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The constantly increasing life expectancy is raising the issue of treating oncological older patients, who were traditionally candidates to best supportive care or palliative treatments. Several literature data support SBRT in the treatment of the oligometastatic patient as a potentially curable therapeutic option. However, data on older patients are lacking. This study presents the outcomes of a cohort of 61 oligometastatic patients over the age of 80 years who received SBRT, that was proposed to all patients with a minimum Karnofsky Performance Status ≥ 70 and a life expectancy of at least 6 months, with up to five oligometastatic lesions. Radiotherapy was delivered in 3-10 fractions with VMAT-IGRT technique. Toxicity was retrospectively collected according to CTCAE v4.0. Data were retrospectively collected and analyzed. Univariate and multivariate analysis were performed for assessing any potential predictive factor for clinical outcomes. A total of 90 oligometastases were treated in 61 patients with median age 82 years (range, 80-90). The most frequent histology was colorectal cancer (27% of cases). Median follow-up was 20 months (range, 2-63). Local control rates at 1- and 2-years were 98.8% and 88.2%, with colorectal histology being associated with worse LC rates (p = 0.014) at univariate analysis. Progression-free survival rates at 1- and 2-years were 48.6% and 30.5%. Oligorecurrent lesions and single oligometastases were associated with better PFS rates (respectively, p = 0.04 and p = 0.011). Overall survival rates were 75% and 60.5%, polymetastatic spread being predictive of worse survival outcomes at multivariate analysis (p = 0.012). No G2 or higher adverse events were recorded. Our study supports the role of SBRT for the treatment of elderly oligometastatic patients, highlighting the possibility to further explore this therapeutic option in the management of older oncological patients.

Objectives MR-guided daily-adaptive radiotherapy is improving the accuracy in the planning and delivery phases of the treatment. Rectal hydrogel-spacer may help in mitigating organ motion, but few data are currently available. Methods We aimed to assess any potential impact of the device on seminal vesicles motion by measuring translational and rotational shifts between the pre- and post-treatment MRI scans of a total of 50 fractions in the first 10 patients who underwent MR-guided prostate SBRT (35 Gy/5 fx). Of them, five patients received the hydrogel-spacer. The comparative analysis was performed using the Mann–Whitney U-test Results Median rotational shifts were: in anteroposterior 0° (range, 0.097°/0.112°; SD = 0.05°) vs 0° (−0.162/0.04°; SD = 0.07°) in the no-spacer subgroup (p = 0.36); lateral shifts were 0° (−0.1°/0.54°; SD = 0.28°) vs −0.85° in the no-spacer cohort (−1.56°/0.124°; SD = 0.054°; p = 0.22). Cranio-caudal shifts were 0° (−0.121°/0.029°; SD = 0.06°) in the spacer-cohort vs 0° (−0.066°/0.087°; SD = 0.69°; p = 0.53). Median translational shifts were: in anteroposterior 0.9 mm (−0.014 mm/0.031 mm; SD = 0.036 mm) in the spacer-group vs 0.030 mm (−0.14 mm/0.03 mm; SD = 0.032 mm; p = 0.8); latero-lateral shifts were −0.042 mm (−0.047 mm/0.07 mm; SD = 0.054 mm), vs −0.023 mm (−0.027 mm/−0.01 mm; SD = 0.023 mm) in the no-spacer group (p = 0.94). In cranio-caudal, statistically significant shifts were reported: 0.082 mm (0.06 mm/0.15 mm; SD = 0.04 mm) vs 0.06 mm (−0.06/0.08 mm; SD = 0.09 mm) in the no-spacer cohort (p = 0.031). Conclusions A favorable impact of the hydrogel-spacer on seminal vesicles motion was observed only in cranio-caudal translational shifts, although being not clinically significant. Further studies are required to fully investigate the potential contribution of this device on vesicles motion. Advances in knowledge MR-guided daily adaptive radiotherapy may represent a game changer for prostate stereotactic body radiotherapy, given the possibility to better visualize soft-tissues anatomy and to daily recalculate the treatment plan based on real-time conditions. The use of devices like rectal ballon or rectal gel spacers has gained interest in the last years for the possibility to better spare the rectum during prostate radiotherapy. This is one of the first experiences exploring the role of rectal spacer on seminal vesicles intrafraction motion during MR-guided SBRT for prostate cancer.

