Articles de revues : « Rozzano »

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Weatherill, Jonathan. « Two New Traditional Neighborhoods for the Town of Rozzano, Milan ». Journal of Traditional Building, Architecture and Urbanism, n^o 3 (8 novembre 2022) : 199–208. http://dx.doi.org/10.51303/jtbau.vi3.594.

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A town of 42,000 inhabitants in the agricultural belt on the south side of Milan, Rozzano was developed in the 1960s and 1970s on the Soviet suburban model to house migrant workers from the south. The stock of modular cement high-rises is now deteriorating rapidly and will not be restored or replaced with similar buildings. The town council intends to replace this fabric with one that is more livable, following the principles of New Urbanism. Two projects are being developed for new mixed-use, walkable neighborhoods on municipal sites. The projects will become part of the town’s Development Plan and the sites will be offered to developers who are to build the new quarters as designed. The results will serve as examples of how to renew Rozzano – using traditional local building models of urban, rural, and agricultural architecture. The initiative is a chance to create a ground-breaking example of suburban sprawl repair.

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Polat TOPÇUOĞLU, Gökşen, et Elif ÜNSAL AVDAL. « Rozzano Locsin Teknolojik Yeterlilik Teorisine Göre Uzaktan Diyabet Bakımı ». Turkish Journal of Diabetes Nursing 1, n^o 1 (2021) : 23–27. http://dx.doi.org/10.29228/tjdn.51310.

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Macalam, Trecella May, et Rozzano Locsin. « Humanoid Nurse Robots and Compassion : Dialogical Conversation with Rozzano Locsin ». Journal of Health and Caring Sciences 2, n^o 1 (26 juin 2020) : 71–77. http://dx.doi.org/10.37719/jhcs.2020.v2i1.rna001.

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It is important that in the future, nursing practice is framed with the humanoid nurse robot (HNR) functionality as a sure partner capable of expressing compassion that mimics human persons. Sr. Trecella May Macalam, SPC, a member of the Sisters of St. Paul of Chartres congregation, and doctoral student of St. Paul University Philippines and Dr. Rozzano Locsin, nurse theorist and author of the theory of Technological Competency as Caring in Nursing (TCCN) discuss the futurist idea of HNR’s capability to express compassion in nursing. Locsin’s theory has inspired the utility of advancing machine technologies in health care practice. Framing explanations and descriptions between human persons and HNRs as intelligent healthcare robots (IHRs) stimulate future nursing care in many ways. The theory of TCCN inspired “knowing persons as caring” as a process of nursing. In the future, this theory will most likely influence the inevitability and dependency of nursing through compassion in nursing by HNRs.

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Cecconi, Maurizio, Daniele Piovani, Enrico Brunetta, Alessio Aghemo, Massimiliano Greco, Michele Ciccarelli, Claudio Angelini et al. « Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy ». Journal of Clinical Medicine 9, n^o 5 (20 mai 2020) : 1548. http://dx.doi.org/10.3390/jcm9051548.

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We described features of hospitalized Covid-19 patients and identified predictors of clinical deterioration. We included patients consecutively admitted at Humanitas Research Hospital (Rozzano, Milan, Italy); retrospectively extracted demographic; clinical; laboratory and imaging findings at admission; used survival methods to identify factors associated with clinical deterioration (defined as intensive care unit (ICU) transfer or death), and developed a prognostic index. Overall; we analyzed 239 patients (29.3% females) with a mean age of 63.9 (standard deviation [SD]; 14.0) years. Clinical deterioration occurred in 70 patients (29.3%), including 41 (17.2%) ICU transfers and 36 (15.1%) deaths. The most common symptoms and signs at admission were cough (77.8%) and elevated respiratory rate (34.1%), while 66.5% of patients had at least one coexisting medical condition. Imaging frequently revealed ground-glass opacity (68.9%) and consolidation (23.8%). Age; increased respiratory rate; abnormal blood gas parameters and imaging findings; coexisting coronary heart disease; leukocytosis; lymphocytopenia; and several laboratory parameters (elevated procalcitonin; interleukin-6; serum ferritin; C-reactive protein; aspartate aminotransferase; lactate dehydrogenase; creatinine; fibrinogen; troponin-I; and D-dimer) were significant predictors of clinical deterioration. We suggested a prognostic index to assist risk-stratification (C-statistic; 0.845; 95% CI; 0.802–0.887). These results could aid early identification and management of patients at risk, who should therefore receive additional monitoring and aggressive supportive care.

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Lisa, Andrea Vittorio Emanuele, Leonardo Galtelli, Valeriano Vinci, Alessandra Veronesi, Luca Cozzaglio, Ferdinando Carlo Maria Cananzi, Federico Sicoli et Marco Klinger. « Adoption of a Newly Introduced Dermal Matrix : Preliminary Experience and Future Directions ». BioMed Research International 2020 (16 octobre 2020) : 1–5. http://dx.doi.org/10.1155/2020/3261318.

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Introduction. Acellular dermal matrix (ADM) products are adopted in the management of injuries to soft tissues. ADMs have been increasingly employed for their clinical advantages, and they are acquiring relevance in the future of plastic surgery. The aim of our study is to evaluate the application of ADMs in our patients who could not undergo fast reconstruction. Materials and Methods. We performed a retrospective study on 12 patients who underwent ADM placement for scalp and limb surgical reconstructions at the Humanitas Research Hospital, Rozzano (Milano), Italy. Wounds resulted from 9 tumor resections and 3 chronic ulcers. The ADM substrate used to treat these lesions was PELNAC™ (Gunze, Japan), a double-layered matrix composed of atelocollagen porcine tendon and silicon reinforcement. All patients underwent a second surgical operation to complete the treatment with a full-thickness skin graft to cover the lesion. Results. In this study, 12 patients were treated with PELNAC™: 11 out of 12 patients showed a good attachment over a median time of 21.3 days (range 14-27). After almost 23 days, all patients were ready to undergo a full-thickness skin grafting. Conclusion. This study assesses the benefits of PELNAC™ and proposes this method as an alternative to traditional approaches, especially in situations where the latter techniques cannot be applied.

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Santoro, A., R. Cavina, H. Soto Parra, F. Latteri, E. Campagnoli, V. Ginanni, G. Biancofiore, V. Pedicini, M. Alloisio et A. Sala. « Oral ZD1839 (iressa) in non-small cell lung cancer (NSCLC) : preliminary results from a series of patients at the Istituto Clinico Humanitas, Rozzano-Milano ». European Journal of Cancer 37 (avril 2001) : S60. http://dx.doi.org/10.1016/s0959-8049(01)80702-4.

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Cavina, Raffaele, Hector J. Soto Parra, Paolo A. Zucali, Elisabetta Campagnoll, Latteri Fiorenza, Giuseppe Biancofiore, Giovanni Abbadessa, Emanuela Morenghi et Armando Santoro. « P-618 ZD 1839 (Iressa) in elderly patients with progressive pretreated non small cell lung cancer (NSCLC) : Results at the Istituto clinico humanitas, Rozzano, Milano ». Lung Cancer 41 (août 2003) : S248. http://dx.doi.org/10.1016/s0169-5002(03)92585-2.

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Beidler, Philip D. « South Pacific and American Remembering ; or, “Josh, We're Going to Buy This Son of a Bitch!” ». Journal of American Studies 27, n^o 2 (août 1993) : 207–22. http://dx.doi.org/10.1017/s0021875800031534.

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For many post-1945 Americans, the title South Pacific does not describe a text so much as a process of remembering. For the cultural historian, it offers an account of production. It is the relationship of these that will be my subject. The pattern of the former will largely depend, of course, on the rememberer – something of a book perhaps, a play, a movie, a song, another song. The latter, albeit complicated, is traceable. It has a literary provenance in a 1947 collection of fictional narratives by James A. Michener entitled Tales of the South Pacific, variously described as short stories or a novel, but always noted as winner of the Pulitzer Prize. In translation to Rodgers and Hammerstein's 1949 Broadway classic, it adds another Pulitzer and a paperback fortune for the original honoree: to one of the most celebrated runs in the golden era of the American musical. It parlays that success into one of the first widely popular 33⅓ RPM long-playing records, memorialized in its dramatic connection by a cover photograph of Mary Martin and Ezio Pinza in the lead roles of U.S. Navy nurse Nellie Forbush and French planter Emile DeBecque. It then reappears as a 1958 movie musical spectacular, leading to another joyride of the Michener narrative on the best-seller lists, and to yet another best-selling LP, now in stereo, with the cover photo of the lovers, here Mitzi Gaynor and Rozzano Brazzi, resituated against a Hollywood backdrop of wide-screen tropical splendors. Along the way, it proliferates into endless road productions and revivals; television showings and VCR rentals; re-recordings and new recordings on LP, tape, and compact disk.

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Stefanini, Giulio G., Mauro Chiarito, Giuseppe Ferrante, Francesco Cannata, Elena Azzolini, Giacomo Viggiani, Andrea De Marco et al. « Early detection of elevated cardiac biomarkers to optimise risk stratification in patients with COVID-19 ». Heart 106, n^o 19 (14 août 2020) : 1512–18. http://dx.doi.org/10.1136/heartjnl-2020-317322.

