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Abstract Background Patients with hematological malignancies (HM) have a high risk of severe coronavirus disease 2019 (COVID‐19), also in the Omicron period. Material and methods Retrospective single‐center study including HM patients with severe acute respiratory syndrome Coronavirus 2 (SARS‐CoV2) infection from January 2022 to March 2023. Study outcomes were respiratory failure (RF), mechanical ventilation (MV), and COVID‐related mortality, comparing patients according to SARS‐CoV2 serology. Results Note that, 112 patients were included: 39% had negative SARS‐CoV2 serology. Seronegative were older (71.5 vs. 65.0 years, p = 0.04), had more often a lymphoid neoplasm (88.6% vs. 69.1%, p = 0.02), underwent anti‐CD20 therapy (50.0% vs. 30.9% p = 0.04) and had more frequently a severe disease (23.0% vs. 3.0%, p = 0.02) than seropositive. Kaplan‐Meier showed a higher risk for seronegative patients for RF (p = 0.014), MV (p = 0.044), and COVID‐related mortality (p = 0.021). Negative SARS‐CoV2 serostatus resulted in a risk factor for RF (hazards ratio [HR] 2.19, 95% confidence interval [CI] 1.03–4.67, p = 0.04), MV (HR 3.37, 95% CI 1.06–10.68, p = 0.04), and COVID‐related mortality (HR 4.26, 95% CI 1.09–16.71, p = 0.04). Conclusions : HM patients with negative SARS‐CoV2 serology, despite vaccinations and previous infections, have worse clinical outcomes compared to seropositive patients in the Omicron era. The use of serology for SARS‐CoV2 diagnosis could be an easy tool to identify patients prone to developing complications.

Abstract Background Vancomycin-resistant enterococcus (VRE) was the fastest growing pathogen in Europe in 2022 (+ 21%) but its clinical relevance is still unclear. We aim to identify risk factors for acquired VRE rectal colonization in hematological patients and evaluate the clinical impact of VRE colonization on subsequent infection, and 30- and 90-day overall mortality rates, compared to a matched control group. Methods A retrospective, single center, case–control matched study (ratio 1:1) was conducted in a hematological department from January 2017 to December 2020. Case patients with nosocomial isolation of VRE from rectal swab screening (≥ 48 h) were matched to controls by age, sex, ethnicity, and hematologic disease. Univariate and multivariate logistic regression compared risk factors for colonization. Results A total of 83 cases were matched with 83 controls. Risk factors for VRE colonization were febrile neutropenia, bone marrow transplant, central venous catheter, bedsores, reduced mobility, altered bowel habits, cachexia, previous hospitalization and antibiotic treatments before and during hospitalization. VRE bacteraemia and Clostridioides difficile infection (CDI) occurred more frequently among cases without any impact on 30 and 90-days overall mortality. Vancomycin administration and altered bowel habits were the only independent risk factors for VRE colonization at multivariate analysis (OR: 3.53 and 3.1; respectively). Conclusions Antimicrobial stewardship strategies to reduce inappropriate Gram-positive coverage in hematological patients is urgently required, as independent risk factors for VRE nosocomial colonization identified in this study include any use of vancomycin and altered bowel habits. VRE colonization and infection did not influence 30- and 90-day mortality. There was a strong correlation between CDI and VRE, which deserves further investigation to target new therapeutic approaches.

Objectives: Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in people without HIV. Decompensated liver cirrhosis is not currently considered a risk factor for PCP. The aim of this paper is to describe a case series of patients with decompensated liver cirrhosis and PCP. Methods: All consecutive patients hospitalized with decompensated cirrhosis and microbiology-confirmed PCP at Policlinico Modena University Hospital from January 1, 2016 to December 31, 2021 were included in our series. Results: Eight patients were included. All patients had advanced-stage liver disease with a model for end-stage liver disease score above 15 (6/8 above 20). Four were on an active orthotopic liver transplant waiting list at the time of PCP diagnosis. Five patients did not have any traditional risk factor for PCP, whereas the other three were on glucocorticoid treatment for acute-on-chronic liver failure. All patients were treated with cotrimoxazole, except two who died before the diagnosis. Five patients died (62.5%), four of them within 30 days from PCP diagnosis. Of the remaining three, one patient underwent liver transplantation. Conclusion: Although further studies are needed, liver cirrhosis can be an independent risk factor for PCP in patients with decompensated cirrhosis that is mainly due to severe alcoholic hepatitis and who are on corticosteroids therapy, and primary prophylaxis for PCP should be considered.

