3D digital technologies for architectural analysis. The case of the ‘Pagan Shrine’ in the Catacombs of Santa Lucia (Siracusa, Sicily)

The Catacombs of Santa Lucia are one of the oldest and most important monuments in the Christian communities of Siracusa and Sicily in the late Roman period. The name of the complex derives from a tradition, according to which Saint Lucy was buried here, after her martyrdom in the early 4th century AD, under the reign of Diocletian. A large underground cemetery extends beneath the homonymous square. The cemetery gradually expanded from the 3rd to the 5th century AD, as it incorporated pre-existing constructions once used for funerary, religious and industrial purposes, by transforming them into monumental burial chambers. One of the most significant structures is the so-called ‘Pagan Shrine’: a chamber that is dated between the 3rd century BC and 1st century AD, prior to the foundation of the cemetery and frescoed with worldly themes and pagan deities. The Shrine is located in the South-western corner of Regio C, an area that is hard and rather dangerous to reach, never opened to the public and visited only by few scholars over the past decades. The excavation project undertaken in the years 2011-2015 by the Pontifical Commission of Sacred Archaeology, in association with the Arcadia University and the University of Catania, led to the development of the first virtual replica of the Shrine, using Digital Photogrammetry. This new approach facilitated an accurate examination of both its structure and its decoration, allowing us to propose a new theory about the original purpose of the room, traditionally regarded by scholars as a place for worshipping Zeus Peloros

Diet and mobility in Late Antique Sicily: Isotopic data from the catacombs of Santa Lucia, Siracusa (Italy)

The catacombs of Santa Lucia were built during the 3rd century CE in Siracusa, Sicily, Italy, as a burial site for members of the local Christian community until the early 8th century CE. This site is an important cemeterial context of the Late Roman and Byzantine periods. The tombs and artifacts found suggest that individuals of varying wealth were buried in the catacombs. Historical accounts also confirm the presence of a significant Christian community from Syria and the Levant in Siracusa during this period. The objective of this research is to investigate the life histories of the Late Antique community interred in the catacombs using stable isotope analysis. This technique aimed to clarify the dietary differences between individuals of different social status and geographical origins, in order to re-evaluate the data from historical documents. To achieve this, we conducted stable carbon, nitrogen, and oxygen isotope analyses on skeletal samples from 25 individuals recovered from the catacombs of Santa Lucia, using established methods. The results revealed significant dietary diversity among the individuals buried in the catacombs, with evidence of the consumption of both C3 and C4 plants, as well as fish from both freshwater and sea sources. The oxygen isotopes show a particularly broad range in both the small sample set of bones and the larger set of teeth, suggesting a significant degree of mobility for most of the individuals tested. The high variability found in the diet and the evidence of mobility for most of the individuals tested not only between early age and adulthood, but also throughout their lives. It raises new questions and calls for the consideration of the archaeological and historical implications of these novel discoveries

The serological prevalence of SARS-CoV-2 infection in patients with chronic myeloid leukemia is similar to that in the general population

Background: Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19. Methods: We conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in five hematologic centers representative of three Italian regions. Results: The estimated serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population (about 2%), both at national and regional levels. CML patients with positive anti-SARS-CoV-2\ua0serology were more frequently male (p\ua0=\ua00.027) and active workers (p\ua0=\ua00.012), while there was no significant association with TKI treatment type. Only 3 out of 11 IgG-positive patients had previously received a molecular diagnosis of COVID-19, while the remainders were asymptomatic or with mild symptoms. Conclusions: Our data confirm that the course of SARS-CoV-2 infection in patients with CML is generally mild and reassure about the safety of continuing TKIs during the COVID-19 pandemic. Furthermore, we suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2, similar to the general population

Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front-line with paediatric-inspired regimens: A retrospective multicentre Campus ALL study

Within the Campus ALL network we analyzed the incidence, characteristics, treatment and outcome of a central nervous system (CNS) relapse in 1035 consecutive adult acute lymphoblastic leukemia (ALL) patients treated frontline with pediatric-inspired protocols between 2009 and 2020. Seventy-one patients (6.8%) experienced a CNS recurrence, more frequently in T- (28/278; 10%) than in B-ALL (43/757; 5.7%) (p = 0.017). An early CNS relapse—< 12 months from diagnosis—was observed in 41 patients. In multivariate analysis, risk factors for early CNS relapse included T-cell phenotype (p = <0.001), hyperleucocytosis >100 × 109/L (p<0.001) and male gender (p = 0.015). Treatment was heterogeneous, including chemotherapy, radiotherapy, intrathecal therapy and novel agents. A complete remission (CR) was obtained in 39 patients (55%) with no differences among strategies. After CR, 26 patients underwent an allogenic transplant, with a significant overall survival benefit compared to non-transplanted patients (p = 0.012). After a median observation of 8 months from CNS relapse, 23 patients (32%) were alive. In multivariate analysis, the time to CNS relapse was the strongest predictor of a lower 2-year post-relapse survival (p<0.001). In conclusion, in adult ALL the outcome after a CNS relapse remains very poor. Effective CNS prophylaxis remains the best approach and allogenic transplant should be pursued when possible

