Critical concepts, practice recommendations, and research perspectives of pixantrone therapy in non-Hodgkin lymphoma: a SIE, SIES, and GITMO consensus paper

Objectives: In this paper, we present a review of critical concepts and research perspectives and produce recommendations on the optimal use of pixantrone in non-Hodgkin lymphoma (NHL) by group discussion from an expert panel appointed by the Italian Society of Hematology and the affiliate societies, Societa Italiana di Ematologia Sperimentale and Gruppo Italiano Trapianto di Midollo Osseo. Methods: Recommendations were produced using the Delphi process. Scientific evidence on pixantrone efficacy was analyzed using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology in the areas where at least one randomized trial was published. The following key issues were addressed for practical recommendations: pixantrone monotherapy in aggressive relapsed or refractory non-Hodgkin B-cell lymphomas and toxicity risk management in patients candidates to pixantrone. Results and conclusions: After a balanced and value-oriented discussion, the panel agreed that the benefit/risk profile was in favor of pixantrone in the treatment of adult patients with multiply relapsed or refractory aggressive NHL B-cell lymphomas. Pixantrone was deemed to be contraindicated in patients with uncontrolled cardiovascular disease. Despite a low rate of cardiotoxicity of pixantrone reported in clinical trials, the panel recommended that all patients receiving pixantrone should undergo periodical cardiac monitoring

Main phases of wood formation in chestnut (Castanea sativa) in Central Italy: comparison of seasons 2008 and 2009

We present wood formation in chestnut (Castanea sativa) during the growing seasons 2008 and 2009, compare its dynamics in the two years and discuss possible effects on wood quality. To this purpose, microcores containing wood, cambium and phloem were collected at weekly intervals from 10 chestnut trees growing at the Cimini mountains near Viterbo, Central Italy. In 2008, the onset of wood formation started before the first sampling on 17 April 2008. Onset of lignifi cation of the fi rst formed vessels was observed around 23 April (day of the year DOY 113.8 ± 5.3) and the fi rst latewood vessels were observed around 5 June 2008 (DOY 156.5 ± 7.7). Latewood formation continued until 29 September 2008 (DOY 273.9 ± 10.5) when the terminal cells of the newly formed xylem ring were fully lignifi ed. In 2009, the main phases of wood formation generally occurred earlier than in 2008. The expansion of earlywood vessels was observed around 10 April (DOY 99.7 ± 6.1), the onset of lignifi cation around 22 April (DOY 111.9 ± 7.4) and the first latewood vessels around 28 May 2009 (DOY 147.9 ± 4.7). Lignifi cation of the last formed cells was completed by 26 September 2009 (DOY 273.9 ± 10.5). The average duration of tree-ring formation was 161 days in 2008 and 169 days in 2009, the average ring widths were 3296 ± 1514 μm in 2008 and 3166 ± 1073 μm in 2009, and latewood percentages comprised 76% and 74% of the 2008 and 2009 tree-rings, respectively. The small differences in timing of wood formation phases in the two study years are probably due to small variations in climatic conditions between the two years and they did not seem to have a major impact on ring widths and latewood percentages, which are two important parameters affecting wood quality in ring porous wood species

Glavne faze razvoja drva pitomog kestena (Castanea sativa) u središnjoj Italiji – usporedba sezone 2008 i 2009

