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The primary objective was to explore weight and BMI changes in people with HIV (PWH) undergoing integrase strand transfer inhibitors (INSTI)-based regimens (vs. non-INSTI) in a large cohort and in the subsets of individuals without diabetes and insulin resistance (IR) at the time of switch to INSTI. The secondary objective was to identify risk factors for IR and cut-off of weight or BMI increase associated with IR in PWH switching to INSTI.A longitudinal matched-cohort study including PWH attending Modena HIV Metabolic Clinic, Italy.PWH were divided into two groups: non-INSTI and INSTI-switch. The effect of switching to INSTI on weight and BMI change was tested through a linear mixed model. A mediation analysis explored the mediation effect of weight and BMI change in the association between the switch to INSTI and IR.We analyzed 2437 PWH (1025 INSTI-switch, 1412 non-INSTI), in 54 826 weight assessments. Trends for weight increase were significantly higher in early-INSTI-switch (vs. early-non-INSTI), but no difference was observed in the late period after the switch. In the subset of 634 PWH without IR, switching to INSTI (vs. non-INSTI) was associated with a lower risk of IR (hazard ratio = 0.70, 95% confidence interval: 0.51, 0.98). A weight increase by 1% reduced the total protective effect of INSTI by 21.1% over 1 year of follow-up, which identifies a 5% weight increase as a clinically meaningful weight gain definition.A cut-off of 5% weight gain from the time of INSTI-switch is associated with IR, which may be a clinically meaningful endpoint that could be used in clinical and research settings.

Purpose The most abundant among the separately collected waste materials in Italy is food waste. This research aims to evaluate the influence of the type of collection bag on the food waste management chain. In Italy, the food waste collection is mainly based on bioplastic bags. As an alternative, a new type of recycled paper bag shows potential advantages. Methods The two types of collection bag were compared evaluating the weight loss of food waste during the household storage, by means of an experimental assessment simulating the domestic dynamic bag filling. Moreover, the biomethane production of bags under anaerobic conditions was measured at the lab-scale level with Biochemical Methane Potential (BMP) tests. Results During the household storage, the breathable fabric of the paper allows for higher weight losses, ranging on average between + 29 and + 44% compared to bioplastic. BMP tests, carried out under different conditions (temperature, inoculum), showed a 2–14 times higher generation of methane by paper bags compared to bioplastic bags, when referred to 1 kg of inserted food waste. Conclusions Collecting the food waste inside paper bags shows advantages compared to the use of bioplastic bags. First, the waste collection is benefitted thanks to the lower weight of material to be transported to treatment plants, leading also to the possibility of decreasing the collection frequency. Moreover, paper resulted more compatible than bioplastic with the anaerobic digestion treatment, which is currently rapidly increasing as a food waste management option. Graphic Abstract

Introduction: Reports regarding the external validity of randomized controlled trials (RCTs) are scarce. We aimed to assess the population external validity of an investigator-initiated RCT on the duration of antibiotics for the treatment of Gram-negative bacteremia by comparing patients included in the RCT to patients that were not included in the trial. Methods: Hospitalized patients with Gram-negative bacteremia were recruited into an RCT and randomized to receive 7 or 14 days of covering antibiotic therapy in Israel and Italy from 2013 to 2017. In a concomitant observational study, RCT participants were compared with patients who fulfilled the inclusion criteria but were not included in the trial due to participation in other trials, discharge before approached by researchers, refusal to participate, or unwillingness of the treating physician to allow participants’ recruitment. Results: Six hundred and four RCT patients were compared with 613 nonincluded patients. Almost 50% of nonincluded patients (288/613) were dependent on others for activities of daily living at baseline compared to 37.7% of RCT participants (228/604). Dementia was nearly 2-fold more frequent in nonincluded patients than those included (5.9% [36/613] versus 3.6% [22/604], p = 0.07). Patients who were not included in the RCT were more likely to acquire their infection in the hospital (53.3% [327/613] versus 29.1% [176/604], p < 0.001). The primary composite outcome of mortality, clinical failure, readmissions, or extended hospitalization at 90 days occurred in 353 of 613 nonincluded patients (57.6%) compared to 299 of 604 RCT participants (49.6%), p = 0.005. However, on multivariate analysis noninclusion in the RCT was not an independent risk factor for clinical failure and mortality. Conclusions: RCTs, even with broad eligibility criteria, do not represent the whole spectrum of patients and leave out a population with more severe illness for whom the evidence is lacking.

