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T1 Magnetization Prepared Two Rapid Acquisition Gradient Echo (MP2RAGE) with compress sensing (CS) has been proposed as an improvement of the standard MPRAGE sequence with multiple advantages including reduced acquisition time needed to provide a quantitative 3D anatomical image coupled with T1-map. Here we investigated the agreement between FreeSurfer-derived volume measurements obtained from MPRAGE and CS MP2RAGE acquisitions.MPRAGE and CS MP2RAGE images of 37 subjects (14 patients with neurodegenerative disorders and 23 healthy controls) were acquired on a 3 T MR scanner and grey matter volumes were extracted using standard FreeSurfer parcellation. Lin's concordance correlation coefficient (Lin's CCC), Bland-Altman analysis, Passing-Bablok regression and DICE similarity coefficient were calculated to assess the agreement between the two.We found a good correspondence for most of the regions examined, with 93.5 % of them showing a mean DICE index0.70. Poorer results were found with Lin's CCC especially for subcortical labels across patients. The Bland-Altman analysis showed CS MP2RAGE tended to measure lower cortical volumes compared to MPRAGE but in most cases the difference wasn't statistically relevant. The Passing-Bablock regression indicated overall an absence of systematic constant and proportional bias when CS MP2RAGE was used instead of MPRAGE.We found a good concordance for volumes obtained from MPRAGE and CS MP2RAGE images using FreeSurfer, suggesting a possible role of CS MP2RAGE for structural analysis with significant advantages like shorter acquisition time and the possibility to simultaneously obtain quantitative T1-maps of the brain enriching the diagnostic power of this technique.

Randomised controlled trials (RCTs) with systemic therapies for patients with pre-treated mesothelioma have reported equivocal efficacy results and generated a degree of clinical uncertainty about the choice of active treatment in this poor prognosis malignancy.To compare the effectiveness and safety and weigh the benefit of different systemic treatments in patients with pre-treated mesothelioma by systematic review, meta-analysis and network meta-analysis of RCTs. Full-text articles and abstracts were searched on PubMed, EMBASE, Cochrane Library and oncology conferences proceedings from 2005 through November 2021 for phase 2 and 3 RCTs. The protocol was submitted to the PROSPERO registry. Reporting followed the PRISMA guideline. Outcomes of interest were overall survival (OS) and progression-free (PFS), grade ≥3 treatment-related (Tr) adverse events (AEs), Tr-deaths and Tr-AEs leading to treatment discontinuation.Nine trials at low risk of bias by Cochrane Collaboration's methodology were included, encompassing 2789 patients. Five studies showed PFS benefit in the experimental treatment. In two studies, OS was prolonged by immunotherapy (versus placebo) or by adding an antiangiogenic agent to chemotherapy. Reported Tr-AE were lower with single-agent anti-PD1 compared with chemotherapy or placebo. The meta-analysis revealed a beneficial global effect on OS and PFS from experimental treatments (HR 0.86, 95% CI 0.77-0.96, p = 0.0083 and HR 0.79, 95% CI 0.72-0.86, p 0.001), that for the PFS significantly favoured the comparison with non-active treatments (HR 0.73, 95% CI 0.66-0.81, p 0.001). Younger patients (i.e. 65-70 years) appeared to benefit the most in OS (HR 0.71, 95% CI 0.55-0.92, p = 0.04). The risk of serious Tr-AEs and Tr-deaths was not significantly increased by experimental treatments (RR 1.38, 95% CI 0.81-2.35, p = 0.24 and RR 2.07, 95% CI 0.69-6.24, p = 0.19, respectively) that instead increased TrAEs leading to treatment discontinuation (RR 2.9, 95% CI 1.44-6.08, p = 0.003). The network meta-analysis did not identify any superior treatment in PFS.For patients with pre-treated MPM, single-agent anti-PD1 or chemotherapy ± the antiangiogenic agent can be considered active and safe systemic therapeutic options, particularly for younger patients.

Background Biologic therapy for psoriasis is effective but not always long-lasting and sometimes needs to be switched. Objective We aimed to evaluate the drug survival (ie, the time from initiation to discontinuation) of each biologic and the factors affecting survival to identify better switching strategies and improve drug survival. Methods In total, 195 psoriasis patients treated in our unit during 2006-2018 were retrospectively observed. Descriptive statistical analyses and logistic regression models were performed. Kaplan–Meier survival curves and multivariate Cox models adjusted for confounding variables were used to estimate and compare drug survival. Results Overall, 90.6% of patients achieved an ≥75% reduction in their baseline Psoriasis Area and Severity Index score. In 2018, the most frequently used biologic was ustekinumab (47/169, 27.8%). Patients with higher baseline Psoriasis Area and Severity Index scores were more likely to be switched (P = .0399, odds ratio 1.08). In naive patients, ustekinumab showed longer drug survival (>7.0 years), but in biologic-experienced patients, we found no significant differences in drug survival. Previous biologic therapies increased the need for switching (P = .014, hazard ratio 1.20). Switching between biologic classes yielded longer drug survival than switching within biologic classes (P = .003, hazard ratio 0.48). Limitations As a single-center, retrospective real-life study, the data were not perfectly homogeneous. Conclusion Switching between biologic classes might increase drug survival but retrospective studies designed ad hoc are needed to confirm this better switching strategy.

