Publications by authors named "Elena Rossi"

164 Publications

Eltrombopag second-line therapy in adult patients with primary immune thrombocytopenia in an attempt to achieve sustained remission off-treatment: results of a phase II, multicentre, prospective study.

Br J Haematol 2021 Feb 22. Epub 2021 Feb 22.

Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.

Up to 30% immune thrombocytopenia (ITP) patients achieve a sustained remission off-treatment (SROT) after discontinuation of thrombopoietin receptor agonists (TPO-RAs). Factors predictive of response are lacking. Patients aged ≥18 years with newly diagnosed or persistent ITP were treated with eltrombopag for 24 weeks. Primary end-point was SROT: the proportion of responders that were able to taper and discontinue eltrombopag maintaining the response during a period of observation (PO) of six months. Secondary end-points included the association between some immunological parameters (TPO serum levels, cytokines and lymphocyte subsets) and response. Fifty-one patients were evaluable. Primary end-point was achieved in 13/51 (25%) treated patients and 13/34 (38%) patients who started the tapering. Baseline TPO levels were not associated with response at week 24 nor with SROT. Higher baseline levels of IL-10, IL-4, TNF-α and osteopontin were negative factors predictive of response (P = 0·001, 0·008, 0·02 and 0·03 respectively). This study confirms that SROT is feasible for a proportion of ITP patients treated with eltrombopag. Some biological parameters were predictive of response.
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http://dx.doi.org/10.1111/bjh.17334DOI Listing
February 2021

Bone marrow megakaryocytic activation predicts fibrotic evolution of Philadelphia-negative myeloproliferative neoplasms.

Haematologica 2020 11 19. Epub 2020 Nov 19.

Department of Life Sciences and Public Health, Universita Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome.

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have been traditionally considered as indistinctly slowly progressing conditions; recent evidence proves that a subset of cases have a rapid evolution, so that MPNs' prognosis needs to be personalized. We identified a new morphological parameter, defined as Megakaryocytic Activation (M-ACT) based on the coexistence of megakaryocytic emperipolesis, megakaryocytes (MK) clusters formation and evidence of arrangement of collagen fibers around the perimeter of MK. We retrospectively analyzed the bone marrow biopsy of two MPNs cohorts of patients with polycythemia (PV) (n=64) and non-PV patients [including essential thrombocythemia (ET), and early/prefibrotic primary myelofibrosis (PMF)] (n=222). M-ACT showed a significant correlation with splenomegaly, white blood cell (WBC) count, and LDH serum levels in both groups, with JAK2 V617F allele burden in PV patients, and with CALR mutations, and platelet count in non-PV patients. Progression-free survival, defined as PV-to-secondary MF progression and non-PV-to-overt PMF, was worse in both PV and early/prefibrotic PMF patients with M-ACT in comparison to those without M-ACT (P<.0001). Interestingly, M-ACT was not found in the subgroup of ET patients. In conclusion, M-ACT can be helpful in the differential diagnosis of MPNs and can represent a new morphologic parameter with a predictive value for progression of MPNs.
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http://dx.doi.org/10.3324/haematol.2020.264143DOI Listing
November 2020

Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial.

Lancet Haematol 2021 Mar 18;8(3):e175-e184. Epub 2021 Jan 18.

UOC Ematologia, ASST Papa Giovanni XXIII, Bergamo, Italy; Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Milan, Italy.

Background: There is no evidence that phlebotomy alone is sufficient to steadily maintain haematocrit on target level in low-risk patients with polycythaemia vera. This study aimed to compare the efficacy and safety of ropeginterferon alfa-2b on top of the standard phlebotomy regimen with phlebotomy alone.

Methods: In 2017, we launched the Low-PV study, a multicentre, open-label, two-arm, parallel-group, investigator-initiated, phase 2 randomised trial with a group-sequential adaptive design. The study involved 21 haematological centres across Italy. Participants were recruited in a consecutive order. Participants enrolled in the study were patients, aged 18-60 years, with a diagnosis of polycythaemia vera according to 2008-16 WHO criteria. Eligible patients were randomly allocated (1:1) to receive either phlebotomy and low-dose aspirin (standard group) or ropeginterferon alfa-2b on top of the standard treatment (experimental group). Randomisation sequence was generated using five blocks of variable sizes proportional to elements of Pascal's triangle. Allocation was stratified by age and time from diagnosis. No masking was done. Patients randomly allocated to the standard group were treated with phlebotomy (300 mL for each phlebotomy to maintain the haematocrit values of lower than 45%) and low-dose aspirin (100 mg daily), if not contraindicated. Patients randomly allocated to the experimental group received ropeginterferon alfa-2b subcutaneously every 2 weeks in a fixed dose of 100 μg on top of the phlebotomy-only regimen. The primary endpoint was treatment response, defined as maintenance of the median haematocrit values of 45% or lower without progressive disease during a 12-month period. Analyses were done by intention-to-treat principle. The study was powered assuming a higher percentage of responders in the experimental group (75%) than in the standard group (50%). Here we report results from the second planned interim analysis when 50 patients had been recruited to each group. The trial is ongoing, and registered with ClinicalTrials.gov, NCT03003325.

