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High-dose interleukin-2 (HD IL-2) has curative potential in metastatic melanoma (MM) and renal cell carcinoma (RCC). Radiotherapy (RT) kills cancer cells and induces immunomodulatory effects. Prospective trials exploring clinical and immunological properties of combined RT/HD IL-2 are still needed. We designed a phase II, single-arm clinical trial for patients with MM and RCC. The treatment schedule consisted of 3 daily doses of 6-12 Gy of RT to 1-5 non-index metastatic fields, before IL-2 at the first and third treatment cycle. HD IL-2 was administered by continuous infusion for 72 hours and repeated every 3 weeks for up to 4 cycles, thereafter every 4 weeks for a maximum of 2 cycles. The primary endpoint was the immunological efficacy of the combined RT/HD IL-2 treatment (assessed by IFN-γ ELISPOT). Nineteen out of 22 patients were evaluable for immunological and clinical response. Partial response occurred in 3 (15.7%) patients and stable disease was observed in 7 (36.8%). The disease control rate was 52.6% after a median follow up of 39.2 months. According to Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0), the majority of toxicities were grade 1-2. Immunological responses were frequent and detected in 16 (84.2%) patients. Increased levels of IL-8 and IL-10 in melanoma, circulating effector memory CD4+ and intratumoral CD8+ T cells in both tumor types were detected after therapy. Overall the treatment was well tolerated and immunologically active. Immunomonitoring and correlative data on tumor and peripheral blood cell subsets suggest that this combination treatment could be a promising strategy for patients progressing after standard treatments., 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 © 2021 Bulgarelli, Piccinini, Petracci, Pancisi, Granato, de Rosa, Guidoboni, Petrini, Ancarani, Foschi, Romeo, Tontini, De Giorgi, Lolli, Gentili, Valmorri, Rossi, Ferroni, Casadei, Cortesi, Crudi and Ridolfi.)

Come si leggerà nell'Introduzione della sezione propriamente scientifica del Volume, il presente testo nasce dalla volontà e, soprattutto, dall'esigenza culturale di omaggiare il fu Prof. Antonio Fusco. Un debito scientifico ed umano che trova il suo locus naturale in questa prima parte del testo stesso, cui farà poi seguito la parte propriamente scientifica. In siffatta parentesi dovuta per le ragioni appena menzionate, il lettore, l'amico o l'allievo dell'opera del Prof. Fusco potranno trovare un suo sintetico Curriculum Vitae, correlato da una specifica ed accurata prosa, svolta dal già Magnifico Rettore Carlo Cipolli; il quale, oltre che evidenziare, ricordando, i meriti del collega oramai scomparso, aggiunge alsuo scritto un elemento che sarebbe imprescindibile a non trasformare lo stesso in una mera sequenza di parole: l'amicizia e l'affetto per un amico che, oramai, non c'è più. A fine lettura, evidente risuonerà il fatto che la vita di ognuno, se mossa dalla passione per ciò per cui si è predisposti cognitivamente e psicologicamente, può essere ricca di riconoscimenti, riconoscenze e soddisfazioni che, lungi dal divenire un cuscino di allori su cui adagiarsi, per una mente creativa come quella del Prof. Fusco hanno funto solo da motivazioni ad agire instancabilmente guardando sempre al futuro. Il lavoro di una vita che, materialmente, è sancito da un supporto poco più di cm 25x15: una targa. Una materialità evidente che, con grande commozione e riconoscenza, è stata affissa il 25 ottobre 2019 sull'aula fronte l'Aula Magna del Campus "La Folcara", a testimonianza che quello spirito creativo in continua evoluzione non si ferma; non si arresta neppure con la fine biologica di chi lo ha "posseduto". Rimangono le opere ed il pensiero del Prof. Fusco e restano gli affetti. A tal proposito, il lettore troverà una breve e sentita sezione su Testimonianze; coloro i quali hanno avuto modo, nell'arco della vita accademica ed umana, personale, di Fusco di conoscerlo. Ecco, allora, che i ricordi saranno i veri protagonisti di questa parentesi. Dopo di ciò, prima dei contributi prettamente scientifici dei lavori, tenutisi in occasione del Convegno Internazionale Psicologia, Arte, Letteratura. Antiche e Nuove Tendenze, seguiranno i saluti delle autorità che in quei due giorni si sono succedute a rappresentare non solo l'istituzione affiliata, ma anche la relazione di stima e di affetto che le legava al compianto Professore. Si passerà, infine, al volume tradizionalmente inteso.

