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Ischemic preconditioning (IP) has been proposed as an endogenous form of protection against ischemia reperfusion injury. IP, however, does not prevent post-ischemic dysfunction in the aging heart but may be partially corrected by exercise training and food restriction. We investigated the role of exercise training combined with food restriction on restoring IP in the aging heart. Effects of IP against ischemia-reperfusion injury in isolated hearts from adult (A, 6 months old), sedentary 'ad libitum' fed (SL), trained ad libitum fed (TL), sedentary food-restricted (SR), trained- and food-restricted senescent rats (TR) (24 months old) were investigated. Norepinephrine release in coronary effluent was determined by high performance liquid cromatography. IP significantly improved final recovery of percent developed pressure in hearts from A (p

Background: The prognosis of patients with advanced gastric cancer remains overall poor despite some recent innovations and the development of new therapeutic approaches. Current European guidelines do not recommend any specific treatment for patients with advanced gastric cancer refractory to two or more previous chemotherapy regimens, making this setting “orphan.” Immunotherapy is quickly evolving also for this malignancy even if with controversial results and the correct patient selection is still debated, especially for Western patients. The phase III ONO-4538-12 “ATTRACTION-2” represents the current landmark trial for the development of immunotherapy for pretreated Asian patients and led to the approval of Nivolumab in some Asian countries, while only previous phase trials are available for Caucasians. Complete radiological response is anecdotic and has never been described both in the pivotal trial both in the others with Western patients enrolled. Case presentation: We report two cases of heavily pretreated Western elderly patients with metastatic gastric cancer who experienced durable complete radiological response to Nivolumab “off label” (more than 20 months to date) in a clinical practice context. Molecular analysis of potential predictive factors has been performed (PD-L1, EBV, MSI, and TMB) on primary tumor sample. Conclusions: Despite the lack of evidence for Western patients and the controversial outcome with the use of checkpoint inhibitors in previous settings, immunotherapy may dramatically change the prognosis and the natural history of pretreated Western metastatic gastric cancer, in a correctly selected population. Microsatellite instability and tumor mutational burden may be reliable predictive factors also for Caucasians. There is an urgent need for a change in clinical practice also for this “orphan” patients and more efforts are needed in order to clarify the role of predictive factors for a correct patient selection and better chances of survival for this awful malignancy.

Aims The assessment of frailty in older adults with heart failure (HF) is still debated. Here, we compare the predictive role and the diagnostic accuracy of physical vs. multidimensional frailty assessment on mortality, disability, and hospitalization in older adults with and without HF. Methods and results A total of 1077 elderly (≥65 years) outpatients were evaluated with the physical (phy‐Fi) and multidimensional (m‐Fi) frailty scores and according to the presence or the absence of HF. Mortality, disability, and hospitalizations were assessed at baseline and after a 24 month follow‐up. Cox regression analysis demonstrated that, compared with phy‐Fi score, m‐Fi score was more predictive of mortality [hazard ratio (HR) = 1.05 vs. 0.66], disability (HR = 1.02 vs. 0.89), and hospitalization (HR = 1.03 vs. 0.96) in the absence and even more in the presence of HF (HR = 1.11 vs. 0.63, 1.06 vs. 0.98, and 1.14 vs. 1.03, respectively). The area under the curve indicated a better diagnostic accuracy with m‐Fi score than with phy‐Fi score for mortality, disability, and hospitalizations, both in absence (0.782 vs. 0.649, 0.763 vs. 0.695, and 0.732 vs. 0.666, respectively) and in presence of HF (0.824 vs. 0.625, 0.886 vs. 0.793, and 0.812 vs. 0.688, respectively). Conclusions The m‐Fi score is able to predict mortality, disability, and hospitalizations better than the phy‐Fi score, not only in absence but also in presence of HF. Our data also demonstrate that the m‐Fi score has better diagnostic accuracy than the phy‐Fi score. Thus, the use of the m‐FI score should be considered for the assessment of frailty in older HF adults.

Modifications of lean mass are a frequent critical determinant in the pathophysiology and progression of heart failure (HF). Sarcopenia may be considered one of the most important causes of low physical performance and reduced cardiorespiratory fitness in older patients with HF. Sarcopenia is frequently misdiagnosed as cachexia. However, muscle wasting in HF has different pathogenetic features in sarcopenic and cachectic conditions. HF may induce sarcopenia through common pathogenetic pathways such as hormonal changes, malnutrition, and physical inactivity; mechanisms that influence each other. In the opposite way, sarcopenia may favor HF development by different mechanisms, including pathological ergoreflex. Paradoxically, sarcopenia is not associated with a sarcopenic cardiac muscle, but the cardiac muscle shows a hypertrophy which seems to be “not-functional.” First-line agents for the treatment of HF, physical activity and nutritional interventions, may offer a therapeutic advantage in sarcopenic patients irrespective of HF. Thus, sarcopenia is highly prevalent in patients with HF, contributing to its poor prognosis, and both conditions could benefit from common treatment strategies based on pharmacological, physical activity, and nutritional approaches.