We present wood formation in chestnut (Castanea sativa) during the growing seasons 2008 and 2009, compare its dynamics in the two years and discuss possible effects on wood quality. To this purpose, microcores containing wood, cambium and phloem were collected at weekly intervals from 10 chestnut trees growing at the Cimini mountains near Viterbo, Central Italy. In 2008, the onset of wood formation started before the first sampling on 17 April 2008. Onset of lignification of the first formed vessels was observed around 23 April (day of the year DOY 113.8 ± 5.3) and the first latewood vessels were observed around 5 June 2008 (DOY 156.5 ± 7.7). Latewood formation continued until 29 September 2008 (DOY 273.9 ± 10.5) when the terminal cells of the newly formed xylem ring were fully lignified. In 2009, the main phases of wood formation generally occurred earlier than in 2008. The expansion of earlywood vessels was observed around 10 April (DOY 99.7 ± 6.1), the onset of lignification around 22 April (DOY 111.9 ± 7.4) and the first latewood vessels around 28 May 2009 (DOY 147.9 ± 4.7). Lignification of the last formed cells was completed by 26 September 2009 (DOY 273.9 ± 10.5). The average duration of tree-ring formation was 161 days in 2008 and 169 days in 2009, the average ring widths were 3296 ± 1514 μm in 2008 and 3166 ± 1073 μm in 2009, and latewood percentages comprised 76% and 74% of the 2008 and 2009 tree-rings, respectively. The small differences in timing of wood formation phases in the two study years are probably due to small variations in climatic conditions between the two years and they did not seem to have a major impact on ring widths and latewood percentages, which are two important parameters affecting wood quality in ring porous wood species.Rad obrađuje stvaranje drva pitomog kestena (Castanea sativa) tijekom vegetacije u 2008. i 2009. godini. Uspoređuje se dinamika stvaranja drva u te dvije godine i raspravlja o mogućem utjecaju na njegovu kvalitetu. Za tu su svrhu s deset stabala pitomog kestena u planinama Cimini, pokraj mjesta Viterbo u središnjoj Italiji, u tjednim intervalima skupljeni mikroizvrtci koji su sadržavali drvo, kambij i floem. Početak stvaranja drva u 2008. godini dogodio se prije uzimanja prvih uzoraka 17. travnja 2008. Početak lignifikacije prvooblikovanih traheja primijećen je oko 23. travnja (dan u godini DOY 113,8 ± 5,3), a prve traheje kasnog drva primijećene su oko 5. lipnja (DOY 156,5 ± 7,7). Stvaranje kasnog drva nastavljeno je do 29. rujna 2008. (DOY 273,9 ± 10,5), kad su završne stanice novostvorenoga goda drva bile potpuno lignificirane. U 2009. godini glavne su se faze stvaranja drva uglavnom pojavile ranije nego u 2008. godini. Širenje traheja ranog drva primijećeno je oko 10. travnja (DOY 99,7 ± 6,1), početak lignifikacije oko 22. travnja (DOY 111,9 ± 7,4), a prve traheje kasnog drva oko 28. svibnja 2009. (DOY 147,9 ± 4,7). Lignifi kacija zadnjih proizvedenih stanica završena je do 26. rujna 2009. (DOY 273,9 ± 10,5). Prosječno trajanje stvaranja goda drva u 2008. godini iznosilo je 161 dan, a u 2009. godini 169 dana. Prosječne širine godova bile su 3296 ± 1514 μm u 2008. godini i 3166 ± 1073 μm u 2009. godini, a postotni udjel kasnog drva iznosio je 76 i 74% godova u 2008., odnosno u 2009. godini. Male razlike u vremenu početka pojedine faza stvaranja drva u dvjema promatranim godinama vjerojatno su posljedica malih varijacija klimatskih uvjeta između te dvije godine i čini se da nemaju velik utjecaj na širinu godova ni na postotak kasnog drva, a to su dva važna čimbenika koji utječu na kvalitetu drva prstenasto poroznih vrsta

Unexpected Hypertensive Pneumothorax after Digestive Upper Endoscopy: A Case Report

We report an unexpected massive left pneumothorax at the end of a digestive upper endoscopy without evidences of perforation or airway over-pressure. The possible air passage through a diaphragmatic failing is discussed

The Evaluation Culture to Build a Network of Competitive Cities in the Mediterranean

The gradual shift of the economic centre of gravity to the east, with the consequent marginalization of the majority parts of Europe, requires an approximation, in a short time, for the Mediterraneans peoples and their cultures to create a common space that will strengthen the interdependencies and complementarities

Growth Hormone Axis in Skeletal Dysplasias

Introduction: Skeletal dysplasias, also termed as osteochondrodysplasias, are a large heterogeneous group of disorders characterized by abnormalities of bone or cartilage growth or texture. They occur due to genetic mutations and their phenotype continues to evolve throughout life. Reduced growth is a common feature

Feasibility of inter-hospital transportation using extra-corporeal membrane oxygenation (ECMO) support of patients affected by severe swine-flu(H1N1)-related ARDS