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ObjectiveRisk stratification is crucial to optimise treatment strategies in patients with COVID-19. We aimed to evaluate the impact on mortality of an early assessment of cardiac biomarkers in patients with COVID-19.MethodsHumanitas Clinical and Research Hospital (Rozzano-Milan, Lombardy, Italy) is a tertiary centre that has been converted to the management of COVID-19. Patients with confirmed COVID-19 were entered in a dedicated database for cohort observational analyses. Outcomes were stratified according to elevated levels (ie, above the upper level of normal) of high-sensitivity cardiac troponin I (hs-TnI), B-type natriuretic peptide (BNP) or both measured within 24 hours after hospital admission. The primary outcome was all-cause mortality.ResultsA total of 397 consecutive patients with COVID-19 were included up to 1 April 2020. At the time of hospital admission, 208 patients (52.4%) had normal values for cardiac biomarkers, 90 (22.7%) had elevated both hs-TnI and BNP, 59 (14.9%) had elevated only BNP and 40 (10.1%) had elevated only hs-TnI. The rate of mortality was higher in patients with elevated hs-TnI (22.5%, OR 4.35, 95% CI 1.72 to 11.04), BNP (33.9%, OR 7.37, 95% CI 3.53 to 16.75) or both (55.6%, OR 18.75, 95% CI 9.32 to 37.71) as compared with those without elevated cardiac biomarkers (6.25%). A multivariate analysis identified concomitant elevation of both hs-TnI and BNP as a strong independent predictor of all-cause mortality (OR 3.24, 95% CI 1.06 to 9.93).ConclusionsAn early detection of elevated hs-TnI and BNP predicts mortality in patients with COVID-19. Cardiac biomarkers should be systematically assessed in patients with COVID-19 at the time of hospital admission in order to optimise risk stratification.

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Jean, el-Cheikh, Crocchiolo Roberto, Fürst Sabine, Bramanti Stefania, Sarina Barbara, Granata Angela, Faucher Catherine et al. « Micafungin Versus Fluconazole Or Itraconazole For Prophylaxis Against Invasive Fungal Infections During Neutropenia In Patients Undergoing Haplo-Identical Hematopoietic Stem Cell Transplantation ». Blood 122, n^o 21 (15 novembre 2013) : 4564. http://dx.doi.org/10.1182/blood.v122.21.4564.4564.

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Objectives Over the past decade, invasive fungal infections (IFI) have remained an important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. Patients and Methods we conducted a retrospective, bi-institutional comparative clinical study, (Institut Paoli-Calmettes at Marseille France and Humanitas cancer center at Rozzano, Italy), and we compared the efficacy and safety of Micafungin 50mg/day (iv) with those of fluconazole (400mg/day) or itraconazole 200mg/day (iv) as prophylaxis for adult patients with various haematological diseases receiving haplo-identical allogeneic stem cell transplantation (haplo-SCT). Patients received prophylaxis with the beginning of the transplant conditioning regimen until the hospital discharge, or until occurrence of an IFI. We compared the incidence of proven or probable IFI (the primary end point) between the micafungin and fluconazole or itraconazole groups; death from any cause and time to death was secondary end points. Patients were followed for 100 days after haplo-SCT and for 30 days after the last dose of the prophylaxis drug administrated. Results From January 2009 to May 2013, a total of 99 patients were identified; 30 patients received micafungin, and 69 patients received fluconazole or itraconazole. 81 patients (82%) received a non myeloabaltive conditioning regimen (NMA), with Fludarabine, Cyclophosphamide and Total body irradiation (TBI) 2 Gy based , or Fludarabine, Busulfan, and Cyclophosphamide based (3%) or other (9%), while five patients (5%) received a thiotepa-based conditioning regimen. The patients and transplant details are shown in the table 1. Proven or probable invasive fungal infections were reported in 2 patients (7%) in the micafungin group and 8 patients (12%) in the fluconazole or itraconazole group (absolute reduction in the micafungin group, −5%; 95% confidence interval, 0.0565-3.1395, P=0.72). Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 5 [7%], P=0.6). A total of 4 (13%) patients in the micafungin group and 23 (33%) patients in the fluconazole or itraconazole group received empirical antifungal therapy (P = 0.14). No serious adverse events related to treatment were reported by patients and there was no treatment discontinuation because of drug related adverse event in both groups. Overall Survival and disease free survival were similar among the two groups (P = 0.97). 6 patients (20%) in the micafungin group died within 100 days, as did 10 patients (14%) in the fluconazole or itraconazole group (P = 0.57). Interestingly the transplant related mortality (TRM) at 100 days was 0% in the micafungin group vs 13% in the second group [CI 95% (0-22)] (p=0,06), whereas the relapse or progression rate at 100 days was 27% vs. 8% respectively [CI 95% (14-44)] (p=0,14). Conclusions In patients undergoing to haplo-SCT, antifungal prophylaxis with micafungin is well tolerated and effective to prevent IFI. Furthermore, the incidence of IFI and invasive aspergillosis seems lower even if this did not attend statistical power, probably due to low number of patients. Disclosures: No relevant conflicts of interest to declare.

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Hu, Peifeng, et David B. Reuben. « Response Letter to Dr. Rozzini ». Journal of the American Geriatrics Society 52, n^o 3 (mars 2004) : 471. http://dx.doi.org/10.1111/j.1532-5415.2004.52125_5.x.

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White-Chu, E. Foy, William J. Graves, Sandra M. Godfrey, Alice Bonner et Philip Sloane. « Response to Rozzini and Trabucchi ». Journal of the American Medical Directors Association 11, n^o 1 (janvier 2010) : 79. http://dx.doi.org/10.1016/j.jamda.2009.09.012.

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Luchsinger, Jose A., et Richard Mayeux. « RESPONSE LETTER TO ROZZINI ET AL. » Journal of the American Geriatrics Society 53, n^o 1 (janvier 2005) : 176–77. http://dx.doi.org/10.1111/j.1532-5415.2005.t01-1-53031_9.x.

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Jean, El-Cheikh, Crocchiolo Roberto, Fürst Sabine, Bramanti Stefania, Sarina Barbara, Granata Angela, Faucher Catherine et al. « Comparison Of Umbilical Cord Blood and Haploidentical Donor Grafts In Adults With High Risk Hematologic Diseases After Fludarabine Cyclophosphamide and TBI 2 Gy Based Reduced-Intensity Conditioning Regimen Stem Cell Transplantation ». Blood 122, n^o 21 (15 novembre 2013) : 3288. http://dx.doi.org/10.1182/blood.v122.21.3288.3288.

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Abstract Introduction Human leukocyte antigens (HLA)-matched sibling or unrelated donor are available for around only 50-60% of patients. However, for patients without a suitably matched related donor, Alternative donors such as mismatched unrelated, cord blood and mismatched family donors could be searched. The aim of this retrospective study was to compare the results of graft source on outcome of patients after haploidentical related donor (Haplo), and the unrelated umbilical cord blood (UCB) transplantation in the setting of Non myeloabalative conditioning regimen (NMA). Patients and methods We retrospectively analyzed outcomes in 150 adult patients with high risk hematologic diseases who received Allo-SCT from alternative donors from two centers (Institut Paoli-Calmettes at Marseille France and Humanitas cancer center at Rozzano, Italy): These two centres have been applying common transplant approaches and procedures during the study period. 69 patients received Haplo and 81 patients received UCB. In the UCB group, the NMA regimen consisted of fludarabine (Flu), cyclophosphamide (Cy) and low dose TBI (2 Gy) combination in the two groups. The GVHD prophylaxis consisted of Cyclosporine A (CsA) and MMF in all patients in the two groups. In the Haplo group all patients received also 50 mg/kg Cy at day 3 and 4 post transplant. Of note, supportive care was the same during the whole study period. CMV infection management was also homogeneous. Patient characteristics are shown in Table 1. Results With a median follow-up of 59 months (8-101) and 18 months (3-51), in the UCB group versus the Haplo group, respectively. Nine patients (11%) in the UCB and 8 patients (12%) in the Haplo group had a spontaneous autologous reconstitution subsequent to primary graft failure. The median times to neutrophil and platelet recovery were 20 d (14–39) and 29 d (14–50) after Haplo and 22 d (6–67) and 41 d (18–80) after cord blood. All supportive care measures included red blood cell, and platelet transfusions were significantly increased in cord blood transplantation group. The cumulative incidence of transplant related mortality (TRM) at one year was 23% in the UCB group versus 17% in the Haplo group (P=0.39). Grade 2-4 acute graft-vs.-host disease (GVHD) and extensive chronic GVHD incidences were 52% versus 29% (P=0.05), and 12% versus 6% (P<0.0001), in the UCB group versus the Haplo group, respectively. The Kaplan-Meier estimate of overall survival at 2 years was 45% (95%CI, 34-56%) in the UCB group versus 69% (95%CI, 58-80%) in the Haplo group, (P=0.10). The estimate of progression-free survival at 2 years was 36% (95%CI, 25-47%) in the UCB group versus 65% (95% CI, 53-77%) in the Haplo group (P=0.01). Figure 1 Conclusion In this study, relapse and PFS was lower in Haplo group than in UCB transplants. The main difference between the 2 groups was the significantly higher incidence of acute and chronic GVHD in the UCB group. Surprisingly, this did not translate into a decrease of the cumulative incidence of OS nor increase of the TRM, which may be explained by a slightly shorter follow-up in this group. Our results suggest that haploidentical transplants are a good and promising alternative option for patients with high risk hematological diseases who lack an HLA-matched donor (sibling or unrelated donor). This should be now investigated in prospective comparative studies. Disclosures: No relevant conflicts of interest to declare.

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Flaherty, Joseph H., et Syed H. Tariq. « RESPONSE LETTER TO DR. ROZZINI ET AL. » Journal of the American Geriatrics Society 53, n^o 5 (mai 2005) : 915–16. http://dx.doi.org/10.1111/j.1532-5415.2005.t01-1-53278_5.x.

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Mehta, K. M., et K. E. Covinsky. « Response to Rozzini and Colleagues' Letter to the Editor ». Journals of Gerontology Series A : Biological Sciences and Medical Sciences 58, n^o 12 (1 décembre 2003) : M1146. http://dx.doi.org/10.1093/gerona/58.12.m1146.

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Fitzgerald, Stephen P., et Nigel G. Bean. « Response to Rozzini and Trabucchi’s Letter to the Editor ». Journal of the American Medical Directors Association 12, n^o 4 (mai 2011) : 318. http://dx.doi.org/10.1016/j.jamda.2011.01.012.

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Morley, John E. « Response to the Letter to the Editor by Renzo Rozzini ». Journal of the American Medical Directors Association 9, n^o 5 (juin 2008) : 368. http://dx.doi.org/10.1016/j.jamda.2008.03.009.

