Increased cancer risk in patients undergoing dialysis: a population-based cohort study in North-Eastern Italy

open116noBACKGROUND: In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy. METHODS: A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998-2013). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15-1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42-2.45 for age 40-59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89-10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06-4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46-2.22), oral cavity (SIR = 2.42, 95% CI: 1.36-4.00), and Kaposi's sarcoma (SIR = 10.29, 95% CI: 1.25-37.16). CONCLUSIONS: The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.openTaborelli, Martina; Toffolutti, Federica; Del Zotto, Stefania; Clagnan, Elena; Furian, Lucrezia; Piselli, Pierluca; Citterio, Franco; Zanier, Loris; Boscutti, Giuliano; Serraino, Diego for the Italian Transplant & Cancer Cohort Study; Sarah Shalaby, Raffaella Petrara, Patrizia Burra, Giacomo Zanus, Stefano Zanini,Paolo Rigotti; Maria Rendina, AlfredoDi Leo, Francesco Paolo Schena, Giuseppe Grandaliano, Marco Fiorentino, Augusto Lauro, Antonio Daniele Pinna, PaoloDi Gioia, Sara Pellegrini, Chiara Zanfi, Maria Piera Scolari, Sergio Stefoni, PaolaTodeschini, Laura Panicali, Chiara Valentini, Umberto Baccarani, Andrea Risaliti, Gian Luigi Adani, Dario Lorenzin, Giuseppe Maria Ettorre, Giovanni Vennarecci,Marco Colasanti, Manuela Coco, Fabrizio Ettorre, Roberto Santoro, LuciaMiglioresi, Francesco Nudo, Massimo Rossi,Gianluca Mennini, Luca Toti, GiuseppeTisone, Annachiara Casella, Laura Fazzolari, Daniele Sforza, Giuseppe Iaria,Carlo Gazia, Chiara Belardi, ClaudiaCimaglia, Alessandro Agresta, Gianpiero D’Offizi, Ubaldo Visco Comandini,Raffaella Lionetti, Marzia Montalbano, Chiara Taibi, Giovanni Fantola, Fausto Zamboni, Gian Benedetto Piredda,Maria Benigna Michittu, Maria Gavina Murgia, Bruno Onano, Lucia Fratino, Luigino Dal Maso, Paolo De Paoli, Diana Verdirosi,Emanuela Vaccher, Francesco Pisani, Antonio Famulari, Federica Delreno, Samuele Iesari, LindaDe Luca, Maurizio Iaria, Enzo Capocasale,Elena Cremaschi, Silvio Sandrini, Francesca Valerio,Valentina Mazzucotelli, Nicola Bossini, Gisella Setti, Massimiliano Veroux, Pierfrancesco Veroux, Giuseppe Giuffrida,Alessia Giaquinta, Domenico Zerbo, GhilBusnach, Laura Di Leo, Maria Luisa Perrino, Marialuisa Querques, ValerianaColombo, Maria Chiara Sghirlanzoni , Piergiorgio Messa, Antonio Leoni , Laura Galatioto, Salvatore Gruttadauria, Vito Sparacino, FlaviaCaputo, Barbara Buscemi ,Franco Cit-terio, Gionata Spagnoletti, Maria Paola Salerno, Evaldo Favi Giuseppe Paolo Segoloni, Luigi Biancone, AntonioLavacca, Maria Cristina Maresca, CarmeloCascone, Bice Virgilio, Donato Donati, Fiorella Dossi, Andrea Fontanella, Andrea Ambrosini, Marco Di CiccoTaborelli, Martina; Toffolutti, Federica; Del Zotto, Stefania; Clagnan, Elena; Furian, Lucrezia; Piselli, Pierluca; Citterio, Franco; Zanier, Loris; Boscutti, Giuliano; Serraino, Diego for the Italian Transplant & Cancer Cohort Study; Shalaby, Sarah; Petrara, MARIA RAFFAELLA; Burra, Patrizia; Zanus, Giacomo; Zanini, Stefano; Rigotti, Paolo; Maria, Rendina; Alfredodi, Leo; Francesco Paolo Schena, ; Giuseppe, Grandaliano; Marco, Fiorentino; Augusto, Lauro; Antonio Daniele Pinna, ; Paolodi, Gioia; Sara, Pellegrini; Chiara, Zanfi; Maria Piera Scolari, ; Sergio, Stefoni; Paolatodeschini, ; Laura, Panicali; Chiara, Valentini; Umberto, Baccarani; Andrea, Risaliti; Gian Luigi Adani, ; Dario, Lorenzin; Giuseppe Maria Ettorre, ; Giovanni, Vennarecci; Marco, Colasanti; Manuela, Coco; Fabrizio, Ettorre; Roberto, Santoro; Luciamiglioresi, ; Francesco, Nudo; Massimo, Rossi; Gianluca, Mennini; Luca, Toti; Giuseppetisone, ; Annachiara, Casella; Laura, Fazzolari; Daniele, Sforza; Giuseppe, Iaria; Carlo, Gazia; Chiara, Belardi; Claudiacimaglia, ; Alessandro, Agresta; Gianpiero, D’Offizi; Ubaldo Visco Comandini, ; Raffaella, Lionetti; Marzia, Montalbano; Chiara, Taibi; Giovanni, Fantola; Fausto, Zamboni; Gian Benedetto Piredda, ; Maria Benigna Michittu, ; Maria Gavina Murgia, ; Bruno, Onano; Lucia, Fratino; Luigino Dal Maso, ; Paolo De Paoli, ; Diana, Verdirosi; Emanuela, Vaccher; Francesco, Pisani; Antonio, Famulari; Federica, Delreno; Samuele, Iesari; Lindade, Luca; Maurizio, Iaria; Enzo, Capocasale; Elena, Cremaschi; Silvio, Sandrini; Francesca, Valerio; Valentina, Mazzucotelli; Nicola, Bossini; Gisella, Setti; Massimiliano, Veroux; Pierfrancesco, Veroux; Giuseppe, Giuffrida; Alessia, Giaquinta; Domenico, Zerbo; Ghilbusnach, ; Laura Di Leo, ; Maria Luisa Perrino, ; Marialuisa, Querques; Valerianacolombo, ; Maria Chiara Sghirlanzoni, ; Piergiorgio, Messa; Antonio, Leoni; Laura, Galatioto; Salvatore, Gruttadauria; Vito, Sparacino; Flaviacaputo, ; Barbara, Buscemi; Franco, Cit-terio; Gionata, Spagnoletti; Maria Paola Salerno, ; Evaldo Favi Giuseppe Paolo Segoloni, ; Luigi, Biancone; Antoniolavacca, ; Maria Cristina Maresca, ; Carmelocascone, ; Bice, Virgilio; Donato, Donati; Fiorella, Dossi; Andrea, Fontanella; Andrea, Ambrosini; Marco Di Cicco

