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Background: Nutrition exerts a fundamental role in the prevention of obesity (OB). The aim of this study was to assess the extent to which well recognized risk factors for early OB can be associated to overweight (OW) or OB under a standardized nutritional approach and surveillance in toddlers., Methods: The eligible population was represented by 676 toddlers aged 24-36 months, assigned to 18 primary care pediatricians trained on nutritional issues who shared a standardized nutritional approach. Six-hundred-twenty-nine children (333 boys), mean age 27.8 ± 4.2 months were effectively included in this observational study. Parents received nutritional advice with particular emphasis to proteins and sugar composition supported by leaflets and reinforced at each visit. Body mass index was assessed at the age of 24-36 months. The following individual and family risk factors were considered: gestational age, birth weight, eutocic/caesarean delivery, milk feeding history, household smoking or antibiotics exposure, parents' weight, height and educational level. Prevalence of OW/OB was compared to a group of 742 toddlers (373 boys) under usual care., Results: Under a standardized nutritional counselling, 28.1% toddlers were classified as OW/OB compared to 36.9% toddlers under usual care (p = 0.005). In unadjusted models, parental OW/OB was significantly associated to OW/OB in toddlers (p < 0.01), while high birth weight did not reach statistical significance (p = 0.07). In adjusted models, including all the explanatory variables studied, only paternal OW/OB vs. normal weight was significantly associated to OW/OB in toddlers (OR 2.035, 95% confidence interval 1.206-3.436). No protective effect of exclusive breast feeding during the first 6 months of age was demonstrated., Conclusions: Toddlers under a standardized nutrition counselling focused to limit protein and simple sugars, showed lower prevalence of OW/OB compared to usual care. Healthy promotion activities should take into account the influence of paternal BMI on the offspring adiposity., (© 2024. The Author(s).)

Early detection of disease progression is a crucial issue in the management of cancer patients, especially in metastatic settings. Currently, treatment selection mostly relies on criteria based on radiologic evaluations (RECIST). The aim of the present retrospective study is to evaluate the potential inclusion of circulating tumor cells (CTCs) in hybrid criteria. CTC counts from a total of 160 patients with different metastatic tumors were analyzed for this purpose. In our cohort, 73 patients were affected by breast cancer, 69 by colorectal cancer and 18 by prostate cancer. PFS and OS were evaluated according to the corresponding prediction of disease progression by CTCs and RECIST criteria. In breast cancer, CTC-I has an important impact on the progression-free survival (PFS) and overall survival (OS) values. When CTC-I predicted earlier than RECIST-I, the disease progression, the PFS and OS were shorter with respect to the opposite case. In particular, PFS was 11 (5-16) vs. 34 (23-45)-with p < 0.001-and OS was 80 (22-138) vs. 116 (43-189), p = 0.33. The results suggest a promising role of CTCs as complementary information which could significantly improve the clinical outcomes, and they encourage consideration of future trials to evaluate new hybrid criteria, particularly for patients with breast cancer.

This work is aimed to investigate the carbon emissions trend in the European Union. Logarithmic Mean Divisia Index and Tapio's methodology are used for decomposing the carbon emissions and investigating the decoupling factors respectively. Seven indexes are identified, namely carbon intensity of the energy sector, energy consumption structure, energy intensity, climatic factor, Gross Domestic Product per Capita, population distribution, and population evolution. These indexes are then grouped in three macro-categories, specifically technical factors, climatic effect, and socio-economic factors. The study covers the period 1995-2019 and considers EU 27 countries at an aggregate and individual level. Carbon emissions in EU 27 reduced of 689 Mt from 1995 to 2019. Technical factors are responsible for a decrease of 1723 Mt, the climatic effect determines a reduction of 362 Mt, whereas socio-economic factors cause an increase of 1397 Mt. The Strong Decoupling status is achieved in EU 27 in the period 1995-2019 with a decoupling index equal to -0.4. This means that carbon emissions reduced while Gross Domestic Product increased. To provide more precise insights, the paper also presents analyses at individual country level and the splitting in five temporal sub-periods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cefiderocol is a novel siderophore cephalosporin with promising activity against most carbapenem-resistant Gram-negative bacteria (CRGNB). However, extensive postmarketing experiences are lacking. This study aimed to analyse the early experience on cefiderocol postmarketing use at three tertiary care hospitals in Italy., Methods: We retrospectively included patients with infections caused by CRGNB treated with cefiderocol at three Italian tertiary care hospitals from 1 March 2021 to 30 June 2022. A multivariate Cox model was used to identify predictors of 30 day mortality. A propensity score (PS) analysis with inverse probability weighting (IPW) was also performed to compare the treatment effect of cefiderocol monotherapy (CM) versus combination regimens (CCRs)., Results: The cohort included 142 patients (72% male, median age 67 years, with 89 cases of Acinetobacter baumannii infection, 22 cases of Klebsiella pneumoniae, 27 cases of Pseudomonas aeruginosa and 4 of other pathogens). The 30 day all-cause mortality was 37% (52/142). We found no association between bacterial species and mortality. In multivariate analysis, a Charlson Comorbidity Index >3 was an independent predictor of mortality (HR 5.02, 95% CI 2.37-10.66, P < 0.001). In contrast, polymicrobial infection (HR 0.41, 95% CI 0.21-0.82, P < 0.05) was associated with lower mortality. There was no significant difference in mortality between patients receiving CM (n = 70) and those receiving a CCR (n = 72) (33% versus 40%, respectively), even when adjusted for IPW-PS (HR 1.11, 95% CI 0.63-1.96, P = 0.71)., Conclusions: Real-life data confirm that cefiderocol is a promising option against carbapenem-resistant Gram-negative infections, even as monotherapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background and Aim: The nature of the association between obesity and poor prognosis of COVID-19 without the evaluation of other co-pathologies associated has not yet been clearly evaluated. The aim of the present pair-matched case-control study was to investigate the outcome of patients with SARS-CoV-2 infection in obese and non-obese patients matched considering gender, age, number of comorbidities, and Charlson Comorbidity Index., Methods: All the adults hospitalized for SARS-CoV-2 infection and with BMI ≥ 30 kg/m 2 were included (Cases). For each Case, two patients with BMI < 30 kg/m 2 pair matched for gender, age (±5 years), number of comorbidities (excluding obesity), and Charlson Comorbidity Index (±1) were enrolled (Controls)., Results: Of the 1282 patients with SARS-CoV-2 infection followed during the study period, 141 patients with obesity and 282 patients without were enrolled in the case and control groups, respectively. Considering matching variables, there was no statistical difference between the two groups. Patients in the Control group developed more frequently a mild-moderate disease (67% vs. 46.1%, respectively), whereas obese patients were more prone to need intensive care treatment (41.8% vs. 26.6%, respectively; p = 0.001). Moreover, the prevalence of death during hospitalization was higher in the Case group than in the Control group (12.1% vs. 6.4%, p = 0.046)., Discussion: We confirmed an association between obesity and severe outcome of patients with COVID-19, also considering other factors associated with a severe outcome of COVID-19. Thus, in the case of SARS-CoV-2 infection, the subjects with BMI ≥ 30 kg/m 2 should be evaluated for early antiviral treatment to avoid the development of a severe course.

