank test showed significantly worse survival in the either low HGS or low LS and dynapenia groups than in the robust group (P < 0.001). After adjusting for age, sex, body mass index, HD vintage, comorbidity index, serum albumin, serum hemoglobin, serum creatinine and C-reactive protein levels, patients with either low HGS or low LS [hazard ratio (HR), 1.81; 95% confidence intervals (95% CIs), 1.51-2.17] and dynapenia (HR 2.77, 95% CI 2.48-3.08) were found to have a higher mortality risk than those in the robust group. Similarly, compared with the robust group, either the low HGS or low LS [incidence rate ratio (IRR) 1.45, 95% CI 1.04-2.03] and dynapenia (IRR 2.06, 95% CI 1.48-2.89) groups had higher multiple CV hospitalization and all-cause mortality risks. CONCLUSION: Dynapenia, characterized by both low HGS and LS, was significantly associated with increased CV hospitalization and mortality risk in patients on HD. Clinical assessments of muscle strength and screening patients with low muscle strength are crucial for disease management in this population. Measuring the muscle strength of the entire extremity, and not only the upper or lower extremities, may be necessary for accurate prognostic stratification.

The administration of hemodialysis (HD) treatment leads to the continuous collection of a vast qu... more The administration of hemodialysis (HD) treatment leads to the continuous collection of a vast quantity of medical data. Many variables related to the patient health status, to the treatment, and to dialyzer settings can be recorded and stored at each treatment session. In this study a dataset of 42 variables and 1526 patients extracted from the Fresenius Medical Care database EuCliD was used to develop and apply a random forest predictive model for the prediction of cardiovascular events in the first year of HD treatment. A ridge-lasso logistic regression algorithm was then applied to the subset of variables mostly involved in the prediction model to get insights in the mechanisms underlying the incidence of cardiovascular complications in this high risk population of patients.

Nephrology Dialysis Transplantation, May 1, 2022

BACKGROUND AND AIMS: Chronic kidney disease-associated pruritus (CKD-aP) is common, yet underreco... more BACKGROUND AND AIMS: Chronic kidney disease-associated pruritus (CKD-aP) is common, yet underrecognized condition among end-stage kidney disease patients. We sought to evaluate the prevalence of CKD-aP and its impact on health-related quality of life (HRQOL) among dialysis patients across five European countries. METHOD: This is a retrospective, observational analysis of data abstracted from the EuCliD R database (European Clinical database), the clinical information system adopted in Fresenius Medical Care (FMC) outpatient dialysis facilities in several European countries. Patient-Reported Outcomes Measures (PROM) were collected as part of a continuous quality improvement program launched for the first time in all centres belonging to the Nephrocare network in France, Italy, Spain, United Kingdom and Ireland. The presence and severity of CKD-aP were documented based on information captured by both the Kidney Disease Quality of Life (KDQOL TM-36) and the 5-D Itch questionnaires. HRQOL was assessed with KDQOL TM-36. Clinical and demographic data have been extracted from EuCliD R. The relationship between CKD-aP and HRQOL was evaluated with generalized linear models. RESULTS: The ePROM campaign attained a large participation rate with very low attrition. Among 9974 who were actively treated in the clinics and were able to fill in a self-reported questionnaire, 8157 responded to the survey and only 1033 (11.2%) refused to participate. We enrolled 6221 patients in the present secondary analysis. The study flowchart is reported in Figure 1. Slightly more than half of patients (52%) reported no CKD-aP, 25% mild, whereas roughly 23% reported moderate-to-severe CKD-aP. Patients reporting more severe CKD-aP had shorter dialysis vintage, higher phosphate and parathormone, and more frequently diabetes. Average KDQOL-36 scores are reported in Figure 2a. We observed a strong, graded relationship between CKD-aP severity and KDQOL-36 scores (Figure 2b). The association was robust to adjustment for potential confounders. The quality of life penalty associated with more severe pruritus was clinically significant based on distribution based minimal clinically important difference threshold for the KDQOL-36 scales. CONCLUSION: CKD-aP was common in a large, representative sample of the dialysis population in five European countries. We observed a large, clinically important, quality of life penalty associated with CKD-aP even after adjusting for potential confounders.