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Castagna, Luca, Stefania Bramanti, Sabine Furst, Barbara Sarina, Roberto Crocchiolo, Laura Giordano, Jean El Cheikh et al. « Tacrolimus (FK) Compared to Cyclosporine a (CyA) after Haploidentical T Cell Replete Stem Cell Transplantation (Haplo-SCT) with Post-Infusion Cyclophosphamide : A Retrospective Analysis ». Blood 124, n^o 21 (6 décembre 2014) : 3902. http://dx.doi.org/10.1182/blood.v124.21.3902.3902.

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Abstract Introduction. Investigators from Johns Hopkins University pioneered the use of post-transplantation cyclophosphamide (PT-Cy) after T cell-replete haploidentical bone marrow (BM) infusion. A significant component of this scheme is tacrolimus (FK), associated to mycophenolate mofetil (MMF), to prevent immunological complications. FK is a calcineurin inhibitor, almost 100-fold more potent than cyclosporine A (CyA) in its inhibitory activity. In this retrospective study, we analyzed 100 patients grafted with Haplo-SCT with PT-Cy, and receiving FK or CyA. Patients and Methods. From April 2009 until April 2013, we analyzed 100 consecutive patients at two institutions (Institut Paoli Calmettes Marseille, France and Humanitas Cancer Center, Rozzano, Italy). Conditioning regimen was identical consisting of Fludarabine, Cyclophosphamide, and low dose TBI. GVHD prophylaxis consisted of Cy 50 mg/kg on days +3 and +4, FK or CyA and MMF. FK (at a total dose of 1 mg) was administered as a continuous infusion and then converted to oral formulation. CyA was dosed at 3 mg/kg as a continuous infusion and was then converted to oral formulation. MMF was administered at 45 mg/kg/day until day +35. FK, CyA and MMF were started on day +5. FK and CyA were tapered by day +100-180. Stem cell source was BM or peripheral blood stem cells (PBSC). Results. Patient and transplant characteristics are shown in Table 1. The cumulative incidence of engraftment was similar between FK and CyA groups: 30-days absolute neutrophil count > 500 was 79% vs 91% (p 0.3), and unsupported platelet count more than 20 000 at 60 days was 77% vs 84% (p 0.7), respectively. The incidence of grade 2-4 acute GVHD was 26% vs 30% (p 0.5) and the incidence of chronic GVHD was 13% vs 8% (p 0.9), respectively. The 2-year progression free survival (PFS) and overall survival (OS) were 53% vs 64% (p 0.2) and 65% vs 65%, respectively (p 0.7). The 2-year relapse incidence (RI) was 28% vs 12% (p 0.08) and the 2-year non relapse mortality was 16% vs 14% (p 0.7), respectively. In univariate analysis, only disease status (CR vs not CR) impacted the PFS, OS, and RI. Patients were regrouped in 3 cohorts (1 patient excluded because received FK + PBSC): FK + BM (n 42), CyA + BM (n 14), and CyA + PBSC (n 43). 1-year NRM was not different (17% vs 14% vs 15%, p 0.8). Compared to FK +BM and CyA + PBSC, a trend in favor of CyA + BM was observed in terms of aGVHD (7% vs 24% vs 38%, p 0.05) and cGVHD (0 vs 13% vs 10%, p 0.9). Conclusions. Although this is a retrospective study with potential selection bias, using CyA instead of standard FK did not seem to affect any major clinical outcome, with special interest for aGVHD and cGVHD. The NRM is acceptable in line with that published. GVHD incidence was lower in the group CyA + BM compared to other 2 groups. Disease status before haplo SCT was the only prognostic factor for survival and relapse. Table 1. Patient and transplant characteristics. All pts FK CSA p N % N % 100 43 57 Male Female 58/42 22/21 51/49 36/21 63/37 0.229 Age (mean) 46 44 48 0.135 Disease status at haplo 0.466 CR 56 23 53 33 58 PR 29 14 33 15 26 SD 6 1 2 5 9 PD 9 5 12 4 7 Armand Risk 0.646 Low 9 3 7 6 11 Int 72 33 77 39 68 High/Very high 19 7 16 12 21 Previous transplant <0.001 Relapse after ALLO 8 0 0 8 14 Relapse after HDC 40 21 49 19 33 Sex D/R 0.533 F/F 16 9 21 7 12 F/M 21 8 19 13 23 M/M 38 14 33 24 42 M/F 25 12 28 13 23 CMV D/R 0.009 POS/POS 70 35 81 35 61 NEG/NEG 18 2 5 16 28 POS/NEG 11 6 14 5 9 Donor 0.578 children 26 12 28 14 25 Mother 15 7 16 8 14 Father 11 6 14 5 9 Sibling 47 17 40 30 53 Cousin 1 Stem cell source <0.001 BM 56 42 98 14 25 PBSC 44 1 2 43 75 HCT-CI 0.007 0 31 18 42 13 23 1-2 23 13 30 10 18 >3 46 12 28 34 60 CD34 (mean) 4,4 3,5 5,2 <0.001 Disclosures No relevant conflicts of interest to declare.

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McCusker, J., M. Cole, E. Latimer, A. Ciampi et S. Windholz. « REPLY TO LETTER FROM ROZZINI AND COLLEAGUES ABOUT DEPRESSION IN OLDER MEDICAL INPATIENTS ». Journals of Gerontology Series A : Biological Sciences and Medical Sciences 62, n^o 7 (1 juillet 2007) : 798. http://dx.doi.org/10.1093/gerona/62.7.798.

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van der Steen, Jenny T., David R. Mehr, Robin L. Kruse et Miel W. Ribbe. « Pneumonia and Mortality in Elderly Patients : Response to a Letter by Dr Rozzini et al ». Journal of the American Medical Directors Association 9, n^o 1 (janvier 2008) : 66–67. http://dx.doi.org/10.1016/j.jamda.2007.09.004.

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Periansya, Sopiyan.AR, Ardiyan Natoen et Susi Ardiani. « Pendampingan Penyusunan Sumber Dan Penggunaan Modal Kerja Usaha Kerajinan Tenun Tajung Rozzaq Jaya ». JURPIKAT (Jurnal Pengabdian Kepada Masyarakat) 2, n^o 1 (20 avril 2021) : 171–78. http://dx.doi.org/10.37339/jurpikat.v2i1.519.

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Pengabdian kepada masyarakat ini bertujuan untuk memberikan pendampingan penyusunan Sumber dan penggunaan modal kerja. Pelaksanaan kegiatan ini dilakukan dengan memberikan pendampingan ,penyuluhan dan pembimbingan dalam keterkaitannya dengan modal kerja. Hasil keiatan menunjukkan bahwa pemilik usaha yang selama ini tidak memahami pentingnya penyusunan modal kerja akhirnya menyadari manfaat penyusunan modal kerja tersebut. Pendampingan dalam pengabdian ini dimulai dengan dengan mengenalkan laporan keuangan setelah dengan memperkenalkan akun yang diperlukan seperti aset lancar, aset tetap, hutang dan modal. Setelah pemilik memahami cara menyusun secara sederhana, pendampingan dilanjutkan dengan memsimulasikan penyusunan modal kerja. Dalam simulasi tersebut pengabdi memperagakan laporan keuangan yang telah dibuat. Pemilik diajarkan bagaimana menyusun modal kerja, setelah di damping secara perlahan pemilik memahami cara penyusunan modal kerja. Dari simulasi penyusunan modal kerja yang dibuat ternyata usaha ini cukup baik dalam pengelolaan modal kerjanya.

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Solms, Alexander, Anita Shah, Sara Wiegmann, Maurice Ahsman, Erik Berntorp, Andreas Tiede, Alfonso Iorio, Maria Elisa Mancuso, Tihomir Zhivkov et Toshko Lissitchkov. « Potency-Adjusted Analyses of a Head-to-Head Pharmacokinetic Study of Damoctocog Alfa Pegol (BAY 94-9027) and Efmoroctocog Alfa (rFVIIIFc) in Patients with Severe Hemophilia A ». Blood 136, Supplement 1 (5 novembre 2020) : 24–25. http://dx.doi.org/10.1182/blood-2020-136586.

