Risk Factors of Positive Resection Margin in Laparoscopic and Open Liver Surgery for Colorectal Liver Metastases: A New Perspective in the Perioperative Assessment: A European Multicenter Study.

OBJECTIVE: To assess the risk factors associated with R1 resection in patients undergoing OLS and LLS for CRLMs. BACKGROUND: The clinical impact of R1 resection in liver surgery for CRLMs has been continuously appraised, but R1 risk factors have not been clearly defined yet. METHODS: A cohort study of patients who underwent OLS and LLS for CRLMs in 9 European high-volume referral centers was performed. A multivariate analysis and the receiver operating characteristic curves were used to investigate the risk factors for R1 resection. A model predicting the likelihood of R1 resection was developed. RESULTS: Overall, 3387 consecutive liver resections for CRLMs were included. OLS was performed in 1792 cases whereas LLS in 1595; the R1 resection rate was 14% and 14.2%, respectively. The risk factors for R1 resection were: the type of resection (nonanatomic and anatomic/nonanatomic), the number of nodules and the size of tumor. In the LLS group only, blood loss was a risk factor, whereas the Pringle maneuver had a protective effect. The predictive size of tumor for R1 resection was >45 mm in OLS and >30 mm in LLS, > 2 lesions was significative in both groups and blood loss >350 cc in LLS. The model was able to predict R1 resection in OLS (area under curve 0.712; 95% confidence interval 0.665-0.739) and in LLS (area under curve 0.724; 95% confidence interval 0.671-0.745). CONCLUSIONS: The study describes the risk factors for R1 resection after liver surgery for CRLMs, which may be used to plan better the perioperative strategies to reduce the incidence of R1 resection during OLS and LLS.

Are perceptual disorder signs in diplegic cerebral palsied children stable over time? A retrospective cohort analysis.

BACKGROUND: A group of diplegic cerebral palsied (CP) children presents six precise signs that can be easily observed during clinical examinations, physiotherapy sessions and everyday activities. These signs are: startle reaction, upper limbs in startle position, averted-eye gaze, grimaces, eye blinking and posture freezing. METHODS: In a population of 32 diplegic CP children (aged 1-8 years) perceptual signs were retrospectively identified through videos to verify their stability in the same child over time. RESULTS: Startle reaction, upper limb in startle position and posture freezing were the most frequently observed signs and the easiest to recognize with the highest agreement in both observations (P<0.001). Eye signs (eye blinking and averted-eye gaze) were more difficult to detect in our recordings. CONCLUSIONS: Signs of perceptual disorders were present in our sample of diplegic CP children from the second year of age and could still be observed after 1- to 3-year intervals, demonstrating they remain unaltered over time. Furthermore, if absent in the first observation, they did not appear later on. CP children with these perceptual signs could represent a new clinical entity, which we are currently describing and defining.

Care Pathways in Rehabilitation for Children and Adolescents with Cerebral Palsy: Distinctiveness of the Adaptation to the Italian Context.

BACKGROUND: In 2020, a multiprofessional panel was set up in collaboration with the Italian FightTheStroke Foundation family association to produce evidence-based recommendations for the management and neuromotor rehabilitation of persons with cerebral palsy aged 2-18 years to implement in clinical practice in Italy. METHODS: The recommendations of these care pathways were developed according to the American Academy for Cerebral Palsy and Developmental Medicine guidelines for Care Pathways Development and the Grading of Recommendations Assessment Development and Evaluation working group for adoption, adaptation, or de novo development of recommendations from high-quality guidelines (GRADE-ADOLOPMENT). RESULTS: Four strong positive recommendations were developed regarding comprehensive management, and twenty-four addressed neuromotor treatment. CONCLUSIONS: A holistic, individualized approach was affirmed in terms of both multidimensional patient profile and interdisciplinary management in a network with the school where children and adolescents are integrated. It was defined that all motor rehabilitation approaches must be individually tailored considering age and developmentally appropriate activities as interventions and goals, in light of the reference curves addressing prognosis for Gross Motor Function and Manual Ability Classification Systems. Intervention must be structured with adaptations of the task and/or of the context (objects and environment) based on the analysis of the child's skills to support motivation and avoid frustration.