Nefrología, Sep 1, 2018

Introduction: Anaemia is common in haemodialysis patients and treating it with erythropoiesis-sti... more Introduction: Anaemia is common in haemodialysis patients and treating it with erythropoiesis-stimulating agents (ESAs) is complex due to many factors. Objectives: To assess the usefulness of the anaemia control model (ACM) in the treatment of anaemia in haemodialysis. Methods: ACM is a software that predicts the optimal dose of darbepoetin and iron sucrose to achieve target haemoglobin (Hb) and ferritin levels, and makes prescription suggestions. Study conducted in dialysis clinics lasting 18 months with two intervention phases (IPs) with ACM (IP1, n: 213; IP2, n: 218) separated by a control phase (CP, n: 219). The primary outcome was the percentage of Hb in range and the median dose of ESAs, and the secondary outcomes were transfusion, hospitalisation and cardiovascular events. Clinical and patient analyses were performed. Hb variability was assessed by the standard deviation (SD) of the Hb. We also analysed the patients with most of the suggestions confirmed (ACM compliant group). Results: ACM increased the percentage of Hb in range: 80.9% in IP2, compared with 72.7% in the CP and reduced the intake of darbepoetin (IP1: 20 [70]; CP 30 [80] g, p = 0.032) with less Hb fluctuation (0.91 ± 0.49 in the CP to 0.82 ± 0.37 g/dl in IP2, p < 0.05), improving in the ACM compliant group. The secondary outcomes decreased with the use of ACM. Conclusions: ACM helps to obtain better anaemia results in haemodialysis patients, minimising the risks of treatment with ESAs and reducing costs.

Nephrology Dialysis Transplantation, May 1, 2021

Springer eBooks, 2010

Abstract—Ca2+ is an intracellular signal that can regulate many cellular functions. It is at the ... more Abstract—Ca2+ is an intracellular signal that can regulate many cellular functions. It is at the basis of the communication of different cellular populations, as astrocytes. Astrocytes are cells of the brain endowed with supportive functions towards neurons. They also regulate and ...

IEEE Transactions on Biomedical Engineering, Sep 1, 2011

Calcium (Ca 2+) waves and Ca 2+ oscillations within cells initiate a wide range of physiological ... more Calcium (Ca 2+) waves and Ca 2+ oscillations within cells initiate a wide range of physiological processes including control of cell signaling, gene expression, secretion, and cell migration. A thorough analysis of Ca 2+ waves in glial cells provides information not only about the subcellular location of signaling processing events but also about nonneuronal or intercellular signaling pathways, their timing, routes, spatial domains, and coordination. In this study, three novel image processing methods have been applied to the study of Ca 2+ dynamics in cells. These bring additional information to the methods already available in the literature, providing insight into the analysis of calcium dynamics in fluorescence recordings and defining bidimensional maps that give a complete and detailed description of calcium intracellular behavior. The application of these processing methods to glial cells highlighted the complex 2-D Ca 2+ dynamics phenomena, the location of calcium uptake and release microdomains on the endoplasmic reticulum, and the correlation between different calcium signals inside the cell. A perinuclear zone acting as a filter and regulator of intracellular calcium waves was detected: it acts as a controller of calcium fluxes between the cytoplasm and the nucleus. Index Terms-Biomedical image processing, calcium signaling, cell signaling, molecular biology, signal processing. I. INTRODUCTION C a 2+ SIGNALING has a fundamental role in the central nervous system (CNS): it plays an important role in synaptic communication among neurons and between neurons and glial cells [1]. It also participates in different forms of intercellular communication among astrocytes and between astrocytes and other cell types such as neurons [2] and smooth muscle cells around brain blood vessels [3], [4]. The flexibility of calcium signaling is due to the ability of intracellular organelles to control calcium uptake and release into the cytoplasm, in particular the endoplasmic reticulum (ER) stores. When calcium is released, [Ca 2+ ] i rises but then rapidly

