Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

<p>Abstract</p> <p>Background</p> <p>PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor^®EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration.</p> <p>Methods</p> <p>In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC.</p> <p>Results</p> <p>NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested.</p> <p>Conclusion</p> <p>These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.</p

The cervical fracture as first symptom of multiple myeloma: A case report

Introduction: Multiple Myeloma (MM) is a clonal disorder characterized by proliferation and accumulation of malignant plasma cells in the bone marrow. Bone disease occurs in approximately 80% of patients with newly diagnosed MM. The cervical spine is the least common site of disease involvement. Case presentation: A 60-year-old female patient was referred to the Department of Neurosurgery for bone pain. A magnetic resonance imaging (MRI) scan showed a pathological fracture of the sixth cervical vertebra (C6). The laboratory tests and the bone marrow examination led to a diagnosis of IgA Ï MM (Durie Salmon stage IIIA). The patient underwent a cervical arthrodesis and started systemic Bortezomib-Thalidomide-Dexamethasone (VTD) combination chemotherapy. During chemiotherapic treatment the patient underwent a vertebroplasty of L4-L5. After 4 VTD cycles, the patient was dismissed showing a very good partial remission (VGPR). Later the patient subjected herself to hematopoietic stem cell transplantation (HSCT) obtaining a complete remission. Discussion: We report a clinical case of MM in which the fracture of cervical spine represents the clinical onset. Indeed this clinical presentation is not common in this type of monoclonal gammopathy. This case underlines the importance of suspecting MM in all cases of compromised bone

Risk factors for COVID-19 associated pulmonary aspergillosis and outcomes in patients with acute respiratory failure in a respiratory sub-intensive care unit

Abstract Background COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients. Materials and methods This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients. Results Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155–314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12–31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75–4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12–4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19–5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p  65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20–26.92), p = 0.035]. No differences were observed in hematological cohort. Conclusion CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia

Bioartificial Sponges for Auricular Cartilage Engineering

Auricle reconstruction due to congenital, post-infective or post-traumatic defects represents a challenging procedure in the field of aesthetic and reconstructive surgery due to the highly complex three-dimensional anatomy of the outer ear. Tissue engineering aims to provide alternatives to overcome the shortcomings of standard surgical reconstructive procedure. In the present study, poly(vinyl alcohol)/gelatin (PVA/G) sponges at different weight ratios were produced via emulsion and freeze-drying, and crosslinked by exposure to glutaraldehyde vapors. PVA/G sponges gave rise to highly porous, water stable and hydrophilic scaffolds. Characterization of PVA/G sponges showed round-shaped interconnected pores, high swelling capacity (>200%) and viscoelastic mechanical behavior. The PVA/G 70/30 (w/w) scaffold was selected for in vitro biological studies. Bone marrow derived human mesenchymal stromal cells (hMSCs) were used and differentiated towards chondrogenic lineage under different culture conditions: 1) commercial versus handmade differentiation medium; 2) undifferentiated versus pre-differentiated hMSC seeding; and 3) static versus dynamic culture [i.e. ultrasound (US) or bioreactor stimulation]. Histological results highlighted intense glycosaminoglycan, glycoprotein and collagen syntheses after three weeks, mostly using the commercial medium, whereas round morphology was observed in pre-differentiated cells. In static culture, immunohistochemistry for chondrogenic markers revealed an early differentiation stage, characterized by the expression of Sox-9 and collagen type I fibers. The application of US on cell/scaffold constructs increased extracellular matrix deposition and resulted in 30% higher collagen type II expression at the gene level. Bioreactor culture induced collagen type II, aggrecan and elastin formation. This study demonstrated that 70/30 PVA/G sponge is a suitable candidate for auricle reconstruction

Hypertension and migraine comorbidity: prevalence and risk of cerebrovascular events: evidence from a large, multicenter, cross-sectional survey in Italy (MIRACLES study)

OBJECTIVES: To estimate the prevalence of hypertension-migraine comorbidity; to determine their demographic and clinical characteristics versus patients with hypertension or migraine alone; and to see whether a history of cerebrovascular events was more common in the comorbidity group. METHODS: The MIRACLES, multicenter, cross-sectional, survey included 2973 patients with a known diagnosis of hypertension or migraine in a general practitioner setting in Italy. RESULTS: Five hundred and seventeen patients (17%) suffered from hypertension-migraine comorbidity, whereas 1271 (43%) suffered from hypertension only, and 1185 (40%) from migraine only. In the comorbidity group, the onset of comorbidity occurred at about 45 years of age, with migraine starting significantly later than in the migraine-only group, and hypertension significantly before than in the hypertension-only group; a familial history of both hypertension and migraine had a significantly higher frequency as compared with the hypertension and migraine group. Compared to hypertension (3.1%) and migraine (0.7%), the comorbidity group had a higher prevalence (4.4%) of history of cerebrovascular events, with an odds ratio of a predicted history of stroke/transient ischemic attack (TIA) of 1.76 [95% confidence interval (CI) 1.01-3.07] compared to the hypertension group. In patients without other recognized risk factors for stroke, stroke/TIA occurred more frequently in the comorbidity group, compared to the hypertension group. In the age range 40-49 years, prevalence of history of stroke/TIA was five-fold greater (4.8% in comorbidity vs. 0.9% in hypertension group). CONCLUSION: This cross-sectional study indicates that the prevalence of comorbidity hypertension-migraine is substantial and that patients with comorbidity have a higher probability of history of cerebrovascular events, compared to hypertensive patient

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

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