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Background Damoctocog alfa pegol (BAY 94-9027; Jivi®) is a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated with a single, dual-branched 60 kDa polyethylene glycol molecule to extend its half-life. A previous head-to-head crossover study demonstrated that damoctocog alfa pegol has an improved pharmacokinetic (PK) profile compared with efmoroctocog alfa (rFVIIIFc; Elocta®/Eloctate®), an extended-half-life (EHL), recombinant FVIII fusion protein. A single infusion of damoctocog alfa pegol resulted in 25% higher area under the curve (AUClast) and 20% lower clearance (CL) compared with efmoroctocog alfa. Owing to differences in batch-specific FVIII activity, the actual dose of efmoroctocog alfa administered was subsequently found to be higher than for damoctocog alfa pegol. Thus, to provide a more accurate assessment of the differences in PK parameters between these two products, actual dosing should be considered. In the present study, dose-normalized analyses considering the dosing based on actual potency were performed for an accurate and valid comparison of PK parameters between damoctocog alfa pegol and efmoroctocog alfa. Methods The head-to-head comparison of the PK of EHL FVIII products was a single-center, randomized, open-label, crossover study of damoctocog alfa pegol and efmoroctocog alfa (ClinicalTrials.gov identifier: NCT03364998). Eligible patients were male, aged 18-65 years with severe hemophilia A (FVIII <1%). After a wash-out period of ≥3 or ≥5 days for prior treatment with standard-half-life or EHL FVIII products respectively, patients were randomized 1:1 to receive a single 60 IU/kg dose of either damoctocog alfa pegol or efmoroctocog alfa. Patients received a single dose of the other product following a ≥7-day wash-out after the dose of the first product. In the study, doses were determined based on the nominal potency value as labeled on the vial. In the present study, PK parameters including normalized AUC (AUCnorm), CL, normalized maximum concentration (Cmax norm), volume of distribution at steady state (Vss) and incremental recovery, were assessed using doses adjusted for actual potencies, according to the certificates of analysis provided by the manufacturers for the actual batches used. Results As previously described elsewhere, one patient with pre-existing anti-PEG antibodies was considered an outlier for the PK analysis and was excluded from this analysis. In total, 17 patients were included in this analysis, and had a median age of 34 years (Table 1). For both drugs, vials with nominal potency of 1000 IU/vial were used, while actual potencies of efmoroctocog alfa and damoctocog alfa pegol used in this study were 1093 IU/vial and 990 IU/vial, respectively. Hence, the actual dose of efmoroctocog alfa administered was approximately 10.4% higher than the administered dose of damoctocog alfa pegol. After potency-adjustment, AUCnorm and CL were in favor of damoctocog alfa pegol (Table 2). AUCnorm was significantly increased by 39% (P < 0.001) for damoctocog alfa pegol compared with efmoroctocog alfa; an increase with damoctocog alfa pegol compared with efmoroctocog alfa was observed in 16 (94.1%) out of 17 patients. Geometric mean CL was significantly reduced with damoctocog alfa pegol versus efmoroctocog alfa (0.0198 dL/h/kg vs 0.0273 dL/h/kg; P < 0.001), with 16 (94.1%) patients exhibiting a difference in favor of damoctocog alfa pegol. No significant differences in Cmax norm between the two products were observed. Conclusion In the precedent analysis, published elsewhere, damoctocog alfa pegol demonstrated improvements in AUC, CL and t½ compared with efmoroctocog alfa. The improvements are confirmed in this potency-adjusted analysis, while, compared with the unadjusted analysis, a greater improvement for AUCnorm is observed for damoctocog alfa pegol versus efmoroctocog alfa. These data further support the superior PK profile of damoctocog alfa pegol compared with efmoroctocog alfa. Disclosures Solms: Bayer: Current Employment, Current equity holder in private company. Shah:Bayer: Current Employment, Current equity holder in private company. Wiegmann:Bayer: Current Employment. Ahsman:Bayer: Consultancy. Berntorp:Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Research Funding; Shire: Research Funding; Sobi/Bioverativ: Research Funding; Octapharma: Consultancy, Honoraria; Shire/Takeda: Consultancy, Honoraria. Tiede:Biotest: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; Chugai: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria. Iorio:Bayer: Research Funding; BioMarin: Research Funding; CSL: Research Funding; Freeline: Research Funding; Grifols: Research Funding; Sanofi: Research Funding; Spark: Research Funding; Takeda: Research Funding; Uniqure: Research Funding; NovoNordisk: Research Funding; Octapharma: Research Funding; Pfizer: Research Funding; Roche: Research Funding. Mancuso:Center for Thrombosis and Hemorrhagic Diseases, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy: Current Employment; Bayer, CSL Behring, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd, Octapharma, Kedrion, Grifols, Catalyst, Kedrion, Sobi: Membership on an entity's Board of Directors or advisory committees; Bayer, CSL Behring, Novo Nordisk, F. Hoffmann-La Roche Ltd, Octapharma, Grifols, Sobi: Speakers Bureau; Bayer, CSL Behring, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd, Octapharma, Kedrion, Grifols, Sobi, PedNet Foundation: Consultancy. Zhivkov:Bayer: Other: Sub-Investigator of clinical trials, Research Funding; Apellis: Other: Sub-Investigator of clinical trials; Catalyst: Other: Sub-Investigator of clinical trials; Octapharma: Other: Sub-Investigator of clinical trials; Sanofi: Other: Sub-Investigator of clinical trials. Lissitchkov:Bayer: Other: Principal investigator of clinical trials ; CSL Behring: Other: Principal investigator of clinical trials ; Novo Nordisk: Other: Principal investigator of clinical trials ; Octapharma: Other: Principal investigator of clinical trials ; Sanofi: Other: Principal investigator of clinical trials ; Roche: Membership on an entity's Board of Directors or advisory committees, Other: lecturer; Shire: Other: lecturer; Sobi: Membership on an entity's Board of Directors or advisory committees, Other: lecturer; Catalyst Biosciences: Other: Principal investigator of clinical trials .

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Bernard, Enrico. « L’italiano ha mille anni : Spunti drammatici sull’origine della lingua e della letteratura italiane in occasione della svolta millenaria del nostro idioma ». Forum Italicum : A Journal of Italian Studies 48, n^o 3 (10 septembre 2014) : 551–61. http://dx.doi.org/10.1177/0014585814542583.

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La lingua italiana è nata circa un millennio fa dalla trasformazione della liturgia drammatica in dramma liturgico. Attori di questo processo sono stati i “comici” che hanno sviluppato il dramma per la comprensione liturgica e per intrattenere il pubblico su temi religiosi conosciuti. Si è innescato così un processo abbastanza rapido di delatinizzazione e “involgarimento” delle sacre rappresentazioni che, spostandosi dall’altare alle piazze, hanno preso la forma meno solenne di laudi e misteri buffi. Questo processo è stato però messo in ombra dal tentativo – che ha origini lontane, addirittura in Dante – di nobilitare e idealizzare la genesi dell’italiano distinguendo il volgare dal “dolce stil novo”. La dicotomia ha scatenato discussioni secolari sul dialetto, in particolare sul fiorentino, che per Dante rappresenta quell’idioma “illustre, regale, curiale, cardinale” che si differenzia dal volgare come lingua d’ élite, letteraria e burocratica. Questa interpretazione, contrastata da Petrarca e Machiavelli, finì per eclissare l’origine drammatica, teatrale, dell’italiano. Ciò ha comportato un’interpretazione puramente letteraria e “fiorentinocentrica” della nostra storia linguistica e la “miseria” del teatro italiano sempre considerato, secondo una linea che va da Dante a Croce, come uno strumento troppo “volgare” e rozzo per sublimarsi in letteratura.

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Spaziante, Ermenegildo. « L’aborto provocato : dimensioni planetarie del fenomeno ». Medicina e Morale 45, n^o 6 (31 décembre 1996) : 1083–134. http://dx.doi.org/10.4081/mem.1996.893.

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La concentrazione del dibattito sulla liceità etica dell’aborto terapeutico espone al rischio di trascurare la realtà molto più consistente e diffusa dell’abortività provocata volontariamente e legalmente non per ragioni mediche, ma per libera opzione personale (aborto volontario), o per il controllo demografico delle nascite (aborto sociale). L’autore con questo studio si propone di fornire una visione globale del fenomeno abortivo su basi essenzialmente statistiche che consenta una migliore conoscenza delle dimensioni epidemiologiche e dell’estensione planetaria dell’abortività provocata così da evidenziarne il rapporto sia con l’evoluzione demografica sia con le prospettive di contenimento e prevenzione. La pratica abortiva è di fatto una acquisizione del costume corrente in ampi strati della popolazione in molti Paesi, mentre è sovente coperta in altri Paesi da un silenzio ingiustificato, ma significativo. Con ogni probabilità - ritiene l’autore - l’evoluzione culturale porterà ad evidenziare sempre più il carattere rozzo e disumano dell’aborto, come si è verificato per altri problemi sociali. La conoscenza oggettiva del problema medico e sociale dell’aborto indotto è auspicabile che solleciti normative e programmi tesi al suo massimo contenimento ed alla sua eliminazione; ma si tratterà di un’evoluzione lenta, progressiva e determinata ancor prima che dalle norme di legge emanate, dalla maturazione della coscienza civile, morale e sanitaria delle popolazioni.

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Corà, Ilaria. « L’arte della memoria per figure con il fac-simile dell’Ars memorandi notabili per figuras evangelistarum (1470), a cura di Mino Gabriele, postfazione di Ugo Rozzo ». Le Journal de la Renaissance 5 (janvier 2007) : 417–19. http://dx.doi.org/10.1484/j.jr.2.302518.

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Callaghan, Michael U., Claude Négrier, Ido Paz-Priel, Tiffany Chang, Sammy Chebon, Michaela Lehle, Johnny Mahlangu et al. « Safety and Efficacy of Emicizumab in Persons with Hemophilia a with or without FVIII Inhibitors : Pooled Data from Four Phase III Studies (HAVEN 1-4) ». Blood 136, Supplement 1 (5 novembre 2020) : 3–5. http://dx.doi.org/10.1182/blood-2020-137438.