<p>Abstract</p> <p>Background</p> <p>To describe the organization of an ECMO-centre from triage by telephone to the phase of inter-hospital transportation with ECMO of patients affected by H1N1-induced ARDS, describing techniques and equipment used.</p> <p>Methods</p> <p>From September 2009 to January 2010, 18 patients with H1N1-induced ARDS were referred to our ECMO-centre from other hospitals. Six patients had contraindications to treatment with ECMO and remained in the local hospital. Twelve patients were transported to our centre and were included in this study. Four patients were transported on ECMO (Group A) and eight on conventional ventilation (Group B). The groups were compared on the basis of adverse events during transport, clinical characteristics and outcome.</p> <p>Results</p> <p>The PaO2/FiO2 ratio was lower in the patients of Group A (46.8 vs 89.7 [median]) despite the PEEP values being higher (15.0 vs 8.5 [median]). The Murray score was higher in Group A (3.50 vs 2.75 [median]). During the transfer there were no significant complications noted in Group A, whereas two patients in Group B were reported with hypoxia (SpO2 < 90%). One patient in Group A died. All the other patients of the two groups have been discharged from hospital.</p> <p>Conclusions</p> <p>The creation of an ECMO team, with various experts in the treatment of ARDS, assured a safe transfer of patients with severe hypoxia, over long distances, when in other cases they wouldn't have been be transportable.</p

Detection of patients with COVID-19 by the emergency medical services in Lombardy through an operator-based interview and machine learning models

BackgroundThe regional emergency medical service (EMS) in Lombardy (Italy) developed clinical algorithms based on operator-based interviews to detect patients with COVID-19 and refer them to the most appropriate hospitals. Machine learning (ML)-based models using additional clinical and geospatial epidemiological data may improve the identification of infected patients and guide EMS in detecting COVID-19 cases before confirmation with SARS-CoV-2 reverse transcriptase PCR (rtPCR).MethodsThis was an observational, retrospective cohort study using data from October 2020 to July 2021 (training set) and October 2021 to December 2021 (validation set) from patients who underwent a SARS-CoV-2 rtPCR test within 7 days of an EMS call. The performance of an operator-based interview using close contact history and signs/symptoms of COVID-19 was assessed in the training set for its ability to determine which patients had an rtPCR in the 7 days before or after the call. The interview accuracy was compared with four supervised ML models to predict positivity for SARS-CoV-2 within 7 days using readily available prehospital data retrieved from both training and validation sets.ResultsThe training set includes 264 976 patients, median age 74 (IQR 55-84). Test characteristics for the detection of COVID-19-positive patients of the operator-based interview were: sensitivity 85.5%, specificity 58.7%, positive predictive value (PPV) 37.5% and negative predictive value (NPV) 93.3%. Contact history, fever and cough showed the highest association with SARS-CoV-2 infection. In the validation set (103 336 patients, median age 73 (IQR 50-84)), the best-performing ML model had an AUC of 0.85 (95% CI 0.84 to 0.86), sensitivity 91.4% (95 CI% 0.91 to 0.92), specificity 44.2% (95% CI 0.44 to 0.45) and accuracy 85% (95% CI 0.84 to 0.85). PPV and NPV were 13.3% (95% CI 0.13 to 0.14) and 98.2% (95% CI 0.98 to 0.98), respectively. Contact history, fever, call geographical distribution and cough were the most important variables in determining the outcome.ConclusionML-based models might help EMS identify patients with SARS-CoV-2 infection, and in guiding EMS allocation of hospital resources based on prespecified criteria

Gaia DR2 view of the Lupus V-VI clouds: The candidate diskless young stellar objects are mainly background contaminants

Extensive surveys of star-forming regions with Spitzer have revealed populations of disk-bearing young stellar objects. These have provided crucial constraints, such as the timescale of dispersal of protoplanetary disks, obtained by carefully combining infrared data with spectroscopic or X-ray data. While observations in various regions agree with the general trend of decreasing disk fraction with age, the Lupus V and VI regions appeared to have been at odds, having an extremely low disk fraction. Here we show, using the recent Gaia data release 2 (DR2), that these extremely low disk fractions are actually due to a very high contamination by background giants. Out of the 83 candidate young stellar objects (YSOs) in these clouds observed by Gaia, only five have distances of ∼150 pc, similar to YSOs in the other Lupus clouds, and have similar proper motions to other members in this star-forming complex. Of these five targets, four have optically thick (Class II) disks. On the one hand, this result resolves the conundrum of the puzzling low disk fraction in these clouds, while, on the other hand, it further clarifies the need to confirm the Spitzer selected diskless population with other tracers, especially in regions at low galactic latitude like Lupus V and VI. The use of Gaia astrometry is now an independent and reliable way to further assess the membership of candidate YSOs in these, and potentially other, star-forming regions

Italian real life experience with ibrutinib: Results of a large observational study on 77 relapsed/refractory mantle cell lymphoma

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients' outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP). An observational, retrospective, multicenter study was conducted. Seventyseven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred. In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world