Findings: Between Feb 2, 2017, and March 13, 2020, 146 patients were screened, and 127 patients were randomly assigned to the standard group (n=63) or the experimental group (n=64). The median follow-up period was 12·1 months (IQR 12·0-12·6). For the second pre-planned interim analysis, a higher response rate in the experimental group was seen (42 [84%] of 50 patients) than in the standard group (30 [60%] of 50 patients; absolute difference 24%, 95% CI 7-41%, p=0·0075). The observed z value (2·6001) crossed the critical bound of efficacy (2·5262), and the stagewise adjusted p value early showed superiority of experimental treatment. Thus, the data safety monitoring board decided to stop patient accrual for overwhelming efficacy and to continue the follow-up, as per protocol, for 2 years. Under the safety profile, no statistically significant difference between groups in frequency of adverse events of grade 3 or higher was observed; the most frequently reported adverse events were neutropenia (four [8%] of 50 patients) in the experimental group and skin symptoms (two [4%] of 50 patients) in the standard group. No grade 4 or 5 adverse events occurred.

Interpretation: Supplementing phlebotomy with ropeginterferon alfa-2b seems to be safe and effective in steadily maintaining haematocrit values on target in low-risk patients with polycythaemia vera. Findings from the current study might have implications for changing the current management of low-risk patients with polycythaemia vera.

Funding: AOP Orphan Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro.
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http://dx.doi.org/10.1016/S2352-3026(20)30373-2DOI Listing
March 2021

Glassy and Polymer Dynamics of Elastomers by H Field-Cycling NMR Relaxometry: Effects of Cross-Linking.

Macromolecules 2020 Nov 5;53(22):10028-10039. Epub 2020 Nov 5.

Istituto di Chimica dei Composti OrganoMetallici, Consiglio Nazionale Delle Ricerche, Via G. Moruzzi 1, 56124 Pisa, Italy.

H spin lattice relaxation rate () dispersions were acquired by field-cycling (FC) NMR relaxometry between 0.01 and 35 MHz over a wide temperature range on polyisoprene (IR), polybutadiene (BR), and poly(styrene--butadiene) (SBR) rubbers, obtained by vulcanization under different conditions, and on the corresponding uncured elastomers. By exploiting the frequency-temperature superposition principle, χ″(ωτ) master curves were constructed by shifting the total FC NMR susceptibility, χ″(ω) = ω(ω), curves along the frequency axis by the correlation times for glassy dynamics, τ. Longer τ values and, correspondingly, higher glass transition temperatures were determined for the sulfur-cured elastomers with respect to the uncured ones, which increased by increasing the cross-link density, whereas no significant changes were found for fragility. The contribution of polymer dynamics, χ (ω), to χ″(ω) was singled out by subtracting the contribution of glassy dynamics, χ (ω), well represented using a Cole-Davidson spectral density. For all elastomers, χ (ω) was found to represent a small fraction, on the order of 0.05-0.14, of the total χ″(ω), which did not show a significant dependence on cross-link density. In the investigated temperature and frequency ranges, polymer dynamics was found to encompass regimes I (Rouse dynamics) and II (constrained Rouse dynamics) of the tube reptation model for the uncured elastomers and only regime I for the vulcanized ones. This is clear evidence that chemical cross-links impose constraints on chain dynamics on a larger space and time scale than free Rouse modes.
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http://dx.doi.org/10.1021/acs.macromol.0c01439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690040PMC
November 2020

Full donor chimerism after allogeneic hematopoietic stem cells transplant for myelofibrosis: The role of the conditioning regimen.

Am J Hematol 2021 02 30;96(2):234-240. Epub 2020 Nov 30.

UO Ematologia e Trapianto di Midollo Osseo, IRCCS Ospedale Policlinico San Martino Genova, Genova, Italy.

The aim of this retrospective study was to assess the rate of full donor chimerism (F-DC) in patients with myelofibrosis, prepared for an allogeneic stem cell transplant, with one or two alkylating agents. We analyzed 120 patients with myelofibrosis, for whom chimerism data were available on day +30. There were two groups: 42 patients were conditioned with one alkylating agent (ONE-ALK), either thiotepa or busulfan or melphalan, in combination with fludarabine, whereas 78 patients were prepared with two alkylating agents, thiotepa busulfan and fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years), were less frequently splenectomized pre-HSCT (31% vs 59%), had more frequently intermediate-2/high DIPSS scores (90% vs 74%), were grafted more frequently from alternative donors (83% vs 33%) and received more frequently ruxolitinib pre-HSCT (26% vs 7%). The proportion of patients with F-DC on day +30, in the TBF vs the ONE-ALK group, was respectively 87% vs 45% (P < .001). The 5-year cumulative incidence of relapse was 9% in the TBF group, vs 43% for the ONE-ALK group (P < .001). The 5-year actuarial disease-free survival was 63% for TBF and 38% for the ONE-ALK group (P = .004). In conclusion, early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis, undergoing an allogeneic HSCT. The combination of two alkylating agents in the conditioning regimen, provides a higher chance of achieving full donor chimerism on day+30, and thus a higher chance of long term disease free survival.
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http://dx.doi.org/10.1002/ajh.26042DOI Listing
February 2021

Analysis of XX -Negative Sex Reversal Dogs.

