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Abstract: We analyzed major and trace elements, Sr and Nd isotopes in ultramafic xenoliths in Miocenic age Hyblean diatremes, along with noble gases of CO2-rich fluid inclusions hosted in the same products. The xenoliths consist of peridotites and pyroxenites, which are considered to be derived from the upper mantle. Although the mineral assemblage of peridotites and their whole-rock abundance of major elements (e.g., Al2O3 =0.8–1.5wt.%, TiO2 =0.03–0.08wt.%) suggest a residual character of the mantle, a moderate enrichment in some incompatible elements (e.g., LaN/YbN =9–14) highlights the presence of cryptic metasomatic events. In this context a deep silicate liquid is considered the metasomatizing agent, which is consistent with the occurrence of pyroxenites as veins in peridotites. Both the Zr/Nb and 143Nd/144Nd ratios of the investigated samples reveal two distinct compositional groups: (1) peridotites with Zr/Nb≈4 and 143Nd/144Nd≈0.5129, and (2) pyroxenites with Zr/Nb≈20 and 143Nd/144Nd≈0.5130. The results of noble-gas analyses also highlight the difference between the peridotite and pyroxenite domains. Indeed, the 3He/4He and 4He/40Ar* ratios measured in the fluid inclusions of peridotites (respectively 7.0–7.4±0.1 Ra and 0.5–8.2, where Ra is the atmospheric 3He/4He ratio of 1.38×10−6) were on average lower than those for the pyroxenites (respectively 7.2–7.6 Ra and 0.62–15). This mantle heterogeneity is interpreted as resulting from a mixing between two end-members: (1) a peridotitic layer with 3He/4He≈7 Ra and 4He/40Ar*≈0.4, which is lower than the typical mantle ratio (~1–4) probably due to melt extraction events, and (2) metasomatizing mafic silicate melts that gave rise to pyroxenites characterized by 3He/4He≈7.6 Ra, with a variable 4He/40Ar* due to degassing processes connected with the ascent of magma at different levels in the peridotite wall rock. The complete geochemical data set also suggests two distinct mantle sources for the xenolithic groups highlighted above: (1) a HIMU (high-μ)-type source for the peridotites and (2) a DM (depleted mantle)-type source for the pyroxenites. [Copyright &y& Elsevier]

This study provides an updated report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified, purging-free, total body irradiation-free, high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft (i-HDS) in advanced-stage follicular lymphoma (FL). Special interest has been devoted to late toxicities and outcome in terms of molecular status. Ninety-two untreated FL patients aged 60 were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis. Main findings are as follows: (1) 5.5-years overall survival projection of 80% (median follow-up: 68 months), with no differences related to age-adjusted IPI score; (2) 46 (50%) of 92 patients presently in continuous complete remission; (3) projected long-term progression-free survival exceeding 80% for patients collecting PCR-negative stem cell harvests or achieving molecular remission within the first 2 years from the end of therapy; (4) actuarial 5-years risk of developing secondary myelodysplasia and acute myeloid leukemia of 3.7%, with most of these events occurring in patients re-treated for recurrent lymphoma. These results demonstrate that i-HDS is feasible, effective and safe even in terms of long-term outcome. As the HDS schedule can be easily supplemented with Rituximab, it is one of the best options for random comparison with Rituximab-supplemented conventional chemotherapy.Leukemia (2006) 20, 1840–1847. doi:10.1038/sj.leu.2404346; published online 24 August 2006 [ABSTRACT FROM AUTHOR]

Geochemical investigations carried out at the Campano–Lucano Apennine (Southern Italy) revealed the presence of fluids composed of a mixing between components of shallow and deep origin, where mantle-derived helium is also detectable. For the gas phase, the deep component is represented by both CH4 and CO2-rich gases, while the shallow one is N2-dominated. Coinciding with the 3 April 1996 ML=4.9 earthquake, the CH4-rich component mixed with the shallow, N2-dominated one at the Tramutola well (Val d’Agri), displaying wide variations in mixing proportions. In contrast, no significant modifications occurred in relation to the 1998 ML=5.5 event. According to the collected data, an earthquake-related transient modification of local crustal permeability is suggested for the 1996 event. The different crustal response to the two events may be related to different stress distributions around the epicentres or may suggest a different tectonic connection between the Val d’Agri and the two earthquake locations. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of this study is to investigate the relationship between a vitamin D receptor polymorphism and the diagnosis of periodontal disease in non-smoker Italian patients with aggressive and chronic periodontitis. Materials and methods: DNA was obtained from the internal cheek mucosa of 115 patients with chronic periodontitis, 58 with aggressive periodontitis and 65 healthy controls. Allelic discrimination was performed using TaqMan® SNP Genotyping Assays. Genotype and allele frequencies were calculated. Results: Comparisons between diseased patients and healthy controls showed significant differences. Moreover, calculating the odds ratio, individuals with the TT genotype, was more susceptible than individuals with tt to chronic periodontitis and individuals with Tt to aggressive periodontitis. Interestingly, the dominant model (TT+Tt vs. tt) was applicable to chronic periodontitis, whilst for aggressive periodontitis the recessive model (TT vs. Tt+tt) gave the highest odds ratio. Conclusions: These data indicated that VDR TaqI polymorphism is differentially associated with development of chronic periodontitis and aggressive periodontitis in Italian population. The study of VDR polymorphisms may therefore be essential for the prevention of periodontitis and for a pre-treatment periodontal and/or for implant assessment. Moreover VDR TaqI polymorphism could be useful to discriminate between aggressive and chronic forms of periodontal disease. [Copyright &y& Elsevier]

Abstract: We investigated the geochemistry of the fumaroles at the summit area of Mt. Etna, including sulfur speciation and the content of acidic gases. The carbon-isotope composition of the Etnean plume was also measured in order to compare it to that of fumaroles. Two types of fumaroles were identified: (i) low-temperature fumaroles, which are dominated by CO2 with minor amounts of SO2 and H2S, and negligible chlorine contents, and (ii) high-temperature fumaroles, which are strongly air-contaminated and characterized by appreciable amounts of volcanogenic carbon, sulfur, and chlorine. As recognized by , both groups of fumaroles are fed by the degassing of an underlying magma; nevertheless, compositional data clearly show that secondary processes affect the composition of the fluids once they leave the magma body. Here a model of cooling and condensation of fluids is proposed to explore such postmagmatic processes. The model, which uses Etnean plume geochemistry as starting composition of fluids exsolved from magma, shows that SO2 and H2S control the redox conditions of the gas mixture during the cooling, until the reactions involving CO/CO2 and H2/H2O ratios are fully quenched at temperatures around 350–450°C. The dissolution of gases in water, subsequent to condensation, must occur at thermobaric conditions over 50bar and 260°C, which allows (a) total removal of HCl, (b) partial removal of sulfur species while preserving the SO2/H2S ratio, and (c) the C/S ratio to increase by almost 10-fold relative to that in the plume. The observed CH4/CO2 ratios are higher than those calculated for the Etnean magmatic gas, and hence they provide evidence of modest contributions from peripheral hydrothermal fluids during the migration of magmatic gases toward the surface in both low- and high-temperature fumaroles. Due to the peculiar thermodynamic conditions, the model predicts that carbon isotopes do not experience any postmagmatic fractionation, and hence the isotopic composition of the fumaroles is representative of magmatic carbon. Measurements of the carbon-isotope composition of the plume corroborate these findings. [Copyright &y& Elsevier]

