Portal vein thrombosis (PVT) is a condition characterized by narrowing or occlusion of portal vein that is usually seen in patients with hepatic cirrhosis or malignancies, but presentation in healthy young patients is rare. In a non-cirrhotic liver, primary myeloproliferative disorders (MPD) are the most common procoagulant state associated with PVT. Non-cirrhotic nonmalignant acute PVT usually presents with abdominal pain (91%), fever (53%), and ascites (38%). Extension of portal vein thrombus into a superior mesenteric vein may lead to intestinal ischemia, bowel infarction, and sepsis and is responsible for high mortality in this subset of patients. We herein report a relatively rare presentation of myeloproliferative disease in a 42-year-old woman who sought medical attention for fever and abdominal pain associated with high levels of CA-125. Standard diagnostic workup did not reveal clear PVT signs. The thrombosis progressively involved splenic and superior mesenteric veins leading to bowel perforation and septic shock. Recovery was slow and optimal long-term management with anticoagulant is still under question. Despite a wide range of therapeutic options for the management of non-cirrhotic PVT are described in the literature, the efficacy of those available therapies in advanced and complicated cases like this is not well established.
Circular RNAs (circRNAs) are emerging molecular players in leukemogenesis and promising therapeutic targets. In KMT2A::AFF1 (MLL::AF4) rearranged leukemia, an aggressive disease compared to other pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), data about circRNAs are limited. Here we disclose the circRNA landscape of KMT2A::AFF1 translocated BCP-ALL infant patients, showing dysregulated, mostly ectopically expressed, circRNAs in leukemia cells. Most of these circRNAs, apart from circHIPK3 and circZNF609 previously associated with oncogenic behavior in ALL, are still uncharacterized. A loss-of-function screening in vitro identified an oncogenic role of circFKBP5, circKLHL2, circNR3C1 and circPAN3 in KMT2A::AFF1 ALL, whose silencing impacted cell proliferation and apoptosis. Further study in an extended cohort disclosed a significantly correlated expression of these oncogenic circRNAs and their putative involvement in common regulatory networks. Moreover, it showed that circAFF1 upregulation occurs in a subset of cases with HOXA KMT2A::AFF1 ALL. Collectively, functional analyses and patient data reveal oncogenic circRNA upregulation as a relevant mechanism that sustains the malignant cell phenotype in KMT2A::AFF1 ALL.-
Background Little research has been undertaken on the benefits of frailty management within different hospital settings. The objective of this study is to provide evidence on the viability and effectiveness of frailty management in non‐geriatric hospital settings on mortality and functional decline after discharge. Methods Data from the FRAILCLINIC (NCT02643069) study were used. FRAILCLINIC is a randomized controlled trial developed in non‐geriatric hospital inpatient settings (emergency room, cardiology and surgery) from Spain (2), Italy (2) and the United Kingdom (1). Inpatients must met frailty criteria (according to the Frailty Phenotype and/or FRAIL scale), ≥75 years old. The control group (CG) received usual care. The intervention group (IG) received comprehensive geriatric assessment (CGA) and a coordinated intervention consisting in recommendations to the treating physician about polypharmacy, delirium, falls, nutrition and physical exercise plus a discharge plan. The main outcomes included functional decline (worsening ≥5 points in Barthel Index) and mortality at 3 months. We used multivariate logistic regression models adjusted by age, gender and the Charlson index. Intention‐to‐treat (ITT) and per‐protocol (PP) analyses were used. Results Eight hundred twenty one participants (IG: 416; mean age 83.00 ± 4.91; 51.44% women; CG: 405; mean age 82.46 ± 6.03; 52.35% women) were included. In the IG, 77.16% of the participants followed the geriatric team's recommendations as implemented by the treating physicians. The intervention showed a benefit on functional decline and mortality [OR: 0.67(0.47–0.96), P ‐value 0.027 and 0.29(0.14–0.57), P ‐value < 0.001, respectively) when fully followed by the treating physician. A trend to benefit (close to statistical significance) in functional decline and mortality were also observed when any of the recommendations were not followed [OR (95% CI): 0.72 (0.51–1.01), P ‐value: 0.055; and 0.64 (0.37–1.10), P ‐value: 0.105, respectively]. Conclusions An individualized intervention in frail in‐patients reduces the risk of functional deterioration and mortality at 3 months of follow‐up when a care management plan is designed and followed.
