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Aseptic abscesses syndrome is a rare but increasingly recognized disease that falls within the spectrum of autoinflammatory disorders. Here, we describe the case of a patient who presented with abdominal pain and fever, along with multiple abdominal and extra-abdominal abscesses, in the absence of underlying hematologic, autoimmune, infectious, or neoplastic conditions. Initially, the patient responded to glucocorticoids, but experienced several flares upon discontinuation, leading to the initiation of treatment with a TNFα inhibitor. After 5 years, an attempt to discontinue treatment resulted in a new flare of the disease. Remission was eventually achieved with a biosimilar TNFα inhibitor, albeit requiring shortened infusion intervals.

Objective. Patients Acceptable Symptom State (PASS) is a single dichotomized question assessing health satisfaction. We aimed to investigate PASS achievement within 4 weeks of treatment with Janus kinase (JAK) inhibitors (Jakinibs) and its association with treatment response after 4 and 12 weeks in rheumatoid arthritis (RA) patients. Methods. We recruited consecutive RA patients starting baricitinib or tofacitinib. At baseline, 4 and 12 weeks, we calculated disease activity [Disease Activity Score on 28 joints (DAS28), Clinical Disease Activity Index, Simplified Disease Activity Index], disease status [remission and low-disease activity (LDA)], percentage of patients achieving PASS, and the time to attain PASS. We assessed the impact of clinically relevant variables on PASS achievement by logistic regression analysis. Results. We enrolled 113 patients [98 (86.7%) females; median age 59.6 (interquartile range 16.9), median disease duration 144 (132) months]. 90 (79.6%) patients achieved PASS after 10 (8) days. A similar percentage of PASS achievers and non-achievers was in remission/LDA at weeks 4 and 12, but the reduction of disease activity was significantly greater in PASS achievers. All patients achieving Boolean remission at weeks 4 and 12 had achieved PASS within 4 weeks. The impact of Patients Global Assessment (PGA) on DAS28 was significantly greater in PASS non-achievers compared to PASS achievers; inversely, the impact of C-reactive protein was more relevant in PASS achievers. At multivariate analysis, pain and PGA were significantly associated with PASS. Conclusions. In our cohort, Jakinibs allowed an early achievement of PASS in a great percentage of RA patients. PASS is strictly dependent on PGA and pain and could suggest, early in the management of RA patients, therapeutic success.

Surgery for lesions of the proximal part of the pancreatic body or neck can be challenging, and when enucleation is not possible, central pancreatectomy is an option. Laparoscopic central pancreatic resection is rarely described worldwide; it is considered a difficult procedure mainly because of the risk of double pancreatic fistula developing at two sites of resection. However, it seems to be an excellent alternative to distal pancreatectomy or pancreaticoduodenectomy, with the advantages of preserving functioning parenchyma and reducing endocrine and exocrine failure. Nevertheless, patients with pancreatic lesions requiring central resection are often managed with the open approach in many hospitals due to the complexity of total laparoscopic central pancreatectomy, which requires advanced laparoscopic skills, expertise and experience. Here, we report a case of a 29-year-old female who underwent total laparoscopic central pancreatic resection with gastro-pancreatic anastomosis for symptomatic serous cystadenoma. We discuss the details of case management and review the relevant literature.

Objective. Data from trials demonstrated that abatacept (ABA) has a good safety and efficacy profile in treating rheumatoid arthritis. We have studied the retention rate of ABA in a real-life cohort of patients with rheumatoid arthritis. Methods. This is a monocentric, retrospective study including patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism 2010 criteria who started treatment with ABA. The Kaplan-Meier method was applied to evaluate the ABA retention rate. Results. This analysis was conducted on 161 patients [male/female 21/140, median age 65 years, interquartile range (IQR) 18.7, median disease duration 169 months, IQR 144.0]. 111 patients (68.9%) received ABA subcutaneously. ABA was associated with methotrexate in 61.9% of patients and was the first biological disease-modifying antirheumatic drug in 41%. We observed a median ABA survival of 66 months [95% confidence interval (CI) 57.3-74.7], with a retention rate of 88% at 6 months and 50.9% at 5 years. Drug survival was significantly higher in patients treated with ABA subcutaneously and in male patients (p=0.039 and p=0.018, respectively). Adjusted for main confounders, female gender was the main predictor of withdrawal (hazard ratio 5.1, 95% CI 1.2-21.3). Conclusions. Our study shows that better survival is associated with subcutaneous administration and male gender, confirming ABA effectiveness.