Dalbavancin represents a promising treatment for cardiovascular prosthetic infections due to its prolonged half-life, bactericidal activity, large spectrum of activity, and excellent biofilm penetration. However, the use of dalbavancin in this setting is limited, and only a few cases have performed therapeutic drug monitoring (TDM) analysis to optimize dosage in suppressive treatments longer than 4 weeks. Our retrospective case series reports the use of dalbavancin in a small cohort of patients with cardiovascular prosthetic infections (cardiac implantable electronic device infections (CEDIs), prosthetic valve endocarditis (PVE), prosthetic vascular graft infections (PVGIs)) treated with dalbavancin as sequential therapy. From May 2019 to May 2023, 14 patients were included: eight cases of PVE (57.1%), seven cases of PVGI (50%), three cases of CEDI (21.4%), and four cases with overlap of infection sites (28.6%). The main pathogen was Staphylococcus aureus (35.7%). Prosthesis replacement was obtained in four patients (28.6%). The median time between symptom onset and the end of treatment was 15 weeks (IQR 7–53), with a median duration of dalbavancin therapy of 8 weeks (IQR 1 to 45 weeks) and 3.5 doses per patient. Among patients managed with TDM-guided strategy, dalbavancin infusion intervals ranged from 4 to 9 weeks. The median length of follow-up was 65 weeks (IQR 23 to 144 weeks). Clinical success was achieved in 10 cases (76.9%); all clinical failures occurred in patients with the implant retained. Among patients monitored by TDM, clinical success was 87.5% vs. 60% in patients treated without TDM. Because of pharmacokinetic individual variability, dalbavancin TDM-guided administration could improve clinical outcomes by individualizing dosing and selecting dosing intervals. This case series seems to suggest a promising role of long-term suppressive dalbavancin treatment for difficult-to-treat cardiovascular prosthesis infection, also with limited surgical indications.

Background The prognostic value of within-day sCr variation serum creatinine variation is unknown in the setting of the novel coronavirus disease 2019 (COVID-19). We evaluated the prognostic significance of 24-hour serum creatinine variation in COVID-19 patients. Methods A monocentric retrospective analysis was conducted in COVID-19 patients not admitted to the intensive care unit. Three groups were subdivided based on 24 hours serum creatinine variation from admission. In the stable kidney function group, 24-hour serum creatinine variation ranged from +0.05 to –0.05 mg/dL; in the decreased kidney function group, 24-hour serum creatinine variation was >0.05 mg/dL; in the improved kidney function group, 24-hour serum creatinine variation was