Proposed global prognostic score for systemic mastocytosis: a retrospective prognostic modelling study

[Background]: Several risk stratification models have been proposed in recent years for systemic mastocytosis but have not been directly compared. Here we designed and validated a risk stratification model for progression-free survival (PFS) and overall survival (OS) in systemic mastocytosis on the basis of all currently available prognostic factors, and compared its predictive capacity for patient outcome with that of other risk scores.[Methods]: We did a retrospective prognostic modelling study based on patients diagnosed with systemic mastocytosis between March 1, 1983, and Oct 11, 2019. In a discovery cohort of 422 patients from centres of the Spanish Network on Mastocytosis (REMA), we evaluated previously identified, independent prognostic features for prognostic effect on PFS and OS by multivariable analysis, and designed a global prognostic score for mastocytosis (GPSM) aimed at predicting PFS (GPSM-PFS) and OS (GPSM-OS) by including only those variables that showed independent prognostic value (p<0·05). The GPSM scores were validated in an independent cohort of 853 patients from centres in Europe and the USA, and compared with pre-existing risk models in the total patient series (n=1275), with use of Harrells' concordance index (C-index) as a readout of the ability of each model to risk-stratify patients according to survival outcomes.[Findings]: Our GPSM-PFS and GPSM-OS models were based on unique combinations of independent prognostic factors for PFS (platelet count ≤100 × 109 cells per L, serum β2-microglobulin ≥2·5 μg/mL, and serum baseline tryptase ≥125 μg/L) and OS (haemoglobin ≤110 g/L, serum alkaline phosphatase ≥140 IU/L, and at least one mutation in SRSF2, ASXL1, RUNX1, or DNMT3A). The models showed clear discrimination between low-risk and high-risk patients in terms of worse PFS and OS prognoses in the discovery and validation cohorts, and further discrimination of intermediate-risk patients. The GPSM-PFS score was an accurate predictor of PFS in systemic mastocytosis (C-index 0·90 [95% CI 0·87–0·93], vs values ranging from 0·85 to 0·88 for pre-existing models), particularly in non-advanced systemic mastocytosis (C-index 0·85 [0·76–0·92], within the range for pre-existing models of 0·80 to 0·93). Additionally, the GPSM-OS score was able to accurately predict OS in the entire cohort (C-index 0·92 [0·89–0·94], vs 0·67 to 0·90 for pre-existing models), and showed some capacity to predict OS in advanced systemic mastocytosis (C-index 0·72 [0·66–0·78], vs 0·64 to 0·73 for pre-existing models).[Interpretation]: All evaluated risk classifications predicted survival outcomes in systemic mastocytosis. The REMA-PFS and GPSM-PFS models for PFS, and the International Prognostic Scoring System for advanced systemic mastocytosis and GPSM-OS model for OS emerged as the most accurate models, indicating that robust prognostication might be prospectively achieved on the basis of biomarkers that are accessible in diagnostic laboratories worldwide.Carlos III Health Institute, European Regional Development Fund, Spanish Association of Mastocytosis and Related Diseases, Rare Diseases Strategy of the Spanish National Health System, Junta of Castile and León, Charles and Ann Johnson Foundation, Stanford Cancer Institute Innovation Fund, Austrian Science Fund

Blinatumomab differentially modulates peripheral blood and bone marrow immune cell repertoire: a Campus ALL study

Blinatumomab is the first bi-specific T-cell engager approved for relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (B-ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study, we characterized the peripheral blood (PB) and, for the first time, the bone marrow (BM) immune cell repertoire upon blinatumomab treatment. Twenty-nine patients with B-ALL received blinatumomab according to clinical practice. Deep multiparametric flow cytometry was used to characterize lymphoid subsets during the first treatment cycle. Blinatumomab induced a transient redistribution of PB effector T-cell subsets and Treg cells with a persistent increase in cytotoxic NK cells, which was associated with a transient upregulation of immune checkpoint receptors on PB CD4 and CD8 T-cell subpopulations and of CD39 expression on suppressive Treg cells. Of note, BM immune T-cell subsets showed a broader post-treatment subversion, including the modulation of markers associated with a T-cell-exhausted phenotype. In conclusion, our study indicates that blinatumomab differentially modulates the PB and BM immune cell repertoire, which may have relevant clinical implications in the therapeutic setting