Publications by authors named "Tiziana Lazzarotto"

109 Publications

Recent Advances in the Evaluation of Serological Assays for the Diagnosis of SARS-CoV-2 Infection and COVID-19.

Front Public Health 2020 18;8:620222. Epub 2021 Feb 18.

Microbiology Unit, Department of Specialized, Experimental, and Diagnostic Medicine, Istituto di Ricovero e Cura a Carattere Scientifico St. Orsola Polyclinic, University of Bologna, Bologna, Italy.

Few data on the diagnostic performance of serological tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are currently available. We evaluated sensitivity and specificity of five different widely used commercial serological assays for the detection of SARS-CoV-2-specific IgG, IgM, and IgA antibodies using reverse transcriptase-PCR assay in nasopharyngeal swab as reference standard test. A total of 337 plasma samples collected in the period April-June 2020 from SARS-CoV-2 RT-PCR positive ( = 207) and negative ( = 130) subjects were investigated by one point-of-care lateral flow immunochromatographic assay (LFIA IgG and IgM, Technogenetics) and four fully automated assays: two chemiluminescence immunoassays (CLIA-iFlash IgG and IgM, Shenzhen YHLO Biotech and CLIA-LIAISON XL IgG, DiaSorin), one electrochemiluminescence immunoassay (ECLIA-Elecsys total predominant IgG, Roche), and one enzyme-linked immunosorbent assay (ELISA IgA, Euroimmune). The overall sensitivity of all IgG serological assays was >80% and the specificity was >97%. The sensitivity of IgG assays was lower within 2 weeks from the onset of symptoms ranging from 70.8 to 80%. The LFIA and CLIA-iFlash IgM showed an overall low sensitivity of 47.6 and 54.6%, while the specificity was 98.5 and 96.2%, respectively. The ELISA IgA yielded a sensitivity of 84.3% and specificity of 81.7%. However, the ELISA IgA result was indeterminate in 11.7% of cases. IgG serological assays seem to be a reliable tool for the retrospective diagnosis of SARS-CoV-2 infection. IgM assays seem to have a low sensitivity and IgA assay is limited by a substantial rate of indeterminate results.
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http://dx.doi.org/10.3389/fpubh.2020.620222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929977PMC
February 2021

Maternal perception of the risk of vertically transmitted infections: the impact of expert counselling.

Am J Obstet Gynecol MFM 2021 Feb 27:100341. Epub 2021 Feb 27.

Obstetric Unit, Department of Medical and Surgical Sciences, University of Bologna and IRCCS Azienda Ospedaliero-Universitaria S.Orsola-Malpighi, Italy. Electronic address:

Background: Insufficient and imprecise information during pregnancy can lead to an overestimation of maternal and fetal risk associated to various exposures during gestation.

Objective: The aim of this study was to assess if expert obstetric counseling in cases of maternal infections at risk of vertical transmission could impact maternal perception of risk and the tendency to terminate pregnancy.

Study Design: This is a monocentric prospective observational study of 185 consecutive pregnant women with confirmed diagnosis of infectious diseases at risk of vertical transmission during the first or second trimester of pregnancy. Patients were divided into two different groups, according to the type infectious disease: infections at high risk of fetal damages and infections at low risk. Every woman included in the study underwent medical counselling with a physician with experience of vertically transmitted infections. Moreover, each woman involved in the study was offered a detailed second trimester ultrasound scan. Maternal concern for their pregnancy and the disposition to interrupt the pregnancy were investigated by two questionnaires submitted to patients before and after medical expert counseling; a third questionnaire was completed only by those women who decided to undergo second trimester ultrasound scan at our Hospital.

Results: Of the 185 consecutive patients meeting the inclusion criteria, 171 (92.4%) filled out the VAS for concern about the baby's health both before and after medical consultation. Following medical consultation, there was a significant decrease in mean VAS for concern; from 67.1±26.0 to 41.3±28.8 (change score -25.8; 95% CI -29.9, -21.7). Higher baseline levels of concern had more room for reduction, and infections at high fetal risk of damage were associated with lower decrease in concern. However, risk perception decreased in both low-risk and high-risk pregnancies. Eighty-two patients (53.2%) underwent ultrasonography and filled out the VAS following examination. Mean score after examination was 28.3±24.4 and significantly lower than mean score registered after consultation (change score -16.6; 95% CI -22.9, -10.3). A total of 162 (87.6%) women declared their tendency to interrupt pregnancy both before and after the consultation. There was a significant decrease in mean tendency from 42.1±32.6 to 22.7±27.1 (change score -19.4; 95% CI -23.6, -15.2). Regression analysis revealed that both low- and high-risk patients significantly reduced their tendency. Seventy-three (45.1%) patients underwent ultrasonography and filled out the VAS following examination. Mean score after examination was 9.9±20.6 and significantly lower than mean score registered after consultation (change score -13.4; 95% CI -19.1, -7.7).

Conclusion: Our results confirm the importance of a comprehensive and sufficient expert medical counselling that, on one hand, can reduce maternal risk perception, improving quality of life for mothers, and on the other hand, can lead to feasible results, reducing a woman's disposition to termination of pregnancy.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100341DOI Listing
February 2021

Chilblains in a child with confirmed SARS-CoV-2 infection: a red flag for late onset skin manifestation in previously infected individuals.

J Eur Acad Dermatol Venereol 2021 Mar 2. Epub 2021 Mar 2.

Dermatology Division, IRCCS Policlinico di Sant'Orsola.

