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Whitin Istituto Nazionale di Fisica Nucleare (INFN) outreach activities, the Lab2Go project is of great significance. Its goal is involving high school teachers and students in several laboratory activities, aiming at increasing the weight of experimental contents in teaching and learning. In this article we present the measurement, carried out in the framework of the Lab2Go project, of the cosmic muon flux made by an ArduSiPM-based muon telescope.

Purpose Single-limb stance is a demanding postural task featuring a high number of daily living and sporting activities. Thus, it is widely used for training and rehabilitation, as well as for balance assessment. Muscle activations around single joints have been previously described, however, it is not known which are the muscle synergies used to control posture and how they change between conditions of normal and lack of visual information. Methods Twenty-two healthy young participants were asked to perform a 30 s single-limb stance task in open-eyes and closed-eyes condition while standing on a force platform with the dominant limb. Muscle synergies were extracted from the electromyographical recordings of 13 muscles of the lower limb, hip, and back. The optimal number of synergies, together with the average recruitment level and balance control strategies were analyzed and compared between the open- and the closed-eyes condition. Results Four major muscle synergies, two ankle-dominant synergies, one knee-dominant synergy, and one hip/back-dominant synergy were found. No differences between open- and closed-eyes conditions were found for the recruitment level, except for the hip/back synergy, which significantly decreased (p = 0.02) in the closed-eyes compared to the open-eyes condition. A significant increase (p = 0.03) of the ankle balance strategy was found in the closed-eyes compared to the open-eyes condition. Conclusion In healthy young individuals, single-limb stance is featured by four major synergies, both in open- and closed-eyes condition. Future studies should investigate muscle synergies in participants with other age groups, as well as pathological conditions.

Additional file 1. Example of muscle synergies in one of the participants. Activation coefficients and weight vectors obtained from a representative healthy subject of the sample population considering two different task conditions: eyes open and eyes closed conditions

Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare life-threatening thrombotic microangiopathy (TMA) affecting more frequently women of 30–50 years of age. There is scarce information on the clinical features of aTTP occurring in the elderly. Our goal was to evaluate the impact of an elderly-onset disease on the expression, severity and management of aTTP. Materials and methods: We performed a cross-sectional study of patients enrolled in the Milan TTP Registry (www.ttpdatabase.org) after a first acute episode of aTTP from January 2002 to March 2018. The aTTP diagnosis was suspected on the basis of the presence of thrombocytopenia and microangiopathic hemolytic anemia with no alternative causes, and was confirmed centrally by a severe plasma deficiency of ADAMTS13 activity (

Background Traumatic coagulopathy is thought to increase mortality and its treatment to reduce preventable deaths. However, there is still uncertainty in this field, and available literature results may have been overestimated. Methods We searched the MEDLINE database using the PubMed platform. We formulated four queries investigating the prognostic weight of traumatic coagulopathy defined according to conventional laboratory testing, and the effectiveness in reducing mortality of three different treatments aimed at contrasting coagulopathy (high fresh frozen plasma/packed red blood cells ratios, fibrinogen, and tranexamic acid administration). Randomized controlled trials were selected along with observational studies that used a multivariable approach to adjust for confounding. Strict criteria were adopted for quality assessment based on a two-step approach. First, we rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Then, this rating was downgraded if other three criteria were not met: high reporting quality according to shared standards, absence of internal methodological and statistical issues not detailed by the GRADE system, and absence of external validity issues. Results With few exceptions, the GRADE rating, reporting and methodological quality of observational studies was “very low”, with frequent external validity issues. The only two randomized trials retrieved were, instead, of high quality. Only weak evidence was found for a relation between coagulopathy and mortality. Very weak evidence was found supporting the use of fibrinogen administration to reduce mortality in trauma. On the other hand, we found high evidence that the use of 1:1 vs. 1:2 high fresh frozen plasma/packed red blood cells ratios failed to obtain a 12% mortality reduction. This does not exclude lower mortality rates, which have not been investigated. The use of tranexamic acid in trauma was supported by “high” quality evidence according to the GRADE classification but was downgraded to “moderate” for external validity issues. Conclusions Tranexamic acid is effective in reducing mortality in trauma. The other transfusion practices we investigated have been inadequately studied in the literature, as well as the independent association between mortality and coagulopathy measured with traditional laboratory testing. Overall, in this field of research literature quality is poor.

background The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial. methods We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years. results Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71). conclusions Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment.

