87 research outputs found
Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth
AbstractTaxane efficacy in triple negative breast cancer (TNBC) is limited by insufficient tumor accumulation and severe off-target effects. Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug. Here, 1,000 nm × 400 nm discoidal polymeric nanoconstructs (DPN) encapsulating docetaxel (DTXL) and the near infrared compound lipid-Cy5 were engineered. DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol) template with a polymer mixture comprising poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) diacrylate (PEG-DA) chains together with therapeutic and imaging agents. The resulting "multi-passage" DPN exhibited higher DTXL loading, lipid-Cy5 stability, and stiffness as compared to the conventional "single-passage" approach. Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof. Empty DPN had no toxicity on TNBC cells, whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL (IC50 = 2.6 nM ± 1.0 nM vs. 7.0 nM ± 1.09 nM at 72 h). In orthotopic murine models, DPN accumulated in TNBC more efficiently than free-DTXL. With only 2 mg/kg DTXL, intravenously administered every 2 days for a total of 13 treatments, DTXL-DPN induced tumor regression and were associated to an overall 80% survival rate as opposed to a 30% survival rate for free-DTXL, at 120 days. All untreated mice succumbed before 90 days. Collectively, this data demonstrates that vascular confined multi-passage DPN, biomimicking the behavior of circulating platelets, can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses
Common peroneal nerve injuries at the knee: outcomes of nerve repair
Background. Common peroneal nerve (CPn) lesion at the knee is one of the most frequent neurologic injury of the lower limb. Among the etiologies there are also open and closed trauma. If direct nerve repair is not possible, nerve grafting is indicated as a primary or delayed procedure. Nerve and tendon transfer are other possible therapeutic options.
Material and methods. In this retrospective double center study, 35 patients with post-traumatic CPn lesion at the knee, that underwent surgical repair, were analyzed. Exclusion criteria were severe concomitant neurological pathologies, complex injury of the lower leg including major vessels lesion and or tibial nerve injury. The objective of the study is to demonstrate the degree of foot dorsiflexion recovery based on the type of trauma and the corresponding performed surgery: the Medical Research Council classification (M0-M5) was used as rating scale.
Results. There were 23 closed and 12 open injuries. Time of surgery varied from 6 to 11 months after closed trauma, whereas 2 open traumas were explored at emergency and the remaining 10 patients were explored 3 to 9 months after injury. Neurolysis was performed in 12 cases. Neurorraphy was performed in 2 cases. Sural nerve grafting was performed in 21 patients, with a length range of 6-10,5 cm and 4-9 cm for closed and open trauma respectively.
Conclusions. Our series confirms that repairs of traumatic CPn injuries have an unfavorable outcome. Motor recovery score ≥ M3 was obtained in only 10 cases (28,57%). Neurolysis and nerve suture show better results than nerve graft alone, although no statistically significant differences emerged; CPn reconstructions with grafts show unsatisfactory results, particularly if the length of the grafts exceeds 6 cm and when patients are treated over 6 months after the trauma. Patients with closed trauma achieve less satisfactory results than those with open injury (13 vs 58%) and this was statistically significant (p < 0.05), so palliative surgery may be indicated as the first surgical approach for these patients to achieve good foot dorsiflexion
Epidemiology, Clinical Features and Prognostic Factors of Pediatric SARS-CoV-2 Infection: Results From an Italian Multicenter Study
Background: Many aspects of SARS-CoV-2 infection in children and adolescents
remain unclear and optimal treatment is debated. The objective of our study was
to investigate epidemiological, clinical and therapeutic characteristics of pediatric
SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease.
Methods: The present multicenter Italian study was promoted by the Italian Society
of Pediatric Infectious Diseases, involving both pediatric hospitals and general
pediatricians/family doctors. All subjects under 18 years of age with documented
SARS-CoV-2 infection and referred to the coordinating center were enrolled from
March 2020.
Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years,
IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common
symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was
inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014).
One hundred forty-nine children (19.6%) developed complications. Comorbidities were
risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions,
age 5\u20139 years and lymphopenia were statistically related to ICU admission (p < 0.05).