During the COVID-19 pandemic an outbreak of chilblain lesions has been described worldwide. The relationship with SARS-CoV-2 infection is still debated. Emerging literature regarding this possible correlation focuses on two hypotheses: an endothelial infection or the result of an IFN type I-mediated immune response.
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http://dx.doi.org/10.1111/jdv.17194DOI Listing
March 2021

SARS-CoV-2/COVID-19 Testing: The Tower of Babel.

Acta Biomed 2020 11 9;91(4):e2020144. Epub 2020 Nov 9.

Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum - Università di Bologna.

Background And Aim: Testing represents one of the main pillars of public health response to SARS-CoV-2/COVID-19 pandemic. This paper shows how accuracy and utility of testing programs depend not just on the type of tests, but on the context as well.

Methods: We describe the testing methods that have been developed and the possible testing strategies; then, we focus on two possible methods of population-wide testing, i.e., pooled testing and testing with rapid antigen tests. We show the accuracy of split-pooling method and how, in different pre-test probability scenarios, the positive and negative predictive values vary using rapid antigen tests.

Results: Split-pooling, followed by retesting of negative results, shows a higher sensitivity than individual testing and requires fewer tests. In case of low pre-test probability, a negative result with antigen test could allow to rule out the infection, while, in case of a positive result, a confirmatory molecular test would be necessary.

Conclusions: Test performance alone is not enough to properly choose which test to use; goals and context of the testing program are essential. We advocate the use of pooled strategies when planning population-wide screening, and the weekly use of rapid tests for close periodic monitoring in low-prevalence populations.
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http://dx.doi.org/10.23750/abm.v91i4.10911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927496PMC
November 2020

Positive HCMV DNAemia in stem cell recipients undergoing letermovir prophylaxis is expression of abortive infection.

Am J Transplant 2020 Dec 15. Epub 2020 Dec 15.

Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Letermovir (LMV) inhibits HCMV replication by binding to components of the HCMV-terminase complex showing a potential role in prevention of HCMV-related complications in allogenic hematopoietic stem cell transplant recipients (allo-HSCTRs). However, little is known about breakthrough HCMV infection and the relevance of HCMV DNAemia during prophylaxis. We reported the results of a multicenter prospective study involving five Italian centers in the management of HCMV DNAemia in 75 adult HCMV-seropositive allo-HSCTRs undergoing LMV prophylaxis. The aim of the present study was to characterize the presence of real HCMV reactivation during LMV prophylaxis. Then, the presence of circulating infectious HCMV particles was determined by virus isolation and degradation of free-floating viral DNA. This report provides the first evidence that during LMV prophylaxis the clinical relevance of HCMV DNAemia should be critically considered.
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http://dx.doi.org/10.1111/ajt.16450DOI Listing
December 2020

Spectrum of cardiovascular diseases in children during high peak COVID-19 period infection in Northern Italy: is there a link?

J Pediatric Infect Dis Soc 2020 Dec 6. Epub 2020 Dec 6.

Department of Pediatrics, University of Bologna, S.Orsola Hospital, Bologna, Italy.

Background: Children with COVID-19 have a milder clinical course than adults. We describe the spectrum of cardiovascular manifestations during a COVID-19 outbreak in Emilia-Romagna, Italy.

Methods: Cross-sectional multicenter study including all diagnosis of KD, myocarditis and multisystem inflammatory syndrome in children (MIS-C) from February to April,2020. KD patients were compared to those diagnosed before the epidemic.

Results: KD: 8 patients (6/8 boys, all negative for SARS-CoV-2); complete presentation in 5/8; 7/8 IVIG-responders; 3/8 showed transient coronary lesions (CALs).

Myocarditis: one 5-year-old girl negative for SARS-CoV-2, positive for Parvovirus B19. She responded to IVIG.

Mis-c: 4 SARS-CoV-2 positive boys (3 patients with positive swab and serology, 1 patient with negative swab and positive serology). Three presented myocardial dysfunction and pericardial effusion, one developed multicoronary aneurysms and hyperinflammation; all responded to treatment. The fourth boy had mitral and aortic regurgitation that rapidly regressed after steroids.

Conclusions: KD, myocarditis and MIS-C were distinguishable cardiovascular manifestations. KD did not show a more aggressive form compared to previous years: coronary involvement was frequent, but always transient. MIS-C and myocarditis rapidly responded to treatment without cardiac sequelae despite high markers of myocardial injury at onset suggesting a myocardial depression due to systemic inflammation rather than focal necrosis. Evidence of actual or previous SARS-CoV-2 infection was documented only in patients with MIS-C.
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http://dx.doi.org/10.1093/jpids/piaa162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798942PMC
December 2020

Rescue Therapies for Helicobacter pylori Infection in Foreign Patients Treated in Italy.

J Clin Gastroenterol 2020 Oct 29. Epub 2020 Oct 29.

Departments of Surgical and Medical Sciences.

Background And Aims: Helicobacter pylori prevalence remains high worldwide, especially in developing areas where infection acquisition occurs in early childhood. H. pylori eradication fails in a definite number of patients, despite one or more therapeutic attempts. Curing these patients is progressively more difficult, due to development of antibiotic resistance. While the cure rate of first-line therapies in foreigners was found to be different from that of Italians, no data are available on rescue therapies.

Materials And Methods: Consecutive foreigner patients with H. pylori infection following at least one therapy failure were enrolled. All patients underwent upper endoscopy with gastric biopsies used for both histologic examination and culture/susceptibility test. Rescue therapies administered accordingly to susceptibility testing were rifabutin-based therapy, levofloxacin-based therapy, sequential. Pylera was prescribed regardless the resistance pattern.

