Publications by authors named "Marco Rizzi"

41 Publications

Surviving COVID-19 in Bergamo province: a post-acute outpatient re-evaluation.

Epidemiol Infect 2021 01 19;149:e32. Epub 2021 Jan 19.

ASST Papa Giovanni XXIII Hospital, Bergamo, Italy.

Bergamo province was badly hit by the coronavirus disease 2019 (COVID-19) epidemic. We organised a public-funded, multidisciplinary follow-up programme for COVID-19 patients discharged from the emergency department or from the inpatient wards of 'Papa Giovanni XXIII' Hospital, the largest public hospital in the area. As of 31 July, the first 767 patients had completed the first post-discharge multidisciplinary assessment. Patients entered our programme at a median time of 81 days after discharge. Among them, 51.4% still complained of symptoms, most commonly fatigue and exertional dyspnoea, and 30.5% were still experiencing post-traumatic psychological consequences. Impaired lung diffusion was found in 19%. Seventeen per cent had D-dimer values two times above the threshold for diagnosis of pulmonary embolism (two unexpected and clinically silent pulmonary thrombosis were discovered by investigating striking D-dimer elevation). Survivors of COVID-19 exhibit a complex array of symptoms, whose common underlying pathology, if any, has still to be elucidated: a multidisciplinary approach is fundamental, to address the different problems and to look for effective solutions.
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http://dx.doi.org/10.1017/S0950268821000145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873454PMC
January 2021

At the peak of COVID-19 age and disease severity but not comorbidities are predictors of mortality: COVID-19 burden in Bergamo, Italy.

Panminerva Med 2021 Mar 27;63(1):51-61. Epub 2020 Nov 27.

Unit of Gastroenterology 1, Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy.

Background: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak.

Methods: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020.

Results: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2: 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N.=171). Thirty-nine percent of patients were treated with continuous positive airway pressure (CPAP), 9.5% with noninvasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to Semi-Intensive Respiratory Care Unit, and 18.9% to Intensive Care Unit. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio [OR], 95% confidence interval [CI]: 38.91 [10.67-141.93], P<0.001; 70-77 years: 17.30 [5.40-55.38], P<0.001; 60-69 years: 3.20 [1.00-10.20], P=0.049), PaO2/FiO2<200 at presentation (3.50 [1.70-7.20], P=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], P<0.001), and blood urea value at admission (1.01 [1.00-1.02], P=0.015).

Conclusions: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in COVID-19.
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http://dx.doi.org/10.23736/S0031-0808.20.04063-XDOI Listing
March 2021

Efficacy of β-lactam/β-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

Transpl Infect Dis 2020 Nov 22:e13520. Epub 2020 Nov 22.

Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.

Background: Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear.

Methods: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively.

Results: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes.

Conclusions: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
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http://dx.doi.org/10.1111/tid.13520DOI Listing
November 2020

Potential role of subcutaneous tocilizumab injections in patients with COVID-19 associated pneumonia.

J Med Virol 2021 02 5;93(2):686-688. Epub 2020 Oct 5.

Division of Infectious Diseases, ASST Papa Giovanni XXIII, Bergamo, Italy.

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http://dx.doi.org/10.1002/jmv.26494DOI Listing
February 2021

Efficacy and safety of dalbavancin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and other infections in a real-life setting: data from an Italian observational multicentric study (DALBITA study).

Expert Rev Anti Infect Ther 2020 12 14;18(12):1271-1279. Epub 2020 Aug 14.

Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo E Carlo, University of Milan , Milan, Italy.

Objectives: We evaluated the efficacy and safety of dalbavancin in ABSSSI and 'other sites' infections' (OTA).

Methods: Observational study involving 11 Italian hospitals including patients that received ≥1 dose of dalbavancin in 2016-2019. The outcome was end-of-treatment efficacy and safety in ABSSSI and OTA in a real-life setting.

Results: 206 patients enrolled (males 50%, median age 62 [IQR 50-76] years), 60.2% ABSSSI, 39.8% OTA. 69.7% ABSSSI 90.7% OTA (p = 0.003) and 46.3% ABSSSI 37.2% OTA (p = 0.786) received previous and concomitant antibiotics, respectively. 82.5% reached clinical cure . Eleven (5.4%) patients had non-serious adverse events (AE). OTA patients showed longer hospitalization (13.5 days, 5.5-22 3, 0-11.7; p<0.0001) and received longer previous (18 days, 9-30 11, 7-19; p = 0.007)/concomitant antibiotic treatments (21 days, 14-52 11, 8-14; p < 0.0001), compared to ABSSSI. ABSSSI and OTA showed similar efficacy (85.5% 75%, p = 0.459) and safety (no AE: 81.5% 64.3%, p = 0.258); efficacy was independent of previous/concomitant therapies.

Conclusions: Dalbavancin demonstrated a success rate of >80%, with similar efficacy/safety in ABSSSI and off-label indications. The preferential use of dalbavancin as second-line or combination therapy would seem to suggest the need for in-depth studies focused on its off-label use.
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http://dx.doi.org/10.1080/14787210.2020.1798227DOI Listing
December 2020

Calculated Decisions: Brescia-COVID Respiratory Severity Scale (BCRSS)/Algorithm.