Background: Sclerotherapy with 3% polidocanol foam is becoming increasingly popular for the treatment of symptomatic I-II or III degree haemorrhoidal disease (HD). However, there are no studies that have reported a follow-up of more than 1 year. The purpose of this study was to analyse the long-term outcomes of sclerotherapy with 3% polidocanol foam in the treatment of II-degree HD., Methods: This was an open label, single-arm, phase 2b trial conducted in 10 tertiary referral centres for HD. A total of 183 patients with II-degree HD, aged between 18 and 75 years with symptomatic HD according to the Goligher classification and unresponsive to medical treatment, were included in the study and underwent sclerotherapy with 3% polidocanol foam. The efficacy was evaluated in terms of bleeding score, haemorrhoidal disease symptom score (HDSS) and short health scale for HD (SHS-HD) score. Successful treatment was defined as the complete absence of bleeding episodes after 7 days (T1) according to the bleeding score., Results: The overall success rate ranged from 95.6% (175/183) at 1 year to 90.2% (165/183) after the final 3 year follow-up. The recurrence rate, based on the primary outcome, ranged from 12% (15/125) to 28% (35/125). The greatest increase in recurrence (15) was recorded between 12 and 18 months of follow-up, then another five between 18 and 24 months. Both the HDSS and the SHS score remained statistically significant (p < 0.001) from a median preoperative value of 11 (10-13) and 18 (15-20) to 0 (0-2) and 4 (0-4), respectively. Symptom-free (HDSS = 0) patients, excluding patients converted to surgery, increased from 55.5% (101/182) at 1 year to 65.1% at 3 years (110/169). There were no intraoperative complications in redo-sclerotherapy nor additional adverse events (AEs) compared to the first 12 months., Conclusions: Sclerotherapy with 3% polidocanol foam is gradually establishing itself in the treatment of bleeding HD due to its repeatability, safety, convenience in terms of direct and indirect costs with the absence of discomfort for the patient as well as AEs rather than an excellent overall success rate., (© 2022 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background/aim: We conducted a retrospective analysis in our center (Umberto I Polyclinic) in collaboration with Campus Biomedico Polyclinic to assess the results of the REFLECT study, which was the first study that demonstrated the non-inferiority of Lenvatinib to Sorafenib., Patients and Methods: We identified 21 patients affected by advanced hepatocellular carcinoma during the last 3 years who were treated in our centers. They were subdivided according to the treatment administered (Lenvatinib or Sorafenib). Progression-free survival (PFS) and overall survival (OS) were calculated, and subgroups were compared using the log-rank test. Specific predictive and prognostic factors were identified. The safety profile of the two drugs and the collateral effects were evaluated., Results: The OS in patients in the Lenvatinib arm was 19 (months and 12.5 months in the Sorafenib arm. PFS in patients in the Lenvatinib arm was 6 months and 2.5 months in the Sorafenib arm. OS and PFS in patients treated with Lenvatinib were higher in any subcategory analyzed whereas no positive predictors of response to Sorafenib were found. Based on data from literature, the albumin bilirubin index (ALBI) grade was found to be a key prognostic factor. Patients treated with Sorafenib had more adverse events than those treated with Lenvatinib (100% versus 81.8%, respectively). Patients treated with Sorafenib had more frequently hand-foot syndromes, diarrhea, and nausea whereas patients treated with Lenvatinib commonly had hypertension, proteinuria, and weight loss., Conclusion: Lenvatinib was found to be better than Sorafenib in terms of both survival and toxicity, in advanced hepatic cell carcinoma patients., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: To describe clinical characteristics and outcomes of COVID-19 patients who developed secondary infections due to carbapenem-resistant Enterobacterales (CRE)., Methods: Retrospective observational study including COVID-19 patients admitted to 12 Italian hospitals from March to December 2020 who developed a superinfection by CRE. Superinfection was defined as the occurrence of documented bacterial infection >48 h from admission. Patients with polymicrobial infections were excluded. Demographic, clinical characteristics and outcome were collected. Isolates were classified as KPC, metallo-β-lactamase (MBL) and OXA-48-producing CRE. A Cox regression analysis was performed to identify factors independently associated with 30 day mortality., Results: Overall, 123 patients (median age 66 years, IQR 59-75) were included. The majority of infections occurred in the ICU (81, 65.9%), while 42 (34.1%) in medical wards. The most common types of infection were bloodstream infections (BSI) ( n  = 64, 52%), followed by urinary-tract infections (UTI) ( n  = 28, 22.8%), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) ( n  = 28, 22.8%), intra-abdominal infections ( n  = 2, 1.6%) and skin infections ( n  = 1, 0.8%). Sixty-three (51.2%) infections were caused by KPC-, 54 (43.9%) by MBL-, and 6 (4.8%) by OXA-48-producing CRE. Thirty-day mortality was 33.3% (41/123). On Cox regression analysis, HAP/VAP compared with UTI (HR 7.23, 95% CI 2.09-24.97, P  = 0.004), BSI compared with UTI (HR 3.96, 95% CI, 1.33-11.77, P  = 0.004), lymphopenia on admission (HR 3, 95% CI 1.44-6.26, P  = 0.003) and age (HR 1.05, 95% CI 1.02-1.08, P  = 0.002) were predictors of 30 day mortality., Conclusions: Superinfections by CRE were associated with high risk of 30 day mortality in patients with COVID-19. HAP/VAP was the strongest predictor of death in these patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

