Occupational Exposure Assessment to Antineoplastic Drugs in Nine Italian Hospital Centers over a 5-Year Survey Program.

In the present study, surface contamination where antineoplastic drugs (ADs) are present was investigated, as occupational exposure risk is still an open debate. Despite recommendations and safety standard procedures being in place in health care settings, quantifiable levels of ADs are being reported in the recent literature. Thus, a survey monitoring program was conducted over five years (2016-2021) in nine Italian hospitals. The repeated surveys produced 8288 data points that have been grouped according to the main hospital settings, such as pharmacy areas and patient care units. Based on the most often prepared ADs, the investigated drugs were cyclophosphamide (CP), gemcitabine (GEM), 5-fluorouracil (5-FU), and platinum compounds (Pt). Patient care units had a frequency of positive wipe samples (59%) higher than pharmacies (44%). Conversely, pharmacies had a frequency of positive pad samples higher (24%) than patient care units (10%). Moreover, by statistical analysis, pad samples had a significantly higher risk of contamination in pharmacy areas than in patient care units. In this study, the 75th and the 90th percentiles of the contamination levels were obtained. The 90th percentile was chosen to describe a suitable benchmark that compares results obtained by the present research with those previously reported in the literature. Based upon surface contamination loads, our data showed that 5-FU had the highest concentration values, but the lowest frequency of positive samples. In pharmacy areas, the 90th percentile of 5-FU data distribution was less than 0.346 ng/cm2 and less than 0.443 ng/cm2 in patient care units. AD levels are higher than those reported for health care settings in other European countries yet trends of contamination in Italy have shown to decrease over time.

Fermentation of Vaccinium floribundum Berries with Lactiplantibacillus plantarum Reduces Oxidative Stress in Endothelial Cells and Modulates Macrophages Function.

Accumulating evidence suggests that high consumption of natural antioxidants promotes health by reducing oxidative stress and, thus, the risk of developing cardiovascular diseases. Similarly, fermentation of natural compounds with lactic acid bacteria (LAB), such as Lactiplantibacillus plantarum, enhances their beneficial properties as regulators of the immune, digestive, and cardiovascular system. We investigated the effects of fermentation with Lactiplantibacillus plantarum on the antioxidant and immunomodulatory effects of Pushgay berries (Vaccinium floribundum, Ericaceae family) in human umbilical vein endothelial cells (HUVECs) and macrophage cell line RAW264.7. Polyphenol content was assayed by Folin-Ciocalteu and HPLC-MS/MS analysis. The effects of berries solutions on cell viability or proliferation were assessed by WST8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt and Lactate dehydrogenase (LDH) release, Trypan blue exclusion test, and Alamar blue assay. Antioxidant activity was evaluated by a cell-based chemiluminescent probe for the detection of intracellular H2O2 production in HUVECs. Heme oxygenase-1 (HO-1) expression levels were investigated by RT-qPCR. Glutathione reductase (GR), glutathione peroxidase (Gpx), superoxide dismutase (SOD), and catalase (CAT) activities, as markers of intracellular antioxidant defense, were evaluated by spectrophotometric analysis. The immunomodulatory activity was examined in RAW 264.7 by quantification of inducible nitric oxide synthase (iNOS) and Tumor Necrosis Factor-alpha (TNFα) by RT-qPCR. Data showed that fermentation of Pushgay berries (i) enhances the content of quercetin aglycone, and (ii) increases their intracellular antioxidant activity, as indicated by the reduction in H2O2-induced cell death and the decrease in H2O2-induced HO-1 gene expression in HUVECs treated for 24 h with fermented berries solution (10 µg/mL). Moreover, treatment with Pushgay berries for 72 h (10 µg/mL) promotes cells growth in RAW 264.7, and only fermented Pushgay berries increase the expression of iNOS in the same cell line. Taken together, our results show that LAB fermentation of Pushgay berries enhances their antioxidant and immunomodulatory properties.

A Smartphone-Based Chemosensor to Evaluate Antioxidants in Agri-Food Matrices by In Situ AuNP Formation.