Molecular profiling of a tumor allows the opportunity to design specific therapies which are able to interact only with cancer cells characterized by the accumulation of several genomic aberrations. This study investigates the usefulness of next-generation sequencing (NGS) and mutation-specific analysis methods for the detection of target genes for current therapies in non-small-cell lung cancer (NSCLC), metastatic colorectal cancer (mCRC), and melanoma patients. We focused our attention on EGFR, BRAF, KRAS, and BRAF genes for NSCLC, melanoma, and mCRC samples, respectively. Our study demonstrated that in about 2% of analyzed cases, the two techniques did not show the same or overlapping results. Two patients affected by mCRC resulted in wild-type (WT) for BRAF and two cases with NSCLC were WT for EGFR according to PGM analysis. In contrast, these samples were mutated for the evaluated genes using the therascreen test on Rotor-Gene Q. In conclusion, our experience suggests that it would be appropriate to confirm the WT status of the genes of interest with a more sensitive analysis method to avoid the presence of a small neoplastic clone and drive the clinician to correct patient monitoring.

Type 2 myocardial infarctions (T2-MI) is a type of necrosis that results from reduced oxygen supply and/or increased demand secondary to other causes unrelated to acute coronary atherothrombosis. The development and implementation of sensitive and high-sensitivity cardiac necrosis marker and the age-related increase of comorbidity lead to a boost of the frequency of T2-MI. T2-MI is often a complication of a high degree of clinical frailty in older adults, emerging as a "geriatric syndrome". Age-related non-cardiovascular causes may be the triggering factors and are strongly associated with the diagnosis, treatment, and prognosis of T2-MI. To date, there are no guidelines on management of this pathology in advancing age. Patient-centered approach and comprehensive geriatric assessment play a key role in the diagnosis, therapy and prognosis of geriatric patients with T2-MI.

Chronic heart failure (CHF) is frequently linked to clinical frailty, a complex geriatric condition associated with negative outcomes. However, the full characterization of frailty is still debated. Fried and colleagues focused on a ‘physical phenotype’ of frailty based on the assessment of unintentional weight loss, muscle weakness, slow walking speed, low physical activity, and exhaustion,1 while Rockwood and colleagues fostered a multidimensional concept involving, besides physical impairments, comorbidity, disability, mental, nutritional, and social components (known as the ‘Canadian frailty index’).

Aim: Systemic inflammatory response affects survival of gastric cancer (GC) patients. This study was carried out to create a prognostic inflammatory-based score to predict survival in metastatic GC (mGC) before first-line chemotherapy. Materials & methods: We studied the prognostic value of neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio in 151 patients with mGC at the diagnosis. Results: Median overall survival (OS) was significantly lower in patients with high NLR. Performance status 1–2 according to the Eastern Cooperative Oncology Group scale and NLR were predictors of shorter OS at multivariate analysis. Based on these results, we defined a prognostic OS score, showing a better median OS in favorable risk group. Conclusion: Elevated pretreatment NLR and Eastern Cooperative Oncology Group are independent predictors of shorter OS in mGC patients before first-line chemotherapy.

BaCKgrOuND: The prognosis of right colon cancer remains disappointing. Complete mesocolic excision (CMe) with central vascular ligation (CVL), based on the same oncological principles of total mesorectal excision, has been speculated to result in a better outcome. To evaluate the oncological adequacy of CMe with CVL, we carried out a comparative study with propensity score-matched analysis between two different surgical procedures performed at italian and egyptian university cancer centers. MeThODS: Forty-six egyptian patients underwent conventional right hemicolectomy, while eighty-eight italian patients underwent CMe with sharp dissection between the embryological planes, exposure of the superior mesenteric vessels with extended lymphadenectomy, and CVL. RESULTS: All operations were successful with no increase in postoperative complications (10% in the patients undergoing CMe vs. 19.5% in Egyptian patients). Number of harvested nodes (21 vs. 13) and lymph node ratio (0.08 vs. 0.22) were signifcantly different in patients undergoing CME (P=0.0001 and P=0.005, respectively). In these patients, the risk of cancer relapse was reduced to as much as one third (8% vs. 22%), even in node-positive tumors, and locoregional recurrences were never experienced. The classic operation was signifcantly associated with poor outcome (5-year disease-free survival rates were 89.2% in the group undergoing CME and 49.1% in the classic group, P=0.02). Propensity score-matched analysis warranted optimal balance and confrmed overall results. CONCLUSIONS: Right colon cancer patients undergoing CME beneftted from more oncological adequacy, with no increased postoperative complication rate, a decreased locoregional recurrence rate, and a better long-term outcome than patients operated on with the conventional procedure. BACKGROUND: The prognosis of right colon cancer remains disappointing. Complete mesocolic excision (CME) with central vascular ligation (CVL), based on the same oncological principles of total mesorectal excision, has been speculated to result in a better outcome. To evaluate the oncological adequacy of CME with CVL, we carried out a comparative study with propensity score-matched analysis between two different surgical procedures performed at Italian and Egyptian University cancer centers.METHODS: Forty-six Egyptian patients underwent conventional right hemicolectomy, while eighty-eight Italian patients underwent CME with sharp dissection between the embryological planes, exposure of the superior mesenteric vessels with extended lymphadenectomy, and CVL.RESULTS: All operations were successful with no increase in postoperative complications (10% in the patients undergoing CME vs. 19.5% in Egyptian patients). Number of harvested nodes (21 vs. 13) and lymph node ratio (0.08 vs. 0.22) were significantly different in patients undergoing CME (P=0.0001 and P=0.005, respectively). In these patients, the risk of cancer relapse was reduced to as much as one third (8% vs. 22%), even in node-positive tumors, and locoregional recurrences were never experienced. The classic operation was significantly associated with poor outcome (5-year disease-free survival rates were 89.2% in the group undergoing CME and 49.1% in the classic group, P=0.02). Propensity score-matched analysis warranted optimal balance and confirmed overall results.CONCLUSIONS: Right colon cancer patients undergoing CME benefitted from more oncological adequacy, with no increased postoperative complication rate, a decreased locoregional recurrence rate, and a better long-term outcome than patients operated on with the conventional procedure.