Animals (Basel) 2020 Sep 16;10(9). Epub 2020 Sep 16.

Department of Agricultural and Environmental Sciences, Milano University, via Celoria 2, 20133 Milan, Italy.

Impaired fertility associated with disorders of sex development (DSDs) due to genetic causes in dogs are more and more frequently reported. Affected dogs are usually of specific breeds thus representing a cause of economic losses for breeders. The aim of this research is to report the clinical, cytogenetic and molecular genetic findings of four XX -negative DSD dog cases. All the subjects showed a female aspect and the presence of an enlarged clitoris with a penis bone. Morphopathological analyses performed in three of the four cases showed the presence of testes in two cases and ovotestis in another. Conventional and R-banded cytogenetic techniques were applied showing that no chromosome abnormalities were involved in these DSDs. CGH arrays show the presence of 11 copy number variations (CNVs), one of which is a duplication of 458 Kb comprising the genomic region between base 17,503,928 and base 17,962,221 of chromosome 9 (CanFam3 genome assembly). This CNV, confirmed also by qPCR, includes the promoter region of gene and could explain the observed phenotype.
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http://dx.doi.org/10.3390/ani10091667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552623PMC
September 2020

Alazami syndrome: Phenotypic expansion and clinical resemblance to Smith-Lemli-Opitz syndrome.

Am J Med Genet A 2020 11 5;182(11):2722-2726. Epub 2020 Sep 5.

Medical Genetics Unit, IRCCS Mondino Foundation, Pavia, Italy.

Biallelic mutations in the LARP7 gene have been recently shown to cause Alazami syndrome, a rare condition characterized by short stature, intellectual disability, and peculiar facial dysmorphisms. To date, only 24 cases have been reported. Here, we describe two brothers initially suspected to have Smith-Lemli-Opitz syndrome, in whom clinical exome sequencing detected a novel homozygous truncating variant in LARP7. These cases expand the phenotypic spectrum of Alazami syndrome to include toes syndactyly and adaptive behavior, and confirm the power of "genotype first" approach in patients with syndromic presentations overlapping distinct rare conditions.
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http://dx.doi.org/10.1002/ajmg.a.61832DOI Listing
November 2020

An age and space structured SIR model describing the Covid-19 pandemic.

J Math Ind 2020 8;10(1):22. Epub 2020 Aug 8.

Dept. of Mathematics and its Applications, University of Milano-Bicocca, Via R. Cozzi 55, Milan, 20125 Italy.

We present an epidemic model capable of describing key features of the Covid-19 pandemic. While capturing several qualitative properties of the virus spreading, it allows to compute the basic reproduction number, the number of deaths due to the virus and various other statistics. Numerical integrations are used to illustrate the adherence of the evolutions described by the model to specific well known real features of the present pandemic. In particular, this model is consistent with the well known relevance of quarantine, shows the dramatic role of care houses and accounts for the increase in the death toll when spatial movements are not constrained.

Electronic Supplementary Material: The online version of this article (10.1186/s13362-020-00090-4) contains supplementary material.
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http://dx.doi.org/10.1186/s13362-020-00090-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414273PMC
August 2020

Recommendations for Dermatology Office Reopening in the Era of COVID-19.

J Drugs Dermatol 2020 Jul;19(7):e1-e9

The COVID-19 pandemic, originating in Wuhan, China, has become a major public health and economic challenge for countries around the world. As of May 08, 2020, there are over 3 million COVID-19 cases, and 250,000 COVID-19- associated deaths in 215 countries. As more data is collected, updated infection control measures are continuously released and published by government, public health authorities, and physician specialty associations. Across the globe, dermatological practices have had to limit their operations to varying degrees to facilitate disease control, but as the pandemic subsides, they will broaden their operations. In light of the uncertainty surrounding safe and effective practice of medical and aesthetic dermatology in the era of COVID-19, fourteen international experts in the field contributed to recommendations for effective infection control protocols and practice management modifications. While guidance from the World Health Organization and local public health officials comes first, these recommendations are crafted as a starting point for dermatologists worldwide to commence either reopening their doors to patients or expanding available service offerings. This can help ensure that patients receive needed care in the short term and improve long term practice viability. J Drugs Dermatol. 2020;19(7):e-1-e-9. doi:10.36849/JDD.2020.5293.
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http://dx.doi.org/10.36849/JDD.2020.5293DOI Listing
July 2020

Drug-Related Cutaneous Adverse Events in Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Literature Review.

Int J Mol Sci 2020 May 30;21(11). Epub 2020 May 30.

Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy.

