articles by Marianna Menozzi

Objectives: Aging with HIV is associated with multisystem vulnerability that might be well charac... more Objectives: Aging with HIV is associated with multisystem vulnerability that might be well characterized by frailty. We sought to construct a frailty index based on health deficit accumulation in a large HIV clinical cohort and evaluate its validity including the ability to predict mortality and incident multimorbidity. Design and methods: This is an analysis of data from the prospective Modena HIV Metabolic Clinic cohort, 2004–2014. Routine health variables were screened for potential inclusion in a frailty index. Content, construct, and criterion validity of the frailty index were assessed. Multivariable regression models were built to investigate the ability of the frailty index to predict survival and incident multimorbidity (at least two chronic disease diagnoses) after adjusting for known HIV-related and behavioral factors. Results: Two thousand, seven hundred and twenty participants (mean age 46 AE 8; 32{\%} women) provided 9784 study visits; 37 non-HIV-related variables were included in a frailty index. The frailty index exhibited expected characteristics and met validation criteria. Predictors of survival were frailty index (0.1 increment, adjusted hazard ratio 1.63, 95{\%} confidence interval 1.05–2.52), current CD4 þ cell count (0.48, 0.32–0.72), and injection drug use (2.51, 1.16–5.44). Predictors of incident multimorbidity were frailty index (adjusted incident rate ratio 1.98, 1.65–2.36), age (1.07, 1.05–1.09), female sex (0.61, 0.40–0.91), and current CD4 þ cell count (0.71, 0.59–0.85). Conclusion: Among people aging with HIV in northern Italy, a frailty index based on deficit accumulation predicted survival and incident multimorbidity independently of HIV-related and behavioral risk factors. The frailty index holds potential value in quantifying vulnerability among people aging with HIV.

Background: Epicardial adipose tissue (EAT) and coronary artery calcium (CAC) have been associate... more Background: Epicardial adipose tissue (EAT) and coronary artery calcium (CAC) have been associated with incident coronary artery disease (CAD) and all-cause mortality in the general population. Their prognostic impact in HIV is unknown. Methods: Observational study of 843 consecutive HIV-infected patients receiving antiretroviral therapy for at least 6 months. Risk stratification was performed with coronary artery calcium (CAC) scoring and EAT screening. Patients were followed for CAD and all-cause mortality for a median of 2.8 years accounting for a total of 2572 patient-year follow-up. Results: Mean patient age was 50 ± 8 years and 69{\%} were men. At baseline EAT was associated with male gender, age, waist circumference, visceral adipose tissue, and lipodystrophy, while CAC score ≥100 was associated with male gender, age and total cholesterol. During follow-up 33 patients suffered an event (15 incident myocardial infarctions and 18 deaths); the EAT volume was larger and the CAC score was higher in patients with events (p = 0.038 and p = 0.001 respectively). Multivariable regression analyses demonstrated that the upper tertile of EAT (≥93 cc; OR 2.15, 95{\%} CI 1.06 - 4.39, p = 0.034), and CAC score ≥100 (OR 3.37, 95{\%} CI 1.49 - 7.60, p = 0.003) were independent predictors of events after adjusting for age and sex. Conclusions: In this observational cohort of HIV patients, EAT and CAC were independent predictors of hard outcomes after a median follow-up of approximately 3 years.
Papers by Marianna Menozzi
Cardiovascular disease is highly prevalent in HIV-positive patients and can be explored with coro... more Cardiovascular disease is highly prevalent in HIV-positive patients and can be explored with coronary artery calcium score as a biomarker of preclinical coronary disease. Antiretroviral drugs and concomitant treatment including second generation anti-psychotics may contribute to metabolic derangement with potential impact on traditional cardiovascular risk factors associated with the metabolic syndrome phenotype. The objective of the study was to assess the impact of second generation anti-psychotics on subclinical cardiovascular disease in HIV positive patients

Open Forum Infectious Diseases
Background Limited data exist examining the association between incident cancer and cumulative in... more Background Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure. Methods Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months. Results Of 29 340 individuals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36–51). Overall, 13 950 (48%) individuals started an INSTI during follow-up. During 160 657 person-years of follow-up ([PYFU] median 6.2; IQR, 3.9–7.5), there were 1078 cancers (incidence rate [IR] 6.7/1000 PYFU; 95% confidence interval [CI], 6.3–7.1). The commonest cancers were non-Hodgkin lymphoma (n = 113), lung cancer (112), Kaposi’s sarcoma (106), and anal cancer (103)....