Abstract Background During the last decade carbapenem-resistant Acinetobacter baumannii (CRAB) became hyper-endemic in hospitals due to difficult to control spreading. Our aim is to identify risk factors for nosocomial rectal CRAB colonization in an endemic hospital. Methods A retrospective matched case–control study (ratio 1:2) with a prospective inclusion of cases and concurrent selection of controls was conducted from January 2017 to December 2018 in a tertiary-care hospital. Universal active surveillance for CRAB was implemented. Univariate and multivariate logistic regression was carried out using a stepwise selection method to compare prognostic factors between cases and controls. A sub-analysis was carried out according to the type of department. Results Forty-five cases with nosocomial rectal CRAB colonization and 90 controls were included. One hundred and two (75%) patients were hospitalized in medical departments. At multivariable analysis significant risk factors associated with CRAB colonization were: use of permanent devices (OR 10.15, 95% CI 2.27–45.39; P = 0.002), mechanical ventilation (OR 40.01, 95% CI 4.05–395.1; P = 0.002), urinary catheters (OR 4.9, 95% CI 1.52–16.19; P = 0.008), McCabe score (OR 5.45, 95% CI 1.87–15.89; P = 0.002), length of stay (OR 1.03, 95% CI 1.01–1.05; P = 0.002), carbapenem use (OR 5.39, 95% CI 1.14–25.44; P = 0.033). The sub-analysis showed that patients admitted to different departments had different risk factors. In geriatric department a fatal disease and a longer hospital stay represented significant risk factors both in univariate and multivariate analysis, while in internal medicine department the use of permanent devices, current antibiotic therapy and antibiotic polytherapy represented significant risk factors for CRAB at the univariate analysis, also confirmed in multivariate analysis. Conclusions Our data suggest that active surveillance for rectal CRAB colonization should be addressed to patients with an unfavourable prognosis, longer hospitalizations and carriers of multiple devices. To counter CRAB spreading in endemic settings, clinicians must limit the use of carbapenems, and reinforce interventions aimed at proper use of devices.

Objectives: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). Methods: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. Results: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52–73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24–8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69–13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17–0.88; P = 0.024) was associated with use of colistin monotherapy. Conclusion: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

Abstract Background Contemporary HIV care may reduce frailty in older adults living with HIV (OALWH). Objective of the study was to estimate prevalence of frailty at the age of 50 and 75 years, and build a model to quantify the burden of frailty in the year 2030. Methods This study included OALWH attending Modena HIV Metabolic Clinic between 2009 and 2015. Patients are referred from more than 120 HIV clinics well distributed across Italy, therefore being country representative. Our model forecasts the new entries on yearly basis up to 2030. Changes in frailty over a one-year period using a 37-variable frailty index (FI) and death rates were modelled using a validated mathematical algorithm with parameters adjusted to best represent the changes observed at the clinic. In this study, we assessed the number of frailest individuals (defined with a FI > 0.4) at the age of 50 and at the age 75 by calendar year. Results In the period 2015–2030 we model that frailest OALWH at age 50 will decrease from 26 to 7%, and at the age of 75 years will increase from 43 to 52%. This implies a shift of the frailty prevalence at an older age. Conclusion We have presented projections of how the burden of frailty in older adults, living with HIV will change. We project fewer people aged 50+ with severe frailty, most of whom will be older than now. These results suggest a compression of age-related frailty.

Ventilator-associated pneumonia (VAP) in critically ill patients with COVID-19 represents a very huge global threat due to a higher incidence rate compared to non-COVID-19 patients and almost 50% of the 30-day mortality rate. Pseudomonas aeruginosa was the first pathogen involved but uncommon non-fermenter gram-negative organisms such as Burkholderia cepacea and Stenotrophomonas maltophilia have emerged as other potential etiological causes. Against carbapenem-resistant gram-negative microorganisms, Ceftazidime/avibactam (CZA) is considered a first-line option, even more so in case of a ceftolozane/tazobactam resistance or shortage. The aim of this report was to describe our experience with CZA in a case series of COVID-19 patients hospitalized in the ICU with VAP due to difficult-to-treat (DTT) P. aeruginosa, Burkholderia cepacea, and Stenotrophomonas maltophilia and to compare it with data published in the literature. A total of 23 patients were treated from February 2020 to March 2022: 19/23 (82%) VAPs were caused by Pseudomonas spp. (16/19 DTT), 2 by Burkholderia cepacea, and 6 by Stenotrophomonas maltophilia; 12/23 (52.1%) were polymicrobial. Septic shock was diagnosed in 65.2% of the patients and VAP occurred after a median of 29 days from ICU admission. CZA was prescribed as a combination regimen in 86% of the cases, with either fosfomycin or inhaled amikacin or cotrimoxazole. Microbiological eradication was achieved in 52.3% of the cases and the 30-day overall mortality rate was 14/23 (60.8%). Despite the high mortality of critically ill COVID-19 patients, CZA, especially in combination therapy, could represent a valid treatment option for VAP due to DTT non-fermenter gram-negative bacteria, including uncommon pathogens such as Burkholderia cepacea and Stenotrophomonas maltophilia.

