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Background: Human Cytomegalovirus (HCMV) is still one of the major concerning infection in hematopoietic stem cell transplant (HSCT) recipients. Letermovir (LTV) has been recently introduced for HCMV prophylaxis in adult patients who received allogeneic HSCT. However, many aspects related to immune reconstitution need to be further explored. The aim of this study was to define the prognostic role of HCMV-specific T-cell frequency measured at the end of LTV prophylaxis in predicting the risk for clinically significant HCMV infection (i.e. infection requiring antiviral treatment) after the stop of the prophylaxis., Methods: Sixty-six adult patients who underwent allogeneic HSCT were enrolled and HCMV DNAemia was prospectively monitored. Additionally, HCMV-specific T-cell response was evaluated using ELISpot assay against two different antigens (HCMV infected cell lysate and pp65 peptide pool)., Results: Ten patients (15.2%) developed at least one positive HCMV DNAemia episode during LTV prophylaxis, whereas 50/66 (75.8%) patients developed at least one positive HCMV DNA event after LTV prophylaxis. Of note, 25 of them (50%) experienced a clinically significant HCMV infection. The median HCMV-specific T-cell response measured against HCMV lysate but not against pp65 peptide pool was lower in patients who developed HCMV clinically significant infection after prophylaxis. A ROC analysis revealed that the level of 0.04 HCMV-specific T cells/µl should be used as cut-off for development of clinically significant HCMV reactivation after prophylaxis., Conclusion: Assessment of HCMV-specific immunity upon discontinuation of universal prophylaxis with LTV should be considered as a method for identification of patients at risk for clinically significant HCMV infection., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2023. Published by Elsevier B.V.)

Purpose: Infections caused by ESBL-producing Enterobacteriaceae (ESBL-EB) are a major health problem, but data regarding elderly patients is lacking., Methods: We performed a retrospective observational study quantifying the effects of antimicrobial treatment and primary infection site on clinical outcomes in an historical case series of 42 patients aged 80.7±10years admitted to an Internal Medicine ward in Italy for ESBL-EB bloodstream infections (BSI)., Results: At multivariate risk analysis, we found that urinary tract as primary infection site (RR=0.181 [0.037-0.886], p=0.035) and definitive antibiotic therapy (RR=0.517 [0.147-0.799], p=0.038) decreased the relative risk of a negative clinical response, while the respiratory tract origin increased the relative risk (RR=2.788 [1.407-9.228], p=0.025). Also regarding 30days mortality, multivariate risk analysis identified that urinary tract as primary infection site (RR=0.098 [0.011-0.743], p=0.025) and definitive antibiotic therapy (RR=0.236 [0.058-0.961], p=0.044) decreased the relative risk, while the respiratory origin increased the relative risk (RR=4.241 [1.040-17.295], p=0.014). We observed similar outcomes in patients definitively treated with carbapenems or with carbapenem-free treatments. Additionally, an initially inappropriate therapy did not correlate with worse outcomes if a switch to an effective definitive treatment was performed promptly., Conclusions: Carbapenem-sparing regimens (e.g. piperacillin-tazobactam alone or with an aminoglycoside) could be empirically safely used in elderly patients at high risk of ESBL-EB BSI and for definitive treatment of ascertained cases if the primary site is the urinary tract, leaving early carbapenem use for cases at higher risk of death, such as those with pneumonia., (Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

A novel MRI blood-pool contrast agent (Gd-AAZTA-MADEC) has been compared with established blood pool agents for tumor contrast enhanced images and angiography. Synthesis, relaxometric properties, albumin binding affinity and pharmacokinetic profiles are reported. For in vivo studies, angiographic images and tumor contrast enhanced images were acquired on mice with benchtop 1T-MRI scanners and compared with MS-325, B22956/1 and B25716/1. The design of this contrast agent involved the elongation of the spacer between the targeting deoxycholic acid moiety and the Gd-AAZTA imaging reporting unit that drastically changed either the binding affinity to albumin (KA(HSA) = 8.3 × 10(5) M(-1)) and the hydration state of the Gd ion (q = 2) in comparison to the recently reported B25716/1. The very markedly high binding affinity towards mouse and human serum albumins resulted in peculiar pharmacokinetics and relaxometric properties. The NMRD profiles clearly indicated that maximum efficiency is attainable at magnetic field strength of 1 T. In vivo studies showed high enhancement of the vasculature and a prolonged accumulation inside tumor. The herein reported pre-clinical imaging studies show that a great benefit arises from the combination of a benchtop MRI scanner operating at 1 T and the albumin-binding Gd-AAZTA-MADEC complex, for pursuing enhanced angiography and improved characterization of tumor vascular microenvironment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The investigation of new Mn(II)-based MRI/Molecular Imaging probes responsive to the enzyme tyrosinase for potential diagnostic applications is herein described. The expression of the enzyme tyrosinase, an oxidoreductase, is up-regulated in melanoma cancer cells. Three novel ligands (L(1), L(2) and L(3)) were designed as modified acyclic polyaminocarboxylate chelates by introducing an l-tyrosine residue in place of an aminoacetate unit. The corresponding Mn(II) complexes were fully characterised by (1)H NMR relaxometric techniques in aqueous media. The responsive activity towards the expression of tyrosinase was then assessed by monitoring the (1)H 1/T(1) relaxivity changes during incubation experiments in buffered solutions containing tyrosinase at different concentrations and in B16F10 melanoma cell homogenate. New insight on the mechanism of action of these systems was gained by measuring the magnetic field dependence of the relaxivity and ESR spectra of the incubated solutions. The systems developed showed responsive activity to tyrosinase with a relaxation enhancement spanning from 50% (MnL(1)) to 350% (MnL(3)) which augurs well for the development of diagnostic probes to detect melanoma cancer., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The field of molecular imaging aims to visualize and quantify (patho)physiological processes at the cellular and molecular level. Sensitive and site-targeted contrast agents are employed to visualize molecular constituents of processes of interest. The principal aim of this study was to develop a magnetic resonance imaging (MRI) detectable liposome with high relaxivity and stability. To this end, Gd(III)DOTA-DSPE was synthesized and incorporated in a liposomal formulation. The resulting liposomes were extensively characterized in vitro in terms of contrast agent efficiency and structural properties. The liposomes were shown to have a high longitudinal relaxivity, which is crucial for the detection of low concentration molecular markers in molecular imaging studies. We also demonstrated that Gd(III)DOTA-DSPE exhibits no detectable transmetallation upon incubation with Zn(II). This is important as it significantly contributes to the biocompatibility of the contrast agent. The present liposome preparation will serve as versatile and well characterized platform for molecular imaging and targeted drug delivery studies.