Physiological Measurement, Mar 23, 2012

Methods: Total 327 patients were enrolled from 2008 to 2011 in the Korean registry program. They ... more Methods: Total 327 patients were enrolled from 2008 to 2011 in the Korean registry program. They met the criteria of PAH and we investigated the clinical data, the medication prescribed and survival status et al. Results: Their mean age was 40.8 AE 15.8years with female /male patient ratio of 2.7:1. The patients in WHO I/II were 32.4% and WHO III/IV were 67.6%. The peak/mean pulmonary arterial pressure was 86.3/ 56.6 mmHg. Idiopathic PAH (22%), connective tissue disease (24%) and congenital heart disease (46%) were predominant. Small number of patients with familial PAH, portal hypertension, HIV infection, pulmonary capillary hemangiomatosis (PCH) existed. The patients described bosentan were 107, sildenafil 50, iloprost 31, and veraprost 49. After follow-up for mean (AE SD) duration of 37.2 AE 18.1 months of idiopathic PAH, the survival rates at 1, 2, and 3 years were 70.0%, 64%, and 55% respectively. The survival rates of patients with non-idiopathic PAH were better than that of idiopathic PAH patients. Conclusions: The baseline characteristics and survival rates of our cohort study are close to those of the National Institutes of Health Registry of other countries, and the survival rates of patients with idiopathic PAH were worse than that of non-idiopathic PAH patients. Therefore, the target related therapy should be more popular for the improvement of survival rate of idiopathic PAH patients.

Kidney International, Aug 1, 2016

Managing anemia in hemodialysis patients can be challenging because of competing therapeutic targ... more Managing anemia in hemodialysis patients can be challenging because of competing therapeutic targets and individual variability. Because therapy recommendations provided by a decision support system can benefit both patients and doctors, we evaluated the impact of an artificial intelligence decision support system, the Anemia Control Model (ACM), on anemia outcomes. Based on patient profiles, the ACM was built to recommend suitable erythropoietic-stimulating agent doses. Our retrospective study consisted of a 12-month control phase (standard anemia care), followed by a 12-month observation phase (ACM-guided care) encompassing 752 patients undergoing hemodialysis therapy in 3 NephroCare clinics located in separate countries. The percentage of hemoglobin values on target, the median darbepoetin dose, and individual hemoglobin fluctuation (estimated from the intrapatient hemoglobin standard deviation) were deemed primary outcomes. In the observation phase, median darbepoetin consumption significantly decreased from 0.63 to 0.46 mg/kg/month, whereas on-target hemoglobin values significantly increased from 70.6% to 76.6%, reaching 83.2% when the ACM suggestions were implemented. Moreover, ACM introduction led to a significant decrease in hemoglobin fluctuation (intrapatient standard deviation decreased from 0.95 g/dl to 0.83 g/dl). Thus, ACM support helped improve anemia outcomes of hemodialysis patients, minimizing erythropoietic-stimulating agent use with the potential to reduce the cost of treatment.