Abstract: Chemical and isotopic analyses of the main gas manifestations of the island of Pantelleria (Italy) were used to gain insight on the origin of the released methane. Results indicate that the most probable origin is through abiogenic reactions within the hydrothermal system. Methane and CO2 flux measurements from the soils were made with the accumulation chamber method in an area of about 0.015km2 within the main fumarolic area of the island (Favara Grande). The 23 measurements range from −34 to 3550mgm−2 d−1 for CH4 and from 0.6 to 379gm−2 d−1 for CO2. The relationships between CH4 and CO2 fluxes and the CH4/CO2 ratios in the gases collected between the depths of 25 and 100cm provide evidence for methanotrophic processes within the soils. Methane output for the surveyed area was calculated to be 2.5ta−1 and extrapolated to about 5–10ta−1 for the entire volcanic/hydrothermal system of the island. Previous higher estimates of the CH4 output at Pantelleria (Etiope et al., 2007, J. Volcanol. Geotherm. Res., 165, 76–86) were based on soil CO2 output and CH4/CO2 ratios in fumarolic gases; the present work provides the first direct CH4 flux data and it suggests that methanotrophic activity in the soil could be substantial in reducing the CH4 emission to the atmosphere. [Copyright &y& Elsevier]

Axicabtagene ciloleucel showed efficacy for relapsed/refractory large B-cell lymphomas (LBCL), including primary mediastinal B-cell lymphomas (PMBCL); however, only few PMBCLs were reported. Aim was to evaluate efficacy and safety of axicabtagene ciloleucel in patients with PMBCL compared to those with other LBCL, enrolled in the Italian prospective observational CART-SIE study. PMBCLs (n = 70) were younger, with higher percentage of bulky and refractory disease, compared to other LBCLs (n = 190). Median follow-up time for infused patients was 12.17 months (IQR 5.53,22.73). The overall (complete + partial) response rate (ORR,CR + PR) after bridging was 41% for PMBCL and 28% for other LBCL, p = 0.0102. Thirty days ORR was 78% (53/68) with 50% (34) CR in PMBCL, and 75% (141/187) with 53% (100) CR in other LBCL, p = 0.5457. Ninety days ORR was 69% (45/65) with 65% (42) CR in PMBCL, and 54% (87/162) with 47% (76) CR in other LBCL; progressive disease was 21% in PMBCL and 45% in other LBCL, p = 0.0336. Twelve months progression-free survival was 62% (95% CI: 51-75) in PMBCL versus 48% (95% CI: 41-57) in other LBCL, p = 0.0386. Twelve months overall survival was 86% (95% CI: 78-95) in PMBCL versus 71% (95% CI: 64-79) in other LBCL, p = 0.0034. All grade cytokine release syndrome was 88% (228/260); all grade neurotoxicity was 34% (88/260), with 6% of fatal events in PMBCL. Non-relapse mortality was 3%. In conclusion, PMBCLs achieved significantly better response and survival rates than other LBCLs., (© 2024. The Author(s).)

Introduction: As suicide rates increase with age, it is mandatory to carefully assess old age suicidal behaviors. Our aim was to describe the main socio-demographic and clinical features of a sample of suicide attempters aged 65 years and older, and to assess differences within the sample (men vs. women; patients with vs. without a previous history of suicide attempt; patients with vs. without a previous psychiatric history). Methods: Retrospective study conducted at the Maggiore della Carità University Hospital, Novara, Italy. Results: A higher percentage of female patients in our sample were treated by or referred to mental health services, while a greater percentage of male patients required a prolonged clinical observation in the Emergency Room (ER) or in non-psychiatric wards before psychiatric admission. The percentage of patients without previous psychiatric history taking anxiolytic and sedative medications was 25%. Conclusion: It is likely that different clusters and types of suicide attempters exist. Women in our sample appeared more proactive in asking for help, and more likely to be already treated by or referred to a psychiatric service, suggesting the need to facilitate the access to psychiatric services for the male population aged 65 years and older, or to offer support and care for the non-psychiatric reasons (comorbidities, pain, and loss of autonomy) possibly underlying suicidal behavior in this specific group. The use of medications deserves more attention considering the possible critical diagnostic issues in this age group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gramaglia, Martelli, Scotti, Bestagini, Gambaro, Romero and Zeppegno.)

Introduction: The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions., Materials and Methods: In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded., Results: At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006), and platelet count ( χ 2 5.39; p = 0.02), along with age ( χ 2 87.6; p < 0.001) and gender ( χ 2 17.3; p < 0.001), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality (OR) = 3.40 (2.40-4.82), while the OR for a RDW > 13.7% was 4.09 (2.87-5.83); a platelet count > 166,000/ μ L was, conversely, protective (OR: 0.45 (0.32-0.63))., Conclusion: Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2021 Mattia Bellan et al.)