Results: A total of 103 (M/F: 27/76, mean age: 41.9 y, range: 18 to 85) were enrolled. The overall resistance rates toward clarithromycin, metronidazole, and levofloxacin were 76.7%, 66%, and 42.7%, respectively, with triple resistance present in 33.9% of bacterial isolates. Eradication rates were 71.4% on 40 patients for rifabutin-based therapy, 82.8% on 42 cases for levofloxacin-based therapy, 75% on 11 patients treated with sequential therapy, and 100% on 10 cases who received Pylera regimen.

Conclusions: To our knowledge, this is the first study assessing H. pylori eradication rates in foreigner patients, who failed at least one therapeutic attempt, managed in Italy. Even by using a culture-based approach, the infection was not cured in a definite number of patients.
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http://dx.doi.org/10.1097/MCG.0000000000001457DOI Listing
October 2020

Generalized granuloma annulare-like eruption secondary to acute Epstein-Barr virus infection.

Int J Dermatol 2021 Mar 27;60(3):e110-e112. Epub 2020 Oct 27.

Division of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

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http://dx.doi.org/10.1111/ijd.15274DOI Listing
March 2021

Fecal-oral transmission of SARS-CoV-2: review of laboratory-confirmed virus in gastrointestinal system.

Int J Colorectal Dis 2021 Mar 14;36(3):437-444. Epub 2020 Oct 14.

Surgery of the Alimentary Tract, Department of Medical and Surgical Sciences, Sant'Orsola- Malpighi Hospital, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138, Bologna, Italy.

Purpose: The objective was to collect the data available regarding the presence of laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in gastrointestinal system and to evaluate whether the digestive system could contribute to viral transmission.

Methods: Bibliographic databases were searched to identify all studies documenting, in adult patients with a confirmed diagnosis of coronavirus disease 2019 (COVID-19): (1) the presence of SARS-CoV-2 ribonucleic acid in the feces; (2) the presence of SARS-CoV-2 ribonucleic acid in the intestinal cells; (3) live SARS-CoV-2 in the feces.

Results: Twenty seven met the inclusion criteria. In 26 studies, the presence or absence of SARS-CoV-2 ribonucleic acid in the feces of COVID-19 patients had been reported. Out of the 671 patients, 312 (46.5%) had a positive stool sample for viral nucleic acid. Of these patients, 63.9% remained positive for viral nucleic acid in the feces after pharyngeal swabs became negative; Three studies also evaluated the viral ribonucleic acid in the gastrointestinal tissues and the presence of SARS-CoV-2 nucleic acid was found in samples of 3 patients out of 8 examined (37.5%). The presence of the live virus in stool samples was confirmed in two studies but no in in a recent study from Germany. These results suggested that SARS-CoV-2 could infect gastrointestinal epithelial cells and it may be transmitted through the digestive tract.

Conclusion: In order to control the pandemic, every effort should be made to understand all the possible routes of transmission of the infections, even the less important ones.
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http://dx.doi.org/10.1007/s00384-020-03785-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556558PMC
March 2021

Brain ischemic injury in COVID-19-infected patients: a series of 10 post-mortem cases.

Brain Pathol 2021 01 2;31(1):205-210. Epub 2020 Nov 2.

Department of Experimental, Diagnostic and Specialty Medicine, Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, 40138, Italy.

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http://dx.doi.org/10.1111/bpa.12901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536900PMC
January 2021

Valacyclovir for cytomegalovirus infection in pregnancy: additional evidences, additional questions.

Clin Microbiol Infect 2020 Sep 17. Epub 2020 Sep 17.

Infectious and Tropical Diseases Unit, Careggi University and Hospital, Florence, Italy; Referral Centre for Infectious Diseases in Pregnancy of Tuscany, Florence, Italy.

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http://dx.doi.org/10.1016/j.cmi.2020.09.015DOI Listing
September 2020

Pathological post-mortem findings in lungs infected with SARS-CoV-2.

J Pathol 2021 01 4;253(1):31-40. Epub 2020 Nov 4.

Department of Pathology, Bellaria-Maggiore Hospital, University of Bologna School of Medicine, Bologna, Italy.

Italy was the first European nation to be massively infected by SARS-CoV-2. Up to the end of May 2020, more than 33,000 deaths had been recorded in Italy, with a large prevalence among males, those over 75 years of age, and in association with co-morbidities. We describe the lung pathological and immunohistochemical post-mortem findings at the autopsy of nine patients who died of SARS-CoV-2-associated disease. We found in the lung tissues of all patients histological changes consistent with diffuse alveolar damage in various evolution phases ranging from acute exudative to acute proliferative to fibrotic phase. Alveolar damage was associated with prominent involvement of the vascular component in both the interstitial capillaries and the mid-size vessels, with capillary fibrin micro-thrombi, as well as organized thrombi even in medium-sized arteries, in most cases not related to sources of embolism. Eosinophilic infiltrate was also seen, probably reactive to pharmacological treatment. Viral RNA of SARS-CoV-2 was detected from the lung tissues of all the nine patients. Immunohistochemistry for the receptor of the SARS-CoV-2, ACE2, and its priming activator TMPRSS2 revealed that both proteins co-localize in airway cells. In particular, the ACE2 protein was expressed in both endothelial cells and alveolar type I and II pneumocytes in the areas of histological diffuse alveolar damage (DAD). Pneumocytes, but not endothelial cells, also expressed TMPRSS2. There are no distinctive histological features of SARS-CoV-2 infection with respect to SARS-CoV-1 and other DAD with different aetiology. The identification of the cause of death in the course of SARS-CoV-2 infection is more likely multi-factorial. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5549DOI Listing
January 2021

Kinetics of cytomegalovirus and Epstein-Barr virus DNA in whole blood and plasma of kidney transplant recipients: Implications on management strategies.

