European Nephrologists' Attitudes toward the Application of Artificial Intelligence in Clinical Practice: A Comprehensive Survey.

INTRODUCTION: The rapid advancement of artificial intelligence and big data analytics, including descriptive, diagnostic, predictive, and prescriptive analytics, has the potential to revolutionize many areas of medicine, including nephrology and dialysis. Artificial intelligence and big data analytics can be used to analyze large amounts of patient medical records, including laboratory results and imaging studies, to improve the accuracy of diagnosis, enhance early detection, identify patterns and trends, and personalize treatment plans for patients with kidney disease. Additionally, artificial intelligence and big data analytics can be used to identify patients' treatment who are not receiving adequate care, highlighting care inefficiencies in the dialysis provider, optimizing patient outcomes, reducing healthcare costs, and consequently creating values for all the involved stakeholders. OBJECTIVES: We present the results of a comprehensive survey aimed at exploring the attitudes of European physicians from eight countries working within a major hemodialysis network (Fresenius Medical Care NephroCare) toward the application of artificial intelligence in clinical practice. METHODS: An electronic survey on the implementation of artificial intelligence in hemodialysis clinics was distributed to 1,067 physicians. Of the 1,067 individuals invited to participate in the study, 404 (37.9%) professionals agreed to participate in the survey. RESULTS: The survey showed that a substantial proportion of respondents believe that artificial intelligence has the potential to support physicians in reducing medical malpractice or mistakes. CONCLUSION: While artificial intelligence's potential benefits are recognized in reducing medical errors and improving decision-making, concerns about treatment plan consistency, personalization, privacy, and the human aspects of patient care persist. Addressing these concerns will be crucial for successfully integrating artificial intelligence solutions in nephrology practice.

The Use of Anemia Control Model Is Associated with Improved Hemoglobin Target Achievement, Lower Rates of Inappropriate Erythropoietin Stimulating Agents, and Severe Anemia among Dialysis Patients.

INTRODUCTION: The Anemia Control Model (ACM) is a certified medical device suggesting the optimal ESA and iron dosage for patients on hemodialysis. We sought to assess the effectiveness and safety of ACM in a large cohort of hemodialysis patients. METHODS: This is a retrospective study of dialysis patients treated in NephroCare centers between June 1, 2013 and December 31, 2019. We compared patients treated according to ACM suggestions and patients treated in clinics where ACM was not activated. We stratified patients belonging to the reference group by historical target achievement rates in their referral centers (tier 1: <70%; tier 2: 70-80%; tier 3: >80%). Groups were matched by propensity score. RESULTS: After matching, we obtained four groups with 85,512 patient-months each. ACM had 18% higher target achievement rate, 63% smaller inappropriate ESA administration rate, and 59% smaller severe anemia risk compared to Tier 1 centers (all p < 0.01). The corresponding risk ratios for ACM compared to Tier 2 centers were 1.08 (95% CI: 1.08-1.09), 0.49 (95% CI: 0.47-0.51), and 0.64 (95% CI: 0.61-0.68); for ACM compared to Tier 3 centers, 1.01 (95% CI: 1.01-1.02), 0.66 (95% CI: 0.63-0.69), and 0.94 (95% CI: 0.88-1.00), respectively. ACM was associated with statistically significant reductions in ESA dose administration. CONCLUSION: ACM was associated with increased hemoglobin target achievement rate, decreased inappropriate ESA usage and a decreased incidence of severe anemia among patients treated according to ACM suggestion.

Comparison Between a Single-Lead ECG Garment Device and a Holter Monitor: A Signal Quality Assessment.

Wearable electronics are increasingly common and useful as health monitoring devices, many of which feature the ability to record a single-lead electrocardiogram (ECG). However, recording the ECG commonly requires the user to touch the device to complete the lead circuit, which prevents continuous data acquisition. An alternative approach to enable continuous monitoring without user initiation is to embed the leads in a garment. This study assessed ECG data obtained from the YouCare device (a novel sensorized garment) via comparison with a conventional Holter monitor. A cohort of thirty patients (age range: 20-82 years; 16 females and 14 males) were enrolled and monitored for twenty-four hours with both the YouCare device and a Holter monitor. ECG data from both devices were qualitatively assessed by a panel of three expert cardiologists and quantitatively analyzed using specialized software. Patients also responded to a survey about the comfort of the YouCare device as compared to the Holter monitor. The YouCare device was assessed to have 70% of its ECG signals as "Good", 12% as "Acceptable", and 18% as "Not Readable". The R-wave, independently recorded by the YouCare device and Holter monitor, were synchronized within measurement error during 99.4% of cardiac cycles. In addition, patients found the YouCare device more comfortable than the Holter monitor (comfortable 22 vs. 5 and uncomfortable 1 vs. 18, respectively). Therefore, the quality of ECG data collected from the garment-based device was comparable to a Holter monitor when the signal was sufficiently acquired, and the garment was also comfortable.