A retrospective case-control study was conducted at Modena University Hospital from December 2017 to January 2019 to identify risk factors and predictors of MDR/XDR Pseudomonas aeruginosa (PA) isolation with resistance to ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T), and of mortality among patients infected/colonized. Among 111 PA isolates from clinical/surveillance samples, 60 (54.1%) were susceptible to both drugs (S-CZA-C/T), while 27 (24.3%) were resistant to both (R-CZA-C/T). Compared to patients colonized/infected with S-CZA-C/T, those with R-C/T + CZA PA had a statistically significantly higher Charlson comorbidity score, greater rate of previous PA colonization, longer time before PA isolation, more frequent presence of CVC, higher exposure to C/T and cephalosporins, longer hospital stay, and higher overall and attributable mortality. In the multivariable analysis, age, prior PA colonization, longer time from admission to PA isolation, diagnosis of urinary tract infection, and exposure to carbapenems were associated with the isolation of a R-C/T + CZA PA strain, while PA-related BSI, a comorbidity score > 7, and ICU stay were significantly associated with attributable mortality. C/T and CZA are important therapeutic resources for hard-to-treat PA-related infections, thus specific antimicrobial stewardship interventions should be prompted in order to avoid the development of this combined resistance, which would jeopardize the chance to treat these infections.

Purpose: Post-neurosurgical infection caused by extensively drug resistant Pseudomonas aeruginosa (XDR-PA) are becoming a matter of great concern due to limited therapeutic options. Although not approved for these indications, the new BetaLactam-BetaLactamase Inhibitor combinations (BLBLIs) could represent a valid salvage treatment. We describe one nosocomial meningitis and two cervical osteomyelitis due to an XDR-PA who were treated with ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) and review the literature., Methods: The first and the third patients developed an osteomyelitis following cervical stabilization surgery due to an XDR-PA. Although the first patient started treatment with a high dose of C/T, resistance to C/T occurred, so therapy was switched to CZA plus aztreonam. The third patient switched to aztreonam plus CZA due to development of acute kidney injury during therapy with colistin. The second patient had an XDR-PA meningitis following the insertion of an external ventricular catheter and he was treated with C/T plus meropenem and amikacin., Results: All three cases reported were successfully conservatively treated thanks to the use of the new BLBLIs with different combinations. Only few experiences demonstrated an equally favorable outcome: one patient treated with C/T plus fosfomycin for otogenic meningitis caused by an XDR-PA and another case of XDR-PA post-surgical meningitis with CZA in combination with colistin. Finally, the combination of CZA plus aztreonam has proven to be effective on XDR-PA only in limited mostly in vitro studies., Conclusion: These recently developed antibiotics, C/T and CZA are promising and complementary therapy options against post-neurosurgical hard-to-treat P. aeruginosa infections. Further prospective real-life studies are required to validate these findings in this special setting.

The present paper aims to introduce a top down methodology for the forecasting of residential energy demand in four European countries, namely Germany, Italy, Spain, and Lithuania. The methodology employed to develop the estimation is based on econometric techniques. In particular, a logarithmic dynamic linear constant relationship of the consumption is proposed. Demand is estimated as a function of a set of explaining variables, namely heating degree days and gross domestic product per capita. The results confirm that the methodology can be applied to the case of Germany, Italy, and Spain, whereas it is not suitable for Lithuania. The analysis of elasticities of the demand with respect to the gross domestic product per capita shows a negative value for Germany, -0.629, and positive values for Italy, 0.837, and Spain, 0.249. The forecasting of consumption shows that Germany and Italy are more sensitive to weather conditions with respect to Spain and an increase in the demand of 8% and 9% is expected in case of cold climatic conditions.

Objectives: Pregnant women represent a category at high risk of severe measles infection, that negatively affects the fetus as well. A systematic review of clinical outcomes of measles infection in gravid subjects and a meta-analysis of antibodies prevalence among pregnant women was conducted., Methods: MEDLINE and EMBASE databases were searched up to 18 June 2018. The screening focused on: (i) articles describing the outcome of measles in pregnancy, synthesized in a descriptive fashion; (ii) articles addressing the measles seroprevalence in cohorts of gravid women, analysed quantitatively., Results: Twenty-nine articles met inclusion criteria. A total of 420 cases of measles in gravid subjects were described, from 1941 to 2012. Among women, 18 deaths (4.3%) occurred, and the most frequent complication was pneumonia (75/420, 17.9%). Prematurity was the most important complication concerning fetal outcomes (55 out of 410 cases with available data, 13.4%). The random-effects pooled seroprevalence of measles in 20,546 gravid women worldwide was 89.3% (95% CI: 87.3-91.1%), that decreased, although not in a statistically significant way, over time (p = 0.54)., Conclusions: Measles infection in pregnancy is dangerous both for the mother and the foetus. Antibody seroprevalence among gravid women on a global scale is lower than the herd immunity threshold., Competing Interests: Declaration of Competing Interests None., (Copyright © 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Checkpoint kinases 1 and 2 (CHK1 and CHK2) are important multifunctional proteins of the kinase family. Their main function is to regulate DNA replication and DNA damage response. If a cell is exposed to exogenous damage to its DNA, CHK1/CHK2 stops the cell cycle to give time to the cellular mechanisms to repair DNA breakage and apoptosis too, if the damage is not repairable to activate programmed cell death. CHK1/CHK2 plays a crucial role in the repair of recombination-mediated double-stranded DNA breaks. The other important functions performed by these proteins are the beginning of DNA replication, the stabilization of replication forks, the resolution of replication stress and the coordination of mitosis, even in the absence of exogenous DNA damage. Prexasertib (LY2606368) is a small ATP-competitive selective inhibitor of CHK1 and CHK2. In preclinical studies, prexasertib in monotherapy has shown to induce DNA damage and tumor cells apoptosis. The preclinical data and early clinical studies advocate the use of prexasertib in solid tumors both in monotherapy and in combination with other drugs (antimetabolites, PARP inhibitors and platinum-based chemotherapy). The safety and the efficacy of combination therapies with prexasertib need to be better evaluated in ongoing clinical trials.