PurposeWe report preliminary dosimetric data concerning the use of 1.5-T MR-guided daily-adaptive radiotherapy for abdomino-pelvic lymph-nodal oligometastases. We aimed to assess the impact of this technology on mitigating daily variations for both target coverage and organs-at-risk (OARs) sparing. MethodsA total of 150 sessions for 30 oligometastases in 23 patients were analyzed. All patients were treated with MR-guided stereotactic body radiotherapy (SBRT) for a total dose of 35Gy in 5 fractions. For each fraction, a quantitative analysis was performed for PTV volume, V35Gy and Dmean. Similarly, for OARs we assessed daily variations of volume, Dmean, Dmax. Any potential statistically significant change between baseline planning and daily-adaptive sessions was assessed using the Wilcoxon signed-rank test, assuming a p-valueResultsAverage baseline PTV, bowel, bladder and single intestinal loop volumes were respectively 8.9cc (range, 0.7-41.2cc), 1176cc (119-3654 cc), 95cc (39.7-202.9 cc), 18.3cc (9.1-37.7 cc). No significant volume variations were detected for PTV (p=0.21) bowel (p=0.36), bladder (p=0.47), except for single intestinal loops, which resulted smaller (p=0.026). Average baseline V35Gy and Dmean for PTV were respectively 85.6% (72-98.8%) and 35.6 Gy (34.6-36.1 Gy). We recorded a slightly positive trend in favor of daily-adaptive strategy vs baseline planning for improved target coverage, although not reaching statistical significance. (p=0.11 and p=0.18 for PTV-V35Gy and PTV-Dmean). Concerning OARs, a significant difference was observed in favor of daily-adapted treatments in terms of single intestinal loop Dmax [23.05 Gy (13.2-26.9 Gy) at baseline vs 20.5 Gy (12.1-24 Gy); p-value=0.0377] and Dmean [14.4 Gy (6.5-18 Gy) at baseline vs 13.0 Gy (6.7-17.6 Gy); p-value=0.0003].Specifically for bladder, the average Dmax was 18.6 Gy (0.4-34.3 Gy) at baseline vs 18.3 Gy (0.7-34.3 Gy) for a p-value=0.28; the average Dmean was 7.0 Gy (0.2-16.6 Gy) at baseline vs 6.98 Gy (0.2-16.4 Gy) for a p-value=0.66. Concerning the bowel, no differences in terms of Dmean [4.78 Gy (1.3-10.9 Gy) vs 5.6 Gy (1.4-10.5 Gy); p-value=0.23] were observed between after daily-adapted sessions. A statistically significant difference was observed for bowel Dmax [26.4 Gy (7.7-34 Gy) vs 25.8 Gy (7.8-33.1 Gy); p-value=0.0086].ConclusionsDaily-adaptive MR-guided SBRT reported a significantly improved single intestinal loop sparing for lymph-nodal oligometastases. Also bowel Dmax was significantly reduced with daily-adaptive strategy. A minor advantage was also reported in terms of PTV coverage, although not statistically significant.

Immunocytochemical analysis of the laminin alpha-2 (merosin) chain in the muscle of patients with Classic Congenital Muscular Dystrophy (Cl-CMD) differentiates the types of the disease associated with a merosin deficit from those that are merosin positive. Patients with Central Nervous System involvement in merosin negative Cl-CMD always present alterations of the white matter at RMI, but usually these are not clinically significant. While ocular malformations (microphthalmia, alterations of the anterior chamber, of the retina, or of the angle and cataract) and damage to the Central Nervous System are described in some subtypes of CMD (Muscle Eye Brain disease, Walker Warburg Syndrome), ocular involvement and retino-cortical conduction in merosin negative Cl-CMD are not well known. This study reports on four patients affected by merosin negative Cl-CMD. All these patients presented important alterations of the white matter associated with ventricular enlargement and, in one case, with pachygyria and micropolygyria. Refraction, visual acuity, ocular motility, anterior segment and fundus were examined. ERG Maximal, Cone and Rod response, VEP transient pattern reversal was carried out as well. Significant alterations at the standard ophthalmologic examination or of the electroretinogram responses were not registered while, in all cases, important modifications in retino cortical conduction (reduction in amplitude, increase in latency, reduction in amplitude on the lateral derivations) were observed, demonstrating involvement of the optic pathway at different levels during the course of this disease.

In 197 patients with perennial rhinitis, 49 patients (24.9%) were found to be allergic to perennial inhalant allergens, 37 patients (18.8%) allergic to seasonal allergens, 52 patients (26.4%) had food intolerance, 12 patients (6.6%) showed evidence of nasal infection, and in 46 patients (23.3%) etiology was undetermined.

Twenty patients with chronic urticaria exacerbated by aspirin or tartrazine were challenged with the offending substance after pre-treatment with either oral sodium cromoglycate or placebo in a double-blind, crossover study. The sequential vascular response test (SVR) described by Fisherman and Cohen 1-4 was used to assess response to challenge. Eighteen patients were protected by oral sodium cromoglycate and one by placebo, taking as a positive response an increase in the bleeding time of 100% or more over control values.