Frontiers in nephrology, Jul 12, 2022

Background and Objectives: Cardiovascular (CV) disease is the main cause of morbidity and mortali... more Background and Objectives: Cardiovascular (CV) disease is the main cause of morbidity and mortality in patients suffering from chronic kidney disease (CKD). Although it is widely recognized that CV risk assessment represents an essential prerequisite for clinical management, existing prognostic models appear not to be entirely adequate for CKD patients. We derived a literature-based, naïve-bayes model predicting the yearly risk of CV hospitalizations among patients suffering from CKD, referred as the CArdiovascular, LIterature-Based, Risk Algorithm (CALIBRA). Methods: CALIBRA incorporates 31 variables including traditional and CKD-specific risk factors. It was validated in two independent CKD populations: the FMC NephroCare cohort (European Clinical Database, EuCliD ®) and the German Chronic Kidney Disease (GCKD) study prospective cohort. CALIBRA performance was evaluated by c-statistics and calibration charts. In addition, CALIBRA discrimination was compared with that of three validated tools currently used for CV prediction in CKD, namely the Framingham Heart Study (FHS) risk score, the atherosclerotic cardiovascular disease risk score (ASCVD), and the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) calculator. Superiority was defined as a DAUC>0.05. Results: CALIBRA showed good discrimination in both the EuCliD ® medical registry (AUC 0.79, 95%CI 0.76-0.81) and the GCKD cohort (AUC 0.73, 95%CI 0.70-0.76). CALIBRA demonstrated improved accuracy compared to the benchmark models in EuCliD ®

Nephrology Dialysis Transplantation, May 1, 2022

Blood pressure (BP) response to volume depletion induced by hemodialysis (HD) treatment may be im... more Blood pressure (BP) response to volume depletion induced by hemodialysis (HD) treatment may be important to understand the pathophysiology of the increased mortality in HD patients with vascular calcification. In the present study a comparison between end stage renal disease (ESRD) patients affected by peripheral vascular disease (PVD) and ESRD patients without PVD was performed. Continuous blood pressure was recorded at the beginning and at the end of HD. BP and heart rate variability (HRV) were analyzed to quantify the autonomic nervous system regulation of heart beat and peripheral resistance. PVD patients showed an increase of pulse pressure (PP) during HD, an altered autonomic peripheral control, a lower sympathetic activity, with respect to ESRD patients without PVD.

Nephrology Dialysis Transplantation, Apr 21, 2021

Background. Treatment of end-stage kidney disease patients is extremely challenging given the int... more Background. Treatment of end-stage kidney disease patients is extremely challenging given the interconnected functional derangements and comorbidities characterizing the disease. Continuous quality improvement (CQI) in healthcare is a structured clinical governance process helping physicians adhere to best clinical practices. The digitization of patient medical records and data warehousing technologies has standardized and enhanced the efficiency of the CQI's evidence generation process. There is limited evidence that ameliorating intermediate outcomes would translate into better patient-centred outcomes. We sought to evaluate the relationship between Fresenius Medical Care medical patient review CQI (MPR-CQI) implementation and patients' survival in a large historical cohort study. Methods. We included all incident adult patients with 6-months survival on chronic dialysis registered in the Europe, Middle East and Africa region between 2011 and 2018. We compared medical key performance indicator (KPI) target achievements and 2-year mortality for patients enrolled prior to and after MPR-CQI policy onset (Cohorts A and B). We adopted a structural equation model where MPR-CQI policy was the exogenous explanatory variable, KPI target achievements was the mediator variable and survival was the outcome of interest. Results. About 4270 patients (Cohort A: 2397; Cohort B: 1873) met the inclusion criteria. We observed an increase in KPI target achievements after MPR-CQI policy implementation. Mediation analysis demonstrated a significant reduction in mortality due to an indirect effect of MPR-CQI implementation through improvement in KPI target achievement occurring in the post-implementation era [odds ratio 0.70 (95% confidence interval 0.65-0.76); P < 0.0001]. Conclusions. Our study suggests that MPR-CQI achieved by standardized clinical practice and periodic structured MPR may improve patients' survival through improvement in medical KPIs.