The yeast mitochondrial transport of GTP and GDP is mediated by Ggc1p, a member of the mitochondrial carrier family. The physiological role of Ggc1p in S. cerevisiae is probably to transport GTP into mitochondria in exchange for GDP generated in the matrix. ggc1Δ cells exhibit lower levels of GTP and increased levels of GDP in mitochondria, are unable to grow on nonfermentable substrates and lose mtDNA. Because in yeast, succinyl-CoA ligase produces ATP instead of GTP, and the mitochondrial nucleoside diphosphate kinase is localized in the intermembrane space, Ggc1p is the only supplier of mitochondrial GTP required for the maturation of proteins containing Fe-S clusters, such as aconitase [4Fe-4S] and ferredoxin [2Fe-2S]. In this work, it was demonstrated that citrate is a regulator of purified and reconstituted Ggc1p by trans-activating unidirectional transport of GTP across the proteoliposomal membrane. It was also shown that the binding site of Ggc1p for citrate is different from the binding site for the substrate GTP. It is proposed that the citrate-induced GTP uniport (CIGU) mediated by Ggc1p is involved in the homeostasis of the guanine nucleotide pool in the mitochondrial matrix.

ObjectiveTo identify risk factors for functional decline after hospitalization for Gram-negative bacteremia.Patients and methodsA 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.ResultsFive 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).ConclusionsPatients 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.

BackgroundThe 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.MethodsIn 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.ResultsTwo 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.ConclusionTo 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.

Introduction: Aim of the study is to evaluate the prevalence of HBV, HIV, HCV, tuberculosis and syphilis infection among immigrants assigned to the immigrant centre of the province of Modena. Methods: At the time of arrival all immigrant were tested for: HBsAg, HBsAb, HBcAb, Ag p24/HIVAb, HCVAb, RPR, TPPA, Mantoux test (>10 mm diameter of induration was considered to be positive), Chest X-rays. In case of positive samples, second level tests were performed (HbeAg, HBeAb, HDVAb, and baseline management and treatment of the infection detected). Results: A total of 304 immigrant people were enrolled in the study. HBsAg positivity was 12.2%, HCVAb 3.3%, HIVAb 1.6%, TPPA + RPR positivity in the 0.7%; 10.2% had a positive Mantoux test; 5.6% had Chest X-rays positive for signs of infection and 6 patients had an active tuberculosis. 83.8% HBsAg were HBeAb positive/HBeAg negative. HDVAb resulted positive in 1 patient (2.7%). Previous HBV infection was detected in 28.6% of cases, isolated HBcAb in 2.3%; 5.6% of patients resulted to be positive to HbsAb alone (probable vaccinated). Conclusion: Our study confirms the high prevalence of HBsAg positivity and latent tuberculosis among immigrants, underlying the importance of screening for infections in this special population. Keywords: Immigrant population, Sexually transmitted infections, Tuberculosis, Screening

