A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

Trade-Offs with rehabilitation Effectiveness (REs) and Efficiency (REy) in a sample of Italian disabled persons in a in post-acuity rehabilitation unit.

BACKGROUND: Intensive Rehabilitation Centres, known in Italy as "code 56", admit patients who need to recover from an acute episode. Different Rehabilitation Impact Indices have been proposed as composite rehabilitation outcomes measuring the rate of improvement due to a rehabilitation program. The most widely employed measure the performance of Activities of daily living in rehabilitation is the modified Barthel Index. The Barthel Index-based Rehabilitation Impact Indices are the Rehabilitation Effectiveness and the Rehabilitation Efficiency. AIM: The aim of our study was to evaluate the trade-off between Rehabilitation Effectiveness tayand Rehabilitation Efficiency with respect to the Barthel Index admission score and the Length Of Stay, and their ideal ranges that optimized both indices. METHODS: We retrospectively evaluated data of all patients admitted to intensive rehabilitation unit of the Scientific Institute for Research and Healthcare San Raffaele Pisana of Rome, from January 2006 to March 2018. The primary outcome measures of our study were patient's Rehabilitation Effectiveness and Rehabilitation Efficiency during the hospital stay. RESULTS: A database of 3,466 patients was analysed and the Rehabilitation Effectiveness and Rehabilitation Efficiency indexes were calculated. We calculated the median rank ratio of the Rehabilitation Effectiveness to the Rehabilitation Efficiency against Barthel Index scores. We calculated the median rank ratio of the Rehabilitation Effectiveness to Rehabilitation Efficiency against Barthel Index scores and days of stay. The median rank ratio of the Rehabilitation Effectiveness to the Rehabilitation Efficiency value were 1 in the range of Barthel Index scores from 32 to 42. The median rank ratio of the Rehabilitation Effectiveness to Rehabilitation Efficiency value were 1 for a Length of Stay corresponding to 33 days. CONCLUSIONS: In our study we calculated the Trade-offs between Rehabilitation Effectiveness and Rehabilitation Efficiency with respect to admission Barthel Index Score and Length Of Stay in a population of 3,466 patients affected by orthopedic (1,707) and neurological (1,759) diseases. Every member of the healthcare team should be aware of such trade-offs when they make decisions about rehabilitation services.

N6L pseudopeptide interferes with nucleophosmin protein-protein interactions and sensitizes leukemic cells to chemotherapy.

NPM1 is a multifunctional nucleolar protein implicated in several processes such as ribosome maturation and export, DNA damage response and apoptotic response to stress stimuli. The NPM1 gene is involved in human tumorigenesis and is found mutated in one third of acute myeloid leukemia patients, leading to the aberrant cytoplasmic localization of NPM1. Recent studies indicated that the N6L multivalent pseudopeptide, a synthetic ligand of cell-surface nucleolin, is also able to bind NPM1 with high affinity. N6L inhibits cell growth with different mechanisms and represents a good candidate as a novel anticancer drug for a number of malignancies of different histological origin. In this study we investigated whether N6L treatment could drive antitumor effect in acute myeloid leukemia cell lines. We found that N6L binds NPM1 at the N-terminal domain, co-localizes with cytoplasmic, mutated NPM1, and interferes with its protein-protein associations. N6L toxicity appears to be p53 dependent but interestingly, the leukemic cell line harbouring the mutated form of NPM1 is more resistant to treatment, suggesting that NPM1 cytoplasmic delocalization confers protection from p53 activation. Moreover, we show that N6L sensitizes AML cells to doxorubicin and cytarabine treatment. These studies suggest that N6L may be a promising option in combination therapies for acute myeloid leukemia treatment.

Incidence of traumatic spinal cord injury in Italy during 2013-2014: a population-based study.