Since myeloproliferative neoplasms (MPN) pose a significant risk for vascular and thrombotic complications, cytoreductive therapies, such as hydroxyurea (HU), interferon (IFN) inhibitors, and Janus kinase (JAK) inhibitors are recommended for patients at high risk. However, these agents also place patients at increased risk for drug-related cutaneous adverse events. Herein, we review the literature on skin toxicity related to the use of drugs for the treatment of MPN. Overall, the cytoreductive agents used for MPN are generally well tolerated and considered to be safe, except IFN, for which dropout rates as high as 25% have been reported. While IFN is known to give rise to flu syndrome, it rarely leads to hematological alterations. The most common hematological side effects of HU are mild and include granulocytopenia, anemia, and thrombocytopenia. The JAK inhibitor ruxolitinib has been associated with cytopenia and a higher incidence of viral infections, as well as increased risk for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Based on the present analysis, it can be concluded that cutaneous toxicity is not a negligible complication of commonly used treatments for MPN. While further research is needed, patients on these agents, and especially those with a history of cutaneous malignancies, should undergo thorough skin examination before and during therapy. In addition, detailed history is critical since many patients who develop non-melanoma skin cancer have multiple preexisting risk factors for cutaneous carcinogenesis.
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http://dx.doi.org/10.3390/ijms21113900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312244PMC
May 2020

Splenectomy in Myelofibrosis: Indications, Efficacy, and Complications.

Clin Lymphoma Myeloma Leuk 2020 09 30;20(9):588-595. Epub 2020 Apr 30.

Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Splenomegaly, which may range from a few centimeters below the left costal border to massive dimensions, is one of the most characteristic features in patients with advanced myelofibrosis (MF). Splenectomy may offer an effective therapeutic option for treating massive splenomegaly in patients with MF, and especially in cases of disease refractory to conventional drugs, but it is associated with a number of complications as well as substantial morbidity and mortality. Whether splenectomy should be performed before allogeneic hematopoietic stem-cell transplantation is also controversial, and there is a lack of prospective randomized clinical trials that assess the role of splenectomy before hematopoietic stem-cell transplantation in patients with MF. Although splenectomy is not routinely performed before transplantation, it may be appropriate in patients with massive splenomegaly and related symptoms, so long as the higher risk of graft failure in such cases is taken into account. This review aims to describe the efficacy, indications, and complications of splenectomy in patients with MF; and to evaluate the long-term impact of splenectomy on patient survival and risk of disease transformation.
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http://dx.doi.org/10.1016/j.clml.2020.04.015DOI Listing
September 2020

Venous Thromboembolism in Lymphoma: Risk Stratification and Antithrombotic Prophylaxis.

Cancers (Basel) 2020 05 20;12(5). Epub 2020 May 20.

Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Lymphoma is listed among the neoplasias with a high risk of venous thromboembolism (VTE). Risk factors for VTE appear to differ from risk factors in solid tumors. We review the literature of the last 20 years for reports identifying these risk factors in cohorts consisting exclusively of lymphoma patients. We selected 25 publications. The most frequent studies were analyses of retrospective single-center cohorts. We also included two reports of pooled analyses of clinical trials, two meta-analyses, two analyses of patient registries, and three analyses of population-based databases. The VTE risk is the highest upfront during the first two months after lymphoma diagnosis and decreases over time. This upfront risk may be related to tumor burden and the start of chemotherapy as contributing factors. Factors consistently reported as VTE risk factors are aggressive histology, a performance status ECOG ≥ 2 leading to increased immobility, more extensive disease, and localization to particular sites, such as central nervous system (CNS) and mediastinal mass. Association between laboratory values that are part of risk assessment models in solid tumors and VTE risk in lymphomas are very inconsistent. Recently, VTE risk scores for lymphoma were developed that need further validation, before they can be used for risk stratification and primary prophylaxis. Knowledge of VTE risk factors in lymphomas may help in the evaluation of the individual risk-benefit ratio of prophylaxis and help to design prospective studies on primary prophylaxis in lymphoma.
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http://dx.doi.org/10.3390/cancers12051291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281118PMC
May 2020

Methane oxidation of residual landfill gas in a full-scale biofilter: human health risk assessment of volatile and malodours compound emissions.

Environ Sci Pollut Res Int 2020 Apr 20. Epub 2020 Apr 20.

Department of Energy, Systems Territory and Construction Engineering, University of Pisa, Via C.F. Gabba 22, 56122, Pisa, Tuscany, Italy.