The coronavirus disease 2019 (COVID-19)-pandemic-related overload of health systems has compromised the application of antimicrobial stewardship (AS) models and infection prevention and control (IPC) programs. We aimed to evaluate the impact of COVID-19 on antimicrobial consumption (AC) and antimicrobial resistance (AMR) in the University Hospital of Modena. A time series analysis with an autoregressive integrated moving average model was conducted from January 2015 to October 2021 to evaluate the AC in the whole hospital and the intensive care unit (ICU), the incidence density (ID) of bloodstream infections (BSIs) due to the main multidrug-resistant organisms, and of C. difficile infections (CDIs). After an initial peak during the COVID-19 period, a decrease in the trend of AC was observed, both at the hospital (CT: −1.104, p = 0.025) and ICU levels (CT: −4.47, p = 0.047), with no significant difference in the single classes. Among the Gram-negative isolates, we observed a significant increase only in the level of BSIs due to carbapenem-susceptible Pseudomonas aeruginosa (CL: 1.477, 95% CI 0.130 to 2.824, p = 0.032). Considering Gram-positive bacteria, an increase in the level of BSIs due to methicillin-resistant Staphylococcus aureus and in the trend of CDIs were observed, though they did not reach statistical significance (CL: 0.72, 95% CI −0.039 to 1.48, p = 0.062; CT: 1.43, 95% CI −0.002 to 2.863, p = 0.051; respectively). Our findings demonstrated that the increases in AMR and AC that appeared in the first COVID-19 wave may be later controlled by restoring IPC and AS programs to pre-epidemic levels. A coordinated healthcare effort is necessary to address the longer-term impact of COVID-19 on AC to avoid irreversible consequences on AMR.

Human blood cells all develop from haematopoietic stem cells (HSCs), classically thought to be multipotent. Here the authors show, using single-cell RNA-seq and functional assays, that loss of erythroid potential and commitment to the myelo-lymphoid lineage occurs within the purest HSC compartment to date.

The Wnt pathway is one of the core de-regulated pathways in chronic lymphocytic leukaemia (CLL) and is activated in only a subset of patients; however, no universal drivers of the disease have been identified. Here the authors show that Notch2 and β-catenin pathways are the main drivers of the pro-survival bidirectional crosstalk between stromal cells and leukemic cells.

AimsThe aim of this study was to estimate a 48 hour prediction of moderate to severe respiratory failure, requiring mechanical ventilation, in hospitalized patients with COVID-19 pneumonia.MethodsThis was an observational prospective study that comprised consecutive patients with COVID-19 pneumonia admitted to hospital from 21 February to 6 April 2020. The patients' medical history, demographic, epidemiologic and clinical data were collected in an electronic patient chart. The dataset was used to train predictive models using an established machine learning framework leveraging a hybrid approach where clinical expertise is applied alongside a data-driven analysis. The study outcome was the onset of moderate to severe respiratory failure defined as PaO2/FiO2 ratio ResultsA total of 198 patients contributed to generate 1068 usable observations which allowed to build 3 predictive models based respectively on 31-variables signs and symptoms, 39-variables laboratory biomarkers and 91-variables as a composition of the two. A fourth "boosted mixed model" included 20 variables was selected from the model 3, achieved the best predictive performance (AUC = 0.84) without worsening the FN rate. Its clinical performance was applied in a narrative case report as an example.ConclusionThis study developed a machine model with 84% prediction accuracy, which is able to assist clinicians in decision making process and contribute to develop new analytics to improve care at high technology readiness levels.

Background: Herpes simplex 1 co-infections in patients with COVID-19 are considered relatively uncommon; some reports on re-activations in patients in intensive-care units were published. The aim of the study was to analyze herpetic re-activations and their clinical manifestations in hospitalized COVID-19 patients, performing HSV-1 PCR on plasma twice a week. Methods: we conducted a prospective, observational, single-center study involving 70 consecutive patients with severe/critical SARS-CoV-2 pneumonia tested for HSV-1 hospitalized at Azienda Ospedaliero-Universitaria of Modena. Results: of these 70 patients, 21 (30.0%) showed detectable viremia and 13 (62%) had clinically relevant manifestations of HSV-1 infection corresponding to 15 events (4 pneumonia, 5 herpes labialis, 3 gingivostomatitis, one encephalitis and two hepatitis). HSV-1 positive patients were more frequently treated with steroids than HSV-1 negative patients (76.2% vs. 49.0%, p = 0.036) and more often underwent mechanical ventilation (IMV) (57.1% vs. 22.4%, p = 0.005). In the unadjusted logistic regression analysis, steroid treatment, IMV, and higher LDH were significantly associated with an increased risk of HSV1 re-activation (odds ratio 3.33, 4.61, and 16.9, respectively). The association with the use of steroids was even stronger after controlling for previous use of both tocilizumab and IMV (OR = 5.13, 95% CI:1.36–19.32, p = 0.016). The effect size was larger when restricting to participants who were treated with high doses of steroids while there was no evidence to support an association with the use of tocilizumab Conclusions: our study shows a high incidence of HSV-1 re-activation both virologically and clinically in patients with SARS-CoV-2 severe pneumonia, especially in those treated with steroids.