The research investigated the influence of different collection bag types on the environmental and energy performances of the food waste management chain, comparing paper and bioplastic bags. First, the use of bags during the food waste household storage was examined. Subsequently, the behavior of bags when subjected to anaerobic digestion was evaluated, performing Biochemical Methane Potential tests and semi-continuous co-digestion tests with the food waste, to simulate the operating conditions of full-scale digesters. Finally, the performances of the food waste management chain were evaluated, with a Life Cycle Assessment (LCA). The experimental tests showed a more favorable behavior of paper bags, showing a very good compatibility with the anaerobic digestion. The LCA results revealed how paper bags lead to improvements in the impact associated to the food waste management. Graphical Abstract

RationalePulse glucocorticoid therapy is used in hyperinflammation related to coronavirus disease 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia.MethodsIn this multicentre, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with COVID-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for three consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need for supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival.ResultsOverall, 112 (75.4%) out of 151 patients in the pulse methylprednisolone arm and 111 (75.2%) of 150 in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups (15 days, 95% CI 13.0–17.0 days and 16 days, 95% CI 13.8–18.2 days, respectively; hazard ratio (HR) 0.92, 95% CI 0.71–1.20; p=0.528). No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to intensive care unit with orotracheal intubation or death (20.0%versus16.1%; HR 1.26, 95% CI 0.74–2.16; p=0.176) or overall mortality (10.0%versus12.2%; HR 0.83, 95% CI 0.42–1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups.ConclusionsMethylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia.

Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2–3 and 6–7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2-3 and 6-7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase=1.79; 95% confidence interval [CI]=1.23-2.62) at 2-3 months and CRP integral (OR for one SD increase=2.24; 95%CI=1.53-3.28) at 6-7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.

Objective To estimate the effect of tocilizumab or glucocorticoids in preventing death and intubation in patients hospitalized with SARS-CoV-2 pneumonia. Methods This was a retrospective cohort study enrolling all consecutive patients hospitalized at Reggio Emilia AUSL between February the 11th and April 14th 2020 for severe COVID-19 and treated with tocilizumab or glucocorticoids (at least 80 mg/day of methylprednisolone or equivalent for at least 3 days). The primary outcome was death within 30 days from the start of the considered therapies. The secondary outcome was a composite outcome of death and/or intubation. All patients have been followed-up until May 19th 2020, with a follow-up of at least 30 days for every patient. To reduce confounding due to potential non-comparability of the two groups, those receiving tocilizumab and those receiving glucocorticoids, a propensity score was calculated as the inverse probability weighting of receiving treatment conditional on the baseline covariates. Results and conclusion Therapy with tocilizumab alone was associated with a reduction of deaths (OR 0.49, 95% CI 0.21-1.17) and of the composite outcome death/intubation (OR 0.35, 95% CI 0.13-0.90) compared to glucocorticoids alone. Nevertheless, this result should be cautiously interpreted due to a potential prescription bias.

Background A proposal has recently been advanced to change the traditional definition of nonalcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long coronavirus disease 2019 (COVID-19) is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with postacute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods We included 235 patients observed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, and dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first postdischarge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P Conclusions Metabolic-associated fatty liver disease was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

The amount of compostable bioplastics collected with the food waste is constantly growing, particularly due to the bags used for collection. According to the Italian legislation, compostable bioplastics must be accepted by all biological treatment plants, including aerobic and anaerobic facilities. Anyway, the compostability standard requires only the assessment of the aerobic degradability, while it is generally not required to test the behaviour under anaerobic conditions. This aspect is evaluated in the paper, where the anaerobic degradability of bioplastic bags used for the food waste collection is assessed. First, Biochemical Methane Potential (BMP) tests were performed on four commercial types of bioplastic bags, including those designed only for the collection of food waste and the shoppers, that can be reused for the same purpose. Subsequently, an innovative approach for this kind of substrate was applied, subjecting two bags to semi-continuous co-digestion tests together with the food waste. Both tests were performed by comparing the behaviour of bioplastic bags with that of an alternative collection paper bag. Finally, tests to evaluate the influence of physical phenomena on the degradation of bioplastics were performed to better understand the results of biological tests. BMP tests indicated a good degradability (71%) of bioplastic bags, while semi-continuous tests showed a much lower degradability (27%), confirmed by the observation of the undigested bag pieces. On the contrary, the paper bag presents interesting characteristics, because its degradability in the semi-continuous tests (82%) resulted even higher than that observed in the BMP tests (74%). These results highlight an important difference between the bags mono-digestion by means of BMP tests and the semi-continuous co-digestion tests with food waste, which better simulate the full-scale operational conditions.

