The use of thrombopoietin-receptor agonists (TPO-RAs) in immune thrombocytopenia (ITP): a “real life” retrospective multicenter experience of the Rete Ematologica Pugliese (REP)

Immune thrombocytopenia (ITP) is a disease which sees one-third of patients failing first and subsequent therapeutic approaches, including splenectomy. Thrombopoietin-receptor agonists (TPO-RAs) are recommended for adults who relapse after splenectomy or who have contraindications for splenectomy. In this multicenter study, a total of 124 patients were retrospectively evaluated: 55 (44.3 %) were treated by romiplostim and 69 (55.6 %) by eltrombopag. Mean age, number of young patients (<60 years), time from primary diagnosis of ITP to TPO-RA treatment, and previous lines of therapy were similar in both groups. The overall response rate was 80 % (44/55) for romiplostim and 94.2 % (65/69) for eltrombopag; the duration of response and the time to response were similar (p = NS). The response rate to both drugs in non-splenectomized patients was higher than that of splenectomized patients (p < 0.05). The mean duration of response was 30 months for romiplostim and 15 months for eltrombopag, due to later commercialization of eltrombopag. Failure was the most frequent cause of discontinuation. Thrombotic events were the most consistent adverse events and were recorded in 2 and 3 % of patients treated by romiplostim and eltrombopag, respectively. In conclusion, romiplostim and eltrombopag are effective in the majority of patients with chronic ITP who failed several lines of therapy; whether TPO-RAs could substitute splenectomy is under discussion and studies are warranted

Primary, Bilateral and Diffuse Renal Non-Hodgkin's Lymphoma in a Young Woman Suffering from Turner Syndrome

Primary renal lymphoma (PRL) is a rare form of non-Hodgkin's lymphoma (NHL) restricted to and primarily involving one or both kidneys, with no lymph node extension. It accounts for &lt;1% of extranodal lymphomas, and descriptions in the literature are limited. Here, we describe an unprecedented case of bilateral PRL in a 44-year-old woman with Turner syndrome and discuss both diagnostic and therapeutic issues in the light of the available literature in the field. A personalized approach to this rare disease is necessary

Producción de antraquinonas por cultivo in vitro de suspensiones celulares y raíces transformadas de Rubia tinctorum: un modelo para la enseñanza en el estudio de bioprocesos por cultivo de tejidos de plantas

El cultivo vegetal in vitro es una alternativa atractiva y factible para la producción de metabolitos secundarios. Este tipo de cultivos asegura una producción continua en condiciones controladas, bajo Buenas Prácticas de Fabricación. Estos procesos biotecnológicos constituyen una excelente herramienta para la formación de estudiantes de postgrado. Efectivamente, los estudiantes pueden adquirir experiencia en diferentes áreas, tales como bioquímica vegetal, biología molecular, metabolismo primario y secundario vegetal e ingeniería bioquímica. En este trabajo, la producción de antraquinonas en diferentes cultivos vegetales in vitro de Rubia tinctorum se presenta como un modelo sencillo y versátil para introducir a los estudiantes de postgrado en la producción de metabolitos secundarios vegetales. Los estudiantes pudieron analizar la cinética de formación de biomasa y productos en cultivos en batch de suspensiones y raíces transformadas, evaluando el efecto de la elicitación con metiljasmonato, una estrategia muy conocida utilizada para inducir la producción de metabolitos secundarios en cultivos de células vegetales. Además, se evaluó el efecto de la remoción in situ del producto, ampliamente utilizada en biocatálisis y fermentaciones microbianas. El resultado de las autoevaluaciones reveló que el trabajo en el laboratorio y el subsiguiente análisis de resultados favorecieron la consolidación de conceptos teóricos adquiridos durante los seminarios. En resumen, se presenta un trabajo de laboratorio económico, accesible y robusto, aplicable a estudiantes de cursos de postgrado en diferentes programas de biotecnología vegetal, química e ingeniería bioquímica. Palabras clave: trabajo de laboratorio, aprendizaje práctico, producción de metabolitos secundarios, cultivo de células vegetales, remoción in situ de producto.Plant cell culture bioprocesses constitute an excellent tool for the formation of undergraduate, magister, and Ph.D. students. In fact, students can acquire experience in the field of plant biochemistry and molecular biology; plant primary and secondary metabolism; and biochemical engineering. In the present manuscript, the production of anthraquinones in different plant cell tissue cultures is showed as easy and versatile model to introduce magister students in the field of plant secondary metabolite production. AQs are extracted with ethanol 80% and spectrophotometrically quantified, which also makes it environmentally friendly and easy to manipulate in the laboratory. The students were able to analyse biomass and product formation kinetics in batch suspension and hairy root cultures and evaluate the effect of MeJa elicitation an extended used strategy to trigger secondary metabolite production in plant cell cultures. Moreover, the performance of in situ product removal, which has been extensively used in biocatalyst and microbial fermentations, was evaluated. In summary, an inexpensive, accessible, and robust laboratory work is presented that can be adapted to undergraduate, magister, and/or Ph.D. students´ courses in different plant biology, chemistry, and biochemical engineering programs.Fil: Perassolo, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; ArgentinaFil: Busto, Víctor Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Minoia, Juan Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; ArgentinaFil: Cerezo, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; ArgentinaFil: Smith, María Emilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Martínez, C. A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Quevedo, Carla Verónica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Giuletti, A. M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Rodriguez Talou, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; ArgentinaFil: Cardillo, Alejandra Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentin

Real-world Outcomes of Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated With Polatuzumab Vedotin-based Therapy

