Oral Sucrosomial® iron versus intravenous iron for recovering iron deficiency anaemia in ND-CKD patients: a cost- minimization analysis.

BACKGROUND: Oral iron is recommended as first line treatment of anemia in non-dialysis chronic kidney disease (ND-CKD) patients. Sucrosomial® iron, a new generation oral iron with high absorption and bioavailability and a low incidence of side effects, has shown to be not inferior to intravenous (IV) iron in the replacement of iron deficiency anemia in patients with ND-CKD. Besides the clinical benefit, it is also important to determine the comparative total costs of oral versus IV iron administrations. The aim of this study was to perform a cost-minimization analysis of oral Sucrosomial iron, compared with IV iron gluconate from an Italian societal perspective. METHODS: Cost analysis was performed on the 99 patients with ND-CKD and iron-deficiency anemia of the randomized trial by Pisani et al. Human and material resources utilization was recorded during each iron administration. According to study perspective, direct and indirect costs were considered. Costs for each resource unit were taken from official Italian sources. Probabilistic sensitivity analyses were carried out to test the robustness of the results. RESULTS: The base case analysis showed an average cost/cycle per patient of € 111 for oral iron and € 1302 for IV iron. Thus, the potential saving was equal to € 1191 per patient/cycle. The sensitivity analysis showed that the most sensitive driver is the time loss by patient and caregivers for the therapy and related-care, followed by the minutes of nursing care and the number of kilometres travelled to reach the referral centre. DISCUSSION: This study showed that oral Sucrosomial® iron could offer specific advantages in terms of potential savings, and allowed identifying some implications for future research. Such advantages still persist with the new single dose IV iron formulation available in the market, although to a lesser extent.

Idiosyncratic hepatic toxicity in autosomal dominant polycystic kidney disease (ADPKD) patient in combined treatment with tolvaptan and amoxicillin/clavulanic acid: a case report.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease characterized by the presence of renal cysts. Over time the expanding cysts lead to progressive renal failure. The use of tolvaptan, a V2-receptor antagonist, was recently approved in ADPKD patients. It was demonstrated that tolvaptan get slower decline in Kidney function compared with placebo. Idiosyncratic hepatic toxicity was described in patients receiving tolvaptan, with elevations in aminotransferases levels. We describe the first case reported in the literature in which hepatic toxicity is caused by the association of amoxicillin/clavulanic acid and tolvaptan. CASE PRESENTATION: A 41 years old woman with diagnosis of ADPKD had been in treatment with tolvaptan for 16 weeks when an elevation of liver enzyme levels was detected. She had taken autonomously amoxicillin/clavulanic acid (in doses of 825/175 mg twice a day for 7 days) about 5 weeks before. The timing of the event and the kind of hepatocellular injury could be attributed to the concomitance of medication of tolvaptan and amoxicillin/clavulanic acid. CONCLUSION: We highlight the need to careful monitor hepatic enzyme levels in order to recognize early hepatic side effects in ADPKD patients in treatment with tolvaptan and amoxicillin/clavulanic acid.

Parapelvic cysts, a distinguishing feature of renal Fabry disease.

Background: Fabry's disease (FD) is a rare, multi-organ lysosomal disease, caused by the deficiency of the enzyme α-galactosidase A, and is difficult to diagnose. Although parapelvic cysts (PC) were previously associated with FD, their prevalence and significance are unclear. Methods: The present study aimed to: (i) evaluate, by renal ultrasound, the real prevalence of PC and of their determinants in a multicentre, nationwide cohort of FD patients (n = 173, Study 1) and (ii) ascertain whether a greater accuracy of PC detection improved their identification, in FD patients from a single centre (n = 67, Study 2). In both studies, for each FD patient, an age- and renal function-matched subject was selected for comparison (1:1). Results: In Study 1, PC were detected in 28.9% of FD subjects and in only 1.1% of control subjects (P < 0.001). The presence of other renal abnormalities did not differ between the groups, nor differences exist in the main demographic and laboratory parameters between the groups. In Study 2, the greater accuracy of ultrasound increased PC prevalence from 29.8% to 43.3% in the same subjects (P < 0.05). In both studies, no correlation was detected between PC and the main demographic, clinical and biochemical parameters, including use of enzyme replacement therapy (P < 0.1, minimum value). Finally, no difference existed between FD patients with and without PC. Conclusions: The present study suggests that the presence of PC in renal patients should alert physicians to consider the diagnosis of FD, primarily in subjects with an unclear family history of renal disease and in the presence of other stigmata of the disease.