STUDY DESIGN: Observational prospective population-based incidence study. OBJECTIVES: The main objective of this study was to assess the incidence of traumatic spinal cord injuries (TSCIs) and incidence rates, in order to provide estimates by age, gender, characteristics and cause. SETTING: This study was conducted at acute-care spinal cord injury (SCI) hospitals and SCI centers from 11 Italian regions, between 1 October 2013 and 30 September 2014. METHODS: Data of all consecutive patients with acute TSCI who met the inclusion criteria were obtained through case reporting by clinicians. The data were collected into a web database. Incidence rates and incidence rate ratios were calculated and stratified by age, gender, cause, level and completeness. RESULTS: From 50% of the entire population of Italy, 445 new cases of TSCI were included. The crude incidence rate of TSCI was 14.7 cases per million per year (95% CI: 13.4-16.4); the overall male to female ratio was 4:1 and the mean age was 54. Complete information was available in 85% of the sample and revealed tetraplegia in 58% and incomplete lesion in 67% of cases. The leading cause of TSCI was falls (40.9%) followed by road traffic accidents (33.5%). The leading cause was falls for patients over 55 and road traffic accidents for patients under 55. CONCLUSION: The changing trend of TSCI epidemiology concerns the increase in the average age of TSCI people and the increase of both cervical and incomplete lesions. The etiology shows the primacy of falls over road traffic accidents and suggests the need for a change in prevention policies.

Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ.

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment.

The coefficient of friction in Parkinson's disease gait.

This study aimed to characterize the coefficient of friction (COF) curves of patients with Parkinson's disease (PD) during barefoot gait and to evaluate the relationships between this variable and functional scales. Twenty-two subjects with PD (ON phase of levodopa) and 22 healthy subjects participated in this study. The participants walked barefoot along a pathway that went over two force plates embedded in the floor of the data collection room. The instantaneous COF was calculated as the ratio between the horizontal and vertical components of the ground reaction forces. Two-sample t-tests applied to every 1% of the support phase of the COF curve were used to compare the groups and to identify the phases in which the two groups were different. Specifically, three COF areas were computed: Area 1 (for the loading response phase), Area 2 (for the midstance phase) and Area 3 (for the terminal stance phase). Pearson's tests were applied to assess the associations between the COF curve areas and the clinical scales. The subjects with PD exhibited lower COF values during the loading response and terminal stance phases and higher COF values during the mid-stance phase compared with the control group. A strong positive correlation was observed between Area 1 and the Timed Up and Go Test (90.3%). In conclusion, the patients' COFs exhibited patterns that were different from those of the control group. Moreover, during the loading response phase, these differences were well-correlated with the Timed Up and Go Test scale data; Timed Up and Go Test data can be used to identify the risk of falls among PD patients.

Robot-assisted gait training versus treadmill training in patients with Parkinson's disease: a kinematic evaluation with gait profile score.

The purpose of this study was to quantitatively compare the effects, on walking performance, of end-effector robotic rehabilitation locomotor training versus intensive training with a treadmill in Parkinson's disease (PD). Fifty patients with PD were randomly divided into two groups: 25 were assigned to the robot-assisted therapy group (RG) and 25 to the intensive treadmill therapy group (IG). They were evaluated with clinical examination and 3D quantitative gait analysis [gait profile score (GPS) and its constituent gait variable scores (GVSs) were calculated from gait analysis data] at the beginning (T0) and at the end (T1) of the treatment. In the RG no differences were found in the GPS, but there were significant improvements in some GVSs (Pelvic Obl and Hip Ab-Add). The IG showed no statistically significant changes in either GPS or GVSs. The end-effector robotic rehabilitation locomotor training improved gait kinematics and seems to be effective for rehabilitation in patients with mild PD.

A proposal for an Italian minimum data set assessment protocol for robot-assisted rehabilitation: a Delphi study.