Riassunto. L'angiogenesi svolge un ruolo importante sia nei tessuti epiteliali normali sia in quelli maligni. Negli ultimi anni questo fenomeno è stato ampiamente studiato in oncologia sperimentale e clinica perché ci sono evidenze che sia coinvolto nella diffusione e nella diffusione metastatica del carcinoma ovarico. Il fattore di crescita dell'endotelio vascolare (vascular endothelial growth factor - VEGF) è l'attore principale nel meccanismo di angiogenesi e svolge un ruolo strategico nella proliferazione e migrazione delle cellule neoplastiche, con un impatto significativo sulla sopravvivenza e sull'outcome clinico. Secondo quanto emerge da molti studi sperimentali e clinici, le nostre conoscenze sulla biologia dell'angiogenesi e del VEGF sono aumentate portando allo sviluppo farmacologico di specifici agenti in grado di targeting VEGF. Questo nuovo campo di indagine offre agli scienziati l'opportunità di testare nuove possibilità terapeutiche nei pazienti con carcinoma ovarico con nuovi agenti mirati. Il bevacizumab, un anticorpo monoclonale anti-VEGF umanizzato, è stato il primo farmaco anti-VEGF scoperto ed è usato oggi per il trattamento di diversi tumori solidi. Negli ultimi anni questo agente è stato ampiamente testato nei pazienti con carcinoma ovarico, mostrando un'attività clinica interessante e un profilo di tossicità tollerabile sia nelle pazienti giovani sia in quelle anziane. Il bevacizumab, combinato con carboplatino e paclitaxel e successivamente utilizzato come agente singolo, è indicato per il trattamento del carcinoma epiteliale dell'ovaio di stadio III o IV, tuba di Falloppio o carcinoma peritoneale primario dopo iniziale resezione chirurgica. Il bevacizumab è anche usato per il trattamento di pazienti con carcinoma ovarico epiteliale ricorrente e resistente al platino, delle tube di Falloppio o dal tumore peritoneale primario che hanno ricevuto non più di 2 regimi precedenti di chemioterapia. Inoltre, il bevacizumab, combinato con carboplatino e paclitaxel o con carboplatino e gemcitabina (e usato come agente singolo), è indicato per il trattamento di pazienti con carcinoma epiteliale dell'ovario sensibile al platino, tuba di Falloppio o tumore peritoneale primario. Le linee guida più accreditate suggeriscono quando bevacizumab deve essere usato nel trattamento del carcinoma ovarico avanzato e ricorrente. Altri agenti anti-VEGF, come gli inibitori della tirosin-chinasi del recettore VEGF (VEGFR), sono stati ampiamente testati nel carcinoma ovarico e molti altri sono in corso di studi al fine di testare la loro attività e sicurezza rispetto a bevacizumab. Gli agenti anti-VEGF e gli inibitori di PARP svolgono oggi un ruolo strategico nel trattamento del cancro ovarico con agenti mirati in associazione con la chemioterapia e la chirurgia in un'ottica multidisciplinare e personalizzata.

Worldwide the needlestick injuries of health care workers (HCWs) still represent a major health problem. The authors aimed to evaluate the risk of HCW needlestick injuries in a tertiary university hospital in southern Italy in relation to some HCW characteristics (age, sex, professional profile, work department) and the source of infection. All HCWs of the University Hospital "Federico II" in Naples, Italy, attending the Infectious Diseases Unit after potential accidental contact to blood-borne viruses through needlestick injuries were enrolled during a 22-year period. HCWs underwent clinical analysis and were administered a specific questionnaire to collect (in anonymous fashion) data about age, sex, professional profile and work department. From 1995 to 2016 1,477 needlestick injuries in the same number of people (one accident per person) were recorded by our service. The HCWs were predominately males (n = 806, 55%) and the mean age was 39.4 years (±10.1 SD). The job categories most involved were: physicians (41%), followed by nurses (33%) and healthcare assistants (HCAs, 10%). The incidence proportion was calculated for these highest-risk categories in three defined time points (at the beginning, in the middle and at the end of the study period): 104/2149 (4.86%) in 1995, 41/2498 (1.64%) in 2005 and 25/2057 (1.22%) in 2015. Most injuries occurred in General Surgery (14.21%), Gynecology and Obstetrics (9%) and Pediatrics (6.49%). In about 34% the HCWs had been exposed to HCV infected fluids. Over time, a significant decrease in accidental exposure was recorded for physicians (p= 0.019), nurses (p< 0.0001) and HCAs (p< 0.0001). Our results confirm that some profiles, namely physicians, nurses and healthcare assistants, are still at risk of needlestick injuries, especially in surgical areas, including obstetric wards. Further primary and secondary prevention strategies are needed to decrease the incidence of new cases of needlestick injuries.

Radium-223 has improved overall survival (OS) and reduced symptomatic skeletal events (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases (ALSYMPCA trial). Our aim was to assess clinical and biochemical factors related to survival, safety and survival outcomes of Radium-223 in a clinical practice setting. We retrospectively analysed 32 mCRPC patients treated with Radium-223, assessing bone scan, pain reduction, alkaline phosphatase (ALP) and prostate-specific antigen (PSA) response (≥30% reduction). At scintigraphic assessment, 41% had partial response with a disease control rate of 91%; 56% had ALP response and 25% had PSA response; 41% had pain reduction with pain control of 72%. Scintigraphic response and stability were correlated with longer median progression-free survival (mPFS) (13 and 12 vs. 6 months; P=0.002) and mOS (16 and 12 vs. 6 months; P=0.003). ALP response was associated with longer mPFS (13 vs. 12 months; P=0.2) and mOS (16 vs. 12 months; P=0.2). PSA response was associated with longer mPFS (13 vs. 12 months; P=0.02), whereas mOS could not be computed. Pain response and stability were associated with survival benefit according to mPFS (13 and 12 vs. 9 months) and mOS (both 16 vs. 12 months) without statistical significance. Baseline ALP <220 UI/l, Eastern Cooperative Oncology Group (ECOG) performance status 0 and absence of previous chemotherapy correlated with statistically significantly longer survival outcomes. Skeletal-related events (SRE) occurred in three patients and median time to first SRE was 9.5 months, mPFS was 12 months and mOS 14 months. G3-G4 toxicities developed in 16% of patients. Our results are in line with those reported in the pivotal trial and in other retrospective studies. In conclusion, Radium-223 was associated with high scintigraphic, biochemical and pain response rates and was tolerated well by most patients. Response to Radium-223 and better baseline factors correlated to longer survival in clinical practice experience as in the clinical trial setting.