Importance: Although plenty of data exist regarding clinical manifestations, course, case fatality rate, and risk factors associated with mortality in severe coronavirus disease 2019 (COVID-19), long-term respiratory and functional sequelae in survivors of COVID-19 are unknown., Objective: To evaluate the prevalence of lung function anomalies, exercise function impairment, and psychological sequelae among patients hospitalized for COVID-19, 4 months after discharge., Design, Setting, and Participants: This prospective cohort study at an academic hospital in Northern Italy was conducted among a consecutive series of patients aged 18 years and older (or their caregivers) who had received a confirmed diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection severe enough to require hospital admission from March 1 to June 29, 2020. SARS-CoV-2 infection was confirmed via reverse transcription-polymerase chain reaction testing, bronchial swab, serological testing, or suggestive computed tomography results., Exposure: Severe COVID-19 requiring hospitalization., Main Outcomes and Measures: The primary outcome of the study was to describe the proportion of patients with a diffusing lung capacity for carbon monoxide (Dlco) less than 80% of expected value. Secondary outcomes included proportion of patients with severe lung function impairment (defined as Dlco <60% expected value); proportion of patients with posttraumatic stress symptoms (measured using the Impact of Event Scale-Revised total score); proportion of patients with functional impairment (assessed using the Short Physical Performance Battery [SPPB] score and 2-minute walking test); and identification of factors associated with Dlco reduction and psychological or functional sequelae., Results: Among 767 patients hospitalized for severe COVID-19, 494 (64.4%) refused to participate, and 35 (4.6%) died during follow-up. A total of 238 patients (31.0%) (median [interquartile range] age, 61 [50-71] years; 142 [59.7%] men; median [interquartile range] comorbidities, 2 [1-3]) consented to participate to the study. Of these, 219 patients were able to complete both pulmonary function tests and Dlco measurement. Dlco was reduced to less than 80% of the estimated value in 113 patients (51.6%) and less than 60% in 34 patients (15.5%). The SPPB score was suggested limited mobility (score <11) in 53 patients (22.3%). Patients with SPPB scores within reference range underwent a 2-minute walk test, which was outside reference ranges of expected performance for age and sex in 75 patients (40.5%); thus, a total of 128 patients (53.8%) had functional impairment. Posttraumatic stress symptoms were reported in a total of 41 patients (17.2%)., Conclusions and Relevance: These findings suggest that at 4 months after discharge, respiratory, physical, and psychological sequelae were common among patients who had been hospitalized for COVID-19.

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO 2 /FiO 2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Background: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19., Methods: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing., Findings: We enrolled 536 patients with a median follow-up of 20 days (IQR 10-34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77-2·34) in our whole study cohort and 3·72 (2·86-4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1-44·9). Older age (hazard ratio 1·03, 95% CI 1·01-1·05); progressive disease status (2·10, 1·41-3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56-7·81), indolent non-Hodgin lymphoma (2·19, 1·07-4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34-4·89), or plasma cell neoplasms (2·48, 1·31-4·69), and severe or critical COVID-19 (4·08, 2·73-6·09) were associated with worse overall survival., Interpretation: This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available., Funding: Associazione italiana contro le leucemie, linfomi e mieloma-Varese Onlus., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Patients with cancer may be more susceptible to and have higher morbidity and mortality rates from COVID-19 than the general population, while epidemiologic data specifically addressed to hematologic patients are limited. To investigate whether patients with hematologic diseases undergoing therapy are at increased risk for acquiring SARS CoV-2 infection compared to the general population, a retrospective study was carried out at a referral hematologic center in Rome, Italy, during the period of the greatest epidemic spread (March 8 to May 14, 2020)., Methods: All adult and pediatric patients with a diagnosis of a neoplastic or a nonneoplastic hematologic disease who underwent treatment (chemotherapy or immunosuppressive or supportive therapy) during the study period or in the previous 6 months were considered. The prevalence of COVID-19 in the overall outpatient and inpatient population undergoing hematologic treatment compared to that of the general population was analyzed. The measures taken to manage patients during the epidemic period are described., Results: Overall, 2,513 patients with hematological diseases were considered. Out of 243 (9.7%) patients who were screened for SARS CoV-2, three of 119 (2.5%) outpatients with fever or respiratory symptoms and none of 124 asymptomatic patients were diagnosed with COVID-19. Three further patients were diagnosed with COVID-19 and managed in other hospitals in Rome. As of May 14, 2020, the prevalence of COVID-19 in our hematologic population accounted for 0.24% (95% CI 0.23-0.25; 6 of 2,513 patients: 1 case in every 419 patients) as compared to 0.12% (7,280 of 5,879,082 residents; 1 case in every 807 residents) in the general population (p = 0.14). Three of 6 patients diagnosed with COVID-19 required critical care and 2 died while still positive for SARS CoV-2. Out of 225 healthcare providers on duty at our Institution during the study period, 2 (0.9%) symptomatic cases were diagnosed with COVID-19., Conclusion: In our experience, the prevalence of COVID-19 in hematologic patients, mainly affected by malignancies, was not significantly higher compared to that of the general population. Definition of adapted strategies for healthcare services, while continuing to administer the standard hematologic treatments, represents the crucial challenge for the management of hematologic diseases in the COVID-19 era., (© 2020 S. Karger AG, Basel.)

Background: Recent evidence proved the necessity to improve health care and pain management in newborns. Osteopathic manipulative treatment (OMT) has been largely used to treat painful syndromes as well as term and preterm newborns. Recent studies have demonstrated positive results of osteopathy in reducing length of stay and costs. However, no trials were carried out on pain in newborns. The aim of the present clinical trial is to explore the effectiveness of osteopathic treatment in reducing pain in a sample of preterms., Methods/design: A three-armed single blinded placebo-control randomised controlled trial protocol has been designed to primarily evaluate the extent to which OMT is effective in reducing pain in preterms. One hundred and twenty newborns will be enrolled from one tertiary neonatal intensive care unit in central Italy and randomised in three groups: study, sham and control. The study group will be further prospectively randomised in two subgroups: experienced osteopaths and students. All preterms will receive standard medical care. Osteopathic treatment will be applied to the study group only whilst 'soft touch' will be administer to the sham group only. Newborns will undergo manual sessions once a week for the entire period of hospitalisation. Blinding will be assured for neonatal staff and outcome assessor. Primary outcome will be the mean difference in baseline score changes of PIPP questionnaire between discharge and entry among the three groups. Secondary outcomes will be: mean difference in length of stay and costs between groups. Statistical analyses will use per-protocol analysis method. Missing data will be handled using last observation carried forward imputation technique., Discussion: The present single blinded randomised controlled trial has been designed to explore potential advantages of OMT in the management of newborns' pain. Currently, based on a patient-centred need-based approach, this research will be looking at the benefit of osteopathic care rather than the efficacy of a specific technique or a pre-determined protocol., Trial Registration: The protocol has been registered on ClinicalTrials.gov ( NCT02146677 ) on 20 May 2014.