Emerg Med Pract 2020 Apr 16;22(5 Suppl):CD1-CD2. Epub 2020 Apr 16.

Department of Infectious Diseases, Azienda Ospedaliera Papa Giovanni XXIII Hospital, Bergamo, Italy.

The Brescia-COVID respiratory severity scale/algorithm is a stepwise management approach to COVID-19 patients based on clinical severity. The BCRSS was rapidly developed in Brescia, Italy, during that nation's COVID-19 crisis. The scale has not been validated or tested in other populations. The BCRSS uses patient examination features along with the need for escalating levels of respiratory support (NIV, intubation, proning) to suggest treatment recommendations. The scale simplifies the clinical summary of a patient's status, and allows clinicians to compare patients to one another and to track the trend of a patient's level of respiratory severity over time.
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April 2020

SARS-CoV-2 invades the West. How to face a COVID-19 epidemic in Lombardy, Northern Italy?

Infez Med 2020 Ahead of print Jun 1;28(2):133-134

Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Unit of Infectious and Tropical Diseases, ASST Spedali Civili Hospital, Brescia, Italy.

Not available.
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April 2020

Papa Giovanni XXIII Bergamo Hospital at the time of the COVID-19 outbreak: Letter from the warfront….

Int J Lab Hematol 2020 06;42 Suppl 1:8-10

Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine, Papa Giovanni XXIII Hospital, Bergamo, Italy.

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http://dx.doi.org/10.1111/ijlh.13207DOI Listing
June 2020

Congenital Chagas disease in a non-endemic area: Results from a control programme in Bergamo province, Northern Italy.

Travel Med Infect Dis 2018 Sep - Oct;25:31-34. Epub 2018 Apr 20.

Malattie Infettive, ASST Papa Giovanni XXIII, Piazza OMS 1, Bergamo, Italy.

Introduction: In non-endemic countries, one of the most important routes of transmission of Trypanosoma cruzi is vertical transmission. The objective of this work is to report the results of the screening activities for the control of congenital Chagas Disease (CD) implemented in Bergamo province between January 2014 and December 2016.

Methods: The programme addressed Bolivian pregnant women settled in Bergamo province. All the eight hospitals offering antenatal and delivery care in that area were involved. We retrospectively calculated the coverage rate of the screening programme, the prevalence of CD in this population, as well as transmission rate to their offspring.

Results: During the study period, 376 Bolivian women accounted for 387 deliveries. The coverage rate of serologic screening was 85.6%. Confirmed seropositive women were 28, accounting for a prevalence of CD of 8.7% (95% IC 5.9-11.5). Among 29 children born to positive mothers, one infected child was detected (transmission rate of 4.3%, 95% IC 0-12.6) and treated accordingly. Other 13 children previously born from the same mothers were retrieved and tested for CD: no additional congenital cases were diagnosed.

Discussion: Our screening programme presented a high coverage, although widely variable in the different birthing facilities. National guidelines recommending CD testing in pregnant women would help to increase case detection countrywide.
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http://dx.doi.org/10.1016/j.tmaid.2018.04.011DOI Listing
November 2018

Risk Factors and Outcomes of Endocarditis Due to Non-HACEK Gram-Negative Bacilli: Data from the Prospective Multicenter Italian Endocarditis Study Cohort.

Antimicrob Agents Chemother 2018 04 27;62(4). Epub 2018 Mar 27.

ASST Papa Giovanni XXIII, Infectious Diseases, Bergamo, Italy.

The objective of this study was to investigate predisposing factors and outcomes of infective endocarditis (IE) caused by non-HACEK Gram-negative bacilli (GNB) in a contemporary multicenter cohort. Patients with IE due to GNB, prospectively observed in 26 Italian centers from 2004 to 2011, were analyzed. Using a case-control design, each case was compared to three age- and sex-matched controls with IE due to other etiologies. Logistic regression was performed to identify risk factors for IE due to GNB. Factors associated with early and late mortality were assessed by Cox regression analysis. The study group comprised 58 patients with IE due to GNB. We found that was the most common pathogen, followed by and The genitourinary tract as a source of infection (odds ratio [OR], 13.59; 95% confidence interval [CI], 4.63 to 39.93; < 0.001), immunosuppression (OR, 5.16; 95% CI, 1.60 to 16.24; = 0.006), and the presence of a cardiac implantable electronic device (CIED) (OR, 3.57; 95% CI, 1.55 to 8.20; = 0.003) were factors independently associated with IE due to GNB. In-hospital mortality was 13.8%, and mortality rose to 30.6% at 1 year. A multidrug-resistant (MDR) etiology was associated with in-hospital mortality (hazard ratio [HR], 21.849; 95% CI, 2.672 to 178.683; = 0.004) and 1-year mortality (HR, 4.408; 95% CI, 1.581 to 12.287; = 0.005). We conclude that the presence of a genitourinary focus, immunosuppressive therapy, and an indwelling CIED are factors associated with IE due to GNB. MDR etiology is the major determinant of in-hospital and long-term mortality.
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http://dx.doi.org/10.1128/AAC.02208-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913980PMC
April 2018

Autoimmune hepatitis and HIV infection: two case reports and review of the literature.