Objective: The objective of this study was to compare the use of pulmonary regurgitation volume (PRV) or indexed PRV (PRVi) with that of pulmonary regurgitation fraction (PRF) in the assessment of patients with pulmonary regurgitation (PR) undergoing cardiac magnetic resonance (CMR) imaging., Materials and Methods: CMR of 176 patients with PR were retrospectively evaluated. Their right ventricular diastolic (end-diastolic volume index [EDVi]) and systolic (end-systolic volume index) volume indexes, stroke volume, and ejection fraction were obtained from cine CMR sequences, whereas phase-contrast flow sequences were analyzed to obtain PRV, PRVi, and PRF. Patients were divided into subgroups, according to underlying pathology and according to PR severity. Correlations between PRV or PRF and RV parameters were studied through Spearman ρ, both in the main group and subgroups. Follow-up examinations were analyzed, and correlations between PRV or PRF from the first CMR examination and volume data from the second were calculated., Results: Tetralogy of Fallot was the main setting of PR (98/179). Overall, EDVi strongly correlates with PRV (ρ=0.592, P<0.001) than with PRF (ρ=0.522, P<0.001), and end-systolic volume index strongly correlates with PRV (ρ=0.454, P<0.001) and PRF (ρ=0.406, P <0.001). As regards subgroup analysis, in moderate or severe PR patients, EDVi strongly correlates (P=0.043) with PRV (ρ=0.499, P<0.001) than with PRF (ρ=0.317, P<0.001). Follow-up EDVi correlates with PRV (ρ=0.450, P=0.031), but not with PRF., Conclusions: Especially when assessing moderate to severe PR, PRV and PRVi may be better indicators of right ventricular dysfunction than PRF. Moreover, PRV may be a predictor of worsening RV dilation.

Aim: The aim of this work was to evaluate the correlation between different methods (organoleptic evaluation, gas chromatography, salivary ?-galactosidases activity) for the evaluation of halitosis in children. The secondary purpose was to investigate the influence of orthodontic treatment on halitosis., Materials and Methods: Study Design: Oral malodour was detected with different methods in 50 children in the Paediatric Dentistry Unit, University of Rome Tor Vergata, Rome, Italy. During the dental visit, level of oral hygiene, tongue coating scores and presence of an orthodontic device, fixed or mobile, were recorded. Two trained and calibrated operators performed the organoleptic evaluation; the Oral ChromaTM device was used for the volatile sulfur compounds (VSCs) quantification and salivary ?-galactosidases (S?-g) activity was evaluated through the spectrophotometric method., Statistics: The Cohen's Kappa score was used to evaluate the level of agreement between the operators. The Pearson's correlation coefficient was used to evaluate the linear relationship between continuous variables (e.g. S?-g vs. VSCs values) and the Spearman's correlation coefficient was calculated for ordinal variables (e.g. organoleptic scores) vs. other parameters. The LSD test was used to compare the parameters analysed in the study., Results: A positive and significant correlation between the organoleptic evaluation, the S?-g, the levels of hydrogen sulfide (H2S) and methyl mercaptan (CH3SH) was found. The Spearman's correlation has shown that organoleptic scores were significantly correlated with S?-g (0.664, p<0.001) and the Oral ChromaTM measurements of H2S (0.538, p<0.001) and Ch3SH (0.316, p=0.026). The Pearson's correlation showed that S?-g was statistically significantly correlated with the Oral ChromaTM measurements of H2S (0.379 p=0.007) and Ch3SH (0.299, p=0.0035). Stratifying results for orthodontic treatment, it was possible to show that children under orthodontic treatment, both fixed or removable, were characterised by higher level of S?-g. The organoleptic evaluation and Oral ChromaTM measurements showed that children wearing fixed orthodontic were characterised by higher scores., Conclusions: There was a significant correlation between the three different techniques for the evaluation of oral malodour in children. Like in the adult population, the increase of S?-g activity was associated with oral malodour. The presence of fixed orthodontic appliances was correlated to increased scores of all methods for the evaluation of halitosis.

