Final Results from the First European Real-World Experience on Lusutrombopag Treatment in Cirrhotic Patients with Severe Thrombocytopenia: Insights from the REAl-World Lusutrombopag Treatment in ITalY Study

Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the “Club Epatologi Ospedalieri” (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/μL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000–44,000/μL) to 58,000 (49,000–82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04–1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/μL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/μL are unlikely to respond to the drug

A Preliminary Analysis of Adaptive Responding under Open and Closed Economies

In the current investigation, we evaluated the effects of open and closed economies on the adaptive behavior of 2 individuals with developmental disabilities. Across both types of economy, progressive-ratio (PR) schedules were used in which the number of responses required to obtain reinforcement increased as the session progressed. In closed-economy sessions, participants were able to obtain reinforcement only through interaction with the PR schedule requirements (i.e., more work resulted in more reinforcer access). In open-economy sessions, participants obtained reinforcers by responding on the PR schedule and were given supplemental (free) access to the reinforcers after completion of the session. In general, more responding was associated with the closed economy

Oral health in patients with Marfan syndrome

Introduction: The role of this study is to highlight a correlation between patients with Marfan syndrome and oral health status by evaluating and reviewing the relevant scientific literature. The syndrome is characterized by an abnormal production of the fibrillin1 protein. The manifestations of Marfan syndrome affect organs that contain connective tissue such as the skeletal system, the eyes, the heart and the blood vessels, the lungs and the fibrous membranes that cover the brain and the spine. The facial bony and soft structures can therefore be affected, influencing the stage of tooth formation and the structure of the teeth, we also want to analyze in this study, the periodontal complications and the management of the latter, with the use of surgical techniques that include the use of biomaterials. Materials and methods: A comprehensive review of the literature was conducted according to PRISMA guidelines. After a careful analysis of the work obtained by two independent academics, there have been 18. All data from the studies were compared and many of these highlighted the presence of abnormalities in the oral district. Results: The studies taken into consideration a whole series of oral manifestations related to the Marfan syndrome. Oral mucosa, periodontal, dental abnormalities, bone abnormalities or joint dysfunction are frequently involved in patients affected by this disease. Conclusions: All the research have given positive results in terms of dental or oral anomalies. This information may be essential to limit and intervene early improving the oral health of syndromic patients

THE EFFECTS OF CHOICE ON SELF-CONTROL

Three adolescents with traumatic brain injury performed a physical therapy task in the absence of programmed consequences or duration requirements. Next, the experimenter gave the participants the options of a smaller immediate reinforcer with no response requirement or a larger delayed reinforcer with a response requirement. Self-control training exposed participants to a procedure during which they chose between a smaller immediate reinforcer and a progressively increasing delayed reinforcer whose values varied and were determined by a die roll. The participants chose whether they or the experimenter rolled the die. All participants initially demonstrated low baseline durations of the physical therapy task, chose the smaller immediate reinforcer during the choice baseline, and changed their preference to the larger delayed reinforcer during self-control training

Cell-selective proteomics segregates pancreatic cancer subtypes by extracellular proteins in tumors and circulation

"In-depth cell-selective proteomics and secretomics has remained challenging. Here, the authors devise an optimised azidonorleucine labelling, mass spectrometry method and detect over 10,000 proteins in a pancreatic ductal adenocarcinoma model. Cell-selective proteomics is a powerful emerging concept to study heterocellular processes in tissues. However, its high potential to identify non-cell-autonomous disease mechanisms and biomarkers has been hindered by low proteome coverage. Here, we address this limitation and devise a comprehensive azidonorleucine labeling, click chemistry enrichment, and mass spectrometry-based proteomics and secretomics strategy to dissect aberrant signals in pancreatic ductal adenocarcinoma (PDAC). Our in-depth co-culture and in vivo analyses cover more than 10,000 cancer cell-derived proteins and reveal systematic differences between molecular PDAC subtypes. Secreted proteins, such as chemokines and EMT-promoting matrisome proteins, associated with distinct macrophage polarization and tumor stromal composition, differentiate classical and mesenchymal PDAC. Intriguingly, more than 1,600 cancer cell-derived proteins including cytokines and pre-metastatic niche formation-associated factors in mouse serum reflect tumor activity in circulation. Our findings highlight how cell-selective proteomics can accelerate the discovery of diagnostic markers and therapeutic targets in cancer

A Preliminary Analysis of Instructional Control in the Maintenance of Appropriate Behavior

This bridge study evaluated the effects of contingency-specifying instructions (CSIs) and incomplete instructions (IIs) in terms of establishing instructional control of appropriate behavior. Results suggested that instructional control and maintenance were achieved with CSIs but not with IIs. Results are discussed in terms of the potential use of instructional control in the maintenance of appropriate behavior for children with attention deficit hyperactivity disorder

DIFFERENTIAL REINFORCEMENT WITH AND WITHOUT BLOCKING AS TREATMENT FOR ELOPEMENT

Blocking is a frequent component of treatments for elopement. Unfortunately, blocking may not always be feasible because elopement often occurs when supervision is low or the behavior cannot be prevented. The present study evaluated the use of blocking in the treatment of elopement by using differential reinforcement of other behavior with and without blocking. In this case, results suggested that blocking may be an essential component for differential reinforcement–based treatments of elopement