Phantom validation of quantitative Y-90 PET/CT based dosimetry in liver radioembolisation

Background PET/CT has recently been shown to be a viable alternative to traditional post-infusion imaging methods providing good quality images of 90Y-laden microspheres after selective internal radiation therapy (SIRT). In the present paper, first we assessed the quantitative accuracy of 90Y-PET using an anthropomorphic phantom provided with lungs, liver, spine, and a cylindrical homemade lesion located into the hepatic compartment. Then, we explored the accuracy of different computational approaches on dose calculation, including (I) direct Monte Carlo radiation transport using Raydose, (II) Kernel convolution using Philips Stratos, (III) local deposition algorithm, (IV) Monte Carlo technique (MCNP) considering a uniform activity distribution, and (V) MIRD (Medical Internal Radiation Dose) analytical approach. Finally, calculated absorbed doses were compared with those obtained performing measurements with LiF:Mg,Cu,P TLD chips in a liquid environment. Results Our results indicate that despite 90Y-PET being likely to provide high-resolution images, the 90Y low branch ratio, along with other image-degrading factors, may produce non-uniform activity maps, even in the presence of uniform activity. A systematic underestimation of the recovered activity, both for the tumor insert and for the liver background, was found. This is particularly true if no partial volume correction is applied through recovery coefficients. All dose algorithms performed well, the worst case scenario providing an agreement between absorbed dose evaluations within 20%. Average absorbed doses determined with the local deposition method are in excellent agreement with those obtained using the MIRD and the kernel-convolution dose calculation approach. Finally, absorbed dose assessed with MC codes are in good agreement with those obtained using TLD in liquid solution, thus confirming the soundness of both calculation approaches. This is especially true for Raydose, which provided an absorbed dose value within 3% of the measured dose, well within the stated uncertainties. Conclusions Patient-specific dosimetry is possible even in a scenario with low true coincidences and high random fraction, as in 90Y–PET imaging, granted that accurate absolute PET calibration is performed and acquisition times are sufficiently long. Despite Monte Carlo calculations seeming to outperform all dose estimation algorithms, our data provide a strong argument for encouraging the use of the local deposition algorithm for routine 90Y dosimetry based on PET/CT imaging, due to its simplicity of implementation

Fondazione Italiana Linfomi (FIL) expert consensus on the use of intensity-modulated and image-guided radiotherapy for Hodgkin's lymphoma involving the mediastinum

Advances in therapy have resulted in improved cure rates and an increasing number of long-term Hodgkin's lymphoma (HL) survivors. However, radiotherapy (RT)-related late effects are still a significant issue, particularly for younger patients with mediastinal disease (secondary cancers, heart diseases). In many Centers, technological evolution has substantially changed RT planning and delivery. This consensus document aims to analyze the current knowledge of Intensity-Modulated Radiation Therapy (IMRT) and Image-Guided Radiation Therapy (IGRT) for mediastinal HL and formulate practical recommendations based on scientific evidence and expert opinions

Properties of the permeability transition of pea stem mitochondria

In striking analogy with Saccharomyces cerevisiae, etiolated pea stem mitochondria did not show appreciable Ca2+ uptake. Only treatment with the ionophore ETH129 (which allows electrophoretic Ca2+ equilibration) caused Ca2+ uptake followed by increased inner membrane permeability, membrane depolarization and Ca2+ release. Like the permeability transition (PT) of mammals, yeast and Drosophila, the PT of pea stem mitochondria was stimulated by diamide and phenylarsine oxide and inhibited by MgADP and Mg-ATP, suggesting a common underlying mechanism; yet, the plant PT also displayed distinctive features: (i) as in mammals it was desensitized by cyclosporin A, which does not affect the PT of yeast and Drosophila; (ii) similarly to S. cerevisiae and Drosophila it was inhibited by Pi, which stimulates the PT of mammals; (iii) like in mammals and Drosophila it was sensitized by benzodiazepine 423, which is ineffective in S. cerevisiae; (iv) like what observed in Drosophila it did not mediate swelling and cytochrome c release, which is instead seen in mammals and S. cerevisiae. We find that cyclophilin D, the mitochondrial receptor for cyclosporin A, is present in pea stem mitochondria. These results indicate that the plant PT has unique features and suggest that, as in Drosophila, it may provide pea stem mitochondria with a Ca2+ release channel

COVID-19 outbreak in Italy: an opportunity to evaluate extended interval dosing of ocrelizumab in MS patients