Primary hemophagocytic lymphohistiocytosis (pHLH) is an immune‐mediated, hyperinflammatory disorder. Interferon‐γ (IFNγ) plays a key role in the pathophysiology of pHLH. Emapalumab, a fully human, anti‐IFNγ monoclonal antibody neutralizes both free and receptor‐bound IFNγ. However, inhibiting IFNγ‐mediated signaling could result in immune dysfunction and immunosuppression. This exploratory exposure–safety analysis investigated the relationship between emapalumab and the incidence of adverse events in patients with pHLH. Increased exposure to emapalumab was not associated with an increased predicted risk of severe adverse events, infection, or infusion‐related reactions. Emapalumab was associated with a favorable and manageable safety profile across all assessed doses and treatment durations.
Background The 30‐day hospital re‐admission rate is a quality measure of hospital care to monitor the efficiency of the healthcare system. The hospital re‐admission of acute stroke (AS) patients is often associated with higher mortality rates, greater levels of disability and increased healthcare costs. The aim of our study was to identify predictors of unplanned 30‐day hospital re‐admissions after discharge of AS patients and define an early re‐admission risk score (RRS). Methods This observational, retrospective study was performed on AS patients who were discharged between 2014 and 2019. Early re‐admission predictors were identified by machine learning models. The performances of these models were assessed by receiver operating characteristic curve analysis. Results Of 7599 patients with AS, 3699 patients met the inclusion criteria, and 304 patients (8.22%) were re‐admitted within 30 days from discharge. After identifying the predictors of early re‐admission by logistic regression analysis, RRS was obtained and consisted of seven variables: hemoglobin level, atrial fibrillation, brain hemorrhage, discharge home, chronic obstructive pulmonary disease, one and more than one hospitalization in the previous year. The cohort of patients was then stratified into three risk categories: low (RRS = 0–1), medium (RRS = 2–3) and high (RRS >3) with re‐admission rates of 5%, 8% and 14%, respectively. Conclusions The identification of risk factors for early re‐admission after AS and the elaboration of a score to stratify at discharge time the risk of re‐admission can provide a tool for clinicians to plan a personalized follow‐up and contain healthcare costs.
A growing number of gene therapy‐ and gene editing‐based treatments for patients with sickle cell disease (SCD) are entering clinical trials. These treatments, designed to target the underlying cause of SCD, have the potential to provide functional cures, which until now were possible only through allogeneic hematopoietic stem cell transplant. However, as these novel approaches advance from early‐ to late‐stage clinical trials, it is essential to identify physiologically and clinically relevant endpoints that can demonstrate the achievement of a functional cure for SCD. Here, we present an overview of the pathophysiology of SCD and current treatment options, review ongoing SCD clinical trials using gene therapy or gene editing approaches, and identify the most relevant endpoints for demonstrating the attainment of a functional cure for SCD.
The authors report a singular case of post-operative exogenous fungal endophthalmitis caused by a non-pathogenic fungal agent: Aspergillus oryzae. A 75-year-old Caucasian woman with post-penetrating keratoplasty fungal endophthalmitis due to a nonpathogenic A. oryzae, resistant to the current azoles anti-fungal agents, was treated with subtotal vitrectomy, intravitreal injection, and systemic voriconazole therapy. Complete resolution of the endophthalmitis occurred after two subsequent intravitreal injections and a 2-month-long systemic delivery of voriconazole. The quick identification of the fungal agent allowed immediate and targeted therapy. In the article, the safety and efficacy of both systemic and intravitreal voriconazole treatments are discussed.
In addition to the role of skeletal muscle in movement and locomotion, muscle plays a critical role in a broad array of metabolic processes that can contribute to improved health or risk of disease. The age-associated loss of muscle has been termed sarcopenia. The muscle is the primary site of insulin-stimulated glucose disposal and the largest component of basal metabolic rate, directly and indirectly affects bone density, produces myokines with pleiotropic effect on muscle and other tissues including the brain, and stores essential amino acids essential for the maintenance of protein synthesis during periods of reduced food intake and stress. As such, not surprisingly deterioration of skeletal muscle health, typically operationalized as decline of muscle mass and muscle strength is both a powerful risk factor and main consequence of chronic diseases, disability, and loss of independence, and it is one of the strongest risk factors for mortality. However, skeletal muscle remains one of the most plastic of all tissues, with rapid changes in rates of protein synthesis and degradation in response to physical activity and inactivity, inflammation, and nutritional and hormonal status. This has made the development of pharmacological therapies to increase muscle mass (or prevent loss), an important goal for decades. However, while remarkable advances in the understanding of molecular and cellular regulation of muscle protein metabolism have occurred recently, there are no approved drugs for the treatment of sarcopenia, the loss of skeletal muscle affecting millions of older people. The goal of this paper is to describe the possible reasons for the lack of new and effective pharmacotherapies to treat one of the most important risk factors for age-associated disease and loss of independence.
