Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532).

BACKGROUND: Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on binding of the viral spike (S) proteins to angiotensin-converting enzyme 2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is up-regulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections. MATERIALS AND METHODS: We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the coronavirus disease 2019 (COVID-19) pandemic. The parameters used for each COVID-19-positive patient were sex, hospitalization, admission to intensive care unit, death, tumor diagnosis, prostate cancer diagnosis, and ADT. RESULTS: There were evaluable 9280 SARS-CoV-2-positive patients in Veneto on 1 April 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2-positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT (OR 4.05; 95% CI 1.55-10.59). A greater difference was found comparing prostate cancer patients receiving ADT with patients with any other type of cancer (OR 4.86; 95% CI 1.88-12.56). CONCLUSION: Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.

Determination of mercury in hair of children.

Although high or repeated exposure to different forms of Hg can have serious health consequences, the most important toxicity risk for humans is as methylmercury (MeHg) which exposure is mainly through consumption of fish. Generally, more than the 80% of Hg in hair is as MeHg, which is taken up by hair follicles as MeHg-cysteine complexes. In this context, hair samples were collected from 200 children (7 years) living in a coastal site in the North-East (A) of Italy and from 299 children (6-11 years) living in a urban area of South of Italy (B) to determine the levels of MeHg. Considering the neurotoxicity of MeHg, children were subjected to cognitive and neuropsychological tests. The hair values of Hg in the children population groups were comparable with data reported in other international surveys. On the other hand, combining results of the neurological tests with Hg levels, a possible relationship between Hg and an increase of the errors average reported in some neurological tests has been noted. Although the Hg levels were not elevated, a possible neurological influence in children, a population more susceptible than adults, might not be excluded, but the influence on neurological performances of the children could be also due to the family environment (socio economic status, educational level, etc.).

The occurrence of chemical elements and POPs in loggerhead turtles (Caretta caretta): an overview.

Chemical elements and persistent organic pollutants (POPs) are globally present in aquatic systems and their potential transfer to loggerhead marine turtles (Caretta caretta) has become a serious threat for their health status. The environmental fate of these xenobiotics may be traced by the analysis of turtles' tissues and blood. Generally, loggerhead turtles exhibited a higher metal load than other turtle species, this could be explained by differences in diet habits being food the main source of exposure. Literature shows that muscle, liver and kidney are most considered for the quantification of chemical elements, while, organic compounds are typically investigated in liver and fat. This paper is an overview of the international studies carried out on the quantification of chemical elements, polychlorinated biphenyls (PCBs), organochlorines (OCs) and perfluorinated compounds (PFCs), in tissues, organs and fluids of C. caretta from the Mediterranean Sea, the Atlantic and the Pacific Oceans.

Hip viscosupplementation under ultra-sound guidance riduces NSAID consumption in symptomatic hip osteoarthritis patients in a long follow-up. Data from Italian registry.