Development and validation of a score assessing the risk of severe asthma in primary care.

OBJECTIVE: To develop and validate the Asthma Severity-Health Search (AS-HScore), predicting severe asthma risk in Italian primary care. According to the current asthma treatment guidelines, the AS-HScore intended to serve as a clinical decision support system (CDSS) for General Practitioners (GPs). METHODS: Using the Health Search Database (HSD), a cohort of 32,917 asthma-diagnosed patients between 2013 and 2021 was identified. The AS-HScore was developed using multivariable Cox regression in a two-part cohort: development and validation. Candidate determinants were estimated and linearly combined to form the score; its predictive accuracy was evaluated in the validation sub-cohort. RESULTS: AS-HScore performance in the validation cohort revealed a 73% area under the curve (i.e. discrimination power) and a 22% pseudo-R2 (explained variation). Calibration slope of 1.07 indicated strong calibration without rejecting the equivalence hypothesis (p = 0.157). Estimating a mean 10% (SD: 6.8%) 1-year risk of severe asthma, GPs might be provided with risk thresholds for patient categorization. CONCLUSION: The AS-HScore emerges as an accurate tool predicting severe asthma risk in the Italian primary care. It therefore shows promising application to enhance asthma care by early identification of severe cases. Implementing a score-based CDSS for Italian GPs holds potential for significantly improving asthma management and patients' outcomes.

[New perspectives in cardiovascular risk reduction: focus on HDL]. / Nuove prospettive nella riduzione del rischio cardiovascolare: focus su HDL.

Cardiovascular diseases represent the leading cause of morbidity and mortality worldwide, mostly contributing to hospitalizations and health care costs. Dyslipidemias represent one of the major cardiovascular risk factor and its management, throughout life-style modifications and pharmacological interventions, has shown to reduce cardiac events. The risk of adverse cardiovascular events is related not only to elevated LDL blood levels, but also to decreased HDL concentrations, that exhibit protective effects in the development of atherosclerotic process. Aim of this review is to summarize current evidences about defensing effects of such lipoproteins and to show the most recent pharmacological strategies to reduce cardiovascular risk through the increase of their circulating levels.

[Endothelial function as a marker of pre-clinical atherosclerosis: assessment techniques and clinical implications]. / Funzione endoteliale quale marker di aterosclerosi subclinica: metodiche di valutazione ed applicazioni cliniche.

Endothelium plays a key role in maintenance of vascular homeostasis. Cardiovascular risk factors promote development of endothelial dysfunction, characterized by increased vasoconstriction and by procoagulant/pro-inflammatory endothelial activities. In coronary artery, endothelium-dependent dilation improves blood flow, while the occurrence of endothelial dysfunction reduces myocardial perfusion, so new methods have been developed for assessment of endothelial function in coronary and peripheral arteries. The quantitative angiography with intracoronary infusion of acetylcholine remains the "gold standard" to assess the endothelium-dependent vasodilatation. The use of this technique is restricted to patients who have a clinical indication for coronary angiography, so new imaging methods have been considered for noninvasive diagnosis of coronary microvascular disease, such as magnetic resonance imaging phase contrast and positron emission tomography. The advent of new techniques has facilitated testing of endothelial dysfunction in peripheral arteries with non-invasive methods. This review presents available in-vivo and ex-vivo methods for evaluating endothelial function with special focus on more recent ones. The diagnostic tools include local vasodilatation by venous occlusion plethysmography and assessment of flow-mediated dilatation, arterial pulse wave analysis and pulse amplitude tonometry, laser Doppler flowmetry. The possibility to detect endothelial dysfunction as an early marker of atherosclerosis makes these instruments useful for early stratification of patients at risk for cardiovascular events. Aim of this review is to summarize the characteristics of non-invasive assessment of endothelial function in order to optimize cardiovascular risk management.

