Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors.

Precise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66b+CD10+CD16+CD11b+ PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments. Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs.

Transfusional Approach in Multi-Ethnic Sickle Cell Patients: Real-World Practice Data From a Multicenter Survey in Italy.

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03397017.

Mature CD10+ and immature CD10- neutrophils present in G-CSF-treated donors display opposite effects on T cells.

The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b+ neutrophil populations, exerting either immunosuppressive or proinflammatory functions, has been described in several acute and chronic inflammatory conditions. However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear. Herein, we report that CD10, also known as common acute lymphoblastic leukemia antigen, neutral endopeptidase, or enkephalinase, can be used as a marker that, within heterogeneous populations of circulating CD66b+ neutrophils present in inflammatory conditions, clearly distinguishes the mature from the immature ones. Accordingly, we observed that the previously described immunosuppressive neutrophil population that appears in the circulation of granulocyte colony-stimulating factor (G-CSF)-treated donors (GDs) consists of mature CD66b+CD10+ neutrophils displaying an activated phenotype. These neutrophils inhibit proliferation and interferon γ (IFNγ) production by T cells via a CD18-mediated contact-dependent arginase 1 release. By contrast, we found that immature CD66b+CD10- neutrophils, also present in GDs, display an immature morphology, promote T-cell survival, and enhance proliferation and IFNγ production by T cells. Altogether, our findings uncover that in GDs, circulating mature and immature neutrophils, distinguished by their differential CD10 expression, exert opposite immunoregulatory properties. Therefore, CD10 might be used as a phenotypic marker discriminating mature neutrophils from immature neutrophil populations present in patients with acute or chronic inflammatory conditions, as well as facilitating their isolation, to better define their specific immunoregulatory properties.

Severe maternal morbidity in a tertiary care centre of northern Italy: a 5-year review.

OBJECTIVE: To assess prevalence and causes of severe acute maternal morbidity cases and evaluate their impact on feto-maternal wellbeing and on facility resources. STUDY DESIGN: Observational retrospective study adopting management-based criteria in a tertiary care public hospital during a 5-year period. Criteria adopted were: intensive care unit admission, blood transfusion ≥ 4 units, emergency peripartum hysterectomy and arterial embolization at any time during pregnancy. RESULTS: A total of 80 cases were identified, most of them (97.5%) through a combination of two criteria, ICU admission and blood transfusion. Commonest severe obstetric morbidities were major obstetric haemorrhage (48.8%) and hypertensive disorders (27.5%). Immigrant status (OR 1.68, 95% CI 1.03-2.7), pre-term birth (OR 4.15, 95% CI 2.5-6.8), Caesarean section (OR 7.74,95% CI 4.2-14.3) were factors significantly associated with SAMM cases. Major abdominal surgery was necessary in 26 women (32.5%), with emergency peripartum hysterectomy in 11 (13.5%). These events led to an average blood consumption per woman of 6.5 ± 12.8 units and a mean hospital stay of 8.9 ± 5.0 days, significantly longer (p < 0.001) than the average duration of post-delivery care. Maternal mortality to morbidity ratio was 1:80. CONCLUSIONS: An integrated intervention-based approach proved to be effective in finding severe acute maternal morbidity cases. Information on underlying causes and associated risk factors may improve prevention and treatment of obstetric morbidities, thus reducing feto-maternal adverse effects and hospital expenditures.

The use of banked skin in the Burns Centre of Verona.