Objectives: To investigate the immunoexpression of aquaporin-1 (AQP-1), a major transmembrane water channel, in high-grade varicocele testes, which are known to imply an unbalanced transmembrane water flow, in both tubular and extratubular compartments., Methods: Light microscopy and AQP-1 immunohistologic examination were carried out on incisional testicular biopsies from 20 adolescent boys, aged 13 to 18 years, with grade 2 or 3 idiopathic varicocele. Testicular tissue from 4 autopsied subjects of matched age were also investigated as parallel controls., Results: At microscopic examination, the tubular lumina and extracellular matrix were expanded and venular profiles dilated. Cytoplasmic vacuoles were frequent in the Sertoli cells, spermatogonia, and spermatocytes, together with premature sloughing of germ cells and residual cytoplasmic droplets inside the spermatozoa, if present. Diffuse AQP-1 positivity occurred at venular endothelial cell membranes and, unexpectedly, at the cell membranes of the Sertoli cells, diploid germ cells, and haploid cells. In the control testes, focal AQP-1 immunolabeling was confined to the microvessel endothelial cells, without any positive reaction in the tubular or extratubular compartments., Conclusions: This is the first report showing AQP-1 cell expression in adolescent varicocele testes in both tubular and extratubular compartments. It was associated with the main histologic features of unbalanced water flow in the tubular and interstitial compartments of the testis. Immunocytochemical patterns revealed AQP-1 as a possible critical reabsorption factor, acting to reduce abnormal fluid retention in endotubular cells and the extracellular matrix and, to a lesser extent, in Leydig cells.

A rare case of primary penile B cell non-Hodgkin's lymphoma is reported. We reported on 75-year-old man with primary penile lymphoma with consideration of the diagnosis and the various therapeutic approaches. We treated this case with local radiotherapy and systemic chemotherapy with good cosmetic and functional results. There was absence of recurrence 42 months after therapy.

Objective: Different etiopathological mechanisms of enuresis are today under study, and different therapies and drugs have been proposed. The Italian Multicentric Trial was undertaken in twelve pediatric and urological centers in order to assess the efficacy of two of the most popular drugs, desmopressin (DDAVP) and oxybutynin., Methods: 114 enuretic patients were enrolled in the study. After a 2-week observation period, 66 patients with primary monosymptomatic enuresis were treated with DDAVP, 30 micrograms/day intranasally, for 6 weeks, 48 patients with enuresis and voiding dysfunction were randomly assigned to a protocol with oxybutynin alone or oxybutynin plus DDAVP. The efficacy of the two drugs was measured in terms of reduction of wet nights per week during the 6-week treatment period and a 2-week follow-up period. Children with 0-3 dry nights/week were considered as nonresponders., Results: Patients with monosymptomatic enuresis treated with DDAVP reported a significantly lower number of wet night during treatment than during the baseline period, with 79% showing a 'good' (6-7 dry nights/week) or 'intermediate' response (4-5 dry nights/week). Of the patients with diurnal voiding disturbances and enuresis, those treated with oxybutynin alone had a 54% success rate. The patients treated with both oxybutynin and DDAVP showed a better response, with a 71% rate of success., Conclusions: The efficacy of the two drugs is confirmed in patients carefully selected on the clinical basis of voiding disturbances. In patients with enuresis and voiding dysfunction, the reduced urinary output and the lower bladder filling rate due to DDAVP can reduce uninhibited bladder contractions, thus enhancing the oxybutynin action.