In vitro pharmacological modulation of NKG2D expression in immune cells from Behçet syndrome patients Martina Bonacini, Francesco Muratore, Laura Albertazzi, Luca Cimino, Rossana Colla, et al. Clinical and Experimental Immunology, 2026 Glucocorticoids, interferon-2α, colchicine, and azathioprine are recommended by EULAR for various manifestations of Behçet syndrome (BS). Curcumin is a natural compound with anti-inflammatory activities. NKG2D is a receptor expressed by NK, NKT, and CD8pos T cells implicated in recognizing stressed cells. This study aimed to: (i) evaluate the effects of selected drugs used in the management of BS plus curcumin on NKG2D expression by lymphocytes; (ii) test the effects of these drugs on immune cell subsets; and (iii) determine whether immune cells from BS patients respond differently to those from healthy controls (CTR). Peripheral blood mononuclear cells from BS patients and CTR were treated with dexamethasone, interferon-2α, colchicine, azathioprine, or curcumin for 48 h in the presence or absence of IL-15. NKG2D expression on NK, NKT, and CD8pos T cells and the percentages/absolute counts of NK, NKT, T, and B cells were evaluated by flow cytometry. All drugs down-regulated NKG2D expression. The reduction was more pronounced in CTR than in BS patients following dexamethasone treatment, in BS patients than in CTR following colchicine treatment. Dexamethasone reduced NK cells in the absence of IL-15, but increased them in its presence. Colchicine reduced B cells regardless of IL-15 stimulation. Azathioprine also down-regulated B cells, but only in the presence of IL-15 stimulation. Drugs used in the management of BS reduced NKG2D expression, potentially decreasing the activation of cytotoxic cells. Immune cells from BS patients responded differently to dexamethasone and colchicine compared to those from CTR.
Variant analysis and biochemical investigation in two siblings with late onset idiopathic secondary erythrocytosis: A case report Vincenza Ylenia Cusenza, Beatrice Melli, Chiara Marraccini, Agnese Razzoli, Margherita Genitoni, et al. Medicine United States, 2025 Rationale: The potential etiological factors for acquired secondary erythrocytosis (SE) include sleep apnea, smoking, and renal cysts. However, there is limited evidence to consistently support an association between these factors and SE. Additionally, identifying the genetic variants underlying SE requires specific and expensive testing methods. These diagnostic challenges mean that many cases of SE are classified as idiopathic, which complicates the development of tailored diagnostic and therapeutic strategies. Patient concerns: This study examined 2 brothers (brother I [BI] and brother II [BII]) with idiopathic SE who were undergoing monthly phlebotomy. Diagnoses: A diagnosis of polycythemia vera or other acquired causes, such as pulmonary disease or malignancy, was excluded. Both subjects exhibited mild to moderate sleep apnea, while their erythropoietin levels were within the normal range. Interventions: To identify potential disease-causing variants shared by the brothers, gene panel exome-sequencing and further biochemical investigations were conducted. Outcomes: The following was identified in BI and BII: potential causative mutations in the EPAS1 gene, which were ruled out as causative factors through variant annotation and gene expression analysis; a heterozygous missense variant in the PIGV gene (p.Ala341Glu), which is known to damage proteins. The red blood cells of the brothers exhibited reduced fragility and lower hemolysis levels compared to healthy controls, with a slight increase in CD59 surface exposure. Lessons: These findings suggest that red blood cells from BI and BII are more resistant to hemolysis. However, given that PIGV is involved in glycosylphosphatidylinositol biosynthesis and that CD59 exposure affects hemolysis, further investigation is required to elucidate these pathogenic mechanisms. Molecular and biochemical characterization of patients with idiopathic SE may pave the way for identifying novel mechanisms involved in the disease.
Incidence, mortality, and survival of hematological malignancies in Northern Italian patients: an update to 2020 Lucia Mangone, Domenico Penna, Francesco Marinelli, Francesca Roncaglia, Isabella Bisceglia, et al. Frontiers in Oncology, 2023 BackgroundHematological malignancies (HMs) represent a heterogeneous group of diseases with diverse etiology, pathogenesis, and prognosis. HMs’ accurate registration by Cancer Registries (CRs) is hampered by the progressive de-hospitalization of patients and the transition to molecular rather than microscopic diagnosis.Material and methodsA dedicated software capable of automatically identifying suspected HMs cases by combining several databases was adopted by Reggio Emilia Province CR (RE-CR). Besides pathological reports, hospital discharge archives, and mortality records, RE-CR retrieved information from general and biomolecular laboratories. Incidence, mortality, and 5-year relative survival (RS) reported according to age, sex, and 4 HMs’ main categories, were noted.ResultsOverall, 7,578 HM cases were diagnosed from 1996 to 2020 by RE-CR. HMs were more common in males and older patients, except for Hodgkin Lymphoma and Follicular Lymphoma (FL). Incidence showed a significant increase for FL (annual percent change (APC)=3.0), Myeloproliferative Neoplasms (MPN) in the first period (APC=6.0) followed by a significant decrease (APC=-7.4), and Myelodysplastic Syndromes (APC=16.4) only in the first period. Over the years, a significant increase was observed in 5-year RS for Hodgkin -, Marginal Zone -, Follicular - and Diffuse Large B-cell-Lymphomas, MPN, and Acute Myeloid Leukemia. The availability of dedicated software made it possible to recover 80% of cases automatically: the remaining 20% required direct consultation of medical records.ConclusionsThe study emphasizes that HM registration needs to collect information from multiple sources. The digitalization of CRs is necessary to increase their efficiency.