PLoS One 2020 25;15(8):e0238062. Epub 2020 Aug 25.

Molecular Virology Unit, Microbiology and Virology Department, Foundation IRCCS Polyclinic San Matteo, Pavia, Italy.

This retrospective multicenter cohort study investigated the kinetics (ascending and descending phases) of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-DNA in whole blood (WB) and plasma samples collected from adult kidney transplant (KT) recipients. CMV-DNA kinetics according to antiviral therapy were investigated. Three hundred twenty-eight paired samples from 42 episodes of CMV infection and 157 paired samples from 26 episodes of EBV infection were analyzed by a single commercial molecular method approved by regulatory agencies for both matrices. CMV-DNAemia followed different kinetics in WB and plasma. In the descending phase of infection, a slower decay of viral load and a higher percentage of CMV-DNA positive samples were observed in plasma versus WB. In the 72.4% of patients receiving antiviral therapy, monitoring with plasma CMV-DNAemia versus WB CMV-DNAemia could delay treatment interruption by 7-14 days. Discontinuation of therapy based on WB monitoring did not result in relapsed infection in any patients. Highly different EBV-DNA kinetics in WB and plasma were observed due to lower positivity in plasma; EBV positive samples with a quantitative result in both blood compartments were observed in only 11.5% of cases. Our results emphasize the potential role of WB as specimen type for post-KT surveillance of both infections for disease prevention and management.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238062PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447038PMC
October 2020

Parechovirus infection causing sepsis-like illness in newborns: a NICU approach.

New Microbiol 2020 Jul 13;43(3):144-147. Epub 2020 Jun 13.

Neonatal Intensive Care Unit, St. Orsola-Malpighi Hospital, University of Bologna, Italy.

Human parechovirus (HpeV) is an important emerging infection in young infants, able to cause sepsis-like disease and meningoencephalitis, especially in newborns. Among the 19 identified genotypes, HPeV1, 3 and 6 are the most common types involved in human infections; HPeV3 is the type mainly responsible for neonatal infections and for infections involving the central nervous system. Signs and symptoms overlap with those of a bacterial infection and patients are usually treated with broad spectrum antibiotics. In the majority of cases lumbar puncture shows absence of pleocytosis, even in the presence of signs of meningitis. In these cases, cerebrospinal fluid cultures are negative for bacteria but, in the absence of diagnosis of viral infection, a full and unnecessary antibiotic cycle is often continued. Moreover, high sensitivity neuroimaging, i.e., magnetic resonance, and follow-up are often missed, thus resulting in substandard care. Availability of a real time PCR assay for HPeV RNA allows rapid and sensitive diagnosis as long as the disease is suspected. In this case study, we present cases of HPeV infections in newborns requiring neonatal intensive care admission, discuss their optimal management, and highlight the most relevant findings in the literature.
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July 2020

Rifabutin-Based Triple Therapy Or Bismuth-Based Quadruple Regimen As Rescue Therapies For Helicobacter pylori Infection.

Eur J Intern Med 2020 11 6;81:50-53. Epub 2020 Jul 6.

Department of Surgical and Medical Sciences, University of Bologna, Bologna, Italy. Electronic address:

Background/aims: H. pylori treatment remains a challenge for clinicians, and a definite quote of patients require two or more treatments. We evaluated the efficacy of rifabutin-based therapy and Pylera® regimen as rescue therapies.

Methods: Between January 2016 and December 2019, dyspeptic patients with at least one therapeutic failure observed in clinical practice received either a 12-day rifabutin-based triple therapy (esomeprazole 40 mg and amoxicillin 1 g, both twice daily, and rifabutin 150 mg once daily) or 10-day quadruple therapy with Pylera® (three in one capsule containing 140 mg bismuth subcitrate potassium, 125 mg metronidazole and 125 mg tetracycline). The eradication rates according to previous number of eradication failure therapies were calculated. The role antibiotic resistance pattern in H. pylori isolates was also investigated.

Results: Data of 423 patients were available. A total of 270 patients were treated with rifabutin-based therapy, and the overall eradication rate was 61.9%. Pylera® therapy was administered to 153 patients and the cure rate was 88.3%. According to the number of previous therapeutic failures, the eradication rate for the rifabutin-based therapy was 68.3% as second-line and further decreased to 63.1% in fourth-line therapy. Following Pylera® regimen, the cure rate was 94.8% in second-line, and remained 89.6% in fourth-line therapy. Efficacy of rifabutin-based and Pylera® therapies significantly decreased when clarithromycin and levofloxacin resistance, respectively, were present.

Conclusions: Our data documented a decreasing trend for rifabutin-based therapy efficacy according to previous therapy failures, whilst this did not occur for Pylera®.
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http://dx.doi.org/10.1016/j.ejim.2020.06.029DOI Listing
November 2020

Immune Monitoring Using QuantiFERON®-CMV Assay in Congenital Cytomegalovirus Infection: Correlation With Clinical Presentation and CMV DNA load.

Clin Infect Dis 2020 Jun 5. Epub 2020 Jun 5.

