Rationally cubic connected manifolds I: manifolds covered by lines

In this paper we study smooth complex projective polarized varieties (X,H) of dimension n \ge 2 which admit a dominating family V of rational curves of H-degree 3, such that two general points of X may be joined by a curve parametrized by V, and such that there is a covering family of rational curves of H-degree one. Our main result is that the Picard number of these manifolds is at most three, and that, if equality holds, (X,H) has an adjuction theoretic scroll structure over a smooth variety

The effect of COVID-19 on the frequency of Pneumocystis jirovecii pneumonia: a monocentric, retrospective, and observational study

Background: Pneumocystis jirovecii pneumonia (PCP) and SARS-CoV2 share some similarities in their effects on the respiratory system, clinical presentation, and management. The COVID-19 pandemic required rapid action to curb transmission and mitigate its lethiferous impact. Non-pharmaceutical interventions (NPIs) were globally adopted. We hypothesized that these measures reduced the transmission and acquisition of P. jirovecii in both hospital and community settings. Methods: We conducted a retrospective observational study on 2950 respiratory specimens from patients with suspected pulmonary infection, analyzed at the Laboratory of Parasitology Unit of the Policlinico Tor Vergata of Rome, Italy, from January 2014 to December 2022. Results: We show a significant reduction in the frequency of PCP in the COVID-19 pandemic era compared to the previous period. Among the four sequence types of P. jirovecii identified, genotype 1 was the most prevalent (37%). We observed a non-significant trend of decreasing cases with genotype 1 and increasing cases with genotype 3 over the study period. Conclusions: The nationwide implementation of NPIs against COVID-19 may have changed the microbiological landscape of exposure, thereby decreasing the exposure to P. jirovecii and consequently reducing the incidence of PCP

Clinical relevance of an objective - limit of detection - limit of quantification - based flow cytometry approach for measurable residual disease assessment in acute myeloid leukemia. A post-hoc analysis of the GIMEMA AML1310 trial

Using a multiparametric flow cytometry (MFC) assay, we assessed the predictive power of a threshold calculated applying the criteria of limit of detection (LOD) and limit of quantitation (LOQ) in adult patients affected with Acute Myeloid Leukemia (AML). This was a post-hoc analysis of 261 patients enrolled in the GIMEMA AML1310 prospective trial. According to the protocol design, using the predefined MRD threshold of 0.035% bone marrow residual leukemic cell (RLC) calculated on mononuclear cells, 154 (59%) were negative (MRD<0.035%) and 107 (41%) were positive (MRD≥0.035%). Using LOD and LOQ, we selected the following categories of patients: 1) LODneg if RLC were below LOD (74; 28.4%); 2) LODpos-LOQneg if RLC were between LOD and LOQ (43; 16.5%); and 3) LOQpos if RLC were above LOQ (144; 54.4%). Two-year overall survival (OS) of these 3 categories was 75.4% vs. 79.8% vs. 66.4%, respectively (p=0.1197). Due to superimposable outcome, LODneg and LODpos-LOQneg categories were combined. Two-year OS of LODneg/LODpos- LOQneg patients was 77.0% versus 66.4% of LOQpos individuals (P=0.043). Such a figure was challenged in multivariate analysis (p=0.048, HR 0.628, 95% CI 0.396-0.997) that confirmed the independent role of LOD-LOQ approach in influencing OS. In the AML1310 protocol, using the threshold of 0.035%, 2-year OS of MRD<0.035% and MRD≥0.035% patients was 74.5% vs. 66.4%, respectively (p=0.3521). In conclusion, the use of LOD-LOQ method results in a more sensitive detection of MRD that, in turn, translates in a more accurate recognition of patients with different outcome

Predictors of Early Thrombotic Events in Adult Patients with Acute Myeloid Leukemia: A Real-World Experience

Information regarding the incidence and the prognostic impact of thrombotic events (TE) in non-promyelocytic acute myeloid leukemia (AML) is sparse. Although several risk factors associated with an increased risk of TE development have been recognized, we still lack universally approved guidelines for identification and management of these complications. We retrospectively analyzed 300 consecutive patients with newly diagnosed AML. Reporting the incidence of venous TE (VTE) and arterial TE (ATE) was the primary endpoint. Secondarily, we evaluated baseline patient- and disease-related characteristics with a possible influence of VTE-occurrence probability. Finally, we evaluated the impact of TE on survival. Overall, the VTE incidence was 12.3% and ATE incidence was 2.3%. We identified three independent predictors associated with early-VTE: comorbidities (p = 0.006), platelets count >50x10e9/L (p = 0.006), and a previous history of VTE (p = 0.003). Assigning 1 point to each variable, we observed an overall cumulative incidence of VTE of 18.4% in the high-risk group (>2 points) versus 6.4% in the low-risk group (0–1 point), log-rank = 0.002. Overall, ATE, but not VTE, was associated with poor prognosis (p < 0.001). In conclusion, TE incidence in AML patients is not negligible. We proposed an early-VTE risk score that could be useful for a proper management of VTE prophylaxis