Nefrologia, Sep 1, 2018

Resumen Introduccion La anemia es frecuente en los pacientes en hemodialisis, y su tratamiento co... more Resumen Introduccion La anemia es frecuente en los pacientes en hemodialisis, y su tratamiento con estimulantes de la eritropoyesis (AEE) resulta complejo debido a multiples factores. Objetivos Valorar la utilidad del modelo de control de anemia (MCA) en el tratamiento de la anemia en hemodialisis. Metodos El MCA es un software que predice la dosis optima de darbepoetina y hierro sacarosa para alcanzar niveles de hemoglobina (Hb) y ferritina deseados, emitiendo sugerencias de prescripcion. Estudio realizado en clinicas de dialisis de 18 meses de duracion en dos fases de intervencion (FI) con MCA (FI1, n: 213; FI2, n: 218) separadas por una fase de control (FC, n: 219). El resultado primario fue el porcentaje de Hb en rango y la mediana de dosis de AEE y los resultados secundarios fueron las transfusiones, las hospitalizaciones o los acontecimientos cardiovasculares. Analisis a nivel de clinica y de pacientes valorando la variabilidad de la Hb mediante la desviacion estandar (DE) de esta. Tambien se analizaron pacientes con la mayoria de sugerencias confirmadas (grupo MCA cumplidores) Resultados El MCA aumento el porcentaje de Hb en rango: 80,9% FI2 frente a 72,7% en FC, y redujo el consumo de darbepoetina (FI1: 20 [70]; FC 30 [80] μg, p = 0,032) con menor fluctuacion de la Hb (0,91 ± 0,49 en FC a 0,82 ± 0,37 g/dl en FI2; p Conclusiones El MCA ayuda a obtener mejores resultados de anemia en los pacientes en hemodialisis, minimizando los riesgos del tratamiento con AEE y reduciendo costes.

Springer eBooks, 2014

Chronic renal failure (CRF) patients experience a 30% higher risk of cardiovascular (CV) death co... more Chronic renal failure (CRF) patients experience a 30% higher risk of cardiovascular (CV) death compared to the general population. In this study data of 3581 incident hemodialysis (HD) patients were considered, i.e. patients who started for the first time the HD treatment. In this work supervised SOM were used with an innovative strategy to built a predictive model to estimate the probability that incident CRF patients experience a CV event in the second semester after a semester of HD treatment. A feature selection approach based on the minimum redundancy maximum relevance (mRMR) algorithm, was wrapped on the self-organizing maps (SOMs) model and a subset of 17 physiological variables with higher performance capability than the complete set of 39 variables was identified. AUC of the ROC curve of the shrunk model was 67±4%. The obtained model permits to investigate non-linear relationships among features related to an increased CV risk condition.

A crucial point in the haemodialysis (HD) treatment is the reliable assessment of hydration statu... more A crucial point in the haemodialysis (HD) treatment is the reliable assessment of hydration status. An inadequate removed volume may lead to chronic fluid overload which can lead to hypertension, left ventricular hypertrophy and heart failure. Therefore, the estimation of the hydration state and the management of a well-tolerated water removal is an important challenge. This exploratory study aims at identifying new parameters obtained from continuous Blood Volume Monitoring (BVM) allowing a qualitative evaluation of hydration status for verifying the adequacy of HD setting parameters (e.g UFR, target dry weight). The percentage of blood volume reduction (BVR%) during HD was compared against a gold standard method for hydration status assessment. The slope of the first 30 minute of blood volume reduction (BVR) was proposed as a useful parameter to identify overhydrated patients.

Abstract The main objective of this work is to develop and apply data mining methods for the pred... more Abstract The main objective of this work is to develop and apply data mining methods for the prediction of patient outcome in nephrology care. Cardiovascular events have an incidence of 20% in the first year of hemodialysis (HD). Real data routinely collected during HD administration were extracted from the Fresenius Medical Care database EuCliD (39 independent variables) and used to develop a random forest predictive model for the forecast of cardiovascular events in the first year of HD treatment. Two feature selection ...