Operative Unit of Clinical Microbiology, Department of Specialized, Experimental and Diagnostic Medicine, St.Orsola Polyclinic, University of Bologna, Bologna, Italy.

Background: CMV-specific CD8+ T-cell responses can be detected early in fetal life, but their role in the manifestations of congenital CMV (cCMV) infection remains largely unknown.

Methods: CMV-specific CD8+ T-cell responses were assessed in neonates with cCMV using QuantiFERON®-CMV assay, within day 14th of life (T0) and during the second month of life (T1). Detection and quantification of CMV DNA in whole blood and urine samples were performed at both time points. QuantiFERON®-CMV results were evaluated in relation to timing of maternal infection, clinical manifestations of cCMV and CMV DNA levels.

Results: Thirty neonates were enrolled (10/30 [33%] symptomatic; 20/30 [67%] asymptomatic). At T0 16/30 (53%) subjects had a reactive QuantiFERON®-CMV result and 16/16 (100%) were asymptomatic, while 14/30 (47%) had a non-reactive or indeterminate QuantiFERON®-CMV result and 4/14 (29%) were asymptomatic. At T1, 17/29 (59%) subjects had a reactive QuantiFERON®-CMV result and 17/17 (100%) were asymptomatic, while 12/29 (41%) had a non-reactive or indeterminate result and 3/12 (25%) were asymptomatic. At both T0 and T1 reactive QuantiFERON®-CMV results correlated with lack of symptoms (P=0.0001). At T1 median CMV DNAemia was lower in subjects with reactive QuantiFERON®-CMV results as compared with subjects with non-reactive or indeterminate results (1.82 log IU/mL [1.82-2.89] versus 2.55 log IU/mL [1.82-4.42], P=0.009). No correlation was found between QuantiFERON®-CMV results and gestational age at maternal infection nor with urine CMV DNA levels.

Conclusions: A detectable CMV-specific CD8+ T-cell response, evaluated using the QuantiFERON®-CMV assay, correlates with the lack of CMV-related symptoms and the control of CMV DNAemia.
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http://dx.doi.org/10.1093/cid/ciaa704DOI Listing
June 2020

Pathophysiology of Hyperechogenic Bowel in Congenitally Human Cytomegalovirus Infected Fetuses.

Microorganisms 2020 May 22;8(5). Epub 2020 May 22.

Department of Specialized, Experimental, and Diagnostic Medicine, Operative Unit of Clinical Microbiology, St. Orsola Polyclinic, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.

Hyperechogenic bowel (HB) is a nonspecific ultrasound finding that can be associated with human cytomegalovirus (CMV) congenital infection. In this study, we investigated HB pathophysiology in CMV-infected fetuses. We examined small and large intestine as well as pancreas in 8 fetuses at 22 weeks of gestation with congenital CMV infection. Ultrasound findings showed 4 fetuses with HB and 4 without. As negative group, 4 fetuses without CMV infection and without HB were studied. Immunohistochemistry for CMV, lymphocytic infiltrate, B-cell leukemia/lymphoma-2 (bcl-2), CD-117, cystic fibrosis transmembrane regulator (CFTR) were performed. HB fetuses showed multiple and sequential CMV-positive ganglion cells of Auerbach's myenteric plexus. In the ganglia, bcl-2 was weakly expressed representing a reduced neuronal functionality. CD-117 revealed a regular distribution of Cajal cells, the pacemakers of intestinal contractility. Pancreas showed normal CFTR staining, indicating a preserved exocrine secretion, thus unlikely a contributory factor in HB. In CMV-infected fetuses without HB, CMV-positive cells were scatteredly found in ganglion cells and bcl-2 was strongly expressed. Intestinal CD-117 and pancreatic CFTR expression were similar to fetuses with HB. In conclusion, fetal CMV infection of the bowel may lead to peristalsis impairment (paralytic ileus) due to intestinal plexus involvement, which at ultrasound appeared as HB.
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http://dx.doi.org/10.3390/microorganisms8050779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285288PMC
May 2020

Antimicrobial Efficacy of Five Probiotic Strains Against Helicobacter pylori.

Antibiotics (Basel) 2020 May 11;9(5). Epub 2020 May 11.

Department of Surgical and Medical Sciences, University of Bologna, 40138 Bologna, Italy.

Treatment of Helicobacter pylori (H. pylori) infection is a challenge for clinicians. The large increase in drug-resistant strains makes the formulation of new therapeutic strategies fundamental. The frequent onset of side effects during antibiotic treatment (mainly due to intestinal dysbiosis) should not be underestimated as it may cause the interruption of treatment, failure of H. pylori eradication and clonal selection of resistant bacteria. Probiotic integration during antibiotic treatment can exert a dual function: a direct antagonistic effect on H. pylori and a balancing effect on dysbiosis. Therefore, it fulfills the definition of a new therapeutic strategy to successfully treat H. pylori infection. Data reported in literature give promising but discrepant results.

Aim: To assess in vitro bacteriostatic and bactericidal activity of probiotic strains against H. pylori.

Materials And Methods: L. casei, L. paracasei, L. acidophilus, B. lactis and S. thermophilus strains were used. Agar well diffusion and time-kill curves were carried out to detect bacteriostatic and bactericidal activity, respectively.

Results: All probiotic strains showed both bacteriostatic and bactericidal activity vs. H. pylori.

Conclusions: Such findings prompted us to plan a protocol of treatment in which probiotics are given to infected patients in association with antibiotic therapy.
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http://dx.doi.org/10.3390/antibiotics9050244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277513PMC
May 2020

Antibiotic Resistance and Therapy for Infection in Immigrant Patients Treated in Italy.