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Introduction: Emicizumab-a subcutaneously administered, bispecific, humanized, monoclonal antibody-promotes effective hemostasis in people with hemophilia A (PwHA). The primary efficacy and safety of emicizumab were reported previously, but long-term data are limited. Here, data from a wide age-range of PwHA with/without factor (F)VIII inhibitors enrolled in the Phase III HAVEN 1 (NCT02622321), HAVEN 2 (NCT02795767), HAVEN 3 (NCT02847637), and HAVEN 4 (NCT03020160) studies are pooled to establish the durable efficacy and safety of emicizumab. Methods: The studies enrolled pediatric and adult PwHA with/without FVIII inhibitors. Participants received emicizumab prophylaxis 1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks. All participants assigned to receive emicizumab (including those assigned to control arms who later switched) are included in this analysis. Participants and/or caregivers recorded outcomes of bleeding events via the Bleed and Medication Questionnaire (BMQ). Data from HAVEN 1-4 were pooled for an aggregate analysis of emicizumab efficacy and safety. Efficacy endpoints include calculated mean annualized bleed rates (ABRs; discrete, consecutive 24-week treatment intervals), model-based ABRs (calculated via negative binomial regression for full study period), percentage of participants with zero and 1-3 treated bleeds, and annualized cumulative dose of coagulation factor (ACD). Safety endpoints include incidence of adverse events (AEs) and AEs of special interest. Results: Overall, 400 PwHA in HAVEN 1, 2, 3 and 4 (n=113, 88, 151, and 48, respectively) are included in the efficacy analysis for a total of 970.3 patient years (cutoff: 15 May 2020). The safety population comprises 399 PwHA who received ≥1 dose of emicizumab (1 PwHA was randomized to receive emicizumab but did not start treatment). The median age at baseline was 28.5 (range 1-77) years. The majority of participants were White (66.8%) or Asian (18.8%); 52.3% had FVIII inhibitors. In the 24 weeks prior to study entry, 60.9% of participants had target joints. The median duration of efficacy period was 120.4 (interquartile range 89.0-164.4) weeks; 85.0% of participants had an efficacy period of ≥74 weeks; 11 participants (2.8%) discontinued study treatment. Across all 4 studies, 90.9-94.8% of the observation period was covered by completed BMQs. Across all studies, the model-based treated bleed ABR was 1.4 (95% confidence interval 1.1-1.7); treated bleed ABRs remained low throughout, and were seen to decrease with successive 24-week treatment intervals (Table 1). During Weeks 121-144 (n=170), 82.4% of participants had zero treated bleeds, and 15.3% of participants had 1-3 treated bleeds. During the same period, 91.8% and 90.0% had zero treated spontaneous/joint bleeds respectively (Figure 1). The proportion of participants with target joints reduced from 60.9% prior to study entry to 4.6% at Weeks 1-24, then <1.5% in all subsequent treatment intervals. ACD of FVIII (Table 2), activated prothrombin complex concentrate (aPCC) and activated recombinant FVII (rFVIIa, Table 3) generally decreased across each 24-week treatment interval. Emicizumab was well tolerated (Table 4), and no participants discontinued due to AEs beyond the five previously described (Oldenburg et al. N Engl J Med 2017; Young et al. Blood 2019; Mahlangu et al. N Engl J Med 2018; Pipe et al. Lancet Haem 2019). At data cut, 1 fatality, 3 thrombotic microangiopathies (TMAs), and 4 thromboembolic events (TEs) have been reported; all but 1 occurred in HAVEN 1. All TMAs and 2 of 4 TEs were associated with concomitant aPCC use. The percentage of participants with ≥1 drug-related AE in Weeks 1-24, 25-48 and 49-72 were 28.8%, 6.8%, and 3.0% respectively; over the same intervals, injection site reactions were observed in 23.3%, 4.8%, and 2.5% of participants. Conclusions: With nearly 3 years of follow-up, emicizumab maintained low bleed rates in PwHA of all ages, with/without FVIII inhibitors. ABRs continued to decrease and the proportion of participants with zero treated bleeds increased with each consecutive 24-week period; the trend was the same for the proportion of participants with zero joint bleeds and almost all target joints resolved. The ACDs of FVIII, aPCC, and rFVIIa decreased with successive treatment intervals. Emicizumab remains well tolerated over long-term follow-up, and no new safety concerns have been identified to date. Disclosures Callaghan: Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Speakers Bureau; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Research Funding; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Hema Biologics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alnylum: Current equity holder in publicly-traded company; Spark: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Roche/Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Speakers Bureau; NovoNordisk: Other, Speakers Bureau; Sancillio: Other. Négrier:CSL Behring, Octapharma, Shire/Takeda, Sobi: Research Funding; CSL, F. Hoffmann-La Roche Ltd, Sobi: Other: Travel support; Bayer, Biomarin, CSL Behring, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Shire/Takeda, Sobi, Spark: Consultancy. Paz-Priel:Genentech, Inc: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Other: All authors received editorial support for this abstract, provided by Scott Battle, PhD, of Health Interactions and funded by F. Hoffmann-La Roche.. Chang:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Chebon:F. Hoffmann-La Roche Ltd: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Lehle:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in private company. Mahlangu:CSL Behring, Catalyst Biosciences, Freeline Therapeutics, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi, Spark and Takeda: Consultancy; South Africa Medical Research Council, Wits Health Consortium, Colleges of Medicine of South Africa: Membership on an entity's Board of Directors or advisory committees; CSL Behring, Catalyst Biosciences, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi, Spark and Takeda: Speakers Bureau; BioMarin, CSL Behring, Freeline Therapeutics, Novo Nordisk, Novartis, Pfizer, Sanofi, F. Hoffmann-La Roche Ltd, uniQure: Research Funding. Young:Bayer, CSL Behring, Freeline, UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding; BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria. Kruse-Jarres:Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Consultancy; CSL Behring, Genentech, Inc., Spark: Research Funding; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Honoraria; F. Hoffmann-La Roche Ltd: Speakers Bureau. Mancuso:Bayer, CSL Behring, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd, Octapharma, Kedrion, Grifols, Sobi, PedNet Foundation: Consultancy; Bayer, CSL Behring, Novo Nordisk, F. Hoffmann-La Roche Ltd, Octapharma, Grifols, Sobi: Speakers Bureau; Bayer, CSL Behring, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd, Octapharma, Kedrion, Grifols, Catalyst, Kedrion, Sobi: Membership on an entity's Board of Directors or advisory committees; Center for Thrombosis and Hemorrhagic Diseases, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy: Current Employment. Niggli:F Hoffmann-La Roche Ltd: Current Employment. Kuebler:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Selak Bienz:F. Hoffmann-La Roche Ltd: Current Employment. Shima:Chugai Pharmaceutical Co., F. Hoffmann-La Roche Ltd, BioMarin, Bayer, Sanofi: Membership on an entity's Board of Directors or advisory committees; Chugai Pharmaceutical Co. , Sanofi, Bayer, Sysmex: Speakers Bureau; Patents related to anti-FIXa/FX bispecific antibodies: Patents & Royalties; Chugai Pharmaceutical Co.: Honoraria; Chugai Pharmaceutical Co. , F. Hoffmann-La Roche Ltd, Sanofi, CSL Behring, KM Biologics, Novo Nordisk, Shire/Takeda: Research Funding; Chugai Pharmaceutical Co.: Consultancy. Jimenez-Yuste:F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer, Grifols, Octapharma, CSL Behring, Bayer: Honoraria; F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer: Consultancy; Grifols, Novo Nordisk, Takeda, Sobi, Pfizer: Research Funding. Schmitt:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Asikanius:Fimea: Current Employment; F Hoffman-La Roche Ltd: Ended employment in the past 24 months; F Hoffmann-La Roche Ltd: Divested equity in a private or publicly-traded company in the past 24 months. Levy:F Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Ended employment in the past 24 months; Spark Therapeutics: Current Employment; Baxalta US: Patents & Royalties: Royalties from ADAMTS13 patent . Pipe:Medical and Scientific Advisory Council to the National Hemophilia Foundation; Medical Advisory Board to World Federation of Hemophilia: Membership on an entity's Board of Directors or advisory committees; Apcintex, Bayer, BioMarin, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., Sangamo Therapeutics, Sanofi, Takeda, Spark Therapeutics, uniQure: Consultancy; Siemens: Research Funding. Oldenburg:Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche, Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Speakers Bureau; Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche. Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Other; Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche, Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Membership on an entity's Board of Directors or advisory committees; University Clinic Bonn: Current Employment; Bayer, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer and Takeda: Research Funding; Bayer, BioMarin, Biotest, Chugai Pharmaceuticals Co., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche, Ltd, Spark, Swedish Orphan Biovitrum and Takeda: Honoraria.

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Peach, Joe James, et Quoc Thong Le Gia. « A spectral method to the stochastic Stokes equations on the sphere ». ANZIAM Journal 60 (26 juin 2019) : C52—C64. http://dx.doi.org/10.21914/anziamj.v60i0.13987.

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We construct numerical solutions to the stochastic Stokes equations on the unit sphere with additive noise. By characterising the noise as a tangential vector field, the weak formulation is derived and a spectral method is used to obtain a numerical solution. The theory is illustrated through a numerical experiment. References P. Benner and C. Trautwein. Optimal distributed and tangential boundary control for the unsteady stochastic Stokes equations. Technical Report, 2018. URL https://arxiv.org/abs/1809.00911. P. Chen, A. Quarteroni, and G. Rozza. Stochastic optimal Robin boundary control problems of advection-dominated elliptic equations. SIAM J. Numer. Anal., 51(5):27002722, 2013. doi:10.1137/120884158. A. Ciraudo, C. D. Negro, A. Herault, and A. Vicari. Advances in modelling methods for lava flow simulation. Commun. SIMAI Cong., 2:18, 2007. doi:10.1685/CSC06067. W. Freeden and M. Schreiner. Spherical functions of mathematical geosciences. Advances in Geophysical and Environmental Mechanics and Mathematics. Springer-Verlag, 2009. doi:10.1007/978-3-540-85112-7. M. Ganesh and Q. T. L. Gia. A radial basis Galerkin method for spherical surface Stokes equation. ANZIAM J., 52:C56C71, 2011. doi:10.21914/anziamj.v52i0.3921. M. Ganesh, Q. T. L. Gia, and I. H. Sloan. A pseudospectral quadrature method for NavierStokes equations on rotating spheres. Math. Comput., 80:13971430, 2011. doi:10.1090/S0025-5718-2010-02440-8. A. A. Il'in. The NavierStokes and Euler equations on two-dimensional manifolds. Math. USSR Sbornik, 69:559579, 1991. doi:10.1070/sm1991v069n02abeh002116. F. Narcowich, J. Ward, and G. Wright. Divergence-free RBFs on surfaces. J. Fourier Anal. Appl., 13:634663, 2007. doi:10.1007/s00041-006-6903-2. S. S. Sritharan. Optimal control of viscous flow. SIAM, 1998. doi:10.1137/1.9781611971415. D. A. Varshalovich, A. N. Moskalev, and V. K. Khersonskii. Quantum theory of angular momentum. World Scientific, 2008. doi:10.1142/0270.

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Nichols, James. « Coarse reduced model selection for nonlinear state estimation ». ANZIAM Journal 62 (7 février 2022) : C192—C207. http://dx.doi.org/10.21914/anziamj.v62.16169.