Twenty-four adult patients with adverse reactions to foods and food additives took part in a double-blind crossover study to compare the efficacy of oral sodium cromoglycate, 1600 mg daily, with placebo. Duration of treatment was eight weeks. There were statistically significant differences (p less than 0.01) in favor of active treatment as assessed by patients' diary card scores during the last week of treatment. Few side effects were observed. Oral sodium cromoglycate appears to be both effective and well tolerated in the treatment of food allergies, particularly when used in conjunction with a maintenance elimination diet.

We have studied 262 patients suffering from hay fever and oral allergy syndrome after fruit and vegetable ingestion. The history and the results of RAST and skin test for pollen showed a contemporary presence of systemic and local symptoms in most of the patients; a close connection between age of onset of hay fever and oral allergy syndrome; a frequent association between allergy to some pollens and some vegetables, such as between apple, carrot, pear, cherry with birch pollen and tomato, melon, watermelon with grass pollen.

The aim of this prospective study was to evaluate the incidence of allergic reactions to drugs compared to other kinds of medical emergencies admitted to the main Hospital in Milan during a 6 months period. At the same time we drew a list of drugs most frequently involved in allergic reactions, and a list of the most frequent symptoms. Using special forms, the medical staff collected patients' data: age, history of atopy, identification of the drug causing the reaction, and any previous reactions. Among 11,407 cases of medical emergencies, we found 163 (1.43%) patients showing drug reactions: the mean age was 27.3; 58.90% were female; atopy was present in 16.56%. The drugs most frequently involved were: pyrazon group (22%); ASA (20.86%); penicillin and derivatives (9.20%); sulfa drugs (6.14%); group B vitamins (4.30%); tetanus toxoid (4.30%); hyposensitizing extracts (3.68%); propionic acid derivatives (2.46%); paracetamol (1.84%); indomethacin (1.23%); rifampicin (1.23%); erythromycin (1.23%); glafenine (1.23%); others (17.80%). Urticaria and/or angioedema were the most frequent symptoms (86.51%), then anaphylactic shock (9.81%) and asthma (3.68%) with regard to anaphylactic shock only 6.20% of the patients had had a previous reaction to the same drug. From these data we can see that the incidence of drug reactions is very low compared to other medical emergencies; penicillin evidenced fewer reactions than expected, while the pyrazon group and ASA confirmed the data from literature.

Facioscapulohumeral muscular dystrophy has been genetically linked to reduced numbers (≤ 8) of D4Z4 repeats at 4q35 combined with 4A(159/161/168) DUX4 polyadenylation signal haplotype. However, we have recently reported that 1.3% of healthy individuals carry this molecular signature and 19% of subjects affected by facioscapulohumeral muscular dystrophy do not carry alleles with eight or fewer D4Z4 repeats. Therefore, prognosis for subjects carrying or at risk of carrying D4Z4 reduced alleles has become more complicated. To test for additional prognostic factors, we measured the degree of motor impairment in a large group of patients affected by facioscapulohumeral muscular dystrophy and their relatives who are carrying D4Z4 reduced alleles. The clinical expression of motor impairment was assessed in 530 subjects, 163 probands and 367 relatives, from 176 unrelated families according to a standardized clinical score. The associations between clinical severity and size of D4Z4 allele, degree of kinship, gender, age and 4q haplotype were evaluated. Overall, 32.2% of relatives did not display any muscle functional impairment. This phenotype was influenced by the degree of relation with proband, because 47.1% of second- through fifth-degree relatives were unaffected, whereas only 27.5% of first-degree family members did not show motor impairment. The estimated risk of developing motor impairment by age 50 for relatives carrying a D4Z4 reduced allele with 1-3 repeats or 4-8 repeats was 88.7% and 55%, respectively. Male relatives had a mean score significantly higher than females (5.4 versus 4.0, P = 0.003). No 4q haplotype was exclusively associated with the presence of disease. In 13% of families in which D4Z4 alleles with 4-8 repeats segregate, the diagnosis of facioscapulohumeral muscular dystrophy was reported only in one generation. In conclusion, this large-scale analysis provides further information that should be taken into account when counselling families in which a reduced allele with 4-8 D4Z4 repeats segregates. In addition, the reduced expression of disease observed in distant relatives suggests that a family's genetic background plays a role in the occurrence of facioscapulohumeral muscular dystrophy. These results indicate that the identification of new susceptibility factors for this disease will require an accurate classification of families.