In recent years, there has been a continuously growing interest in antioxidants by both customers and food industry. The beneficial health effects of antioxidants led to their widespread use in fortified functional foods, as dietary supplements and as preservatives. A variety of analytical methods are available to evaluate the total antioxidant capacity (TAC) of food extracts and beverages. However, most of them are expensive, time-consuming, and require laboratory instrumentation. Therefore, simple, cheap, and fast portable sensors for point-of-need measurement of antioxidants in food samples are needed. Here, we describe a smartphone-based chemosensor for on-site assessment of TAC of aqueous matrices, relying on the antioxidant-induced formation of gold nanoparticles. The reaction takes place in ready-to-use analytical cartridges containing an hydrogel reaction medium preloaded with Au(III) and is monitored by using the smartphone's CMOS camera. An analytical device including an LED-based lighting system was developed to ensure uniform and reproducible illumination of the analytical cartridge. The chemosensor permitted rapid TAC measurements of aqueous samples, including teas, herbal infusions, beverages, and extra virgin olive oil extracts, providing results that correlated with those of the reference methods for TAC assessment, e.g., oxygen radical absorbance capacity (ORAC).

Midline lumbar fusion with cortical bone trajectory as first line treatment in a selected series of patients with lumbar instability.

BACKGROUND: The aim of the present study was to proof that for certain complex spinal conditions, midline lumbar fusion (MIDLF) technique is very convenient in terms of length of hospitalization, functional recovery and pain relief and time to back to work. METHODS: MIDLF indications were set for patients with not more than 3 unstable levels, presence of osteoporosis (alternative to cemented screws), or cardiomyopathy with anticoagulation with or without spinal stenosis, and or discopathy. Surgical difficulties, operative time, hemoglobin loss and postoperative 45 days, 6 months and one-year follow-up data are shown. RESULTS: In one-year period MIDLF was applied for 9 patients. For all cases motor deficits improved, pain decreased from a high VAS Score to VAS 1. No complications were seen so far. In one case small pedicles prevented the use of MIDLF technique. CONCLUSIONS: Operative time, acceptable hemoglobin loss, short length of stay and encouraging follow-up result indicate that this technique is a valid option to improve patient's quality of life where osteoporosis makes traditional transpedicular screws less stable or where the surgeon has the need to reduce intraoperative blood loss or has to work in a deep surgical field.

Infection with Spinal Instrumentation: A 20-Year, Single-Institution Experience with Review of Pathogenesis, Diagnosis, Prevention, and Management.

OBJECTIVE AND IMPORTANCE: Instrumentation has become an integral component in the management of various spinal pathologies. The rate of infection varies from 2% to 20% of all instrumented spinal procedures. Postoperative spinal implant infection places patients at risk for pseudo-arthrosis, correction loss, spondylodiscitis, and adverse neurological sequelae and increases health-care costs. MATERIALS AND METHODS: We performed a cohort study of 1065 patients who underwent instrumented spinal procedures in our institution between 1995 and 2014. Fifty-one patients (4.79%) contracted postoperative spinal infection. Isolated bacterial species, infection severity, diagnosis/treatment timing, surgical/medical strategy treatment, and patient's medical background were evaluated to assess their relationship with management outcome. RESULTS: Multiple risk factors for postoperative spinal infection were identified. Infections may be early or delayed. C-reactive protein and magnetic resonance imaging are important diagnostic tools. Prompt diagnosis and aggressive therapy (debridement and parenteral antibiotics) were responsible for implant preservation in 49 of 51 cases, whereas implant removal noted in two cases was attributed to delayed treatment and uncontrolled infection with implant loosening or late infection with spondylodesis. Infection in the setting of instrumentation is more difficult to diagnose and treat due to biofilm. CONCLUSION: Retention of the mechanically sound implants in early-onset infection permits fusion to occur, whereas delayed treatment and multiple comorbidities will most likely result in a lack of effectiveness in eradicating the infecting pathogens. An improved understanding of the role of biofilm and the development of newer spinal implants has provided insight into the pathogenesis and management of infected spinal implants. It is important to accurately identify and treat postoperative spinal infections. The treatment is multimodal and prolonged.

The relationship between obesity and hypertension: an updated comprehensive overview on vicious twins.

Obesity is a growing global health concern, with a rapid increase being observed in morbid obesity. Obesity is associated with an increased cardiovascular risk and earlier onset of cardiovascular morbidity. The growing obesity epidemic is a major source of unsustainable health costs and morbidity and mortality because of hypertension, type 2 diabetes mellitus, dyslipidemia, certain cancers and major cardiovascular diseases. Similar to obesity, hypertension is a key unfavorable health metric that has disastrous health implications: currently, hypertension is the leading contributor to global disease burden, and the direct and indirect costs of treating hypertension are exponentially higher. Poor lifestyle characteristics and health metrics often cluster together to create complex and difficult-to-treat phenotypes: excess body mass is such an example, facilitating a cascade of pathophysiological sequelae that create such as a direct obesity-hypertension link, which consequently increases cardiovascular risk. Although some significant issues regarding assessment/management of obesity remain to be addressed and the underlying mechanisms governing these disparate effects of obesity on cardiovascular disease are complex and not completely understood, a variety of factors could have a critical role. Consequently, a comprehensive and exhaustive investigation of this relationship should analyze the pathogenetic factors and pathophysiological mechanisms linking obesity to hypertension as they provide the basis for a rational therapeutic strategy in the aim to fully describe and understand the obesity-hypertension link and discuss strategies to address the potential negative consequences from the perspective of both primordial prevention and treatment for those already impacted by this condition.

Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein.

Previous studies have shown that tumor-driving glioma stem cells (GSC) may promote radio-resistance by constitutive activation of the DNA damage response started by the ataxia telangiectasia mutated (ATM) protein. We have investigated whether GSC may be specifically sensitized to ionizing radiation by inhibiting the DNA damage response. Two grade IV glioma cell lines (BORRU and DR177) were characterized for a number of immunocytochemical, karyotypic, proliferative and differentiative parameters. In particular, the expression of a panel of nine stem cell markers was quantified by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. Overall, BORRU and DR177 displayed pronounced and poor stem phenotypes, respectively. In order to improve the therapeutic efficacy of radiation on GSC, the cells were preincubated with a nontoxic concentration of the ATM inhibitors KU-55933 and KU-60019 and then irradiated. BORRU cells were sensitized to radiation and radio-mimetic chemicals by ATM inhibitors whereas DR177 were protected under the same conditions. No sensitization was observed after cell differentiation or to drugs unable to induce double-strand breaks (DSB), indicating that ATM inhibitors specifically sensitize glioma cells possessing stem phenotype to DSB-inducing agents. In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB-inducing agents while sparing nonstem cells.

Occupational exposure to antineoplastic drugs in seven Italian hospitals: the effect of quality assurance and adherence to guidelines.

In health care facilities, dermal contact and inhalation are considered to be the main routes of exposure to cytotoxic antineoplastic drugs (ADs). Hand-to-mouth contamination or accidental needle sticks as well as events due to inadequate disposal may also contribute to exposure. In order to measure the extent of contamination, biological and environmental monitoring are essential tools for routine testing. Moreover, reliable sampling and analytical procedures are required. During the last decade, several methods have been developed and validated. The appropriate analytical techniques were used to quantify even very low levels of some of the more commonly used ADs, such as cyclophosphamide, 5-fluoruracil, taxol, anthracyclines, and platinum-compounds. The main objective of this study is to assess the adherence to existing standards of practice through an effective monitoring program, including environmental and biological measurements. In seven hospitals located in Northern-Central Italy, periodic surveys were scheduled to verify continuing compliance with guidelines over a 5-year period. All biological samples were found to be below detection limits and a progressive, significant decrease in workplace contamination was observed. Our results confirm that a cost-effective monitoring regime, including fast and simple sample pre-treatment procedures, simultaneous determination of the analytes and their metabolites, validated procedures including uncertainty evaluation, and periodic surveys, is the adequate approach for the collection of reliable exposure data and hence for effective intervention.

Peritumoral and intratumoral hemorrhage after stereotactic radiosurgery for renal cell carcinoma metastasis to the brain.

Stereotactic Radiosurgery (SRS), provides in a single session, a high dose of radiation to a localized brain tumor volume. Acute adverse reactions after treatment are not uncommon, but are usually transient and generally are well controlled by medication. The authors wish to report this rare complication of intratumoral and peritumoral hemorrhage immediately after LINAC SRS treatment of single temporal lobe metastasis from renal cell carcinoma and discuss plausible causes for this case and its management. A review of the literature on acute intracranial hemorrhage after radiosurgery for metastatic lesions is provided. A 68-year-old man underwent SRS treatment for a single left temporal lobe metastasis. No complications were noticed during frame fixation, treatment itself, or frame removal. Thirty minutes after the end of treatment session the patient acutely became aphasic and right hemiplegic. An urgent CT-scan revealed peritumoral and intratumoral hemorrhage. Patient underwent urgent surgical treatment during which was performed gross total excision of the brain metastasis and total removal of the clot. The patient had a good recovery after surgery and he was discharged with moderate aphasia but able to walk with no other neurological deficits. Stereotactic radiosurgery for metastatic brain tumors should not be considered as a risk-free procedure, especially in cases of neoplasms with high propensity for intratumoral bleeding and, while extremely rare, hemorrhagic complications can occur after treatment. The possibility of acute complications and their consequences have to be discussed with the patient and his or her relatives before radiosurgical treatment.