[Which is the role of the oral iron therapies for iron deficiency anemia in non-dialysis-dependent chronic kidney disease patients? Results from clinical experience].

Iron deficiency afflicts about 60% of dialysis patients and about 30% of non-dialysis-dependent CKD patients (ND-CKD). The role of iron deficiency in determining anemia in CKD patients is so relevant that guidelines from the Kidney Disease Improving Global Outcomes (KDIGO) initiative recommend treating it before starting with erythropoiesis-stimulating agents. KDIGO guidelines suggest oral iron therapy because it is commonly available and inexpensive, although it is often characterized by low bioavailability and low compliance due to adverse effects. A new-generation oral iron therapy is now available and seems to be promising. We therefore conducted a study to determine whether an association of iron sucrose, folic acid and vitamins C, B6, B12, can improve anemia in ND-CKD patients, stage 3-5. Our study shows that iron sucrose is a safe and effective oral iron therapy and that it is capable of correcting anemia in ND-CKD patients, although it does not seem to replete low iron stores.

[Mortality and morbidity cohort study of residents in the neighbourhood of Milazzo industrial area (Sicily)]. / Studio di mortalità e morbosità di una coorte di residenti in prossimità dell'area industriale di Milazzo, nel Comune di Pace del Mela (Messina).

OBJECTIVE: The municipality of Pace del Mela, together with Milazzo and San Filippo del Mela, has been recognized as a contaminated site of national concern. The purpose of the present study is to evaluate the health status of subjects resident in the Gabbia district, which is close to the industrial areas of both, Pace del Mela and Milazzo. SETTING AND PARTICIPANTS: All streets and addresses of the area of interest have been identified, taking into account their changes in name over time. The cohort of subjects who lived in the area for any period of time from September 1st, 1984, through December 31st, 2007 has been reconstructed by manual consultation of the Registrar Office files. Standardized mortality ratios, specific for cause, age class, gender and calendar period, have been computed using as reference the Sicilian population. Standardised incidence ratios, based on regional hospital discharge files, have been computed for the years 2001-2007. The cohort is constituted by 457 subjects, 230 men and 227 women. Ascertainment of vital status has not been possible for 39 subjects, corresponding to 8.5% of the cohort. RESULTS: Observed mortality for all causes and for all cancers is consistent with expected figures (62 observed vs 63 expected and 14 observed vs 15 expected, respectively). Observed cancer morbidity is inferior to the corresponding expected figure (SIR=0.49, CI 95%: 0.31-0.79). CONCLUSION: The health profile of the Gabbia district population, as estimated from mortality and hospital discharge records, does not show major departures from expected figures.

Renal Resistive Index of the Main Renal Arteries and Transmitral Flow in Hypertensive Patients.

In hypertensive patients, diastolic dysfunction is related to increased resistive index (RI) of parenchymal renal arteries. To determine the existence of a link between RI of the main renal arteries (RRI) and diastolic dysfunction, a group of 127 hypertensive patients, with glomerular filtration rates >50 mL/min (mean estimated glomerular filtration rate: 88.6 ± 15.2 mL/min) and no comorbidities, was studied. RRI and transmitral flow were evaluated using the deceleration time (DT) and E/A ratio. A statistically significant correlation between RRI and DT (>240 ms) was noted (p < 0.001). The RRI cutoff that best discriminated patients with DT >240 ms was 0.675. For each unitary increment of 10 mm in DT, the log-transformed RRI significantly increased by a mean of 0.006 point (p < 0.001). This study revealed the importance of the link between RRI and transmitral DT in addition to the renowned significance of the increase in RI as a cardiovascular risk factor in hypertensive patients without comorbidities.

Prominent longitudinal strain reduction of left ventricular basal segments in treatment-naïve Anderson-Fabry disease patients.