BACKGROUND: At present there is no agreement on a common evaluation protocol to assess improvement in stroke patients after robotic therapy. AIM: The aim of this study was to identify a Minimum Data Set Assessment Protocol, using an agreement-based survey. DESIGN: A Delphi survey. SETTING: This study was conceived by the Italian Robotic Neurorehabilitation Research Group (IRNRG), an Italian group involved in the clinical application of robot-assisted rehabilitation devices POPULATION: Stroke subjects. METHODS: A 3-round Delphi survey was carried out through the electronic submission of questionnaires to a panel of experts identified in fourteen rehabilitation centers. For each generated item, experts were asked to rate questions on a 5 point Likert Scale. RESULTS: After the 1st round the questionnaire was filled out by 43 (84.3%) out of 51 experts invited to participate in the study. In the 2nd and 3rd rounds we explored the specific evaluation tools for each of the ICF domains identified in the 1st round. The experts identified the following assessment tools for the upper limb: the Ashworth Scale, the Fugl-Meyer assessment scale, the Frenchay Arm Test, the Medical Research Council scale, the Motricity Index, Frenchay Activities Index and Modified Barthel Index; and for the lower limb: the Ashworth Scale, the Motricity Index, the 10 meter walking Test, the 6 minutes walking Test, the Functional Ambulatory Classification, the Timed Up and Go Test, the Walking Handicap Scale, the Borg Rating of Perceived Exertion, the Heart Rate, the Medical Research Council Scale, the Tinetti Balance Scale and the Modified Barthel Index. CONCLUSION: The Delphi survey presented in this study allows the identification of a shared assessment protocol to be applied in clinical practice and research for the evaluation of the real improvement related to robot-assisted rehabilitation of the upper and lower limb in patients after stroke. CLINICAL REHABILITATION IMPACT: Clinicians and researchers could use the results of this study to obtain a common language in robotic rehabilitation assessments.

Management of stroke patients submitted to botulinum toxin type A therapy: a Delphi survey of an Italian expert panel of specialist injectors.

BACKGROUND: Spasticity is a common disabling symptom of several neurological conditions including stroke. Botulinum toxin type A (BTX-A) injection represents the gold standard therapy for focal spasticity. Post-stroke management of patients receiving BTX-A therapy has been variously investigated, but general agreement on how and when to implement rehabilitation is lacking. AIM: To perform a national survey of experts on the most appropriate rehabilitation procedures after BTX-A therapy for the focal treatment of spasticity. DESIGN: The study employed the Delphi technique through the COSMO project (Consensus on Post-Injection Management in Post-stroke Spasticity). METHODS: Italian neurologists and physiatrists with experience in BTX-A therapy were selected to participate in the survey. Their anonymous opinions on key issues in treatment strategies in post-stroke spasticity were collected in three sequential rounds facilitated by a web platform. Consensus on a given issue was defined as agreed opinion by at least 66% of the survey participants. RESULTS: In all, 44 Italian experts were involved. Positive consensus was reached on the need to start rehabilitation during the first week after BTX-A injection therapy, with a rehabilitation program comprising both stretching combined with electrical stimulation and exercise therapy. Functional surgery may be considered only after 12-24 months in cases of BTX-A therapy failure. The use of commercial or custom-made orthoses in selected cases was recommended. The appropriate time interval between two BTX-A injections is 3-6 months, and clinical assessment should be performed 1 month after injection. CONCLUSION: The results of this national survey confirm that clinical experts on the use of BTX-A therapy for spasticity after stroke agree on the need to initiate rehabilitation treatment immediately after BTX-A injection: muscle stretching exercises, eventually combined with neuromuscular electrical stimulation, may enhance the effect of BTX-A therapy. Outcome after BTX-A therapy should be assessed at repeated follow-up visits. CLINICAL REHABILITATION IMPACT: This expert panel survey can provide guidance for clinicians in the assessment of patients treated with BTX-A therapy.

Age structure and feeding of the neotropical grasshopper Cornops aquaticum (Bruner) (Orthoptera: Acrididae) on water hyacinth.

We aimed to evaluate the variation in the age structure of Cornops aquaticum (Bruner) population and its relation to the host plant biomass and the feeding of the different age classes of this grasshopper on the water hyacinth Eichhornia crassipes along 2 years, in a Paraná River floodplain lake (Chaco, Argentina). Individuals of C. aquaticum were captured with a 70-cm diameter sweep and separated in nymphs A (instars I and II), nymphs B (instars III to VI), adult females, and adult males; host plant biomass was sampled using a ring with a 0.30-m(2) diameter. Relative daily feeding of C. aquaticum population was calculated by multiplying the number of individuals captured per minute by the daily consumption by individual obtained in each age classes. We found that the age structure and the relative daily feeding of C. aquaticum varied between seasons and years. The highest values of grasshopper abundance, leaf biomass, and relative daily feeding of C. aquaticum population were observed in summer 2006. Plant biomass was directly correlated with nymph abundance and not correlated with adult abundance. Plant biomass available as refuge (leaves), food (laminas), and oviposition site (petioles) to C. aquaticum represented up to 62% of the total plant biomass. The results obtained in C. aquaticum show the importance of considering total plant biomass and plant biomass available for herbivores separately. Our study highlights the need to find an adequate method to estimate the density of C. aquaticum and other semiaquatic grasshoppers in the Paraná River floodplain involving different seasons, years, and water phases (rising and falling).

