Hepatocellular carcinoma locoregional therapies for patients in the waiting list. Impact on transplantability and recurrence rate

The practice of treating candidates to liver transplantation (LT) for hepatocellular carcinoma (HCC) with locoregional therapies is common in most transplant centers. However, for T1 tumors and expected waiting times to LT <6 months, there is no evidence that these treatments are beneficial. For T2 tumors and for longer waiting times, neo-adjuvant treatments are usually performed with transarterial chemoembolization (TACE), ablation techniques, and liver resection in selected cases. The treatment choice should be based on the BCLC staging system. At present, there is no evidence of the superiority of ablation/resection vs. TACE, but some studies showed better results of the former in achieving a complete response. The response to neo-adjuvant treatments should be evaluated through mRECIST criteria, but few studies adopted these criteria and properly analyzed factors affecting response. The simultaneous evaluation of the impact of neo-adjuvant therapies on dropout rate, post-LT HCC recurrence and patient survival is rarely reported. Tumor stage and volume, alpha-fetoprotein levels, response to treatments and liver function affect pre-LT outcomes. These same factors, together with vascular invasion and poor tumor differentiation are major determinants of poor post-LT outcomes. Due to the low number of prospective studies with well defined entry criteria and the variability of results, the role of downstaging is still to be defined. Novel molecular markers seem promising for the estimation of prognosis and/or response to treatments. With a persistent scarcity of organ donors, neo-adjuvant treatments can help in identifying patients with different probabilities of cancer progression, and consequently in balancing the priority of HCC and non-HCC-candidates through revised additional scores for HCC

Can People with Chronic Neck Pain Recognize Their Own Digital Pain Drawing?

Background: Although the reliability of pain drawings (PDs) has been confirmed in people with chronic pain, there is a lack of evidence about the validity of the PD, that is, does the PD accurately represent the pain experience of the patient? Objectives: We investigate whether people with chronic neck pain (CNP) can recognize their own PD to support the validity of the PD in reporting the experience of pain. Moreover, we examined the association between their ability to recognize their own PD with their levels of pain intensity and disability and extent of psychosocial and somatic features. Study Design: Experimental. Setting: University Laboratory. Methods: Individuals with CNP completed their PD on a digital body chart, which was then automatically modified with specific dimensions using a novel software, providing an objective range of distortion and eliminating errors, which could potentially occur in manually controlled visual-subjective based methods. Following a 10-minute break listening to music, a series of 20 PDs were presented to each patient in a random order, with only 2 being their original PD. For each PD, the patients rated its likeliness to their own original PD on a scale from 0 to 100, with 100 representing “this is my pain.” Results: Overall, the patients rated their original PD with a median score of 92% similarity, followed by 91.8% and 89.5% similarity when presented with a PD scaled down to 75% and scaled up by 150% of the original size, respectively; these scores were not significantly different to the ratings given for their original PD. The PD with horizontal translation by 40 pixels (8%) and vertical translation by 70 pixels (12.8%) were rated as the most dissimilar to their original PD; these scores were significantly different to their original PD scores. The Spearman correlation coefficient revealed a significant negative association between their ability to recognize their original PD and their Modified Somatic Perceptions Questionnaire scores. Limitations: The patients in the study presented with relatively mild CNP, and the results may not be generalized to those with more severe symptoms. Conclusions: People with CNP are generally able to identify their own PD but that their ability to recognize their original PD is negatively correlated with the extent of somatic awareness

Two-stage hepatectomy with radioembolization for bilateral colorectal liver metastases: A case report

BACKGROUND Two-stage hepatectomy (TSH) is a well-established surgical technique, used to treat bilateral colorectal liver metastases (CRLM) with a small future liver remnant (FLR). However, in classical TSH, drop-out is reported to be around 25%- 40%, due to insufficient FLR increase or progression of disease. Trans-arterial radioembolization (TARE) has been described to control locally tumor growth of liver malignancies such as hepatocellular carcinoma, but it has been also reported to induce a certain degree of contralateral liver hypertrophy, even if at a lower rate compared to portal vein embolization or ligation. CASE SUMMARY Herein we report the case of a 75-year-old female patient, where TSH and TARE were combined to treat bilateral CRLM. According to computed tomography (CT)-scan, the patient had a hepatic lesion in segment VI-VII and two other confluent lesions in segment II-III. Therefore, one-stage posterior right sectionectomy plus left lateral sectionectomy (LLS) was planned. The liver volumetry estimated a FLR of 38% (segments I-IV-V-VIII). However, due to a more than initially planned, extended right resection, simultaneous LLS was not performed and the patient underwent selective TARE to segments II-III after the first surgery. The CT-scan performed after TARE showed a reduction of the treated lesion and a FLR increase of 55%. Carcinoembryonic antigen and CA 19.9 decreased significantly. Nearly three months later after the first surgery, LLS was performed and the patient was discharged without any postoperative complications. CONCLUSION According to this specific experience, TARE was used to induce liver hypertrophy and simultaneously control cancer progression in TSH settings for bilateral CRLM