Age-associated neurodegenerative disorders demonstrating tau-laden intracellular inclusions are known as tauopathies. We previously linked a loss-of-function mutation in the TSC1 gene to tau accumulation and frontotemporal lobar degeneration. Now, we have identified genetic variants in TSC1 that decrease TSC1/hamartin levels and predispose to tauopathies such as Alzheimer’s disease and progressive supranuclear palsy. Cellular and murine models of TSC1 haploinsufficiency, as well as human brains carrying a TSC1 risk variant, accumulated tau protein that exhibited aberrant acetylation. This acetylation hindered tau degradation via chaperone-mediated autophagy, thereby leading to its accumulation. Aberrant tau acetylation in TSC1 haploinsufficiency resulted from the dysregulation of both p300 acetyltransferase and SIRT1 deacetylase. Pharmacological modulation of either enzyme restored tau levels. This study substantiates TSC1 as a novel tauopathy risk gene and includes TSC1 haploinsufficiency as a genetic model for tauopathies. In addition, these findings promote tau acetylation as a rational target for tauopathy therapeutics and diagnostic.

Background: Phosphorylcholine has emerged as a potential adjunctive agent in cardiopulmonary bypass (CPB) circuits. Phosphorylcholine serves as a coating for the CPB circuit, potentially enhancing biocompatibility and reducing thrombotic events. However, its impact on specific patient populations and procedural outcomes remains underexplored. Materials and Methods: In this retrospective study, we analyzed data from 60 patients who underwent cardiac surgery with CPB, comprising 20 cases each of coronary artery bypass grafting (CABG), mitral valve repair, and aortic valve replacement. The patient cohort was divided into two groups—30 patients whose CPB circuits were coated with phosphorylcholine (phosphorylcholine-coated group) and 30 patients who did not receive phosphorylcholine supplementation or circuit coating. Both groups underwent surgery with identical CPB circuit designs. We assessed the absence of adverse events, safety, and efficacy parameters, including blood loss, clotting, and the structural integrity of the CPB circuit. Additionally, we measured changes in mean albumin levels (g/dL), mean platelet counts (×109/L), and antithrombin III (ATIII) levels before and after CPB. Results: The retrospective analysis revealed an absence of adverse events in both groups. In the phosphorylcholine-coated group compared to the non-phosphorylcholine-coated group, there was a notable difference in the delta change in mean albumin levels (0.87 ± 0.1 vs. 1.65 ± 0.2 g/dL, p-value 0.021), mean platelet counts (42.251 ± 0.121 vs. 54.21 ± 0.194 × 109/L, p-value 0.049), and ATIII levels (16.85 ± 0.2 vs. 31.21 ± 0.3 p-value 0.017). There was a notable reduction in the perioperative consumption of human complex units after CPB (3 vs. 12, p-value 0.019). Conclusions: Both groups, phosphorylcholine and non-phosphorylcholine, demonstrated the absence of adverse events and that the systems are safe for iatrogenic complication. Our findings suggest that the use of phosphorylcholine coating on the CPB circuit, in the absence of supplementary phosphorylcholine, in cardiac surgery is associated with favorable changes in mean albumin levels, mean platelet counts, and ATIII levels. Further research is warranted to elucidate the full extent of phosphorylcholine’s impact on patient outcomes and CPB circuit performance.