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) consumption is strictly related to a high gastrointestinal and cardiovascular mortality and morbidity rate. Osteoarthritis Research Society International (OARSI) recommendations in patients with symptomatic hip or knee OA stated that NSAIDs should be used at the lowest effective dose but their long-term use should be avoided if possible. OARSI guidelines for the treatment of the hip OA include the use of viscosupplementation, which aims to restore physiological and rheological features of the synovial fluid. OBJECTIVE: Aim of this multicentric, open and retrospective study is to investigate if NSAID consumption may be reduced by the use of ultrasound-guided intra-articular injection of several hyaluronic acid (HA) products in hip joint administered in patients affected by symptomatic hip OA. MATERIALS AND METHODS: Patients affected by mono or bilateral symptomatic hip OA according to American Rheumatology Association (ARA) criteria, radiological OA graded II-IV (Kellgren and Lawrence) entered the study and were administered with ultrasound-guided intra-articular injection of hyaluronic acid products. As a primary endpoint, consumption of NSAIDs was evaluated by recording the number of days a month (range 0-30) the patient had used NSAID during the previous month, reported at each visit during the 24 months follow-up period. Secondary endpoints included further analysis for subgroups of patients categorized for Lequesne index score, Kellgren-Lawrence score, pain visual analogue scale (VAS) score, ultrasound pattern, age, hyaluronic acid used. RESULTS: 2343 patients entered the study. Regarding primary endpoint, the consumption of NSAIDs was reduced of 48.2% at the third month when compared with baseline values. This sparing effect increased at 12th and 24th month with a reduction respectively of 50% and 61% in comparison to baseline values. These differences were statistically significant. CONCLUSIONS: These data point out that intraarticular hyaluronan preparations provide OA pain relief and reduce NSAIDs consumption in a large cohort of patients for a long period of follow-up. Multiple courses of viscosupplementation (vs) are required to maintain low dose of NSAID consumption over time. NSAIDs consumption is strictly related to an high gastrointestinal and cardiovascular mortality and morbidity rate, instead HA intra-articular treatment is well tolerated and is associated with a low incidence of adverse effects. For these reasons further studies evaluating cost-effectiveness and cost-utility of VS in the management of hip OA are required.

Serum elements and oxidative status in clinically isolated syndromes: imbalance and predictivity.

BACKGROUND: Metals are suspected of being involved in the pathogenesis of various neurologic diseases. We previously found a complex imbalance in serum chemical elements and oxidative status in patients with clinically definite multiple sclerosis (CDMS). OBJECTIVE: To understand whether this imbalance affects people with clinically isolated syndrome (CIS) and, if so, whether it predicts conversion to CDMS. METHODS: We studied 22 chemical elements and the oxidative status in 49 patients with CIS, 49 patients with CDMS, and 49 healthy donors (HD). Univariate and multivariate approaches were used to identify profiles for each group. A logistic regression analysis was used to identify the predictive potential of baseline data (elements, oxidative status, and MRI findings) for conversion to CDMS over 36 months. RESULTS: Several elements and oxidative status values differed significantly among the 3 groups. Discriminant analysis revealed a major contribution of Ca, Fe, Sn, Zn, serum antioxidant capacity, and serum oxidative status, which resulted in distinct profiles (the prediction of group membership was 96% [cross-validated 92%] for HD, 92% [cross-validated 92%] for CDMS, and 90% [cross-validated 86%] for CIS). A weighted combination of element concentrations and oxidative status values, adjusting for all other predictors, would predict a reduction in the risk of conversion to CDMS within 3 years (odds ratio 0.37; 95% confidence interval 0.18-0.76; p = 0.007), thereby proving more effective than MRI at baseline. CONCLUSIONS: The peculiar imbalance in serum elements and oxidative status that characterizes patients with CIS and may predict conversion to CDMS warrants studies on larger sample sizes.

Availability and comparability of human biomonitoring data across Europe: a case-study on blood-lead levels.

Recently, it has become clear that the complexity of environmental health issues requires an approach that takes into account the complexities, interdependencies and uncertainties of the real world. An urgent issue that has surfaced is the need for accurate tools to better describe exposure characterization to environmental chemicals. By including human biomonitoring (HBM) data, a greater precision in exposure and associated risk estimates and more accurate dose-response relationships may be achieved. A restricting issue still is the availability of reliable and comparable HBM data. The aim of the current study was twofold: (1) to find out whether it is practically feasible to collect raw, individual HBM data across Europe; and (2) to evaluate the comparability and use of these HBM data for environmental health impact assessment at a European scale. Blood-lead (B-Pb) was selected as the chemical of choice because of its long history as an environmental pollutant in HBM programs and its known public health relevance. Through literature search and identification of HBM experts across Europe, HBM programs that measured B-Pb were identified and asked to share individual data on age, gender and B-Pb levels. Following this request, more than 20,000 individual data points from 8 European countries were collected. Analysing these data made clear that it is difficult to use disparate data collections because of the inherent variability with respect to the gender and age of participants and calendar-years sampled. When these confounders were taken however, there was no additional variability in B-Pb distributions among different countries. It was concluded that while it is possible to collect HBM data from different sources across Europe, the need to get data from comparable (sub-)populations is essential for appropriate use and interpretation of HBM data for environmental health impact assessment.