AIDS 2017 Sep;31(15):2172-2175

aDepartment of Clinical and Experimental Medicine, Clinic of Infectious Diseases, University of Foggia, Foggia bDivision of Infectious Diseases, ASST Papa Giovanni XXIII, Bergamo, Italy.

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http://dx.doi.org/10.1097/QAD.0000000000001608DOI Listing
September 2017

Candida endocarditis: systematic literature review from 1997 to 2014 and analysis of 29 cases from the Italian Study of Endocarditis.

Expert Rev Anti Infect Ther 2017 09 14;15(9):807-818. Epub 2017 Sep 14.

a Department of Public Health and Infectious Diseases , Policlinico Umberto I 'Sapienza' University of Rome , Rome , Italy.

Introduction: Candida Endocarditis (CE) is a deadly disease. It is of paramount importance to assess risk factors for acquisition of both Candida native (NVE) and prosthetic (PVE) valve endocarditis and relate clinical features and treatment strategies with the outcome of the disease. Areas covered: We searched the literature using the Pubmed database. Cases of CE from the Italian Study on Endocarditis (SEI) were also included. Overall, 140 cases of CE were analyzed. Patients with a history of abdominal surgery and antibiotic exposure had higher probability of developing NVE than PVE. In the PVE group, time to onset of CE was significantly lower for biological prosthesis compared to mechanical prosthesis. In the whole population, greater age and longer time to diagnosis were associated with increased likelihood of death. Patients with effective anti-biofilm treatment, patients who underwent cardiac surgery and patients who were administered chronic suppressive antifungal treatment showed increased survival. For PVE, moderate active anti-biofilm and highly active anti-biofilm treatment were associated with lower mortality. Expert commentary: Both NVE and PVE could be considered biofilm-related diseases, pathogenetically characterized by Candida intestinal translocation and initial transient candidemia. Cardiac surgery, EAB treatment and chronic suppressive therapy might be crucial in increasing patient survival.
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http://dx.doi.org/10.1080/14787210.2017.1372749DOI Listing
September 2017

Reduced adherence to antiretroviral therapy is associated with residual low-level viremia.

Pragmat Obs Res 2017 26;8:91-97. Epub 2017 May 26.

USC of Infectious Diseases.

The source and significance of residual low-level viremia (LLV) during combinational antiretroviral therapy (cART) remain a matter of controversy. It is unclear whether residual viremia depends on ongoing release of HIV from the latent reservoir or if viral replication contributes to LLV. We examined the relationship between adherence and LLV. Adherence was estimated by pharmacy refill and dichotomized as ≥95% or <95%. Plasma HIV-RNA was determined, with an ultrasensitive test having a limit of detection of 3 copies/mL at least 2 times over the follow-up period. Patients were grouped according to HIV-RNA over time as K<3: constantly <3 copies/mL; V<3: sometimes below or above the cutoff limit but always <50 copies/mL; K>3: constantly between 3 and 50 copies/mL; and V>50: a measure of >50 copies/mL minimum. Overall, 2789 patients were included. At each time point approximately 92% of the patients presented an HIV-RNA <50 copies/mL and two-thirds of those <3 copies/mL, 34.6% of patients had <3 copies/mL constantly, 32.7% sometimes below or above the cutoff limit but always <50 copies/mL, 9.5% constantly between 3 and 50 copies/mL, and 23.2% a measure of >50 copies/mL minimum. The mean adherence rate was 92.1% (95% confidence interval [CI] from 91.1% to 93.1%) in K<3 patients, similar in V<3 patients (91.9%), but lowered to 88.8% in K>3 patients and to 88.4% in V>50 patients (<0.0001). Approximately 55% of patients in groups K<3 and V<3 showed an adherence rate ≥95%; this proportion lowered to ~51% in K>3 and to 48% in V>50. Moreover, 34% of patients with a steady adherence <95% were categorized as K>3, whereas 21.7% of those with a drug holiday (21.7%) were observed in the V>50 group (=0.002). A steady viral suppression can occur despite moderate cART non-adherence, but reduced adherence is associated with low-level residual viremia, which could reflect new rounds of HIV replication. However, a detectable HIV-RNA could also be detected in patients with optimal cART adherence, indicating additional mechanisms favoring HIV persistence.
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http://dx.doi.org/10.2147/POR.S127974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457149PMC
May 2017

Efficacy, safety and pharmacokinetics of atazanavir (200mg twice daily) plus raltegravir (400mg twice daily) dual regimen in the clinical setting.

J Clin Virol 2017 02 1;87:30-36. Epub 2016 Dec 1.

Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, Torino, Italy. Electronic address:

Background: Unboosted atazanavir with raltegravir has been investigated at 300mg twice daily showing frequent hyperbilirubinemia and selection of resistance-associated mutations.

Objectives: Atazanavir 200mg twice daily could increase tolerability and plasma exposure.

Study Design: Patients on atazanavir/raltegravir (200/400 twice daily), with self-reported adherence >95% and no concomitant interacting drugs were retrospectively evaluated.