J Clin Med 2020 May 1;9(5). Epub 2020 May 1.

Department of Medicine and Surgery Sciences, University of Bologna, 40138 Bologna, Italy.

: () infection is the leading cause of both peptic ulcers and gastric tumors, including low-grade MALT-lymphoma and adenocarcinoma. Although it is decreasing in developed countries, prevalence remains high in developing areas, mainly due to low socio-economic levels, and the potential consumption of contaminated water. Moreover, a different pattern of primary antibiotic resistance is expected in their isolates, potentially affecting the efficacy of standard eradication therapies. Indeed, a previous study showed the eradication rate following triple therapy was distinctly lower in dyspeptic infected immigrants living in Italy as compared to Italian patients. : to evaluate the resistance pattern in isolates from immigrant patients in Italy, and the success rate of first-line therapy in these patients. : This retrospective study evaluated data of consecutive immigrant patients, diagnosed with infection in a single center (Bologna, Italy) between January 2009 and January 2019. Patients underwent first-line therapy with either sequential or Pylera (Allergan USA, Inc. Madison, NJ, USA) therapy. : A total of 609 immigrants were diagnosed with infection during the study period, but 264 previously received an eradication therapy. Therefore, the study was focused on 294 out of 345 naïve patients with a successful bacterial culture with antibiogram. Latin America immigrants had the highest overall resistance rate. Levofloxacin resistance rate was significantly higher in Latin Americans and Asians as compared with Europeans. Based on resistance patterns, sequential therapy showed a clear decreasing trend in eradication rates. Conclusions: while antibiotic resistance rates are generally increasing worldwide, Pylera seems to achieve a good performance as first-line treatment in all naïve foreigner patients, except for Africans.
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http://dx.doi.org/10.3390/jcm9051299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288298PMC
May 2020

Multidrug-resistant cytomegalovirus infection in a patient with granulomatosis with polyangiitis during immunosuppressive treatment.

Antivir Ther 2020 ;25(2):111-114

Department of Specialized, Experimental and Diagnostic Medicine, Microbiology Unit, Laboratory of Virology, St. Orsola Polyclinic, University of Bologna, Bologna, Italy.

Cytomegalovirus (CMV) infection is a major complication in immunocompromised patients, including those with autoimmune diseases. Here, we describe the first case of granulomatosis with polyangiitis treated with steroids and cyclophosphamide, complicated by a multidrug-resistant (MDR) CMV infection in presence of weak antiviral cellular immunity. Since reports regarding CMV infection in rheumatological patients are rarely described and no guidelines on its management exist, the described case contributes to identify potential strategies to predict the risk of CMV disease and developing of MDR-CMV in these patients, through virological and immunological surveillance.
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http://dx.doi.org/10.3851/IMP3352DOI Listing
January 2020

Clinical Diagnostic Testing for Human Cytomegalovirus Infections.

J Infect Dis 2020 03;221(Suppl 1):S74-S85

Viral Vaccine Preventable Diseases Branch, Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States.
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http://dx.doi.org/10.1093/infdis/jiz601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057790PMC
March 2020

Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts.

Front Pediatr 2020 31;8:13. Epub 2020 Jan 31.

Hôpital Necker-Enfants Malades and Université Paris Descartes, Paris, France.

Maternal primary and non-primary cytomegalovirus (CMV) infection during pregnancy can result in transmission to the developing fetus. Congenital CMV (cCMV) can result in significant morbidity, mortality or long-term sequelae, including sensorineural hearing loss, the most common sequela. As a leading cause of congenital infections worldwide, cCMV infection meets many of the criteria for screening. However, currently there are no universal programs that offer maternal or neonatal screening to identify infected mothers and infants, no vaccines to prevent infection, and no efficacious and safe therapies available for the treatment of maternal or fetal CMV infection. Data has shown that there are several maternal and neonatal screening strategies, and diagnostic methodologies, that allow the identification of those at risk of developing sequelae and adequately detect cCMV. Nevertheless, many questions remain unanswered in this field. Well-designed clinical trials to address several facets of CMV treatment (in pregnant women, CMV-infected fetuses and both symptomatic and asymptomatic neonates and children) are required. Prevention (vaccines), biology and transmission factors associated with non-primary CMV, and the cost-effectiveness of universal screening, all demand further exploration to fully realize the ultimate goal of preventing cCMV. In the meantime, prevention of primary infection during pregnancy should be championed to all by means of hygiene education.
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http://dx.doi.org/10.3389/fped.2020.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006044PMC
January 2020

Microbial Contamination of Medical Staff Clothing During Patient Care Activities: Performance of Decontamination of Domestic Versus Industrial Laundering Procedures.

Curr Microbiol 2020 Jul 15;77(7):1159-1166. Epub 2020 Feb 15.

Department of Specialized, Experimental, and Diagnostic Medicine, Operative Unit of Clinical Microbiology, St. Orsola Polyclinic, University of Bologna, Via Giuseppe Massarenti 9, 40138, Bologna, Italy.