Background: Placebo effect has been largely studied and debated in medicine. Research focused mainly on children and adults but not on newborns. In osteopathy, few studies documented this effect and no research has been conducted in newborns., Objectives: To assess the presence of placebo effect in newborns using sham osteopathic manipulative treatment., Design: Randomized control trial., Setting: Neonatal Intensive Care Unit in Italy., Interventions: Two groups (103 patients each) of preterm infants aged 29-36 weeks without medical complications received routine pediatric care and osteopathic sham therapy was administrated to the study group only for the entire period of hospitalization., Main Outcome Measures: Primary end point was the mean reduction of length of stay at discharge. Secondary objective was the change in daily weight gain., Results: 206 newborns entered the study. No difference between sham and control group was found for the primary outcome length of stay (30.0±20.3; 28.8±18.9; p=0.70). Multivariate analysis showed no difference between study and control group on length of stay. A negative association was found for gestational age (-2.33; 95% CI -3.81 to -0.85; p=0.002), birth weight (-0.01; 95% CI -0.02 to -0.01; p<0.001) and milk volume at study enrollment (-0.02; 95% CI -0.05 to -0.01; p=0.01)., Conclusions: To the best of our knowledge, this study is the first in the field showing no placebo effect on newborns. Further discussions are opened concerning the age when placebo effect starts., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: Pneumonectomy with en bloc chest wall resection is often denied because of the procedure-related high risk. We evaluated the short- and long-term outcome of this procedure., Methods: From January 1995 to October 2011, 34 patients (30 males and 4 females; mean age: 61.8 years) underwent pneumonectomy with en bloc chest wall resection for 33 non-small-cell lung cancer and 1 metastatic osteosarcoma in two institutions. Data were retrospectively reviewed., Results: Operative (30-day) mortality was 2.9% (1 of 34), and morbidity was 38.2% (13 of 34). There were 14 (41.1%) right-side procedures and 20 (58.8%) left-side procedures. Three (8.8%) patients developed bronchopleural fistulas. The mean number of resected ribs per patient was 2.7 ± 1.1. In 13 (38.2%) patients, a prosthetic reconstruction of the chest wall was needed. In 3 (8.8%) cases, the bronchial step was buttressed. Preoperative pain was statistically significantly related to the depth of chest wall invasion (P = 0.026). The N status was N0 in 18 (52.9%) cases, N1 in 9 (26.4%), N2 in 6 (17.6%) and Nx in 1 (metastatic osteosarcoma). Patients were followed-up for a total of 979 months. The median survival was 40 months. The overall 5-year survival was 46.8% (± 95% confidence interval [CI]: 0.2-0.6): 45.2 (± 95% CI: 0.03-0.8) for right-side and 48.4% (± 95% CI: 0.2-0.7) for left-side procedures, respectively. According to the N status, the 5-year survival was 59.7 (± 95% CI: 0.3-0.8) in N0, 55.5 (± 95% CI: 0.06-1) in N1 and 16.6% (± 95% CI: 0-0.4) in N2. The subgroup N0 plus N1 (27 patients) showed a 58.08% (± 95% CI: 0.3-0.8) 5-year survival compared with 16.6% (± 95% CI: 0-0.4) in N2 (χ(2): 3.7; P = 0.053)., Conclusions: Pneumonectomy with en bloc chest wall reconstruction can be safely offered to selected patients. The addition of en bloc chest wall resection to pneumonectomy does not affect operative mortality and morbidity compared with standard pneumonectomy. The pivotal additional effect of the chest wall resection should not be considered a contraindication for such procedures. Survival showed a clinically relevant difference by comparing N0 plus N1 with N2 (58.1 vs 16.6%), not confirmed by the statistical analysis (P = 0.053).

Purpose: The aim of this study is to evaluate whether periodontopathogens are transmitted from husband to wife or vice versa., Materials and Methods: We tested the microbiological profile of 9 couples married for at least 10 years suffering from periodontitis. The microbiological analysis provides the quantification by Real-Time PCR of six main periodontopathogens, including P. gingivalis, T. denticola, T. forsythia, F. nucleatum ssp. polymorphum, P. intermedia, A. actinomycetemcomitans and genotype of P. gingivalis FimA in 90 subgingival plaque samples., Results: The microbiological profiles highlighted a quite similar composition of oral microbial flora among husband and wife. Statistical results revealed a very high Pearson correlation values for the microbiological profiles in all 9 spouses. Additionally, five couples out of nine showed statistically similar values for the microbiological profile as determined by the Wilcoxon rank Sign test. We provided also a strong validation for the horizontal transmission of oral pathogens in the detection of the same genotype of P. gingivalis FimA in the spouses., Conclusions: The presence of periodontitis in one member of the couple is a strong indicator of risk for the colonization of the spouse by periodontophatic bacteria. This study confirms that periodontal disease can be transmitted suggesting the importance of an early detection of oral pathogens in familial pattern of periodontitis to clarify the source of infection in order to assess correct prevention protocols based on potential infectivity within spouses.

Young patients (aged 18-60 years) with good-prognosis diffuse large B-cell lymphoma (DLBCL) [0 and 1 risk factor according to age-adjusted international prognostic index (aa-IPI)] are distinguished from patients with poor-prognosis. Six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) in combination with rituximab achieved best results in young patients with low-risk DLBCL. We retrospectively analyzed the data of 82 patients (18-60 years) with untreated aa-IPI 0-1 DLBCL, from six Italian institutions, who underwent, between January 2002 and January 2007, rituximab-cyclophosphamide, doxorubicin, vincristine, methotrexate, bleomicin and prednisone (R-MACOP-B) therapy followed, in patients with bulky presentation, by 30-36 Gy involved-field radiation therapy (34 patients). An overall response rate was noted in 77 out of 82 (94%) patients (75 patients had a complete response (91%), 2 patients had a partial response). With a median follow-up of 46 months, 7-year progression-free and overall survival were estimated to be 91% and 94%, respectively. R-MACOP-B regimen followed by involved-field radiation on bulky presentation is safe and very effective in the treatment of young patients with low-risk DLBCL.

Purpose: To report the clinical findings and long-term results of front-line, third-generation MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin) chemotherapy and mediastinal involved-field radiotherapy (IFRT) in 85 consecutive, previously untreated patients with primary mediastinal large B cell lymphoma (PMLBCL) diagnosed and managed at a single institution., Methods and Materials: Between 1991 and April 2004, 92 consecutive, untreated patients with PMLBCL were treated at our institution. The median age was 33 years (range, 15-61 years), 46 patients (50%) showed a mediastinal syndrome at onset; 52 patients (57%) showed a low/low-intermediate (0 to 1) and 40 patients (43%) an intermediate-high/high (2 to 3) International Prognostic Index (IPI) score. Eighty-five patients were treated with standard chemotherapy (MACOP-B), and 80 underwent mediastinal IFRT at a dose of 30-36 Gy., Results: After a MACOP-B regimen, the overall response rate was 87% and the partial response rate 9%. After chemotherapy, (67)Ga scintigraphy/positron emission tomography results were positive in 43 of 52 patients (83%), whereas after IFRT 11 of 52 patients (21%) remained positive (p < 0.0001). After a median follow-up of 81 months (range, 2-196 months), progression or relapse was observed in 15 of 84 patients (18%). The projected 5-year overall survival and progression-free survival rates were 87% and 81%, respectively. The 5-year overall survival and progression-free survival rates were better for patients with an IPI of 0 to 1 than for those with an IPI of 2 to 3 (96% vs. 73% [p = 0.002] and 90% vs. 67% [p = 0.007], respectively)., Conclusions: Combined-modality treatment with intensive chemotherapy plus mediastinal IFRT induces high response and lymphoma-free survival rates. Involved-field RT plays an important role in inducing negative results on (67)Ga scintigraphy/positron emission tomography in patients responsive to chemotherapy.