Effectiveness of cold HD for the prevention of HD hypotension and mortality in the general HD population.

BACKGROUND: Cold hemodialysis (HD) prevented intradialysis hypotension (IDH) in small, short-term, randomized trials in selected patients with IDH. Whether this treatments prevents IDH and mortality in the HD population at large is unknown. METHODS: We investigated the relationship between dialysate temperature and the risk of IDH, i.e. nadir blood pressure <90 mmHg (generalized estimating equation model) and all-cause mortality (Cox's regression) in an incident cohort of HD patients (n = 8071). To control for confounding by bias by indication and other factors we applied instrumental variables adjusting for case mix at facility level. RESULTS: Twenty-seven percent of patients in the study cohort were systematically treated with a dialysate temperature ≤35.5°C. Over a median follow-up of 13.6 months (interquartile range 5.2-26.1 months), a 0.5°C reduction of the dialysate temperature was associated with a small (-2.4%) reduction of the risk of IDH [odds ratio (OR) 0.976, 95% confidence interval (CI) 0.957-0.995, P = .013]. In case-mix, facility-level adjusted analysis, the association became much stronger (OR 0.67, 95% CI 0.63-0.72, risk reduction = 33%, P < .001). In contrast, colder dialysate temperature had no effect on mortality both in the unadjusted [hazard ratio (HR) (0.5°C decrease) 1.074, 95% CI 0.972-1.187, P = .16] and case-mix-adjusted analysis at facility level (HR 1.01, 95% CI 0.88-1.16, P = .84). Similar results were registered in additional analyses by instrumental variables applying the median dialysate temperature or the facility percentage of patients prescribed a dialysate temperature <36°C. Further analyses restricted to patients with recurrent IDH fully confirmed these findings. CONCLUSIONS: Cold HD was associated with IDH in the HD population but had no association with all-cause mortality.

Chronic kidney disease-associated pruritus (CKD-aP) is associated with worse quality of life and increased healthcare utilization among dialysis patients.

PURPOSE: Chronic pruritus significantly impairs hemodialysis patients' health status and quality of life (QOL) and it is associated with higher mortality rate, more frequent hospitalizations, poorer dialysis and medication adherence, and deteriorated mental status. However, pruritus is still underestimated, underdiagnosed, and undertreated in the real-life clinical scenario. We investigated prevalence, clinical characteristics, clinical correlates, severity as well as physical and psychological burden of chronic pruritus among adult hemodialysis patients in a large international real-world cohort. METHODS: We conducted a retrospective cross-sectional study of patients registered in 152 Fresenius Medical Care (FMC) NephroCare clinics located in Italy, France, Ireland, United Kingdom, and Spain. Demographic and medical data were retrieved from the EuCliD® (European Clinical) database, while information on pruritus and QoL were abstracted from KDQOL™-36 and 5-D Itch questionnaire scores. RESULTS: A total of 6221 patients were included, of which 1238 were from France, 163 Ireland, 1469 Italy, 2633 Spain, and 718 UK. The prevalence of mild-to-severe pruritus was 47.9% (n = 2977 patients). Increased pruritus severity was associated with increased use of antidepressants, antihistamines, and gabapentin. Patients with severe pruritus more likely suffered from diabetes, more frequently missed dialysis sessions, and underwent more hospitalizations due to infections. Both mental and physical QOL scores were progressively lower as the severity of pruritus increased; this association was robust to adjustment for potential confounders. CONCLUSION: This international real-world analysis confirms that chronic pruritus is a highly prevalent condition among dialysis patients and highlights its considerable burden on several dimensions of patients' life.

Algorithm for Mobile Platform-Based Real-Time QRS Detection.