The therapeutic management of recurrent malignant gliomas (MGs) is not determined. Therefore, the efficacy of a multimodal approach and a combination systemic therapy was investigated. A retrospective analysis of 26 MGs patients at first relapse treated with multimodal therapy (chemotherapy plus surgery and/or reirradiation) or chemotherapy alone was performed. Second-line chemotherapy consisted of fotemustine (FTM) in combination with bevacizumab (BEV) (cFTM/BEV) or followed by third-line BEV (sFTM/BEV). Subgroup analyses were performed. Multimodal therapy provided a higher overall response rate (ORR) (73 vs. 47%), disease control rate (DCR) (82 vs. 67%), median progression-free survival (mPFS) (11 vs. 7 months; P=0.08) and median overall survival (mOS) (13 vs. 8 months; P=0.04) compared with chemotherapy. Concomitant FTM/BEV resulted in higher ORR (84 vs. 36%), DCR (92 vs. 57%), mPFS (10 vs. 5 months; P=0.22) and mOS (11 vs. 5.2 months; P=0.15) compared with sFTM/BEV. Methylated patients did not experience additional survival benefits with multimodality treatment but had higher mPFS (10 vs 7.1 months; P=0.33) and mOS (11 vs. 8 months; P=0.33) with cFTM/BEV. Unmethylated patients experienced the greatest survival benefit with the multimodal approach (mPFS: 10 vs. 5 months; mOS 11 vs 6 months; both P=0.02) and cFTM/BEV (mPFS: 5 vs. 2 months; mOS 6 vs. 3.2 months; both P=0.01). In conclusion, in recurrent MGs, multimodal therapy and cFTM/BEV provide survival and response benefits. Methylated patients benefit from a cFTM/BEV but not from a multimodal approach. Notably, unmethylated patients had the highest survival benefit with the two strategies.

Fotemustine (FTM) is a treatment option in recurrent malignant gliomas (MGs) after first-line Stupp treatment. The efficacy and the safety of fractionated FTM schedule proposed by Addeo et al was analysed in the present study in recurrent MGs patients. A retrospective analysis on 40 recurrent MGs patients and second-line fractionated FTM chemotherapy was performed. Response evaluation was assessed using RANO criteria and safety was assessed using CTCAE v.4.03. Subgroup analyses based on MGMT methylation, resurgery and reirradiation were performed. A review of the literature was also performed. The results revealed 5 partial responses (13%) and 19 stable diseases (47%) with a disease-control rate of 60%. Median progression-free survival (PFS) was 4 months, with a PFS of 33% at 6 months and 13% at 1 year. The median overall survival (OS) was 9 months and OS at 6 months was of 55% and at 1 year of 30%. Methylated patients experienced longer mPFS (6 vs. 3 months; p=0.004) and mOS (10 vs. 4 months; p<0.0001) compared with unmethylated patients. Patients treated with reirradiation experienced longer mPFS (5 vs. 3.5 months; p=0.48) and mOS (10 vs. 5 months; p=0.11). No survival benefit with resurgery was observed. Furthermore, the fractioned schedule was well tolerated, only 15% of patients developed severe myelotoxicities. Considering the present findings, fractionated FTM schedule is an efficient second-line option for MGs associated with an acceptable myelotoxicity profile. Additionally, MGMT methylation is associated with improved survival outcomes. However, this study highlights the requirement for further prospective randomized studies on resurgery and reirradiation.

Introduction: The pregnancy-associated immunological and hormonal changes may alter the immune response to infectious agents, including hepatitis viruses. Therefore, this phenomenon may affect the clinical course and the outcome of acute viral hepatitis in pregnant women., Evidence Acquisition: For this reason, we have focused on epidemiological and pathogenetic aspects of the fulminant liver failure caused by acute viral hepatitis reviewing PubMED in April of 2017., Evidence Synthesis: Although all the viruses might cause a fulminant acute viral hepatitis in a pregnant woman, the large majority of fulminant failure reported in the literature had been related to hepatits E virus (HEV) mainly and had been concentrated in Indian subcontinent and some African areas, whereas the problem seems to be very low or absent in the remaining geographical areas. However, the rate of maternal mortality due to fulminant E hepatitis may vary inside the endemic areas of India and Africa, likely due to the circulation of HEV genotypes with different degree of virulence. The other hepatitis viruses have not been reported to cause a greater risk for fulminant hepatitis in pregnant women respect to non-pregnant ones, except Herpes simplex virus, that has been associated to some cases of fatal hepatitis in absence of a prompt antiviral therapy., Conclusions: AVH should be considered when the pregnant woman develop fever, abdominal pain, malaise, nausea and anicteric hepatic dysfunction.

Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence.

Bevacizumab (BV) is a humanized monoclonal antibody targeting vascular endothelial growth factor and it is the first molecular-targeted agent to be used for the treatment of ovarian cancer (OC). Randomized Phase III trials evaluated the combination of BV plus standard chemotherapy for first-line treatment of advanced OC and for platinum-sensitive and platinum-resistant recurrent OC. These trials reported a statistically significant improvement in progression-free survival but not in overall survival. Furthermore, BV effectively improved the quality of life with regard to abdominal symptoms in recurrent OC patients. Bevacizumab is associated with adverse events such as hypertension, bleeding, thromboembolism, proteinuria, delayed wound healing, and gastrointestinal events. However, most of these events can be adequately managed. This review describes the latest evidence for BV treatment of OC and selection of patients for personalized treatment.