Context Pancreatic cancer cells produce various proteases involved in invasion, angiogenesis and metastatic spread. Gabexate mesylate (GM), a serine protease inhibitor, may reduce invasive capabilities and enhance chemotherapy effects. Objective To evaluate the effect of treatment with GM and gemcitabine (GEM), alone or combined. Materials and methods Studies have been performed on cancer cell lines PANC-1, SW1990 and endothelial cell EA.hy926. Treatment consisted of GM (50-100 µM for 24 h), alone or followed by GEM (250 µM for 24 h). Aspects studied included: cell viability (MTT assay), cell invasiveness and migration (Boyden chambers chemoinvasion and chemotaxis assay), angiogenesis (endothelial tube formation assay) and VEGF levels (ELISA) in EA.hy926 cell, MMP-2 and MMP-9 activity (gelatin zymography). Results Cell viability: this parameter decreased by 40% with GM alone only in EA.hy926 cells (P

Background. Anti-angiogenic treatment with targeted agents is effective in advanced hepatocellular carcinoma (HCC). This trial evaluated the safety and efficacy of metronomic capecitabine in patients with HCC. Methods. This single-institution phase II trial included 59 previously untreated patients with advanced HCC and 31 patients resistant to or intolerant of sorafenib. The treatment schedule was capecitabine 500 mg twice daily until progression of disease, unacceptable toxicity level, or withdrawal of informed consent. Progression-free survival (PFS) was chosen as the primary endpoint. Results. A total of 59 previously untreated and 31 previously treated patients with HCC were enrolled. The first cohort achieved a median PFS of 6.03 months and an overall survival (OS) of 14.47 months. Two patients achieved a complete response, 1 patient achieved partial response, and in 30 patients, stable disease was the best outcome. The second cohort achieved a median PFS of 3.27 months and a median OS of 9.77 months. No complete or partial responses were observed, but 10 patients had stable disease. An unscheduled comparison of the first cohort of patients with 3,027 untreated patients with HCC from the Italian Liver Cancer (ITA.LI.CA) database was performed. One-to-one matching according to demographic/etiologic/oncologic features was possible for 50 patients. The median OS for these 50 capecitabine-treated patients was 15.6 months, compared with a median OS of 8.0 months for the matched untreated patients (p = .043). Conclusion. Metronomic capecitabine is well tolerated by patients with advanced HCC and appears to have activity both in treatment-naive patients and in those previously treated with sorafenib.

A systematic review of the published literature clearly demonstrates the usefulness of thromboelastometry (ROTEM®) in detecting coagulation disorders in severe trauma, cardiac and aortic surgery, liver transplantation, and postpartum haemorrhage reliably and within a clinically acceptable turn-around time. In all of the above-mentioned scenarios, the transfusion of any allogeneic blood products could be reduced significantly using ROTEM®-guided bleeding management, thereby minimising or avoiding transfusion-related side effects. Based on the current body of evidence as assessed by the GRADE system, the use of ROTEM® may be recommended in particular for management of severe bleeding after trauma and during cardiac and aortic surgery. However, as laboratory testing contributes only one part of severe bleeding management, the implementation of safe and effective treatment algorithms must be ensured at the same time.