The aging population is increasing and, therefore, a higher prevalence of cardiac disease is emerging; including hypertension, coronary artery disease, atrial fibrillation and chronic heart failure. Large cohort studies have revealed a relationship among increased risk for cognitive impairment and dementia in cardiovascular diseases probably due to embolic stroke or chronic cerebral hypoperfusion. Thus, the aim of the present review is to overview the studies that investigate the presence and/or the development of cognitive impairments and dementia in patients with varied types of cardiovascular disease. Finally, a continuum among hypertension, coronary artery disease, atrial fibrillation and chronic heart failure with to the development of cognitive impairment and progression to dementia has been hypothesized. © 2014 Elsevier B.V.

Indocyanine green (ICG) is a near-infrared fluorescent contrast agent, which preferentially accumulates in cancer tissue. The aim of our study was to investigate the role of fluorescence imaging (FI) with ICG (ICG-FI) for detecting peritoneal carcinomatosis (PC) from colorectal cancer (CRC).Four CRC patients with PC scheduled for cytoreductive surgery + hyperthermic intraperitoneal chemotherapy were enrolled in this prospective study. At a median time of 50 min after 0.25 mg/kg ICG injected intravenously, intraoperative ICG-FI using Fluobeam(A (R)) was performed in vivo and ex vivo on all specimens. The Peritoneal Cancer Index was used to estimate the likelihood of complete cytoreduction.No severe complications were recorded. ICG-FI took a median of 20 min (range 10-30, IQR 15-25). Sixty-nine nodules were harvested. Fifty-two nodules had been diagnosed preoperatively by conventional imaging (n = 30; 43%) or intraoperatively by visual inspection/palpation (n = 22; 32%). With ICG-FI, 47 (90%) nodules were hyperfluorescent, and five hypofluorescent. Intraoperative ICG-FI identified 17 additional hyperfluorescent nodules. On histopathology, 16 were metastatic nodules. Sensitivity increased from 76.9%, with the conventional diagnostic procedures, to 96.9% with ICG-FI. The positive predictive value of ICG-FI was 98.4%, and test accuracy was 95.6%. Diagnostic performance of ICG-FI was significantly better than preoperative (p = 0.027) and intraoperative conventional procedures (p = 0.042). The median PCI score increased from 7 to 10 after ICG-FI (p < 0.001).Our results suggest that intraoperative ICG-FI can improve outcomes in patients undergoing CS for PC from CRC. Further studies are needed to determine the role of ICG-FI in this patient population.

Background Cancer outcome is considered to result from the interplay of several factors, among which host inflammatory and immune status are deemed to play a significant role. The neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to-monocyte ratio (LMR) have been profitably used as surrogate markers of host immunoinflammatory status and have also been shown to correlate with outcome in several human tumors. However, only a few studies on these biomarkers have been performed in gastric cancer patients, yielding conflicting results.Methods Data were retrieved from a prospective institutional database. Overall survival (OS) of 401 patients undergoing surgery for gastric cancer between January 2000 and June 2015 as well as disease-free survival (DFS) rates in 297 radically resected patients were calculated. MaxStat analysis was used to select cutoff values for NLR and LMR.Results NLR and LMR did not significantly correlate with tumor stage. Patients with a high NLR and a low LMR experienced more tumor recurrences (p < 0.001) and had a higher hazard ratio (HR) for both OS (HR = 2.4 and HR = 2.10; p < 0.001) and DFS (HR = 2.99 and HR = 2.46; p < 0.001) than low NLR and high LMR subjects. Both biomarkers were shown to independently predict OS (HR = 1.65, p = 0.016; HR = 2.01, p = 0.002, respectively) and DFS (HR = 3.04, p = 0.019; HR = 4.76, p = 0.002, respectively). A score system combining both biomarkers was found to significantly correlate with long-term results.Conclusions A simple prognostic score including preoperative NLR and LMR can be used to easily predict outcome in gastric cancer patients undergoing surgery.

