PubMed | Ospedale San Pellegrino, VieCuri Medical Center, Azienda Istituti Ospitalieri di Cremona, University of Porto and 3 more.
Type: Journal Article | Journal: JACC. Heart failure | Year: 2016
The aim of this study was to analyze the prognostic value and attainability of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in young and elderly acute decompensated heart failure (ADHF) patients.Less-effective NT-proBNP-guided therapy in chronic heart failure (HF) has been reported in elderly patients. Whether this can be attributed to differences in prognostic value ofNT-proBNP or to differences in attaining a prognostic value is unclear. The authors studied this question in ADHF patients.Our study population comprised 7 ADHF cohorts. We defined absolute (<1,500 ng/l,<3,000 ng/l, <5,000ng/l, and<15,000 ng/l) and relative NT-proBNP discharge cut-off levels (>30%, >50%, and >70%). Six-month all-cause mortality after discharge was studied for each level in Cox regression analyses, and compared between elderly (age >75 years) and young patients (age 75 years). Thereafter, we compared percentages of elderly andyoung patients attaining NT-proBNP levels (= attainability).A total of 1,235 patients (59% male, 45% >75 years of age) was studied. Admission levels of NT-proBNP were significantly higher in elderly versus younger patients. The prognostic value of absolute and relative NT-proBNP levels was similar in elderly and young patients. Attainability was significantly lower in elderly patients for all absolute levelsand a >50% relative reduction, but not for >30% and >70%. For absolute levels, attainability differences between age groups were decreased to a large extent after correction for admission NT-proBNP and anemia at discharge. For relative levels, attainability differences disappeared after correction for HF etiology and anemia atdischarge.In young and elderly ADHF patients, it is not the prognostic value of absolute and relative NT-proBNP levels that is different, but the attainability of these levels that is lower in the elderly. This can largely be attributed tofactors other than age.
Challenging the two concepts in determining the appropriate pre-discharge N-terminal pro-brain natriuretic peptide treatment target in acute decompensated heart failure patients: absolute or relative discharge levels?
PubMed | Azienda Istituti Ospitalieri di Cremona, University of Porto, University of Florence, Hospital Universitari Germans Trias i Pujol and 2 more.
Type: Journal Article | Journal: European journal of heart failure | Year: 2015
NT-proBNP is a strong predictor for readmissions and mortality in acute decompensated heart failure (ADHF) patients. We assessed whether absolute or relative NT-proBNP levels should be used as pre discharge treatment target.Our study population was assembled from seven ADHF cohorts. We defined absolute (<1500, <3000, <5000, and <15 000 ng/L) and relative NT-proBNP targets (>30, >50, and >70%). Population attributable risk fraction (PARF) is the proportion of all-cause 6-month mortality in the population that would be reduced if all patients attain the NT-proBNP target. PARF was determined for each target as well as the percentage of patients attaining the NT-proBNP target. Attainability was investigated by logistic regression analysis. A total of 1266 patients [age 74 (64-80), 60% male] was studied. For every absolute NT-proBNP level, a corresponding percentage reduction was found that resulted in similar PARFs. The highest PARF (60-70%) was observed for <1500 or >70%, but attainability was low (27% and 22%, respectively). The strongest predictor for not attaining these targets was admission NT-proBNP. In admission NT-proBNP tertiles, PARFs were significantly different for absolute, but not for relative targets.In an ADHF population, pre-discharge absolute or relative NT-proBNP targets may both be useful as they have similar effects on PARF. However, depending on admission NT-proBNP, absolute targets show varying PARFs, while PARFs for relative targets were similar. A relative target is predicted to reduce mortality consistently across the whole spectrum of ADHF patients, while this is not the case using a single absolute target.
Miceli R.,Fondazione IRCCS Instituto Nazionale Tumori |
Tomasello G.,Azienda Istituti Ospitalieri di Cremona |
Bregni G.,Fondazione IRCCS Instituto Nazionale Tumori |
Di Bartolomeo M.,Fondazione IRCCS Instituto Nazionale Tumori |
Pietrantonio F.,Fondazione IRCCS Instituto Nazionale Tumori
World Journal of Gastroenterology | Year: 2014
Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that diseasefree survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
Tomasello G.,Concordia Medical |
Liguigli W.,Concordia Medical |
Poli R.,Concordia Medical |
Lazzarelli S.,Concordia Medical |
And 8 more authors.
