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Objective: To establish the precision of sonographic measurement of the thickness of the articular cartilage of the hip and knee in children.Design: The precision was assessed by evaluating the intra- and interobserver variations in sonographic measurements.Patients: A total of 65 healthy children were in the study. The articular cartilage of the right hip and knee of 40 subjects (mean age 10.3 years, range 4-16.9 years) was evaluated in masked fashion by two observers to assess the interobserver variability. The articular cartilage of the right hip and knee of 25 children (mean age 10.4 years, range 6.2-15.5 years) was examined twice by the same observer to assess the intraobserver variability.Results and Conclusions: Discrepancies between repeated measurements were expressed as data differences. The "limits of agreement" of data differences, i.e. the mean +2 SD and the mean -2 SD, ranged from -0.26 to +0.22 mm and from -0.56 to +0.48 mm for the interobserver analysis of the femoral head cartilage (FHC) and femoral condylar cartilage (FCC), respectively. The "limits of agreement" for the intraobserver analysis ranged from -0.16 to +0.15 mm and from -0.51 to +0.41 mm for the FHC and the FCC, respectively. The overall precision of the sonographic measurements was satisfactory. When used for determination of skeletal age, sonographic assessment of FHC thickness resulted in under/overestimation of skeletal age by about 7.5 months. In conclusion, sonographic measurement of articular cartilage is precise enough to be used in clinical practice. [ABSTRACT FROM AUTHOR]

The Patient Preference Survey aims to understand unmet needs related to riluzole management in people with Amyotrophic Lateral Sclerosis (ALS) and to identify which characteristics of a new formulation could better match their preferences. The survey involved 117 people with ALS (PALS) treated with riluzole in four European countries. The dysphagic PALS were least satisfied with the riluzole tablet and oral suspension and with ease in self-administration; up to 68% of respondents postponed or missed the treatment due to swallowing difficulties and need of caregiver assistance. Overall, 51% of tablet and 53% of oral suspension users regularly crushed or mixed riluzole with beverages, respectively; PALS who always manipulated riluzole showed low satisfaction with the formulation and considered the risk of choking and pneumonia the most worrisome event. The survey evaluated the driving factors in choosing/switching the therapy: 67% of PALS declared a low risk of choking. The research finally evaluated which attributes of a new formulation would be preferred: the most relevant were ease of use (4.3/5), convenient/portable packaging (4.0/5) and oral-dissolving properties without tongue motility (3.9/5). The Patient Preference Survey suggests that patients have several unmet needs and preferences that could be addressed by a different formulation, e.g. using oral film technologies., (© 2023. The Author(s).)

Purpose: The investigation of multiple molecular targets with next-generation sequencing (NGS) has entered clinical practice in oncology, yielding to a paradigm shift from the histology-centric approach to the mutational model for personalized treatment. Accordingly, most of the drugs recently approved in oncology are coupled to specific biomarkers. One potential tool for implementing the mutational model of precision oncology in daily practice is represented by the Molecular Tumor Board (MTB), a multidisciplinary team whereby molecular pathologists, biologists, bioinformaticians, geneticists, medical oncologists, and pharmacists cooperate to generate, interpret, and match molecular data with personalized treatments., Patients and Methods: Since May 2020, the institutional MTB set at Fondazione IRCCS Istituto Nazionale Tumori of Milan met weekly via teleconference to discuss molecular data and potential therapeutic options for patients with advanced/metastatic solid tumors., Results: Up to October 2021, among 1,996 patients evaluated, we identified >10,000 variants, 43.2% of which were functionally relevant (pathogenic or likely pathogenic). On the basis of functionally relevant variants, 711 patients (35.6%) were potentially eligible to targeted therapy according to European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets tiers, and 9.4% received a personalized treatment. Overall, larger NGS panels (containing >50 genes) significantly outperformed small panels (up to 50 genes) in detecting actionable gene targets across different tumor types., Conclusion: Our real-world data provide evidence that MTB is a valuable tool for matching NGS data with targeted treatments, eventually implementing precision oncology in clinical practice.

Background: Trial of Rivaroxaban in AntiPhospholipid Syndrome was a prospective randomized, open-label, noninferiority study conducted in 14 centers in Italy. Rivaroxaban was compared with warfarin for the prevention of thromboembolic events, major bleeding, and vascular death in high-risk, triple-positive patients with antiphospholipid syndrome., Objective: The aim of this paper is to report the events during the 2-year follow-up after the study closure., Methods: On January 28, 2018, the trial was prematurely stopped by adjudication and safety committee for an excess of events in the rivaroxaban group. Randomized patients were advised on trial results and those randomized to rivaroxaban were solicited to switch to warfarin. All 14 participating centers were asked and accepted to follow their patients for clinical events. This report describes the rate of events that occurred between January 28, 2018, and January 28, 2020., Results: Of 120 randomized patients, 115 were available for follow-up. Outcome events were two in six (33.3%) patients who remained on direct oral anticoagulants (DOACs) and six in 109 (5.7%) patients on warfarin (hazard ratio [HR] 6.9; 95% confidence interval [CI] 1.4-34.5, P = .018). The two patients on DOACs (one taking dabigatran and one taking rivaroxaban) suffered from thromboembolic events, whereas of the six patients with composite outcomes on warfarin, three had thromboembolic events (HR for thrombosis 13.3; 95% CI 2.2-79.9, P = .005)., Conclusion: These data further support the use of warfarin in high-risk patients with antiphospholipid syndrome., (© 2020 International Society on Thrombosis and Haemostasis.)

Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272., (© 2018 by The American Society of Hematology.)

Among the diagnostic assays for anti-phospholipid syndrome (APS), lupus anticoagulant (LA) is the strongest predictor of thrombosis; however, it presents several limitations as interference with anticoagulant therapy and poor inter-laboratory agreement. Two-thirds of LA activity is apparently due to antibodies against prothrombin (PT), usually detectable by ELISA. Binding of PT to phosphatidylserine (PS) has been shown to enhance solid-phase anti-PT assay sensitivity. To determine the prevalence of antibodies against PS/PT (aPS/PT) in APS, we tested the semiquantitative QUANTA Lite(®) aPS/PT ELISA in a cohort of 80 APS patients. The prevalence of aPS/PT was 81.3%, rising to 87.6% when considering LA-positive subjects only. We observed a strong correlation between aPS/PT and LA (p = 0.006). To note, APS patients with thrombotic manifestations displayed significantly higher IgG aPS/PT titers compared to 20 aPL asymptomatic carriers (p = 0.012). To rule out a possible cross-reactivity of anti-β2 glycoprotein I antibodies (aβ2GPI) with PS/PT complex, we tested two monoclonal aβ2GPI antibodies and an affinity-purified (AP) polyclonal aβ2GPI IgG obtained from the serum of a patient reacting against both β2GPI and PS/PT. The two monoclonal antibodies did not show any reactivity against PS/PT complex, similarly the AP IgGs did not react toward PS/PT antigen while preserved their aβ2GPI activity. Our findings suggest that aPS/PT are a definite antibody population in APS. Moreover, the good correlation between aPS/PT ELISA and LA may support its use as a surrogate test for LA, particularly useful to overcome the technical limitations of the functional assay.

Persistent antiphospholipid (aPL) antibodies are occasionally found in subjects without prior history of thromboembolic events (TEs), raising the dilemma of whether to initiate or not a primary thromboprophylaxis. A first TE is considered rare in aPL carriers, but previous studies did not consider the aPL profile nor was the test positivity confirmed in a reference laboratory. In this study, 104 subjects with high-risk aPL profile (positive lupus anticoagulant, anticardiolipin, and anti-β(2)-glycoprotein I antibodies, triple positivity) confirmed in a reference laboratory, were followed up for a mean of 4.5 years. There were 25 first TEs (5.3% per year): the cumulative incidence after 10 years was 37.1% (95% confidence interval [CI], 19.9%-54.3%). On multivariate analysis, male sex (hazard ratio = 4.4; 95% CI, 1.5-13.1, P = .007) and risk factors for venous thromboembolism (hazard ratio = 3.3; 95% CI, 1.3-8.5, P = .01) were independent predictors for TEs. Aspirin did not significantly affect the incidence of TE. In conclusion, the occurrence of a first TE in carriers of high-risk aPL profile is considerable; it is more frequent among male subjects and in the presence of additional risk factors for venous TE. These data can help in the decision to initiate primary thromboprophylaxis in these subjects.

Population samples from Liguria, Piacenza and Pavia provinces, and North Lombardy are compared for surnames and HLA gene frequencies. The genetic structure inferred from the principal coordinate analysis of surname frequencies is different from that inferred from HLA gene frequencies. The latter may represent ancient migrations, since surnames are relatively recent genetic markers dating from A.D. 1500. Ligurian and Celts were the ancient inhabitants of this northern Italy geographic area. Genetic distances, derived from HLA gene frequencies, and represented with an unrooted tree show the presence of a Ligurian and a Celtic pole. The aggregation of the subpopulations to each pole accords with the history and the archaeological findings in the area.

The aim of the present study was to investigate the in vitro mitotic response and cytokine production after allogeneic stimulation of peripheral blood mononuclear cells (PBMC) from healthy elderly subjects. Interleukin-1 (IL-1), interleukin-2 (IL-2), gamma-Interferon (gamma-IFN), and Tumor Necrosis Factor alpha (TNF-alpha) were detected in the supernatants of mixed lymphocyte cultures (MLC). The in vitro proliferative response was significantly reduced in the elderly subjects. The amount of IL-2 detected in the supernatant from cultures of cells from elderly donors was higher than for young controls, as were the production of cytokines predominantly secreted by the macrophage population (IL-1 and TNF-alpha). There was no difference in the production of gamma-IFN by cells of elderly and young subjects.

Fifty-seven subjects aged 1.5-14 years (mean: 6.5; standard deviation: 3.3) complaining of hip pain and/or limp underwent clinical, US and radiologic examinations on admission and after variable time intervals. Twenty-eight of them were found to be affected with transient synovitis, 2 with rheumatic fever, 2 with slipped capital femoral epiphysis and 5 with Legg-Calvè-Perthes disease. The extant 20 subjects with normal US and X-ray findings were diagnosed as having irritable hip without effusion. No false-negative results were obtained from US (100% sensitivity), whereas X-ray provided false-negative results in 28 of 37 patients with hip disorders other than irritable hip without effusion (24.3% sensitivity). No significant difference in the extent of hip joint effusion was found at US between the various groups. In the transient synovitis group, joint effusion was apparent on X-ray image in 3 of 28 patients, in whom the effusion was significantly more severe than in the extant 25 patients. Capsular joint effusion resolved more rapidly in transient synovitis than in Legg-Calvè-Perthes disease. The patients with both rheumatic fever and transient synovitis exhibited the most rapid onset of symptoms. On the basis of our results, we suggest that each patient complaining of hip pain and/or limp should undergo US first and that X-rays be performed second, in selected cases only.