Recent advancements in smart, wearable technologies have allowed the detection of various medical conditions. In particular, continuous collection and real-time analysis of electrocardiogram data have enabled the early identification of pathologic cardiac rhythms. Various algorithms to assess cardiac rhythms have been developed, but these utilize excessive computational power. Therefore, adoption to mobile platforms requires more computationally efficient algorithms that do not sacrifice correctness. This study presents a modified QRS detection algorithm, the AccYouRate Modified Pan-Tompkins (AMPT), which is a simplified version of the well-established Pan-Tompkins algorithm. Using archived ECG data from a variety of publicly available datasets, relative to the Pan-Tompkins, the AMPT algorithm demonstrated improved computational efficiency by 5-20×, while also universally enhancing correctness, both of which favor translation to a mobile platform for continuous, real-time QRS detection.

Electrocardiogram Monitoring Wearable Devices and Artificial-Intelligence-Enabled Diagnostic Capabilities: A Review.

Worldwide, population aging and unhealthy lifestyles have increased the incidence of high-risk health conditions such as cardiovascular diseases, sleep apnea, and other conditions. Recently, to facilitate early identification and diagnosis, efforts have been made in the research and development of new wearable devices to make them smaller, more comfortable, more accurate, and increasingly compatible with artificial intelligence technologies. These efforts can pave the way to the longer and continuous health monitoring of different biosignals, including the real-time detection of diseases, thus providing more timely and accurate predictions of health events that can drastically improve the healthcare management of patients. Most recent reviews focus on a specific category of disease, the use of artificial intelligence in 12-lead electrocardiograms, or on wearable technology. However, we present recent advances in the use of electrocardiogram signals acquired with wearable devices or from publicly available databases and the analysis of such signals with artificial intelligence methods to detect and predict diseases. As expected, most of the available research focuses on heart diseases, sleep apnea, and other emerging areas, such as mental stress. From a methodological point of view, although traditional statistical methods and machine learning are still widely used, we observe an increasing use of more advanced deep learning methods, specifically architectures that can handle the complexity of biosignal data. These deep learning methods typically include convolutional and recurrent neural networks. Moreover, when proposing new artificial intelligence methods, we observe that the prevalent choice is to use publicly available databases rather than collecting new data.

Bowel ischemia as onset of COVID-19 in otherwise asymptomatic patients with persistently negative swab.

BACKGROUND: Asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS-CoV-2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID-19) and with persistently real-time polymerase chain reaction negative pharyngeal swab. METHODS: Three consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co-existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID-19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS-CoV-2 on resected tissue was performed. RESULTS: All tested samples were strongly positive for SARS-CoV-2. CONCLUSIONS: This is the first case report in which patients with severe intestinal symptoms presented a marked SARS-CoV-2 positivity in the resected tissues, without any usual clinical manifestations of COVID-19. These results suggest that the patients might be infected with SARS-CoV-2 presenting acute abdominal distress but without respiratory or constitutional symptoms.

Optical tissue clearing associated with 3D imaging: application in preclinical and clinical studies.

Understanding the inner morphology of intact tissues is one of the most competitive challenges in modern biology. Since the beginning of the twentieth century, optical tissue clearing (OTC) has provided solutions for volumetric imaging, allowing the microscopic visualization of thick sections of tissue, organoids, up to whole organs and organisms (for example, mouse or rat). Recently, tissue clearing has also been introduced in clinical settings to achieve a more accurate diagnosis with the support of 3D imaging. This review aims to give an overview of the most recent developments in OTC and 3D imaging and to illustrate their role in the field of medical diagnosis, with a specific focus on clinical applications.

Relevance of VEGF and CD147 in different SARS-CoV-2 positive digestive tracts characterized by thrombotic damage.