Current Challenges in Fostering the European Innovation Ecosystem

The present report discusses innovation challenges under the following headings: The 3% R&D target and industrial structure: is it still a relevant goal? if we cannot achieve the 3% target, does it make sense to keep it? Technology diffusion: how can we combat its sluggishness and speed up adoption? Access to finance: is the large amount of liquidity being funnelled to "zombie" companies instead of highly innovative ones? Universities and skills: are higher education institutions adequately playing their role in driving innovation? The governance of the R&I system: how to remove administrative barriers and increase flexibility? Can SSH research contribute more to shaping R&I policies?JRC.B.7-Knowledge for Finance, Innovation and Growt

FEVER OF UNKNOWN ORIGIN AND MULTIDRUG-RESISTANT ORGANISMS COLONIZATION IN AML PATIENTS.

Abstract. Background: Colonization by multidrug-resistant organisms (MDRO) is a frequent complication in hematologic departments, which puts patients at risk of life-threatening bacterial sepsis. Fever of unknown origin (FUO) is a condition related to the delivery of chemotherapy in hematologic malignancies, in which the use of antibiotics is debated. The incidence, risk factors, and influence on the outcome of these conditions in patients with acute myeloid leukemia (AML) are not clearly defined. Methods: We retrospectively analyzed 132 consecutive admissions of non-promyelocytic AML patients at the Hematology Unit of the University Tor Vergata in Rome between June 2019 and February 2022. MDRO swab-based screening was performed in all patients on the day of admission and once weekly after that. FUO was defined as fever with no evidence of infection. Results: Of 132 consecutive hospitalizations (69 AML patients), MDRO colonization was observed in 35 cases (26%) and resulted independently related to a previous MDRO colonization (p=0.001) and length of hospitalization (p=0.03). The colonization persistence rate in subsequent admissions was 64%. MDRO-related bloodstream infection was observed in 8 patients (23%) and correlated with grade III/IV mucositis (p=0.008) and length of hospitalization (p=0.02). FUO occurred in 68 cases (51%) and correlated with an absolute neutrophilic count <500μ/L at admission (0.04). Conclusion: In our experience, MDRO colonization is a frequent and difficult-to-eradicate condition that can arise at all stages of treatment. Prompt discharge of patients as soon as clinical conditions allow could limit the spread of MDRO. In addition, the appropriate use of antibiotics, especially in the case of FUO, and the contraction of hospitalization length, when feasible, are measures to tackle the further spread of MDRO

Special rationally connected manifolds

We consider smooth complex projective varieties X which are rationally connected by rational curves of degree d with respect to a fixed ample line bundle L on X, and we focus our attention on conic connected manifolds (d=2) and on rationally cubic connected manifolds (d=3). Conic connected manifolds were studied by Ionescu and Russo; they considered conic connected manifolds embedded in projective space (i.e. L is very ample) and they proved a classification theorem for these manifolds. We show that their classification result holds true assuming just the ampleness of L. Moreover we give a different proof of a theorem due to Kachi and Sato; this result characterizes a special subclass of conic connected manifolds. As already said before, we study also rationally cubic connected manifolds. We prove that if rationally cubic connected manifolds are covered by “lines”, i.e. by curves of degree 1 with respect to L, then the Picard number of X is equal to or less than 3; moreover we show that if the Picard number is equal to 3 then there is a covering family of “lines” whose numerical class spans a negative extremal ray of the Kleiman-Mori cone of X. Unfortunately, for rationally cubic connected manifolds which don't admit a covering family of “lines” there isn't an upper bound on the Picard number. However we prove that if we consider rationally cubic connected manifolds which are not covered by “lines” but are Fano then up to a few exceptions in dimension 2 also the Picard number of these manifolds is equal to or less than 3. In particular, supposing that the dimension of X is greater than 2, we show that either the Picard number is equal to or less than 2 or X is the blow up of projective space along two disjoint subvarieties that are linear subspaces or quadrics