Results: 102 patients [72.5% male, age 46.4 years (42-54), BMI 24kg/m (22-26)] were included. CD4+ T lymphocytes were 417 cell/μL (302-704) and 76 patients (74.5%) had HIV-RNA <50 copies/ml. After 123 weeks 18.6% patients showed virological failure and 3.9% discontinued for intolerance. Available genotypes showed selection of major integrase (7/10 patients) and protease resistance-associated mutations (5/13 patients). In patients switching with dyslipidemia (n=67) total, LDL cholesterol and triglycerides significantly decreased. Patients switching with eCRCL<60ml/min (n=27) had no significant changes while patients with eCRCL >60ml/min showed significant decrease (-9.8ml/min, p=0.003) at 96-weeks. Atazanavir and raltegravir trough concentrations were 321ng/mL (147-720) and 412ng/mL (225-695). Self-reported non-adherence (n=4) was significantly associated with virological failure (p=0.02); patients with virological success had borderline longer previous virological control (33 vs. 18 months, p=0.07).

Discussion: Switch to atazanavir/raltegravir was safe and well tolerated allowing optimal drugs' plasma exposure. However, a concerning rate (18.6%) failed with newly selected mutations and stopped ATV/RAL because of DDI and intolerance issues or were lost to follow-up. This regimen might be considered in selected patients, without history of protease inhibitors failure or HBV infection, showing optimal adherence and prolonged suppression.
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http://dx.doi.org/10.1016/j.jcv.2016.11.015DOI Listing
February 2017

Anodic stripping voltammetry with gold electrodes as an alternative method for the routine determination of mercury in fish. Comparison with spectroscopic approaches.

Food Chem 2017 Apr 25;221:737-745. Epub 2016 Nov 25.

Department of Chemistry, University of Torino, 10125 Torino, Italy.

The applicability to the determination of mercury in tuna of square wave anodic stripping voltammetry (SW-ASV) conducted at both solid gold electrode (SGE) and a gold nanoparticle-modified glassy carbon electrode (AuNPs-GCE) was demonstrated. Mercury content in two certified materials and in ten samples of canned tuna was measured. The performances of the electrodes were compared with one another as well as with two spectroscopic techniques, namely cold vapour atomic absorption spectroscopy (CV-AAS) and a direct mercury analyser (DMA). The results found pointed out that both SW-ASV approaches were suitable and easy-to-use method to monitor mercury concentration in tunas, since they allowed accurate quantification at concentration values lower than the maximum admissible level in this matrix ([Hg]=1mg/kg). In particular, mercury detection at the AuNPs-GCE showed a LOQ in fish-matrix of 0.1μg/l, corresponding to 0.06mg/kg, with performance comparable to that of DMA.
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http://dx.doi.org/10.1016/j.foodchem.2016.11.111DOI Listing
April 2017

Current features of infective endocarditis in persons on hemodialysis: a prevalence study with case control design from the prospective multicenter SEI cohort.

Infection 2016 Aug 19;44(4):467-74. Epub 2016 Jan 19.

Infectious Diseases, Papa Giovanni XXIII Hospital, Bergamo, Italy.

Purpose: Persons on hemodialysis (HD) are at high risk of infective endocarditis (IE). In non-comparative retrospective studies, a higher rate of mortality was reported in IE on HD. We assessed risk factors, clinical characteristics, and outcomes of IE in HD.

Methods: This was a prevalence study with a case control methodology on a set of data from the prospectively followed cohort of the Studio Endocarditi Italiano (SEI), conducted between 2004 and 2011. Included were 42 consecutive cases of IE HD subjects and 126 controls not on HD, matched for age, sex, type of IE, and heart side involved. Clinical, echocardiographic, microbiological features, and disease complications and therapeutic modalities were assessed.

Results: HD patients were more often diabetics (42.9 vs 18.2 % in no-HD; p = 0.007) and immune-suppressed (16.7 vs 3.2 %; p = 0.02), and had a higher rate of predisposing cardiac conditions (45 vs 25 %; p = 0.031). A higher prevalence of health care-related acquisition and a shorter diagnostic delay was observed in IE on HD, that was more likely to be caused by staphylococci and less by streptococci (p < 0.002). Cardiac surgery was performed in 38 % of HD patients and 36.5 % of no-HD patients (p = 0.856). Complications were similar and in-hospital mortality did not differ significantly (26.2 % in HD vs 15.9 % in no-HD; p = 0.168).

Conclusions: IE in persons on HD is characterized by distinctive clinical features, including a higher prevalence of some important comorbidities. Inconsistent with prior studies, we could not confirm a higher rate of complications and mortality in HD patients with IE.
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http://dx.doi.org/10.1007/s15010-015-0870-yDOI Listing
August 2016

Pulmonary complications associated with pegylated interferon and ribavirin in HIV/hepatitis C virus coinfected patients.

AIDS 2014 Nov;28(17):2633-5

Infectious Diseases Unit, A.O. Papa Giovanni XXIII, Bergamo, Italy.

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http://dx.doi.org/10.1097/QAD.0000000000000464DOI Listing
November 2014

What is hiding behind bubbles of air? An unusual Streptococcus pyogenes meningitis.