Objective. To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. Methods. We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. Results. The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p

Objectives We aimed to evaluate whether obese patients with psoriatic arthritis (PsA) were less likely to be in remission/low disease activity (LDA).Methods We used data from the ReFlaP, an international multi-centre cohort study (NCT03119805), which recruited consecutive adults with definite PsA (disease duration ≥ 2 years) from 14 countries. Demographics, clinical data, comorbidities, and patient-reported outcomes were collected. Remission/LDA was defined as Very Low Disease Activity (VLDA)/minimal disease activity (MDA), Disease Activity in PSoriatic Arthritis (DAPSA) ≤4/≤14, or by patients’ opinion. Obesity was defined as physician-reported and/or body mass index ≥30 kg/m2. We evaluated the association between obesity and the presence of remission/LDA, with adjustment in multivariable regression models.Results Among 431 patients (49.3% women), 136 (31.6%) were obese. Obese versus non-obese patients were older, more frequently women, had higher tender joint and enthesitis counts and worse pain, physical function and health-related quality of life. Obese patients were less likely to be in VLDA; DAPSA remission and MDA, with adjusted ORs of 0.31 (95% CI 0.13 to 0.77); 0.39 (95% CI 0.19 to 0.80) and 0.61 (95% CI 0.38 to 0.99), respectively. Rates of DAPSA-LDA and patient-reported remission/LDA were similar for obese and non-obese patients.Conclusion PsA patients with comorbid obesity were 2.5–3 folds less likely to be in remission/LDA by composite scores compared with non-obese patients; however, remission/LDA rates were similar based on the patients’ opinion. PsA patients with comorbid obesity may have different disease profiles and require individualised management.

Introduction It is estimated that of those who die in high-income countries, 69%–82% would benefit from palliative care with a high prevalence of advanced chronic conditions and limited life prognosis. A positive response to these challenges would consist of integrating the palliative approach into all healthcare settings, for patients with all types of advanced medical conditions, although poor clinician awareness and the difficulty of applying criteria to identify patients in need still pose significant barriers. The aim of this project is to investigate whether the combined use of the NECPAL CCOMS-ICO and Palliative Prognostic (PaP) Score tools offers valuable screening methods to identify patients suffering from advanced chronic disease with limited life prognosis and likely to need palliative care, such as cancer, chronic renal or chronic respiratory failure.Methods and analysis This multicentre prospective observational study includes three patient populations: 100 patients with cancer, 50 patients with chronic renal failure and 50 patients with chronic pulmonary failure. All patients will be treated and monitored according to local clinical practice, with no additional procedures/patient visits compared with routine clinical practice. The following data will be collected for each patient: demographic variables, NECPAL CCOMS-ICO questionnaire, PaP Score evaluation, Palliative Performance Scale, Edmonton Symptom Assessment System, Eastern Cooperative Oncology Group Performance Status and data concerning the underlying disease, in order to verify the correlation of the two tools (PaP and NECPAL CCOMS-ICO) with patient status and statistical analysis.Ethics and dissemination The study was approved by local ethics committees and written informed consent was obtained from the patient. Findings will be disseminated through typical academic routes including poster/paper presentations at national and international conferences and academic institutes, and through publication in peer-reviewed journals.

Aseptic abscesses syndrome is a rare but increasingly recognized disease that falls within the spectrum of autoinflammatory disorders. Here, we describe the case of a patient who presented with abdominal pain and fever, along with multiple abdominal and extra-abdominal abscesses, in the absence of underlying hematologic, autoimmune, infectious, or neoplastic conditions. Initially, the patient responded to glucocorticoids, but experienced several flares upon discontinuation, leading to the initiation of treatment with a TNFα inhibitor. After 5 years, an attempt to discontinue treatment resulted in a new flare of the disease. Remission was eventually achieved with a biosimilar TNFα inhibitor, albeit requiring shortened infusion intervals. [ABSTRACT FROM AUTHOR]

Oliguric acute kidney injury due to traumatic rhabdomyolysis can be potentially lethal if the proper medical therapy combined with extracorporeal detoxification is not performed. Different extracorporeal techniques are available to overcome this syndrome. Here, we report the first case of removal of myoglobin and successful recovery from acute kidney injury in an elderly septic patient using supra-hemodiafiltration with endogenous reinfusion technique (HFR-Supra) combined with the medical therapy.