COVID-19 and kidney transplantation: an Italian Survey and Consensus

Italy was the first Western country to face the COVID-19 pandemic. Here we report the results of a national survey on kidney transplantation activity in February and March 2020, and the results of a three-round Delphi consensus promoted by four scientific societies: the Italian Society of Organ Transplantation, the Italian Society of Nephrology, the Italian Society of Anesthesia and Intensive Care, and the Italian Group on Antimicrobial Stewardship. All 41 Italian transplant centers were invited to express their opinion in the Delphi rounds along with a group of seven experts. The survey revealed that, starting from March 2020, there was a decline in kidney transplantation activity in Italy, especially for living-related transplants. Overall, 60 recipients tested positive for SARS-CoV2 infection, 57 required hospitalization, 17 were admitted to the ICU, and 11 died. The online consensus had high response rates at each round (95.8%, 95.8%, and 89.5%, respectively). Eventually, 27 of 31 proposed statements were approved (87.1%), 12 at the first or second round (38.7%), and 3 at the third (9.7%). Based on the Italian experience, we discuss the reasons for the changes in kidney transplantation activity during the COVID-19 pandemic in Western countries. We also provide working recommendations for the organization and management of kidney transplantation under these conditions

Effects of periodic breathing on sleep at high altitude: a randomized, placebo-controlled, crossover study using inspiratory CO2