A human health risk assessment was performed to evaluate if a biofilter for the biological methane oxidation reduces the risk from exposure to landfill gas emissions and improves the air quality mitigating odour emissions from an aftercare landfill. Accordingly, three different scenarios of landfill gas management were defined, 9 volatile organic compounds (VOCs) (cyclohexane, n-hexane, 2-methylpentane, 3-methylpentane, benzene, xylenes, toluene, dichlorodifluoromethane, vinyl chloride) were identified and using the CALPUFF dispersion model; the pollutant concentration at eleven sensitive receptors was determined. Consequently, the risk (for cancer and non-cancer compounds) was assessed applying the methodology proposed by USEPA 2009. From one hand, to determine concentration and emission rates of VOCs and hydrogen sulphide, a sample of raw landfill gas and three air samples from the biofilter surface were collected with dynamic flux chamber method and analysed in accordance with US EPA, 1986 and USEPA TO-15, 1999. To the other hand, odour emissions were assessed based both on chemical and dynamic olfactometric measurements (EN 13725:2003). The field surveys results showed a reduction of the cancer risk on average by 79% and of the hazard quotient on average by 92%. In contrast, the results of olfactometry measurements showed a lower efficiency on odour reduction than the target value of 70%. Nonetheless, the odour concentration was always far below 300 uo m at the biofilter surface and odour concentration never exceed 1 uo m at the sensitive receptors.
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http://dx.doi.org/10.1007/s11356-020-08773-6DOI Listing
April 2020

A randomized double-blind trial of 3 aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia.

Blood 2020 07;136(2):171-182

Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase-1 (COX-1) inhibition. We performed a multicenter double-blind trial to investigate the efficacy of 3 aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2-dependent vascular thromboresistance. Patients on chronic once-daily low-dose aspirin (n = 245) were randomized (1:1:1) to receive 100 mg of aspirin 1, 2, or 3 times daily for 2 weeks. Serum thromboxane B2 (sTXB2), a validated biomarker of platelet COX-1 activity, and urinary prostacyclin metabolite (PGIM) excretion were measured at randomization and after 2 weeks, as primary surrogate end points of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the twice-daily and thrice-daily regimens showed substantially reduced interindividual variability and lower median (interquartile range) values for sTXB2 (ng/mL) compared with the once-daily arm: 4 (2.1-6.7; n = 79), 2.5 (1.4-5.65, n = 79), and 19.3 (9.7-40; n = 85), respectively. Urinary PGIM was comparable in the 3 arms. Urinary TXM was reduced by 35% in both experimental arms. Patients in the thrice-daily arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75 to 100 once daily for cardiovascular prophylaxis appears to be largely inadequate in reducing platelet activation in the vast majority of patients with ET. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement with further reductions (EudraCT 2016-002885-30).
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http://dx.doi.org/10.1182/blood.2019004596DOI Listing
July 2020

A modeling framework for biological pest control.

Math Biosci Eng 2019 11;17(2):1413-1427

Department of Mathematics and its Applications, University of Milano - Bicocca, via R. Cozzi, 55, 20126 Milano, Italy.

We present an analytic framework where biological pest control can be simulated. Control is enforced through the choice of a time and space dependent function representing the deployment of a species of predators that feed on pests. A sample of different strategies aimed at reducing the presence of pests is considered, evaluated and compared. The strategies explicitly taken into account range, for instance, from the uniform deployment of predators on all the available area over a short/long time interval, to the alternated insertion of predators in different specific regions, to the release of predators in suitably selected regions. The effect of each strategy is measured through a suitably defined cost, essentially representing the total amount of prey present over a given time interval over all the considered region, but the variation in time of the total amount of pests is also evaluated. The analytic framework is provided by an integro-differential hyperbolic-parabolic system of partial differential equations. While prey diffuse according to the usual Laplace operator, predators hunt for prey, moving at finite speed towards regions of higher prey density.
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http://dx.doi.org/10.3934/mbe.2020072DOI Listing
November 2019

Effectiveness of stress-relieving strategies in regulating patterns of cortisol secretion and promoting brain health.

Int Rev Neurobiol 2020 28;150:219-246. Epub 2020 Feb 28.

School of Life Sciences, University of Westminster, London, England.

Stress leads to ill-health and disease, and with today's fast-pace western society, engaging in strategies to relieve stress is crucial for good health across the life-course. Activities such as focusing on positive characteristics, art/music therapies, mindfulness, yoga and engaging with nature and/or physical activity have been shown to reduce stress and enhance well-being. It is thought that patterns of cortisol secretion, which are regulated by the brain, are a key mediator of stress-disease and well-being-health links. Measurement of cortisol in saliva is a non-invasive and ecologically valid tool for detecting early changes in brain health, as well as evaluating the effectiveness of strategies in relieving stress and improving brain health as well as monitoring stress-related brain changes. This chapter will review the evidence that engaging in stress-relieving strategies promotes regulation and/or restoration of patterns of cortisol secretion. If such strategies are found to be effective in healthy populations, they could potentially inform ways of promoting brain health and the prevention or delay of clinical disorders involving disorders in the brain (e.g., Parkinson's disease) and symptoms experienced with such disorders. To inform this field of research, recommendations are provided for the use of salivary cortisol as a marker of early monitoring of brain health and effectiveness of stress-alleviating interventions.
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http://dx.doi.org/10.1016/bs.irn.2020.01.003DOI Listing
November 2020

Arterial thrombosis in Philadelphia-negative myeloproliferative neoplasms predicts second cancer: a case-control study.

Blood 2020 01;135(5):381-386

FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy.