Abstract The aim of the study was to investigate the presence of subclinical vascular damage in polymyalgia rheumatica (PMR). We enrolled PMR patients having major cardiovascular risk factors (MCVRF) and, as controls, patients with MCVRF. All underwent: color Doppler ultrasound to evaluate the common carotid intima-media thickness (IMT), the anterior–posterior abdominal aortic diameter (APAD), and the prevalence of carotid artery stenosis; the cardio-ankle vascular index (CAVI) to measure arterial stiffness together with the ankle-brachial index (ABI) to investigate the presence of lower-extremity peripheral arterial disease. Finally, we measured the serum levels of adipocytokines implicated in vascular dysfunction. As a result, 48 PMR and 56 MCVRF patients were included. An increase of IMT (1.07/0.8–1.2 vs 0.8/0.8–1.05; p = 0.0001), CAVI (8.7/7.8–9.3 vs 7.6/6.9–7.8; p

BackgroundScreening for latent tuberculosis infection is recommended in patients with rheumatoid arthritis (RA) starting Janus kinase inhibitors (Jaki). Interferon (IFN)-gamma release assays (IGRAs) are increasingly used for this purpose. Jaki tend to decrease the levels of IFNs, questioning the reliability of IGRAs during treatment with these drugs.ObjectivesTo compare the performance of QuantiFERON-TB Gold Plus (QFT-P) and QFT Gold In-tube (QFT-GIT) in RA patients treated with Jaki.MethodsRA patients underwent QFT-P and QFT-GIT at baseline (T0), and after 3 (T3) and 12 months (T12) of treatment with Jaki. The agreement between the two tests was calculated. The agreement between IGRAs and tuberculin skin test (TST) or chest radiography at baseline was also determined. The variability of QTF-P results was longitudinally assessed.ResultsTwenty-nine RA patients (F/M 23/6; median age/IQR 63/15.5 years; median disease duration/IQR 174/216 months) were enrolled. A perfect agreement was found between QFT-P and QFT-GIT at all times (κ = 1). At T0, no agreement was recorded between IGRAs and TST (κ = -0.08) and between TST and chest radiography (κ = -0.07), a low agreement was found between QFT-P and chest radiography (κ = 0.17). A variation of 33.3% in the results of QFT-P was recorded at T3 vs T0, of 29.4% at T12 vs T0, and of 11.8% at T12 vs T3. The median levels of IFN-γ produced by lymphocytes in response to the mitogen of QFT-P decreased after 3 months followed by an increase after 12 months (not significant). No change in the median number of circulating lymphocytes was documented. Glucocorticoids intake was associated with a higher probability of negative or indeterminate IGRA results at T0 (pConclusionA response to IGRAs is detectable during treatment with Jaki. However, fluctuations in the results of IGRAs have been observed in the absence of correlation with clinical outcomes, thus challenging their interpretation.