Intensive Care Medicine
Purpose: Cytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common ... more Purpose: Cytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common and relates to a worsening outcome. In this large observational study, we evaluated the incidence and the risk factors associated with CMV reactivation and its effects on mortality in a large cohort of patients affected by coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Methods: Consecutive patients with confirmed SARS-CoV-2 infection and acute respiratory distress syndrome admitted to three ICUs from February 2020 to July 2021 were included. The patients were screened at ICU admission and once or twice per week for quantitative CMV-DNAemia in the blood. The risk factors associated with CMV blood reactivation and its association with mortality were estimated by adjusted Cox proportional hazards regression models. Results: CMV blood reactivation was observed in 88 patients (20.4%) of the 431 patients studied. Simplified Acute Physiology Score (SAPS) II score (HR 1031, 95% CI 1010-1053, p = 0.006), platelet count (HR 0.0996, 95% CI 0.993-0.999, p = 0.004), invasive mechanical ventilation (HR 2611, 95% CI 1223-5571, p = 0.013) and secondary bacterial infection (HR 5041; 95% CI 2852-8911, p < 0.0001) during ICU stay were related to CMV reactivation. Hospital mortality was higher in patients with (67.0%) than in patients without (24.5%) CMV reactivation but the adjusted analysis did not confirm this association (HR 1141, 95% CI 0.757-1721, p = 0.528). Conclusion: The severity of illness and the occurrence of secondary bacterial infections were associated with an increased risk of CMV blood reactivation, which, however, does not seem to influence the outcome of COVID-19 ICU patients independently.

Antibiotics
The coronavirus disease 2019 (COVID-19)-pandemic-related overload of health systems has compromis... more 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 signific...

Antimicrobial Resistance & Infection Control
Background During the last decade carbapenem-resistant Acinetobacter baumannii (CRAB) became hype... more 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 C...

BMJ Open, 2022
ObjectiveThe first COVID-19–19 epidemic wave was over the period of February–May 2020. Since 1 Oc... more ObjectiveThe first COVID-19–19 epidemic wave was over the period of February–May 2020. Since 1 October 2020, Italy, as many other European countries, faced a second wave. The aim of this analysis was to compare the 28-day mortality between the two waves among COVID-19 hospitalised patients.DesignObservational cohort study. Standard survival analysis was performed to compare all-cause mortality within 28 days after hospital admission in the two waves. Kaplan-Meier curves as well as Cox regression model analysis were used. The effect of wave on risk of death was shown by means of HRs with 95% CIs. A sensitivity analysis around the impact of the circulating variant as a potential unmeasured confounder was performed.SettingUniversity Hospital of Modena, Italy. Patients admitted to the hospital for severe COVID-19 pneumonia during the first (22 February–31 May 2020) and second (1 October–31 December 2020) waves were included.ResultsDuring the two study periods, a total of 1472 patients w...

Le infezioni in medicina, 2021
Cardiovascular complications after a SARS-CoV-2 infection are a phenomenon of relevant scientific... more Cardiovascular complications after a SARS-CoV-2 infection are a phenomenon of relevant scientific interest. The aim of this study was to analyze the onset of post-COVID-19 cardiovascular events in patients hospitalized in a tertiary care center. This is a retrospective study conducted on patients hospitalized over a period of three months. The patients were older than 18 years of age and had a diagnosis of COVID-19 infection confirmed from a nasopharyngeal swab sample. Anamnestic and clinical-laboratory data were collected. Cardiovascular events at 30 days were defined as follows: arrhythmias, myocardial infarction, myocarditis, and pulmonary embolism. Univariate analysis (Student's t-test or Mann-Whitney U test, as appropriate) and multivariate analysis (multinomial logistic regression) were applied to the data. A total of 394 patients were included; they were mostly males and had a median age of 65.5 years. Previous cardiovascular disease was present in 14.7% of patients. Oxyg...
Clinical Kidney Journal, 2021

JAC-Antimicrobial Resistance, 2021
Objectives To describe our real-life experience with cefiderocol in XDR and difficult-to-treat re... more Objectives To describe our real-life experience with cefiderocol in XDR and difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) infections without any other available treatment options. Methods We included patients with a proven infection due to an XDR/DTR-P, who had failed on previous regimens, and were treated with cefiderocol, following them prospectively to day 90 or until hospital discharge or death. Results Seventeen patients treated for >72 h with cefiderocol were included: 14 receiving combination regimens (82.4%) and 3 receiving monotherapy (17.6%). Fourteen patients were males (82%) with a median age of 64 years (IQR 58–73). Fifteen patients (88.2%) were admitted to the ICU and five had septic shock (29%). Seven cases (41.2%) were ventilator-associated pneumonia, of which 71% (5/7) occurred in COVID-19 patients. Four were complicated intrabdominal infections, one ecthyma gangrenosum, one nosocomial pneumonia and one empyema, one osteomyelitis, one primary bacter...