BACKGROUND Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. OBJECTIVES This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. METHODS A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms

[No abstract available]

Cannabis sativa is the most used controlled substance in Europe. With the advent of new and less restrictive European laws on cannabis sale for recreational use (including in Italy), an increase in indoor cannabis crops were observed. This increase was possible due to the availability of cannabis seeds through the internet market. Genetic identification of cannabis can link seizures and if in possession then might aid in an investigation. A 13-locus multiplex STR method was previously developed and validated by Houston et al. A collaborative exercise was organized by the Italian Forensic Geneticists – International Society of Forensic Genetics (Ge.F.I. – ISFG) Working Group with the aim to test the reproducibility, reliability and robustness of this multiplex cannabis STR kit. Twenty-one laboratories from three European countries participated in the collaborative exercise and were asked to perform STR typing of two cannabis samples. Cannabis DNA samples and the multiplex STR kit were provided by the University of Barcelona and Sam Houston State University. Different platforms for PCR amplification, capillary electrophoresis (CE) and genotyping software were selected at the discretion of the participating laboratories. Although the participating laboratories used different PCR equipment, CE platforms and genotyping software, concordant results were obtained from the majority of the samples. The overall genotyping success ratio was 96%. Only minor artifacts were observed. The mean peak height ratio was estimated to be 76.3% and 78.1% for sample 1 and sample 2, respectively. The lowest amount of -1 / + 1 stutter percentage produced, when the height of the parent allele was higher than 8000 RFU, resulted to be less than 10% of the parent allele height. Few common issues were observed such as a minor peak imbalance in some heterozygous loci, some artifact peaks and few instances of allelic drop-out. The results of this collaborative exercise demonstrated the robustness and applicability of the 13-locus system for cannabis DNA profiling for forensic purposes.

In the study of muscle synergies during the maintenance of single-leg stance there are several methodological issues that must be taken into account before muscle synergy extraction. In particular, it is important to distinguish between epochs of surface electromyography (sEMG) signals corresponding to “ well-balanced ” and “ unbalanced ” single-leg stance, since different motor control strategies could be used to maintain balance. The aim of this work is to present and define a robust procedure to distinguish between “ well-balanced ” and “ unbalanced ” single-leg stance to be chosen as input for the algorithm used to extract muscle synergies. Our results demonstrate that the proposed approach for the selection of sEMG epochs relative to “ well-balanced ” and “ unbalanced ” single-leg stance is robust with respect to the selection of the segmentation threshold, revealing a high consistency in the number of muscle synergies and high similarity among the weight vectors (correlation values range from 0.75 to 0.97). Moreover, differences in terms of average recruitment levels and balance control strategies were detected, suggesting a slightly different modular organization between “ well-balanced ” and “ unbalanced ” single-leg stance. In conclusion, this approach can be successfully used as a pre-processing step before muscle synergy extraction, allowing for a better assessment of motor control strategies during the single-leg stance task.

A 55-year-old man affected by a psychotic disorder suddenly died during a quarrel with his father. The autopsy excluded traumatic causes of death, and the cardiac examination identified a severe cardiomegaly with biventricular dilatation of very likely multifactorial origin. Toxicological and pharmacogenetic analyses excluded a fatal intoxication and identified the presence of the antipsychotic drug fluphenazine in the therapeutic range in a normal metabolizer. The screening for genetic variations highlighted a novel heterozygous single-nucleotide variant in the exon 36: c 0.4750C>A (p.Pro1584Thr) of the Ryanodine Receptor Type 2 (RYR2) gene. The mutation detected can be classified as Likely Pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria. RYR2 variation has been associated to catecholaminergic polymorphic ventricular tachycardia (CPVT), a disease currently recognized as one of the most malignant cardiac channelopathies, expressed mostly in young patients, normally in the absence of structural heart disease. The victim late middle age, compared to juvenile onset of CPVT reported in literature, his clinical history, his structurally altered heart, circumstances at death and the absence of phenotype-related variations of dilated cardiomyopathy genes, suggested that the fatal arrhythmia could have been caused by an acquired form of dilated cardiopathy/cardiomyopathy. However, the contribution of the genetic variant to death cannot be completely ruled out, since the significance of a VUS or of a novel variant depends on the data available at the time of investigation, and should be periodically evaluated. We discuss the contribution of the structural alteration and of the variant detected, as well as the role of the molecular autopsy in forensic examination, which can make a significant contribution for inferring both cause and manner of death.

