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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.

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.

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.

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.

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

Kidney transplantation is a safe and effective option for HIV-positive (HIV+) patients. We conducted a retrospective study on HIV+ kidney transplant recipients who underwent transplantation from March 2008 to September 2016. Inclusion criteria for transplantation were CD4+ T-cell count ≥200 per mm3 and undetectable HIV load. The current study reports the outcome of 19 HIV+ recipients, mostly of Caucasian origin (79%) with a median age of 50 years (interquartile range [IQR], 42–52), who were followed up for a median period of 2.4 years (IQR, 1.2–4.6) after transplantation. Compared with HIV-negative (HIV−) controls, HIV+ recipients had similar one- and three-year graft and patient survival, but significantly lower five-year patient survival (P = 0.03). The differences in graft outcome became less evident with the analysis of death-censored graft survival rates. Cumulative incidence of allograft rejection at one year was 32.9%. Rates of infections were not particularly elevated and HIV replication remained well controlled in all but one patient. A high prevalence of metabolic and endocrine complications (68%) was reported after transplantation. Further studies are needed to evaluate long-term outcomes of HIV+ recipients who underwent kidney transplantation.

Background We hypothesized that frailty acts as a measure of health outcomes in the context of LT. The aim of this study was to explore frailty index across LT, as a measure of morbidity and mortality. This was a retrospective observational study including all consecutive 47 HIV+patients who received LT in Modena, Italy from 2003 to June 2015. Methods frailty index (FI) was constructed from 30 health variables. It was used both as a continuous score and as a categorical variable, defining ‘most frail’ a FI > 0.45. FI change across transplant (deltaFI, ΔFI) was calculated as the difference between year 1 FI (FI–Y1) and pre-transplant FI (FI–t0). The outcomes measures were mortality and “otpimal LT” (defined as being alive without multi-morbidity). Results Median value of FI–t0 was 0.48 (IQR 0.42–0.52), FI–Y1 was 0.31 (IQR 0.26–0.41). At year five mortality rate was 45%, “optimal transplant” rate at year 1 was 38%. All the patients who died in the post-LT were most frail in the pre-LT. ΔFI was a predictor of mortality after correction for age and MELD (HR = 1.10, p = 0.006) and was inversely associated with optimal transplant after correction for age (HR = 1.04, p = 0.01). Conclusions We validated FI as a valuable health measure in HIV transplant. In particular, we found a relevant correlation between FI strata at baseline and mortality and a statistically significant correlation between, ΔFI and survival rate. Electronic supplementary material The online version of this article (doi:10.1186/s12981-017-0163-x) contains supplementary material, which is available to authorized users.

Background Late presentation (LP) at the time of HIV diagnosis is defined as presentation with AIDS whatever the CD4 cell count or with CD4

Objectives To evaluate the relationship between polypharmacy and ART, delivered as conventional multi-tablet three-drug regimens, single-tablet regimens or less-drug regimens (simplified mono or dual regimens). Methods We conducted a cross-sectional analysis of electronic data from the prospective Modena HIV Metabolic Clinic Cohort Study. We included the last clinical observation for each patient from January 2006 to December 2015. Polypharmacy was defined as the use of five or more medications (excluding ART). Multi-morbidity was classified as the presence of two or more non-infectious comorbidities. Factors associated with different ART regimens were analysed using multivariable multinomial logistic regression analyses with multi-tablet three-drug regimens as the reference. Results A total of 2944 patients (33.7% females) were included in the analysis. Multinomial logistic regression analysis identified polypharmacy to be negatively associated with single-tablet regimens [relative risk reduction (RRR) = 0.48, 95% CI = 0.28-0.81] independently from frailty (RRR = 0.68, 95% CI = 0.59-0.78), after correction for age, gender, HIV infection duration, current and nadir CD4 and calendar year. This association was not found comparing multi-tablet three-drug regimens and less-drug regimens. Conclusions Single-tablet regimens are less likely to be prescribed in patients with polypharmacy. Single-tablet regimens are perceived to be less flexible in patients with multi-morbidity and at higher risk of drug-drug interaction.

Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12–3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23–6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01–11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients., This work was supported by: PI-0118-2013, PI-0481-2012, AC-0095-2013, RH-0024-2013, B-0037 and C-0009-2015, Consejería de Salud, Junta de Andalucía, http://www.juntadeandalucia.es/salud/sites/csalud/portal/index.jsp; RD12/0017/0012, EC11-2086, I3SNS, Instituto de Salud Carlos III, http://www.isciii.es/; PTA2014-09009-I, Ministerio de Economía y Competitividad, http://www.mineco.gob.es/portal/site/mineco/; and GLDL13-00145, Gilead fellowship program, https://www.fellowshipgilead.es/.

Objective. In this study we examine the efficacy of anti-retraction devices in preventing microbial contamination of dental unit water lines (DUWLs). Methods. The study was performed on 54 randomly selected DUs in use at private and public institutions for over six months. The selected DUs were all currently commercially available. To evaluate the efficiency of anti-retraction devices, two different methods were employed, mechanical and microbiological. The ADA/ANSI specification #47 (corresponding to a water retraction of less than 40.3 μl) was used for the evaluation of the retraction determined using the mechanical method; the presence/absence of test microorganisms in DUWLs upstream the turbine after the test was used for evaluating the microbiological assay. Results. Both evaluation methods indicated correct amounts of retraction and prevention of DUWL contamination occurred in only two cases (3.7%). Correct retraction was noted in six other dental units (DUs), but their DUWLs became contaminated during testing. Six other produced the opposite results—improper retraction, yet no contamination. The remaining 40 DUs (74.0%) failed both evaluations. Conclusion. The results showed that the overwhelming majority of the anti-retraction devices did not prevent retraction when the turbine stopped running, leading to a contamination of the water lines, and to a consequent possible cross-contamination of the patients.