Objective To evaluate inter- and intra-rater reliability of background parenchymal enhancement (BPE) assessment across breast MRI sequences. Materials and methods Institutional review board approval was obtained and the requirement for consent was waived. Three radiologists qualitatively categorized BPE on 150 breast MRI using a four-point scale (minimal, mild, moderate or marked) according to BI-RADS category system. According to MR-sequence used for the assessment of BPE, inter-rater and intra-rater reliability across a simulated reading strategy with four options was performed: (1) initial contrast-enhanced (CE) fat-suppressed T1-weighted images (2) initial CE subtracted images (3) maximum-intensity-projection (MIP) of the first CE subtracted images (4) combination of initial CE fat-suppressed T1-weighted, initial CE subtracted and MIP images. Raters repeated BPE assessment of 45 breast MRI four weeks after the initial assessment. Gwet’s AC1 index with ordinal weights was used to assess reliabilities. Results Gwet’s index for the reliability among the three raters was 0.68 (0.63-0.74) using initial contrast-enhanced fat-suppressed T1 weighted images, 0.74 (0.69-0.80) using subtracted images, 0.80 (0.76-0.83) using MIP, 0.80 (0.77-0.84) using a combination of the initial contrast-enhanced fat-suppressed T1 weighted, initial contrast-enhanced subtracted and MIP images. Test-retest reliability was 0.81 (0.60–1.00) for rater 1, 0.77 (0.55-0.98) for rater 2, 0.79 (0.59-0.99) for rater 3 using the combination of initial contrast-enhanced fat-suppressed T1 weighted, initial contrast-enhanced subtracted and MIP images. Conclusions Overall, the combination of all CE MRI images showed the highest reliability of BPE assessment. However, MIP showed a high reliability with lower reading time compared to the combination of all CE MRI images.

Introduction: Early studies have shown that patients with chronic kidney disease (CKD) are able to maintain nitrogen balance despite significantly lower protein intake, but how and to what extent muscle protein metabolism adapts to a low-protein diet (LPD) or to a supplemented very LPD (sVLPD) is still unexplored. Methods: We studied muscle protein turnover by the forearm perfusion method associated with the kinetics of 2H-phenylalanine in patients with CKD: (i) in a parallel study in subjects randomized to usual diet (1.1 g protein/kg, n = 5) or LPD (0.55 g protein/kg, n = 6) (Protocol 1); (ii) in a crossover, self-controlled study in subjects on a 0.55 g/kg LPD followed by a sVLPD (0.45 g/kg + amino/ketoacids 0.1 g/kg, n = 6) (Protocol 2). Results: As compared with a 1.1 g/kg containing diet, a 0.55 g/kg LPD induced the following: (i) a 17% to 40% decrease in muscle protein degradation and net protein balance, respectively, (ii) no change in muscle protein synthesis, (iii) a slight (by approximately 7%, P < 0.06) decrease in whole-body protein degradation, and (iv) an increase in the efficiency of muscle protein turnover. As compared with an LPD, an sVLPD induced the following: (i) no change in muscle protein degradation, and (ii) an approximately 50% decrease in the negative net protein balance, and an increase in the efficiency of muscle protein turnover. Conclusion: The results of these studies indicate that in patients with CKD the adaptation of muscle protein metabolism to restrained protein intake can be obtained via combined responses of protein degradation and the efficiency of recycling of amino acids deriving from protein breakdown. Keywords: amino acids, chronic kidney disease, ketoacids, low-protein diet, nutrition

We studied the impact of HLA mismatching on the outcome of 318 consecutive patients who received an unmanipulated haploidentical bone marrow transplant, followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched antigens was tested for its impact on overall survival (OS) and nonrelapse mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction were tested for prediction of graft-versus-host disease (GVHD and relapse. Finally, we studied whether graft rejection correlated with the number of HLA mismatched antigens in host-versus-graft (HVG) direction. Two hundred thirty-one donor–recipient pairs (72%) had 4/8 mismatches at the -A, -B, -C, -DRB1 HLA loci. HLA mismatches did not predict the 2-year OS (hazard ratio, .83; P = .58) and NRM (subhazard ratio, 1.08; P = .93). The cumulative incidence of acute GVHD (P = .13), 1-year chronic GVHD (P = .84), and relapse rate (P = .26) did not correlate with univectorial GVH mismatches. Similarly, no correlation was observed between the amount of HLA mismatch in the HVG direction and graft rejection. In multivariate analysis advanced disease at transplant was the strongest predictor of survival, NRM, relapse, and graft rejection. In conclusion, the degree of HLA mismatching should not be used as a criterion to select family haploidentical donors when using bone marrow as stem cell source and PTCy for GVHD prophylaxis.

