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Splanchnic vein thrombosis (SVT) is a potentially life-threatening complication of liver cirrhosis. This study aimed to evaluate the impact of a multi-disciplinary approach and early anticoagulation therapy (AT) on bleeding/thrombotic events, recanalization rates and outcome of cirrhotic patients with SVT. This is a single-center, registry-based cohort study. Over 17 years, 149 SVT patients were enrolled and prospectively evaluated. Regarding cirrhotic-SVT, a pre-specified algorithm, guiding initial posology of AT and follow-up visits schedule, was performed. Major bleeding (MB), thrombotic events, functional liver scores and all cause-mortality were investigated. Efficacy of AT was evaluated by radiological imaging. In cirrhotic-SVT, the incidence rate of MB was 8.4 per 100 patient-year (95% CI, 3.83-15.97), while the incidence rate of thrombosis was 5.6 per 100 patient-year (95% CI, 2.05-12.2). In incidental SVT treated with AT, MB incidence was 6.5 per 100 patient-year (95% CI: 2.8-12.82), while in symptomatic SVT was 2.2 per 100 patient-year (95% CI: 0.25-8.02). All thrombotic recurrences occurred in incidental SVT (7.7 per 100 patient-years; 95% CI, 3.71-14.26). Overall survival was significantly higher in patients who had at least a partial recanalization (p < 0.01) and partial/total recanalization was independently associated with improved MELD score at multivariate analysis (HR 2.62, 95% CI 1.1-6.47, p = 0.03). In cirrhotic SVT patients, partial or total resolution of thrombosis ameliorates liver function and is associated with higher overall survival. A multidisciplinary approach together with radiological follow-up at pre-fixed time improves patient selection and monitoring.

The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS). The availability of techniques such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment allowed the design of MRD-based response-adjusted trials that will define, in particular, the role of consolidation and maintenance therapies. In this review, we will provide an overview of the most recent evidence and the future prospects of ASCT in MM patients.

The present study was aimed to investigate the relationships between thyroid stimulating hormone (TSH), freeT3 (fT3) and freeT4 (fT4) and brain glucose consumption as detectable by means of 2-deoxy-2-(F-18) fluoro-D-glucose (F-18 FDG) Positron Emission Tomography/Computed Tomography (PET/CT) in a selected population with Alzheimer disease (AD). We evaluated 87 subjects (37 males and 50 females, mean age 70 (±6) years old) with AD. All of them were subjected to TSH, fT3 and fT4 assay and to cerebrospinal fluid amyloid (Aβ1-42) and tau [phosphorylated-tau (p-tau) and total-tau (t-tau)] assay prior PET/CT examination. Values for TSH, fT3 and fT4 were in the normal range. The relationships were evaluated by means of statistical parametric mapping (SPM8) using age, sex, MMSE, scholarship and CSF values of amyloid and tau as covariates. We found a significant positive correlation between TSH values and cortical glucose consumption in a wide portion of the anterior cingulate cortex bilaterally (BA32) and left frontal lobe (BA25) (p FWE-corr <0.001; p FDRcorr <0.000; cluster extent 66950). No significant relationships were found between cortical F-18 FDG uptake and T3 and T4 serum levels. The results of our study suggest that a cortical dysfunction in anterior cingulate and frontal lobes may affect serum values of TSH in AD patients.

Introduction : few studies so far have attempted to validate the ELN risk stratification in a «real life» setting. Moreover the prognostic role of NPM1 mutation in several subsets of patients is still controversial. Although post-induction MRD has a well defined prognostic role, there are few to no data about its relationships with ELN risk stratification. Material and methods :Our retrospective study included a total of 608 AML patients treated at our institute between 1997 and 2019. Mutation testing was performed in all patient with suitable bone marrow or peripheral blood specimen. All the patients were assigned to ELN 2017 risk class according their genetics. Results : ELN 2017 classification effectively stratified AML patients treated with intensive chemotherapy (p<0.01) but it wasn't able to predict outcome in AML patients aged >65 years old (p=0.25). Within the class of ELN 2017 favorable genetic risk, NPM+ AML had a significantly worse outcome, in terms of OS and EFS, compared to CBF AML (p<0.01). Post-induction MRD had a significant prognostic impact only regarding intermediate (p=0.04) and high (p=0.04) ELN risk class, while its effects was neglegible (p=0.56) regarding favorable ELN risk class. Conclusions : although ELN2017 risk stratification offers a validated prognostic significance in AML patients treated with intensive chemotherapy, it could be amendable with patient- and treatment- factors.