PTEN breast cancer susceptibility: a matter of dose.

The phosphatase and tensin homolog located on chromosome ten, PTEN, is one of the most commonly mutated tumor suppressor genes (TSGs) in human cancer [1-3]. PTEN catalyzes the conversion of the membrane lipid second messenger PIP3 to PIP2 and is therefore a key mediator of the AKT/PKB pathway [4,5]. Although inherited PTEN mutations predispose to the development of Cowden syndrome, which is also a breast cancer susceptibility syndrome, the role of PTEN in breast tumorigenesis has been considered minor when compared to that of other TSGs such as BRCA1 or p53 [6]. There is no current evidence that mutations in PTEN account for a substantial proportion of familial breast cancer in the absence of Cowden syndrome [6]. Moreover, PTEN mutations or deletions are not common in sporadic breast tumors, especially when compared with other tumor types (<5%) such as prostate cancer [7, 8].Despite this evidence, recent studies have demonstrated that PTEN protein down-regulation is frequently observed (more than 50%) in sporadic breast tumors, highlighting the relevance of the dose of this TSG for the pathogenesis of breast cancer [7-9]. Our paper, in the last month's issue of Nature Genetics provides additional evidence of the role of PTEN dose in breast cancer susceptibility, braking current dogmas regarding the development of cancer and opening to novel clinical and therapeutic implications [10].

High serum levels of TNF-α and IL-6 predict the clinical outcome of treatment with human recombinant erythropoietin in anaemic cancer patients.

BACKGROUND: A number of anaemic cancer patients are not responsive to treatment with recombinant human erythropoietin (rHuEPO). The aim of the present study is to investigate whether serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and additional laboratory parameters, together with clinical variables, can predict the clinical outcome of treatment with rHuEPO in anaemic cancer patients. PATIENTS AND METHODS: Thirty-five cancer patients and 25 healthy controls were enrolled in this study. Patients were treated with epoetin alfa at the dose of 150 IU/kg s.c. three times a week for 12 weeks. If the haemoglobin (Hb) level failed to improve at least 2 g/dl above baseline by week 6 of treatment, dose was increased to 300 IU/kg s.c. for the remainder of the treatment period. All patients filled out the Brief Fatigue Inventory (BFI), a questionnaire for the self-evaluation of cancer-related fatigue. Serum samples from patients and control groups were frozen at -80 degrees C and TNF-alpha, IL-1beta and IL-6 were later examined by enzyme-linked immunosorbent assay. RESULTS: Fatigued cancer patients had significant higher levels of circulating TNF-alpha, IL-1beta and IL-6 than healthy controls. Responders (Rs) to erythropoietin had significant lower medium levels of TNF-alpha and IL-6 than nonresponders (NRs). Fatigued patients with a general BFI score > or =6 presented higher medium level of cytokines than nonfatigued patients (general BFI score <6), but each group responded similarly to treatment with rHuEPO. CONCLUSIONS: High serum levels of TNF-alpha and IL-6 at the baseline are significantly correlated with a negative response to administration with rHuEPO. Thus, pretreatment evaluation of TNF-alpha and IL-6 serum levels can help to select those patients who are most likely to benefit from treatment with rHuEPO. On the contrary, Hb level, red blood cell count, lactate dehydrogenase and BFI score do not predict the outcome of treatment with rHuEPO.

Iron, zinc and aluminium ferritin content of hemodialysis hyperferritinemic patients: comparison with other hyperferritinemic clinical conditions and normoferritinemic blood donors.