Background and Objectives: Chronic hemodialysis (CHD) patients are at increased risk of SARS-CoV-2 infection and the related complications and mortality of COVID-19 due to the high rate of comorbidities combined with advanced age. This observational study investigated the clinical manifestations of SARS-CoV-2 infection in CHD and the risk factors for patients′ death. Materials and Methods: The study included 26 CHD patients with SARS-CoV-2 pneumonia detected by positive RT-PCR on nasopharyngeal swabs and high-resolution computed tomography at hospital admission, aged 71 + 5.9 years, 14 of which (53.8%) were male, 20 (77%) under hemodiafiltration, and 6 (23%) on standard hemodialysis, with a median follow-up of 30 days. Results: Simple logistic regression analysis revealed that the factors associated with a higher risk of death were older age (OR: 1.133; 95%CI: 1.028–1.326, p = 0.0057), IL-6 levels at admission (OR: 1.014; 95%CI: 1.004–1.028, p = 0.0053), and C-reactive protein (OR: 1.424; 95%CI: 1.158–2.044, p < 0.0001). In the multiple logistic regression model, circulating IL-6 values at admission remained the only significant prognosticator of death. The ROC curve indicated the discriminatory cut-off value of 38.20 pg/mL of blood IL-6 for predicting death in chronic hemodialysis patients with SARS-CoV-2 pneumonia (sensitivity: 100%; specificity: 78%; AUC: 0.8750; p = 0.0027). Conclusions: This study identified a threshold of IL-6 levels at hospital admission for death risk in CHD patients with SARS-CoV-2 pneumonia. This might represent a valuable outcome predictor, feasibly better than other clinical, radiological, or laboratory parameters and preceding the IL-6 peak, which is unpredictable.

Chaperone mediated autophagy (CMA) is selective but its activity in different tissue types has been unclear due to a lack of tools. Here, the authors generate transgenic mice expressing a CMA reporter that provides spatial and temporal in vivo data, uncovering differences in CMA in distinct tissues.

Background: Phosphorylcholine has emerged as a potential adjunctive agent in cardiopulmonary bypass (CPB) circuits. Phosphorylcholine serves as a coating for the CPB circuit, potentially enhancing biocompatibility and reducing thrombotic events. However, its impact on specific patient populations and procedural outcomes remains underexplored. Materials and Methods: In this retrospective study, we analyzed data from 60 patients who underwent cardiac surgery with CPB, comprising 20 cases each of coronary artery bypass grafting (CABG), mitral valve repair, and aortic valve replacement. The patient cohort was divided into two groups—30 patients whose CPB circuits were coated with phosphorylcholine (phosphorylcholine-coated group) and 30 patients who did not receive phosphorylcholine supplementation or circuit coating. Both groups underwent surgery with identical CPB circuit designs. We assessed the absence of adverse events, safety, and efficacy parameters, including blood loss, clotting, and the structural integrity of the CPB circuit. Additionally, we measured changes in mean albumin levels (g/dL), mean platelet counts (×109/L), and antithrombin III (ATIII) levels before and after CPB. Results: The retrospective analysis revealed an absence of adverse events in both groups. In the phosphorylcholine-coated group compared to the non-phosphorylcholine-coated group, there was a notable difference in the delta change in mean albumin levels (0.87 ± 0.1 vs. 1.65 ± 0.2 g/dL, p-value 0.021), mean platelet counts (42.251 ± 0.121 vs. 54.21 ± 0.194 × 109/L, p-value 0.049), and ATIII levels (16.85 ± 0.2 vs. 31.21 ± 0.3 p-value 0.017). There was a notable reduction in the perioperative consumption of human complex units after CPB (3 vs. 12, p-value 0.019). Conclusions: Both groups, phosphorylcholine and non-phosphorylcholine, demonstrated the absence of adverse events and that the systems are safe for iatrogenic complication. Our findings suggest that the use of phosphorylcholine coating on the CPB circuit, in the absence of supplementary phosphorylcholine, in cardiac surgery is associated with favorable changes in mean albumin levels, mean platelet counts, and ATIII levels. Further research is warranted to elucidate the full extent of phosphorylcholine's impact on patient outcomes and CPB circuit performance. [ABSTRACT FROM AUTHOR]

Membrane elongation is fundamental to autophagy and is controlled by an ubiquitin-conjugating cascade orchestrated by ATG16L1. Here, the authors identify that the E3 ligase Gigaxonin regulates autophagosome formation by controlling ATG16L1 turnover.