Infez Med 2014 Dec;22(4):317-21

Department of Anaesthesia and Intensive Care, Papa Giovanni XXIII Hospital; Neurosurgery Unit, Department of Neurosurgery and Neurological Sciences, Papa Giovanni XXIII Hospital; Bergamo, Italy; Faculty of Health, Medicine, and Life Science, Maastricht University, Maastricht, The Netherlands; Department of Neuroradiology, Papa Giovanni XXIII Hospital; Section of Infectious Diseases, Department of Clinical Medicine, Papa Giovanni XXIII Hospital, Bergamo, Italy.

Streptococcus pyogenes is a rare but aggressive cause of meningitis, which often evolves in a poor outcome with fatal consequences. Although lumbar puncture and CT scan of the brain are the gold standard of diagnosis of cerebral infections, they can have some limitations. We report and describe the clinical history and neuroimaging of a 36-year-old woman admitted to the emergency department of our hospital three days after the onset of earache and otorrhoea. When the patient developed an emergent refractory status epilepticus, the CT scan of the brain showed an unusual pneumocephalus. However, the MRI study of the brain revealed a pachymeningitis with partial thrombosis of the right transverse sinus and subdural empyema due to a S. pyogenes otitis media. Prompt diagnosis and the specific findings of the MRI allowed rapid correct treatment and thus led to a good outcome for the patient.
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December 2014

Long-term effect of a four-drugs induction regimen for patients with high baseline viral load.

J Int AIDS Soc 2014 2;17(4 Suppl 3):19776. Epub 2014 Nov 2.

Laboratory of Virology and Microbiology, AO Papa Giovanni XXIII Bergamo, Bergamo, Italy.

Introduction: The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load.

Methods: Naive patients with HIV-RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab-initio with TDF+FTC+EFV (E) or TDF+FTC+RAL (R) were used.

Results: 19 patients with a mean age of 38 years and mean baseline CD4 count of 334 (SD 216) cells/mcL and HIV-RNA of 5.47 log (SD 0.32) copies/mL were enrolled. No baseline significant difference was observed among groups. Early HIV-RNA reduction was significantly higher in ER compared to the other groups from week 1 to week 4 (P from 0.026 to 0.003) (figure 1), thereafter HIV-RNA values were comparable among the groups. At week 96, all patients had an HIV-RNA < 50 copies/mL, however only patients in the ER group had in all cases an HIV-RNA level < 3 copies/mL with a statistically significant difference compared to E (60%; P=0.038) and R (50%; P=0.020). At 96 weeks, CD4 cell median counts were 765 cells/mcL for ER, 600 cells/mcL for E and 771 for R (P=0.16), however patients in the ER group presented a lower proportion of activated CD4+CD38+HLADR+ cells (1.9% versus 3.9 and 3.8%) and CD8+CD38+HLADR+ cells (10.3% versus 16.8 and 16.5%) and a significantly better CD4/CD8 ratio (0.98 versus 0.53 and 0.61; P=0.03).

Conclusions: A four-drug regimen in naive patients with high pre-therapy viral load improves early virologic response. A quick drop of HIV-RNA seems to correlate with a sustained virologic response. Although limited in time (four months), the four-drug regimens correlates with an improved immunological response as measured by the CD4/CD8 ratio or the percentage of activated CD4+ and CD8+ cells. The reasons why this happens deserve further studies. This study highlights the importance of a personalised therapy especially in high risk patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225274PMC
http://dx.doi.org/10.7448/IAS.17.4.19776DOI Listing
January 2016

Early clinical response and presence of viral resistant minority variants: a proof of concept study.

J Int AIDS Soc 2014 2;17(4 Suppl 3):19759. Epub 2014 Nov 2.

USC Infectious Diseases, AO Papa Giovanni XXIII, Bergamo, Italy.

Introduction: Traditional genotyping assays detect viral variants present in at least 15-25% of the entire virus population. We tested the Next generation GS Junior System (NGS) setted with a detection limit of 0.05% and evaluated the clinical relevance of low prevalent mutations.

Methods: NGS was performed on the plasma of 26 infected individuals who started a TDF/FTC/RPV (15 subjects) or TDF/FTC/EFV (11 subjects) cART after a routine HIV-1 drug-resistance negative test by Viroseq HIV-1 Genotyping System. Amplicon Sequencing of HIV-1 RT and PR Plate (Roche) was performed following the manufacturer's instructions. HIV-1 variants were analyzed by a specific HIV-1 tool by AVA software v. 2.7. The updated IAS resistance mutations list (March 2013) was considered for the analysis of resistance positions. Patients were followed testing viral load and immunologic parameters.