Expert Systems With Applications, Sep 1, 2013

End stage renal disease condition increases the risk of cardiovascular disease. The mortality rat... more End stage renal disease condition increases the risk of cardiovascular disease. The mortality rates among hemodialysis patients are 20% higher than the general population, thus in recent years the preservation of the cardiovascular system has become a major point of focus for nephrology care in patients. Cardiovascular events jeopardize the life of a dialysis patient and must therefore be prevented. The aim of this study is to develop forecast models that can predict the cardiovascular outcome of incident hemodialysis (HD) patients. Data relating to the treatment methods and the physiological condition of patients was collected during the first 18 months of renal replacement therapy and then used to predict the insurgence of cardiovascular events within a 6-month time window. Information regarding 4246 incident hemodialysis patients was collected. A Lasso logistic regression model and a random forest model were developed and used for predictive comparison. Every forecast model was tested on 20% of the data and a 5-fold cross validation approach was used to validate the random forest model. Random forest showed higher performance with AUC of the ROC curve and sensitivity higher than 70% in both the temporal windows models, proving that random forests are able to exploit non-linear patterns retrieved in the feature space. Out of bag estimates of variable importance and regression coefficients were used to gain insight into the models implemented. We found out that malnutrition and an inflammatory condition strongly influence cardiovascular outcome in incident HD patients. Indeed the most important variables in the model were blood test variables such as the total protein content, percentage value of albumin, total protein content, creatinine and C reactive protein. Age of patients and weight loss in the first six months of renal replacement therapy were also highly involved in the prediction. A greater understanding of the mechanisms involved in the insurgence of cardiovascular events in dialysis patients can ensure physicians to intervene in the appropriate manner when a high-risk cardiovascular condition is identified.

Springer eBooks, 2010

... Abstract— Astrocytes perinuclear zone is an intracellular region of great interest for its ro... more ... Abstract— Astrocytes perinuclear zone is an intracellular region of great interest for its role in calcium intracellular dynamics regulation. ... Keywords— Astrocytes, fluorescence,calcium dynamics, IP3 receptors, SERCA pumps. I. INTRODUCTION ...

Nephrology Dialysis Transplantation, Jun 1, 2020

Nephrology Dialysis Transplantation, May 1, 2022

BACKGROUND AND AIMS: Low muscle strength is associated with adverse clinical outcomes in patients... more BACKGROUND AND AIMS: Low muscle strength is associated with adverse clinical outcomes in patients on hemodialysis (HD). However, the association between dynapenia, characterized by both low handgrip strength (HGS) and leg strength (LS) and long-term clinical outcomes in patients on HD has not yet been reported. Therefore, this study investigated whether dynapenia was associated with higher cardiovascular (CV) hospitalization risk and all-cause mortality in patients on HD. METHOD: This retrospective study used the data of outpatients on HD from two dialysis facilities between October 2002 and March 2020. This study was approved by the Institutional Review Board/Ethics Committee of Kitasato University of Allied Health Sciences and was conducted in accordance with the principles of the Declaration of Helsinki. All participants provided written informed consent before inclusion in the study. Low muscle strength was defined as an HGS of < 28 kg for men and < 18 kg for women and an LS of < 40% dry weight. Furthermore, dynapenia was categorized into three groups: robust ('high HGS and high LS'), either low HGS or low LS ('low HGS only' or 'low LS only') and dynapenia ('low HGS and low LS'). The outcomes were all-cause mortality and a composite of CV hospitalizations and mortality. These associations were examined using Cox proportional hazards and negative binomial models. RESULTS: Data from 616 patients (mean age, 65.4 ± 12.2 years; men, 61%) were analyzed. During the follow-up (median, 3.0 years), 163 deaths and 288 CV hospitalizations occurred. Figure 1 shows the results of the Kaplan-Meier survival analyses of the robust, either low HGS or low LS, and dynapenia groups. The logrank test showed significantly worse survival in the either low HGS or low LS and dynapenia groups than in the robust group (P < 0.001). After adjusting for age, sex, body mass index, HD vintage, comorbidity index, serum albumin, serum hemoglobin, serum creatinine and C-reactive protein levels, patients with either low HGS or low LS [hazard ratio (HR), 1.81; 95% confidence intervals (95% CIs), 1.51-2.17] and dynapenia (HR 2.77, 95% CI 2.48-3.08) were found to have a higher mortality risk than those in the robust group. Similarly, compared with the robust group, either the low HGS or low LS [incidence rate ratio (IRR) 1.45, 95% CI 1.04-2.03] and dynapenia (IRR 2.06, 95% CI 1.48-2.89) groups had higher multiple CV hospitalization and all-cause mortality risks. CONCLUSION: Dynapenia, characterized by both low HGS and LS, was significantly associated with increased CV hospitalization and mortality risk in patients on HD. Clinical assessments of muscle strength and screening patients with low muscle strength are crucial for disease management in this population. Measuring the muscle strength of the entire extremity, and not only the upper or lower extremities, may be necessary for accurate prognostic stratification.