: After FDA and EMA approval of the regimen containing polatuzumab vedotin plus rituximab and bendamustine (PolaBR), eligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients in Italy were granted early access through a Named Patient Program. A multicentric observational retrospective study was conducted focusing on the effectiveness and safety of PolaBR in everyday clinical practice. Fifty-five patients were enrolled. There were 26 females (47.3%), 32 patients were primary refractory and 45 (81.8%) resulted refractory to their last therapy. The decision to add or not bendamustine was at physician's discretion. Thirty-six patients underwent PolaBR, and 19 PolaR. The 2 groups did not differ in most of baseline characteristics. The final overall response rate was 32.7% (18.2% complete response rate), with a best response rate of 49.1%. Median disease-free survival was reached at 12 months, median progression-free survival at 4.9 months and median overall survival at 9 months, respectively. Overall, 88 adverse events (AEs) were registered during treatment in 31 patients, 22 of grade ≥3. Eight cases of neuropathy occurred, all of grades 1-2 and all related to polatuzumab. The two groups of treatment did not differ for effectiveness endpoints but presented statistically significant difference in AEs occurrence, especially in hematological AEs, in AEs of grade equal or greater than 3 and in incidence of neuropathy. Our data add useful information on the effectiveness of Pola(B)R in the setting of heavily pretreated DLBCL and may also suggest a better tolerability in absence of bendamustine without compromise of efficacy

Effectiveness and Safety of Biosimilars in Pediatric Non-infectious Uveitis: Real-Life Data from the International AIDA Network Uveitis Registry

IntroductionSince many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU).MethodsData from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behcet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE).ResultsForty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12 months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38-5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4-14.9, p = 0.0003). Three minor AEs were reported.ConclusionsTNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications.Trial RegistrationClinicalTrials.gov ID NCT05200715

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Uveitis

Introduction: The aim of this paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry for paediatric and adult patients with non-infectious uveitis (NIU). Methods: This is a physician-driven, population- and electronic-based registry implemented for both retrospective and prospective collection of real-world demographics, clinical, laboratory, instrumental and socioeconomic data of patients with uveitis and other non-infectious inflammatory ocular diseases recruited through the AIDA Network. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is thought to collect standardised information for real-life research and has been developed to change over time according to future scientific acquisitions and potentially communicate with other similar instruments. Security, data quality and data governance are cornerstones of this platform. Results: Ninety-five centres have been involved from 19 countries and four continents from 24&nbsp;March to 16&nbsp;November 2021. Forty-eight out of 95 have already obtained the approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers). The AIDA Registry collects baseline and follow-up data using 3943 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger/risk factors, therapies and healthcare utilization for patients with NIU. Conclusions: The development of the AIDA Registry for patients with NIU will facilitate the collection of standardised data leading to real-world evidence and enabling international multicentre collaborative research through inclusion of patients and their families worldwide

Energy Demand and Temperature: A Dynamic Panel Analysis

This paper is a first attempt to investigate the effect of climate on the demand for different energy vectors from different final users. The ultimate motivation for this is to arrive to a consistent evaluation of the impact of climate change on key consumption goods and primary factors such as energy vectors. This paper addresses these issues by means of a dynamic panel analysis of the demand for coal, gas, electricity, oil and oil products by residential, commercial and industrial users in OECD and (a few) non-OECD countries. It turns out that temperature has a very different influence on the demand of energy vectors as consumption goods and on their demand as primary factors. In general, residential demand responds negatively to temperature increases, while industrial demand is insensitive to temperature increases. As to the service sector, only electricity demand displays a mildly significant negative elasticity to temperature changes

The Nontradable Share Reform in the Chinese Stock Market

Nontradable shares (NTS) are an unparalleled feature of the ownership structure of Chinese listed companies and represented a major hurdle to domestic financial market development. After some failed attempts, in 2005 the Chinese authorities have launched a structural reform program aiming at eliminating NTS. In this paper, we evaluate the stock price effects of the actual implementation of this reform in 368 firms. The NTS reform generated a statistically significant 8 percent positive abnormal return over the event window, adjusting prices for the compensation requested by tradable shareholders. Results are consistent with the expectation of improved economic fundamentals such as better corporate governance and enhanced liquidity

Technology Transfers and the Clean Development Mechanism in a North-South General Equilibrium Model

This paper analyzes the potential welfare gains of introducing a technology transfer from Annex I to non-Annex I in order to mitigate greenhouse gas emissions. Our analysis is based on a numerical general equilibrium model for a world economy comprising two regions, North (Annex I) and South (non-Annex I). As our model allows for labor mobility between the formal and informal sectors in the South, we are also able to capture additional aspects of how the transfer influences the Southern economy. In a cooperative equilibrium, a technology transfer from the North to the South is clearly desirable from the perspective of a global social planner, since the welfare gain for the South outweighs the welfare loss for the North. However, if the regions do not cooperate, then the incentives to introduce the technology transfer appear to be relatively weak from the perspective of the North; at least if we allow for Southern abatement in the pre-transfer Nash equilibrium. Finally, by adding the emission reductions associated with the Kyoto agreement to an otherwise uncontrolled market economy, the technology transfer leads to higher welfare in both regions

Entry and Exit Strategies in Migration Dynamics

This work is devoted to study the role of combined entry and exit strategies in the migration process. We develop a real option model in which the community of immigrants in the host country is described as a club and the immigrants benefits is a U-shaped function, depending on the dimension of the district. There exist two threshold levels: the first one triggers the migration choice, while the second triggers the return to the country of origin. The theoretical results show that the phenomenon of hysteresis is amplified by the existence of a community both in the entry case and in the exit case. Furthermore, the community can reduce the minimum wage level required to trigger both exit and entry: this fact could explain why in some cases we observe migration inflows with a low wage differential and also with underunemployment. We show also some possible further extensions of the model: in one case we introduce a possible way to select the entrants skills and in another case we show some theoretical implementations to include possible policy shocks in the migrants choice