Gastric Cancer | Year: 2014
Background: We previously studied a dose-dense TCF (TCF-dd) regimen demonstrating its feasibility and an activity comparable to epirubicin-based chemotherapy and TCF q3w in terms of overall survival and time to progression (TTP). We report here the final results of a phase II study of chemotherapy with a modified TCF-dd regimen in locally advanced or metastatic gastric cancer (MGC).Methods and study design: Patients with histologically confirmed measurable MGC, not previously treated for advanced disease, received docetaxel 70 mg/m2day 1, cisplatin 60 mg/m2day 1, l-folinic acid 100 mg/m2days 1 and 2, followed by 5-fluorouracil (5-FU) 400 mg/m2bolus days 1 and 2, and then 600 mg/m2as a 22-h continuous infusion days 1 and 2, every 14 days, plus pegfilgrastim 6 mg on day 3. Patients aged ≥65 years received the same schedule with a dose reduction of 30 %.Results: Study duration: December 2007–November 2010. Forty-six consecutive patients were enrolled (78 % male, 22 % female; median age, 66 years, range, 38–76 years; ECOG PS: 0, 48 %, 1, 46 %). Primary endpoint was overall response rate (ORR). A median of four cycles (range, one to six) was administered. Forty-three patients were evaluated for response (93.5 %) and all for toxicity: 3 complete response (CR), 25 partial response (PR), 10 stable disease (SD), and 5 progressive disease (PD) were observed, for an ORR by intention to treat (ITT) of 61 % (95 % CI 47–75). Median overall survival (OS) was 17.63 months (95 % CI, 13.67–20.67); median progression-free survival was 8.9 months (95 % CI, 6.5–13.4). Twenty-one patients (46.0 %) were treated at full doses without any delay, thus respecting the dose-dense criterion. Most frequent grade 3–4 toxicities were neutropenia (20 %), leukopenia (4 %), thrombocytopenia (2 %), anemia (2 %), febrile neutropenia (6 %), asthenia (22 %), diarrhea (4 %), nausea/vomiting (11 %), and hypokalemia (6 %). Overall, TCF-dd was shown to be safe.Conclusions: The TCF-dd regimen in locally advanced or MGC is confirmed to be feasible and very active and needs to be further tested in randomized studies. © 2013, The International Gastric Cancer Association and The Japanese Gastric Cancer Association.
Pecchini P.,Azienda Istituti Ospitalieri di Cremona |
Malberti F.,Azienda Istituti Ospitalieri di Cremona |
Mieth M.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Quinn R.,University of Calgary |
And 5 more authors.
Journal of Nephrology | Year: 2012
Background: Asymmetric dimethylarginine (ADMA) is increasingly being investigated as a renal and cardiovascular risk factor in chronic kidney disease (CKD). We assessed the degree of agreement of an enzymelinked immunosorbent assay (ELISA) of ADMA and the gold standard liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). Methods: ADMA was measured in an incident cohort of 126 stable CKD patients. Correlations between methods were studied by estimating the interclass Pearson coefficient (IPC), Lin's concordance correlation coefficient (CCC) and the maximum likelihood intraclass correlation coefficient (ICC). Limits of agreement (LOA) were estimated using the Bland-Altman method. Results: ADMA values were normally distributed with means of 0.78 ± 0.16 (ELISA) and 0.59 ± 0.09 mol/L (LCMS/MS). IPC was 0.69 (95% confidence interval [95% CI], 0.59-0.78). Overall CCC was 0.29 (95% CI, 0.230.37), with a difference in means of 0.19 mol/L (95% LOA, -0.043 to 0.43), delta slope of 0.577 and delta intercept of 0.14 (vs. perfect agreement line). Data were similar across categories of clinical characteristics. Mixed models provided an ICC of 0.58 (95% CI, 0.460.69). Bias was larger among patients with glomerular filtration rate (GFR) <30 ml/min. When values obtained from ELISA were corrected using the slope and intercept estimates from concordance analyses, the adjusted ICC improved to 0.67 (95% CI, 0.57-0.76), and bias modification by GFR levels canceled out. Conclusions: In CKD, ELISA overestimates ADMA concentration as compared with LC-MS/MS. Appropriate calibration is needed when ADMA is measured by ELISA in CKD patients. © 2012 Società Italiana di Nefrologia.
Ravani P.,University of Calgary |
Maas R.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Malberti F.,Azienda Istituti Ospitalieri di Cremona |
Pecchini P.,Azienda Istituti Ospitalieri di Cremona |
And 5 more authors.