Several evidence suggests that, in addition to the respiratory tract, also the gastrointestinal tract is a main site of severe acute respiratory syndrome CoronaVirus 2 (SARS-CoV-2) infection, as an example of a multi-organ vascular damage, likely associated with poor prognosis. To assess mechanisms SARS-CoV-2 responsible of tissue infection and vascular injury, correlating with thrombotic damage, specimens of the digestive tract positive for SARS-CoV-2 nucleocapsid protein were analyzed deriving from three patients, negative to naso-oro-pharyngeal swab for SARS-CoV-2. These COVID-19-negative patients came to clinical observation due to urgent abdominal surgery that removed different sections of the digestive tract after thrombotic events. Immunohistochemical for the expression of SARS-CoV-2 combined with a panel of SARS-CoV-2 related proteins angiotensin-converting enzyme 2 receptor, cluster of differentiation 147 (CD147), human leukocyte antigen-G (HLA-G), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 was performed. Tissue samples were also evaluated by electron microscopy for ultrastructural virus localization and cell characterization. The damage of the tissue was assessed by ultrastructural analysis. It has been observed that CD147 expression levels correlate with SARS-CoV-2 infection extent, vascular damage and an increased expression of VEGF and thrombosis. The confirmation of CD147 co-localization with SARS-CoV-2 Spike protein binding on gastrointestinal tissues and the reduction of the infection level in intestinal epithelial cells after CD147 neutralization, suggest CD147 as a possible key factor for viral susceptibility of gastrointestinal tissue. The presence of SARS-CoV-2 infection of gastrointestinal tissue might be consequently implicated in abdominal thrombosis, where VEGF might mediate the vascular damage.

Prolonged patient survival after implementation of a continuous quality improvement programme empowered by digital transformation in a large dialysis network.

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.

Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives.

Recent studies have shown that G protein-coupled receptors (GPCRs), the largest signal-conveying receptor family, are targets for mutations occurring frequently in different cancer types. GPCR alterations associated with cancer development represent significant challenges for the discovery and the advancement of targeted therapeutics. Among the different molecules that can activate GPCRs, we focused on two molecules that exert their biological actions regulating many typical features of tumorigenesis such as cellular proliferation, survival, and invasion: somatostatin and melatonin. The modulation of signaling pathways, that involves these two molecules, opens an interesting scenario for cancer therapy, with the opportunity to act at different molecular levels. Therefore, the aim of this review is the analysis of the biological activity and the therapeutic potential of somatostatin and melatonin, displaying a high affinity for GPCRs, that interfere with cancer development and maintenance.

Practice Patterns and Outcomes of Online Hemodiafiltration: A Real-World Evidence Study in a Russian Dialysis Network.

BACKGROUND: Evidence suggests that online hemodiafiltration (OL-HDF) is associated with improved survival. Whether the dose-response relationship between convective volume and mortality may be confounded by selection bias or descends from practice patterns is not clear. We sought to evaluate the role of patients' characteristics and practice patterns on OL-HDF dose and mortality in a large private dialysis network in the Republic of Russia. METHODS: In this multicenter, historical cohort study, we included adult incident patients on OL-HDF with at least 90 days of survival on renal replacement therapy in centers belonging to the Russian Federation Fresenius Medical Care network (January 1, 2011, to December 31, 2016). We evaluated predictors and outcomes (survival) of substitution volume target achievement (Qsub > 21 L/session). RESULTS: Among 1,081 enrolled patients, the average Qsub was 22.9 (±3.2) L/session; the mean ultrafiltration volume was 1.6 (±0.8) L/session. The mean age was 55.8 ± 13.2; 42% were woman. Most common comorbidities were congestive heart failure (39.7%) and peripheral vascular disease (21.7%). The average hemoglobin was 9.3 ± 1.3. The case-mix adjusted center effect accounted for 20% of variance in Qsub. The top 10 most important variables associated with higher Qsub were effective Qb, serum protein, Charlson's comorbidity index, hemoglobin, year of dialysis initiation (proxy of high Qsub treatment policy in the clinic network), predialysis heart rate, serum bicarbonate, serum phosphate, age, serum sodium, and dry body weight. In addition, we found that the association of Qb with Qsub is moderated by year of enrollment, intradialytic weight gain, and coronary artery disease, whereas higher hemoglobin concentration moderated the relationship between treatment time and Qsub. Finally, Qsub between 21 and 25 L/session was associated with longer 5-year survival. CONCLUSIONS: Both center-dependent clinical practice standards and patient clinical conditions substantially contributed to the risk of low Qsub. We confirmed previous evidence indicating better survival among patients with Qsub ≥ 21 L/session.