The present study describes the specific content of ferritin iron, zinc and aluminium in four different groups: 1) hemodialysis hyperferritinemic patients; 2) septic patients; 3) iron overloaded patients with hematologic diseases; and 4) blood donors. In all four groups high levels of aluminium and zinc were found in addition to those of iron. However, the sum of the ferritin ions of the control group is significantly higher than that of the other three groups. Furthermore, while ferritin of hemodialysis patients has the same molecular ratio of metal ions as control group (high Al content vs. Fe and Zn), a lower Al/Fe ratio is found both in septic and hematological patients. The results of the present paper might help to explain the high percentage of hyperferritinemia found in hemodialysis patients also in presence of low transferrin saturation and in absence of inflammatory markers. Moreover, the high content of ions other than iron in the ferritin core leads us to believe that ferritin is not only an iron storage protein but rather a regulator of redox active ions.

Viscosupplementation: a suitable option for hip osteoarthritis in young adults.

INTRODUCTION: Young adult hip osteoarthritis (OA) is a noteworthy problem, although rarer than the elderly form of the disease, causing limitations in social and working activities and prospects. Treatment options are scarce and surgical procedures, frequently necessary, imply the major drawback of revising the prostheses periodically, whereas chronic nonsteroidal anti-inflammatory drugs (NSAID) consumption may provoke side effects. To explore alternative options to both surgery and long-term NSAID use, especially in the case of young patients, viscosupplementation seems to appear as an appropriate tool to relieve pain, ameliorate the function and delay surgery. AIM OF THE STUDY: In this study we tackle the issue of the use of hyaluronic acid (HA) injections in young adults with symptomatic hip OA. RESULTS AND CONCLUSIONS: These data, collected from 78 young patients, show that viscosupplementation is a safe procedure, and may provide significant relief from pain and functional recovery. Larger controlled studies are needed to establish otpimal treatment strategies and clinical factors predictive of treatment response.

Distribution and elimination of palladium in male wistar rats following 14-day oral exposure in drinking water.

The Pd tissue distribution and elimination in rats following oral exposure in drinking water of dipotassium hexachloropalladate at doses of 100 or 250 ng/ml for 14 d were determined. The sector field inductively coupled plasma mass spectrometry used for Pd quantification showed the adequate sensitivity (10 ng/l) and accuracy (96-105%), and all the more in consideration of the very low levels of Pd accumulated. Tissues were taken and analyzed after 14 d. The tissue containing the highest Pd concentration was the kidney (4 ng/g dry weight in controls and 75 ng/g dry weight at the maximum dose), with left and right kidneys showing a comparable accumulation. The Pd kidney levels rose, but not significantly, with the administered dose. None of the other organs (liver, lung, spleen, adrenal glands, and bones) appeared to accumulate Pd, even at the highest dose. At the 250-ng/ml dose, small amounts of Pd were found in serum (0.27 ng/ml vs. 0.19 ng/ml in controls), while they were higher in urine (1.2 ng/ml vs. 0.16 ng/ml in controls) and in feces (3,231 ng/g dry weight vs. 69 ng/g dry weight in controls). Feces were the main excretion route for Pd, with a significant linear correlation with exposed dose, which is likely due to low intestinal absorption of Pd.

Ferritin iron content in haemodialysis patients: comparison with septic and hemochromatosis patients.

OBJECTIVES: Hemodialysis (HD) population commonly show high plasma ferritin levels with a poor diagnostic value. The objective of this study is to elucidate the meaning of HD hyperferritinemia through the analysis of its ferritin iron content (FIC). DESIGN AND METHODS: FIC (iron atoms/ferritin molecule) was measured by atomic emission spectrometry. Ferritin and FIC values were correlated with iron storage and inflammation markers and the results of HD patients compared to those of septic and hemochromatosis patients. RESULTS: 1) In the whole HD population, high ferritin levels were associated to low FIC values; 2) the correlation of ferritin with iron indices and inflammation markers in HD patients was intermediate in between that of septic and hemochromatosis patients; 3) the FIC level of HD patients was lower than that of the other two groups. CONCLUSIONS: The high ferritin levels of HD patients are not synonymous with either inflammation or of high levels of iron storage. Their high levels and the low FIC values might be due to the presence inside the ferritin core of oligoelements other than iron.