FLT3 ITD and TKD mutations occur in 20% and 10% of Acute Myeloid Leukemia (AML), respectively, and they represent the target of the first approved anti-leukemic therapies in the 2000s. Type I and type II FLT3 inhibitors (FLT3i) are active against FLT3 TKD/ITD and FLT3 ITD mutations alone respectively, but they still fail remissions in 30–40% of patients due to primary and secondary mechanisms of resistance, with variable relapse rate of 30–50%, influenced by NPM status and FLT3 allelic ratio. Mechanisms of resistance to FLT3i have recently been analyzed through NGS and single cell assays that have identified and elucidated the polyclonal nature of relapse in clinical and preclinical studies, summarized here. Knowledge of tumor escape pathways has helped in the identification of new targeted drugs to overcome resistance. Immunotherapy and combination or sequential use of BCL2 inhibitors and experimental drugs including aurora kinases, menin and JAK2 inhibitors will be the goal of present and future clinical trials, especially in patients with FLT3-mutated (FLT3mut) AML who are not eligible for allogeneic transplantation.

Background Infections remain a leading cause of morbidity and mortality among liver transplant (LT) recipients. The aim of our study was to define the factors associated with outcome of early bacterial and fungal infections in a cohort of patients who underwent LT at the University Hospital of Ancona over a nine year period. Methods All consecutive patients who underwent LT in our center were considered. An early infection was defined as occurring in the first month post-transplantation. Results Among 330 patients who underwent LT from August 2005 to October 2014, 88 (27 %) had at least one infection documented within 30 days after transplantation. In 54 cases only one site was involved, in 34 cases ≥2 sites. There were 43 (30 %) pneumonia, 40 (27 %) surgical site infections, 31 (22 %) blood stream infections, and 30 (21 %) urinary tract infections. Gram-negative bacteria accounted for 64 % of the culture-positive cases, followed by Gram-positive bacteria (30 %) and fungi (6 %). A high proportion of drug-resistant strains was found within either Gram-negative (79 %) or Gram-positive (81 %) bacteria. There were 27 out 88 patients (31 %) who died within 180 days from the transplant. Factors independently associated with a higher risk of mortality were: renal replacement therapy (HR 11.797 [CI95 % 3.082–45.152], p  < 0.0001), multisite infections (HR 4.865 [CI95 % 1.417–16.700], p  = 0.012) and being infected with carbapenem-resistant Klebsiella pneumoniae (CRKP; HR 5.562 [CI95 % 1.186–26.088], p  = 0.030). Conclusions Overall, these data indicate that early infections in LT patients are characterized by significant mortality. In particular, an early infection caused by CRKP has an adverse impact on survival in these patients suggesting an urgent need for adopting preventive measures to avoiding this complication.

Purpose To investigate the relationships among cerebrospinal fluid (CSF) levels of t-Tau, p-Tau and Aβ 1-42 amyloid peptide and 123 I-FP-CIT uptake. Methods The study included 58 subjects (31 men and 27 women, age 67 ± 9 years) with a clinical diagnosis of Parkinson disease diagnosed according to the United Kingdom Parkinson Disease Society Brain Bank criteria. All subjects underwent a CSF assay 28 ± 3 days before 123 I-FP-CIT SPECT scanning. The relationships were evaluated by means of linear regression analysis and Pearson correlation. Results Striatal 123 I-FP-CIT was positively related to both t-Tau and p-Tau CSF values with low levels of t-Tau and p-Tau being related to a low uptake of 123 I-FP-CIT. In particular, differences with higher statistical significance were found for the striatum between the contralateral side and the side mainly affected on clinical examination ( P  < 0.001). No significant relationships were found between Aβ 1-42 amyloid peptide and 123 I-FP-CIT binding. Conclusion The results of our study suggest that the presynaptic dopaminergic system is more involved in Parkinson disease patients with lower t-Tau and p-Tau CSF values while values of Aβ 1-42 amyloid peptide seems not to be related to nigrostriatal degeneration in our series.

To investigate the relationships among cerebrospinal fluid (CSF) levels of t-Tau, p-Tau and A[beta]^sub 1-42^ amyloid peptide and ^sup 123^I-FP-CIT uptake. The study included 58 subjects (31 men and 27 women, age 67 ± 9 years) with a clinical diagnosis of Parkinson disease diagnosed according to the United Kingdom Parkinson Disease Society Brain Bank criteria. All subjects underwent a CSF assay 28 ± 3 days before ^sup 123^I-FP-CIT SPECT scanning. The relationships were evaluated by means of linear regression analysis and Pearson correlation. Striatal ^sup 123^I-FP-CIT was positively related to both t-Tau and p-Tau CSF values with low levels of t-Tau and p-Tau being related to a low uptake of ^sup 123^I-FP-CIT. In particular, differences with higher statistical significance were found for the striatum between the contralateral side and the side mainly affected on clinical examination (P<0.001). No significant relationships were found between A[beta]^sub 1-42^ amyloid peptide and ^sup 123^I-FP-CIT binding. The results of our study suggest that the presynaptic dopaminergic system is more involved in Parkinson disease patients with lower t-Tau and p-Tau CSF values while values of A[beta]^sub 1-42^ amyloid peptide seems not to be related to nigrostriatal degeneration in our series.[PUBLICATION ABSTRACT] Erratum DOI: 10.1007/s00259-014-2918-0