The immunological mechanisms that modulate immune response to SARS‐CoV‐2 infection remain elusive. Little is known on the magnitude and the durability of antibody response against COVID‐19. There is consensus that patients with immune dysfunction, such as dialysis patients, may be unable to mount a robust and durable humoral immunity after infections. Recent studies showed that dialysis patients seroconverted after COVID‐19, but data on the durability of the immune response are missing. We reported the data of a durable anti‐spike protein seroconversion after natural SARS‐CoV‐2 infection in three patients on hemodialysis with a mean age of 67.2 ± 13.8 years. A mean antibody titer of 212.6 ± 174.9 UA/ml (Liaison®, DiaSorin) was found after one year (range, 366–374 days) from the diagnosis of COVID‐19. In conclusion, this case series provided evidence that patients receiving hemodialysis who recovered from severe COVID‐19 were able to mount a long‐lasting immune response against SARS‐CoV‐2. Although the protective capacity of this long‐term immunity remains to be determined, these patients did not report signs of reinfection after recovery from COVID‐19.

A high incidence of thrombotic events has been reported in patients with coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We report 3 clinical cases of patients in Italy with COVID-19 who developed abdominal viscera infarction, demonstrated by computed tomography.

Sirolimus (SIR) is a potent immunosuppressive agent with multiple proprieties. We report beneficial antiviral effects of SIR in an HIV-positive kidney transplant recipient who experienced low-level HIV-1 replication. The immunosuppressive agent was well tolerated by the patient, and no side effects were reported during follow-up. Despite immunosuppressive monotherapy, SIR ensured stable graft function.

This paper describes the potential application of a new patented technology for the storage of carbon dioxide (CO2) in glass containers into the deep seabed (confined submarine carbon storage (CSCS)) to cement plants located in four different locations in the world. This technology is based on the bottling of liquid CO2 at high pressure inside capsules made of glass that are delivered to the bottom of the ocean via a proper pipeline. A Life Cycle Assessment that considers all the stages of the process and 13 impact categories, with a focus on climate change, shows an impact in the four case studies between 0.084 and 0.132 ton of CO2 equivalent (eq) per ton of CO2 stored. Since carbonation of cement materials over their life cycle is a significant and growing net sink of CO2, the capture and storage of CO2 emissions generated during the production of cement might lead to negative emissions. A cost analysis was also performed, including the capital costs and the operational costs, even considering the funding structure through financing and equity. The costs of the four case studies are from 16 to 29 $/tCO2. Although further work is needed to assess in detail some aspects of the design, the result of this stage of the research allows concluding that the application of the CSCS in cement plants is an interesting option for achieving negative emissions, even if limited due the slowness of CO2 uptake during the lifetime of cement materials.

The organic fraction (mainly food waste) is typically the most abundant of the separately collected waste streams. The research aims at investigating the influence of different types of collection bag on the environmental performances of the food waste management chain in Italy. A comparative life cycle assessment (LCA) between two alternative systems based on paper or bioplastic collection bags was carried out. It included the collection bags manufacturing and distribution, their use at the household, the transportation of collected food waste and its subsequent anaerobic digestion, including the valorisation of useful outputs and the management of residues. The two systems were modelled mainly with primary data related to the current management system and to tests performed on bags. The LCA was performed with two different modelling approaches applied in the environmental product declaration (EPD) system and in the product environmental footprint (PEF) studies, respectively. In the scenario representing the average conditions, higher environmental impacts are shown by the use of bioplastic bags compared to paper ones with the EPD approach (+257%/+576%). With the PEF approach, the differences between the two systems are lower (−55%/+133%). Moreover, paper bags could allow for further impact reductions assuming a decrease of the food waste collection frequency, allowed by higher weight losses and a lower generation of leachate and odour during the household storage.