BACKGROUND: Differential diagnosis between syncope and epilepsy in patients with transient loss of consciousness of uncertain etiology is still unclear. Thus, the aim of the present work is to evaluate the prevalence of syncope in patients with "possible" or "drug-resistant" epilepsy. METHODS: The Overlap between Epilepsy and SYncope Study (OESYS) is a multicenter prospective observational study designed to estimate the prevalence of syncope in patients followed in Epilepsy Centers for "possible" or "drug-resistant" epilepsy and assessed according the European Society of Cardiology (ESC) guidelines of syncope diagnosis. RESULTS: One hundred seven patients were evaluated; 63 (58.9%) had possible and 44 (41.1%) drug-resistant epilepsy. A final diagnosis of isolated syncope was in 45 patients (42.1%), all with possible epilepsy (45/63, 71.4%). Isolated epilepsy was found in 21 patients (19.6%) and it was more frequent in the drug-resistant than in the possible epilepsy group (34.1% vs. 9.5%, p = 0.002). More importantly, syncope and epilepsy coexisted in 37.4% of all patients but the coexistence was more frequent among patients with drug-resistant than possible epilepsy (65.9% vs. 17.5%, p

OBJECTIVE Elderly subjects are characterized by a high prevalence of OA and clinical frailty. This study aimed to examine the predictive role of clinical frailty on long-term mortality in elderly subjects with and without OA. METHODS Mortality was evaluated after a 12-year follow-up in 698 subjects with and 590 subjects without OA recruited in 1992. Clinical frailty was assessed according to the Frailty Staging System and stratified in tertiles. RESULTS After a 12-year follow-up, mortality was 42.2% in subjects without and 55.8% in subjects with OA (P = 0.256). With increasing frailty, mortality increased by 30.5% (P for trend < 0.001) in subjects without and by 45.6% in subjects with OA (P for trend < 0.001). Multivariate analysis showed that frailty [hazard ratio (HR) = 1.49 for each unit of increase, 95% CI 1.32, 1.94, P < 0.001) but not OA (HR = 1.28, 95% CI 0.987, 1.39, P = 0.412) was predictive of long-term mortality. Moreover, when Cox regression analysis was performed, frailty enhanced the risk of long-term mortality for each unit of increase by 32% (HR = 1.32, 95% CI 1.06, 1.65, P = 0.03) in the absence of OA and by 98% in the presence (HR = 1.98, 95% CI 1.63, 2.95, P < 0.01) of OA. CONCLUSION Clinical frailty significantly predicts mortality in subjects without OA and even more in those with OA. Thus clinical frailty may be considered a new prognostic factor to identify subjects with OA at high risk of mortality.

NTRODUCTION: Circulating tumor cells are thought to play a crucial role in the development of distant metastases. Their detection in the blood of colorectal cancer patients may be linked to poor outcome, but current evidence is controversial. MATERIALS AND METHODS: Pre- and postoperative flow cytometric analysis of blood samples was carried out in 76 colorectal cancer patients undergoing surgical resection. The EpCAM/CD326 epithelial surface antigen was used to identify circulating tumor cells. RESULTS: Fifty-four (71%) patients showed circulating tumor cells preoperatively, and all metastatic patients showed high levels of circulating tumor cells. Surgical resection resulted in a significant decrease in the levels of circulating tumor cells. Among 69 patients undergoing radical surgery, 16 had high postoperative levels of circulating tumor cells, and 12 (75%) experienced tumor recurrence. High postoperative level of circulating tumor cells was the only independent variable related to cancer relapse. In patients without circulating tumor cells, the progression-free survival rate increased from 16 to 86%, with a reduction in the risk of tumor relapse greater than 90%. CONCLUSIONS: High postoperative levels of circulating tumor cells accurately predicted tumor recurrence, suggesting that assessment of circulating tumor cells could optimize tailored management of colorectal cancer patients.

Permanent AF is characterized by an increased mortality in elderly subjects with CHF. Moreover, AF increased the risk of mortality also in elderly subjects without CHF. Thus, we examined long-term mortality in community-dwelling elderly people with and without CHF. A total of 1332 subjects aged 65 and older were selected from the electoral rolls of Campania, a region of southern Italy. The relationship between AF and mortality during a 12-year follow-up in 125 subjects with CHF and in 1.143 subjects without CHF were studied. Elderly subjects showed a higher mortality in those with respect to those without AF (72.1% vs. 51.8%; p< 0.01). Similarly, elderly subjects without CHF showed a higher mortality in those with respect to those without AF (61.8% vs. 49.8%; p< 0.05). In contrast, elderly subjects with CHF showed a similar mortality in those with respect to those without AF (74.7% vs. 82.4%; p=. 0.234). Multivariate analysis shows that AF was predictive of mortality in all elderly subjects (Hazard Risk = HR = 1.39, 95% confidence interval (CI) = 1.25-2.82; p< 0.001). When the analysis was conducted considering the presence and the absence of CHF, AF was strongly predictive of mortality in elderly subjects without CHF (HR = 1.95, 95%CI = 1.25-4.51; p< 0.001) but not in those with CHF (HR = 1.12, 95%CI = 0.97-3.69; p=. 0.321). We concluded that AF is able to predict long-term mortality in elderly subjects. Moreover, AF is strongly predictive of long-term mortality in the absence but not in the presence of CHF. © 2011 Elsevier Ireland Ltd.