Informal caregivers are the unpaid persons who take care of a not self-sufficient family member, due to old age or chronic illness or disability. As in all the European countries, the demand for informal cares is further increased as a result of the ageing societies and the social and political fallout of informal caregiving is a very current and important issue. We have overviewed some international scientific literature, with the aim of understanding the key research objectives to be firstly pursued to address this problem. In particular, we focused on the psycho-physical health differences in informal caregivers, subjected to long lasting load and prolonged stress, as compared to non caregiver persons. We also underlined the relationship between caregiver health differences and stress, gender type, kind of the care recipient (autism) and social and political situation in Europe and Italy. The collected data indicate the necessity to prevent caregiver psychological and physical health by appropriate laws, especially supporting women, often most involved in care activities.

Aim: The aim of this work was to evaluate the oral health status in children and to correlate it with time spent in physical activity per week., Materials and Methods: Fifty children (mean age 9±2 years) attending the first visit at the Paediatric Dental Unit of the University of Rome "Tor Vergata" have been included in the study. The parents of all patients were interviewed about the medical history of the children and specific data, in particular, the time spent in physical activity per week. A trained dentist examined the oral cavity of the patients and the following clinical parameters were recorded: number of deciduous and permanent teeth, caries (on deciduous and permanent teeth), presence of gingivitis (0=no; 1=yes), tongue coating score (from 0=none to 3= > 2/3 tongue dorsum surface covered)", oral infections (0=no; 1=yes), oral hygiene index (0=insufficient, 1=sufficient, 2=good), presence of at least one incongruous restoration (0=no, 1=yes), oral breathing (0=no; 1=yes), fissured tongue (0=no, 1=yes), presence of aftous ulcers, herpetic lesions or candidiasis (0=no, 1=yes), food stagnation (0=no; 1=yes). The level of salivary ?-galactosidases activity was measured spectrophotometrically. The subjects were classified into "Group 0": children who did not practice any sports beside physical education class; "Group 2": 2 hours per week; "Group 3": 3 hours; and "Group 4": 4 hours., Statistics: Statistical analysis was performed using SPSS for Windows version 21 (IBM SPSS Inc., Chicago, IL, USA). The Pearson's correlation coefficient (P) was used to evaluate the linear relationship between continuous variables, and the Spearman's correlation coefficient (S) was calculated for ordinal variables. Analysis of variance (ANOVA) and the Fischer's Least Significant Difference (LSD) test were used to compare the parameters analysed in the study. Data were analysed using linear regression and descriptive statistics. The significance threshold was set at 0.05., Results: A more physically active lifestyle was significantly associated with a better oral hygiene and a reduced level of salivary ?-galactosidases, halitosis, gingivitis and tongue coating. Results of the organoleptic evaluation of halitosis performed by the parents and sport hours/week practiced have shown that Group 0 and 2 were characterised by statistically significant higher scores with respect to the other groups (Group 0 vs. Group 3, p=0.014; Group 2 vs. Group 3, p=0.030; Group 0 vs. Group 4, p=0.001; Group 2 vs. Group 4, p=0.002) (P= -0.458). The spectrophotometric quantification of salivary ?-galactosidases has shown that increasing the hours of sports, the enzyme activity significantly decreases (S= -0,330); similar levels were found with 0 and 2 hours of sports, but an important decrease has been recorded with both 3 (Group 0 vs. Group 3, p=0,011; Group 2 vs. Group 3, p=0,006) and 4 hours of sports practiced (Group 0 vs. Group 4, p=0,014; Group 2 vs. Group 4, p=0,008). The level of significance between children who did not practice sport and those who did for 3 and 4 hours a week was 0.005 (Group 0 vs. Group 3) and 0.0018 (Group 2 vs. Group 4) with respect to tongue coating scores (P= -0,511) and 0.012 for both groups with respect to gingivitis (Group 0 vs. Group 3; Group 0 vs. Group 4) (P=-0,427)., Conclusion: Children who practiced sport showed a better oral hygiene level and lower halitosis, with respect to those who did not.