Survey of the chemical, physical, and sensory characteristics of currently produced mortadella bologna.

In recent years, formulations of the Italian cold cut mortadella have changed to meet evolving tastes and nutritional trends. The aim of the present study was to analyze the physical, chemical, and sensory characteristics of currently produced mortadella. Representative samples of Italian mortadella (13 brands, 3 samples/brand) were analyzed. Three groups of products were identified according to their chemical compositions. The median cluster was composed of 54.80% moisture, 26.19% fat, and 15.02% protein, whereas the other two clusters were characterized by a higher percentage of moisture or fat. These results indicate that, on average, the current products are characterized by less fat (-5%) and salt (-10%) content compared to products 20 years ago.

Management of shoulder periprosthetic fractures: our institutional experience and review of the literature.

Fractures of the humerus in patients with total shoulder replacement are rare and difficult to treat. The treatment of periprosthetic humeral fractures depends on the location of the fracture in relation to the humeral stem and the stability of the stem/bone interface. We wished to determine the treatment outcomes in a series of patients managed in our institution with periprosthetic humeral fractures. We also carried out a review of the literature. Over a 5 year period, out of 10 patients, 7 were available at the final follow up with a mean age of 72 years (range 68-75). A fall from standing height was the most common mechanism of injury. All patients were found to have stable prosthesis in situ and were treated with angular stable plates and cerclage wiring. The mean time from the total shoulder replacement to injury (fracture) was 11.2 months (range 8-21). All fractures united without complications at a mean time of 5.1 months (range 4-6). The literature review revealed a limited number of publications reporting on the management of approximately 40 patients. The outcome noted in these patients is also presented.

The relation between Parkinson's disease and ageing. Comparison of the gait patterns of young Parkinson's disease subjects with healthy elderly subjects.

BACKGROUND: The gait of healthy elderly and of subjects with Parkinson's disease (PD) displays some common features, suggesting that PD may be a model of ageing. AIM: The aim of the study was to quantify highlight the differences and similarities between the gait patterns of young PD and healthy elderly, to uncover if PD could be assumed as a model of ageing. DESIGN: An optoelectronic system was used for 3D gait analysis evaluation. POPULATION AND METHODS: We compared the gait parameters of 15 young PD (YPD) with the gait of 32 healthy elderly subjects (ES) and 21 healthy subjects age-matched with the PD subjects. RESULTS. Common features between YPD and ES were majorly found in the parameters that reflect the presence of an unstable, uncertain gait, and of corrective strategies employed to reduce instability. On the other side, typical features were present in the gait patterns of PD subjects. CONCLUSION. Our study helped identifying some typical characteristics of the onset disease, and to unravel the symptoms of ageing from those of PD by comparing young PD subjects to elderly healthy subjects. CLINICAL REHABILITATION IMPACT: This allows a deeper understanding of the mechanisms underlying the gait in ageing and PD.

Cartilaginous metaplasia of varicose veins: a case report.

Cartilaginous metaplasia of superficial veins was found in a 64-year-old woman who underwent surgery for varicose veins. At operation, some varicose veins of the medial thigh were semi-rigid and fibroelastic to the touch. Histology revealed that half the lumen was occupied by chondroid tissue. The other half was obliterated by fibrous tissue, typical of post-thrombotic involution. Possible causes of cartilaginous metaplasia are briefly discussed.

Kinetics of nitrite evaluated in a meat product.