BACKGROUND: The use of glycerol and subsequent research enabling the conservation of tissues over time have led to the establishment and development of tissue banks, first in the USA and then in Europe. The Verona Tissue Bank was instituted in 2003 as the Regional Centre for the storage of skin and bone, adding to the already existing Italian banks at Turin, Milan, Cesena and Siena. This retrospective study analyses the use of banked skin (autologous and allogeneic grafts) from April 2003 (date of starting activity) to December 2007, in 171 patients with burns and four with necrotising fasciitis at the Burns Centre of Verona. MATERIALS AND METHODS: Homologous skin was used for superficial and deep skin burns to protect the residual structures, thus facilitating healing by spontaneous re-epithelialisation, and for deep burns after eschar removal to clean and prepare the base of the lesion for the definitive autologous graft. The placement of a homologous graft alone led to spontaneous healing of lesions in 65 patients (36 aged >15 years and 29 aged <15 years) with superficial skin burns, while the remaining 106 patients (84 aged >15 years and 22 aged <15 years) with deeper burns underwent surgery. CONCLUSIONS: The results obtained confirm the essential role of banked skin in covering superficial burns in order to protect important underlying structures and in deep burns by guaranteeing a good preparation of the base of the lesion for the subsequent definitive autologous graft.

Evaluation of cryopreserved donor skin viability: the experience of the regional tissue bank of Verona.

BACKGROUND: Allogeneic human skin removed from cadaveric donors is the covering of choice for deep burns, since it accelerates the re-epithelialisation of autologous skin. In this study we evaluated the cellular viability of cryopreserved skin at the regional tissue bank of Verona (Italy). METHODS: From 1st June 2007 to 30th September 2007, tests of cutaneous cell viability were carried out on 21 consecutive skin donors using the MTT (tetrazolium salt) method on samples prior to freezing and on thawed samples after a period of cryopreservation. RESULTS: The mean percentage viability was 45.1% (+/-20.1%), which is similar to results obtained in other tissue banks. It was noted that viability decreased with increasing age of the donor. CONCLUSIONS: The results of the evaluation of cutaneous cell viability document the validity of the skin cryopreservation procedure in use at the tissue bank in Verona.

Comparison of CT features of Aspergillus and bacterial pneumonia in severely neutropenic patients.

PURPOSE: To establish whether a relationship exists between computed tomography features of lung opacities in severely neutropenic patients and their Aspergillus or bacterial etiology. METHODS: Computed tomography scans of 124 patients with lung opacities larger than 5 mm occurring during severe (neutrophils <500/mm) and prolonged (>7 d) neutropenia-induced by bone marrow transplantation and/or high-dose chemotherapy for hematologic malignancies-were reviewed. Invasive pulmonary aspergillosis or bacterial pneumonia were assessed by means of bronchoalveolar lavage, bronchial washing, trans-bronchial biopsy or (for bacteria only) blood cultures. Pulmonary opacities were classified as nodules or as consolidations. The presence of a perinodular ground-glass halo, the similarity of consolidations to a pulmonary infarction and the presence of cavitation (crescent-shaped or not) were recorded. RESULTS: Invasive pulmonary aspergillosis was diagnosed in 68 patients; bacterial pneumonia in 56. Nodules (85) were more common than consolidations (39); their distribution among the patients with aspergillosis (52 nodules and 16 consolidations) and those with bacterial pneumonia (33 nodules and 23 consolidations) was even. Out of the 19 nodules surrounded by a halo 17 were due to aspergillosis. Nine consolidations (3 due to aspergillosis) were infarctionlike shaped. Cavitation appeared during 22/68 aspergillosis and 31/56 bacterial pneumonias; an air-crescent in 6 patients with aspergillosis and in 24 with bacterial pneumonia. CONCLUSIONS: Although rare enough, the perinodular halo is highly specific for invasive aspergillosis. The nodular pattern of lung opacities, their similarity to a pulmonary infarction, the occurrence of cavitation and the air-crescent are not related to aspergillosis.

A pilot study on the efficacy of ketorolac plus tramadol infusion combined with erythrocytapheresis in the management of acute severe vaso-occlusive crises and sickle cell pain.

One of the major causes of hospitalization for patients with sickle cell disease (SCD) are vaso-occlusive crises (VOC), which are characterized by acute pain and organ damage related to the presence of dense red cells. Here we report a pilot study which combined balanced analgesia with tramadol plus ketorolac and erythrocytapheresis. Key words: sickle cell disease, therapeutic erythrocytapheresis, HbS, visual analog scale, vaso-occlusive crisis.