Patients with Philadelphia-negative myeloproliferative neoplasm (MPN) are prone to the development of second cancers, but the factors associated with these events have been poorly explored. In an international nested case-control study, we recruited 647 patients with carcinoma, nonmelanoma skin cancer, hematological second cancer, and melanoma diagnosed concurrently or after MPN diagnosis. Up to 3 control patients without a history of cancer and matched with each case for center, sex, age at MPN diagnosis, date of diagnosis, and MPN disease duration were included (n = 1234). Cases were comparable to controls for MPN type, driver mutations and cardiovascular risk factors. The frequency of thrombosis preceding MPN was similar for cases and controls (P = .462). Thrombotic events after MPN and before second cancer were higher in cases than in controls (11.6% vs 8.1%; P = .013), because of a higher proportion of arterial thromboses (6.2% vs 3.7%; P = .015). After adjustment for confounders, the occurrence of arterial thrombosis remained independently associated with the risk of carcinoma (odds ratio, 1.97; 95% confidence interval, 1.14-3.41), suggesting that MPN patients experiencing arterial events after MPN diagnosis deserve careful clinical surveillance for early detection of carcinoma. This study was registered at www.clinicaltrials.gov as NCT03745378.
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http://dx.doi.org/10.1182/blood.2019002614DOI Listing
January 2020

Tracing the decision-making process for myelofibrosis: diagnosis, stratification, and management of ruxolitinib therapy in real-word practice.

Ann Hematol 2020 Jan 12;99(1):65-72. Epub 2019 Dec 12.

Institute of Hematology "L. and A. Seràgnoli", Sant'Orsola-Malpighi University Hospital, Bologna, Italy.

The management of patients with myelofibrosis (MF) has dramatically changed since the introduction of ruxolitinib as a tailored treatment strategy. However, the perceptions about the use of this drug in clinical practice remain, at times, a matter of discussion. We conducted a survey about the diagnostic evaluation, prognostic assessment, and management of ruxolitinib in real-life clinical practice in 18 Italian hematology centers. At diagnosis, most hematologists do not use genetically or molecularly inspired score systems to assess prognosis, mainly due to scarce availability of next-generation sequencing (NGS) methodology, with NGS conversely reserved only for a subset of lower-risk MF patients with the aim of possibly improving the treatment strategy. Some common points in the management of ruxolitinib were 1) clinical triggers for ruxolitinib therapy, regardless of risk category; 2) evaluation of infectious risk before the starting of the drug; and 3) schedule of monitoring during the first 12 weeks with the need, in some instances, of supportive treatment. Further development of international recommendations and insights will allow the achievement of common criteria for the management of ruxolitinib in MF, before and after treatment, and for the definition of response and failure.
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http://dx.doi.org/10.1007/s00277-019-03847-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944647PMC
January 2020

Second cancers in MPN: Survival analysis from an international study.

Am J Hematol 2020 03 22;95(3):295-301. Epub 2019 Dec 22.

FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy.

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A "poor prognosis" SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a "non-poor prognosis" SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.
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http://dx.doi.org/10.1002/ajh.25700DOI Listing
March 2020

Management of elderly patients with immune thrombocytopenia: Real-world evidence from 451 patients older than 60 years.

Thromb Res 2020 01 21;185:88-95. Epub 2019 Nov 21.

Institute of Hematology "L. and A. Seràgnoli", Sant'Orsola-Malpighi University Hospital, Bologna, Italy.

Introduction: Primary Immune thrombocytopenia (ITP) in the elderly is a major clinical challenge which is increasingly frequent due to global ageing population.

Materials And Methods: To describe baseline ITP features, management, and outcome, a centralized electronic database was established, including data of 451 patients aged ≥60 years that were treated from 2000 onwards and were observed for ≥1 year (total observation of 2704 patient-years).

Results: At ITP diagnosis, median age was 71.1 years (age ≥ 75: 42.8%); 237 (53.9%) patients presented with haemorrhages (grade ≥ 3: 7.5%). First-line therapy included prednisone (82.9%), dexamethasone (14.6%), thrombopoietin-receptor agonists (TRAs, 1.3%), and oral immunosuppressive agents (1.1%). Prednisone starting dose ≥1 mg/kg/d (p = .01) and dexamethasone 40 mg/d (p < .001) were mainly reserved to patients aged 60-74, who were more treated with rituximab (RTX, p = .02) and splenectomy (p = .03) second-line. Overall response rates to first and second-line therapies were 83.8% and 84.5%, respectively, regardless of age and treatment type/dose. A total of 178 haemorrhages in 101 patients (grade ≥ 3: n. 52, 29.2%; intracranial in 6 patients), 49 thromboses in 43 patients (grade ≥ 3: n. 26, 53.1%) and 115 infections in 94 patients (grade ≥ 3: n. 23, 20%) were observed during follow-up. Incidence rates of complications per 100 patient-years were: 4.5 (haemorrhages, grade ≥ 3: 1.7), 1.7 (thromboses, grade ≥ 3: 0.9), and 3.9 (infections, grade ≥ 3: 0.7). TRAs use were associated with reduced risk of bleeding and infections, while cardiovascular risk factors (particularly, diabetes) significantly predicted thromboses and infections.