In the study of muscle synergies during the maintenance of single-leg stance (SLS) there are methodological issues that must be taken into account before performing the synergy extraction. In particular, it is important to distinguish between epochs of surface electromyographic (sEMG) signals corresponding to a 'good' balance control during the SLS test, from those characterized by an 'excessive' body sway. The aim of this work is to assess the robustness in the segmentation and selection of sEMG signal epochs to be chosen as input for the synergy extraction algorithm. The robustness is evaluated in terms of: 1) consistency of the number of muscle synergies, and 2) weight vector correlation. Our results show that the same number of muscle synergies and similar weight vectors are obtained, independently from the threshold chosen to build the segmentation mask. The methodology proposed may help the interpretation of muscle synergies in SLS test.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) deficiency, recurring in 30&ndash, 50% of patients. The common human leukocyte antigen (HLA) variant rs6903608 was found to be associated with prevalent iTTP, but whether this variant is associated with disease relapse is unknown. To estimate the impact of rs6903608 on iTTP onset and relapse, we performed a case-control and cohort study in 161 Italian patients with a first iTTP episode between 2002 and 2018, and in 456 Italian controls. Variation in rs6903608 was strongly associated with iTTP onset (homozygotes odds ratio (OR) 4.68 (95% confidence interval (CI) 2.67 to 8.23), heterozygotes OR 1.64 (95%CI 0.95 to 2.83)), which occurred over three years earlier for each extra risk allele (&beta, &minus, 3.34, 95%CI &minus, 6.69 to 0.02). Of 153 survivors (median follow-up 4.9 years (95%CI 3.7 to 6.1)), 44 (29%) relapsed. The risk allele homozygotes had a 46% (95%CI 36 to 57%) absolute risk of relapse by year 6, which was significantly higher than both heterozygotes (22% (95%CI 16 to 29%)) and reference allele homozygotes (30% (95%CI 23 to 39%)). In conclusion, HLA variant rs6903608 is a risk factor for both iTTP onset and relapse. This newly identified biomarker may help with recognizing patients at high risk of relapse, who would benefit from close monitoring or intensified immunosuppressive therapy.

BACKGROUND Cardiac tumors are rare and complex entities. Surgery represents the cornerstone of therapy, while the role of adjuvant treatment remains unclear and, in case of relapse or metastatic disease, the prognosis is very poor. Lack of prospective, randomized clinical trials hinders the generation of high level evidence for the optimal diagnostic workup and multimodal treatment of cardiac sarcomas. Herein, we describe the multidisciplinary clinical management and molecular characterization of a rare case of cardiac myxofibrosarcoma in an elderly woman. CASE SUMMARY A 73-year-old woman presented signs and symptoms of acute left-sided heart failure. Imaging examination revealed a large, left atrial mass. With suspicion of a myxoma, she underwent surgery, and symptoms were promptly relieved. Histology showed a cardiac myxofibrosarcoma, a rare histotype of cardiac sarcoma. Eight months later, disease unfortunately relapsed, and after a multidisciplinary discussion, a chemotherapy with doxorubicin and then gemcitabine was started, achieving partial radiologic and complete metabolic response, which was maintained up to 2 years and is still present. This report is focused on the entire clinical path of our patient from diagnosis to follow-up, through surgery and strategies adopted at relapse. Moreover, due to their rarity, very little is known about the molecular landscape of myxofibrosarcomas. Thus, we also performed and described preliminary genome analysis of the tumor tissue to get further insight on mechanisms involved in tumor growth, and to possibly unveil new clinically actionable targets. CONCLUSION We report a case of cardiac myxofibrosarcoma that achieved a very good prognosis due to an integrated surgical, cardiac and oncologic treatment strategy.