No data on antibiotic resistance in bloodstream infection (BSI) in people living with HIV (PLWH) exist. The objective of this study was to describe BSI epidemiology in PLWH focusing on multidrug resistant (MDR) organisms. A retrospective, single-center, observational study was conducted including all positive blood isolates in PLWH from 2004 to 2017. Univariable and multivariable GEE models using binomial distribution family were created to evaluate the association between MDR and mortality risk. In total, 263 episodes (299 isolates) from 164 patients were analyzed; 126 (48%) BSI were community-acquired, 137 (52%) hospital-acquired. At diagnosis, 34.7% of the patients had virological failure, median CD4 count was 207/μL. Thirty- and 90-day mortality rates were 24.2% and 32.4%, respectively. Thirty- and 90-day mortality rates for MDR isolates were 33.3% and 46.9%, respectively (p < 0.05). Enterobacteriaceae were the most prevalent microorganisms (29.8%), followed by Coagulase-negative staphylococci (21.4%), and S. aureus (12.7%). In BSI due to MDR organisms, carbapenem-resistant K. pneumoniae and methicillin-resistant S. aureus were associated with mortality after adjustment for age, although this correlation was not confirmed after further adjustment for CD4 < 200/μL. In conclusion, BSI in PLWH is still a major problem in the combination antiretroviral treatment era and it is related to a poor viro-immunological status, posing the question of whether it should be considered as an AIDS-defining event.

Background. Posttransplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality in solid organ transplants. Epstein Barr virus (EBV) plays a major role in PTLD development. Guidelines recommend EBV viral load (VL) monitoring in high-risk populations in the first year. Methods. Retrospective observational study in all adult patients who had at least 1 EBV-VL performed in the postkidney transplant (KT) period from January 2005 to December 2014 at the Policlinico Modena Hospital. We compared patients with negative EBV-DNA to patients with positive EBV-DNA and we described PTLD developed in the study period. Results. One hundred ninety (36.3%) KT patients of 523 were screened for EBV-DNA with 796 samples. One hundred twenty-eight (67.4%) of 190 tested patients presented at least 1 positive sample for EBV. Older age, the use of sirolimus, everolimus, and steroids were associated with EBV-DNA positivity in the univariate analysis. Nine (1.7%) of 523 patients had PTLD. Incidence rate of PTLD in the KT cohort was 0.19/100 person year follow-up (95% confidence interval, 0.09-0.37). One of 9 patients developed early PTLD and was a high-risk patient. Only this PTLD case was positive for EBV. No PTLD case had an EBV-VL superior to 4000 copies/mL. Conclusions. Our results suggest that the keystone of PTLD diagnosis is the clinical suspicion. Our study suggests that, in line with guidelines, EBV-VL assays may be avoided in low-risk patients in the absence of a strong clinical PTLD suspicion without increasing patients' risk of developing PTLD. This represents a safe and cost-saving clinical strategy for our center.