Sub-cellular localization of manganese in the basal ganglia of normal and manganese-treated rats An electron spectroscopy imaging and electron energy-loss spectroscopy study.

We have studied at the ultrastructural level the presence of manganese (Mn) in rat basal ganglia, which are target regions of the brain for Mn toxicity. The rats underwent a moderate level of Mn exposure induced per os for 13 weeks. Mn was detected by means of electron spectroscopy imaging (ESI) and electron energy-loss spectroscopy (EELS) analyses on perfusion fixed samples embedded in resin. While no significant contamination by exogenous Mn occurred during the processing procedures, less than 50% of endogenous Mn was lost during fixation and dehydration of the brain samples. The residual Mn ions in the samples appeared as discrete particles, localized in selected sub-cellular organelles in a cell, suggesting that no significant translocation had occurred in the surrounding area. In control rats, the Mn sub-cellular localization and relative content were the same in neurons and astrocytes of rat striatum and globus pallidus: the Mn level was highest in the heterochromatin and in the nucleolus, intermediate in the cytoplasm, and lowest in the mitochondria (p<0.001). After chronic Mn treatment, while no ultrastructural damage was detected in the neurons and glial cells, the largest rate of Mn increase was noted in the mitochondria of astrocytes (+700%), an intermediate rate in the mitochondria of neurons (+200%), and the lowest rate in the nuclei (+100%) of neurons and astrocytes; the Mn level in the cytoplasm appeared unchanged. EELS analysis detected the specific spectra of Mn L(2,3) (peak at DeltaE = 665 eV) in such organelles, confirming the findings of ESI. Although a consistent loss of Mn occurred during the processing of tissue samples, ESI and EELS can be useful methods for localization of endogenous Mn in embedded tissues. The high rate of Mn sequestration in the mitochondria of astrocytes in vivo may partly explain the outstanding capacity of astrocytes to accumulate Mn, and their early dysfunction in Mn neurotoxicity. The high level of Mn in the heterochromatin and nucleoli of neurons and astrocytes in basal conditions and its further increase after Mn overload should provide insight into new avenues of investigating the role of Mn in the normal brain and a baseline for future Mn toxicity studies.

[Correlation between radiologic and ultrasonographic patterns and clinical manifestations in symptomatic hip osteoarthritis]. / Correlazione tra quadro clinico e patterns radiologici ed ecografici in pazienti affetti da artrosi sintomatica dell'anca.

Increasing amounts of data have recently been published regarding ultrasonographic (US) findings of osteoarthritic joints, but very few data concern hip joints. In the current study we described US patterns concerning 490 patients affected by symptomatic hip osteoarthritis (OA) who underwent to intra-articular injections of hyaluronic products under US guidance. All patients were studied by US and X-ray of hip, clinical evaluation was assessed by the followings indexes: Lequesne, pain VAS, ICED, Global Physician Assessment and Global Patient Assessment. US findings were summarized in four main patterns, effusion and synovial proliferation were also detected. The aim of this study was to correlate US findings with clinical assessment and radiographic findings (according to Kellgren-Lawrence classification). Pearson's r correlation coefficient were computed and come out significant and positive between X ray and US patterns and between clinical indexes and US patterns. Also the correlation between K-L score and US patterns showed a significant positive correlation indicating that higher K-L scores are associated with increasing abnormal US findings. Our data suggest that ultrasonography of the hip may give useful information about the state of synovial membrane, synovial fluid, joint margins and bone profile in hip OA. Further studies are needed to evaluate their prevalence in hip OA symptomatic and not-symptomatic patients and their correlation to treatment outcome.