Within the course of medical care in the most advanced health care settings, an increasing attention is being paid to the so-called care humanization. According to this perspective, we try to integrate the usual care pathways with aspects related to the spiritual and religious dimension of all people and their families, as well as the employees themselves. It is clearly important to establish this kind of practices on the basis of scientific evidences. That is the reason why it's a necessity to improve the knowledge about the importance that spiritual assistance can offer within the current health service. The aim of this work is to show the relevance of the integration of spiritual perspectives in the hospital setting according to a multidisciplinary point of view. In this work many data that emerge from the international scientific literature, as well as the definition that is given to the concept of "spirituality" are analyzed; about this definition in fact there is not unanimous consent even today. It is also analyzed the legal situation in force within the European territory according to the different laws and social realities. Finally, the possible organizational practices related to spiritual support are described and the opportunity to specific accreditation pathways and careful training of chaplains able to integrate traditional religious practices with modern spiritual perspectives is discussed.

PURPOSE AND BASIC PROCEDURE OF THE STUDY: The availability of new targeted therapies has revolutionised the treatment of multiple myeloma (MM), for both the newly diagnosed and the relapsed and refractory settings. A panel of Italian experts provided guidelines for optimal clinical practice in the treatment of MM., Main Findings and Conclusions: The panel recommended that treatment should only be initiated in symptomatic patients. Autologous stem cell transplantation (ASCT) with melphalan is the treatment of choice in patients younger than 65 yr, and induction therapy including new drugs seems the most suitable preparatory regimen before ASCT. In patients who fail to achieve at least a very good partial response (VGPR) after transplant, a consolidation with a second transplant is of clinical benefit. Also, there is evidence that maintenance with thalidomide after ASCT in young patients failing to reach at least VGPR could prolong survival. In elderly patients, the combination of an alkylating drug with a novel agent should be considered as standard approach. Relapsed MM should be retreated after the reappearance of symptoms and signs of organ and tissue damage. Salvage regimens should include corticosteroids plus bortezomib, thalidomide or lenalidomide.

Individual differences in xenobiotica metabolising capacity can influence susceptibility to multiple myeloma. NQO1 and GSTT1 polymorphisms were recently reported as risk factors for multiple myeloma and GSTP1 genotype was found to be a prognostic marker for therapy outcome in multiple myeloma. The aim of this study was to determine whether specific defective alleles of NQO1 (P187S) and GSTP1 (I105V) genes are associated with increased risk of multiple myeloma. Individual genotypes of 128 patients affected by multiple myeloma and 245 healthy controls were determined and our results do not support any major role of NQO1 or GSTP1 polymorphisms in multiple myeloma pathogenesis.

The infectious complications are an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Our retrospective study has the objective to evaluate the incidence, clinical and bacteriologic features of documented infections in these patients. The frequency of infectious complications was analysed in 42 patients with hematologic malignancies who received HSCT from January to December 2002 at Pisa General Hospital. Thirty-three patients underwent autologous HSCT and 9 received allogeneic HSCT. All patients received acyclovir, fluconazole and fluoroquinolones as prophylactic regimen. A total of 38 infectious episodes were recognized in 22 patients during the early post-HSCT period (N=27) and in the late post-HSCT period (N=11). Infectious complications rate correlated positively with the deepness and length of neutropenia in the early period. There were 21 episodes of sepsis (the majority by coagulase negative staphylococci), 2 pneumonias and 1 vertebral osteomyelitis. All staphylococcus strains were, in vitro, resistant to oxacillin and ciprofloxacin and 8 out of 15 gram negative rods were resistant to ciprofloxacin. Most of the infectious complications were cured with appropriated antimicrobial therapy and/or with engraftment and, in 4 cases, with central catheter removal. One patient developed a positive CMV antigenemia; a pre-core mutant form of HBV reactivation was diagnosed in another patient. No cases of invasive fungal infections were recognised. Five patients died but only one from infection (septic shock). Pneumonia was a coexisting cause of death in 2 patient in the late period. We can conclude that most of infectious complications, that occurred in the early period post-HSCT were due to coagulase negative staphylococci and gram negative rods resistant to ciprofloxacin. For this reason, the usefulness of fluoroquinolone prophylaxis in HSCT recipients should be reevaluated.