Extranodal non-Hodgkin's lymphomas constitute 20-25% of overall non-Hodgkin's lymphomas cases and can be managed with very different therapeutic strategies. Therefore, the Italian Society of Hematology and the two affiliate societies (the Italian Society of Experimental Hematology and the Italian Group of Bone Marrow Transplantation) appointed a panel of experts to produce clinical practice-guidelines for the management of these conditions. Primary lung and mediastinal lymphomas were the objective of this part of the project. The panel of experts produced the following key recommendations that were graded according to the strength of evidence and clinical judgement. The first-line therapy for non-MALT primary lung non-Hodgkin's lymphomas should include anthracycline-based chemotherapy with CHOP or CHOP-like, MACOP-B or MACOP-B-like regimens (grade D). Rituximab association with chemotherapy needs to be evaluated within approved clinical trials. Second-line therapy with high-dose chemotherapy and autologous stem cell transplantation is recommended (grade B). In patients with MALT primary lung non-Hodgkin's lymphomas, the recommended first-line therapy should include chlorambucil, CHOP, CHOP-like or fludarabine-containing regimens (grade B). Radiotherapy is to be reserved for patients with a unique, small lesion in a poorly mobile site and with contraindication to surgery (grade D). Rituximab should be administered only within approved clinical trials. For treatment of primary mediastinal large B-cell lymphomas, the recommended first-line therapy is a chemotherapy and radiotherapy association (grade B). An anthracycline-based chemotherapy with CHOP, MACOP-B or VACOP-B is recommended (grade B). Rituximab combination with chemotherapy is highly suggested but only for patients enrolled into approved clinical trials. Patients with an inadequate early response should be candidates for early intensification with high-dose chemotherapy (grade C). Patients with refractory or relapsed disease should undergo rescue programs including intensive, non-cross-resistant debulking treatment followed, in chemosensitive patients, by high-dose chemotherapy and autologous stem cell transplantation (grade B).

Spontaneous pneumothorax, in both the primary and secondary variants, is a relatively frequent disease, occurring at all ages. Management of spontaneous pneumothorax is not standardised. Furthermore, few attempts have been made in the literature to codify the diagnostic workup and treatment. The aim of the present study is to report the results of a nationwide fact-finding survey, focused on current practice in the management of spontaneous pneumothorax by thoracic surgeons. A questionnaire, consisting of items in 6 major areas, was prepared and e-mailed to 49 thoracic surgery units in Italy. Thirty-five centres responded. The results (collected in a database presented at the XXX Congress of the Italian Society of Thoracic Surgeons in October 2006) show agreement on some questions (surgical indications, thoracoscopy as the first-choice surgical technique, use of mechanical staplers...) and a great variability of ideas and attitudes on others (CT scanning in primary spontaneous pneumothorax, definition of persistent air-leak, clamping of the chest tube before removal, pleurodesis techniques, postoperative chest X-ray schedule...). It is the authors' opinion that further work is needed in order to achieve a greater measure of agreement in the management of primary and secondary pneumothorax.

The Italian Society of Hematology (SIE) and two affiliate societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of nodal diffuse large B-cell non Hodgkin lymphomas (DLBCL). Key questions clinically relevant to the management of patients with nodal DLBCL were formulated by an Advisory Committee (AC) and approved by an Expert Panel (EP) composed of eight senior hematologists. After a comprehensive and systematic literature review, the EP formulated therapy recommendations and graded them according to the supporting evidence. An explicit approach to consensus methodologies was used for evidence interpretation and for producing recommendations in the absence of strong evidence. The EP formulated recommendations on which first-line therapy to choose in patients with nodal DLBCL. Patients of all ages, with stage I-II disease and no adverse prognostic factors should receive abbreviated chemotherapy with an anthracycline-containing regimen plus involved field radiotherapy (35-40 Gy). Patients with stage I-II disease and at least one adverse prognostic factor, or with stage III-IV disease, should receive frontline chemoimmunotherapy with CHOP, CHOP-like or third-generation chemotherapy plus rituximab. Recommendations on stem cell transplantation and on which therapy to adopt for refractory or relapsed patients were also formulated.

Serum interleukin-6 (sIL6) is an acknowledged predictor of all-cause mortality in older age. A common G/C polymorphism has been identified at position -174 of the IL6 gene promoter (IL6-174G>C), but its associations with sIL6 and mortality are still unclear. Data from a population-based elderly cohort (n=824) were used to study the associations of baseline sIL6 with the IL6-174 C-allele (C+) carrier status and all-cause mortality at 4 years, in the presence and absence of preexisting major diseases (PMD). Analyses were adjusted for socio-demographic factors and body-mass-index. Three-hundred-eighty-eight participants (47.1%) had PMD. Compared to the bottom sIL6 quartile, mortality increased both in presence [Hazard Ratio (HR)=3.04; 95% confidence interval (CI): 1.48-6.25] and absence of PMD [HR=3.91; 95%CI: 1.42-10.72] for the third higher sIL6 quartile, but only in presence of PMD for the top sIL6 quartile [HR=2.30; 95%CI: 1.09-4.83]. In absence of PMD, C+ carrier status did not affect both sIL6 and mortality. In presence of PMD, C+ carrier status was associated with increased baseline sIL6 [odds ratio 2.01; 95%CI: 1.25-3.22, for all sIL6 quartiles above the bottom] but not with increased mortality risk. A survival advantage was even found for C+ carriers with PMD and sIL6 in the top quartile [HR=0.31, 95%CI: 0.13-0.76]. In conclusion, although associated with increased sIL6 levels in presence of major diseases, the IL6-174 C-allele does not seem to have direct detrimental effects on survival in older age.

