Intermediate hepatocellular carcinoma: current treatments and future perspectives

Current guidelines recommend transarterial chemoembolization (TACE) as the standard treatment of Barcelona-Clinic Liver Cancer (BCLC)-B patients. However, the long-term survival outcomes of patients managed with this technique do not appear fully satisfactory; in addition, intermediate-stage hepatocellular carcinoma (HCC) includes a heterogeneous population of patients with varying tumour burdens, liver function and disease aetiology. Therefore, not all patients with intermediate-stage HCC may derive similar benefit from TACE, and some patients may benefit from other treatment options, which are currently approved or being explored. These include different TACE modalities, such as selective TACE or drug-eluting beads TACE and radioembolization. The introduction of sorafenib in the therapeutic armamentarium for HCC has provided a new therapeutic option for the treatment of BCLC-B patients who are unsuitable to TACE or in whom TACE resulted in unacceptable toxicity. In addition, clinical trials aimed at investigating the potential role of this molecule in the treatment of patients with intermediate-stage HCC within combination therapeutic regimens are ongoing. This narrative review will present and discuss the most recent evidence on the locoregional or medical treatment with sorafenib in patients with intermediate-stage HC

Synthesizing Speech from Intracranial Depth Electrodes using an Encoder-Decoder Framework

Speech Neuroprostheses have the potential to enable communication for people with dysarthria or anarthria. Recent advances have demonstrated high-quality text decoding and speech synthesis from electrocorticographic grids placed on the cortical surface. Here, we investigate a less invasive measurement modality in three participants, namely stereotactic EEG (sEEG) that provides sparse sampling from multiple brain regions, including subcortical regions. To evaluate whether sEEG can also be used to synthesize high-quality audio from neural recordings, we employ a recurrent encoder-decoder model based on modern deep learning methods. We find that speech can indeed be reconstructed with correlations up to 0.8 from these minimally invasive recordings, despite limited amounts of training data

Decoding executed and imagined grasping movements from distributed non-motor brain areas using a Riemannian decoder

Using brain activity directly as input for assistive tool control can circumventmuscular dysfunction and increase functional independence for physically impaired people. The motor cortex is commonly targeted for recordings, while growing evidence shows that there exists decodable movement-related neural activity outside of the motor cortex. Several decoding studies demonstrated significant decoding from distributed areas separately. Here, we combine information from all recorded non-motor brain areas and decode executed and imagined movements using a Riemannian decoder. We recorded neural activity from 8 epilepsy patients implanted with stereotactic-electroencephalographic electrodes (sEEG), while they performed an executed and imagined grasping tasks. Before decoding, we excluded all contacts in or adjacent to the central sulcus. The decoder extracts a low-dimensional representation of varying number of components, and classified move/no-move using a minimum-distance-to-geometric-mean Riemannian classifier. We show that executed and imagined movements can be decoded from distributed non-motor brain areas using a Riemannian decoder, reaching an area under the receiver operator characteristic of 0.83 ± 0.11. Furthermore, we highlight the distributedness of the movement-related neural activity, as no single brain area is the main driver of performance. Our decoding results demonstrate a first application of a Riemannian decoder on sEEG data and show that it is able to decode from distributed brain-wide recordings outside of the motor cortex. This brief report highlights the perspective to explore motor-related neural activity beyond the motor cortex, as many areas contain decodable information.</p

Severe forms of partial androgen insensitivity syndrome due to p.L830F novel mutation in androgen receptor gene in a Brazilian family

<p>Abstract</p> <p>Background</p> <p>The androgen insensitivity syndrome may cause developmental failure of normal male external genitalia in individuals with 46,XY karyotype. It results from the diminished or absent biological action of androgens, which is mediated by the androgen receptor in both embryo and secondary sex development. Mutations in the androgen receptor gene, located on the X chromosome, are responsible for the disease. Almost 70% of 46,XY affected individuals inherited mutations from their carrier mothers.</p> <p>Findings</p> <p>Molecular abnormalities in the androgen receptor gene in individuals of a Brazilian family with clinical features of severe forms of partial androgen insensitivity syndrome were evaluated. Seven members (five 46,XY females and two healthy mothers) of the family were included in the investigation. The coding exons and exon-intron junctions of androgen receptor gene were sequenced. Five 46,XY members of the family have been found to be hemizygous for the c.3015C>T nucleotide change in exon 7 of the androgen receptor gene, whereas the two 46,XX mothers were heterozygote carriers. This nucleotide substitution leads to the p.L830F mutation in the androgen receptor.</p> <p>Conclusions</p> <p>The novel p.L830F mutation is responsible for grades 5 and 6 of partial androgen insensitivity syndrome in two generations of a Brazilian family.</p