Background: Epidemiologic evidences suggest a strong association between low birth weight and some diseases in adult life ( hypertension, diabetes, cardiovascular diseases).Aim of this study was to evaluate the obesity/overweight prevalence in a population of children born small for gestation age, SGA children 400, 208 males and 192 females compared to a population of children born appropriate for gestational age 6818 AGA children, 3502 males and 3316 females, during childhood. Our intention was also to build the natural history of weight gain during prepubertal age in children born SGA and AGA., Design and Methods: Observational prospective longitudinal study. We followed our patients from January2001 up to December 2010; weight, height and body mass index (BMI) were evaluated in all the SGA and AGA children. BMI z-score range for defining overweight and obesity was, respectively, 1.13 to 1.7 and >1.7 according to CDC growth charts., Results: In transversal evaluation, we prove that 10-year-old SGA females are twice obese and more overweight compared to equal age AGA females. In longitudinal evaluation, we highlight different observations: SGA children obese at 2 years are still obese at 10 years; the number of obese SGA children increases gradually until the age of 10; AGA children, appear to be less obese than SGA children at 10 years., Conclusion: SGA males and females are more obese at 5 and 10 years compared to the AGA population. Primary care pediatricians, through early detection of the children at risk, can carry out an effective obesity prevention project in SGA children., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Small cell carcinoma of the urinary bladder is a rare and aggressive form of bladder cancer that mainly presents at an advanced stage. As a result of its rarity, it has been described in many case reports and reviews but few retrospective and prospective trials, showing there is no standard therapeutic approach. In the literature the best therapeutic strategy for limited disease is the multimodality treatment and most authors have extrapolated treatment algorithms from the therapy recommendations of small cell lung cancer., Case Report: A 71-year-old male patient was referred to our hospital with gross hematuria and dysuria. Imaging and cystoscopy revealed a vegetative lesion of the bladder wall. A transurethral resection of the bladder was performed. Pathological examination revealed a pT2 high-grade urothelial carcinoma with widespread neuroendocrine differentiation. Multimodal treatment with neoadjuvant platinum-based chemotherapy was performed. A CT scan performed after chemotherapy demonstrated a radiological complete response. The patient underwent radical cystectomy and lymphadenectomy. The histopathological finding of bladder and node specimen confirmed a pathological complete response. A post-surgery CT scan showed no evidence of local or systemic disease. Six months after surgery, the patient is still alive and disease-free., Conclusions: A standard treatment strategy of small cell cancer of the urinary bladder is not yet well established, but a multimodal treatment of this disease is the best option compared to surgical therapy alone. The authors confirm the use of neoadjuvant chemotherapy in limited disease of small cell carcinoma of the urinary bladder.

Unlabelled: Cisplatin and etoposide (PE) is the most used chemotherapy regimen in extensive-stage disease small-cell lung cancer (ED-SCLC), and usually achieves a high initial response rate. An intriguing maintenance strategy could be the combination of the angiogenic agent bevacizumab (Bev) with a convenient and well tolerated chemotherapy agent such as oral etoposide. Results of the current single-institutional phase II study suggest that a regimen that includes conventional PE chemotherapy combined with Bev followed by oral etoposide and Bev as maintenance treatment is feasible and effective in terms of 9-month disease control rate in patients with ED-SCLC., Background: In the present study we evaluated the efficacy and safety of a cisplatin (P), etoposide (E), and bevacizumab (Bev) regimen followed by maintenance oral E and Bev in patients with extensive-stage disease small-cell lung cancer (ED-SCLC)., Patients and Methods: Patients were administered 3-day fractionated P 25 mg/m(2) and E 100 mg/m(2) on days 1 to 3, every 3 weeks. After 3 PE cycles, all patients whose disease did not progress continued treatment with PE combined with Bev 15 mg/kg on day 3 every 3 weeks. After completion of 3 PE/Bev cycles, patients who did not experience tumor progression continued maintenance treatment with oral E 50 mg on days 1 to 14 every 21 days combined with Bev 3 times per week until occurrence of disease progression or unacceptable toxicity., Results: At our institution, 22 patients were enrolled and their median age was 66 years (range, 38-79 years). After completion of induction chemotherapy (3 PE cycles with 3 PE/Bev cycles) the objective response rate was in 17 patients (77.2%) (95% confidence interval [CI], 54.6-92.1). Twenty-one patients received maintenance treatment with oral E and Bev. The 9-month disease control rate was 8 patients (36.3%). Median progression-free survival was 7.8 months (95% CI, 7.0-11.3 months) and median overall survival was 13.2 months (95% CI, 11.8-18.7 months). Grade 3 to 4 neutropenia occurred in 12 patients (54.4%) and 14 patients (63.6%) of patients during cycles 1 to 3 and cycles 4 to 6 of induction chemotherapy, respectively. Severe adverse events during maintenance treatment were rarely observed., Conclusion: A PE and Bev regimen followed by oral E and Bev maintenance treatment appears feasible and effective in terms of 9-month disease control rate in patients with ED-SCLC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The aim of this phase 2 study was to evaluate the activity and tolerability of low-dose estramustine phosphate (EMP) with concomitant low-dose acetylsalicylic acid (ASA) as a thromboprophylactic agent in heavily pretreated patients with advanced castration-resistant prostate cancer., Methods: Patients received 420 mg of oral EMP twice daily and oral ASA 100 mg once daily. The primary endpoint was prostate-specific antigen response. All of the patients had been previously treated with docetaxel and abiraterone acetate, and 12 had also received cabazitaxel., Results: Thirty-one patients were enrolled. Prostate-specific antigen response was observed in 9 patients (29.0%; 95% confidence interval [CI], 14-48). Median progression-free survival was 3.6 months (95% CI, 2.2-5.6), and median overall survival was 7.6 months (95% CI, 6.9-9.7). Treatment was generally well tolerated, and no grade 3/4 toxicity was observed. Ten patients (32.2%) had grade 2 nausea and vomiting. No cardiovascular event and no major bleeding occurred. No venous thromboembolism event was observed., Conclusion: Low-dose EMP with concomitant low-dose ASA seems to be a safe treatment option with some activity for patients with advanced castration-resistant prostate cancer who have been heavily pretreated., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To evaluate the efficacy and safety of maintenance treatment with oral cyclophosphamide (Cy) and bevacizumab (Bev) in patients with recurrent ovarian cancer., Patients & Methods: Induction treatment consisted of cisplatin, epirubicin, Cy and Bev every 3 weeks, for a maximum of six cycles. Maintenance treatment consisted of oral Cy 50 mg, days 1-14 and Bev 15 mg/kg, every 3 weeks until disease progression occurred., Results: In total, 39 patients were enrolled: after induction chemotherapy, the objective response was 74.3%. The median progression-free survival was 13.3 months, and the median overall survival was 33.2 months. Toxicity during maintenance treatment was mild., Conclusion: Maintenance with Cy and Bev may achieve encouraging results in terms of progression-free survival and overall survival in recurrent ovarian cancer patients.