This article represents one of the first attempts at building a direct measure of occupational exposure to robotic labour‐saving technologies. After identifying robotic and labour‐saving robotic patents, the underlying 4‐digit CPC (Cooperative Patent Classification) code definitions, together with O*NET (Occupational Information Network) task descriptions, are employed to detect functions and operations which are more directed to substituting the labour input and their exposure to labour‐saving automation. This measure allows us to obtain fine‐grained information on tasks and occupations according to their text similarity ranking. Occupational exposure by wage and employment dynamics in the United States is then studied, and complemented by investigating industry and geographical penetration rates.
Background Ticagrelor improves clinical outcomes in patients with acute coronary syndrome compared with clopidogrel. Ticagrelor also inhibits cell uptake of adenosine and has been associated with cardioprotective effects in animal models. We sought to investigate the potential cardioprotective effects of ticagrelor, as compared with clopidogrel, in stable patients undergoing percutaneous coronary intervention (PCI). Methods and results This was a Prospective Randomized Open Blinded End-points (PROBE) trial enrolling stable patients with coronary artery disease (CAD) requiring fractional flow reserve (FFR)-guided PCI of intermediate epicardial coronary lesions. ST-segment elevation at intracoronary (IC)-ECG during a two-step sequential coronary balloon inflations in the reference vessel during PCI was used as an indirect marker of cardioprotection induced by ischemic preconditioning. The primary endpoint of the study was the comparison of the delta (Δ) (difference) ST-segment elevation measured by intracoronary-ECG during two-step sequential coronary balloon inflations. Results Fifty-three patients were randomized to either clopidogrel or ticagrelor. The study was stopped earlier because the primary endpoint was met at a pre-specified interim analysis. ΔST-segment elevation was significantly higher in ticagrelor as compared to clopidogrel arms (p<0.0001). Ticagrelor was associated with lower angina score during coronary balloon inflations. There was no difference in coronary microvascular resistance between groups. Adenosine serum concentrations were increased in patients treated with ticagrelor as compared to those treated with clopidogrel. Conclusions Ticagrelor enhances the cardioprotective effects of ischemic preconditioning compared with clopidogrel in stable patients with CAD undergoing PCI. Further studies are warranted to fully elucidate the mechanisms through which ticagrelor may exert cardioprotective effects in humans. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique Identifier: NCT02701140.
For decades, we have known from autopsy studies that the proximate cause of most acute myocardial infarctions (AMIs) is an occlusive thrombosis caused by the frank rupture of a lipid-rich plaque, responsible for approximately two third of cases. Subsequent studies revealed other plaque morphologies at the basis of AMI, including plaque erosion and eruptive calcified nodule. Mounting evidence, also obtained with the availability of optical coherence tomography, supports the concept that these morphologic substrates are separate entities, with distinct pathogeneses, clinical presentations, therapeutic targets, and prognosis.
Anomalous aortic origin of a coronary artery (AAOCA) is a congenital anomaly in the origin and course of a coronary artery that arises from the aorta.
Intimate partner violence (IPV) is a complex and pervasive global phenomenon. Despite extensive research on physical and sexual violence, there has been a relative lack of investigation into the detrimental and distinctive consequences of psychological violence against women. This is surprising given the profound impact it has on the psychological well-being of victims, notably in the form of depression, which is commonly observed as an outcome in cases of psychological IPV victimization. The present study analyzes the impact of psychological IPV on depressive symptoms, considering the moderating influence of personal positivity, defined as positive self-perceptions, optimistic life perspectives, and a hopeful view of the future in a sample of 171 Italian women seeking assistance from anti-violence centers in different localities of Italy. The findings show that in line with the hypothesis, the association between psychological violence and depressive symptoms is moderated by the levels of perceived positivity, even when controlling for instances of physical violence. These results and implications for interventions are discussed within the framework of existing literature on positive psychology and psychological well-being in the context of IPV.
This paper deals with the complex relationship between innovation and the labor market, analyzing the impact of new technological advancements on overall employment, skills, and wages. After a critical review of the extant literature and the available empirical studies, novel evidence is presented on the distribution of labor-saving automation [namely robotics and artificial intelligence (AI)], based on natural language processing of US patents. This mapping shows that both upstream high-tech providers and downstream users of new technologies—such as Boeing and Amazon—lead the underlying innovative effort.
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