introduction during the COVID-19 pandemic, ocrelizumab (OCR) infusions for MS patients were often re-scheduled because of MS center's disruption and concerns regarding immunosuppression. The aim of the present study was to assess changes in OCR schedule during the first wave of pandemic in italy and to evaluate the effect of delayed infusion on clinical/radiological endpoints.methods data were extracted from the Italian MS register database. standard interval dosing was defined as an infusion interval <= 30 weeks, while extended interval dosing was defined as an infusion interval > 30 weeks at the time of the observation period. clinico-demographics variables were tested as potential predictors for treatment delay. time to first relapse and time to first MRI event were evaluated. Cumulative hazard curves were reported along their 95% confidence intervals. a final sample of one-thousand two patients with MS from 65 centers was included in the analysis: 599 pwMS were selected to evaluate the modification of OCR infusion intervals, while 717 pwRMS were selected to analyze the effect of infusion delay on clinical/MRI activity. results mean interval between two OCR infusions was 28.1 weeks before pandemic compared to 30.8 weeks during the observation period, with a mean delay of 2.74 weeks (p < 0.001). No clinico-demographic factors emerged as predictors of infusion postponement, except for location of MS centers in the north of italy. clinical relapses (4 in SID, 0 in EID) and 17 MRI activity reports (4 in SID, 13 in EID) were recorded during follow-up period. discussion despite the significant extension of OCR infusion interval during the first wave of pandemic in Italy, a very small incidence of clinical/radiological events was observed, thus suggesting durable efficacy of OCR, as well as the absence of rebound after its short-term suspension

MAGNIMS recommendations for harmonization of MRI data in MS multicenter studies

There is an increasing need of sharing harmonized data from large, cooperative studies as this is essential to develop new diagnostic and prognostic biomarkers. In the field of multiple sclerosis (MS), the issue has become of paramount importance due to the need to translate into the clinical setting some of the most recent MRI achievements. However, differences in MRI acquisition parameters, image analysis and data storage across sites, with their potential bias, represent a substantial constraint. This review focuses on the state of the art, recent technical advances, and desirable future developments of the harmonization of acquisition, analysis and storage of large-scale multicentre MRI data of MS cohorts. Huge efforts are currently being made to achieve all the requirements needed to provide harmonized MRI datasets in the MS field, as proper management of large imaging datasets is one of our greatest opportunities and challenges in the coming years. Recommendations based on these achievements will be provided here. Despite the advances that have been made, the complexity of these tasks requires further research by specialized academical centres, with dedicated technical and human resources. Such collective efforts involving different professional figures are of crucial importance to offer to MS patients a personalised management while minimizing consumption of resource

Familial Clustering of Unexplained Transient Respiratory Distress in 12 Newborns from Three Unrelated Families Suggests an Autosomal-Recessive Inheritance

We report on 12 near-term babies from three families in which an unexplained transient respiratory distress was observed. No known risk factor was present in any family and no sequelae were recorded at follow-up. The most common causes of respiratory distress at birth are Neonatal Respiratory Distress Syndrome (NRD) and Transient Tachypnea of the Newborn (TTN), and their cumulative incidence is estimated to be about 2%. Genetic factors have been identified in NRD (surfactant genes) or suggested for TTN (genes affecting lung liquid clearance). Survivors from NRD may develop clinically relevant sequelae, while TTN does not cause any problem later in life. Our cases do not immediately fit NRD or TTN, while familial recurrence suggests the existence of a previously unreported subgroup on patients with respiratory distress for which autosomal-recessive inheritance is likely

Familial Clustering of Unexplained Transient Respiratory Distress in 12 Newborns from Three Unrelated Families Suggests an Autosomal-Recessive Inheritance

We report on 12 near-term babies from three families in which an unexplained transient respiratory distress was observed. No known risk factor was present in any family and no sequelae were recorded at follow-up. The most common causes of respiratory distress at birth are Neonatal Respiratory Distress Syndrome (NRD) and Transient Tachypnea of the Newborn (TTN), and their cumulative incidence is estimated to be about 2%. Genetic factors have been identified in NRD (surfactant genes) or suggested for TTN (genes affecting lung liquid clearance). Survivors from NRD may develop clinically relevant sequelae, while TTN does not cause any problem later in life. Our cases do not immediately fit NRD or TTN, while familial recurrence suggests the existence of a previously unreported subgroup on patients with respiratory distress for which autosomal-recessive inheritance is likely

Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages

OBJECTIVE Consistent with the cognitive reserve hypothesis, higher education and occupation attainments may help persons with neurodegenerative dementias to better withstand neuropathology before developing cognitive impairment. We tested here the cognitive reserve hypothesis in patients with frontotemporal dementia (FTD), with or without pathogenetic granulin mutations (GRN+ and GRN-), and in presymptomatic GRN mutation carriers (aGRN+). METHODS Education and occupation attainments were assessed and combined to define Reserve Index (RI) in 32 FTD patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional connectivity were estimated by resting state fMRI, focusing on the salience network (SN), executive network (EN) and bilateral frontoparietal networks (FPNs). Cognitive status was measured by FTD-modified Clinical Dementia Rating Scale. RESULTS In FTD patients higher level of premorbid cognitive reserve was associated with reduced connectivity within the SN and the EN. EN was more involved in FTD patients without GRN mutations, while SN was more affected in GRN pathology. In aGRN+, cognitive reserve was associated with reduced SN. CONCLUSIONS This study suggests that cognitive reserve modulates functional connectivity in patients with FTD, even in monogenic disease. In GRN inherited FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical stages

Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies

Background and aims: No consensus exists on how aggressively to treat relapsing-remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC). Methods: RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups. Results: The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5-11.7) years. Mean annual delta-EDSS values were all significantly (p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01-0.19, p = 0.03) at 1 year to 0.30 (0.07-0.53, p = 0.009) at 5 years and to 0.67 (0.31-1.03, p = 0.0003) at 10 years. Conclusion: Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time