Background: Recent prospective studies reported that increased plasma homocysteine levels are an independent predictor of osteoporotic fracture in elderly persons. These studies, however, did not take into account folate and vitamin B12, which are the major nutritional determinants of homocysteinemia., Methods: Incident osteoporotic fractures were assessed in 702 Italian participants aged 65-94 years with a mean follow-up of 4 years (1999/2000-2003/2004). A multivariable logistic regression model was used to study the relation of baseline plasma homocysteine, serum folate, and serum vitamin B12 with risk of fracture., Results: After adjustment for sociodemographic and clinical confounders, the odds ratio (OR) for each increase of 1 standard deviation in log-transformed plasma homocysteine was 1.39 (95% confidence interval [CI], 1.01-1.91), but decreased to 1.22 (95% CI, 0.85-1.74) after further adjustment for serum folate and vitamin B12. The corresponding multivariable-adjusted OR for hyperhomocysteinemia (plasma total homocysteine [tHcy] > 15 micromoL) was 1.58 (95% CI, 0.71-3.53). Participants in the lowest serum folate quartile (< or =9.3 nmol/L) had an increased risk of fracture than did those in higher quartiles (multivariable-adjusted OR = 2.06; 95% CI. 1.02-4.18), but no dose-related protective effect for increasing serum folate levels was found (multivariable-adjusted OR = 0.84 for each increase of 1 standard deviation in log-transformed serum folate, 95% CI, 0.59-1.19). No independent association was found for serum vitamin B12., Conclusions: Low serum folate is responsible for the association between homocysteine and risk of osteoporotic fracture in elderly persons.

Background: In cross-sectional studies, elevated plasma total homocysteine (tHcy) concentrations have been associated with cognitive impairment and dementia. Incidence studies of this issue are few and have produced conflicting results., Objective: We investigated the relation between high plasma tHcy concentrations and risk of dementia and Alzheimer disease (AD) in an elderly population., Design: A dementia-free cohort of 816 subjects (434 women and 382 men; mean age: 74 y) from an Italian population-based study constituted our study sample. The relation of baseline plasma tHcy to the risk of newly diagnosed dementia and AD on follow-up was examined. A proportional hazards regression model was used to adjust for age, sex, education, apolipoprotein E genotype, vascular risk factors, and serum concentrations of folate and vitamin B-12., Results: Over an average follow-up of 4 y, dementia developed in 112 subjects, including 70 who received a diagnosis of AD. In the subjects with hyperhomocysteinemia (plasma tHcy > 15 micromol/L), the hazard ratio for dementia was 2.08 (95% CI: 1.31, 3.30; P = 0.002). The corresponding hazard ratio for AD was 2.11 (95% CI: 1.19, 3.76; P = 0.011). Independently of hyperhomocysteinemia and other confounders, low folate concentrations (< or = 11.8 nmol/L) were also associated with an increased risk of both dementia (1.87; 95% CI: 1.21, 2.89; P = 0.005) and AD (1.98; 95% CI: 1.15, 3.40; P = 0.014), whereas the association was not significant for vitamin B-12., Conclusions: Elevated plasma tHcy concentrations and low serum folate concentrations are independent predictors of the development of dementia and AD.

The Italian Society of Hematology (SIE) and the two affiliated societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of nodal indolent non-Hodgkin's lymphomas (NHL). Key questions clinically relevant to the management of patients with nodal indolent NHL were formulated by an Advisory Committee and approved by an Expert Panel composed of eight senior hematologists. After a comprehensive, systematic review of the literature, the Expert Panel formulated therapy recommendations and graded them according to the supporting evidence. An explicit approach to consensus methodologies was used for evidence interpretation and for providing recommendations based on poor evidence. The Expert Panel formulated recommendations on when to start a lymphoma-specific therapy, which first-line therapy to choose and which therapy to adopt for patients with relapsed, refractory and transformed disease. Treatment deferral was recommended for patients with stage III-IV disease without systemic symptoms, high tumor burden, extranodal disease, cytopenia due to marrow involvement, leukemic phase, serous effusion and high lactate dehydrogenase levels. Patients with stage I-II disease and a low tumor burden should receive frontline external involved-field radiotherapy, while patients with a high tumor burden or a severe prognostic score should receive front-line chemotherapy plus involved-field radiotherapy. Younger patients with stage III-IV disease should receive front-line therapy with anthracycline- or fludarabine-based regimens combined with rituximab, while older patients who are candidates for treatment should receive single-agent alkylating therapy. By using a systematic literature review and an explicit approach to consensus among experts, recommendations for the key therapeutic decisions in patients with nodal indolent NHL are provided.

Background: Chronic low-grade inflammation, as measured with the peripheral serum marker C-reactive protein (sCRP), may be a risk factor for dementia in elderly persons., Methods: The relationship between sCRP and score on the Mini-Mental State Examination (MMSE), a commonly used screening cognitive measure, was investigated in 540 well functioning, healthy, and cognitively normal elders (age 73 +/- 6 years). Sociodemographic status, lifestyle, health status, traditional and nontraditional cardiovascular risk factors including plasma total homocysteine (tHcy), and other peripheral blood markers of vascular inflammation (leukocyte count, serum albumin, and plasma fibrinogen) were also assessed., Results: Risk for having sCRP in the highest decile (>0.7 mg/dl) was significantly higher in individuals with MMSE score 24-25 (odds ratio = 3.07, 95% confidence interval, 1.2-7.9) and 26-28 (odds ratio = 2.10, 95% confidence interval, 1.1-3.9) compared with those scoring above 28 (reference group). Results were unaffected by adjustment for all potential confounders. No association was found between MMSE and peripheral markers of vascular inflammation other than sCRP, but lower MMSE scores were also independently associated with hyperhomocysteinemia (plasma tHcy > 15 mmol/L)., Conclusion: In healthy, cognitively normal elderly community dwellers, increased sCRP levels are associated with concurrent cognitive impairment as measured by MMSE. The association is independent of sociodemographic status, lifestyle, health status, and traditional and nontraditional cardiovascular risk factors including hyperhomocysteinemia. Results support the hypothesis that chronic low-grade inflammation may be involved in age-related cognitive impairment.

Objective: To estimate age- and sex-specific incidence of dementia, Alzheimer disease (AD), and vascular dementia (VaD) in the Conselice Study of Brain Aging, an Italian prospective population-based study, and to assess whether poor education is a risk factor for dementia., Methods: In 1999 to 2000, the baseline study identified a dementia-free cohort of 937 subjects aged 65 years and older who were reexamined in 2003 to 2004 using a two-phase procedure., Results: Information was obtained for 91% of the subjects at risk; 115 incident cases of dementia were identified. Incidence rates per 1,000 person-years were 37.8 (95% CI = 30.0 to 47.7) for dementia, 23.8 (95% CI = 17.3 to 31.7) for AD, and 11.0 (95% CI = 7.2 to 16.9) for VaD. This translates into more than 400,000 new cases of dementia expected per year in Italy. Increasing age was an independent risk factor for both AD and VaD. Poor education was an independent risk factor for AD but not VaD. Sex did not affect dementia risk., Conclusions: In this Italian population-based cohort, incidence of dementia increased with age, and Alzheimer disease (AD) was the most frequent type of dementia. Poor education was associated with a higher risk of AD. Our incidence rates are higher than previously reported in Italy, and provide new estimates for projection of future burden of disease in Italy.