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State estimation is the task of approximately reconstructing a solu- tion u of a parametric partial differential equation when the parameter vector y is unknown and the only information is m linear measurements of u. Cohen et al. [arXiv:2009.02687, Nov. 2020] proposed a method to use a family of linear reduced spaces as a generalised nonlinear reduced model for state estimation. A computable surrogate distance is used to evaluate which linear estimate lies closest to a true solution of the pde problem. In this article we propose a strategy of coarse computation of the surrogate distance while maintaining a fine mesh reduced model, as the computational cost of the surrogate distance is large relative to the reduced modelling task. We demonstrate numerically that the error induced by the coarse distance is dominated by other approximation errors. References P. Binev, A. Cohen, W. Dahmen, R. DeVore, G. Petrova, and P. Wojtaszczyk. Convergence rates for geedy algorithms in reduced basis methods. SIAM J. Math. Anal. 43.3 (2011), pp. 1457–1472. doi: 10.1137/100795772. P. Binev, A. Cohen, W. Dahmen, R. DeVore, G. Petrova, and P. Wojtaszczyk. Data assimilation in reduced modeling. SIAM/ASA J. Uncert. Quant. 5.1 (2017), pp. 1–29. doi: 10.1137/15M1025384 A. Cohen, W. Dahmen, O. Mula, and J. Nichols. Nonlinear reduced models for state and parameter estimation. arXiv:2009.02687 [cs, math] (2020). url: http://arxiv.org/abs/2009.02687 (visited on 01/07/2021) A. Cohen, D. Wolfgang, R. DeVore, and J. Nichols. Reduced basis greedy selection using random training sets. ESAIM: Math. Model. Num. Anal. 54 (2020), pp. 1509–1524. doi: 10.1051/m2an/2020004. J. S. Hesthaven, G. Rozza, and B. Stamm. Certified reduced basis methods for parametrized partial differential equations. SpringerBriefs in Mathematics. Springer, 2016. doi: 10.1007/978-3-319-22470-1. Y. Maday, A. T. Patera, J. D. Penn, and M. Yano. A parameterized-background data-weak approach to variational data assimilation: formulation, analysis, and application to acoustics. Int. J. Num. Meth. Eng. 102.5 (2015), pp. 933–965. doi: 10.1002/nme.4747.

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Davies, Martin. « Ugo Rozzo. La strage ignorata : i fogli volanti a stampa nell'Italia dei secoli XV e XVI. Libri e Biblioteche 19. Udine : Forum Editrice, 2008. 247 pp. index. illus. €24. ISBN : 978–88–8420–494–3. » Renaissance Quarterly 62, n^o 4 (2009) : 1214–16. http://dx.doi.org/10.1086/650034.

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Hannawi, S., K. Naeem et H. Hannawi. « AB0168 BODY MASS INDEX IS ASSOCIATED WITH SIGNIFICANT ECHOCARDIOGRAPHIC ABNORMALITIES IN RHEUMATOID ARTHRITIS ». Annals of the Rheumatic Diseases 80, Suppl 1 (19 mai 2021) : 1110.2–1111. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3125.

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Background:Overweight/obesity is associated with a high incidence of chronic autoimmune diseases such as rheumatoid arthritis (RA). In RA, obesity represents an increasingly prevalent comorbidity even at its first presentation, with more than 60% of patients with RA classified as overweight or obese by the body mass index (BMI ≥25 kg/m2). On the other hand, RA is related with excess cardiovascular disease (CVD) mortality, which accounts for over 50% of premature deaths in RA. Obesity contributes to the development of inflammation via changes in metabolism and function of adipose tissue and it appears to coexist with other CVD risk factors such as hypertension, insulin resistance and dyslipidemia.Objectives:For the first time, this study looks at the effect of the BMI on echocardiography parameters in established RA cases.Methods:A cross section study was carried out to recruit patients meeting the 2010 ACR/EULAR criteria during 2019. Standard trans-thoracic echocardiography examination was performed by a specialist cardio-sonographer who was blinded to the status of the participants. The echocardiography parameters studied included left ventricular dimensions, wall geometry, systolic and diastolic parameters, ejection fraction, right ventricular size and function, valve structure and function, aortic root dimensions, pulmonary pressures and pericardium. Anthropometric measurements of BMI were carried out as weight in kilograms divided by the square of height in meters (kg/m2). Data was analysed using the BMI as the explanatory variable and repeating the simple linear regression analysis using the echocardiography parameters as outcome variables. P value of <0.05 was considered significant.Results:During the one-year period, 44 RA patients were recruited, of which 91% (40) were female and 4 (9 %) male. The mean (SD) of age was 50±13 years (Min 28, Max 72). The mean (SD) of BMI was 30.887 ± 6.348 Kg/m2 (Min 21, Max 44.38). As per BMI classification of obesity, only 11% patients were found to have normal BMI. Echocardiography revealed that 14% patients had aortic regurgitation, 2% had aortic stenosis, 2% had mitral stenosis, and 7% had tricuspid regurgitation.Using BMI as an explanatory variable, with echocardiography parameters as outcome variables, it was found that BMI contributed positively in a linear manner to the Interventricular Septal thickness in diastole (mm) (p=0.004, CI: 0.048-0.227), LV End Diastolic Diameter (mm) (p=0.033, CI: 0.033-0.722), LV mass (g) (0.04, CI: 0.022-6.339), Early Diastolic Velocity, E, by PW mitral inflow measurement (cm/s) (p=0.02, CI: 0.150-1.933), E/E’ ratio by Tissue Doppler study (p=0.01, CI: 0.025-0.225), and to Right Ventricle function measured by Tricuspid Annular Plane Systolic Excursion (TAPSE) (mm) (p=0.02, CI: 0.035-0.346).Conclusion:Obesity and Inflammation overlap syndrome may interplay to produce various cardiovascular abnormalities. Body Mass Index is shown to be associated with significant echocardiographic abnormalities including left ventricular dimension, diastolic parameters and right ventricular function. In view of the complex interrelation between obesity, rheumatoid arthritis and cardiovascular disease, measuring Body Mass Index might help predict adverse cardiovascular events in rheumatoid arthritis patients.References:[1]Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis. Qin B, Yang M, Fu H, Ma N, Wei T, Tang Q, Hu Z, Liang Y, Yang Z, Zhong R. Arthritis Res Ther. 2015; 17(1): 86. doi: 10.1186/s13075-015-0601-x.[2]Cardiac eccentric remodeling in patients with rheumatoid arthritis. Pascale V, Finelli R, Giannotti R, Coscioni E, Izzo R, Rozza F, Caputo D, Moscato P, Iaccarino G, Ciccarelli M. Sci Rep. 2018; 8: 5867. doi: 10.1038/s41598-018-24323-0.Disclosure of Interests:None declared

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Le Gia, Quoc Thong, Michael Clarke, Josef Dick et David Pye. « Elasticity equations with random domains—the shape derivative approach ». ANZIAM Journal 62 (9 mars 2022) : C256—C272. http://dx.doi.org/10.21914/anziamj.v62.16120.

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In this work, we discuss elasticity equations on a two-dimensional domain with random boundaries and we apply these equations to modelling human corneas. References R. C. Augustyn, D. Nankivil, A. Mohamed, B. Maceo, F. Pierre, and J.-M. Parel. Human ocular biometry. Exp. Eye Res. 102 (2012), pp. 70–75. doi: 10.1016/j.exer.2012.06.009. F. Ballarin, A. Manzoni, G. Rozza, and S. Salsa. Shape optimization by free-form deformation: Existence results and numerical solution for Stokes flows. J. Sci. Comput. 60.3 (2014), pp. 537–563. doi: 10.1007/s10915-013-9807-8. S. C. Brenner and L.-Y. Sung. Linear finite element methods for planar linear elasticity. Math. Comp. 59 (1992), pp. 321–338. doi: 10.2307/2153060. M. C. Delfour and J.-P. Zolesio. Shapes and geometries. Advances in Design and Control. SIAM, Philadelphia, 2001. doi: 10.1137/1.9780898719826. J. Dick. Higher order scrambled digital nets achieve the optimal rate of the root mean square error for smooth integrands. Ann. Statist. 39.3 (2011), pp. 1372–1398. doi: 10.1214/11-AOS880. J. Dick, F. Y. Kuo, Q. T. Le Gia, and Ch. Schwab. Multilevel higher order QMC Petrov–Galerkin discretization for affine parametric operator equations. SIAM J. Num. Anal. 4.54 (2015), pp. 2541–2568. doi: 10.1137/16M1078690 A. Eilaghi, J. G. Flanagan, I. Tertinegg, C. A. Simmons, G. W. Brodland, and C. R. Ethier. Biaxial testing of human sclera. J. Biomech. 43 (2010), pp. 1696–1701. doi: 10.1016/j.jbiomech.2010.02.031. U. Fares, A. M Otri, M. A. Al-Aqaba, and H. S. Dua. Correlation of central and peripheral corneal thickness in healthy corneas. Cont. Lens Anterior Eye 35 (2012), pp. 39–45. doi: 10.1016/j.clae.2011.07.004. R. N. Gantner and Ch. Schwab. Computational higher order quasi-Monte Carlo integration. Monte Carlo and quasi-Monte Carlo methods. Vol. 163. Springer Proc. Math. Stat. Springer, 2016, pp. 271–288. doi: 10.1007/978-3-319-33507-0_12. on p. C129). H. Harbrecht. Second moment analysis for Robin boundary value problems on random domains. Singular Phenomena and Scaling in Mathematical Models. Ed. by M. Griebel. Springer, 2014, pp. 361–381. doi: 10.1007/978-3-319-00786-1_16. H. Harbrecht, M. Peters, and M. Siebenmorgen. Analysis of the domain mapping method for elliptic diffusion problems on random domains. Numer. Math. 134.4 (2016), pp. 823–856. doi: 10.1007/s00211-016-0791-4. H. Harbrecht, R. Schneider, and Ch. Schwab. Sparse second moment analysis for elliptic problems in stochastic domains. Numer. Math. 109.3 (2008), pp. 385–414. doi: 10.1007/s00211-008-0147-9. R. Hiptmair and J. Li. Shape derivatives in differential forms I: an intrinsic perspective. Ann. Matematica Pura Appl. 192 (2013), pp. 1077–1098. doi: 10.1007/s10231-012-0259-9. C. R. de Lima, L. A. Mello, R. G. Lima, and E. C. N. Silva. Electrical impedance tomography through constrained sequential linear programming: a topology optimization approach. Meas. Sci. Tech. 18.9 (2007), pp. 2847–2858. doi: 10.1088/0957-0233/18/9/014. M. Loeve. Probability theory I. Graduate Texts in Mathematics. Springer-Verlag, 1978. doi: 10.1007/978-1-4684-9464-8. R. Martin, S. Jonuscheit, A. Rio-Cristobal, and M. J. Doughty. Repeatability of Pentacam peripheral corneal thickness measurements. Cont. Lens Anterior Eye 38 (2015), pp. 424–429. doi: 10.1016/j.clae.2015.05.001. R. von Mises. Mechanik der festen Körper im plastisch-deformablen Zustand. Nachrichten von der Gesellschaft der Wissenschaften zu Göttingen. Mathematisch-Physikalische Klasse 1 (1913), pp. 562–592. url: https://eudml.org/doc/58894 F. Orucoglu and E. Toker. Comparative analysis of anterior segment parameters in normal and keratoconic eyes generated by Scheimpflug tomography. J. Ophthalmol., 925414 (2015), pp. 1–8. doi: 10.1155/2015/925414. D. C. Pye. A clinical method for estimating the modulus of elasticity of the human cornea in vivo. PLOS One 15 (2020), pp. 1–19. doi: 10.1371/journal.pone.0224824.