Results: Twenty four males and two females with a mean age of 43 years were included. Twenty-one were nave for cART. At baseline, median HIV-RNA was 4.57 log copies/mL (range 2.15-6.57) and CD4 count 315 cells/mcL (range 16-648). In 18 patients, NGS did not detect any additional variant relevant for the selected cART compared to population genotyping. In the remaining eight patients resistance conferring mutations to part of the ongoing regimen were detected. Single mutations E138K (two cases) and M184V in three distinct patients and V90I+G190E; M184V+A98S; Y215F+V118I+T215I; L210S+T215I+F227L; and A62V+D67G+K70N+188H in the remaining five subjects. In all cases, the mutation prevalence was inferior to 5%. The mean daily reduction of VL was -3759 copies/mL in patients without NGS detected mutations and -1045 copies/mL in those with mutations. The median KM estimates for reaching an HIV-RNA blood level <50 copies/mL were 127 days and 161 days, respectively. One patient without baseline resistance selected for M184I+E138K+T215I (NGS) after four months of TDF/FTC/RPV therapy.

Conclusions: NGS detected low-frequency HIV-1 variants harbouring RT drug resistance mutations that could have affected the therapy outcome. However, viral decay in an early cART phase was not affected by the presence of resistant minority variants. The low prevalence of the detected mutation, the limited effect on the combination regimen and the potency of cART components could be possible explanations of our findings. Longer follow-up and larger casuistries are needed to determine the clinical relevance of NGS in routine clinical practice and eventually define a clinically relevant mutations' prevalence.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225251PMC
http://dx.doi.org/10.7448/IAS.17.4.19759DOI Listing
January 2016

The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development.

Front Neurosci 2014 15;8:324. Epub 2014 Oct 15.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari School of Medicine Bari, Italy.

This study was conducted on human developing brain by laser confocal and transmission electron microscopy (TEM) to make a detailed analysis of important features of blood-brain barrier (BBB) microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vascularization. The BBB status of cortex microvessels was examined at a defined stage of cortex development, at the end of neuroblast waves of migration, and before cortex lamination, with BBB-endothelial cell markers, namely tight junction (TJ) proteins (occludin and claudin-5) and influx and efflux transporters (Glut-1 and P-glycoprotein), the latter supporting evidence for functional effectiveness of the fetal BBB. According to the well-known roles of astroglia cells on microvessel growth and differentiation, the early composition of astroglia/endothelial cell relationships was analyzed by detecting the appropriate astroglia, endothelial, and pericyte markers. GFAP, chemokine CXCL12, and connexin 43 (Cx43) were utilized as markers of radial glia cells, CD105 (endoglin) as a marker of angiogenically activated endothelial cells (ECs), and proteoglycan NG2 as a marker of immature pericytes. Immunolabeling for CXCL12 showed the highest level of the ligand in radial glial (RG) fibers in contact with the growing cortex microvessels. These specialized contacts, recognizable on both perforating radial vessels and growing collaterals, appeared as CXCL12-reactive en passant, symmetrical and asymmetrical, vessel-specific RG fiber swellings. At the highest confocal resolution, these RG varicosities showed a CXCL12-reactive dot-like content whose microvesicular nature was confirmed by ultrastructural observations. A further analysis of RG varicosities reveals colocalization of CXCL12 with Cx43, which is possibly implicated in vessel-specific chemokine signaling.
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http://dx.doi.org/10.3389/fnins.2014.00324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197642PMC
October 2014

Brain abscess.

N Engl J Med 2014 10;371(18):1756-7

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http://dx.doi.org/10.1056/NEJMc1410501DOI Listing
October 2014

Ischemia/Reperfusion-induced neovascularization in the cerebral cortex of the ovine fetus.

J Neuropathol Exp Neurol 2014 Jun;73(6):495-506

From the Human Anatomy and Histology Unit, Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, Medical School of Bari University, Bari, Italy (DV, FG, MR); and Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island (NA, GBS, JZ, BSS); and Department of Pathology and Neurosurgery, Rhode Island Hospital (EGS), Providence, Rhode Island.

Information on the effects of injury on neovascularization in the immature brain is limited. We investigated the effects of ischemia on cerebral cortex neovascularization after the exposure of fetuses to 30 minutes of cerebral ischemia followed by 48 hours of reperfusion (I/R-48), 30 minutes of cerebral ischemia followed by 72 hours of reperfusion (I/R-72), or sham control treatment (Non-I/R). Immunohistochemical and morphometric analyses of cerebral cortex sections included immunostaining for glial fibrillary acidic protein and collagen type IV (a molecular component of the vascular basal lamina) to determine the glial vascular network in fetal brains and Ki67 as a proliferation marker. Cerebral cortices from I/R-48 and I/R-72 fetuses exhibited general responses to ischemia, including reactive astrocyte morphology, which was not observed in Non-I/R fetuses. Cell bodies of reactive proliferating astrocytes, along with large end-feet, surrounded the walls of cerebral cortex microvessels in addition to the thick collagen type IV-enriched basal lamina. Morphometric analysis of the Non-I/R group with the I/R-48 and I/R-72 groups revealed increased collagen type IV density in I/R-72 cerebral cortex microvessels (p < 0.01), which also frequently displayed a sprouting appearance characterized by growing tip cells and activated pericytes. Increases in cerebral cortex basic fibroblast growth factor were associated with neovascularization. We conclude that increased neovascularization in fetal cerebral cortices occurs within 72 hours of ischemia.
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http://dx.doi.org/10.1097/NEN.0000000000000071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122327PMC
June 2014

Predicting the occurrence of embolic events: an analysis of 1456 episodes of infective endocarditis from the Italian Study on Endocarditis (SEI).