Vocal reaction times (RTs) in naming 3- to 8-letter words were measured in proficient and dyslexic readers (Study 1). In proficient readers, RTs were independent of word length up to 5-letter words, indicating parallel processing. In the 5- to 8-letter range, RTs increased linearly, indicating sequential processing. Reading experience was associated with both faster discrimination of individual elements and parallel processing of increasingly large word parts. In dyslexics, RTs increased linearly with increasing length indicating reliance on sequential decoding. Individual analysis indicated 2 profiles of RTs (Types A and B). In Study 2, the distinction between A and B dyslexics was not associated with the use of different reading procedures. However, a more marked speed deficit characterized Type B dyslexics.

In order to elucidate the role of anthracycline based combination chemotherapy regimens for the treatment of follicular lymphoma we conducted a retrospective study on a large series of patients with a histologically confirmed diagnosis of follicular lymphoma. The Italian lymphoma intergroup (ILI) promoted a retrospective study of patients with follicular lymphoma treated in cooperative trials between 1985 and 1996. Six hundred and thirty three cases were treated with an anthracycline-containing regimen and 128 patients were treated without anthracyclines. The two groups were prognostically comparable; in particular, no difference was observed according to both IPI and ILI prognostic index. Results showed a complete remission (CR) rate for patients treated with anthracyclines was 69.2% and overall response rate was 92.5%. After a median follow-up of 51 months (54 months for patients still alive), the 5- and 10-year overall survival (OS) rates were 80 and 66%, respectively. Disease-free survival (DFS) and failure-free survival (FFS) rates at 5 years were 61 and 49%, respectively. In the group of patients treated with combination chemotherapy not including anthracyclines, the CR rate was 67.5% and the overall response rate was 85.4%. A longer OS (80% at 5 years) was observed in patients treated with anthracyclines compared to 67% OS rate in patients treated without anthracyclines (p = 0.0004). FFS was significantly longer in patients treated with anthracyclines (49 vs. 34% p = 0.006). Patients treated with anthracyclines with low or intermediate risk according to ILI prognostic index showed a significantly longer OS (p = 0.0001 andp = 0.0009, respectively); those in the high-risk group showed a trend for a longer survival. In conclusion, this retrospective study shows that patients with follicular lymphoma treated with an anthracycline containing regimen had a better outcome compared to patients treated with other combination regimens non including anthracyclines in terms of CRs, OS and FFS. On the basis of these results anthracycline-containing regimens (ACR) should be considered as the standard treatment of patients with advanced follicular lymphoma.

Background: Surgery is the primary treatment for patients with stage I, II, or IIIA non-small-cell lung cancer (NSCLC). However, long-term survival of NSCLC patients after surgery alone is largely unsatisfactory, and the role of adjuvant chemotherapy in patient survival has not yet been established., Methods: Between January 1994 and January 1999, 1209 patients with stage I, II, or IIIA NSCLC were randomly assigned to receive mitomycin C (8 mg/m2 on day 1), vindesine (3 mg/m2 on days 1 and 8), and cisplatin (100 mg/m2 on day 1) every 3 weeks for three cycles (MVP group; n = 606) or no treatment (control group; n = 603) after complete resection. Randomization was stratified by investigational center, tumor size, lymph-node involvement, and the intention to perform radiotherapy. The primary endpoint was overall survival and secondary endpoints were progression-free survival and toxicity associated with adjuvant treatment. Survival curves were analyzed using the log-rank test. All statistical tests were two-sided., Results: After a median follow-up time of 64.5 months, there was no statistically significant difference between the two patient groups in overall survival (hazard ratio = 0.96, 95% confidence interval = 0.81 to 1.13; P =.589) or progression-free survival (hazard ratio = 0.89, 95% confidence interval = 0.76 to 1.03; P =.128). Only 69% of patients received the three planned cycles of MVP. Grades 3 and 4 neutropenia occurred in 16% and 12%, respectively, of patients in the MVP arm. Radiotherapy was completed by 65% of patients in the MVP arm and by 82% of patients in the control group. In the multivariable analysis, only disease stage and sex were associated with survival., Conclusion: This randomized trial failed to prospectively confirm a statistically significant role for adjuvant chemotherapy in completely resected NSCLC. Given the poor compliance with the MVP regimen used in this study, future studies should explore more effective treatments.

Single-center experiences have shown that intensified treatments with autologous transplantation are a promising therapeutic strategy for patients with high-risk follicle-center lymphoma (FCL) at diagnosis, whereas data from prospective multicenter trials are still lacking. This paper describes the results of a prospective multicenter study of an intensified purging-free high-dose sequential (i-HDS) chemotherapy schedule with peripheral blood progenitor cell (PBPC) autografting. The main feature of this program is harvesting stem cells after intensified chemotherapeutic debulking, with no ex vivo manipulation of PBPCs. Ninety-two previously untreated patients aged 60 or younger with advanced-stage FCL were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis. i-HDS proved feasible with limited toxicity (87% patients completed the planned treatment schedule). i-HDS led to a complete remission rate of 88%. The projected overall survival and disease-free survival (DFS) were, respectively, 84% and 67% at 4 years. Centralized molecular analysis showed that polymerase chain reaction-negative harvests could be collected in 47% of cases. Following autograft, 65% of molecularly evaluable patients achieved clinical and molecular remission. The projected DFS at 4 years of this subgroup is 85%. This result emphasizes the importance of achieving maximal tumor reduction in these patients. In conclusion, our data show that highly effective intensified treatments can now be routinely offered to young patients with poor-risk FCL even at small institutions, with no need for sophisticated and expensive cell manipulation procedures.

