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.

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.

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis.

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1 expression occurs early in PDAC and correlates with tumour features other than PNI. METHODS: We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in 104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and in PdxCre/LSL-Kras(G12D) mouse model of PDAC. CX3CR1 expression in vitro was studied by a spheroid model, and in vivo by syngenic mouse graft of tumour cells. RESULTS: In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45 (43.3%) both. CX3CR1 expression was independently associated with tumour glandular differentiation (P=0.005) and PNI (P=0.01). Pancreatic Intraepithelial Neoplasias were more frequently CX3CR1+ (80.3%, P<0.001) and CX3CL1+ (86.8%, P=0.002) than matched cancers. The survival of PDAC patients was better in those with CX3CR1+ tumour (P=0.05). Mouse PanINs were also CX3CR1(+) and -CL1(+). In vitro, cytokines significantly increased CX3CL1 but not CX3CR1 expression. Differently, CX3CR1 was upregulated in tumour spheroids, and in vivo only in well-differentiated tumours. CONCLUSION: Tumour differentiation, rather than inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1 expression pattern suggests its early involvement in PDAC progression, outlining a potential target for interfering with the PanIN transition to invasive cancer.

Overdose with levetiracetam: a case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Levetiracetam is an anticonvulsant agent that was first approved for use in the United States in 1999 and has a maximum recommended adult dose of 3000 mg daily. It has been noted to have a relatively mild adverse effect profile, with the most common side effects being somnolence, asthenia, infection, and dizziness. Although it has been widely prescribed, there have been few reports on the safety of this agent in overdose. CASE SUMMARY: We present the case of a 49-year-old man who ingested over 22 500 mg of levetiracetam in a suicide attempt. The patient arrived at the Emergency Department 6·5 h after the ingestion and was noted to have no significant sequelae from the ingestion. Based on the patient's weight, he ingested 358 mg/kg of levetiracetam. WHAT IS NEW AND CONCLUSION: The few cases of levetiracetam overdose reported in the literature were associated with relatively mild, if any, symptoms. However, one patient who overdosed on levetiracetam became obtunded and developed significant respiratory distress that required intubation and ventilatory support. Therefore, clinical vigilance is still required in the cases of levetiracetam overdose.

Tumour necrosis factor alpha and oxidative stress as maintaining factors in the evolution of anorexia nervosa.

OBJECTIVE: Aim of the study was to evaluate tumour necrosis factor α (TNF-α) axis and oxidative status in patients with anorexia nervosa (AN) seeking a possible correlation with both nutritional status and evolution of the disease. SUBJECTS AND METHODS: Thirty-nine consecutive women with AN and an age-matched healthy control group were studied. Patients were 26±9 yr, with a body mass index (BMI) of 13.9±2 kg/m(2). TNF-α, its receptors TNF-R55 and TNF-R75, and oxidative status markers (selenium, ascorbic/ dehydroascorbic acid, retinol, α-tocopherol, selenium-dependent gluthatione peroxidase, reduced/oxidated gluthatione) were measured. A correlation with both nutritional indexes (body weight, BMI, albumin, prealbumin, transferrin, lymphocyte count) and disease duration was investigated. Pearson's correlation and unpaired Student's t-test were used to compare patients and controls. RESULTS: TNF-α and oxidative status markers were significantly higher in patients than controls and TNF-α was directly related to dehydroascorbic acid (p<0.05). Both TNF-R55 and TNF-R75 were higher in patients with duration of disease longer than one year as compared to controls and patients with shorter duration. Receptors inversely correlated with BMI (p<0.05 and p<0.01) and directly with disease duration (p<0.05). Inverse correlation between disease duration and BMI was present (p<0.01). CONCLUSIONS: The study showed activation of TNF-α axis and oxidative stress in AN patients, as well as correlation between the two systems. Due to the correlation between TNF receptors and both BMI and disease duration, a possible role of pro-inflammatory cytokines in the evolution of the eating disorder is suggested.

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.

Antibacterial coatings on haemodialysis catheters by photochemical deposition of silver nanoparticles.

Antibacterial coatings on catheters for acute dialysis were obtained by an innovative and patented silver deposition technique based on the photo-reduction of the silver solution on the surface of catheter, with consequent formation of antibacterial silver nanoparticles. Aim of this work is the structural and morphological characterization of these medical devices in order to analyze the distribution and the size of clusters on the polymeric surface, and to verify the antibacterial capability of the devices treated by this technique against bacterial proliferation. The structure and morphology of the silver nanoparticles were investigated by using scanning and transmission electron microscopy. The antimicrobial capability of the catheters after silver deposition was confirmed by antibacterial tests with Escherichia coli. Both scanning electron microscopy analysis and antibacterial tests were performed also after washing catheters for 30 days in deionized water at 37°C, relating these data to thermogravimetric analysis and to energy dispersive spectroscopy, in order to check the resistance of coating and its antimicrobial capability after the maximum time of life of these devices.

First record of the genus Zygina from a Neotropical region on Populus spp.: taxonomic and biological characteristics.

The typhlocybine, Zygina nivea Mulsant & Rey 1855, was found in urban areas of Argentina colonizing trees of poplar (Populus alba L. and P. nigra L.). This is the first mention of the genus Zygina Fieber from the Neotropical region. In this paper redescription of the male, description of the female, distributional and host plant data, and behavioural observations of this species are given.

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS).

New drugs with anti-tumor activity, also able to modify the expression of selected molecules, are under evaluation in breast cancer which is becoming resistant to conventional treatment, or in metastatic disease. The sodium-iodide symporter (NIS), which mediates iodide uptake into thyroid cells, and is the molecular basis of radioiodine imaging and therapy in thyroid cancer, is also expressed in a large portion of breast tumors. Since NIS expression in breast cancer is not sufficient for a significant iodide uptake, drugs able to induce its expression and correct function are under evaluation. In the present study, we report for the first time that the pan-deacetylase (DAC) inhibitor LBH589 (panobinostat) significantly induced NIS, both as mRNA and as protein, through the increase of NIS promoter activity, with the final consequence of obtaining a significant up-take of iodide in MCF7, T47D, and MDA-MB231 breast cancer cells. Moreover, we observed that LBH589 causes a significant reduction in cell viability of estrogen-sensitive and -insensitive breast cancer cells within nanomolar range. The anti-tumor effect of LBH589 is sustained by apoptosis induction and cell cycle arrest in G(2)/M. In conclusion, our data suggest that LBH589 might be a powerful tool in the management of breast cancer due to its multiple effects and support a potential application of LBH589 in the diagnosis and treatment of this disease.

The effects of the focus ion beam milling process on the optical properties of semiconductor nanostructures.

In this work, the effects of the focus ion beam (FIB) milling process on the optical properties of semiconductor nanostructures were investigated. With this aim, a sensitive materials system based on InGaAs/GaAs quantum dots with well known and excellent optical properties was selected for the FIB treatment. The FIB technique was used to locally remove a metallic mask deposited on top of the quantum dot sample. The photoluminescence (PL) signal, collected from the circular openings, was used to infer the possible damage effects of the ion beam on the properties of the dots.

Detection of Helicobacter and Campylobacter spp. from the aquatic environment of marine mammals.

The mechanism by which Helicobacter species are transmitted remains unclear. To examine the possible role of environmental transmission in marine mammals, we sought the presence of Helicobacter spp. and non-Helicobacter bacteria within the order Campylobacterales in water from the aquatic environment of marine mammals, and in fish otoliths regurgitated by dolphins. Water was collected from six pools, two inhabited by dolphins and four inhabited by seals. Regurgitated otoliths were collected from the bottom of dolphins' pools. Samples were evaluated by culture, PCR and DNA sequence analysis. Sequences from dolphins' water and from regurgitated otoliths clustered with 99.8-100% homology with sequences from gastric fluids, dental plaque and saliva from dolphins living in those pools, and with 99.5% homology with H. cetorum. Sequences from seals' water clustered with 99.5% homology with a sequence amplified from a Northern sea lion (AY203900). Control PCR on source water for the pools and from otoliths dissected from feeder fish were negative. The findings of Helicobacter spp. DNA in the aquatic environment suggests that contaminated water from regurgitated fish otoliths and perhaps other tissues may play a role in Helicobacter transmission among marine mammals.

Helicobacter spp. from gastric biopsies of stranded South American fur seals (Arctocephalus australis).

Gastrointestinal lesions with uncertain etiology have been widely described among pinnipeds. The aim of our study was to investigate the presence of Helicobacter spp. in the gastric mucosa of South American fur seals (Arctocephalusaustralis). Gastric biopsies from thirteen seals, stranded on the shores of the Southwestern Atlantic Ocean in Argentina, were evaluated for the presence of Helicobacter spp. by PCR and DNA sequence analysis. Six gastric biopsies were positive for Helicobacter spp. Pairwise sequence comparisons showed less than 95% identity to novel Helicobacter spp. described from pinnipeds from North America and Australia. However, phylogenetic analysis revealed that the South American fur seal sequences clustered with 99-100% homology with H. cetorum, a species isolated from dolphins and whales. The presence of H. cetorum in pinnipeds, if confirmed by its isolation from the gastric mucosa of these mammals, demonstrates the wide host range of this bacterium in the marine environment.

Stable isotope evidence of ontogenetic changes in the diet of gizzard shad Dorosoma cepedianum.

Stable sulphur isotopic composition (delta(34)S) of gizzard shad Dorosoma cepedianum was used to investigate the seasonal and ontogenetic variation in the diet of young and adult fish. This study evaluated fish from a hypereutrophic lake that had recently undergone a 40% reduction of large (>300 mm total length, L(T)) D. cepedianum biomass as part of a biomanipulation experiment, which aimed at reducing internal nutrient loading. Dorosoma cepedianum delta(34)S values showed evidence of ontogenetic changes with young fish (<200 mm L(T)) depending more on benthic food sources than adults (>200 mm L(T)). The delta(34)S composition of the adult fish suggested an increasing importance of zooplankton in the diet, although benthic food sources remained part of the diet of all D. cepedianum collected in this study. The results indicated that benthic feeding is used by D. cepedianum of all sizes, suggesting that biomanipulation efforts may need to target all sizes of fish to realize benefits.