Background: Although imaging techniques have demonstrated the existence of microvascular abnormalities in hypertrophic cardiomyopathy (HCM), a detailed histopathological assessment is lacking as well as a comparison between different phases of the disease. We aimed to compare microvasculopathy and myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) versus end-stage (ES) HCM. Methods: 27 myectomy specimens of HOCM patients and 30 ES-HCM explanted hearts were analyzed. Myocardial fibrosis was quantitatively determined with dedicated software and qualitatively classified as scar-like or interstitial. Intramural coronary arteries were evaluated separately according to lumen diameter: 100–500 μ versus

Objectives: The study objectives were to describe the aortic histopathologic substrates in patients with type A surgically treated acute aortic syndromes, to provide clinico-pathological correlations, and to identify the possible prognostic role of histology. Methods: We assessed the aortic wall degenerative or inflammatory alterations of 158 patients according to the histopathologic consensus documents. Moreover, we correlated these histologic patterns with the patients' clinical data and long-term follow-up for mortality, major aorta-related events, and nonaorta-related events (including cardiovascular ones). Results: We identified 2 histopathologic patterns: 122 patients (77%) with degenerative alterations and 36 patients (23%) with mixed degenerative-atherosclerotic lesions. Patients with mixed alterations were older (mean 69.6 ± 8.7 years vs 62.2 ± 12.4 years, P = .001) and more hypercholesterolemic (33.3% vs 13.9%, P = .017). The degenerative subgroup showed more intralamellar-mucoid extracellular matrix accumulation (86% vs 66.7%, P = .017) and a lower prevalence of translamellar collagen increase (9.8% vs 50%, P < .001). Patients with mixed degenerative-atherosclerotic abnormalities more frequently had long-term nonaorta-related events compared with those with degenerative abnormalities alone (P = .046); no differences were found between the groups with respect to mortality, major aorta-related events, and cardiovascular nonaorta-related events. Conclusions: Although degenerative lesions of the medial layer were present in all specimens, substantial atherosclerosis coexisted in approximately one quarter of cases. Patients with mixed degenerative-atherosclerotic abnormalities had a coherent clinical risk profile, a clinical presentation frequently mimicking acute coronary syndrome, and a higher incidence of nonaorta-related events during follow-up. Histopathologic characterization may improve the long-term prognostic stratification of patients after surgical treatment. © 2018 The American Association for Thoracic Surgery

Amphetamine congeners can be prescribed as anorexiant drugs despite their potential adverse effects, including cardiac toxicity. However, the morphologic features of cardiac damage related to protracted use of these compounds are unknown. We provide a detailed description of cardiac autopsy findings in 3 cases of sudden death associated with protracted use of high doses of phendimetrazine and/or phenylpropanolamine or bupropion prescribed as anorexiants, in association with other compounds. The main cardiac findings were similar in all 3 cases: (1) mild-moderate hypertrophy of the left ventricle and/or the septum; (2) myocardial nonischemic scarring (midmural and/or subepicardial) appearing as discrete foci or with a bandlike morphology; (3) mild-moderate intramural small vessel disease in the absence of significant epicardial coronary artery stenosis; and (4) acute/recent inflammatory lesions consistent with toxic myocarditis. In summary, the detailed pathology examination of the heart in these 3 cases revealed myocardial lesions identical to those reported in catecholamine myocardial damage in all their various stages of evolution. In the presence of a clinical history of long-term intake of anorexiants of this category, it is most important at autopsy to recognize and correctly interpret the acute and chronic myocardial lesions of the type herein described because they represent an anatomical substrate for arrhythmic death.

Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura. Summary: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case–control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02–3.27, P = 1.64 × 10−14). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10−5 to 7.60 × 10-5). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10-19). Imputation of classic HLA genes followed by stepwise conditional analysis revealed that the combination of rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in acquired TTP. Our results refined the association of the HLA class II locus with acquired TTP, confirming its importance in the etiology of this autoimmune disease.