Effects of 12 Weeks of Essential Amino Acids (EAA)-Based Multi-Ingredient Nutritional Supplementation on Muscle Mass, Muscle Strength, Muscle Power and Fatigue in Healthy Elderly Subjects: A Randomized Controlled Double-Blind Study

Objective: To counteract muscle mass, muscle strength and power loss during aging, and to study age-related change of neuromuscular manifestation of fatigue in relation to nutritional supplementation. Design: randomized controlled double-blind study. Setting: Twice-daily consumption for 12 weeks of an Essential Amino Acids (EAA)-based multi-ingredient nutritional supplement containing EAA, creatine, vitamin D and Muscle Restore Complex®. Participants: 38 healthy elderly subjects (8 male, 30 female; age: 68.91±4.60 years; body weight: 69.40±15.58 kg; height: 1.60±0.09 m) were randomized and allocated in supplement (SUPP) or placebo (PLA) group. Mean Measurements: Vitamin D blood level; Appendicular Lean Mass (ALM); Visceral Adipose Tissue (VAT); Maximal Voluntary Contraction (MVC) and Peak Power (PP); myoelectric descriptors of fatigue: Fractal Dimension and Conduction Velocity initial values (FD iv, CV iv), their rates of change (FD slopes, CV slopes) and the Time to perform the Task (TtT). Mean Results: Significant changes were found in SUPP compared to baseline: Vitamin D (+8.73 ng/ml; p<0.001); ALM (+0.34 kg; p<0.001); VAT (-76.25 g; p<0.001); MVC (+0.52 kg; p<0.001); PP (+4.82 W; p<0.001). Between group analysis (SUPP Vs. PLA) showed improvements: vitamin D blood levels (+11,72 ng/ml; p<0.001); Legs FFM (+443.7 g; p<0.05); ALM (+0.53 kg; p<0.05); MVC (+1.38 kg; p<0.05); PP (+9.87 W; p<0.05). No statistical changes were found for FD iv, CV iv, FD and CV slopes and TtT, either compared to baseline or between groups. Significant correlations between mean differences in SUPP group were also found. Conclusion: The study demonstrates that in healthy elderly subjects an EAA-based multi-ingredient nutritional supplementation of 12 weeks is not effective to change myoelectric manifestation of fatigue and TtT failure but can positively affect muscle mass, muscle strength, muscle power and VAT, counterbalancing more than one year of age-related loss of muscle mass and strength

Families_Share: digital and social innovation for work–life balance

Purpose: The European H2020 Families_Share project aims at offering a grass-root approach and a co-designed platform supporting families for sharing time and tasks related to childcare, parenting, after-school and leisure activities and other household tasks. To achieve this objective, the Families_Share project has been built on current practices which are already leveraging on mutual help and support among families, such as Time Banks, Social Streets and self-organizing networks of parents active at the neighbourhood level and seek to harness the potential of ICT networks and mobile technologies to increase the effectiveness of participatory innovation. The aim of this paper is to present and discuss the Families_Share methodology and platform, as well as the results obtained by several partecipating communities in different European countries. Design/methodology/approach: This paper discusses how the Families Share approach (CAPS project, Horizon 2020) is bringing the sharing economy to childcare. Families Share developed a co-caring approach and a co-designed digital welfare platform to support parents with sharing time and tasks related to childcare, after-school and leisure activities. Families Share conducted two iterative pilot experiments and related socio-economic evaluations in six European cities. More than 3,000 citizens were engaged in the co-design process through their local community organizations and more than 1,700 parents and children actively experimented with the approach by organizing collaborative childcare activities. The authors discuss the challenges and solutions of co-designing a socio-technical approach aimed at facilitating socially innovative childcare models, and how the Families Share approach, based on technology-supported co-production of childcare, may provide a new sustainable welfare model for municipalities and companies with respect to life––work balance. Findings: The authors discuss the challenges and solutions of co-designing a technological tool aimed at facilitating socially innovative childcare models, and how the Families Share approach may provide a new sustainable welfare model for municipalities and companies with respect to work–life balance. Originality/value: As a main difference with state-of-the-art proposals, Families_Share is aimed to provide support to networks of parents in the organization of self-managed activities, this way being orthogonal with respect either to social-network functionalities or to supply and demand services. Furthermore, Families_Share has been based on a participative approach for both the ICT platform and the overall structure

The impact of time interval between hepatic resection and liver transplantation on clinical outcome in patients with hepatocellular carcinoma