Background In gastric cancer, the current AJCC numeric-based lymph node staging does not provide information on the anatomical extent of the disease and lymphadenectomy. A new anatomical location-based node staging, proposed by Choi, has shown better prognostic performance, thus soliciting Western world validation. Study design Data from 284 gastric cancers undergoing radical surgery at the Second University of Naples from 2000 to 2014 were reviewed. The lymph nodes were reclassified into three groups (lesser and greater curvature, and extraperigastric nodes); presence of any metastatic lymph node in a given group was considered positive, prompting a new N and TNM stage classification. Receiver-operating-characteristic (ROC) curves for censored survival data and bootstrap methods were used to compare the capability of the two models to predict tumor recurrence. Results More than one third of node positive patients were reclassified into different N and TNM stages by the new system. Compared to the current staging system, the new classification significantly correlated with tumor recurrence rates and displayed improved indices of prognostic performance, such as the Bayesian information criterion and the Harrell C-index. Higher values at survival ROC analysis demonstrated a significantly better stratification of patients by the new system, mostly in the early phase of the follow-up, with a worse prognosis in more advanced new N stages, despite the same current N stage. Conclusions This study suggests that the anatomical location-based classification of lymph node metastasis may be an important tool for gastric cancer prognosis and should be considered for future revision of the TNM staging system.

Background: To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered; indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. Methods: We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin–5-fluorouracil–oxaliplatin) for 4 cycles, and concurrent computed tomography–based threedimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. Results: All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. Conclusions: In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.

Esophageal cancer (EC) is an aggressive malignancy with increasing incidence worldwide. Surgery is still the most effective treatment, however, both the high rate of local and distant recurrences and surgery-related complications led us to investigate new preoperative strategies. In this review, we discuss the role of neoadjuvant therapy for locally advanced EC with a focus on preoperative chemoradiation (trimodality treatment). Furthermore, the last fifteen years of published literature and our experience have been also reviewed. In the preoperative setting, few trials have reported a significant benefit with fluoropyrimidine and platinum compound-based neoadjuvant chemotherapy, compared to surgery alone. A large number of phase III trials and meta-analyses have demonstrated improved outcomes with preoperative chemoradiation vs. neoadjuvant chemotherapy or surgery alone. Therefore, trimodality therapy can be considered the most effective option in the management of locally advanced EC. Addition of drugs targeting VEGF or HER2 to standard chemotherapy appears to be feasible but needs to be explored more accurately. FDG-PET may predict both response to neoadjuvant treatments and prognosis.

To evaluate the incidence of unexplained falls in elderly patients affected by fall-related fractures admitted to orthopaedic wards, we recruited 246 consecutive patients older than 65 (mean age years, range 65–101). Falls were defined “accidental” (fall explained by a definite accidental cause), “medical” (fall caused directly by a specific medical disease), “dementia-related” (fall in patients affected by moderate-severe dementia), and “unexplained” (nonaccidental falls, not related to a clear medical or drug-induced cause or with no apparent cause). According to the anamnestic features of the event, older patients had a lower tendency to remember the fall. Patients with accidental fall remember more often the event. Unexplained falls were frequent in both groups of age. Accidental falls were more frequent in younger patients, while dementia-related falls were more common in the older ones. Patients with unexplained falls showed a higher number of depressive symptoms. In a multivariate analysis a higher GDS and syncopal spells were independent predictors of unexplained falls. In conclusion, more than one third of all falls in patients hospitalized in orthopaedic wards were unexplained, particularly in patients with depressive symptoms and syncopal spells. The identification of fall causes must be evaluated in older patients with a fall-related injury.

Objective: Moderate alcohol consumption is related to a reduction of mortality. However, this phenomenon is not well established in the elderly, especially in the presence of chronic heart failure (CHF). The aim of the study was to verify the effect of moderate alcohol consumption on 12-year mortality in elderly community-dwelling with and without CHF. Settings: community-dwelling from 5 regions of Italy. Participants: A cohort of 1332 subjects aged 65 and older. Measurement: Mortality after 12-year follow-up in elderly subjects (≥65 years old) with and without CHF was studied. Moderate alcohol consumption was considered ≤250 ml/day (drinkers). Results: In the absence of CHF (n=947), mortality was 42.2% in drinkers vs. 53.7% in non-drinker elderly subjects (p=0.021). In contrast, in the presence of CHF (n=117), mortality was 86.5% in drinkers vs. 69.7% in non-drinker elderly subjects (p=0.004). Accordingly, Cox regression analysis shows that a moderate alcohol consumption is protective of mortality in the absence (HR=0.79; CI 95% 0.66-0.95; p

Elderly subjects are characterized by a high prevalence of diabetes and clinical frailty. This study aimed to examine the predictive role of clinical frailty on long-term mortality in elderly subjects with and without diabetes. The study evaluated mortality after 12-year follow-up in 188 subjects with diabetes and 1,100 subjects without diabetes selected in 1992. Clinical frailty was assessed according to the “Frailty Staging System” and stratified in tertiles. After 12-year follow-up, mortality was 50.5 % in subjects without and 66.5 % in subjects with diabetes (p < 0.001). With increasing frailty, mortality increases from 57.9 to 79.0 % (p for trend