Background The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery. Methods In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery. Results Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2–5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1–0.7) or in OT (HR = 0.1, 95% CI = 0.0–0.8) treated with tocilizumab. Conclusion To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.

The aim of this study was to evaluate both positive outcomes, including reduction of respiratory support aid and duration of hospital stay, and negative ones, including mortality and a composite of invasive mechanical ventilation or death, in patients with coronavirus disease 2019 (COVID-19) pneumonia treated with or without oral darunavir/cobicistat (DRV/c, 800/150 mg/day) used in different treatment durations. The secondary objective was to evaluate the percentage of patients treated with DRV/c who were exposed to potentially severe drug-drug interactions (DDIs) and died during hospitalization. This observational retrospective study was conducted in consecutive patients with COVID-19 pneumonia admitted to a tertiary care hospital in Modena, Italy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare patients receiving standard of care with or without DRV/c. Adjustment for key confounders was applied. Two hundred seventy-three patients (115 on DRV/c) were included, 75.8% males, mean age was 64.6 (±13.2) years. Clinical improvement was similar between the groups, depicted by respiratory aid switch (p > .05). The same was observed for duration of hospital stay [13.2 (±8.9) for DRV/c vs. 13.4 (±7.2) days for no-DRV/c, p = .9]. Patients on DRV/c had higher rates of mortality (25.2% vs. 10.1%, p < .0001. The rate of composite outcome of mechanical ventilation and death was higher in the DRV/c group (37.4% vs. 25.3%, p = .03). Multiple serious DDI associated with DRV/c were observed in the 19 patients who died. DRV/c should not be recommended as a treatment option for COVID-19 pneumonia outside clinical trials.

Objective To identify risk factors for functional decline after hospitalization for Gram-negative bacteremia. Patients and methods A prospective cohort study based on a randomized controlled trial conducted between January 1, 2013 and August 31, 2017 in Israel and Italy. Hospitalized patients with Gram-negative bacteremia who survived until day 90 and were not bedridden at baseline were included. The primary end point was functional decline at 90 days. Results Five hundred and nine patients were included. The median age of the cohort was 71 years (interquartile range [IQR], 60–80 years), 46.4% (236/509) were male and 352 of 509 (69%) patients were independent at baseline. Functional decline at 90 days occurred in 24.4% of patients (124/509). In multivariable analysis; older age (odds ratio [OR], 1.03; for an one-year increment, 95% confidence interval [CI] 1.01–1.05), functional dependence in instrumental activities of daily living at baseline (OR, 4.64; 95% CI 2.5–8.6), low Norton score (OR, 0.87; 95% CI 0.79–0.96) and underlying comorbidities: cancer (OR, 2.01; 95% CI 1.14–3.55) and chronic pulmonary disease (OR, 2.23 95% CI 1.12–4.42) and longer length of hospital stay (OR 1.09; for one-day increment, 95% CI 1.04–1.15) were associated with functional decline. Appropriate empirical antibiotic treatment was associated with lower rates of functional decline within 90 days (OR, 0.4; 95% CI 0.21–0.78). Conclusions Patients surviving bloodstream infections have poor long term trajectories after clinical recovery and hospital discharge. This has vast implications for patients, their family members and health policy makers.

Background Pneumonia is the most frequent complication of COVID-19, due to an aberrant host immune response that is associated with an acute respiratory distress syndrome, and, in most critical patients, with a “cytokine storm”. IL-6 might play a key role in the cytokine storm and might be a potential target to treat severe and critical COVID-19. Tocilizumab is a recombinant humanized monoclonal antibody, directed against IL-6 receptor. Methods This multicentre study project includes a single-arm phase 2 study and a further parallel cohort, enrolling hospitalized patients with COVID-19 pneumonia and oxygen saturation at rest in ambient air ≤93% or requiring respiratory support. Patients receive tocilizumab 8 mg/kg (up to 800 mg) as one intravenous administration. A second administration (same dose) after 12 h is optional. Two-week and one-month lethality rates are the co-primary endpoints. Sample size planned for the phase 2 study is 330 patients. The parallel cohort will include patients who cannot enter the phase 2 study because being intubated from more than 24 h, or having already received tocilizumab, or the phase 2 study has reached sample size. Primary analysis will include patients enrolled in the phase 2 study. Results of the primary analysis will be validated in the prospective cohort of patients consecutively registered after phase 2 closure from March 20 to March 24, who were potentially eligible for the phase 2 study. Conclusion This trial aims to verify the safety and efficacy of tocilizumab in the Italian population with COVID-19 pneumonia and respiratory impairment. EudraCT Number: 2020–001110-38; Clinicaltrials.gov ID NCT04317092

IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile. OBJECTIVE: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao(2)/Fio(2)) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. INTERVENTIONS: Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy. MAIN OUTCOME AND MEASURES: The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao(2)/Fio(2) ratio less than 150 mm Hg, whichever came first. RESULTS: A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao(2)/Fio(2) ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicentre, single-arm, hypothesis-driven phase 2 trial was planned to study the effect of Tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints). A cohort of patients consecutively enrolled after phase 2 was used as a validation dataset. A multivariable logistic regression was performed to generate hypotheses, while controlling for possible confounders.Resultsout of 301 patients in phase 2 intention-to-treat (ITT) analysis, 180 (59.8%) received tocilizumab. With 67 death events, lethality rates were 18.4% (97.5%CI: 13.6-24.0, P=0.52) and 22.4% (97.5%CI: 17.2-28.3, PConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Such result support the use of tocilizumab while waiting for ongoing phase 3 trials.RegistrationEudraCT (2020-001110-38);clinicaltrials.gov(NCT04317092)

Background and Aims The number of simultaneous liver-kidney transplants (SLKT) has been constantly increasing in the past two decades. In the US, the relative proportion of liver transplants performed as part of SLKT augmented from 2.7% in 2000 to 9.3% in 2016. In this rapidly evolving scenario, people living with HIV (PLWH) have been substantially excluded from SLKT. The poor prognosis of SLKT in people living with HIV (PLWH) has refrained transplant centers to perform this procedure. Method We retrospectively describe indications, clinical characteristics and survival of HIV-infected patients who underwent SLKT at the Transplant Centre of Modena, Italy. Results Since 2001 five SLKTs were performed in HIV-affected subjects. With regards to medical eligibility criteria for SLKT all the patients were on hemodialysis and had liver end-stage disease or HCC at time of transplantation (Table 1A). Mean age at transplantation was 47.8± 5.93 years and all patients were Caucasian males. Mean duration of HIV was 25 years and all patients had undetectable HIV-viral load at SLKT. The causes of end-stage renal disease were different in all recipients and only one had biopsy-proven kidney disease. Dialysis vintage was 15.8±10.2 months. Four patients had HCV-related cirrhosis and one had hepato-carcinoma (HCC). Mean HCV-RNA at SOT was 464,327 copies/ml; in three HCV patients, the sustained virologic response to HCV therapy was obtained after transplant with peg-INF in one case (pre-direct antiviral agent era) and with a combination of sofosbuvir, daclatasvir and rifampicin in the other two. Only one patient had HBV-HDV-related cirrhosis and did not experience HBV or HDV relapse during the follow-up. At the end of a mean follow up of 7.6±4.71 years, four out of five patients are still alive One patient died on post-transplant day 41 for disseminated candidiasis with cerebral involvement (Table1 b). During the follow-up period, HIV-VL remained undetectable over nearly 10 years. Clinical outcome was characterized by the reverse of frailty in all the patients. All of them are conducting an independent living with quality of life exceeding 90% using the EUQoL 5D-5L questionnaire. The liver function was normal and remained stable during theobservation period. Bile duct stricture and bile duct calculi were the main surgical complications. Regarding renal function, mean serum creatinine was 1.7±0.4mg/dl corresponding to a mean estimated GFR of 47.7±5.9 ml/min. Only one patient had proteinuria (0.8 gr/daily) after 10 years of transplantation. Contrary to our expectations, no cases of graft rejections occurred during this long-term follow-up despite mean HLA mismatches of 5.75 and underexposure to the immunosuppressive agents. Withdrawn of steroids occurred after 1.8±2.5 years from SLKT. Thereafter, immunosuppressive therapy continued with monotherapy: calcineurin inhibitor in three recipients and inhibitors of the mammalian target of rapamycin in the other one. Conclusion Contrary to the previously published data, this case series describes a favorable clinical outcome in PLWH who received SLKT. The absence of graft rejection despite the reduced immunosuppressive therapy highlights the concept that the liver is able to induce tolerance in kidney transplantation. These results could lead other transplant programs to consider SLKT as a reliable clinical option in PLWH with liver and kidney failure.