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Chohan, S., A. Kavanaugh, V. Strand, R. C. Chou, A. M. Mendelsohn, S. Rozzo et P. J. Mease. « AB0803 EFFICACY OF TILDRAKIZUMAB IN PsA : DAS28-CRP SCORES THROUGH WEEK 52 ». Annals of the Rheumatic Diseases 79, Suppl 1 (juin 2020) : 1702–3. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3907.

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Background:Tildrakizumab (TIL), an anti–interleukin (IL)-23p19 monoclonal antibody, is approved in the US, EU, and Australia for treatment of moderate-to-severe plaque psoriasis.1A randomised, double-blind, placebo-controlled, multiple-dose, phase 2b study (NCT02980692) evaluating efficacy and safety of TIL for treatment of psoriatic arthritis (PsA) was recently completed.Objectives:To evaluate the effect of TIL in PsA, using the DAS28-CRP responses up to week (W)52.Methods:Patients (pts) ≥18 years old with PsA2and ≥3 tender and ≥3 swollen joints were randomised 1:1:1:1:1 to receive TIL (200 mg once every 4 weeks [Q4W], 200 mg every 12 weeks [Q12W], 100 mg Q12W, or 20 mg Q12W) or placebo (PBO Q4W) to W24. Thereafter, PBO Q4W and TIL 20 mg Q12W arms crossed over to TIL 200 mg Q12W to W52. DAS28-CRP was shown to be reliable in PsA studies,3and pts achieving scores <3.2 satisfied responder criteria. Adverse events (AEs), including treatment-emergent AEs (TEAEs) and serious AEs (SAEs), were monitored throughout the study.Results:Overall, 391/500 pts screened met the inclusion criteria; 55% were female with a mean age of 48.8 years. At baseline, disease characteristics were generally consistent across treatment arms (Table).At W24, DAS28-CRP response rates increased across all TIL treatment arms relative to PBO (Figure). After W24, response rates continued to increase and were sustained through W52, including in pts who switched from PBO to TIL.From W0–W24/W25–W52, 50.4%/39.9% and 2.3%/1.0% of pts experienced a TEAE and SAE, respectively. There were no reports of candidiasis, inflammatory bowel disease, major adverse cardiac events or elevated liver enzymes. From W0–W24, 1 pt (0.3%) had urinary tract infection (TIL 100 mg Q12W). From W25–W52, 1 pt (0.3%) had an intraductal proliferative breast lesion (TIL 20→200 mg Q12W). One pt (0.3%) discontinued before 24 weeks due to hypertension. No deaths were reported.Table.Baseline disease characteristics related to DAS28-CRPTIL 200 mg Q4Wn = 78TIL 200 mg Q12Wn = 79TIL 100 mg Q12Wn = 77TIL 20→200 mg Q12Wn = 78PBO→TIL 200 mg Q12Wn = 79hsCRP, mg/L7.8 ± 18.610.5 ± 14.410.6 ± 20.010.7 ± 14.013.0 ± 20.8ESR, mm/h*22.8 ± 18.922.5 ± 19.824.7 ± 19.827.2 ± 20.726.9 ± 20.5Swollen joint count (66)10.4 ± 7.410.0 ± 8.011.0 ± 8.29.4 ± 6.411.8 ± 9.8Tender joint count (68)16.6 ± 11.919.5 ± 13.921.3 ± 14.819.0 ± 13.019.7 ± 14.7PtGA57.8 ± 18.361.1 ± 20.760.3 ± 20.261.9 ± 17.465.2 ± 18.1Data are reported as mean ± standard deviation unless otherwise stated.*Total pts analysed (n) = 71, 69, 70, 68, 62, respectively.ESR, erythrocyte sedimentation rate; hsCRP, high-sensitivity C-Reactive Protein; PBO, placebo; PtGA, Patient Global Assessment; pts, patients; Q4W, every 4 weeks; Q12W, every 12 weeks; TIL tildrakizumab.Conclusion:Treatment with all doses of TIL increased the rate of DAS28-CRP responders in pts with active PsA and was well tolerated, suggesting a reduction in PsA-related disease activity for up to 52 weeks of treatment. Ongoing analyses will assess whether DAS28-CRP responses correlate with baseline clinical characteristics.References:[1]Reich K, et al.Lancet. 2017;390(10091):276−88.[2]Taylor W, et al.Arthritis Rheum. 2006; 54(8):2665−73.[3]Fransen J, et al.Ann Rheum Dis. 2004; 62:151.Disclosure of Interests:Saima Chohan Employee of: Partner/physician at Arizona Arthritis and Rheumatology Associates, Arthur Kavanaugh Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, Janssen, Pfizer, Gilead, UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Novartis, Janssen, Pfizer, Gilead, UCB, Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Richard C Chou Consultant of: Sun Pharmaceutical Industries, Inc, Alan M Mendelsohn Shareholder of: Johnson and Johnson, Employee of: Sun Pharmaceutical Industries, Inc, Stephen Rozzo Employee of: Sun Pharmaceutical Industries, Inc, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

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Gottlieb, A. B., C. T. Ritchlin, R. C. Chou, A. M. Mendelsohn, S. Rozzo et L. Espinoza. « SAT0417 TILDRAKIZUMAB EFFICACY ON PSORIASIS IN PATIENTS WITH PSORIATIC ARTHRITIS—A 52-WEEK ANALYSIS FROM A PHASE 2 STUDY ». Annals of the Rheumatic Diseases 79, Suppl 1 (juin 2020) : 1161.2–1162. http://dx.doi.org/10.1136/annrheumdis-2020-eular.778.

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Background:Tildrakizumab (TIL)—a high-affinity anti–interleukin-23p19 monoclonal antibody—is approved in the US, EU, and Australia to treat moderate to severe plaque psoriasis.1A randomised, double-blind, multidose, placebo-controlled, phase 2b study (NCT02980692) evaluating the efficacy and safety of TIL for the treatment of psoriatic arthritis (PsA) was recently completed.Objectives:To evaluate the proportion with 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI 75/90/100) among patients (pts) with PsA and measurable psoriasis (≥3% of the body surface area [BSA] affected at baseline) over 52 weeks of treatment.Methods:Pts ≥18 years old with PsA2and ≥3 tender and ≥3 swollen joints, stratified by prior anti-TNF use and baseline body weight (≤90 kg and >90 kg), were randomised 1:1:1:1:1 to receive TIL 200 mg every 4 weeks (Q4W) to week 52 (W52), TIL 200 mg every 12 weeks (Q12W) to W52, TIL 100 mg Q12W to W52, TIL 20 mg Q12W to W24→TIL 200 mg Q12W to W52, or placebo (PBO) Q4W to W24→TIL 200 mg Q12W to W52. PASI 75/90/100 were prespecified endpoints and were assessed by an independent assessor. Pts who received ≥1 dose of study drug were analysed. Safety assessments included treatment-emergent adverse event (TEAE) monitoring.Results:Overall, 391/500 pts screened met inclusion criteria; 235 (60.1%) had ≥3% BSA involvement at baseline (41–55/treatment arm). Demographics and baseline disease characteristics were generally consistent across treatment arms. Mean (standard deviation [SD]) age was 48.8 (12.6) years, average body mass index was 29.7, 96.7% of pts were White, and 23.3% were anti–tumour necrosis factor (TNF)-experienced. At baseline, the mean (SD) PASI score was 6.8 (8.2) and mean (SD) BSA affected was 10.5% (14.3%) overall. Among pts with baseline BSA ≥3%, TIL treatment significantly increased the proportion of PASI 75/90/100 responders vs PBO at W24; the proportion of responders continued to increase thereafter and was sustained through W52 (Figure). Similarly, in pts switching from PBO→TIL 200 mg Q12W or escalating from TIL 20→200 mg Q12W after W24, PASI 75/90/100 response rates increased through W36 and remained stable through W52. From W0→W24/W25→W52, 50.4%/39.9% pts experienced a TEAE. The most frequent TEAEs were nasopharyngitis (pooled TIL arms 5.4%/4.2% vs PBO 6.3%/3.8%) and upper respiratory tract infection (pooled TIL arms 3.8%/4.2% vs PBO 1.3%/0.0%). One pt (0.3%) discontinued before 24 weeks due to hypertension. There were no deaths or major adverse cardiac events during W0→W24 or W25→W52.Conclusion:PASI75/90/100 response rates progressively improved with treatment; PASI 75 responses were significantly improved vs placebo as early as W4 (TIL 200 mg Q12W), and all response rates were significantly improved vs placebo at W24. Response rates continued to improve through W36 and were sustained through W52. These results demonstrate TIL significantly reduced psoriasis disease activity and was generally well tolerated in a mixed population of anti–TNF-naïve and -experienced patients with PsA and BSA ≥3% through W52.References:[1]Reich K, et al.Lancet.2017;390(10091):276−88.[2]Taylor W, et al.Arthritis Rheum. 2006; 54(8):2665–73.Disclosure of Interests:Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Richard C Chou Consultant of: Sun Pharmaceutical Industries, Inc, Alan M Mendelsohn Shareholder of: Johnson and Johnson, Employee of: Sun Pharmaceutical Industries, Inc, Stephen Rozzo Employee of: Sun Pharmaceutical Industries, Inc, Luis Espinoza: None declared