The evaluation of the efficiency with which the reactions involving nitrite proceed in mortadella and of the effect exercised on their kinetics by some variables (ingoing amount of sodium nitrite and temperature) is the purpose of this work. Kinetics parameters were calculated at each level of nitrite added (40, 70, 100 and 150 mg/kg) and at five temperature (55°, 60°, 65°, 70° and 72 °C). While the colour formation reaction is favoured by low activation energy, it becomes crucial to enable nitrite to proceed according to direct reduction thus preventing an increase in nitrate concentration as well as an excess of nitric oxide in the product. Kinetics data suggest that this scope is performed when the product achieves the temperature of 65 °C as fast as possible with an ingoing amount of sodium nitrite of 70 mg/kg.

Emergency transanal haemorrhoidal Doppler guided dearterialization for acute and persistent haemorrhoidal bleeding.

AIM: The effectiveness of Doppler guided transanal haemorrhoidal dearterialization (THD) for arresting persistent haemorrhoidal bleeding in patients admitted as an emergency was studied. METHOD: Eleven patients with severe anal bleeding underwent emergency THD as definitive treatment for haemorrhoids. In the majority of patients antiplatelet or anticoagulant therapy was ongoing and severe anaemia was present in six patients. RESULTS: The mean operative time was 39.7 min. Six to nine feeding arteries were ligated. Intra-operative blood loss was nil. Bleeding was well controlled in all patients. No blood transfusion was required. Mean pain score per verbal numeric scale was 3.6 and 1.4 on day 1 and day 3 respectively. The mean time to resumption of normal activities was 8 days. No major complications were experienced. Six months follow-up demonstrated good control of haemorrhoidal disease. CONCLUSION: THD is effective in controlling acute haemorrhoidal bleeding with a low incidence of postoperative complications.

Use of the robot assisted gait therapy in rehabilitation of patients with stroke and spinal cord injury.

Difficulty in walking is a major feature of neurological disease, and loss of mobility is the activity of daily living on which patients place the greatest value. The impact on patients is enormous, with negative ramifications on their participation in social, vocational, and recreational activities. In current clinical practice the gait restoration with robotic device is an integral part of rehabilitation program. Robot therapy involves the use of a robot exoskeleton device or end-effector device to help the patient retrain motor coordination by performing well-focused and carefully directed repetitive practice. The exoskeleton, as an assistive device, is also an external structural mechanism with joints and links corresponding to those of the human body. These robots use joint trajectories of the entire gait cycle and offer a uniform (more or less) stiff control along this trajectory. In this field the new powered exoskeleton ReWalk (Argo Medical Technologies Ltd) was developed to have an alternative mobility solution to the wheelchair and rehabilitation treatment for individuals with severe walking impairments, enabling them to stand, walk, ascend/descent stairs and more. The end-effector-based robot is a device with footplates placed on a double crank and rocker gear system. Alternatives to powered exoskeletons are devices that use movable footplates to which the patient's feet are attached. All devices include some form of body weight support. Prominent goals in the field include: developing implementable technologies that can be easily used by patients, therapists, and clinicians; enhancing the efficacy of clinician's therapies and increasing the ease of activities in the daily lives of patients.

Action observation and mirror neuron network: a tool for motor stroke rehabilitation.

Mirror neurons are a specific class of neurons that are activated and discharge both during observation of the same or similar motor act performed by another individual and during the execution of a motor act. Different studies based on non invasive neuroelectrophysiological assessment or functional brain imaging techniques have demonstrated the presence of the mirror neuron and their mechanism in humans. Various authors have demonstrated that in the human these networks are activated when individuals learn motor actions via execution (as in traditional motor learning), imitation, observation (as in observational learning) and motor imagery. Activation of these brain areas (inferior parietal lobe and the ventral premotor cortex, as well as the caudal part of the inferior frontal gyrus [IFG]) following observation or motor imagery may thereby facilitate subsequent movement execution by directly matching the observed or imagined action to the internal simulation of that action. It is therefore believed that this multi-sensory action-observation system enables individuals to (re) learn impaired motor functions through the activation of these internal action-related representations. In humans, the mirror mechanism is also located in various brain segment: in Broca's area, which is involved in language processing and speech production and not only in centres that mediate voluntary movement, but also in cortical areas that mediate visceromotor emotion-related behaviours. On basis of this finding, during the last 10 years various studies were carry out regarding the clinical use of action observation for motor rehabilitation of sub-acute and chronic stroke patients.