Abstract: Hypoxia at high altitude facilitates changes in ventilatory control that can lead to nocturnal periodic breathing (nPB). Here, we introduce a placebo-controlled approach to prevent nPB by increasing inspiratory CO2 and used it to assess whether nPB contributes to the adverse effects of hypoxia on sleep architecture. In a randomized, single-blinded, crossover design, 12 men underwent two sojourns (three days/nights each, separated by 4 weeks) in hypobaric hypoxia corresponding to 4000 m altitude, with polysomnography during the first and third night of each sojourn. During all nights, subjects’ heads were encompassed by a canopy retaining exhaled CO2, and CO2 concentration in the canopy (i.e. inspiratory CO2 concentration) was controlled by adjustment of fresh air inflow. Throughout the placebo sojourn inspiratory CO2 was ≤0.2%, whereas throughout the other sojourn it was increased to 1.76% (IQR, 1.07%–2.44%). During the placebo sojourn, total sleep time (TST) with nPB was 54.3% (37.4%–80.8%) and 45.0% (24.5%–56.5%) during the first and the third night, respectively (P = 0.042). Increased inspiratory CO2 reduced TST with nPB by an absolute 38.1% (28.1%–48.1%), the apnoea–hypopnoea index by 58.1/h (40.1–76.1/h), and oxygen desaturation index ≥3% by 56.0/h (38.9.1–73.2/h) (all P < 0.001), whereas it increased the mean arterial oxygen saturation in TST by 2.0% (0.4%–3.5%, P = 0.035). Increased inspiratory CO2 slightly increased the percentage of N3 sleep during the third night (P = 0.045), without other effects on sleep architecture. Increasing inspiratory CO2 effectively prevented hypoxia-induced nPB without affecting sleep macro-architecture, indicating that nPB does not explain the sleep deterioration commonly observed at high altitudes. (Figure presented.). Key points: Periodic breathing is common during sleep at high altitude, and it is unclear how this affects sleep architecture. We developed a placebo-controlled approach to prevent nocturnal periodic breathing (nPB) with inspiratory CO2 administration and used it to assess the effects of nPB on sleep in hypobaric hypoxia. Nocturnal periodic breathing was effectively mitigated by an increased inspiratory CO2 fraction in a blinded manner. Prevention of nPB did not lead to relevant changes in sleep architecture in hypobaric hypoxia. We conclude that nPB does not explain the deterioration in sleep architecture commonly observed at high altitude

Immune activation, immune senescence and levels of Epstein Barr Virus in kidney transplant patients: Impact of mTOR inhibitors

Post-transplant lymphoproliferative disorders (PTLD) represent a severe complication in transplanted patients and Epstein-Barr Virus (EBV) is the main driver. Besides immunodepression, immune activation/chronic inflammation play an important role in both virus reactivation and expansion of EBV-positive B cells. The aim of this study was to assess the impact of immunosuppressive strategies on factors involved in the PTLD's pathogenesis. 124 kidney transplanted patients were enrolled in this study: 71 were treated with mycophenolic acid (MPA) and 53 treated with mTOR inhibitor (mTORi), both in combination with different doses of calcineurin inhibitor. At the time of the transplant (T0), profile of inflammation/immune activation and immune senescence didn't differ between the two groups, but after one year of treatment (T1) markers were significantly higher in MPA-treated patients; their immunosenescence process was supported by the greater erosion of telomeres despite their younger age. Percentages of activated B cells and levels of EBV-DNA significantly increased in MPA-treated patients, and at T1 were significantly higher in MPA- than in mTORi-treated patients. Overall, these findings indicate that mTOR inhibitors constrain the inflammation/immune activation and senescence status, thus reducing the expansion of EBV-infected B cells and the risk of virus-associated PTLD in kidney transplant recipients. \ua9 2019 The Author

80,000,000 hooligans. Discourses of resistance to racism and xenophobia in German punk lyrics 1991-1994

The late eighties and early nineties in Germany were not only marked by the fall of the Wall and German unification, but also by the dramatization of the political issue of asylum, resulting in outbreaks of xenophobic violence. In the context of the asylum debate of the early nineties, a number of punk bands produced songs between 1991 and 1994 which criticise the xenophobic climate created by the asylum debate and undermine an exculpatory official discourse about the violent attacks. The lyrics of these songs will be analysed as instances of counter-discourse emerging from a subcultural sphere that nurtures a critical distance towards hegemonic public and political discourse, arguing that Critical Discourse Analysis should pay more attention to defiance of hegemonic discourse