Differences in bleeding behavior after endoscopic band ligation: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Endoscopic band ligation (EBL) is generally accepted as the treatment of choice for bleeding from esophageal varices. It is also used for secondary prophylaxis of esophageal variceal hemorrhage. However, there is no data or guidelines concerning endoscopic control of ligation ulcers. We conducted a retrospective study of EBL procedures analyzing bleeding complications after EBL.</p> <p>Methods</p> <p>We retrospectively analyzed data from patients who underwent EBL. We analyzed several data points, including indication for the procedure, bleeding events and the time interval between EBL and bleeding.</p> <p>Results</p> <p>255 patients and 387 ligation sessions were included in the analysis. We observed an overall bleeding rate after EBL of 7.8%. Bleeding events after elective treatment (3.9%) were significantly lower than those after treatment for acute variceal hemorrhage (12.1%). The number of bleeding events from ligation ulcers and variceal rebleeding was 14 and 15, respectively. The bleeding rate from the ligation site in the group who underwent emergency ligation was 7.1% and 0.5% in the group who underwent elective ligation. Incidence of variceal rebleeding did not vary significantly. Seventy-five percent of all bleeding episodes after elective treatment occurred within four days after EBL. 20/22 of bleeding events after emergency ligation occured within 11 days after treatment. Elective EBL has a lower risk of bleeding from treatment-induced ulceration than emergency ligation.</p> <p>Conclusions</p> <p>Patients who underwent EBL for treatment of acute variceal bleeding should be kept under medical surveillance for 11 days. After elective EBL, it may be reasonable to restrict the period of surveillance to four days or even perform the procedure in an out-patient setting.</p

Mortality rate of patients with asymptomatic primary biliary cirrhosis diagnosed at age 55 years or older is similar to that of the general population

Recent routine testing for liver function and anti-mitochondrial antibodies has increased the number of newly diagnosed patients with primary biliary cirrhosis (PBC). This study investigated the prognosis of asymptomatic PBC patients, focusing on age difference, to clarify its effect on the prognosis of PBC patients. The study was a systematic cohort analysis of 308 consecutive patients diagnosed with asymptomatic PBC. We compared prognosis between the elderly (55 years or older at the time of diagnosis) and the young patients (< 55 years). The mortality rate of the patients was also compared with that of an age- and gender-matched general population. The elderly patients showed a higher aspartate aminotransferase-to-platelet ratio, and lower alanine aminotransferase level than the young patients (P < 0.01 and P = 0.03, respectively). The two groups showed similar values for alkaline phosphatase and immunoglobulin M. Death in the young patients was more likely to be due to liver failure (71%), while the elderly were likely to die from other causes before the occurrence of liver failure (88%; P < 0.01), especially from malignancies (35%). The mortality rate of the elderly patients was not different from that of the age- and gender-matched general population (standardized mortality ratio, 1.1; 95% confidence interval, 0.6-1.7), although this rate was significantly higher than that of the young patients (P = 0.044). PBC often presents as more advanced disease in elderly patients than in the young. However, the mortality rate of the elderly patients is not different from that of an age- and gender-matched general population

TECNOB: study design of a randomized controlled trial of a multidisciplinary telecare intervention for obese patients with type-2 diabetes

Obesity is one of the most important medical and public health problems of our time: it increases the risk of many health complications such as hypertension, coronary heart disease and type 2 diabetes, needs long-lasting treatment for effective results and involves high public and private costs. Therefore, it is imperative that enduring and low-cost clinical programs for obesity and related co-morbidities are developed and evaluated. METHODS/DESIGN: TECNOB (TEChnology for OBesity) is a comprehensive two-phase stepped down program enhanced by telemedicine for the long-term treatment of obese people with type 2 diabetes seeking intervention for weight loss. Its core features are the hospital-based intensive treatment (1-month), that consists of diet therapy, physical training and psychological counseling, and the continuity of care at home using new information and communication technologies (ICT) such as internet and mobile phones. The effectiveness of the TECNOB program compared with usual care (hospital-based treatment only) will be evaluated in a randomized controlled trial (RCT) with a 12-month follow-up. The primary outcome is weight in kilograms. Secondary outcome measures are energy expenditure measured using an electronic armband, glycated hemoglobin, binge eating, self-efficacy in eating and weight control, body satisfaction, healthy habit formation, disordered eating-related behaviors and cognitions, psychopathological symptoms and weight-related quality of life. Furthermore, the study will explore what behavioral and psychological variables are predictive of treatment success among those we have considered. DISCUSSION: The TECNOB study aims to inform the evidence-based knowledge of how telemedicine may enhance the effectiveness of clinical interventions for weight loss and related type-2 diabetes, and which type of obese patients may benefit the most from such interventions. Broadly, the study aims also to have a effect on the theoretical model behind the traditional health care service, in favor of a change towards a new "health care everywhere" approach

Decoding executed and imagined grasping movements from distributed non-motor brain areas using a Riemannian decoder

Using brain activity directly as input for assistive tool control can circumventmuscular dysfunction and increase functional independence for physically impaired people. The motor cortex is commonly targeted for recordings, while growing evidence shows that there exists decodable movement-related neural activity outside of the motor cortex. Several decoding studies demonstrated significant decoding from distributed areas separately. Here, we combine information from all recorded non-motor brain areas and decode executed and imagined movements using a Riemannian decoder. We recorded neural activity from 8 epilepsy patients implanted with stereotactic-electroencephalographic electrodes (sEEG), while they performed an executed and imagined grasping tasks. Before decoding, we excluded all contacts in or adjacent to the central sulcus. The decoder extracts a low-dimensional representation of varying number of components, and classified move/no-move using a minimum-distance-to-geometric-mean Riemannian classifier. We show that executed and imagined movements can be decoded from distributed non-motor brain areas using a Riemannian decoder, reaching an area under the receiver operator characteristic of 0.83 ± 0.11. Furthermore, we highlight the distributedness of the movement-related neural activity, as no single brain area is the main driver of performance. Our decoding results demonstrate a first application of a Riemannian decoder on sEEG data and show that it is able to decode from distributed brain-wide recordings outside of the motor cortex. This brief report highlights the perspective to explore motor-related neural activity beyond the motor cortex, as many areas contain decodable information