[Biomonitoring of iridium in a urban population]. / Biomonitoraggio dell'iridio in una popolazione urbana.

Iridium (Ir) is one of the six elements collectively known as the platinum group metals. For its excellent catalytic properties, Ir was recently introduced into DeNOx, a new generation of automotive catalysts. The aim of our study was to evaluate urinary Ir levels in an urban population. A total of 122 healthy male subjects of Rome (Italy) were studied. Ir quantification in the urine samples of these subjects was carried out by sector field inductively coupled plasma mass spectrometry. The mean urinary Ir level was 10.41 ng/g creatinine (standard deviation: 9.67; 25th-75th percentile: 3,62-12,74 ng/g creatinine). The scientific community should respond to a potential increase in environmental exposure to Ir, due to its growing use as a catalyst, with very careful evaluation of the biological levels of this metal and monitoring of airborne particulate present in the life environment. Further investigation will enable researchers to confirm and integrate the findings of our present study undertaken in the context of surveillance.

Metal changes in CSF and peripheral compartments of parkinsonian patients.

BACKGROUND: Involvement of metals in the risk of developing Parkinson's disease (PD) has been suggested. In the present study, concentration of metals in cerebrospinal fluid (CSF), blood, serum, urine and hair of 91 PD patients and 18 controls were compared. METHODS: Blood and hair were microwave digested, while CSF, serum and urine were water-diluted. Elements quantification was achieved by Inductively Coupled Plasma Atomic Emission Spectrometry and Sector Field Inductively Coupled Plasma Mass Spectrometry. RESULTS: Some metal imbalances in PD were observed: i), in CSF, lower Fe and Si; ii), in blood, higher Ca, Cu, Fe, Mg and Zn; iii), in serum, lower Al and Cu; iv), in urine, lower Al and Mn, higher Ca and Fe; and v), in hair, lower Fe. The ROC analysis suggested that blood Ca, Fe, Mg and Zn were the best discriminators between PD and controls. In addition, hair Ca and Mg were at least 1.5 times higher in females than in males of patients and controls. A decrement with age of patients in hair and urine Ca and, with less extent, in urine Si was observed. Magnesium concentration in CSF decreased with the duration and severity of the disease. Elements were not influenced by the type of antiparkinsonian therapy. CONCLUSIONS: Variation in elements with the disease do not exclude their involvement in the neurodegeneration of PD.

Uncertainty of inductively coupled plasma mass spectrometry based measurements: an application to the analysis of urinary barium, cesium, antimony and tungsten.

The wide use of barium (Ba), cesium (Cs), antimony (Sb) and tungsten (W) in many industrial and agricultural fields causes the increased release of these metals into the environment, laying the basis for health risk. To assess the exposure for the general population, the development of adequate and reliable analytical techniques becomes compulsory. This study refers to the quantification of urinary Ba, Cs, Sb and W levels by both quadrupole (Q) and sector field (SF) inductively coupled plasma mass spectrometry (ICP-MS). The two procedures were compared for their performances and their measurement uncertainties. The limits of detection were (Q and SF) 23.0 and 5.21 ng L(-1) for Ba; 21.1 and 7.52 ng L(-1) for Cs; 1.09 and 0.43 ng L(-1) for Sb; and 0.36 and 0.49 ng L(-1) for W. The trueness was better than 93.3% and the precision less than 12% for both techniques. Relative expanded uncertainties of the analytical procedures, at the median levels found in the general population, were below 5% for all the elements with both ICP-MS techniques. The uncertainties related to the calibration and repeatability were the parameters most influencing the final analytical performance. The urinary median values observed in healthy subjects from central Italy were 1146, 4301, 60.8 and 48.5 ng L(-1) for Ba, Cs, Sb and W, respectively.