AIMS: Little is known about regional longitudinal strain (LS) distribution in early stages of Anderson-Fabry disease (AFD) cardiomyopathy. We investigated regional left ventricular (LV) patterns of LS strain and base-to-apex behaviour of LS in treatment-naïve AFD patients. METHODS AND RESULTS: Twenty-three consecutive AFD patients at diagnosis and 23 healthy controls without cardiovascular risk factors and matched for age and sex to the patients, underwent a comprehensive evaluation of target organs. An echo-Doppler exam, including determination of regional and global LS strain (GLS) was obtained. The average LS of 6 basal (BLS), 6 middle (MLS), and 5 apical (ALS) segments and relative regional strain ratio [ALS/(BLS + MLS)] were also calculated. Ejection fraction and diastolic indices did not differ between the two groups. LV mass index was greater in AFD (P < 0.01). GLS (P = 0.006), BLS (P < 0.0001), and MLS (P = 0.003), but not ALS, were lower in AFD patients and relative regional strain ratio was higher in AFD (P < 0.01) than in controls. These analyses were confirmed separately in the two genders and even after excluding patients with wall hypertrophy. By subdividing AFD patients according to lysoGB3 levels, 9 patients with lysoGB3 ≥ 1.8 ng/L had lower ALS compared to 11 patients with lysoGB3 < 1.8 ng/L (P < 0.01). CONCLUSION: In naïve AFD patients, we observed an early reduction of LV LS, involving mainly LV basal myocardial segments. Nevertheless, the association found between the higher lysoGB3 levels and the lower apical cap LS demonstrates that apical segments LS, despite still normal, is not spared at diagnosis.

Glomerular Hyperfiltration: An Early Marker of Nephropathy in Fabry Disease.

BACKGROUND AND OBJECTIVES: Progressive nephropathy is one of the main features of Fabry disease (FD). It has been supposed that an early phase, clinically silent disease occurs in childhood and adolescence and is characterized by glomerular hyperfiltration (HF). Surprisingly, although HF has been reported in several studies, its prevalence is at present unknown. The focus of our study was to determine the prevalence of HF in a cohort of patients with FD and to identify the factors associated with a high risk of HF. METHODS: To address this issue, a retrospective observational study of 87 patients with genetically confirmed FD was performed. HF was defined as an estimated glomerular filtration rate (eGFR) > 130 mL/min/1.73 m2 corrected for age (> 40 years: -1 mL/min/1.73 m2/year). RESULTS: HF occurred in 21 patients (24% of our population), and increased to 50% when only young adults were considered. Hyperfiltrating patients were younger and had lower proteinuria levels than those without HF. The prevalence of cardiovascular and other manifestations of FD was significantly lower in hyperfiltering patients. CONCLUSIONS: Our study showed a negative correlation between eGFR and age, and with proteinuria levels and the presence of cardiovascular and other manifestations of FD. These data favor the view that HF in Fabry patients could be related predominantly to a predisease state. Even in the absence of a "measured" GFR, HF should be regarded as an early marker of Fabry nephropathy, and its recognition and confirmation by true GFR seems a relevant feature to address the issue of the potential benefit of nephroprotective treatments at the early stage of Fabry nephropathy.

Ischemic heart disease in systemic inflammatory diseases. An appraisal.

Systemic inflammatory diseases are inflammatory syndromes that are associated with increased cardiovascular morbidity and mortality. The link between inflammatory and cardiovascular diseases can be attributed to coexistence of classical risk factors and of inflammatory mechanisms activated in systemic inflammatory diseases and involving the immune system. Yet, clinical implications of these findings are not entirely clear and deeper knowledge and awareness of cardiac involvement in inflammatory diseases are necessary. The aims of this review are to summarize cardiac involvement in systemic inflammatory diseases and to identify areas where evidence is currently lacking that deserve further investigation in the future.

Nuclear imaging in detection and monitoring of cardiotoxicity.