Targeting Wnt/ß-catenin and PI3K/Akt/mTOR pathways in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disorder that results from the clonal transformation of T-cell precursors. Phosphatidylinositol 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) and canonical Wnt/ß-catenin signaling pathways play a crucial role in T-cell development and in self-renewal of healthy and leukemic stem cells. Notably, ß-catenin is a transcriptional regulator of several genes involved in cancer cell proliferation and survival. In this way, aberrations of components belonging to the aforementioned networks contribute to T-ALL pathogenesis. For this reason, inhibition of both pathways could represent an innovative strategy in this hematological malignancy. Here, we show that combined targeting of Wnt/ß-catenin pathway through ICG-001, a CBP/ß-catenin transcription inhibitor, and of the PI3K/Akt/mTOR axis through ZSTK-474, a PI3K inhibitor, downregulated proliferation, survival, and clonogenic activity of T-ALL cells. ICG-001 and ZSTK-474 displayed cytotoxic effects, and, when combined together, induced a significant increase in apoptotic cells. This induction of apoptosis was associated with the downregulation of Wnt/ß-catenin and PI3K/Akt/mTOR pathways. All these findings were confirmed under hypoxic conditions that mimic the bone marrow niche where leukemic stem cells are believed to reside. Taken together, our findings highlight potentially promising treatment consisting of cotargeting Wnt/ß-catenin and PI3K/Akt/mTOR pathways in T-ALL settings.

New biomarkers and therapeutic strategies in acute lymphoblastic leukemias: Recent advances.

Acute lymphoblastic leukemia (ALL) represents a heterogeneous group of hematologic malignancies, and it is normally characterized by an aberrant proliferation of immature lymphoid cells. Moreover, dysregulation of multiple signaling pathways that normally regulate cellular transcription, growth, translation, and proliferation is frequently encountered in this malignancy. ALL is the most frequent tumor in childhood, and adult ALL patients still correlate with poor survival. This review focuses on modern therapies in ALL that move beyond standard chemotherapy, with a particular emphasis on immunotherapeutic approaches as new treatment strategies. Bi-specific T-cell Engagers (BiTE) antibodies, the chimeric antigen receptor (CAR)-T cells, or CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats [CRISPR]-associated nuclease 9) represent other new innovative approaches for this disease. Target and tailored therapy could make the difference in previously untreatable cases, i.e., precision and personalized medicine. Clinical trials will help to select the most efficient novel therapies in ALL management and to integrate them with existing treatments to achieve durable cures.

Long-term mortality risk associated with citric acid- and acetic acid-based bicarbonate haemodialysis: a historical cohort propensity score-matched study in a large, multicentre, population-based study.

BACKGROUND: Citric acid-based bicarbonate dialysate (CiD) is increasingly used in haemodialysis (HD) to improve haemodynamic tolerance and haemocompatibility associated with acetic acid-based bicarbonate dialysate. Safety concerns over CiD have been raised recently after a French ecological study reported higher mortality hazard in HD clinics with high CiD consumption. Therefore, we evaluated the mortality risk associated with various acidifiers (AcD, CiD) of bicarbonate dialysate. METHODS: In this multicentre, historical cohort study, we included adult incident HD patients (European, Middle-East and Africa Fresenius Medical Care network; 1 January 2014 to 31 October 2018). We recorded acidifiers of bicarbonate dialysis and dialysate composition for each dialysis session. In the primary intention-to-treat analysis, patients were assigned to the exposed group if they received CiD in >70% of sessions during the first 3 months (CiD70%), whereas the non-exposed group received no CiD at all. In the secondary analysis, exposure was assessed on a monthly basis for the whole duration of the follow-up. RESULTS: We enrolled 10 121 incident patients during the study period. Of them, 371 met the criteria for inclusion in CiD70%. After propensity score matching, mortality was 11.43 [95% confidence interval (CI) 8.86-14.75] and 12.04 (95% CI 9.44-15.35) deaths/100 person-years in the CiD0% and CiD70% groups, respectively (P = 0.80). A similar association trend was observed in the secondary analysis. CONCLUSIONS: We did not observe evidence of increased mortality among patients exposed to CiD in a large European cohort of dialysis patients despite the fact that physicians were more inclined to prescribe CiD to subjects with worse medical conditions.

Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus.

COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.

Clinical target achievement is associated with better quality of life among dialysis patients: results from a continuous quality improvement program in a Portuguese healthcare network.