Evidence-based management and motor rehabilitation of cerebral palsy children and adolescents: a systematic review.

Background: Evidence regarding the management of several aspects of cerebral palsy improved in recent years. Still, discrepancies are reported in clinical practice. Italian professionals and stakeholders expressed the need of setting up updated, evidenced-based, shared statements, to address clinical practice in cerebral palsy rehabilitation. The objective of the present study was to provide an updated overview of the state of knowledge, regarding the management and motor rehabilitation of children and young people with cerebral palsy, as the framework to develop evidence-based recommendations on this topic. Methods: Guidelines and systematic reviews were searched, relative to evidence-based management and motor treatment, aimed at improving gross motor and manual function and activities, in subjects with cerebral palsy, aged 2-18 years. A systematic search according to the Patients Intervention Control Outcome framework was executed on multiple sites. Independent evaluators provided selection and quality assessment of the studies and extraction of data. Results: Four guidelines, 43 systematic reviews, and three primary studies were included. Agreement among guidelines was reported relative to the general requirements of management and motor treatment. Considering the subject's multidimensional profile, age and developmentally appropriate activities were recommended to set individual goals and interventions. Only a few approaches were supported by high-level evidence (i.e., bimanual therapy and constraint-induced movement therapy to enhance manual performance). Several task-specific active approaches, to improve gross motor function and gait, were reported (mobility and gait training, cycling, backward gait, and treadmill), based on low-level evidence. Increasing daily physical activity and countering sedentary behavior were advised. Based on the available evidence, non-invasive brain stimulation, virtual reality, action-observation therapy, hydrotherapy, and hippotherapy might be complementary to task or goal-oriented physical therapy programs. Conclusion: A multiple-disciplinary family-centered evidence-based management is recommended. All motor rehabilitation approaches to minors affected by cerebral palsy must share the following fundamental characteristics: engaging active involvement of the subject, individualized, age and developmentally appropriate, goal-directed, skill-based, and preferably intensive and time-limited, but suitable for the needs and preferences of the child or young person and their family, and feasible considering the implications for themselves and possible contextual limitations.

PACAP27 is protective against tat-induced neurotoxicity.

Human immunodeficiency virus type-1 (HIV) infection of the central nervous system promotes neuronal injury and apoptosis that culminate in HIV-associated neurocognitive disorders (HAND). Viral proteins, such as transactivator of transcription (Tat), have emerged as leading candidates to explain HIV-mediated neurotoxicity, though the mechanism remains unclear. To determine the effects of Tat, rat cortical neurons were exposed to nanomolar concentrations of Tat for various time points. Within a few hours, Tat induced the production of reactive oxygen species (ROS), and other indices of mitochondrial destabilization. In addition, we observed a significant induction of DNA double-strand breaks (DSBs) by Tat. We next investigated the neuroprotective activity of the pituitary adenylate cyclase-activating polypeptide 27 (PACAP27) against these cardinal features of Tat-induced neurodegeneration. PACAP27 (100 nM) inhibited all Tat-mediated toxic effects including DNA DSBs. Importantly, PACAP27 prevented the induction of neuronal loss induced by Tat. The neuroprotective effect of PACAP27 is correlated with its ability to release the anti-apoptotic chemokine CCL5. Our data support a mechanism of Tat neurotoxicity in which Tat induces mitochondrial destabilization, thus increasing the release of ROS, which causes DNA DSBs leading to cell death. PACAP27, through CCL5, mitigates the effects of Tat-induced neuronal dysfunction, suggesting that PACAP27 could be a new strategy for an adjunct therapy against HIV-associated neurocognitive disorders.