Cardiotoxicity as a result of cancer treatment is a novel and serious public health issue that has a significant impact on a cancer patient's management and outcome. The coexistence of cancer and cardiac disease in the same patient is more common because of aging population and improvements in the efficacy of antitumor agents. Left ventricular dysfunction is the most typical manifestation and can lead to heart failure. Left ventricular ejection fraction measurement by echocardiography and multigated radionuclide angiography is the most common diagnostic approach to detect cardiac damage, but it identifies a late manifestation of myocardial injury. Early non-invasive imaging techniques are needed for the diagnosis and monitoring of cardiotoxic effects. Although echocardiography and cardiac magnetic resonance are the most commonly used imaging techniques for cardiotoxicity assessment, greater attention is focused on new nuclear cardiologic techniques, which can identify high-risk patients in the early stage and visualize the pathophysiologic process at the tissue level before clinical manifestation. The aim of this review is to summarize the role of nuclear imaging techniques in the non-invasive detection of myocardial damage related to antineoplastic therapy at the reversible stage, focusing on the current role and future perspectives of nuclear imaging techniques and molecular radiotracers in detection and monitoring of cardiotoxicity.

Cardiac magnetic resonance for the assessment of myocardial viability: from pathophysiology to clinical practice.

Cardiac magnetic resonance (CMR) is commonly applied for the assessment of myocardial viability in patients with ischemic ventricular dysfunction, and it holds potential advantages over more traditional imaging modalities, including single-photon emission computed tomography (SPECT) and dobutamine stress echocardiography (DSE). CMR-based techniques for viability assessment include the evaluation of transmural extent of the scar using late gadolinium enhancement (LGE) images, the evaluation of end-diastolic wall thickness from resting cine images and the study of inotropic reserve during low-dose dobutamine infusion. During the past decade, the diffusion of the use of CMR for viability assessment confirmed the clinical strengths of this modality and, at the same time, helped to use old techniques with an increased level of awareness. With LGE CMR, both viable and nonviable dysfunctional myocardium can be visualized in a single image, allowing a direct quantification of the amount of regional viability, with a significant impact on the estimation of chance for recovery. As well, studies with CMR applied in the setting of ischemic heart disease allowed a better understanding of the best way to apply and interpret other tests for viability evaluation. For instance, it has been demonstrated that the transmural extension of the scar may influence the level of concordance between SPECT and DSE in assessing myocardial viability. The transmural extent of scar on LGE CMR also correlates with the timing of postrevascularization recovery of systolic function, with significant impact on the diagnostic accuracy of any applied imaging modality.

Effects of ranolazine in symptomatic patients with stable coronary artery disease. A systematic review and meta-analysis.

BACKGROUND: Ranolazine (R), as add-on therapy in symptomatic patients with chronic stable coronary artery disease (CAD), has been tested in randomized clinical studies. Aim of the study was to assess in a meta-analysis the effects of R on angina, nitroglycerin consumption, functional capacity, electrocardiographic signs of ischemia and hemodynamic parameters in patients with chronic CAD. METHODS: Randomized trials assessing the effects of R compared to control on exercise duration, time to onset of angina, time to 1mm ST-segment depression, weekly nitroglycerin consumption and weekly angina frequency were included in the analysis. The effects of R compared to control on heart rate and blood pressure were also analyzed. RESULTS: Six trials enrolling 9223 patients were included in the analysis. At trough and peak levels, R compared to control significantly improved exercise duration, time to onset of angina and time to 1mm ST-segment depression. Additionally, R compared to control significantly reduced weekly angina frequency and weekly nitroglycerin consumption. Finally, R compared to control did not significantly reduce supine systolic and diastolic blood pressure as well as heart rate, standing heart rate and diastolic blood pressure, whereas it modestly reduced standing systolic blood pressure. At sensitivity analysis, results were not influenced by concomitant background therapy. CONCLUSIONS: In symptomatic patients with chronic CAD, R, added to conventional therapy, effectively reduces angina frequency and sublingual nitroglycerin consumption while prolonging exercise duration as well as time to onset of ischemia and to onset of angina with no substantial effects on blood pressure and heart rate.