BMC Infect Dis 2014 Apr 29;14:230. Epub 2014 Apr 29.

USC Malattie Infettive, Ospedale Papa Giovanni XXIII, piazza OMS 1, Bergamo, BG 24127, Italia.

Background: Embolic events are a major cause of morbidity and mortality in patients with infective endocarditis. We analyzed the database of the prospective cohort study SEI in order to identify factors associated with the occurrence of embolic events and to develop a scoring system for the assessment of the risk of embolism.

Methods: We retrospectively analyzed 1456 episodes of infective endocarditis from the multicenter study SEI. Predictors of embolism were identified. Risk factors identified at multivariate analysis as predictive of embolism in left-sided endocarditis, were used for the development of a risk score: 1 point was assigned to each risk factor (total risk score range: minimum 0 points; maximum 2 points). Three categories were defined by the score: low (0 points), intermediate (1 point), or high risk (2 points); the probability of embolic events per risk category was calculated for each day on treatment (day 0 through day 30).

Results: There were 499 episodes of infective endocarditis (34%) that were complicated by ≥ 1 embolic event. Most embolic events occurred early in the clinical course (first week of therapy: 15.5 episodes per 1000 patient days; second week: 3.7 episodes per 1000 patient days). In the total cohort, the factors associated with the occurrence of embolism at multivariate analysis were prosthetic valve localization (odds ratio, 1.84), right-sided endocarditis (odds ratio, 3.93), Staphylococcus aureus etiology (odds ratio, 2.23) and vegetation size ≥ 13 mm (odds ratio, 1.86). In left-sided endocarditis, Staphylococcus aureus etiology (odds ratio, 2.1) and vegetation size ≥ 13 mm (odds ratio, 2.1) were independently associated with embolic events; the 30-day cumulative incidence of embolism varied with risk score category (low risk, 12%; intermediate risk, 25%; high risk, 38%; p < 0.001).

Conclusions: Staphylococcus aureus etiology and vegetation size are associated with an increased risk of embolism. In left-sided endocarditis, a simple scoring system, which combines etiology and vegetation size with time on antimicrobials, might contribute to a better assessment of the risk of embolism, and to a more individualized analysis of indications and contraindications for early surgery.
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http://dx.doi.org/10.1186/1471-2334-14-230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101861PMC
April 2014

Drug reaction with eosinophilia and systemic symptoms associated with raltegravir use: case report and review of the literature.

AIDS 2014 Apr;28(7):1077-9

Infectious Diseases, Ospedale Papa Giovanni XXIII, Bergamo, Italy.

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http://dx.doi.org/10.1097/QAD.0000000000000204DOI Listing
April 2014

Abacavir-induced liver toxicity in an HIV-infected patient.

AIDS 2014 Feb;28(4):613

Department of Infectious Disease, Papa Giovanni XXIII° Hospital, Bergamo, Italy.

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http://dx.doi.org/10.1097/QAD.0000000000000139DOI Listing
February 2014

Diversified expression of NG2/CSPG4 isoforms in glioblastoma and human foetal brain identifies pericyte subsets.

PLoS One 2013 26;8(12):e84883. Epub 2013 Dec 26.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari School of Medicine, Bari, Italy.

NG2/CSPG4 is a complex surface-associated proteoglycan (PG) recognized to be a widely expressed membrane component of glioblastoma (WHO grade IV) cells and angiogenic pericytes. To determine the precise expression pattern of NG2/CSPG4 on glioblastoma cells and pericytes, we generated a panel of >60 mouse monoclonal antibodies (mAbs) directed against the ectodomain of human NG2/CSPG4, partially characterized the mAbs, and performed a high-resolution distributional mapping of the PG in human foetal, adult and glioblastoma-affected brains. The reactivity pattern initially observed on reference tumour cell lines indicated that the mAbs recognized 48 immunologically distinct NG2/CSPG4 isoforms, and a total of 14 mAbs was found to identify NG2/CSPG4 isoforms in foetal and neoplastic cerebral sections. These were consistently absent in the adult brain, but exhibited a complementary expression pattern in angiogenic vessels of both tumour and foetal tissues. Considering the extreme pleomorphism of tumour areas, and with the aim of subsequently analysing the distributional pattern of the NG2/CSPG4 isoforms on similar histological vessel typologies, a preliminary study was carried out with endothelial cell and pericyte markers, and with selected vascular basement membrane (VBM) components. On both tumour areas characterized by 'glomeruloid' and 'garland vessels', which showed a remarkably similar cellular and molecular organization, and on developing brain vessels, spatially separated, phenotypically diversified pericyte subsets with a polarized expression of key surface components, including NG2/CSPG4, were disclosed. Interestingly, the majority of the immunolocalized NG2/CSPG4 isoforms present in glioblastoma tissue were present in foetal brain, except for one isoform that seemed to be exclusive of tumour cells, being absent in foetal brain. The results highlight an unprecedented, complex pattern of NG2/CSPG4 isoform expression in foetal and neoplastic CNS, discriminating between phenotype-specific and neoplastic versus non-neoplastic variants of the PG, thus opening up vistas for more selective immunotherapeutic targeting of brain tumours.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084883PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873429PMC
February 2015

Rilpivirine: drug profile of a second-generation non-nucleoside reverse transcriptase HIV-inhibitor.