Nephrology Dialysis Transplantation, 2021
Background and Aims Acid-base disorders are common in severely ill patients and reflect the sever... more Background and Aims Acid-base disorders are common in severely ill patients and reflect the severity of the underlying pathologic process. The incidence and effects of acid-base derangement in COVID-19 patients have been poorly evaluated until now. Tropism of the virus for the lungs and kidneys may theoretically lead to frequent acid-base alterations due to pneumonia and kidney injury, respectively. To verify the derangement of acid-base disorders in COVID-19, we investigated the distribution and the impact of acid-base disorders on the survival of symptomatic patients with a diagnosis of COVID-19. Method We retrospectively collected data from electronic charts of all COVID-19 patients hospitalized at the University Hospital of Modena from 4 March to 20 June 2020. Arterial blood gas (ABG) analysis was required to monitor pulmonary gas exchange and acid-base status. A pH of less than 7.37 was categorized as acidemia and a pH of more than 7.42 was categorized as alkalemia. 211 patient...
Clinical Microbiology and Infection, 2021
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Microorganisms, 2021
Background: Herpes simplex 1 co-infections in patients with COVID-19 are considered relatively un... more 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 me...

Clinical and Experimental Nephrology, 2021
Background Patients with COVID-19 experience multiple clinical conditions that may cause electrol... more Background Patients with COVID-19 experience multiple clinical conditions that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder closely associated with severe complications. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of patients with confirmed COVID-19. Methods A retrospective analysis was conducted on 290 non-ICU admitted patients with COVID-19 at the tertiary teaching hospital of Modena, Italy, from February 16 to April 14, 2020. Results Hypokalemia was detected in 119 out of 290 patients (41%) during hospitalization. Mean serum potassium was 3.1 ± 0.1 meq/L. The majority of patients (90.7%) patients experienced only a mild decrease in serum potassium level (3-3.4 mEq/L). Hypokalemia was associated with hypocalcemia, which was detected in 50% of subjects. Urine potassiumto-creatinine ratio, measured in a small number of patients (n = 45; 36.1%), revealed an increase of urinary potassium excretion in most cases (95.5%). Risk factors for hypokalemia were female sex (odds ratio (OR) 2.44; 95% CI 1.36-4.37; P 0.003) and diuretic therapy (OR 1.94, 95% CI 1.08-3.48; P 0.027). Hypokalemia, adjusted for sex, age and SOFA score, was not associated with ICU transfer (OR 0.52; 95% CI 0.228-1.212; P = 0.131), in-hospital mortality (OR, 0.47; 95% CI 0.170-1.324; P = 0.154) and composite outcome of ICU transfer or in-hospital mortality (OR 0.48; 95% CI 0.222-1.047; P = 0.065) in our cohort of patients. Conclusions Hypokalemia was a frequent disorder in subjects with COVID-19. Female sex and diuretic therapy were identified as risk factors for low serum potassium levels. Hypokalemia was unrelated to ICU transfer and death in this cohort of patients.

PLOS ONE, 2021
Background The benefit of tocilizumab on mortality and time to recovery in people with severe COV... more 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 ...

Open Forum Infectious Diseases, 2020
BackgroundCurrently, no data are available on the burden of morbidity and mortality in people wit... more BackgroundCurrently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population.MethodsThis was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death.ResultsAmong 148 PWH followed for a median (interquartile range) of 47 (32–84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI ...
Infectious Disease Reports, 2020
We describe a case of acute myocarditis which was reported as the main COVID-19 clinical manifes-... more We describe a case of acute myocarditis which was reported as the main COVID-19 clinical manifes-tation, with a favorable outcome. In addition to symptoms, laboratory tests (BNP and troponin), echo-cardiogram and cardiac MRI contributed to diagnosis. Regardless heart biopsy was not obtained, it is likely an immunological pathogenesis of this condition which pave the way to further therapeutic im-plications, since there are currently no standardized treatments.

The Lancet Rheumatology, 2020
Background No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the... more 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<0•0001) patients treated with tocilizumab (six [7%] treated intravenously and seven [8%] treated subcutaneously). After adjustment for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0•61, 95% CI 0•40-0•92; p=0•020). 24 (13%) of 179 patients treated with tocilizumab were diagnosed with new infections, versus 14 (4%) of 365 patients treated with standard of care alone (p<0•0001). Interpretation Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia.

Background Machine learning can assist clinicians in forecasting patients with COVID-19 who devel... more Background Machine learning can assist clinicians in forecasting patients with COVID-19 who develop respiratory failure requiring mechanical ventilation. This analysis aimed to determine a 48 hours prediction of moderate to severe respiratory failure, as assessed with PaO2/FiO2 < 150 mmHg, in hospitalized patients with COVID-19 pneumonia. Methods This was an observational study that comprised all consecutive adult patients with COVID-19 pneumonia admitted to the Infectious Diseases Clinic of the University Hospital of Modena, Italy from 21 February to 6 April 2020. COVID-19 was confirmed with PCR positive nasopharyngeal swabs while the presence of pneumonia was radiologically confirmed. Patients received standard of care according to national guidelines for clinical management of SARS-CoV-2 infection. The patients' full medical history, demographic and epidemiological features, clinical data, complete blood count, coagulation, inflammatory and biochemical markers were routine...
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articles by Marianna Menozzi
Papers by Marianna Menozzi