Conclusions: Age-adapted treatment strategies are required in elderly and very elderly patients.
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http://dx.doi.org/10.1016/j.thromres.2019.11.026DOI Listing
January 2020

Splanchnic vein thromboses associated with myeloproliferative neoplasms: An international, retrospective study on 518 cases.

Am J Hematol 2020 02 29;95(2):156-166. Epub 2019 Nov 29.

CRIMM, Centro di Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.

Myeloproliferative Neoplasms (MPN) course can be complicated by thrombosis involving unusual sites as the splanchnic veins (SVT). Their management is challenging, given their composite vascular risk. We performed a retrospective, cohort study in the framework of the International Working Group for MPN Research and Treatment (IWG-MRT), and AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM). A total of 518 MPN-SVT cases were collected and compared with 1628 unselected, control MPN population, matched for disease subtype. Those with MPN-SVT were younger (median 44 years) and enriched in females compared to controls; PV (37.1%) and ET (34.4%) were the most frequent diagnoses. JAK2V617F mutation was highly prevalent (90.2%), and 38.6% of cases had an additional hypercoagulable disorder. SVT recurrence rate was 1.6 per 100 patient-years. Vitamin K-antagonists (VKA) halved the incidence of recurrence (OR 0.48), unlike cytoreduction (OR 0.96), and were not associated with overall or gastrointestinal bleeding in multivariable analysis. Esophageal varices were the only independent predictor for major bleeding (OR 17.4). Among MPN-SVT, risk of subsequent vascular events was skewed towards venous thromboses compared to controls. However, MPN-SVT clinical course was overall benign: SVT were enriched in PMF with lower IPSS, resulting in significantly longer survival than controls; survival was not affected in PV and slightly reduced in ET. MPN-U with SVT (n = 55) showed a particularly indolent phenotype, with no signs of disease evolution. In the to-date largest, contemporary cohort of MPN-SVT, VKA were confirmed effective in preventing recurrence, unlike cytoreduction, and safe; the major risk factor for bleeding was esophageal varices that therefore represent a major therapeutic target.
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http://dx.doi.org/10.1002/ajh.25677DOI Listing
February 2020

Extracellular matrix deposition by adipose-derived stem cells and fibroblasts: a comparative study.

Arch Dermatol Res 2020 May 15;312(4):295-299. Epub 2019 Oct 15.

Surgical, Medical and Dental Department of Morphological Sciences Related To Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy.

Cell-based strategies are today widely studied as possible therapies for wound healing. In this setting, fibroblasts play a key role since they are the main dermal cellular component and are responsible for extracellular matrix secretion. Several works report on the possibility of using fibroblast-derived extracellular matrix scaffolds for wound healing in skin injuries. While fibroblast-based substitutes have already been intensively studied by other groups, we focused our attention on the possibility of creating an adipose-derived stem cell (ADSC)-induced dermal scaffold for wound healing. ADSCs are a particular subset of mesenchymal stem cells present in the stromal vascular fraction of the adipose tissue. The aim of our work was to compare the ability of ADSCs and fibroblast to produce in vitro a scaffolding material, both in terms of collagen and fibronectin production. ADSCs turned out to be capable of efficiently producing a collagen and fibronectin-containing dermal matrix upon stimulation with ascorbic acid. We observed fibronectin and collagen production by ADSCs to be even more abundant when compared to fibroblasts'. Our results support the use of ADSC-induced sheets instead of fibroblast-based dermal substitutes as wound-healing strategies in full-thickness skin injuries.
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http://dx.doi.org/10.1007/s00403-019-01997-8DOI Listing
May 2020

A Step-by-Step Problem-Solving Strategy in a Patient With Heart Failure and Cerebral Aneurysm.

Ann Thorac Surg 2020 04 29;109(4):e285-e287. Epub 2019 Aug 29.

Cardiac Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences, and Public Health, University of Padua, Padua, Italy. Electronic address:

Left ventricular assist device implantation is an established treatment for patients with end-stage heart failure. The HeartMate 3 (Abbott Laboratories, Abbott Park, IL) is a continuous-flow centrifugal pump, recently introduced in the clinic, that has shown greater hemocompatibility compared with similar devices of previous generations. Nevertheless, anticoagulation is still required after HeartMate 3 implant to avoid pump dysfunction. Hereafter, we describe the case of a patient candidate to left ventricular assist device implantation for end-stage heart failure presenting a concomitant cerebrovascular lesion, accidentally found during preoperative assessment, that would have contraindicated the procedure (for the prohibitive risk of cerebral hemorrhage), unless a step by step problem-solving approach was adopted.
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http://dx.doi.org/10.1016/j.athoracsur.2019.07.031DOI Listing
April 2020

Diagnostic 'nightmares' in an HIV patient with a cardiac mass and a previous history of tuberculosis.

J Cardiovasc Med (Hagerstown) 2019 Dec;20(12):841-843

Cardiac Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy.