BACKGROUND: Patients with kidney failure have multifaced clinical needs. Continuous quality improvement (CQI) programs initiated by large healthcare provider networks bear the promise of improving guideline adherence and improving patient-centered outcome, including health-related quality of life (HRQOL). We aimed at evaluating the association between key performance indicators (KPI) adopted for our CQI and HRQOL in a large network of dialysis providers. METHODS: We conducted a survey study in 39 centers belonging to the Portuguese Fresenius Medical Care (FME) network, in September 2017. For each participant, we retrospectively extracted clinical information during the 6-month period preceding survey administration. We used this information to calculate KPI as defined by the FME-CQI policy. Those KPI were selected in the FME-CQI policy as modifiable intermediate endpoints for which previous evidence suggested a causal relationship with patients' morbidity and mortality. HRQOL was assessed by the Kidney Disease Quality of Life Short Form 36 (KDQOL-36) questionnaire. RESULTS: Among 4691 eligible patients who were invited to participate in the survey, 2263 (48.2%) answered the self-administered survey. Based on KPI standards, patients had 1.5 (± 1.2) off-target clinical parameters on average. KDQOL-36 score were generally higher than those observed in European reference population. We found a significant linear association between KPI parameters and HRQOL. This pattern was robust to adjustment for satisfaction scores. CONCLUSIONS: Our data demonstrated a graded, monotonic, dose-response relationship between the number of off-target KPIs and HRQOL. Such relationship was not mediated by patients' satisfaction and may be attributed to amelioration of disease-specific symptoms and functional capacity.

Role of physical exercise in the regulation of epigenetic mechanisms in inflammation, cancer, neurodegenerative diseases, and aging process.

The genetic heritage for decades has been considered to respond only to gene promoters or suppressors, with specific roles for oncogenes or tumor-suppressor genes. Epigenetics is progressively attracting increasing interest because it has demonstrated the capacity of these regulatory processes to regulate the gene expression without modifying gene sequence. Several factors may influence epigenetics, such as lifestyles including food selection. A role for physical exercise is emerging in the epigenetic regulation of gene expression. In this review, we resume physiological and pathological implications of epigenetic modification induced by the physical activity (PA). Inflammation and cancer mechanisms, immune system, central nervous system, and the aging process receive benefits due to PA through epigenetic mechanisms. Thus, the modulation of epigenetic processes by physical exercise positively influences prevention, development, and the course of inflammatory and cancer diseases, as well as neurodegenerative illnesses. This growing field of studies gives rise to a new role for PA as an option in prevention strategies and to integrate pharmacological therapeutic treatments.

Detecting high-risk chronic kidney disease-mineral bone disorder phenotypes among patients on dialysis: a historical cohort study.

BACKGROUND: The clinical management of chronic kidney disease-mineral bone disorder (CKD-MBD) remains extremely challenging, partially due to difficulties in defining high-risk phenotypes based on serum biomarkers. We evaluated the prevalence and outcomes of 27 mutually exclusive CKD-MBD phenotypes in a large, multi-national cohort of chronic dialysis patients over a 5-year follow-up study. METHODS: In this historical cohort study, we enrolled all haemodialysis patients registered in EuCliD® on 1 July 2011 across 28 Europe, the Middle East and Africa (EMEA) and South American countries. We created 27 mutually exclusive phenotypes based on combinations of serum parathyroid hormone (PTH), phosphorus (P) and calcium (Ca) 6-month averages (L, low; T, target; H, high). We tested the association between CKD-MBD phenotypes and 5-year mortality and hospitalization risk by outcome risk score-adjusted proportional hazard regression. RESULTS: We enrolled 35 721 eligible patients. Eastern European and South American countries generally achieved poorer CKD-MBD control when compared with Western European countries (prevalence ratio: 0.79; P < 0.001). There were 15 795 deaths [126.7 deaths/1000 person-years; 95% confidence interval (CI) 124.7-128.7]; 18 014 had at least one hospitalization (203.9 hospitalizations/1000 person-years; 95% CI 201.0-206.9); the incidence of the composite endpoint was 280.0 events/1000 person-years (95% CI 276.6-283.5). In the fully adjusted model, relative mortality risk ranged from hazard ratio (HR) = 1.07 (PTH/Ca/P: TLT) to HR = 1.59 (PTH/Ca/P: LTL), whereas the relative composite endpoint risk ranged from HR = 1.07 (PTH/Ca/P: TTH) to HR = 1.36 (PTH/Ca/P: LTL). CONCLUSION: We identified several CKD-MBD phenotypes associated with reduced hospitalization-free survival and increased mortality. Ranking of relative risk estimates or excess events concurs in informing healthcare priority setting.