The primary objective of this study was to determine the activity and safety of carboplatin, methotrexate, vinblastine, and epirubicin (the M-VECa regimen) in patients with advanced bladder cancer after failure of at least one chemotherapy line. Treatment consisted of carboplatin 250 mg/m on day 1, methotrexate 30 mg/m on days 1 and 22, vinblastine 3 mg/m on days 2 and 22, and epirubicin 50 mg/m on day 2 every 28 days until disease progression or death. Response rate was the main end-point. Twenty-five patients were enrolled: the median age was 67 years (range 42-83) and there were 14 patients aged at least 70 years (56%). Fourteen patients had previously received vinflunine as a second-line treatment. Complete remission occurred in one patient (4%), partial remission in five patients (20%), and stable disease in eight patients (32%). The overall response rate was 24% [95% confidence interval (CI), 9.3-45.1%] and the overall disease control rate was 56% (95% CI, 34.9-75.5%). The median progression-free survival was 5.1 months (95% CI, 3.9-6.4) and the median overall survival was 9.5 months (95% CI, 7.1-11.2). Treatment was well tolerated: grade 3 neutropenia was documented in five patients and grade 3 nausea and vomiting in two patients. The M-VECa regimen seems to be feasible as second-line or third-line treatment in patients with advanced bladder cancer who have been pretreated with one or more chemotherapy lines, and may achieve encouraging results in terms of disease control rate, progression-free survival, and overall survival.

Both abiraterone acetate (AA) and cabazitaxel (Cbz) have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing during or after docetaxel (D). Although no standard sequencing has been established as yet, Cbz has recently been proven to be active after AA. However, to date, few data are available on its safety in this setting. Therefore, the primary endpoint of this study was to investigate Cbz tolerability in mCRPC patients treated previously with D and AA. From April 2011 to the present, 43 mCRPC patients received AA after D at our institution. Of these, 22 patients were subsequently treated with Cbz and were evaluable for toxicity in the present retrospective study. Cbz was administered at a dose of 25 mg/m plus 10 mg oral prednisone every 3 weeks. Adverse events (AEs) were reported using the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0. Despite the advanced stage of disease and frailty of our study population, there were no unexpected side effects. The most common AEs were hematologic. Neutropenia was observed in nine (40.9%) patients and of grade≥3 in six (27.2%). No febrile neutropenia occurred. The most common nonhematologic AEs were diarrhea and asthenia, reported in eight (36.3%) and in five (22.7%) patients, respectively. In this setting, Cbz toxicity seems to be manageable and comparable with second-line Cbz. Therefore, our results seem to support the safety of Cbz as a third-line treatment for mCRPC patients.

The present study evaluated the efficacy and safety of cisplatin (Cis), gemcitabine (Gem) and bevacizumab (Bev), followed by maintenance treatment with Bev and oral vinorelbine (Vnb), in patients with advanced non-squamous non-small cell lung cancer (NSCLC). The patients were administered six cycles of induction chemotherapy consisting of intravenously (i.v.) Cis 70 mg/m(2) on day 1 plus i.v. Gem 1000 mg/m(2) on days 1 and 8, plus i.v. Bev 7.5 mg/kg on day 1, every 3 weeks. Patients who did not experience tumor progression remained on maintenance treatment with Bev combined with oral Vnb 60 mg/m(2) weekly until occurrence of disease progression or unacceptable toxicity. Thirty-seven patients were enrolled: The median age was 67 years (range 38-81); 22 patients were male, and 30 patients had stage IV tumors. The response rate was 32.4 % (95 % CI 18-49.7). The 9-month disease-control rate was 45.9 %. The median PFS was 8.4 months (95 % CI 4.4-10.7), and the median OS was 18.1 months (95 % CI 15.3-20.8 months). Grade 3-4 neutropenia occurred in 6 (16.2 %) patients and grade 3-4 thrombocytopenia in four (10.8 %) patients during induction chemotherapy. Bev- or Vnb-associated toxicities were mild. Switch maintenance treatment with Bev and oral Vnb after first-line Cis, Gem and Bev is feasible in patients with non-squamous NSCLC and may achieve encouraging results in terms of PFS and OS.

The aim of this study was to evaluate the activity and tolerability of abiraterone acetate in patients with metastatic castrate-resistant prostate cancer treated previously with more than three lines of chemotherapy. Patients received 1 g of abiraterone acetate (administered as four 250 mg tablets) orally once daily with prednisone at a dose of 5 mg orally twice daily. The primary endpoint was prostate-specific antigen (PSA) response. From August 2011 to January 2013, 36 patients were enrolled. PSA response was observed in 22 patients (61.1%, 95% confidence interval: 0.41-0.81). The median time to PSA progression was 7.3 months and after a median follow-up of 10.1 months, all patients were alive. The treatment was generally well tolerated; side effects secondary to mineralocorticoid excess resulting from blockade of CYP17 were largely controlled with prednisone. Abiraterone acetate seems to be an effective and well-tolerated treatment option for patients with metastatic castrate-resistant prostate cancer irrespective of the number of chemotherapy lines administered previously.