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http://dx.doi.org/10.2459/JCM.0000000000000860DOI Listing
December 2019

Is resting state frontal alpha connectivity asymmetry a useful index to assess depressive symptoms? A preliminary investigation in a sample of university students.

J Affect Disord 2019 10 5;257:152-159. Epub 2019 Jul 5.

Sleep Disorders Unit, Institute of Neurology, Catholic University, Rome, Italy.

Background: Frontal alpha asymmetry (FAA) has been widely investigated in depressive disorders (DDs) with contradictory and not conclusive results. The main aim of the current study was to explore the association between a new neurophysiological index, the so-called frontal alpha connectivity asymmetry index (FACA-I), and depressive symptoms.

Methods: One hundred and thirteen participants (45 men and 68 women, mean age: 22.83 ± 2.26 years) were enrolled. Electroencephalographic (EEG) recordings were performed during 5 min of resting state (RS). FACA-I was computed by subtracting connectivity at left frontal regions from right frontal regions and dividing by their sum. RS FAA were also computed and compared to the FACA-I in all analyses.

Results: After controlling for the presence of potential confounding variables (i.e., sex, age and anxiety symptoms), only FACA-I scores between medial prefrontal cortex and subgenual anterior cingulate cortex were negatively associated with both somatic and cognitive/affective depressive symptoms and were lower in individuals with significant level of depressive symptoms.

Limitations: We focused on a sample of university students with no formal diagnosis of depression and we did not assess FAA and FACA-I during cognitive and/or emotional tasks, which make our interpretation specific to the RS condition.

Conclusions: Taken together our data suggest that alpha connectivity asymmetry between medial prefrontal cortex and subgenual anterior cingulate cortex may be a useful neurophysiological index in the assessment of depressive symptoms.
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http://dx.doi.org/10.1016/j.jad.2019.07.034DOI Listing
October 2019

Efficacy and safety of ruxolitinib and hydroxyurea combination in patients with hyperproliferative myelofibrosis.

Ann Hematol 2019 Aug 14;98(8):1933-1936. Epub 2019 Jun 14.

Institute of Hematology "L. and A. Seràgnoli", Sant'Orsola-Malpighi University Hospital, Bologna, Italy.

Ruxolitinib is the only commercially available JAK1/2 inhibitor approved for the treatment of myelofibrosis-related splenomegaly and symptoms. During treatment, as rare conditions, leukocytosis and/or thrombocytosis could develop and the management of these situations is not well established. We report here 53 myelofibrosis patients that received a combination of hydroxyurea and ruxolitinib because of uncontrolled myeloproliferation. Both drugs were administered outside clinical trials. At 48 weeks, a significant reduction in leucocyte and platelet counts was observed (p = 0.02 and p = 0.04, respectively). Additionally, the spleen volume decreased from a median value of 10 cm below the left costal margin (range, 0-10) to 6 cm (range, 0-15). The rate of spleen response increased from 14% at the start of the combination to 45% after 48 weeks. The safety profile of the combination was consistent with that observed with ruxolitinib single agent. These data require further confirmation in large cohorts of patients prospectively assessed.
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http://dx.doi.org/10.1007/s00277-019-03727-6DOI Listing
August 2019

Synergic effect of plasma exeresis and non-cross-linked low and high molecular weight hyaluronic acid to improve neck skin laxities.

J Cosmet Dermatol 2020 Jan 29;19(1):55-60. Epub 2019 Apr 29.

Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.

Background: Many therapeutic options are today available for neck aging, but little evidence exists about the efficacy of combining such procedures. Nonsurgical treatment of neck laxities and wrinkles is often preferred by patients, and combined strategies are nowadays emerging as the standard of care. Both plasma exeresis and hyaluronic acid (HA) injection are two emerging techniques in this setting.

Aims: To investigate the synergic effect of plasma exeresis and non-cross-linked HA injection, in stabilized hybrid complex of low and high molecular weight, in terms of both tolerability (assessed using VAS scale of pain) and improvement of neck skin laxities, according to the GAIS score assigned by patients and clinicians.

Patients/methods: Ten consecutive patients with signs of neck skin laxities (≥ type 3 according to the Glogau wrinkle scale) aged between 35 and 65 years were enrolled in our study. Two treatment sessions were performed. During the first session, both plasma exeresis and HA injection were performed. Patients were re-evauated after 30 days, and HA injection in the wrinkles of the neck was repeated. After 30 days from the second treatment session, a follow-up visit was performed to assess global efficacy of the two-step combined treatment and to monitor eventual long-term side effects.

Results: A GAIS score of 1 or 2 was present in 90% of the treated cases, according to both patients and clinicians. Mean VAS value for pain was 2.4/10. Minor side effects such as erythema and/or edema were transient and completely resolved. No major adverse events were observed.

Conclusions: We strongly encourage the combined treatment with plasma exeresis and non-cross-linked HA injection for its promising remodeling effects in the field of neck rejuvenation.
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http://dx.doi.org/10.1111/jocd.12976DOI Listing
January 2020