Purpose Limited data suggest that second resections for colorectal cancer metastases may improve survival, but no study has compared surgery with chemotherapy in this setting. Therefore, we retrospectively compared the clinical outcome of potentially resectable patients who received a second metastasectomy with those who did not in our single-centre experience. Methods We retrospectively reviewed the clinical records of all patients treated for metastatic colorectal cancer in our centre over a period of 12 years. We selected patients who relapsed after radical resection of metastases from colorectal cancer and were deemed resectable again by our multidisciplinary team. We then compared the clinical outcome of those who received a second operation with those who refused surgery and also evaluated the role of prognostic factors. Results We identified 60 patients fulfilling the inclusion criteria. Twenty-nine underwent a second resection and 31 refused surgery. Median overall survival rates were 58.7 and 24.0 months, median times to progression were 14.4 and 6.6 months. Patients who received surgery plus perioperatory chemotherapy (18/29) had a significantly better outcome; 4/29 achieved long-term disease-free survival. Conclusions Our study suggests that in highly selected metastatic colorectal cancer patients, a multimodal treatment plan, including a second resection, can achieve longer survival with respect to medical therapy.

Background Hepatocellular carcinoma (HCC) is a highly vascular tumor which is poorly responsive to standard systemic chemotherapy. Recently, various antiangiogenic targeted agents have shown promising activity at different levels of evidence in patients with advanced HCC, suggesting that such treatments might be effective. Case report Since chemotherapy administered with metronomic schedules inhibits angiogenesis, we treated a 64-year-old man with advanced HCC with metronomic capecitabine. After only two months of treatment the HCC nodules disappeared on ultrasonography. This finding was confirmed by a computed tomography scan. After more than three years the patient is still in treatment with minimal toxicity and maintains a complete remission. Conclusions Our case report suggests that metronomic capecitabine may be effective in advanced HCC patients while being also well tolerated. This is important, given the frequent comorbidities of HCC patients. Free full text available at www.tumorionline.it

Purpose Aim of this phase I study was to identify the maximum tolerated dose and dose limiting toxicity of continuous infusion of Irinotecan through a port-a-cath placed in the hepatic artery in patients with hepatocellular carcinoma and cirrhosis to explore new strategies in advanced hepatocellular carcinoma. Response rate and time-to-progression were analysed. Methods Irinotecan was delivered as a five-day continuous infusion every 21 days, with increases of 2.5 mg/m 2 /day every three patients, starting from 7.5 mg/m 2 /day. Dose limiting toxicity corresponded to one patient in each triplet developing G4 haematological or G3 non-haematological toxicity, confirmed in two triplets. Twenty-eight patients (17 Child-Pugh A, 11 B) received treatment and tumour response was assessed after three courses completed by 22 patients. Results Dose limiting toxicity was G3 diarrhoea in two patients, reached at 27.5 mg/m 2 /day and the recommended dose was set at 25 mg/m 2 /day. Nineteen of 30 patients experienced adverse events related to porth-a-cath placement and one died from liver ischemia and sepsis. Median time-to-progression was 11.3 months. Conclusion Intrarterial infusion of Irinotecan is feasible in patients with hepatocellular carcinoma on cirrhosis at a recommended dose of 25 mg/m 2 /day, with no major adverse drug-related events, but with some concerns about the insertion and management of the intra-arterial device.

Gait analysis is widely used in clinics to study walking abnormalities for surgery planning, definition of rehabilitation protocols, and objective evaluation of clinical outcomes. Surface electromyography allows the study of muscle activity non-invasively and the evaluation of the timing of muscle activation during movement. The aim of this study was to present a normative dataset of muscle activation patterns obtained from a large number of strides in a population of 100 healthy children aged 6–11 years. The activity of Tibialis Anterior, Lateral head of Gastrocnemius, Vastus Medialis, Rectus Femoris and Lateral Hamstrings on both lower limbs was analyzed during a 2.5-min walk at free speed. More than 120 consecutive strides were analyzed for each child, resulting in approximately 28,000 strides. Onset and offset instants were reported for each observed muscle. The analysis of a high number of strides for each participant allowed us to obtain the most recurrent patterns of activation during gait, demonstrating that a subject uses a specific muscle with different activation modalities even in the same walk. The knowledge of the various activation patterns and of their statistics will be of help in clinical gait analysis and will serve as reference in the design of future gait studies.