The best management choice in colorectal cancer patients with unresectable liver-only metastases should be represented by conversion chemotherapy aiming to reduce liver cancer deposits, thereby permitting curative surgery. Forty-eight consecutive stage IV colorectal cancer patients were treated with different chemotherapeutic regimens including biological drugs. Objective responses to chemotherapy were seen in 27 patients (56.2%; 95% CI 42.1-70.2%). Four patients (8.3%) showed complete response, 23 patients (47.9%) partial and 13 patients (27.1%) stable response. Eight patients (16.7%) progressed. The conversion rate was 35.4% (95% CI 21.8-48.9%) with 17 patients suitable for liver resection. Four complete responder patients refused surgery. The remaining 13 patients underwent curative hepatic resection (resection rate 27.1%; 95% CI 14.5-39.6%). The likelihood of a successful conversion chemotherapy appeared significantly related to the best response and to the K-Ras status. Wild-type K-Ras patients undergoing cetuximab therapy showed the best conversion rate. The four-year survival rate was significantly enhanced in converted compared to non-converted patients (57.1 and 0%, respectively), and in resected compared to non-resected patients (53.3 and 10.1%, respectively). Synchronous metastases and no conversion were shown to be the only covariates independently associated with a poorer long-term outcome. The possibility of curative liver surgery significantly prolongs outcome for colorectal cancer patients with unresectable liver-limited metastases. Prospective randomized trials are required to define the conversion rates with biological drugs.

Background: The role of ventricular rate response (VRr) on the incidence of dementia in elderly subjects with cognitive impairment and atrial fibrillation (AF) is not known. Thus, we examined the ability of VRr to predict dementia in cognitively impaired elderly subjects with and without AF. Methods: A total of 358 cognitively impaired elderly subjects (MMSE 90) and moderate (>50/90 bpm) is predictive of dementia in the presence (HR = 7.70, 95% CI = 1.10–14.20, p = 0.03) but not in the absence (HR = 1.85; 95% CI = 0.78–4.47; p = 0.152) of AF. Conclusions: This study demonstrates that AF predicts dementia in elderly subjects with cognitive impairment. Moreover, VRr seems to play a key role in the incidence of dementia in cognitively impaired elderly subjects with AF.

Background and aims: Elderly subjects are characterized by a high prevalence of chronic obstructive pulmonary disease (COPD) and frailty. This study examined the predictive role of frailty on long-term mortality in elderly subjects with and without COPD. Methods: The study assessed mortality after a 12-year follow-up in 489 subjects with COPD and 799 subjects without COPD, selected in 1992. Frailty was assessed according to the Frailty Staging System scores ranging from 1 to 7. Results: After 12 years’ follow-up, mortality was 48.1% in subjects without and 60.7% in subjects with COPD (p

Background syncope is a common cause of hospitalisation in the elderly. However, morbidity and mortality in elderly patients with syncope is not well established. Methods two-hundred and forty-two patients older than 65 years consecutively referred to the participating centres for evaluation of transient loss of consciousness were enrolled in a multicentre 2-year longitudinal observational study. Mortality and syncope recurrences were recorded and multidimensionally evaluated at 6, 12, 18 and 24 months. Findings at 24 months, total mortality was 17.2% and syncope recurrence was 32.5%. Cardiac syncope was more frequent in deceased than in survivor patients (21.7 versus 12.3%; P = 0.03), whereas neuro-mediated (62.1 versus 66.2%; P = 0.357) and unexplained syncope (10.8 versus 11.8%; P = 0.397) did not differ between the two groups. Drug-induced and/or multifactorial syncope was less frequent in patients with syncope recurrence (5.7 versus 10.7%; P = 0.02). Kaplan-Meyer curves indicated that mortality and syncope recurrence increased significantly with age (P = 0.006 and P = 0.008, respectively). At multivariate analysis, mortality was significantly predicted by age and comorbidity (hazard ratios: 1.17 and 1.39, and 95% confidence interval 1.01-1.37 and 1.01-1.93, respectively), and syncope recurrence by age and disability (hazard ratio: 1.13 and 1.04, 95% confidence interval 1.01-1.25 and 1.04-2.25, respectively). Depression increased from baseline to the end of follow-up (from 28.3 to 41.4%; P = 0.001). Conclusions in our patients, mortality was related to increasing age and comorbidity, whereas recurrence was related to increasing age and disability. Cardiac syncope was more frequent in deceased than in survivor patients, and syncope recurrence was high despite a low incidence of unexplained syncope.

We evaluated the association of a weekly cisplatin (35 mg/mq) and paclitaxel (45 mg/mq) regimen with radiotherapy (46 Gy) as primary treatment in locally advanced esophageal cancer (LAEC). The main end point was the activity in terms of pathologic complete response (pathCR) rate. Thirty-three LAEC patients received chemoradiation therapy during weeks 1-6 followed by esophagectomy. A pathCR was observed in 10/33 patients; 20/33 and 3/33 patients showed PR and SD, respectively. The EUS maximal transverse cross sectional area reduction >50 significantly correlated with pathCR. Three-year survival rate was 35%. These results support the activity and mild toxicity of this regimen. © 2010 Informa Healthcare USA, Inc.