Renal impairment in Multiple Myeloma (MM) represents one of the most important factors that influences patient survival. In fact, before the introduction of modern chemotherapy, less than 25% of patients with acute kidney injury (AKI) and MM who required dialysis recovered sufficient renal function to become independent from dialysis, with a median overall survival of less than 1 year. There are many other factors involved in determining patient survival. In this study we aimed to investigate the role of double filter-based extracorporeal treatment for removal of serum free light chains (sFLC) in acute myeloma kidney (AKI for MM) and to evaluate patient overall survival. All patients received Bortezomib-based chemotherapy and extracorporeal treatment for sFLC removal. For each session 2 dialyzers of the same kind were used. The dialytic dose was not related to the degree of renal function but to the removal of sFLC. The factors that have been found to be significantly associated with lower mortality were reduction of sFLC at day 12 and day 30, >50% reduction of sFLC at day 30, number of sessions and independence from dialysis. Among baseline characteristics, albumin level was statistically associated with the patients’ outcome. Our analysis highlights the importance of the early treatment for removal of sFLC in AKI for MM. These results indicate that the early removal of sFLC can improve patient’s outcome.

In December 2019, following a cluster of pneumonia cases in China caused by a novel coronavirus (CoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infection disseminated worldwide and, on March 11th, 2020, the World Health Organization officially declared the pandemic of the relevant disease named coronavirus disease 2019 (COVID-19). In Europe, Italy was the first country facing a true health policy emergency, and, as at 6.00 p.m. on May 2nd, 2020, there have been more than 209,300 confirmed cases of COVID-19. Due to the increasing number of patients experiencing a severe outcome, global scientific efforts are ongoing to find the most appropriate treatment. The usefulness of specific anti-rheumatic drugs came out as a promising treatment option together with antiviral drugs, anticoagulants, and symptomatic and respiratory support. For this reason, we feel a duty to share our experience and our knowledge on the use of these drugs in the immune-rheumatologic field, providing in this review the rationale for their use in the COVID-19 pandemic.

Abstract The aim of the study was to clarify the effect of long-term anti-TNF therapy on T cell function in patients with rheumatologic immune-mediated inflammatory diseases (IMID). The production of IFNγ by T cells was evaluated at baseline and after 1, 2, 4, and 8 years of anti-TNF agents by means of a QuantiFERON-TB Gold In-Tube assay. The T cell proliferation and surface co-expression of CD25/CD134 in response to phytohaemagglutinin together with the in vitro impact of anti-TNF therapy on the functional capacity of T cells were evaluated after 8 years from the onset of the biological treatment. Age-matched healthy donors were enrolled as controls. The quantitative mitogen-induced IFNγ responses significantly increased with respect to baseline at each time point, apart from the determination after 4 years. We found an increased expression of CD25/CD134 in CD4+ compared to CD8+ T cells both in patients and controls. The in vitro addition of anti-TNF agents induced a significant decrease of both the IFNγ response and of CD25/CD134, whereas no effect on the intensity of the proliferative response was observed. Our data provide a biological basis for the reassuring issues on the safety of long-term anti-TNF treatment in patients with IMID.