The efficacy of domestic laundering of healthcare staff clothing is still debated. This study aimed to compare the performance of decontamination of different domestic laundering with that of industrial laundering. Fourteen naturally contaminated white coats of healthcare workers (5 fabric squares from each coat) and fabric squares of artificially contaminated cotton cloth (30 fabric squares per each bacterial strain used) were included. Four domestic laundering procedures were performed; two different washing temperatures (40 °C and 90 °C) and drying (tumble dry and air dry) were used. All fabric squares were ironed. Presence of bacterial bioburden on the fabric squares after domestic and industrial laundering was investigated. None of the naturally contaminated fabric squares resulted completely decontaminated after any of the domestic washes. At 24, 48, and 72 h of incubation, bacterial growth was observed in all the laundered fabric squares. Besides environmental microorganisms, potentially pathogenic bacteria (i.e., Acinetobacter lwoffii, Micrococcus luteus, coagulase-negative staphylococci) were isolated. On the artificially contaminated fabric squares, the bioburden was reduced after the domestic laundries; nevertheless, both Gram-negative and -positive pathogenic bacteria were not completely removed. In addition, a contamination of the fabric squares by environmental Gram-negative bacteria was observed. In both the naturally and artificially contaminated fabric squares, no bacterial growth at all the time-points analyzed was observed after industrial laundering, which provided to be more effective in bacterial decontamination than domestic washes. For those areas requiring the highest level of decontamination, the use of specialized industrial laundry services should be preferred.
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http://dx.doi.org/10.1007/s00284-020-01919-2DOI Listing
July 2020

Performance of the Alethia CMV Assay for Detection of Cytomegalovirus by Use of Neonatal Saliva Swabs.

J Clin Microbiol 2020 03 25;58(4). Epub 2020 Mar 25.

Meridian Bioscience Inc., Cincinnati, Ohio, USA.

Congenital cytomegalovirus (cCMV) infection is a major cause of childhood hearing loss and neurodevelopmental delay. Identification of newborns with cCMV infection allows provision of beneficial interventions. However, most infants with cCMV infection have subclinical infection and go undiagnosed. Thus, expanded neonatal CMV testing is increasingly recommended. Saliva is an attractive sample type for CMV testing of newborns, because it is easier to collect than urine and more sensitive for CMV detection than dried blood spots. We evaluated the Alethia CMV assay, a rapid, easy-to-use loop-mediated isothermal amplification method for qualitative detection of CMV DNA in neonatal saliva samples. Saliva swabs were collected prospectively from newborns <21 days old and tested by the Alethia assay according to the manufacturer's instructions. Archived saliva swabs from newborns with cCMV infection were also tested retrospectively. A composite reference method (CRM; two validated PCR assays followed by bidirectional sequencing of amplicons) was performed on all samples as the reference standard comparator. Of 1,480 prospectively collected saliva swabs, 1,472 (99.5%) were negative by both the Alethia assay and CRM, 5 (0.34%) were positive by both the Alethia assay and CRM, and 3 (0.20%) were positive only by the Alethia assay. All 34 (100%) archived swabs from newborns with cCMV infection were positive by both the CRM and the Alethia assay. Overall, the Alethia assay showed 100% and 99.8% positive and negative agreement with the CRM, respectively. The Alethia CMV assay is an accurate method for identifying neonates with cCMV infection and, given its simplicity, appears suitable for CMV testing using neonatal saliva outside a reference laboratory, including remote and resource-limited settings.
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http://dx.doi.org/10.1128/JCM.01951-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098765PMC
March 2020

HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy.

Vaccines (Basel) 2020 Jan 14;8(1). Epub 2020 Jan 14.

Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy.

Human papillomavirus (HPV) persistent infections are associated with cervical cancer and other HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently available HPV vaccines is important. A total of 149 female subjects vaccinated with Cervarix or Gardasil participated to the study and they were stratified according to age (10-12-year-old and 16-20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memory B cells were analyzed after an average of 4-6 years from the third immunization. The humoral responses against HPV-16 and HPV-18 (and HPV-6 and HPV-11 for Gardasil) were high in both age groups and vaccines up to six years from the third dose. However, Cervarix induced significantly higher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memory B cells against HPV-16 and HPV-18. Moreover, the percentage of subjects with vaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individuals with circulating antibodies, but undetectable memory B cells were found. Finally, a higher proportion of Cervarix-vaccinated subjects displayed cross-neutralizing responses against non-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differently affect long-lasting humoral immunity from both the quantitative and qualitative point of view.
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http://dx.doi.org/10.3390/vaccines8010026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175219PMC
January 2020

Antenatal screening for cytomegalovirus infection: to know the chance, the chance to know.

Lancet Child Adolesc Health 2019 10 19;3(10):675-677. Epub 2019 Aug 19.

Unit 73-28, Paris Descartes, University of Paris, Paris 75005, France; Maternity, Assistance Publique-Hopitaux de Paris, Hospital Necker, Paris, France.

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http://dx.doi.org/10.1016/S2352-4642(19)30271-8DOI Listing
October 2019

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies.

Clin Transplant 2019 10 6;33(10):e13666. Epub 2019 Aug 6.

Section of Infectious and Tropical Diseases, Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Cytomegalovirus (CMV) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and solid organ transplantation (SOT) recipients. In view of the uncertainties on the assessment and prevention of CMV infection in both transplant procedures, three Italian scientific societies for HSCT and SOT and for Clinical Microbiology appointed a panel of experts to compose a framework of recommendations. Recommendations were derived from a comprehensive analysis of the scientific literature and from a multidisciplinary consensus conference process. The lack of adequate clinical trials focused on certain diagnostic procedures, and antiviral intervention forced the panel to use the methods of consensus for shaping some recommendations. Recommendations concerning the two types of transplant were given for the following issues: assessment of pretransplant CMV serostatus, immunological monitoring after transplant, CMV prophylaxis with antivirals, CMV preemptive strategy, and CMV prophylaxis with immunoglobulin infusion and with adoptive immunotherapy. The questions raised by and the recommendations resulting from this consensus conference project may contribute to the improvement of certain crucial aspects of the management of CMV infections in allo-HSCT and in SOT populations.
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http://dx.doi.org/10.1111/ctr.13666DOI Listing
October 2019

Clinical utility of measuring Epstein-Barr virus-specific cell-mediated immunity after HSCT in addition to virological monitoring: results from a prospective study.