Background Preinfarction angina (PrA), clinical equivalent of ischemic preconditioning, confers protection against inhospital mortality for acute myocardial infarction (AMI) in adult but not in elderly patients. This study aims to examine the interaction between physical activity and body mass index (BMI) in preserving the cardioprotective effect of PrA in elderly patients with AMI. Design Elderly patients (Z65 years old) with AMI admitted to Coronary Care Unit. Methods Elderly patients with AMI were retrospectively stratified for the presence and absence of PrA, and for quartiles of BMI and physical activity. In-hospital outcomes (death, cardiogenic shock, and reinfarction and creatine kinase-MB peak) were evaluated. Results In-hospital mortality of 1014 elderly patients with AMI was 19.2% in those with PrA and 22.7% in those without (P = 0.18, NS). Mortality further decreased with increased physical activity and reduced BMI, a trend that was not observed in patients without PrA. When physical activity and BMI were considered together, lowest in-hospital mortality was observed in patients with highest physical activity and normal BMI (from 18.2 to 9.6%; P < 0.01) with the greatest reduction observed in patients with PrA (from 18.3 to 5.1%; P =0.02). Multivariate analysis showed that PrA did not exert a protective effect in all patients irrespective of physical activity and BMI. A protective role was, however, observed in patients with highest physical activity or normal BMI and reached a maximum protective role in patients who showed both highest physical activity and normal BMI [odds ratio =0.08; 95% confidence interval = 0.02–0.72; P < 0.01]. Conclusion The cardioprotective effect of PrA was preserved in elderly patients who showed the highest physical activity and a normal BMI.

Background: comorbidity plays a critical role in the high mortality for chronic heart failure (CHF) in the elderly. Charlson Comorbidity Index (CCI) is the most extensively studied comorbidity index. No studies are available on the ability of CCI to predict mortality in CHF elderly subjects. The aim of the present study was to assess if CCI was able to predict long-term mortality in a random sample of elderly CHF subjects. Methods: long-term mortality after 12-year follow-up in 125 subjects with CHF and 1,143 subjects without CHF was studied. Comorbidity was evaluated using CCI. Findings: in elderly subjects stratified for CCI (1‐3 and ≥4), mortality was higher in non-CHF subjects with CCI ≥4 (52.4% versus 70%, P < 0.002) but not in those with CHF (75.9% versus 77.6%, P = 0.498, NS). Cox regression analysis on 12 years mortality indicated that both CCI (HR = 1.15; 95% CI = 1.01‐1.31; P = 0.035) and CHF (HR = 1.27; 95% CI = 1.04‐8.83; P = 0.003) were predictive of mortality. When Cox analysis was performed by selecting the presence and the absence of CHF, CCI was predictive of mortality in the absence but not in the presence of CHF. Conclusion: CCI does not predict long-term mortality in elderly subjects with CHF.

Left atrial enlargement is an important predictor of cardiovascular outcomes in patients after acute myocardial infarction. While the favourable effect of exercise exercise-based Cardiac Rehabilitation (CR) on postinfarction LV remodeling has been well documented, those on LA remodeling have yet to be defined. This study investigated the effects of CR on LA remodeling in postinfarction patients with moderate left ventricular (LV) dysfunction.Sixty postinfarction patients were randomised randomized into two groups, each composed of 30 patients: group T (LV ejection fraction (EF) 43.7+/-4.2%, mean+/-SD) entered a 6-month CR program, whereas group C (EF 44.7+/-4.4%, P=ns) did not. Doppler echocardiography and cardiopulmonary exercise test were performed upon enrolment and at 6-month.At 6-month, trained patients showed a significant (P0.001) improvement in peak oxygen consumption (DeltaVO(2peak)=+5.2+/-2.1 ml/kg/min) and a reduction in LA (DeltaLAV(MAX)=-1.9+/-3.7 ml/m(2)) and in LV volumes (DeltaLVEDV=-3.6+/-4.4 ml/m(2)). At 6-month, untrained patients showed LAV(MAX) (+3.6+/-4.4 ml/m(2), P0.001) and LV dilation (+4.2+/-5.1 ml/m(2), P0.001; group T vs. C, P0.001); whereas no significant changes in VO(2peak) were observed. Multiple linear regression analysis showed that age (beta=0.442, P0.001), inclusion in the training group (beta=-0.599, P0.001), E/A ratio (beta=-0.210, P=0.038), LVEDV (beta=0.376, P0.001), and LVEF (beta=-0.279, P=0.007) are significant predictors of LA remodeling.Six-month exercise-based CR in postinfarction patients with mild to moderate LV dysfunction induced a favourable LA remodeling.

Falls in the elderly are commonly and often wrongly identified as "accidental". We report a case of an elderly woman admitted to first aid for a trauma due to an accidental fall. Geriatric multidisciplinary evaluation revealed mild cognitive impairment associated with depressive symptoms; both findings made the anamnesis uncertain. Syncope algorithm was applied and "tachy-brady form of sick sinus syndrome" was diagnosed. Differential diagnosis between "accidental" and "apparently accidental" falls in elderly patients is very difficult but a multidisciplinary geriatric evaluation can clarify the correct diagnosis.