Hepatic resection (HR) for hepatocellular carcinoma (HCC) may require secondary liver transplantation (SLT). However, a previous HR is supposed to worsen post-SLT outcomes. Data of patients treated by SLT between 2000 and 2018 at two tertiary referral centers were analyzed. The primary outcome of the study was to analyze the impact of HR on post-LT complications. A Comprehensive Complication Index ≥ 29.6 was chosen as cutoff. The secondary outcome was HCC-re-lated death by means of competing-risk regression analysis. In the study period, 140 patients were included. Patients were transplanted in a median of 23 months after HR (IQR 14–41). Among all the features analyzed regarding the prior HR, only time interval between HR and SLT (time HR-SLT) was an independent predictor of severe complications after LT (OR = 0.98, p &lt; 0.001). According to fractional polynomial regression, the probability of severe complications increased up to 15 months after HR (43%), then slowly decreased over time (OR = 0.88, p &lt; 0.001). There was no significant association between HCC-related death and time HR-SLT at the multivariable competing risks regression model (SHR, 1.06; 95% CI: 0.69–1.62, p = 0.796). This study showed that time HR-SLT was key in predicting complications after LT, without affecting HCC-related death

Muscle Fiber Conduction Velocity Correlates With the Age at Onset in Mild FSHD Cases

A majority of patients with facioscapulohumeral muscular dystrophy (FSHD) report severe fatigue. The aim of this study was to explore whether fatigability during a performance task is related to the main clinical features of the disease in mildly affected patients. A total of 19 individuals with a molecular genetic-based diagnosis of FSHD (median D4Z4 deletion length of 27 kb) performed two isometric flexions of the dominant biceps brachii at 20% of their maximal voluntary contraction (MVC) for 2 min, and then at 60% MVC until exhaustion. Fatigability indices (average rectified value, mean frequency, conduction velocity, and fractal dimension) were extracted from the surface electromyogram (sEMG) signal, and their correlations with age, age at onset, disease duration, D4Z4 contraction length, perceived fatigability, and clinical disability score were analyzed. The conduction velocity during the low level contraction showed a significant negative correlation with the age at onset (p &lt; 0.05). This finding suggest the assessment of conduction velocity at low isometric contraction intensities, as a potential useful tool to highlight differences in muscle involvement in FSHD patients

Automatically Extracted Machine Learning Features from Preoperative CT to Early Predict Microvascular Invasion in HCC: The Role of the Zone of Transition (ZOT)

Background: Microvascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma (HCC) recurrence after treatments. No reliable radiological imaging findings are available for preoperatively diagnosing MVI, despite some progresses of radiomic analysis. Furthermore, current MVI radiomic studies have not been designed for small HCC nodules, for which a plethora of treatments exists. This study aimed to identify radiomic MVI predictors in nodules &lt;= 3.0 cm by analysing the zone of transition (ZOT), crossing tumour and peritumour, automatically detected to face the uncertainties of radiologist's tumour segmentation. Methods: The study considered 117 patients imaged by contrast-enhanced computed tomography; 78 patients were finally enrolled in the radiomic analysis. Radiomic features were extracted from the tumour and the ZOT, detected using an adaptive procedure based on local image contrast variations. After data oversampling, a support vector machine classifier was developed and validated. Classifier performance was assessed using receiver operating characteristic (ROC) curve analysis and related metrics. Results: The original 89 HCC nodules (32 MVI+ and 57 MVI-) became 169 (62 MVI+ and 107 MVI-) after oversampling. Of the four features within the signature, three are ZOT heterogeneity measures regarding both arterial and venous phases. On the test set (19MVI+ and 33MVI-), the classifier predicts MVI+ with area under the curve of 0.86 (95%CI (0.70-0.93), p similar to 10(-5)), sensitivity = 79% and specificity = 82%. The classifier showed negative and positive predictive values of 87% and 71%, respectively. Conclusions: The classifier showed the highest diagnostic performance in the literature, disclosing the role of ZOT heterogeneity in predicting the MVI+ status

Circulating miR-122-5p, miR-92a-3p, and miR-18a-5p as Potential Biomarkers in Human Liver Transplantation Follow-Up

The requirement of blood-circulating sensitive biomarkers for monitoring liver transplant (LT) is currently a necessary step aiming at the reduction of standard invasive protocols, such as liver biopsy. In this respect, the main objective of this study is to assess circulating microRNA (c-miR) changes in recipients’ blood before and after LT and to correlate their blood levels with gold standard biomarkers and with outcomes such as rejection or complications after graft. An miR profile was initially performed; then, the most deregulated miRs were validated by RT-qPCR in 14 recipients pre- and post-LT and compared to a control group of 24 nontransplanted healthy subjects. MiR-122-5p, miR-92a-3p, miR-18a-5p, and miR-30c-5p, identified in the validation phase, were also analyzed considering an additional 19 serum samples collected from LT recipients and focusing on different follow-up (FU) times. The results showed significant, FU-related changes in c-miRs. In particular, miR-122-5p, miR-92a-3p, and miR-18a-5p revealed the same trend after transplantation and an increase in their level was found in patients with complications, independently from FU times. Conversely, the variations in the standard haemato-biochemical parameters for liver function assessment were not significant in the same FU period, confirming the importance of c-miRs as potential noninvasive biomarkers for monitoring patients’ outcomes