Background Kidney transplantation in HIV-infected patients is characterized by a concerning high rate of allograft rejections. The etiological mechanisms leading to this increased immunoreactivity are still unknown. Maraviroc is a new antiretroviral agent that has been associated with immunomodulatory proprieties; therefore, its use may be a promising strategy to minimize the rate of rejections in HIV-infected kidney transplant (KT) recipients. Methods We conducted a retrospective study in our cohort of HIV-KT recipients with the aim to explore the effects of maraviroc in reducing the risk of graft rejection. Results Twenty-two HIV-infected KT recipients predominantly of Caucasian origin (86%) and with a median age of 49 (IQR, 51.9-42.2) years were evaluated. Ten HIV-infected patients were treated with maraviroc and 12 with a maraviroc-free antiretroviral regimen. After a median follow-up of 3.01 years, half of the maraviroc-treated patients (n = 5) developed seven episodes of graft rejection, most of them were T cell-mediated rejections (85.7%). Five episodes were recorded in the maraviroc-free group. The difference in the rate of graft rejections was not statistically significant (P = .23). Conclusions The administration of maraviroc was ineffective in preventing graft rejections in our cohort of patients.

Assisted reproduction technologies (ART) are well developed in humans and cattle and are gaining momentum also in the equine industry because of the fact that the mare does not respond to superovulation but can donate large numbers of oocytes through ovum pick up (OPU). After collection, the oocytes can be fertilized by intracytoplasmic sperm injection (ICSI) using a variety of stallion semen samples, even of poor quality, and the resulting embryos can establish high pregnancy rates after cryopreservation and transfer. The discoveries that equine oocytes can be held at room temperature without loss of viability and that an increase in vitro maturation time can double the number of embryos produced are fueling the uptake of the OPU technique by several clinics that are shipping oocytes of their client’s mares to specialized ICSI laboratories for embryo production and freezing. In this article, we present a retrospective analysis of 10 years of work at Avantea with a special focus on the last 3 years. Based on our data, an average production of 1.7 to 2 embryos per OPU-ICSI procedure can be obtained from warmblood donor mares with a pregnancy rate of 70% and a foaling rate in excess of 50%. OPU-ICSI offers the added value of freezing embryos that allows the development of embryo commercialization worldwide to the benefit of top horse breeders who are endorsing this technology as never before.

In the current setting of global containment, peritoneal dialysis (PD) and home haemodialysis are the best modalities of renal replacement therapy (RRT) to reduce the rate of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the shorter and easier training programme of PD compared to home haemodialysis, PD appears a practical solution for patients with end-stage renal disease to reduce the risk of hospital-acquired infection. PD offers the advantage of minimizing the risk of viral transmission through interpersonal contact that commonly occurs during the haemodialysis session and while travelling from home to the haemodialysis facility using public transport services. To overcome barriers to health care access due to the containment measures for this emerging disease, telemedicine is a useful and reliable tool for delivering health care without exposing patients to the risk of contact. However, novel issues including handling of potentially infected dialysate, caregivers' infectious risk and adequacy of PD in critically ill patients with acute respiratory distress syndrome remain to be clarified. In conclusion, PD should be preferred to the other modalities of RRT during the coronavirus disease 2019 (COVID-19) outbreak because it can be a solution to cope with the increased number of infected patients worldwide.