Background and Objectives: Our aim was to identify risk factors in adults with diffuse large cell lymphoma at first relapse., Design and Methods: We studied 474 patients observed at 45 centers in Italy. Median time from diagnosis to relapse was 395 days, median age at relapse was 55 years and median follow-up from relapse was 3.3 years. Salvage therapy consisted of polychemotherapy in 79% of patients, monochemotherapy and/or radiotherapy and/or surgery alone in 16%, and palliative therapy in 5%. Salvage treatment was intensified with high-dose chemotherapy + stem cell transplant in 20% of patients. OS and PFS were compared by sex, International Prognostic Index at diagnosis, histology, B/T phenotype, initial treatment, salvage therapy, and features at relapse: time from diagnosis, LDH, stage, performance status and bone marrow involvement. Cox models, adjusted for salvage therapy, were performed with factors related to overall survival (OS) and progression-free survival (PFS)., Results: Overall response (complete + partial) was 63%, OS at 3 years 35% and PFS at 3 years 26%. Relapse within 12 months from diagnosis, elevated serum lactic dehydrogenase (LDH), advanced stage and poor performance status were independent adverse factors for OS and PFS. The cumulative number of adverse factors is proposed as prognostic index for DLCL at first relapse since it identifies risk groups (p<0.0001) and has been validated (p=0.01). Moreover, it predicts OS and PFS in the selected group of patients with a responsive relapse (p<0.0001)., Interpretation and Conclusion: Delay from initial diagnosis, LDH, stage and performance status at relapse should be balanced in comparative studies of salvage therapy of adults with DLCL. Patients with more than 2 adverse factors are one third of all cases and deserve more effective salvage treatments.

Background and Objective: The outcome of patients with multiple myeloma (MM) has not changed markedly since the introduction of melphalan and prednisone. In recent years several studies have investigated the role of intensive therapy followed by infusion of autologous peripheral blood stem cells (PBSC) together with the administration of hematopoietic growth factors. In this study we evaluated the feasibility and efficacy of a PBSC transplantation program for patients with de novo MM in a multicenter setting., Design and Methods: In a non-randomized controlled trial 52 patients with de novo MM from 6 Italian centers underwent a three phase treatment strategy including 3 cycles of VAD-like chemotherapy for initial debulking, followed by high-dose cyclophosphamide (HD-CY) and collection of PBSC, that were transplanted after a conditioning regimen with melphalan plus busulfan. Maintenance treatment was a conventional dose of interferon, given until relapse. Actuarial survival and response duration curves were plotted according to Kaplan and Meier's method; the groups were compared using the log rank test. Response rates were compared by the c(2) test; multivariate analysis was performed according to the stepwise regression model., Results: Overall 39/52 (75%) of patients responded, with a complete remission (CR) rate of 31%. After a median follow-up of 55 months, median duration of event-free survival (EFS) and overall survival (OS) are 21 and 57 months, with 24% and 48% probabilities of being event-free and alive after 6 years, respectively. Among the group of 39 responders, CR was significantly associated with prolonged response and survival (2 deaths and 6 relapses/16 patients) as compared with PR (11 deaths and 15 relapses/23 patients), and remained the only significant variable also in a multivariate analysis. Myelosuppression did not protract beyond one week in transplanted patients; extra-hematologic toxicity was very low., Interpretation and Conclusions: This multicenter study confirms the feasibility of an aggressive approach to de novo MM patients. Additional confirmation is given of the increased rate of CR, and the significant prolonged survival observed in complete responders. In this experience the association melphalan plus busulfan was shown to be effective, at least as part of conditioning regimens, in the transplant strategy.

143 patients with non-Hodgkin lymphoma (NHL) at the onset entered this perspective study on NHL-associated risk factors. They were 87 males and 56 females with a mean age of 52.3 years (range 14.6-82.3). An associated hepatitis C virus (HCV) infection was found in 16 of the 143 NHL cases (11.2%; 95% CI 6.5-17.5). They were 11 males and 5 females [mean age 59.9] year with disseminated (13/16) or localized NHL disease (3/16)]. The NHL histological subgroup was low grade (6/16), intermediate grade (2/16) or high grade (8/16). The cell origin was B in 15/16 cases and B cell-T cell rich in 1/16. The discovery of HCV infection was contemporary to lymphoma diagnosis in 6/16 cases but preceded the NHL onset in the other 10 patients. In these 10 patients the median time between HCV infection diagnosis and NHL onset was 3.6 years (range 1-14.5). These data confirm that in Italy the prevalence of HCV infection in patients with NHL (11.2%) is significantly higher than expected in the general population (1.3-3.2%). The finding that, in most cases, HCV infection was definitely antecedent to NHL onset, usually by years, adds evidence to the possible causative role of the HCV in lymphomagenesis.

The authors examine 162 cervico-vaginal smears of women in peri-menopause presenting cellular alterations (ASCUS). These patients were treated with a local topic therapy as the persistence of these alterations in 23 cases (14.2%) second level analyses were performed: gynecological visit, colposcopy and biopsy. In addition to inflammatory aspects 2 in situ carcinomas and 2 moderate dysplasias were recorded. We believe therefore that cytology could be a valid aid also in pre-menopausal women in the cervico-vaginal pathology.

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities. Two hundred-eighty-six patients included between 15 and 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucositis among patients treated with MACHOP-B than among those given F-MACHOP (11% vs 3.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Interstitial pneumonia is one of the major causes of morbidity and mortality after bone-marrow transplantation. We here report a series of 58 patients suffering from hematological malignancies who received HLA-matched T-lymphocyte depleted bone-marrow transplants between July 1985 and January 1990. Interstitial pneumonia occurred in 7/58 patients (12%) and was fatal in six. Three different pre-bone-marrow transplantation conditioning regimens were employed. Total body irradiation was delivered according to a hyperfractionated scheme of 12 fractions given three per day 5 hr apart for 4 days. Twenty-three patients received 36 mg/Kg procarbazine, 1275 UL/Kg antithymocite globulin, 14.4 Gy hyperfractionated total body irradiation and 120 mg/Kg cyclophosphamide. Only one patient developed interstitial pneumonia, but two rejected the graft and 10 relapsed. As a consequence, the total hyperfractionated scheme was increased to 15,6 Gy, cyclophosphamide to 200 mg/Kg, antithymocite globulin to 3400 UL/Kg and procarbazine eliminated. There were three cases of interstitial pneumonia, no rejection and four relapses in the 17 patients who received this regimen. In the last 18 patients hyperfractionated total body irradiation was reduced to 15 Gy, cyclophosphamide to 100 mg/Kg, and 10 mg/Kg of the myeloablative agent thiothepa added to enhance the cytoreductive effect without significantly increasing extramedullary toxicity. Three cases of interstitial pneumonia, one relapse but no rejection were recorded. Our results demonstrate that the absence of graft-versus-host disease due to T-cell depletion, and radio-chemotherapy doses and schedules used for the conditioning regimen each contributed to reducing the risk of interstitial pneumonitis. Hyperfractionated total body irradiation therefore, seems to play an important role in lowering the incidence of this complication.

The results obtained by antibodies titration in 1500 subjects, in connection with Toxoplasma infection, are discussed. The determinant influence of some factors is statistically evaluated and recent Italian and foreign results are considered, according to the epidemiology of Toxoplasmosis.