Author
Nicola Giuliani
Other affiliations: Veterans Health Administration, French Institute of Health and Medical Research, University of Pittsburgh
Bio: Nicola Giuliani is an academic researcher from University of Parma. The author has contributed to research in topics: Multiple myeloma & Bone marrow. The author has an hindex of 48, co-authored 227 publications receiving 7549 citations. Previous affiliations of Nicola Giuliani include Veterans Health Administration & French Institute of Health and Medical Research.
Topics: Multiple myeloma, Bone marrow, Osteoclast, Osteoblast, Bortezomib
Papers published on a yearly basis
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TL;DR: Data indicate that myeloma cells affect the OPG/OPGL ratio in the BM environment and tend to confirm that the O PG/OP GL system is involved in the pathogenesis of MM-induced bone disease.
419 citations
University of Insubria1, University of Pavia2, University of Eastern Piedmont3, University of Bologna4, University of Verona5, Humanitas University6, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico7, University of Milan8, University of Genoa9, University of Catania10, University of Parma11, University of Pisa12, University of Turin13, University of Perugia14, Sapienza University of Rome15, University of Padua16, University of Brescia17, University of Modena and Reggio Emilia18, University of Siena19, University of Udine20, Università Campus Bio-Medico21, Catholic University of the Sacred Heart22
TL;DR: This study adds to the evidence that patients with haematological malignancies have worse outcomes and the general Italian population with COVID-19 has high mortality, by calculating standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates.
408 citations
TL;DR: It is found that human myeloma cells suppress the formation of human osteoblast progenitors in bone marrow (BM) cultures and the potential contribution of interleukin-7 (IL-7) in the inhibitory effect on osteooblast formation and RUNX2/CBFA1 activity by human myELoma cells in coculture is shown.
312 citations
TL;DR: Oral MPR therapy is a promising first-line treatment for elderly myeloma patients and aspirin appears to provide adequate antithrombosis prophylaxis.
Abstract: Purpose Lenalidomide has shown significant antimyeloma activity in clinical studies. Oral melphalan, prednisone, and thalidomide have been regarded as the standard of care in elderly multiple myeloma patients. We assessed dosing, efficacy, and safety of melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed elderly myeloma patients. Patients and Methods Oral melphalan was administered in doses ranging from 0.18 to 0.25 mg/kg on days 1 to 4, prednisone at a 2-mg/kg dose on days 1 to 4, and lenalidomide at doses ranging from 5 to 10 mg on days 1 to 21, every 28 days for nine cycles, followed by maintenance therapy with lenalidomide alone. Aspirin was given as a prophylaxis for thrombosis. Results Fifty-four patients were enrolled and evaluated after completing the assigned treatment schedule. The maximum tolerated dose was defined as 0.18 mg/kg melphalan and 10 mg lenalidomide. With these doses, 81% of patients achieved at least a partial response, 47.6% achieved a very good partial response, and ...
312 citations
TL;DR: In this article, the pathophysiology underlying osteoblast inhibition in multiple myeloma (MM) patients is reviewed and the biologic mechanisms involved in the osteoblasts inhibition induced by MM cells have been elucidated.
285 citations
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01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
4,408 citations
Spanish National Research Council1, National and Kapodistrian University of Athens2, Rabin Medical Center3, University of Münster4, Charles University in Prague5, Sapienza University of Rome6, University of Turin7, Medical University of Lublin8, Peking University9, Harvard University10, Millennium Pharmaceuticals11, Johnson & Johnson12
TL;DR: Bortezomib plus melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy was superior to melphAlan-predisonsone alone.
Abstract: The time to progression among patients receiving bortezomib plus melphalan– prednisone (bortezomib group) was 24.0 months, as compared with 16.6 months among those receiving melphalan–prednisone alone (control group) (hazard ratio for the bortezomib group, 0.48; P<0.001). The proportions of patients with a partial response or better were 71% in the bortezomib group and 35% in the control group; complete-response rates were 30% and 4%, respectively (P<0.001). The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group. The hazard ratio for overall survival was 0.61 for the bortezomib group (P = 0.008). Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan–prednisone. Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group (53% vs. 44%, P = 0.02), but there were no significant differences in grade 4 events (28% and 27%, respectively) or treatment-related deaths (1% and 2%). Conclusions Bortezomib plus melphalan–prednisone was superior to melphalan–prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)
1,728 citations
VU University Amsterdam1, Heidelberg University2, University of Barcelona3, Harvard University4, Complutense University of Madrid5, Lille University of Science and Technology6, Marche Polytechnic University7, Mayo Clinic8, Emory University9, Sapienza University of Rome10, University of Bologna11, University of Arkansas for Medical Sciences12, National and Kapodistrian University of Athens13, Cedars-Sinai Medical Center14, Erasmus University Rotterdam15, University of Navarra16, Centre Hospitalier Universitaire de Nantes17
TL;DR: The R-ISS is a simple and powerful prognostic staging system, and it is recommended for use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.
Abstract: Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (l...
1,350 citations
TL;DR: What makes interleukin-6 particularly interesting to physicians is its marked pleiotropy and its involvement not only in inflammation but in the regulation of endocrine and metabolic functions.
Abstract: Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations Furthermore, it is secreted during stress and is positively controlled by catecholamines Administration of interleukin-6 results in fever, anorexia, and fatigue Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism Overproduction of interleukin-6 may contribute to illness during aging and chronic stress Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis
1,121 citations
TL;DR: Understanding the crucial components of the bone microenvironment that influence tumour localization, along with the tumour-derived factors that modulate cellular and protein matrix components of bone to favour tumour expansion and invasion, is central to the pathophysiology of bone metastases.
Abstract: When cancer metastasizes to bone, considerable pain and deregulated bone remodelling occurs, greatly diminishing the possibility of cure. Metastasizing tumour cells mobilize and sculpt the bone microenvironment to enhance tumour growth and to promote bone invasion. Understanding the crucial components of the bone microenvironment that influence tumour localization, along with the tumour-derived factors that modulate cellular and protein matrix components of bone to favour tumour expansion and invasion, is central to the pathophysiology of bone metastases. Basic findings of tumour–bone interactions have uncovered numerous therapeutic opportunities that focus on the bone microenvironment to prevent and treat bone metastases.
1,067 citations