Adaptable Poly-Articulated Bionic Hands EnhanceBoth Performance and User's Perception in Bilateral Amputation: A Case Study.

This article evaluates and compares the performance and perception of prosthetic devices based on different design principles, a traditional rigid gripper and an adaptable poly-articulated hand, in a pre- and post-training protocol with an individual with bilateral amputation. As a representative of the first class, we use commercial hands (Ottobock's MyoHand VariPlus Speed), which is a widely adopted model by prosthesis users worldwide. We compare these with two SoftHand Pro hands, which are experimental prototypes exhibiting 19 articulations actuated by one single motor, and are inspired by human hand motor control models. Results show that the individual with bilateral amputation, who was a non-expert myoelectric user, achieved better performance with adaptive poly-articulated hands. Furthermore, the acceptation, satisfaction and perceived functionality of the user were considerably higher for the SoftHand Pro. An observational analysis of the patient's behaviour by experienced therapists suggests that adaptable poly-articulated hands reduced compensatory movements and cognitive load. Using soft technologies may be especially advantageous for individuals with bilateral amputation, who present a very limited residual mobility and can largely benefit from the active use of their artificial arms in everyday life.

Current status and future perspectives in HER2 positive advanced gastric cancer

Gastric cancer is one of the most common malignancy worldwide with a prognosis less than 1 year in unresectable or metastatic disease. HER2 expression is the main biomarker to lead the addition of trastuzumab to first line systemic chemotherapy improving the overall survival in advanced HER2-positivegastric adenocarcinoma. The inevitable development of resistance to trastuzumab remains a great problem inasmuch several treatment strategies that have proven effective in breast cancer failed to show clinical benefit in advanced gastric cancer. In this review, we summarize the available data on the mechanisms underlying primary and secondary resistance toHER2-targeted therapy and current challenges in the treatment of HER2-positive advanced gastric cancer refractory to trastuzumab. Further, we describe the prognostic value of new non-invasive screening techniques, the current development of novel agents such us HER2 antibody–drug conjugates and bispecific antibodies, and the strategies with antitumor activity on going.

Current status and future perspectives in HER2 positive advanced gastric cancer.

Gastric cancer is one of the most common malignancy worldwide with a prognosis less than 1 year in unresectable or metastatic disease. HER2 expression is the main biomarker to lead the addition of trastuzumab to first line systemic chemotherapy improving the overall survival in advanced HER2-positivegastric adenocarcinoma. The inevitable development of resistance to trastuzumab remains a great problem inasmuch several treatment strategies that have proven effective in breast cancer failed to show clinical benefit in advanced gastric cancer. In this review, we summarize the available data on the mechanisms underlying primary and secondary resistance toHER2-targeted therapy and current challenges in the treatment of HER2-positive advanced gastric cancer refractory to trastuzumab. Further, we describe the prognostic value of new non-invasive screening techniques, the current development of novel agents such us HER2 antibody-drug conjugates and bispecific antibodies, and the strategies with antitumor activity on going.

Critical analysis of major and ancillary features of LI-RADS v2018 in the differentiation of small (≤ 2 cm) hepatocellular carcinoma from dysplastic nodules with gadobenate dimeglumine-enhanced magnetic resonance imaging.