Background: Few studies have evaluated the effectiveness of adalimumab in the real-life setting in psoriatic arthritis (PsA).Objective: To evaluate the 2-year retention rate of adalimumab in PsA patients. Potential baseline parameters influencing persistence on treatment were also evaluated.Methods: PsA patients from 16 Italian Rheumatology Units treated with adalimumab as first- or second-line biological therapy were retrospectively evaluated. Adalimumab retention rate was evaluated at 12 and 24 months. Logistic regression was used to evaluate the association between predictor variables and adalimumab retention rate.Results: From 424 patients (53.5% male, aged 48.3 ± 12.8 years) who started treatment with adalimumab, 367 (86.6%) maintained treatment for 12 months and 313 (73.8%) for 2 years. At 24-months, Disease Activity in PsA (DAPSA) remission (defined as ≤4) and Low Disease Activity (LDA) (≤14) were achieved in 22.8% and 44.4% of patients, respectively. Adalimumab treatment significantly decreased the number of tender (7.0 ± 5.7 at baseline vs. 2.3 ± 3.5 at 24 months, p < 0.001) and swollen joints (2.7 ± 2.8 at baseline vs. 0.4 ± 0.9 at 24 months, p < 0.001), DAPSA (25.5 ± 10.9 at baseline vs. 11.0 ± 8.4 at 24 months, p < 0.001), PASI (5.3 ± 5.7 at baseline vs. 2.7 ± 2.8 at 24 months, p < 0.001) and CRP (3.8 ± 6.3 at baseline vs. 1.2 ± 1.7 at 24 months, p < 0.001). Among a range of laboratory and clinical variables, only female gender was associated with improved adalimumab persistence at 24 months (OR: 1.98, 95% CI: 1.2–3.2, p = 0.005).Conclusions: Independent of a range of predictor variables, adalimumab was shown to be effective, while maintaining a high retention rate after 2 years in PsA patients.

Uremic toxins play a pathological role in atherosclerosis and represent an important risk factor in dialysis patients. Online hemodiafiltration (HDF) has been introduced to improve the clearance of middle- and large-molecular-weight solutes (>500 Da) and has been associated with reduced cardiovascular mortality compared to standard hemodialysis. This non-randomized, open-label observational study will explore the efficacy of two dialyzers currently used for online HDF, a polysulfone-based high-flux membrane, and a cellulose triacetate membrane, in hemodialysis patients with signs of middle-molecule intoxication or intradialytic hypotension. In particular, the two filters will be evaluated for their ability in uremic toxin removal and modulation of inflammatory status. Sixteen subjects in standard chronic bicarbonate hemodialysis requiring a switch to online HDF in view of their clinical status will be enrolled and divided into two treatment arms, according to the previous history of hypersensitivity to polysulfone/polyethersulfone dialysis filters and hypersensitivity to drugs or other allergens. Group A will consist of 16 patients without a previous history of hypersensitivity and will be treated with a polysulfone filter (Helixone FX100), and group B, also consisting of 16 patients, with a previous history of hypersensitivity and will be treated with asymmetric triacetate (ATA; SOLACEA 21-H) dialyzer. Each patient will be followed for a period of 24 months, with monthly assessments of circulating middle-weight toxins and protein-bound toxins, markers of inflammation and oxidative stress, lymphocyte subsets, activated lymphocytes, and monocytes, cell apoptosis, the accumulation of advanced glycation end-products (AGEs), variations in arterial stiffens measured by pulse wave velocity (PWV), and mortality rate. The in vitro effect on endothelial cells of uremic serum collected from patients treated with the two different dialyzers will also be investigated to examine the changes in angiogenesis, cell migration, differentiation, apoptosis and proliferative potential, and gene and protein expression profile. The expected results will be a better awareness of the different effects of polysulfone gold-standard membrane for online HDF and the new ATA membrane on the removal of uremic toxins removal and inflammation due to blood–membrane interaction.

The continuing economic crisis and a slow recovery in the construction sector, is becoming an increasingly important theme of the squandering of financial resources invested for the construction of public works. In recent years it has taken cognizance of this critical and unsustainable financial heaviness that causes considerable economic and social repercussions. In addition to the corruption that requires repressive interventions, there are methodological shortcomings of estimated economic, found both in the sector regulations, and in university courses. The work in this area, shows that one of the main problems arises from the programming phase of the works, when the erroneous assessment of the investment costs is reflected up to the realization of the same work. This paper is a summary of how scientific research into economic estimate, may provide tools and identify shared and effective methodologies for the control of expenditure in the public works sector since their initial programming.