The administration of hemodialysis (HD) treatment leads to the continuous collection of a vast qu... more The administration of hemodialysis (HD) treatment leads to the continuous collection of a vast quantity of medical data. Many variables related to the patient health status, to the treatment, and to dialyzer settings can be recorded and stored at each treatment session. In this study a dataset of 42 variables and 1526 patients extracted from the Fresenius Medical Care database EuCliD was used to develop and apply a random forest predictive model for the prediction of cardiovascular events in the first year of HD treatment. A ridge-lasso logistic regression algorithm was then applied to the subset of variables mostly involved in the prediction model to get insights in the mechanisms underlying the incidence of cardiovascular complications in this high risk population of patients.

Nephrology Dialysis Transplantation, May 1, 2022

BACKGROUND AND AIMS: Chronic kidney disease-associated pruritus (CKD-aP) is common, yet underreco... more BACKGROUND AND AIMS: Chronic kidney disease-associated pruritus (CKD-aP) is common, yet underrecognized condition among end-stage kidney disease patients. We sought to evaluate the prevalence of CKD-aP and its impact on health-related quality of life (HRQOL) among dialysis patients across five European countries. METHOD: This is a retrospective, observational analysis of data abstracted from the EuCliD R database (European Clinical database), the clinical information system adopted in Fresenius Medical Care (FMC) outpatient dialysis facilities in several European countries. Patient-Reported Outcomes Measures (PROM) were collected as part of a continuous quality improvement program launched for the first time in all centres belonging to the Nephrocare network in France, Italy, Spain, United Kingdom and Ireland. The presence and severity of CKD-aP were documented based on information captured by both the Kidney Disease Quality of Life (KDQOL TM-36) and the 5-D Itch questionnaires. HRQOL was assessed with KDQOL TM-36. Clinical and demographic data have been extracted from EuCliD R. The relationship between CKD-aP and HRQOL was evaluated with generalized linear models. RESULTS: The ePROM campaign attained a large participation rate with very low attrition. Among 9974 who were actively treated in the clinics and were able to fill in a self-reported questionnaire, 8157 responded to the survey and only 1033 (11.2%) refused to participate. We enrolled 6221 patients in the present secondary analysis. The study flowchart is reported in Figure 1. Slightly more than half of patients (52%) reported no CKD-aP, 25% mild, whereas roughly 23% reported moderate-to-severe CKD-aP. Patients reporting more severe CKD-aP had shorter dialysis vintage, higher phosphate and parathormone, and more frequently diabetes. Average KDQOL-36 scores are reported in Figure 2a. We observed a strong, graded relationship between CKD-aP severity and KDQOL-36 scores (Figure 2b). The association was robust to adjustment for potential confounders. The quality of life penalty associated with more severe pruritus was clinically significant based on distribution based minimal clinically important difference threshold for the KDQOL-36 scales. CONCLUSION: CKD-aP was common in a large, representative sample of the dialysis population in five European countries. We observed a large, clinically important, quality of life penalty associated with CKD-aP even after adjusting for potential confounders.