Sir, Chronic kidney disease (CKD) is an emerging clinical issue in HIV, particularly in ageing infected patients. Nephrotoxicity is a major issue and a frequent cause of drug switching owing to glomerular or tubular damage and the fear of progressive CKD.However, the incidence and impact of urolithiasis as an independent contributor to CKD are not known in HIV-infected patients. Historically, antiretroviral-induced urolithiasis has been common inpatientstreatedwith indinavir,probablyduetodrugcrystallization and precipitation in the kidneys. At present, with regards to the risk of urolithiasis, the use of boosted or unboosted atazanavir as preferred protease inhibitor (PI) is of concern. In a large retrospective studyof 1240 HIV-infected individuals, Hamada et al. reported a urolithiasis incidence of 23.7 cases per 1000 patient-years among atazanavir-treated patients. Notably, the authors postulated that atazanavir/ritonavir can promote kidney stones via similar mechanisms to indinavir-induced urolithiasis. This single-centre study, as the authors pointed out, had several limitations owing to its observational and retrospective nature and because of the absence of renal stone composition analyses. In particular, the hypothesized pathogenetic mechanism – atazanavir-supersaturated urine inducing crystalluria – is difficult to test in consideration of the lack of association between serum bilirubin levels, surrogate markers of plasma atazanavir concentration and the risk of kidney stones. By contrast, baseline data showed significantly higher uric acid concentrations in patients treated with atazanavir/ritonavir compared with patients treated with other PIs. Even though uric acid levels did not affect the Cox proportional hazard regression model results, and atazanavir/ritonavir exposure was associated with a 10-fold increased risk for kidney stones, these results may have been distorted by a ‘channelling’ bias. Atazanavir/ritonavir is preferentially prescribed to patients with higher metabolic risk profiles (European AIDS Clinical Society; Version 6.1; November 2012; http:// www.europeanaidsclinicalsociety.org/index.php?option1⁄4com_con tent&view1⁄4article&id1⁄459&Itemid=41). An expanding body of evidence supports the notion that kidney stones are not always a separate entity but in some instances represent an epiphenomenon of a systemic metabolic disorder, being associated with insulin resistance and metabolic syndrome.In keeping with the study by Hamada et al., it is plausible that at least some of the reported effects of atazanavir/ritonavir could be confounded by physician prescription. Interestingly, the prevalence of nephrolithiasis seems higher among HIV-infected individuals than the general population (0.8%). Raheem et al. described 46 cases of nephrolithiasis in a cohort of 436 HIV-positive subjects, corresponding to an overall 11% prevalence: similar to what is expected in the general population. Unfortunately, stone analysis was only available in seven subjects and documented four cases of calcium oxalate monohydrate crystals and only one case each of cystine, uric acid and atazanavir crystals. A similar prevalence of kidney stones was described in the Castle study, the largest randomized clinical trial on atazanavir/ritonavir ever performed in naive patients. Though evidence in HIV-infected individuals is far from being conclusive, the study by Hamada et al. suggests a thorough metabolic evaluation for nephrolithiasis in HIV-infected patients with recurrent episodes of kidneystones, a family historyof nephrolithiasis or evidence of multiple kidney stones at imaging. However, we suggest caution in interpreting the epidemiological data linking atazanavir exposure and kidney stones owing to a potential ‘channelling’ bias. Indeed, an excess number of patients with metabolic disturbance may be prescribed the atazanavir/ritonavir regimen in light of its favourable lipid profile, but these patients are in fact at higher risk for urolithiasis. This situation significantly resembles our observation regarding the spurious association between abacavir and cardiovascular disease, which in fact was mediated by CKD, which was in turn the comorbidity that prompted healthcare workers to prefer abacavir to tenofovir. New observational studies and randomized clinical trials are needed to prove this hypothesis.

In recent years, several reports have suggested, but never definitely demonstrated that dental units (DU) could be potential sources of viral cross-infections sustained by viral agents including HBV, HCV and HIV. This work aims at assessing the risk of HCV cross-infection by dental unit water lines (DUWLs). Ten anti-HCV positive viremic patients were submitted to dental treatment on three different DU (one unit fully equipped to minimize viral contamination risk). A PCR method using primers for UTR and E2 regions was used to evaluate HCV RNA presence in DUWLs sprays. A modified RNA extraction protocol was developed to eliminate the risk of low sensibility due to the presence of inhibitors in saliva. Sequences obtained from E2 PCR products amplified from blood and oral fluids were analyzed and compared. Fluids collected from three different DU before treatment were always negative for the presence of HCV RNA; after treatment viral contamination was detected in six out of ten cases in conventional DU, in three out of ten cases on the reduced-retraction DU while was never detected in sprays taken from fully equipped DU. Comparison of E2 region sequences obtained from blood and DUWLs sprays showed identity in each patient. Here we demonstrate that fixed DUWLs and handpieces can be contaminated by viral agents and become a vehicle of cross-infection and that a specific online active decontamination system developed for both handpieces and fixed waterlines can eliminate this risk.