An innovative sleeper with a pre-stressed reinforced concrete inner structure wrapped by an outer shell manufactured with end-of-life tires powder and recycled plastics has been recently designed by the Greenrail company. The external protection is aimed at increasing its lifetime and reducing the maintenance requirements of the railway lines. This study evaluates the environmental performances of this sleeper, under different operational conditions, in comparison with traditional pre-stressed reinforced concrete sleepers, using the Life Cycle Assessment methodology.The assessment includes 16 environmental, energy, and human health impact categories. It is performed considering the following functional unit: 1 railway sleeper, including the fastenings of the rail to the sleeper and the portion of the track bed underneath it, over one year of operation. The evaluated system includes the sleeper production, its installation, the railway maintenance, the sleeper removal at its end-of-life and the final recovery. Moreover, the ballast is included in the analysis considering its mining and transportation to the railway line, the partial replacement during maintenance operations, the removal during a track renewal, and the end-of-life management.For the worst operational conditions of the Greenrail sleeper, the potential impacts between the two sleeper typologies differ by

Background: No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment. Methods: This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score. Findings: Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p

In recent years, alternative food supply chains based on short distance production and delivery have been promoted as being more environmentally friendly than those applied by the traditional retailing system. An example is the supply of seasonal and possibly locally grown fruit and vegetables directly to customers inside a returnable crate (the so-called ‘box scheme’). In addition to other claimed environmental and economic advantages, the box scheme is often listed among the packaging waste prevention measures. To check whether such a claim is soundly based, a life cycle assessment was carried out to verify the real environmental effectiveness of the box scheme in comparison to the Italian traditional distribution. The study focused on two reference products, carrots and apples, which are available in the crate all year round. An experience of a box scheme carried out in Italy was compared with some traditional scenarios where the product is distributed loose or packaged at the large-scale retail trade. The packaging waste generation, 13 impact indicators on environment and human health and energy consumptions were calculated. Results show that the analysed experience of the box scheme, as currently managed, cannot be considered a packaging waste prevention measure when compared with the traditional distribution of fruit and vegetables. The weaknesses of the alternative system were identified and some recommendations were given to improve its environmental performance.

ObjectiveTo investigate the association between current CD4+ T-cell count and CD4/CD8+ ratio with severity of frailty among people aging with HIV.MethodsCross-sectional observational study analysing data from all study visits in the ongoing prospective Modena HIV Metabolic Clinic Cohort between 2006 and 2015. Frailty severity was assessed using a frailty index (FI). We visualized the relationships between frailty index score and current CD4 cell count and CD4/CD8 ratio on two different curves adjusted for age, sex, and duration of HIV infection.ResultsFrailty index scores exhibited an inverse relationship with current CD4 count, up to 900 cells/μL. The CD4/CD8 ratio was inversely correlated with frailty index both below and above the cut-off of 900 CD4 cells/μL.ConclusionsFrailty in PLWH is inversely associated with both immune-activation, depicted by CD4/CD8 ratio and immune-deficit depicted by CD4 count. The first association shows a linear shape while the second shows a hook-shape with a turning point at 900 cells. Above this cut off level CD4 do not represent a significant risk factor for frailty.

Waste prevention is the top priority of the European waste management strategy. In fact, as indicated in the latest Waste Framework Directive, the best option to deal with waste is not to generate it at all. In this framework, the distribution of loose dry food products through self-dispensing systems (so-called "loose distribution") is being considered worldwide as a practice to reduce the generation of packaging waste. This life cycle assessment (LCA) evaluates the environmental convenience of the loose distribution of dry pasta, breakfast cereals, and rice, in comparison with the traditional method of distribution. For each product, several baseline scenarios based on single-use packaging were compared with different waste prevention scenarios in which the product is distributed loose. The comparison addressed waste generation, 13 impact categories on the environment and human health, and the Cumulative Energy Demand (CED) indicator. The results are significantly different for the 3 products. The loose distribution of pasta allows a 50% waste reduction and a decrease in the potential impacts only when compared with single-use cartonboard boxes. Conversely, when the comparison is made with single-use polypropylene bags, the loose distribution can even cause an increase in waste generation (up to 15%) and in the potential life cycle impacts. For breakfast cereals, the loose distribution allows a significant reduction in both the amount of waste (up to 84%) and the potential impacts, compared to the sale of traditional single-use bag-in-box packages. Finally, the loose distribution of rice permits a reduction in both waste generation (up to 86%) and most of the potential impacts. In particular, the impact reduction is higher when the reference single-use packaging that is replaced includes a cartonboard box. Integr Environ Assess Manag 2016;12:445-458. © 2016 SETAC.