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.

Antibody to the rheumatoid arthritis nuclear antigen. Its relationship to in vivo Epstein-Barr virus infection.

Most patients with seropositive rheumatoid arthritis, and a variable but lesser percentage of normal subjects, have precipitating antibodies to a nuclear antigen, rheumatoid arthritis nuclear antigen, present in Epstein-Barr virus-infected human B lymphoblastoid cells. We have used a sensitive indirect immunofluorescence assay for antibody to rheumatoid arthritis nuclear antigen in a study of patients with infectious mononucleosis and healthy control subjects. Of 110 sera from normal, college-age cadets, 58 were from individuals without prior Epstein-Barr virus infection, as indicated by the lack of antibody to viral capsid antigen. All of these also lacked activity to rheumatoid arthritis nuclear antigen. 52 sera were positive for antibody to viral capsid antigen, and antibody to rheumatoid arthritis nuclear antigen was present in 26 (50%) of these. In 67 sequential sera from 11 college-age students with infectious mononucleosis who became positive for antibody to rheumatoid arthritis nuclear antigen, only 2 were positive during the 1 mo. Thereafter the incidence and titers increased progressively through the 1st yr after infection. This time-course resembled that for the development of antibody to Epstein-Barr nuclear antigen, another transformation antigen in Epstein-Barr virus-infected B lymphocytes. The development of positivity for both was much later than that of antibody to the structural viral capsid antigen, which in the current study was always positive by 1 wk. Thus, antibody to rheumatoid arthritis nuclear antigen is present in a large proportion of normal individuals and can now be clearly ascribed, from both in vivo and in vitro studies, to prior infection with Epstein-Barr virus.

Metabolism of autologous and homologous IgG in rheumatoid arthritis.

The metabolism of radioiodinated IgG was studied in 20 patients with rheumatoid arthritis and 11 normal controls using autologous IgG and homologous IgG pooled from normal donors. Fractional catabolic rates in the controls were 4.44% of the autologous- and 4.29% of the homologous-labeled protein per day. The corresponding rates in the rheumatoid patients were 9.67% of the autologous- and 8.64% of the homologous-labeled protein per day. Extravascular catabolism occurred only in the rheumatoid group and accounted essentially for the entire increased catabolism of IgG observed in these patients. 10 patients were especially hypercatabolic, with fractional catabolic rates for autologous IgG greater than 10%. Moreover, they catabolized their autologous IgG significantly faster than the homologous IgG (12.6 vs. 9.9%). The increment of catabolism of autologous over homologous IgG also occurred in the extravascular compartment. These highly hypercatabolic patients had a significantly increased number of manifestations of extra-articular disease. The hypercatabolism of IgG could not be correlated with age, weight, sex, duration of disease, joint erosions, corticosteroid therapy, erythrocyte sedimentation rate, rheumatoid factor titer, serum IgG concentration, or circulating immune complexes as measured by the Raji cell radioimmunoassay. Conceivable sites of extravascular catabolism and possible causes of faster catabolism of autologous (rheumatoid) than of homologous (normal) IgG are discussed.

Modulation of airway inflammation in cystic fibrosis. In vivo suppression of interleukin-8 levels on the respiratory epithelial surface by aerosolization of recombinant secretory leukoprotease inhibitor.

Based on the knowledge that neutrophil elastase (NE) in cystic fibrosis (CF) epithelial lining fluid (ELF) can induce human bronchial epithelial cells to express the gene for interleukin 8 (IL-8), an 8.5-kD neutrophil chemoattractant, we have evaluated CF ELF for the presence of IL-8, and investigated the ability of aerosolized recombinant secretory leukoprotease inhibitor (rSLPI) to suppress NE, and hence IL-8, levels on the respiratory epithelial surface in CF. Enzyme-linked immunoassay revealed 21.9 +/- 4.8 nM IL-8 in CF ELF compared with none in normals. Active NE was detectable in ELF of all individuals with CF and was significantly decreased (P < 0.03) after aerosolization of rSLPI. Human bronchial epithelial cells exposed to CF ELF recovered before rSLPI therapy expressed IL-8 mRNA transcripts, but ELF recovered after rSLPI therapy induced far less bronchial epithelial cell IL-8 gene expression. Consistent with this, rSLPI aerosol therapy caused a marked reduction in CF ELF IL-8 levels (P < 0.05) and neutrophil number (P < 0.02). There was also a clear association between CF ELF active NE and IL-8 levels (r = 0.94). These data suggest that rSLPI therapy not only suppresses respiratory epithelial NE levels, but also breaks a cycle of inflammation on the CF epithelial surface.