The association between clinical laboratory data and chest CT findings explains disease severity in a large Italian cohort of COVID-19 patients Simone Canovi, Giulia Besutti, Efrem Bonelli, Valentina Iotti, Marta Ottone, et al. BMC Infectious Diseases, 2021 Background Laboratory data and computed tomography (CT) have been used during the COVID-19 pandemic, mainly to determine patient prognosis and guide clinical management. The aim of this study was to evaluate the association between CT findings and laboratory data in a cohort of COVID-19 patients. Methods This was an observational cross-sectional study including consecutive patients presenting to the Reggio Emilia (Italy) province emergency rooms for suspected COVID-19 for one month during the outbreak peak, who underwent chest CT scan and laboratory testing at presentation and resulted positive for SARS-CoV-2. Results Included were 866 patients. Total leukocytes, neutrophils, C-reactive protein (CRP), creatinine, AST, ALT and LDH increase with worsening parenchymal involvement; an increase in platelets was appreciable with the highest burden of lung involvement. A decrease in lymphocyte counts paralleled worsening parenchymal extension, along with reduced arterial oxygen partial pressure and saturation. After correcting for parenchymal extension, ground-glass opacities were associated with reduced platelets and increased procalcitonin, consolidation with increased CRP and reduced oxygen saturation. Conclusions Pulmonary lesions induced by SARS-CoV-2 infection were associated with raised inflammatory response, impaired gas exchange and end-organ damage. These data suggest that lung lesions probably exert a central role in COVID-19 pathogenesis and clinical presentation.
The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients Giulia Besutti, Massimo Pellegrini, Marta Ottone, Michele Cantini, Jovana Milic, et al. Plos One, 2021 We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.
Droplet digital PCR is a sensitive tool for the detection of TP53 deletions and point mutations in chronic lymphocytic leukaemia Raffaele Frazzi, Veronica Bizzarri, Laura Albertazzi, Vincenza Ylenia Cusenza, Lia Coppolecchia, et al. British Journal of Haematology, 2020 TP53 gene defects encompassing del(17p) and mutations are associated with adverse disease outcomes in chronic lymphocytic leukaemia (CLL). TP53 disruption is a well-established prognostic marker in CLL with clinical and therapeutic implications, therefore its assessment is recommended prior to initiation of the first and every subsequent line of treatment (Pospisilova et al., 2012). Approximately 90% of del (17p) patients also carry TP53 mutations in the remaining allele and mutations in the absence of del(17p) occur in a significant proportion of CLL patients (c. 5% in first-line treatment situation) (Zenz et al., 2010; Pospisilova et al., 2012; Malcikova et al., 2018). Del(17p) assessment is addressed by means of fluorescence in situ hybridization (FISH). FISH is an informative technique, albeit laborious and time-consuming. Hence, there is the need for a faster and more efficient method to quantitate the percentage of the deletion starting from a limited amount of sample. Droplet digital PCR (ddPCR) is a very sensitive and reproducible technique and is mostly used for research purposes (Del Re et al., 2019; Della Starza et al., 2019; Hamfjord et al., 2019; Kjaer et al., 2019). Here we present an approach based on ddPCR aimed at detecting and measuring the deletions and point mutations within the TP53 gene. The most recent guidelines suggest the evaluation of this gene’s abnormalities for intervention and monitoring purposes (Ladetto et al., 2016; Malcikova et al., 2018). Minimal residual disease (MRD) is an excellent prognostic tool in CLL patients and a surrogate for progression-free survival (PFS) (Ladetto et al., 2016). The achievement of MRD response is associated with prolonged PFS and overall survival and is a desirable goal of CLL therapies (Seymour et al., 2018; Kater et al., 2019). Here we propose the use of ddPCR to assess and monitor MRD in CLL patients.
Prevalence of SARS-CoV-2 (Covid-19) in italians and in immigrants in an area of northern Italy (Reggio Emilia) Epidemiologia E Prevenzione, 2020 It has been hypothesized that bacille Calmette-Guerin (BCG), the anti-tuberculosis vaccine, can be protective against Covid-19. Using data of performed swabs and RT-PCR results for SARS-CoV-2 in the Reggio Emilia province (Emilia-Romagna Region, Northern Italy) from March 6th to March 26th, 2020, we computed age, gender, and place of birth (Italy or abroad) specific risk of being tested, prevalence of positive tests, and probability of testing positive given that a swab has been taken during the epidemic peak. We report that immigrants resident in Reggio Emilia province, mostly coming from Countries with high BCG vaccination coverage, and Italians had a similar prevalence of infection (odds ratio - OR 0.99; 95%CI 0.82-1.20) and similar probability of being tested (OR 0.93; 95%CI 0.81-1.10). Our data do not support the hypothesis that immigrants from Countries where BCG vaccination is recommended have a lower risk of Covid-19 infection.
P-024. Lymphocyte subset populations are altered in adult patients with GH deficiency. Effects of long-term GH replacement therapy Endocrinology and Metabolism Supplement, 1997