European Society for Organ Transplantation (ESOT)-TLJ 3.0 consensus on histopathological analysis of pre-implantation donor kidney biopsy: redefining the role in the process of graft assessment

The ESOT TLJ 3.0. consensus conference brought together leading experts in transplantation to develop evidence-based guidance on the standardization and clinical utility of pre-implantation kidney biopsy in the assessment of grafts from Expanded Criteria Donors (ECD). Seven themes were selected and underwent in-depth analysis after formulation of PICO (patient/population, intervention, comparison, outcomes) questions. After literature search, the statements for each key question were produced, rated according the GRADE approach [Quality of evidence: High (A), Moderate (B), Low (C); Strength of Recommendation: Strong (1), Weak (2)]. The statements were subsequently presented in-person at the Prague kick-off meeting, discussed and voted. After two rounds of discussion and voting, all 7 statements reached an overall agreement of 100% on the following issues: needle core/wedge/punch technique representatively [B,1], frozen/paraffin embedded section reliability [B,2], experienced/non-experienced on-call renal pathologist reproducibility/accuracy of the histological report [A,1], glomerulosclerosis/other parameters reproducibility [C,2], digital pathology/light microscopy in the measurement of histological variables [A,1], special stainings/Haematoxylin and Eosin alone comparison [A,1], glomerulosclerosis reliability versus other histological parameters to predict the graft survival, graft function, primary non-function [B,1]. This methodology has allowed to reach a full consensus among European experts on important technical topics regarding pre-implantation biopsy in the ECD graft assessment.Immunopathology of vascular and renal diseases and of organ and celltransplantationIP

Enhanced hydrogen peroxide generation accompanies the beneficial bioenergetic effects of methylene blue in isolated brain mitochondria

The redox dye methylene blue (MB) is proven to have beneficial effects in various models of neurodegenerative diseases. Here we investigated the effects of MB (100 nM, 300 nM, and 1 μM) on key bioenergetic parameters and on H2O2 production/elimination in isolated guinea pig brain mitochondria under normal as well as respiration-impaired conditions. As measured by high-resolution Oxygraph the rate of resting oxygen consumption was increased, but the ADP-stimulated respiration was unaffected by MB with any of the substrates (glutamate malate, succinate, or α-glycerophosphate) used for supporting mitochondrial respiration. In mitochondria treated with inhibitors of complex I or complex III MB moderately but significantly increased the rate of ATP production, restored ΔΨm, and increased the rate of Ca2+ uptake. The effects of MB are consistent with transferring electrons from upstream components of the electron transport chain to cytochrome c, which is energetically favorable when the flow of electrons in the respiratory chain is compromised. On the other hand, MB significantly increased the production of H2O2 measured by Amplex UltraRed fluorimetry under all conditions, in resting, ATP-synthesizing, and respiration-impaired mitochondria, with each substrate combination supporting respiration. Furthermore, it also decreased the elimination of H2O2. Generation of H2O2 without superoxide formation, observed in the presence of MB, is interpreted as a result of reduction of molecular oxygen to H2O2 by the reduced MB. The elevated generation and impaired elimination of H2O2 should be considered for the overall oxidative state of mitochondria treated with MB

The 2018 Lake Louise Acute Mountain Sickness Score.

Roach, Robert C., Peter H. Hackett, Oswald Oelz, Peter Bärtsch, Andrew M. Luks, Martin J. MacInnis, J. Kenneth Baillie, and The Lake Louise AMS Score Consensus Committee. The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol 19:1-4, 2018.- The Lake Louise Acute Mountain Sickness (AMS) scoring system has been a useful research tool since first published in 1991. Recent studies have shown that disturbed sleep at altitude, one of the five symptoms scored for AMS, is more likely due to altitude hypoxia per se, and is not closely related to AMS. To address this issue, and also to evaluate the Lake Louise AMS score in light of decades of experience, experts in high altitude research undertook to revise the score. We here present an international consensus statement resulting from online discussions and meetings at the International Society of Mountain Medicine World Congress in Bolzano, Italy, in May 2014 and at the International Hypoxia Symposium in Lake Louise, Canada, in February 2015. The consensus group has revised the score to eliminate disturbed sleep as a questionnaire item, and has updated instructions for use of the score

Current preventive strategies and management of Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey

There is limited clinical evidence on the utility of the monitoring of Epstein-Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients