Monitoring Carbon Ion Beams Transverse Position Detecting Charged Secondary Fragments: Results From Patient Treatment Performed at CNAO

Particle therapy in which deep seated tumours are treated using 12C ions (Carbon Ions RadioTherapy or CIRT) exploits the high conformity in the dose release, the high relative biological effectiveness and low oxygen enhancement ratio of such projectiles. The advantages of CIRT are driving a rapid increase in the number of centres that are trying to implement such technique. To fully profit from the ballistic precision achievable in delivering the dose to the target volume an online range verification system would be needed, but currently missing. The 12C ions beams range could only be monitored by looking at the secondary radiation emitted by the primary beam interaction with the patient tissues and no technical solution capable of the needed precision has been adopted in the clinical centres yet. The detection of charged secondary fragments, mainly protons, emitted by the patient is a promising approach, and is currently being explored in clinical trials at CNAO. Charged particles are easy to detect and can be back-tracked to the emission point with high efficiency in an almost background-free environment. These fragments are the product of projectiles fragmentation, and are hence mainly produced along the beam path inside the patient. This experimental signature can be used to monitor the beam position in the plane orthogonal to its flight direction, providing an online feedback to the beam transverse position monitor chambers used in the clinical centres. This information could be used to cross-check, validate and calibrate, whenever needed, the information provided by the ion chambers already implemented in most clinical centres as beam control detectors. In this paper we study the feasibility of such strategy in the clinical routine, analysing the data collected during the clinical trial performed at the CNAO facility on patients treated using 12C ions and monitored using the Dose Profiler (DP) detector developed within the INSIDE project. On the basis of the data collected monitoring three patients, the technique potential and limitations will be discussed

Operationalizing mild cognitive impairment criteria in small vessel disease: The VMCI-Tuscany Study

Introduction Mild cognitive impairment (MCI) prodromic of vascular dementia is expected to have a multidomain profile. Methods In a sample of cerebral small vessel disease (SVD) patients, we assessed MCI subtypes distributions according to different operationalization of Winblad criteria and compared the neuroimaging features of single versus multidomain MCI. We applied three MCI diagnostic scenarios in which the cutoffs for objective impairment and the number of considered neuropsychological tests varied. Results Passing from a liberal to more conservative diagnostic scenarios, of 153 patients, 5% were no longer classified as MCI, amnestic multidomain frequency decreased, and nonamnestic single domain increased. Considering neuroimaging features, severe medial temporal lobe atrophy was more frequent in multidomain compared with single domain. Discussion Operationalizing MCI criteria changes the relative frequency of MCI subtypes. Nonamnestic single domain MCI may be a previously nonrecognized type of MCI associated with SVD

IPERTENSIONE IN BAMBINI ED ADOLESCENTI AFFETTI DA DIABETE DI TIPO 1: ALTA PREVALENZA IDENTIFICATA TRAMITE L’UTILIZZO DEL MONITORAGGIO PRESSORIO AMBULATORIALE

OBIETTIVI - L’ipertensione nei bambini ed adolescenti con diabete di tipo 1 (DM1) è associata ad un aumentato rischio di complicanze cardiovascolari in età adulta. Il monitoraggio pressorio ambulatoriale (24h-ABPM) consente la registrazione dei valori pressori per 24 ore in un ambiente non medico; tuttavia, i dati sulla sua utilità in età evolutiva sono ancora controversi. Gli obiettivi di questo studio sono stati quelli di confrontare la prevalenza di ipertensione utilizzando sia il metodo oscillometrico tradizionale sia il 24h-ABPM ovvero di valutare l’utilità del 24h-ABPM nella diagnosi precoce di ipertensione al fi ne di iniziare un trattamento precoce. METODI - Sono stati reclutati 40 bambini ed adolescenti (52.5% maschi) con DM1 (13.6±2.56 anni; durata DM1 >1 anno) e raccolti dati antropometrici, metabolici (HbA1c, assetto lipidico, funzionalità renale) e pressione arteriosa (sfigmomanometro oscillometrico e 24h-ABPM). L’ipertensione è stata definita come: A) pressione arteriosa sistolica (SBP) superiore al 95° percentile per età, sesso e percentile di altezza con sfigmomanometro oscillometrico; B) SBP superiore al 95° percentile per un tempo >25% con 24h-ABPM. RISULTATI - Utilizzando lo sfigmomanometro oscillometrico durante la visita clinica, sono risultati ipertesi 9 pazienti su 40 (22.5%) mentre, tramite 24h-ABPM, la prevalenza di ipertensione è risultata significativamente maggiore (57.5%; χ2=8.58, p=0.003). I pazienti risultati ipertesi con 24h-ABPM avevano una durata di DM1 più lunga rispetto ai normotesi (8.04±3.22 vs. 5.76±1.85 anni, rispettivamente, p=0.013). Utilizzando le curve ROC abbiamo identificato i 6.5 anni dall’esordio del DM1 come cut-off predittivo di carico SBP >25% (AUC 0.716). L’analisi multivariata ha permesso di identifi care la durata della malattia (β=0.49, SE 0.17, p=0.006) ed il z-score BMI (β=0.41, SE 0.20, p=0.049) come principali fattori predittivi per il carico di SBP >95° percentile. I nostri dati non hanno supportato una relazione tra ipertensione, controllo metabolico, profilo lipidico ed indici di funzionalità renale. CONCLUSIONI - 24h-ABPM ha permesso di identificare una maggiore prevalenza di ipertensione e potrebbe essere introdotta nella comune pratica clinica a distanza di 6 anni dall’esordio del DM1. 24h-ABPM può essere considerato uno strumento utile per identificare precocemente i soggetti con ipertensione che possono beneficiare di un trattamento precoce per prevenire le complicanze renali e cardiovascolari

Immunologic evidence of a strong association between non-Hodgkin lymphoma and simian virus 40

BACKGROUND: Non-Hodgkin lymphoma (NHL), the most common cancer of the lymphatic system, is of unknown etiology. The identification of etiologic factors in the onset of NHL is a key event that could facilitate the prevention and cure of this malignancy. Simian virus 40 (SV40) has been considered an oncogenic agent in the onset/progression of NHL. METHODS: In this study, an indirect enzyme-linked immunosorbent assay with 2 synthetic peptides that mimic SV40 antigens of viral capsid proteins 1 to 3 was employed to detect specific antibodies against SV40. Serum samples were taken from 2 distinct cohorts of NHL-affected patients (NHL1 [n = 89] and NHL2 [n = 61]) along with controls represented by oncologic patients affected by breast cancer (BC; n = 78) and undifferentiated nasopharyngeal carcinoma (UNPC; n = 64) and 3 different cohorts of healthy subjects (HSs; HS1 [n = 130], HS2 [n = 83], and HS3 [n = 87]). RESULTS: Immunologic data indicated that in serum samples from NHL patients, antibodies against SV40 mimotopes were detectable with a prevalence of 40% in NHL1 patients and with a prevalence of 43% in NHL2 patients. In HSs of the same median age as NHL patients, the prevalence was 16% for the HS1 group (57 years) and 14% for the HS2 group (65 years). The difference was statistically significant (P < .0001 and P < .001). Interestingly, the difference between NHL1/NHL2 patients and BC patients (40%/43% vs 15%, P < .001) and between NHL1/NHL2 patients and UNPC patients (40%/43% vs 25%, P < .05) was significant. CONCLUSIONS: Our data indicate a strong association between NHL and SV40 and thus a need for innovative therapeutic approaches for this hematologic malignancy

[Surgical overview on kidney and pancreas transplantation]

The main purpose of this paper, written by a group of Italian expert transplant surgeons, is to provide clinical support and to help through the decision-making process over pre-transplant surgical procedures in potential kidney recipients, as well as selection of pancreas transplant candidates and perioperative management of kidney recipient. Current topics such as different approaches in minimally invasive donor nephrectomy, methods of graft preservation and treatment of failed allograft were addressed

[Surgical overview on kidney and pancreas transplantation]

The main purpose of this paper, written by a group of Italian expert transplant surgeons, is to provide clinical support and to help through the decision-making process over pre-transplant surgical procedures in potential kidney recipients, as well as selection of pancreas transplant candidates and perioperative management of kidney recipient. Current topics such as different approaches in minimally invasive donor nephrectomy, methods of graft preservation and treatment of failed allograft were addressed