Aims and Background: Capecitabine is the reference treatment for anthracycline- and/or taxane-pretreated metastatic breast cancer (MBC). This study examined its efficacy, tolerability and impact on the quality of life of elderly patients with MBC., Materials and Methods: Between January 2002 and December 2009, 75 consecutive elderly patients with MBC received first-line chemotherapy with capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks. Endpoints were efficacy, tolerability and clinical-benefit response measured every 3 cycles., Results: Median age was 76 years (range 65-88); median ECOG performance status was 1 (range 0-2); 51 patients (68%) had received adjuvant chemotherapy and all patients had received hormonal therapy. Median exposure was 6 cycles. After 3 cycles, 11 patients (14.7%) had a partial response, one patient experienced a complete response, and 49 patients (65.3%) had stable disease, amounting to a disease control rate of 81.3%. Stable disease was maintained in 45 patients (60%) after 6 cycles, in 21 patients (28%) after 9 cycles, and in 13 patients (17.3%) after 12 cycles. A clinical-benefit response was experienced by 42 patients (56%), indicating a positive impact on quality of life. Treatment was well tolerated, the most common grade 3 events being diarrhea (12%) hand-foot syndrome (8%), and mucositis (8%). Adverse events were managed with dose adjustments and supportive therapy when required., Conclusions: Our results indicate that capecitabine is active and well tolerated in elderly patients with MBC. This dosing regimen warrants further study in the first-line setting for patients with less aggressive MBC who are not candidates for combination therapy.

In this article, developing turbulent forced convection flow of a water-Al2O3 nanofluid in a square tube, subjected to constant and uniform wall heat flux, is numerically investigated. The mixture model is employed to simulate the nanofluid flow and the investigation is accomplished for particles size equal to 38 nm.An entropy generation analysis is also proposed in order to find the optimal working condition for the given geometry under given boundary conditions. A simple analytical procedure is proposed to evaluate the entropy generation and its results are compared with the numerical calculations, showing a very good agreement.A comparison of the resulting Nusselt numbers with experimental correlations available in literature is accomplished. To minimize entropy generation, the optimal Reynolds number is determined.

The dielectrophoretic separation of individual metallic single-walled carbon nanotubes (SWNTs) from heterogeneous solutions and their simultaneous deposition between electrodes is achieved and confirmed by direct electric transport measurements. Out-of-solution guided parallel assembly of individual SWNTs was investigated for electric field frequencies between 1 and 200 MHz. At 200 MHz, 19 of the 22 deposited SWNTs (86%) displayed metallic behavior, whereas at lower frequencies the expected random growth distribution of 1/3 metallic SWNTs prevailed. A threshold separation frequency of 188 MHz is extracted from a surface-conductivity model, and a conductivity weighting factor is introduced to elucidate the separation frequency dependence. Low-frequency experiments and numerical simulations show that long-range nanotube transport is governed by hydrodynamic effects whereas local trapping is dominated by dielectrophoretic forces. The electrokinetic framework of dielectrophoresis in low-concentration solutions is thus provided and allows a deeper understanding of the underlying mechanisms in dielectrophoretic deposition processes for long and large-diameter SWNT-based low-resistance device integration.

Aim: The primary aims of this study were activity and toxicity evaluation of a new raltitrexed and oxaliplatin-based regimen, as a first-line chemotherapy, in patients with metastatic colorectal cancer (MCC). Survival evaluation was considered a secondary endpoint., Patients and Methods: Forty-four patients were enrolled into this phase II trial. Treatment consisted of raltitrexed 3 mg/m2 iv on d 1 and oxaliplatin 70 mg/m2 iv on d 1 and d 8 every 3 wk., Results: Twenty patients (45.5%) achieved a response [95% confidence interval (CI): 30.1% to 54.1%], 18 (40.9%) had stable disease, and only 6 (13.6%) developed progressive disease. After a median follow-up time of 14.7 mo (range 6.3-18.6 mo), the median time to disease progression was 6 mo (range 2.0-16.7) (95% CI: 4.4-7.6) and the overall survival was 14.8 mo (range 3-23) (95% CI: 11.2-18.4). Neutropenia was the most common hematological side effect, while transient AST/ALT increase, neurotoxicity, asthenia, and diarrhea were the most common nonhematological side effects., Conclusions: Our data confirmed that oxaliplatin administered weekly plus raltitrexed is an active combination in newly diagnosed patients with advanced colorectal carcinoma that merits further investigation versus the classic schedule in a randomized, phase III trial.

Introduction: In the past the unfavourable profile of toxicity of antineoplastic drugs employed (i.e. cisplatinum) weakened the role of chemotherapy in aged patients with non-small cell lung cancer (NSCLC). Recently, new active drugs with lesser toxicity have became widely used in this setting. In this prospective study we evaluated the efficacy and tolerability of gemcitabine in elderly patients with stages III-IV NSCLC., Materials and Methods: From December 1996 to April 1999, we enrolled 52 previously untreated elderly patients with advanced/metastatic NSCLC. Gemcitabine was administered at 1000 mg/mq i.v. over 30 minutes weekly for three consecutive weeks every 28 days. The planned number of cycles was three while responding or stable patients received chemotherapy until disease progression or the ninth cycle. A total of 291 cycles were delivered with a median number of 6 cycles (range: 3-9). An evaluation of the quality of life was performed every three courses of gemcitabine., Results: After three cycles of treatment, a complete response was seen in four patients (7.7%), partial response in 16 patients (30.8%) with an overall response rate of 38.5%. Nineteen patients (36.5%) showed stable disease, while thirteen patients (25%) progressed. Median progression-free survival was 22 weeks, median duration of response 26 weeks, median overall survival 34 weeks and 1-year overall survival 46.1%. A statistically significant improvement in the quality of life was registered only after the first three cycles of gemcitabine (p = 0.045). Toxicity was extremely mild., Conclusion: In elderly patients with stages III-IV NSCLC gemcitabine showed good activity with a mild toxicity and could be considered a valid therapeutic option in this setting.