OBJECTIVE: To evaluate the performance of major features, ancillary features, and categories of Liver Imaging Reporting and Data System (LI-RADS) version 2018 at magnetic resonance (MR) imaging in the differentiation of small hepatocellular carcinoma (HCC) from dysplastic nodules (DNs). PATIENTS AND METHODS: This retrospective study included cirrhotic patients with pathologically proven untreated HCCs and DNs (≤ 2 cm) and liver MR imaging performed with gadobenate dimeglumine contrast agent within 3 months before pathological analysis, between 2015 and 2018. 37 patients with 43 observations (17 HCCs and 26 DNs) met the inclusion criteria. Two radiologists assessed major and ancillary imaging features for each liver observation and assigned a LI-RADS v2018 category in consensus. Estimates of diagnostic performance of major features, ancillary features, and LI-RADS categories were assessed based on their sensitivity, specificity, positive (PPV), and negative predictive values (NPV). RESULTS: Major features (nonrim arterial phase hyperenhancement, nonperipheral "washout", and enhancing "capsule") had a sensitivity of 94.1%, 88.2%, and 41.2%, and a specificity of 57.7%, 42.3%, and 88.5% for HCC, respectively. Ancillary features (hepatobiliary phase hypointensity, mild-moderate T2 hyperintensity, restricted diffusion, and fat in the lesion more than adjacent liver) had a sensitivity of 94.1%, 64.7%, 58.8%, and 11.8%, and a specificity of 26.9%, 61.5%, 65.4%, and 76.9% for HCC, respectively. The LR-5 category (determined by using major features only vs. the combination of major and ancillary features) had a sensitivity of 88.2% at both evaluations and a specificity of 76.9% and 80.8% for HCC, respectively. The combination of LR-4, LR-5 categories (determined by using major features only vs. the combination of major and ancillary features) had a sensitivity of 94.1% at both interpretations and a specificity of 65.4% and 26.9% for HCC, respectively. The use of ancillary features modified LI-RADS category in 25.6% of observations (11/43), predominantly upgraded from LR-3 to LR4 (10/11), increasing the proportion of low-grade DNs and high-grade DNs categorized as LR-4 (from 15.4% to 61.5% and from 7.7% to 46.1%, respectively). CONCLUSIONS: The added value of ancillary features in combination with major features is limited for the non-invasive diagnosis of small HCC; however, their use modifies the final category in a substantial proportion of observations from LR-3 to LR-4, thus allowing possible changes in the management of patients at risk for HCC.

Serum biomarkers for sepsis in children with febrile neutropenia and cancer.

The National Institute for Health and Care Excellence (NICE) defines febrile neutropenia or "neutropenic sepsis" as a patient with an absolute neutrophil count (ANC) less than 0.5 x 109/L and temperature >38°C or signs and symptoms of sepsis.

Extracorporeal shock waves: perspectives in malignant tumor treatment.

Progress in basic research led to the design of new generations of anticancer drugs with some notable achievements. Over the years, more and more powerful drugs have been developed with the purpose of increasing the rate of response to therapy. As molecular power of chemotherapeutic agents increased, unfortunately also toxicity and undesired side-effects increased. The search for new therapeutic strategies to be used in the management of cancer is one of the more promising strategies to reduce chemotherapy toxicity. Extracorporeal Shock Waves (ESW), widely used for the treatment of urolithiasis, have been reported to cause modifications of cell growth both in vitro and in vivo. They exert an agonist cytotoxic effect with several chemotherapeutic agents, such as cisplatin, doxorubicin, bleomycin, paclitaxel. Moreover, as it has been reported that their main mechanism of action is an increase in cell membrane permeability, ESW are also used to deliver oligonucleotides and other small particles to cells. Recently, it was found that certain dye compounds, in particular porphyrins, can achieve a cytopathogenic effect when the disease site is subjected to ultrasound irradiation. This technique is referred to as sonodynamic therapy. Based on the new knowledge regarding the interaction between ultrasound with bulk liquid, several studies have shown a synergic effect of ESW and porphyrins in vitro, thus opening a new perspective in sonodynamic therapy, able to overcome some drawbacks encountered during conventional anticancer drug treatment. Finally, current advances in bioengineering encouraged the application of nano-scale technologies to medicine. Nanobubbles, composed of an external shell and a gas core, can deliver chemotropic drugs and porfirins, to target tumour tissues in response to physical triggers, and ESW features make them an ideal alternative to ultrasound in combination with drug-loaded nanobubbles in delivery strategies.

Characterization of the novel HLA-C*02:106 allele in a hematopoietic stem cell volunteer donor.

HLA-C*02:106 allele differs from C*02:02:02:01 by a C to T substitution in exon 4.

KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages.

Among the strategies adopted by glioma to successfully invade the brain parenchyma is turning the infiltrating microglia/macrophages (M/MΦ) into allies, by shifting them toward an anti-inflammatory, pro-tumor phenotype. Both glioma and infiltrating M/MΦ cells express the Ca(2+)-activated K(+) channel (KCa3.1), and the inhibition of KCa3.1 activity on glioma cells reduces tumor infiltration in the healthy brain parenchyma. We wondered whether KCa3.1 inhibition could prevent the acquisition of a pro-tumor phenotype by M/MΦ cells, thus contributing to reduce glioma development. With this aim, we studied microglia cultured in glioma-conditioned medium or treated with IL-4, as well as M/MΦ cells acutely isolated from glioma-bearing mice and from human glioma biopsies. Under these different conditions, M/MΦ were always polarized toward an anti-inflammatory state, and preventing KCa3.1 activation by 1-[(2-Chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), we observed a switch toward a pro-inflammatory, antitumor phenotype. We identified FAK and PI3K/AKT as the molecular mechanisms involved in this phenotype switch, activated in sequence after KCa3.1. Anti-inflammatory M/MΦ have higher expression levels of KCa3.1 mRNA (kcnn4) that are reduced by KCa3.1 inhibition. In line with these findings, TRAM-34 treatment, in vivo, significantly reduced the size of tumors in glioma-bearing mice. Our data indicate that KCa3.1 channels are involved in the inhibitory effects exerted by the glioma microenvironment on infiltrating M/MΦ, suggesting a possible role as therapeutic targets in glioma.

Comparison of CE-FDG-PET/CT with CE-FDG-PET/MR in the evaluation of osseous metastases in breast cancer patients.

BACKGROUND: Despite improvements in treatments, metastatic breast cancer remains difficult to cure. Bones constitute the most common site of first-time recurrence, occurring in 40-75% of cases. Therefore, evaluation for possible osseous metastases is crucial. Technetium 99 ((99)Tc) bone scintigraphy and fluorodexossyglucose (FDG) positron emission tomography (PET)-computed tomography (PET-CT) are the most commonly used techniques to assess osseous metastasis. PET magnetic resonance (PET-MR) imaging is an innovative technique still under investigation. We compared the capability of PET-MR to that of same-day PET-CT to assess osseous metastases in patients with breast cancer. METHODS: One hundred and nine patients with breast cancer, who underwent same-day contrast enhanced (CE)-PET-CT and CE-PET-MR, were evaluated. CE-PET-CT and CE-PET-MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Binomial confidence intervals and a χ(2) test were used for categorical data, and paired t-test was used for the SUVmax data; a non-informative prior Bayesian approach was used to estimate and compare the specificities. RESULTS: Osseous metastases affected 25 out 109 patients. Metastases were demonstrated by CE-PET-CT in 22 out of 25 patients (88%±7%), and by CE-PET-MR in 25 out of 25 patients (100%). CE-PET-CT revealed 90 osseous metastases and CE-PET-MR revealed 141 osseous metastases (P<0.001). The estimated sensitivity of CE-PET-CT and CE-PET-MR were 0.8519 and 0.9630, respectively. The estimated specificity for CE-FDG-PET-MR was 0.9884. The specificity of CE-PET-CT cannot be determined from patient-level data, because CE-PET-CT yielded a false-positive lesion in a patient who also had other, true metastases. CONCLUSIONS: CE-PET-MR detected a higher number of osseous metastases than did same-day CE-PET-CT, and was positive for 12% of the patients deemed osseous metastasis-negative on the basis of CE-PET-CT.

Detection of a novel HLA-B allele, HLA-B*08:111, in an Italian bone marrow donor.

The newly detected HLA-B*08:111 allele shows two nucleotide differences from B*08:01:01 in codons 113 and 114.