Background: Capecitabine and docetaxel have demonstrated preclinical antitumor synergy and activity in advanced gastric cancer. We assessed the clinical activity and the toxicity of weekly docetaxel in combination with capecitabine in untreated patients with advanced gastric cancer. Patients and methods: A total of 38 patients were treated with docetaxel 36 mg/m2 on days 1, 8, and 15 i.v., plus capecitabine, 625 mg/m2 bid per os on days 5 to 18 repeated every 4 weeks. Results: All patients were assessable for response to treatment and for toxicity. Major responses were observed in eight patients (21%), with three patients achieving a CR (7.8%) and five showing a PR (13%). The median time to progression was 5.4 months and the overall survival was 7.7 months. The safety profile of this schedule was acceptable with a low rate of myelossuppression, diarrhoea and hand-foot syndrome. Conclusions: The combination of docetaxel and capecitabine at the doses and schedule investigated in this study is safe, but does not show significant activity in untreated patients with advanced gastric cancer. Background: Capecitabine and docetaxel have demonstrated preclinical antitumor synergy and activity in advanced gastric cancer. We assessed the clinical activity and the toxicity of weekly docetaxel in combination with capecitabine in untreated patients with advanced gastric cancer. Patients and methods: A total of 38 patients were treated with docetaxel 36 mg/m2 on days 1, 8, and 15 i.v., plus capecitabine, 625 mg/m2 bid per os on days 5 to 18 repeated every 4 weeks. Results: All patients were assessable for response to treatment and for toxicity. Major responses were observed in eight patients (21%), with three patients achieving a CR (7.8%) and five showing a PR (13%). The median time to progression was 5.4 months and the overall survival was 7.7 months. The safety profile of this schedule was acceptable with a low rate of myelossuppression, diarrhoea and hand-foot syndrome. Conclusions: The combination of docetaxel and capecitabine at the doses and schedule investigated in this study is safe, but does not show significant activity in untreated patients with advanced gastric cancer. © 2006 Oxford University Press.

Background The elderly are characterized by a high prevalence of chronic heart failure (CHF) and frailty, which is a complex interaction of physical, psychological and social impairment. This study aimed to examine the predictive role of frailty on long-term mortality in elderly subjects with CHF. Materials and methods The study assessed long-term mortality after 12-year follow up in 120 subjects with CHF and 1139 subjects without CHF, selected in 1992, from a random sample of the elderly population in the Campania region of Italy. Frailty was assessed according to a ‘Frailty Staging System’. Results Subjects with CHF were prevalently female (60%) and older than 75 years (mean 75·9 ± 6·7); subjects without CHF were prevalently female (56·4%) and younger than 75 years (mean 74·0 ± 6·3). In subjects with and without CHF stratified into classes of frailty there was a statistically significant increase in age, comorbidity, disability and low social support, and a decrease in MMSE score. Moreover, death progressively increased more with frailty in subjects (70·0% to 94·4%, P

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m(-2) on day 1, FA 200 mg m(-2) as a 2 h infusion followed by bolus 5-FU 400 mg m(-2) and a 22 h infusion of 5-FU 600 mg m(-2), repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.

Background The aging heart is characterized by structural changes, which are implicated in the development of left ventricular diastolic dysfunction. However, important changes in systolic function may also occur. Left ventricular end-systolic elastance (Ees) is a major determinant of cardiac systolic function and ventricular—arterial interaction. Aim To evaluate left-ventricular Ees in elderly subjects compared with adult control subjects. Methods We studied dilated (DA, n=14) and hypertensive (HA, n=21) cardiomyopathy patients, and both adult control (A, n=25; age 55.6±6.6 years) and elderly (E, n=25; age 76.3±7.1 years) subjects without clinical–instrumental evidence of cardiovascular disease. M-mode, two-dimensional, and pulsed Doppler echocardiogram were performed. Doppler-derived indices of diastolic function were assessed and Ees was calculated by a modified single-beat method. Results Ees was reduced in dilated cardiomyopathy (1.32±0.10 mm Hg/ml) and increased in hypertensive cardiomyopathy (3.12±0.33 mm Hg/ml) patients compared to age-matched control subjects (1.96±0.26 mm Hg/ml; p

A high falls-related mortality rate in the elderly is not exclusively related to injuries. Moreover, the risk of falls increases with urinary disorders such as nocturia. The aim of this study was to investigate the role of nocturia in falls-related long-term mortality in elderly subjects.Longitudinal study.The "Osservatorio Geriatrico Regione Campania" was a cross-sectional study performed in 1992 in Campania, a region of Southern Italy.Long-term mortality (12 years' follow-up) in 178 elderly subjects (mean age 74.0 ± 6.3 years) with falls and 1110 elderly subjects (mean age 75.2 ± 6.4 years) without falls at baseline was measured. Subjects were then stratified for the presence/absence of nocturia.In our sample, the prevalence of falls was 13.8% and the prevalence of nocturia was 45.7%. Long-term mortality was 51.3% in nonfallers and 62.9% in fallers (P.05). In the absence of nocturia, long-term mortality was similar in nonfallers and fallers (49.0% vs 46.7%; P = .514, NS). In contrast, in the presence of nocturia, long-term mortality was higher in fallers than in nonfallers (74.5% vs 53.6%; P.05). Cox regression analysis confirmed the predictive role of falls on long-term mortality in the presence of nocturia (hazard ratio 60; 95% confidence interval 1.01-2.57; P.05) but not in the absence of nocturia (hazard ratio = 1.27; 95% confidence interval 0.81-1.99; P = .28).Our data suggest that falls are related to an increased risk of long-term mortality in the elderly much more in the presence of nocturia. This phenomenon is probably related to the high comorbidity that usually affects elderly subjects with nocturia.