The Elderly Services of USL 3 "Genovese" together with the team for Continuing Education designed and implemented a survey on the elderly clients referred to the home care and nursing home services. The aim of the study was to describe the frequency, distribution and severity of pressure ulcers. The data were collected during a period of seven months: from 1st November 1997 to 31st May 1998. One thousand seven hundred and twenty nine clients were observed; 705 (41%) had single or multiple pressure ulcers. Patients with multiple pressure ulcers accounted for 42% of the total. The sacrum was the most affected site (43% of the patients with a single ulcer and 33% with multiple ulcers). Patients with severe pressure ulcers (stages 3 degrees and 4 degrees NPUAP classification) accounted for 42% of the total. Pressure sores were observed in 15% of "at no risk" patients and in 40% of those at low risk (Norton Scale score). The study highlighted a lack of documentation (90% patients) on treatments performed in the hospital and prescribed at discharge for the pressure sores. These findings reflects possibly the fact that this aspect of care is unduly disregarded by nursing personnel, and that a goal-oriented retraining, underlining also the need of appropriate documentation, is warranted.

A formal variability study has been carried out in a geriatric hospital in Genoa, Italy, in order to estimate the degree of agreement between geriatricians in disability and functional assessment, recommendation for rehabilitation treatments, need for mobility and daily activities aids, and decisions about optimal place of treatment (own home, sheltered housing, old peoples' home, nursing home). Sixteen long-stay geriatric patients, average age 83 years, were visited by eight geriatricians, a patient receiving from two to five visits. The participating physicians could visit the patients at their leisure, had access to clinical records and could interview a nurse well acquainted with the patient. A marked variability was observed for most items, e.g. the agreement concerning the recommendation for individual physiotherapy was only 52%. The results of this study may not be generalized to other situations and to actual practice; however, variability studies of this kind, that assess diagnosis habits, treatment and managerial decisions at the same time, may be useful to pinpoint the most important problems and to stimulate professionals' participation in proper Quality Assurance projects.

Haematological and molecular studies on 32 heterozygotes for G gamma A gamma delta beta(0)-thalassaemia from 15 unrelated families from southern Italy are reported. The haematological features of G gamma A gamma delta beta(0)-thalassaemia carriers are compared with those of beta-thalassaemia and Hb Lepore heterozygotes. Striking similarity exists between the phenotypic expression of beta-thalassaemia and Lepore mutations. Globin gene mapping studies indicated that the molecular lesion underlying delta beta-thalassaemia is a large deletion starting from the large intervening sequence of the delta gene and extending downstream from the beta gene. The possibility that delta beta-thalassaemia haplotypes in southern Italy originated from a single mutational event is discussed.

We report a study of four families of Italian origin in which heterocellular HPFH is inherited linked to beta thalassemia over two or three generations. The HPFH + beta thalassemia carriers showed thalassemic blood pictures and elevated HbF and F-cell number without increase in the HbF/F-cell content. Association of this gene complex with a second beta thalassemia trait gives rise to a mild clinical picture characterized by 9-12 g/dl of mainly HbF in peripheral blood and no transfusion requirement. In two families, independent segregation of the HPFH or beta-thal trait was observed, and in one case the study of the DNA polymorphisms within the gamma delta beta gene cluster indicated that the HPFH mutation lies outside that DNA region. In one family the coexistence of a polymorphic variant of the A gamma chain (the A gamma T chain) allowed us to demonstrate that the increased gamma chain synthesis caused by the heterocellular HPFH determinant is directed by both chromosomes.