Med Microbiol Immunol 2019 Dec 9;208(6):825-834. Epub 2019 Jul 9.

Department of Specialized, Experimental, and Diagnostic Medicine, Operative Unit of Clinical Microbiology, St. Orsola-Malpighi Polyclinic, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.

Lack of virus-specific cell-mediated immunity (CMI) is associated with worse viral infection outcome in hematopoietic stem cell transplantation (HSCT). We aimed to evaluate the role of immunological monitoring of Epstein-Barr virus (EBV) infection in addition to virological one in 33 adult and 18 pediatric allogeneic HSCT recipients. Virological monitoring of infection was performed on whole blood samples by a quantitative real-time PCR assay. Immunological monitoring was performed by Enzyme-linked ImmunoSPOT assay, evaluating EBV-specific CMI, at fixed time-points and when EBV DNAemia was ≥ 10,000 copies/mL. Fifty-one percent of patients developed a post-transplant EBV infection and reduced-intensity conditioning regimen was the only factor associated to infection (P = 0.023). Lack of EBV-specific CMI during active EBV infection was associated with a greater severity of infection. Patients without EBV-specific CMI showed higher median peak level of EBV DNAemia than patients with EBV-specific CMI (P = 0.014), and consequently received more frequently, at EBV DNAemia peak, anti-CD20 therapy (0 versus 54.5%, P = 0.002). No patients with EBV-specific CMI versus 27.2% without EBV-specific CMI developed EBV-related complications (P = 0.063), including two lethal EBV-related post-transplant lymphoproliferative disorders. Combined immunological and virological measurements could improve EBV infection management in HSCT, anticipating the beginning of preemptive treatment from the EBV DNAemia peak to the finding of the lack of EBV-specific CMI.
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http://dx.doi.org/10.1007/s00430-019-00629-2DOI Listing
December 2019

Collaborative national multicenter for the identification of conversion factors from copies/mL to international units/mL for the normalization of HCMV DNA load.

Diagn Microbiol Infect Dis 2019 Oct 25;95(2):152-158. Epub 2019 May 25.

SC Microbiologia e Virologia, AOU Città della Salute e della Scienza, Università di Torino, Italy.

The present multicentric (n = 11 laboratories) study aimed to identify conversion factors from copies/mL to international units (IU)/mL for the normalization of HCMV DNA load using the first WHO International Standard for HCMV nucleic acid amplification techniques and to enhance interlaboratory agreement of HCMV DNA quantification methods. Study protocols for whole blood and plasma (extraction and amplification) were performed to calculate conversion factors from HCMV DNA copy number to IU. The greatest variability was observed in samples with lower HCMV concentrations (3.0 Log) in both biological matrices. Overall, 73.1% (206/282) of whole blood and 82.2% (324/394) of plasma samples analyzed fell within an acceptable variation range (±0.5 Log difference). An average of 0.64 (range 0.21-1.17) was the conversion factor calculated for the HCMV whole blood panel and 0.82 (range 0.39-2.2) for the HCMV plasma panel.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.05.012DOI Listing
October 2019

Low-Dose Anti-T Lymphoglobulin as Prophylaxis for Graft-versus-Host Disease in Unrelated Donor Transplantations for Acute Leukemias and Myelodysplastic Syndromes.

Biol Blood Marrow Transplant 2018 12 17;24(12):2450-2458. Epub 2018 Jul 17.

Department of Hematology "L. and A. Seràgnoli," University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.

Chronic graft-versus-host disease (cGVHD) is a major complication after stem cell transplantation (HSCT). Several randomized studies already demonstrated that anti-T lymphoglobulin (ATLG) is effective in preventing GVHD after myeloablative unrelated and HLA-identical sibling transplants. However, the issue of doses and the potential increase of relapses still remain unsolved. Here we report data on 190 patients with acute leukemia and myelodysplastic syndrome who underwent an unrelated HSCT with low-dose ATLG (15 to 30 mg/kg) given at an earlier timing (days -6 to -2). HSCT was performed from HLA 10/10 (n = 62, 33%), 9/10 (n = 91, 48%), 8/10 (n = 30, 16%), and <8/10 (n = 7, 4%) identical unrelated donor. Peripheral blood was the stem cell source in 42% (n = 80). Median follow-up was 51 months. Grades II to IV and III to IV acute GVHD were 26% and 9%, respectively, and 2-year overall and moderate to severe cGVHD were 23% and 14%, respectively. The 3-year incidences of relapse and nonrelapse mortality were 26% and 18%, respectively. The rates of 3-year overall survival (OS), disease-free survival (DFS), and GVHD-free and relapse-free survival (GRFS) were 60%, 56% and 44%, respectively. Factors such as younger donor, good performance status, and early disease were associated with better outcome in terms of OS, DFS, and GRFS. Our data indicate that doses of ATLG lower that those used in randomized clinical trials can be used for GVHD prevention, even in the adult setting, without clear increases in relapse and infections; these findings need to be further validated by a prospective randomized study.
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http://dx.doi.org/10.1016/j.bbmt.2018.07.011DOI Listing
December 2018