Garazzino et al. SARS-CoV-2 in Children and Adolescents
Conclusions: Complications of COVID-19 in children are related to comorbidities and
increase with age. Viral co-infections are additional risk factors for disease progression
and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for
ICU admission
Comparison and combination of a hemodynamics/biomarkers-based model with simplified PESI score for prognostic stratification of acute pulmonary embolism: findings from a real world study
Background: Prognostic stratification is of utmost importance for management of acute Pulmonary Embolism (PE) in clinical practice. Many prognostic models have been proposed, but which is the best prognosticator in real life remains unclear. The aim of our study was to compare and combine the predictive values of the hemodynamics/biomarkers based prognostic model proposed by European Society of Cardiology (ESC) in 2008 and simplified PESI score (sPESI).Methods: Data records of 452 patients discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. The ESC model and sPESI were retrospectively calculated and compared by using Areas under Receiver Operating Characteristics (ROC) Curves (AUCs) and finally the combination of the two models was tested in hemodinamically stable patients. All cause and PE-related in-hospital mortality and fatal or major bleedings were the analyzed endpointsResults: All cause in-hospital mortality was 25% (16.6% PE related) in high risk, 8.7% (4.7%) in intermediate risk and 3.8% (1.2%) in low risk patients according to ESC model. All cause in-hospital mortality was 10.95% (5.75% PE related) in patients with sPESI score ≥1 and 0% (0%) in sPESI score 0. Predictive performance of sPESI was not significantly different compared with 2008 ESC model both for all cause (AUC sPESI 0.711, 95% CI: 0.661-0.758 versus ESC 0.619, 95% CI: 0.567-0.670, difference between AUCs 0.0916, p=0.084) and for PE-related mortality (AUC sPESI 0.764, 95% CI: 0.717-0.808 versus ESC 0.650, 95% CI: 0.598-0.700, difference between AUCs 0.114, p=0.11). Fatal or major bleedings occurred in 4.30% of high risk, 1.60% of intermediate risk and 2.50% of low risk patients according to 2008 ESC model, whereas these occurred in 1.80% of high risk and 1.45% of low risk patients according to sPESI, respectively. Predictive performance for fatal or major bleeding between two models was not significantly different (AUC sPESI 0.658, 95% CI: 0.606-0.707 versus ESC 0.512, 95% CI: 0.459-0.565, difference between AUCs 0.145, p=0.34). In hemodynamically stable patients, the combined endpoint in-hospital PE-related mortality and/or fatal or major bleeding (adverse events) occurred in 0% of patients with low risk ESC model and sPESI score 0, whilst it occurred in 5.5% of patients with low-risk ESC model but sPESI ≥1. In intermediate risk patients according to ESC model, adverse events occurred in 3.6% of patients with sPESI score 0 and 6.65% of patients with sPESI score ≥1.Conclusions: In real world, predictive performance of sPESI and the hemodynamic/biomarkers-based ESC model as prognosticator of in-hospital mortality and bleedings is similar. Combination of sPESI 0 with low risk ESC model may identify patients with very low risk of adverse events and candidate for early hospital discharge or home treatment.
Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020
Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered
Natural History of Malignant Bone Disease in Renal Cancer: Final Results of an Italian Bone Metastasis Survey
Abstract Background: Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as diseaserelated survival improves. There are few data on the natural history of bone disease in RCC
Implementation and performances of the IPbus protocol for the JUNO Large-PMT readout electronics
The Jiangmen Underground Neutrino Observatory (JUNO) is a large neutrino
detector currently under construction in China. Thanks to the tight
requirements on its optical and radio-purity properties, it will be able to
perform leading measurements detecting terrestrial and astrophysical neutrinos
in a wide energy range from tens of keV to hundreds of MeV. A key requirement
for the success of the experiment is an unprecedented 3% energy resolution,
guaranteed by its large active mass (20 kton) and the use of more than 20,000
20-inch photo-multiplier tubes (PMTs) acquired by high-speed, high-resolution
sampling electronics located very close to the PMTs. As the Front-End and
Read-Out electronics is expected to continuously run underwater for 30 years, a
reliable readout acquisition system capable of handling the timestamped data
stream coming from the Large-PMTs and permitting to simultaneously monitor and
operate remotely the inaccessible electronics had to be developed. In this
contribution, the firmware and hardware implementation of the IPbus based
readout protocol will be presented, together with the performances measured on
final modules during the mass production of the electronics
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