Expert Rev Anti Infect Ther 2014 Jan 28;12(1):13-29. Epub 2013 Nov 28.

Infectious Diseases Unit, Ospedale Papa Giovanni XXIII, Piazza OMS 1 (BG), 24127, Italy.

Rilpivirine (RPV) is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) of the diarylpyrimidine family. RPV can be given once daily, is well absorbed and should be administered with food. It is eliminated mainly by hepatic metabolism. Two phase III noninferiority trials (ECHO and THRIVE), compared RPV 25mg with efavirenz (EFV) 600 mg, both given once daily, and combined with 2NRTI backbone. At week 48, response rate for pooled data were 84 versus 82% (difference: 2%; 95% CI: -2.0 to 6.0%). EFV arms performed better than RPV arms when at higher baseline HIV RNA, so RPV was approved for treatment-naïve patients with HIV RNA below 100,000 copies/ml. Approximately 90% of viruses phenotypically resistant to RPV showed cross-resistance to ETR. Conversely, phenotypic analysis showed that in EFV arm, none were resistant to the second-generation NNRTIs. CD4 count increases were similar between groups, but RPV showed a lower rate of discontinuation due to adverse events and lower rates of central nervous system effects, rash and lipid abnormalities. Potency, tolerability and co-formulation in a single tablet (Eviplera(®), Complera(®)) make this drug a new and attractive option for the treatment of HIV.
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http://dx.doi.org/10.1586/14787210.2014.863708DOI Listing
January 2014

The CXCL12/CXCR4/CXCR7 ligand-receptor system regulates neuro-glio-vascular interactions and vessel growth during human brain development.

J Inherit Metab Dis 2013 May 23;36(3):455-66. Epub 2013 Jan 23.

Department of Basic Medical Sciences, Neurosciences, Sensory Organs-Human Anatomy and Histology Unit, University of Bari School of Medicine, Bari, Italy.

This study investigates glio-vascular interactions in human fetal brain at midgestation, specifically examining the expression and immunolocalization of the CXCL12/CXCR4/CXCR7 ligand-receptor axis and its possible role in the vascular patterning of the developing brain. At midgestation, the telencephalic vesicles are characterized by well developed radial glia cells (RGCs), the first differentiated astrocytes and a basic vascular network mainly built of radial vessels. RGCs have been recognized to contribute to cerebral cortex neuro-vascular architecture and have also been demonstrated to act as a significant source of neural cells (Rakic, Brain Res 33:471-476, 1971; Malatesta et al, Development 127:5253-5263, 2000). According to our hypothesis CXCL12, a potent migration and differentiation chemokine released by RGCs, may act as a linking factor coordinating neuroblast migration with vessel growth and patterning through the activation of different ligand/receptor axes. The obtained results support this hypothesis showing that together with CXCR4/CXCR7-reactive neuroblasts, which migrate in close association with CXCL12 RGCs, layer-specific subsets of CXCL12 RGCs and astrocytes specifically contact the microvessel wall. Moreover, the CXCL12/CXCR4/CXCR7 system appears to be directly involved in microvessel growth, its members being differentially expressed in angiogenically activated microvessels and vascular sprouts.
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http://dx.doi.org/10.1007/s10545-012-9574-yDOI Listing
May 2013

Human renal stem/progenitor cells repair tubular epithelial cell injury through TLR2-driven inhibin-A and microvesicle-shuttled decorin.

Kidney Int 2013 Mar 16;83(3):392-403. Epub 2013 Jan 16.

Department of Emergency and Organ Transplantation, University of Bari, Valenzano (BA), Italy.

Acute kidney injury (AKI) is emerging as a worldwide public health problem. Recent studies have focused on the possibility of using human adult renal stem/progenitor cells (ARPCs) to improve the repair of AKI. Here we studied the influence of ARPCs on the healing of cisplatin-injured renal proximal tubular epithelial cells. Tubular, but not glomerular, ARPCs provided a protective effect promoting proliferation of surviving tubular cells and inhibiting cisplatin-induced apoptosis. The recovery effect was specific to tubular ARPCs, occurred only after damage sensing, and was completely cancelled by TLR2 blockade on tubular ARPCs. Moreover, tubular, but not glomerular, ARPCs were resistant to the apoptotic effect of cisplatin. Tubular ARPCs operate mainly through the engagement of TLR2, the secretion of inhibin-A protein, and microvesicle-shuttled decorin, inhibin-A, and cyclin D1 mRNAs. These factors worked synergistically and were essential to the repair process. The involvement of tubular ARPC-secreted inhibin-A and decorin mRNA in the pathophysiology of AKI was also confirmed in transplant patients affected by delayed graft function. Hence, identification of this TLR2-driven recovery mechanism may shed light on new therapeutic strategies to promote the recovery capacity of the kidney in acute tubular damage. Use of these components, derived from ARPCs, avoids injecting stem cells.
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http://dx.doi.org/10.1038/ki.2012.413DOI Listing
March 2013