Chronic obstructive pulmonary disease (COPD) and emphysema are common amongst patients with human immunodeficiency virus (HIV). We sought to determine the clinical factors that are associated with emphysema progression in HIV.345 HIV-infected patients enrolled in an outpatient HIV metabolic clinic with ≥2 chest computed tomography scans made up the study cohort. Images were qualitatively scored for emphysema based on percentage involvement of the lung. Emphysema progression was defined as any increase in emphysema score over the study period. Univariate analyses of clinical, respiratory, and laboratory data, as well as multivariable logistic regression models, were performed to determine clinical features significantly associated with emphysema progression.17.4% of the cohort were emphysema progressors. Emphysema progression was most strongly associated with having a low baseline diffusion capacity of carbon monoxide (DLCO) and having combination centrilobular and paraseptal emphysema distribution. In adjusted models, the odds ratio (OR) for emphysema progression for every 10% increase in DLCO percent predicted was 0.58 (95% confidence interval [CI] 0.41-0.81). The equivalent OR (95% CI) for centrilobular and paraseptal emphysema distribution was 10.60 (2.93-48.98). Together, these variables had an area under the curve (AUC) statistic of 0.85 for predicting emphysema progression. This was an improvement over the performance of spirometry (forced expiratory volume in 1 second to forced vital capacity ratio), which predicted emphysema progression with an AUC of only 0.65.Combined paraseptal and centrilobular emphysema distribution and low DLCO could identify HIV patients who may experience emphysema progression.

People aging with HIV might have different health conditions compared with people who seroconverted at older ages. The study objective was to assess the prevalence of, and risk factors for, individual co-morbidities and multimorbidity (MM) between HIV-positive patients with a longer duration of HIV infection, and patients who seroconverted at an older age. We compared estimates across both groups to a matched community-based cohort sampled from the general population.We performed a case-control study including antiretroviral therapy (ART)-experienced patients who were HIV seropositive for ≥ 20.6 years ("HIV-Aging"), or who were seropositive for < 11.3 years ("HIV-Aged") having access in 2013 at the Modena HIV Metabolic Clinic. Patients were matched in a 1:3 ratio with controls from the CINECA ARNO database. MM was defined as the concurrent presence of >2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and MM.We analysed 404 HIV-Aging and 404 HIV-Aged participants in comparison to 2424 controls. The mean age was 46.7 ± 6.2 years, 28.9% were women. Prevalence of HIV co-morbidities and MM were significantly higher in the HIV-positive groups compared to the general population (p

The objective of this study was to assess the relationship of pack-years smoking and time since smoking cessation with risk of lung and heart disease.We investigated the history of lung and heart disease in 903 HIV-infected patients who had undergone thoracic computed tomography (CT) imaging stratified by smoking history. Multimorbidity lung and heart disease (MLHD) was defined as the presence of ≥ 2 clinical or subclinical lung abnormalities and at least one heart abnormality.Among 903 patients, 23.7% had never smoked, 28.7% were former smokers and 47.6% were current smokers. Spirometry indicated chronic obstructive pulmonary disease in 11.4% of patients and MLHD was present in 53.6%. Age, male sex, greater pack-years smoking history and smoking cessation less than 5 years earlier vs. more than 10 years earlier (OR 2.59, 95% CI 1.27-5.29, p = 0.009) were independently associated with CT detected subclinical lung and heart disease. Pack-years smoking history was more strongly associated with MLHD than smoking status (p

BackgroundWith the widespread use of anti-retroviral therapy (ART), individuals infected with human immune deficiency virus (HIV) are increasingly experiencing morbidity and mortality from respiratory disorders. However, the prevalence or the risk factors associated with emphysema and bronchiolitis are largely unknown.MethodsThoracic computed tomography (CT) scans were performed in 1,446 patients infected with HIV who were on ART and who attended a tertiary care metabolic clinic (average age 48 years and 29% females). Detailed history and physical examination including anthropometric measurements were performed. Complete pulmonary function tests were performed in a subset of these patients (n = 364). No subjects were acutely ill with a respiratory condition at the time of CT scanning.FindingsNearly 50% of the subjects had CT evidence for emphysema, bronchiolitis or both with 13% (n = 195) showing bronchiolitis, 19% (n = 274) showing emphysema and 16% (n = 238) revealing both. These phenotypes were synergistically associated with reduced regular physical activity (p for interaction InterpretationEmphysema and bronchiolitis are extremely common in HIV-infected patients who are treated with ART and can be identified by use of thoracic CT scanning.