PLoS ONE | Year: 2013
Background and Aims:Homoarginine, a precursor of nitric oxide, is an inverse predictor of death in dialysis patients and in subjects with cardiovascular disease and normal kidney function but its relationship with clinical outcomes in chronic kidney disease (CKD) patients not yet on dialysis is unknown.Design, setting, participants and measurements:We enrolled 168 consecutive predialysis CKD patients (Age: 70±11 yrs; 26% Diabetics; eGFR 34±18 ml/min/1.73 m2) referred to a tertiary care centre and measured laboratory data on kidney function and cardiovascular risk factors. We modeled progression to dialysis or death as a function of homoarginine, using Cox's regression, accounting for clinical characteristics, baseline levels of kidney function, and markers of inflammation.Results:On crude and adjusted analyses homoarginine was directly associated with the eGFR and patients with more compromised renal function exhibited lower homoarginine levels. Furthermore homoarginine was also independently related to L-arginine, serum albumin and body mass index, and inversely related to proteinuria, C-reactive protein and age. During the study (follow up median time 4 years, inter-quartile range 1.7 to 7.0 years) 56 patients started dialysis and 103 died and homoarginine was a strong inverse predictor of the incidence rate of both outcomes (P = 0.002 and P = 0.017).Conclusions:Homoarginine declines with advancing renal disease and is inversely related to progression to dialysis and mortality. The nature of the link between homoarginine and clinical outcomes is amenable to testing in clinical trials. © 2013 Ravani et al.
Buti S.,Azienda Istituti Ospitalieri di Cremona |
Buti S.,University of Parma |
Donini M.,Azienda Istituti Ospitalieri di Cremona |
Lazzarelli S.,Azienda Istituti Ospitalieri di Cremona |
Passalacqua R.,Azienda Istituti Ospitalieri di Cremona
Acta Biomedica | Year: 2012
Background and aim of the work: Sunitinib 50 mg/day given for 4 weeks followed by 2 weeks off treatment (4+2 schedule) is a standard treatment for metastatic renal cell carcinoma, but several patients are forced to reduce the doses and/or had to discontinue therapy permanently due to toxicity. Recent data showed that increased exposure to sunitinib is associated with improved clinical outcome underlining the key role of dose-intensity in the efficacy/toxicity balance. We investigated the tolerability and efficacy of a modified schedule. Patients and methods: This is a retrospective analysis which assessed consecutive non-progressive metastatic renal cell carcinoma patients admitted to our hospital who had at least a grade 2 toxicity during sunitinib therapy, and then switched to a modified schedule maintaining the same dose-intensity of 4+2 schedule: starting on Monday, 1 tablet/day for 5 consecutive days a week (days 6 and 7 off therapy) for 5 weeks and 1 tablet/day on days 1, 3 and 5 in the sixth week (days 2, 4, 6 and 7 off therapy) until disease progression. Primary end points were toxicity changes assessment and schedule feasibility. Results: Complete data from eight nephrectomized patients were collected: 6 males; median age 61; 3 pretreated patient. Median time from start therapy to switch was 7.4 months. After switch, treatment delays and dose reductions decreased from 50% to 25% and from 37% to 12% of patients respectively. Toxicity was reduced. Conclusions: Even though no conclusions can be drawn about the actual effectiveness and toxicity of our schedule compared to the standard dosing schedule, it seems to be well tolerated and able to maintain a high adherence to therapy, resulting in maintenance of antitumour activity. © Mattioli 1885.
PubMed | Azienda Istituti Ospitalieri di Cremona
Type: | Journal: Tumori | Year: 2016
To evaluate the efficacy and safety of dose-dense TCF in elderly (65 years) compared to younger patients.Safety and efficacy data relative to 119 consecutive patients with locally advanced or metastatic gastric cancer treated at our institution and enrolled in different phase II trials were retrospectively collected. All patients were treatment-naive and received docetaxel 70 mg/m2 day 1, cisplatin 60 mg/m2 day 1, l-folinic acid 100 mg/m2 days 1-2, followed by 5-fluorouracil 400 mg/m2 bolus days 1-2, and then 600 mg/m2 as a 22-hour continuous infusion days 1-2, every 14 days, plus pegfilgrastim 6 mg on day 3. Sixty patients (50%) aged 65 years received the same schedule with a dose reduction by 30%.A total of 86% of patients were evaluable for response and all for toxicity. In patients aged 65 years, we observed an overall response rate of 51%. Median overall survival was 11.2 (95% confidence interval [CI] 7.3-15.1) and 11.8 months (95% CI 9.2-16.2) in elderly and younger patients, respectively. In the elderly patients, the most frequent grade 3-4 toxicities were neutropenia (13%), leukopenia (7%), thrombocytopenia (18%), anemia (3%), and febrile neutropenia (8%); in the younger patients, neutropenia (56%), leucopenia (31%), thrombocytopenia (22%), anemia (15%), and febrile neutropenia (15%).Elderly patients can be safely treated with a dose-dense TCF regimen with a 30% dose reduction achieving similar efficacy results as younger patients with lesser toxicity.