Background: To minimize the risk of Progressive Multifocal Leukoencephalopathy and rebound in JCV-positive multiple sclerosis (MS) patients after 24 natalizumab doses, it has been proposed to extend the administrations interval. The objective is to evaluate the EID efficacy on MRI activity compared with the standard interval dosing (SID). Methods: Observational, multicentre, retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Three hundred and sixteen patients were enrolled. The median dose interval (MDI) following the 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Patients were grouped into 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Results: One hundred and eighty-seven patients were in the SID group (MDI = 4.5 weeks) and 129 in the EID group (MDI 6.1 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 4.27% (95% CI:0.84–7.70) vs 4.71% (95% CI:0.16–9.25%) [p = 0.89] and 8.50% (95% CI:4.05–12.95) vs 6.55% (95% CI:2.11–11.00%) [p = 0.56]. The EID regimen does not appear to increase the occurrence of MRI activity during follow-up. Conclusion: There is no evidence of the reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation supports the need for a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, to better manage JCV-positive patients.

Purpose To estimate sensitivity and specificity of CESM for breast cancer diagnosis. Methods Systematic review and meta-analysis of the accuracy of CESM in finding breast cancer in highly selected women. We estimated summary receiver operating characteristic curves, sensitivity and specificity according to quality criteria with QUADAS-2. Results Six hundred four studies were retrieved, 8 of these reporting on 920 patients with 994 lesions, were eligible for inclusion. Estimated sensitivity from all studies was: 0.98 (95% CI: 0.96–1.00). Specificity was estimated from six studies reporting raw data: 0.58 (95% CI: 0.38–0.77). The majority of studies were scored as at high risk of bias due to the very selected populations. Conclusion CESM has a high sensitivity but very low specificity. The source studies were based on highly selected case series and prone to selection bias. High-quality studies are required to assess the accuracy of CESM in unselected cases.

We studied 459 consecutive patients with hematologic malignancies, median age 44 years (range, 15 to 71 years), who underwent transplantation with grafts from identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43), mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105) or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the HAPLO recipients. Conditioning regimens were mostly myeloablative (69%). Advanced disease phase was more frequent, but not significantly so, in the HAPLO and mmUD groups (P = .08). Acute GVHD grade II-IV was significantly less frequent in the HAPLO, UCB, and MUD groups (14% to 21%) compared with the SIB (31%) and mmUD (42%) groups (P

Introduction The purpose of this study was to evaluate the correlations between bone characteristics, orthodontic miniscrew designs, and primary stability. Methods Four different miniscrews were placed in pig ribs. The miniscrews were first scanned with a scanning electron microscope to obtain measurable images of their threads. Subsequently, the maximum insertion torque of the screws and the maximum load value in the pullout force tests were measured; furthermore, bone specimen characteristics were analyzed by using cone-beam computed tomography. For each bone sample, the insertion site cortical thickness as well as both cortical and marrow bone density were evaluated. The nonparametric Kendall rank correlation (tau) was used to evaluate the strength of the associations among the characteristics measured. The nonparametric Kruskall-Wallis test was used to evaluate the differences among the groups, and post-hoc comparisons were assessed by using the Nemenyi-Damico-Wolfe-Dunn test. Results A significant dependence was found between pitch and maximum insertion torque (tau, −0.49). Positive correlations were also found between pullout force and maximum insertion torque (tau, 0.64), cortical thickness (tau, 0.36), and marrow bone density (tau, 0.35). Conclusions In this in-vitro experimental study, strong correlations were observed among miniscrew geometry, bone characteristics, and primary stability.

Objective Nasal obstruction is a common symptom in childhood. It may be frequently observed in children with allergic rhinitis and/or adenoidal hypertrophy. However, its assessment is very difficult. The aim of the study was to compare the use of both a Face Related Scale (FRS), recorded by children and their parents, and a simplified Visual Analogue Scales (sVAS) with nasal endoscopy in children complaining nasal obstruction. Methods 121 children (75 males, mean age 7.5 years) were studied. FRS and sVAS for nasal obstruction and endoscopy were performed in all patients. Results A moderate correlation has been observed between FRS and sVAS and obstruction of nasal anterior segment (r = 0.51 for FRS; r = 0.52 for sVAS), a strong correlation was observed with nasal posterior segment (r = 0.60 for FRS; r = 0.61 for sVAS) assessed by endoscopy. However, parents’ perception did not relate with objective parameters. Conclusions This study suggests that assessment of FRS and sVAS for nasal obstruction may be used in clinical practice to approximately quantify this symptom in children.