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Nash, P., M. E. Luggen, L. Espinoza, F. J. García Fructuoso, R. C. Chou, A. M. Mendelsohn, S. Rozzo et I. Mcinnes. « SAT0431 PROPORTIONS OF PATIENTS ACHIEVING A MINIMAL DISEASE ACTIVITY STATE UPON TREATMENT WITH TILDRAKIZUMAB IN A PSORIATIC ARTHRITIS PHASE 2B STUDY ». Annals of the Rheumatic Diseases 79, Suppl 1 (juin 2020) : 1171.2–1171. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3947.

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Background:Tildrakizumab (TIL) is a high-affinity anti–interleukin-23p19 monoclonal antibody approved in the US, EU, and Australia to treat moderate to severe plaque psoriasis. A randomised, double-blind, placebo-controlled, multiple-dose, phase 2b study evaluating the efficacy and safety of TIL was recently completed (NCT02980692).Objectives:To characterise and evaluate the rate of minimal disease activity (MDA) up to week (W)52 from the phase 2b study.Methods:Patients (pts) ≥18 years old with active psoriatic arthritis (PsA)2and ≥3 tender and ≥3 swollen joints were randomised 1:1:1:1:1 to receive TIL 200 mg every 4 weeks (Q4W) to W52, TIL 200 mg Q12W to W52, TIL 100 mg Q12W to W52, TIL 20 mg Q12W to W24→TIL 200 mg Q12W to W52, or placebo (PBO) Q4W to W24→TIL 200 mg Q12W to W52. MDA was assessed throughout the study; an MDA response was achieved when 5 of 7 criteria were met.3Safety was assessed throughout the study and included treatment-emergent adverse event (TEAE) monitoring.Results:Of 500 pts screened, 391 were randomised and received ≥1 dose of study drug. At baseline (BL), mean age was 48.8 years, 55% were female, 97% were White, mean body mass index was 29.7 kg/m2, and pts had PsA for a median (range) of 4.4 (0–42.8) years since diagnosis. Baseline disease characteristics related to MDA varied little between study arms (Table).By W24, MDA state was achieved in significantly more pts receiving TIL vs PBO (24%–39% vs 7%; p<0.02 for all groups); the proportion further increased with continued TIL treatment to W52 (45%–64%), including pts who switched from PBO to TIL (47%) (Figure).Among the overall pt population from BL→W24/W25→W52, 50.4%/39.9% and 2.3%/1.0% experienced a TEAE and serious TEAE, respectively. From BL→W24, 1 serious infection (chronic tonsillitis) was reported for TIL 20 mg→200 mg Q12W arm. From W25→W52, there was 1 malignancy (TIL 20→200 mg Q12W). There were no reports of candidiasis, uveitis, inflammatory bowel disease, major adverse cardiac events, or deaths from BL→W24 or W25→W52.Table.Baseline disease characteristics related to minimal disease activityTIL 200 mg Q4Wn = 78TIL 200 mg Q12Wn = 79TIL 100 mg Q12Wn = 77TIL 20→200 mg Q12Wn = 78PBO→TIL 200 mg Q12Wn = 79Swollen joint count10.410.011.09.411.8Tender joint count16.619.521.319.019.7Patient GADA score57.861.160.361.965.2Patient pain assessment55.459.659.260.964.2Enthesitis (LEI) score*1.91.52.22.21.5PASI†7.66.28.86.65.0HAQ-DI score1.01.01.01.11.2Data are reported as mean.*Total patients analysed (n) = 76, 79, 76, 78, 78, respectively.†Total patients analysed (n) = 75, 79, 76, 75, 75, respectively.GADA, global assessment of disease activity; HAQ-DI, Health Assessment Questionnaire Disability Index; LEI, Leeds Enthesitis Index; PASI, Psoriasis Area and Severity Index; PBO, placebo; Q4W, every 4 hours; Q12W, every 12 hours; TIL, tildrakizumab.Conclusion:TIL produced clinically meaningful improvement in pts with PsA, resulting in a large proportion of pts achieving MDA by W52, and was well tolerated through W52.References:[1]Reich, et al.Lancet2017;390:276−88.[2]Taylor, et al.Arthritis Rheum2006;54:2665–73.[3]Coates, et al.Ann Rheum Dis2010;69:48−53.Disclosure of Interests:Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Michael E Luggen Grant/research support from: AbbVie; Amgen; Eli Lilly; Genentech; Nichi-Iko; Novartis; Pfizer; R-Pharm; and Sun Pharmaceutical Industries, Inc., Consultant of: AbbVie; Amgen; Eli Lilly; Genentech; Nichi-Iko; Novartis; Pfizer; R-Pharm; and Sun Pharmaceutical Industries, Inc., Speakers bureau: AbbVie; Amgen; Eli Lilly; Genentech; Nichi-Iko; Novartis; Pfizer; R-Pharm; and Sun Pharmaceutical Industries, Inc., Luis Espinoza: None declared, Ferran J García Fructuoso Grant/research support from: AbbVie, Eli Lilly, Gedeon Richter, MedImmune, Nichi-Iko, Pfizer, Sanofi-Aventis, Takeda, and UCB, Consultant of: AbbVie, Eli Lilly, Gedeon Richter, MedImmune, Nichi-Iko, Pfizer, Sanofi-Aventis, Takeda, and UCB, Speakers bureau: AbbVie, Eli Lilly, Gedeon Richter, MedImmune, Nichi-Iko, Pfizer, Sanofi-Aventis, Takeda, and UCB, Richard C Chou Consultant of: Sun Pharmaceutical Industries, Inc, Alan M Mendelsohn Shareholder of: Johnson and Johnson, Employee of: Sun Pharmaceutical Industries, Inc, Stephen Rozzo Employee of: Sun Pharmaceutical Industries, Inc, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB

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Mease, P. J., S. Chohan, F. J. García Fructuoso, A. B. Gottlieb, M. E. Luggen, P. Rahman, S. P. Raychaudhuri et al. « OP0230 EFFICACY AND SAFETY OF TILDRAKIZUMAB, A HIGH-AFFINITY ANTI–INTERLEUKIN-23P19 MONOCLONAL ANTIBODY, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS IN A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIPLE-DOSE, PHASE 2B STUDY ». Annals of the Rheumatic Diseases 79, Suppl 1 (juin 2020) : 145–46. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3908.

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Background:Tildrakizumab (TIL), a high-affinity anti–interleukin-23p19 monoclonal antibody, is approved to treat moderate to severe plaque psoriasis and is under investigation for treatment of psoriatic arthritis (PsA).1Objectives:To evaluate efficacy and safety of TIL up to week (W)52 in a randomised, double-blind, placebo-controlled, multiple-dose, phase 2b study in PsA (NCT02980692).Methods:Patients (pts) ≥18 years with active PsA2were randomised 1:1:1:1:1 to TIL 200 mg every 4 weeks (Q4W) to W52, TIL 200 mg Q12W to W52, TIL 100 mg Q12W to W52, TIL 20 mg Q12W until W24 then TIL 200 mg Q12W to W52, or placebo (PBO) Q4W until W24 then TIL 200 mg Q12W to W52. Efficacy assessments included ACR20/50/70, 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI), proportion of pts with residual minimal disease activity (MDA) response; and mean change from baseline (BL) in HAQ-DI, Leeds Dactylitis Index (LDI, pts with BL LDI ≥1), and Leeds Enthesitis Index (LEI, pts with BL LEI ≥1) to W52. Treatment-emergent adverse events (TEAEs) were monitored.Results:Of 500 pts screened, 391 were randomised and received ≥1 dose of drug. Proportions of ACR20/50/70 responders were superior with TIL vs PBO through W24; after W24 rates of responses further increased for TIL 20→200 mg Q12W and PBO→200 mg Q12W through W52 (Figure 1, 2). Other efficacy results are shown in Table. Overall from BL→W24/W25→W52, 50.4%/39.9% and 2.3%/1.0% of pts experienced a TEAE and serious AE, respectively. From BL→W24, 1 case of pyelonephritis and urinary tract infection was reported in the TIL 100 mg Q12W arm and 1 case of chronic tonsillitis was reported in the TIL 20 mg→200 mg Q12W arm. During W25→W52, 1 malignancy (intraductal proliferative breast lesion) was reported with TIL 20 mg→200 mg Q12W. No deaths or major adverse cardiac events occurred.Table.W52 clinical efficacyTIL 200 mg Q4Wn=78TIL 200 mg Q12Wn=79TIL 100 mg Q12Wn=77TIL 20→200 mg Q12Wn=78PBO→TIL 200 mg Q12Wn=79HAQ-DI, BLa1.0 ± 0.61.0 ±0.61.0 ± 0.71.1 ± 0.61.2 ± 0.6 W52b−0.5 ± 0.5−0.5 ± 0.6−0.5 ± 0.6−0.5 ± 0.5−0.5 ± 0.5LEI, BLa,c1.9 ± 2.01.5 ± 1.92.2 ± 2.12.2 ± 2.01.5 ± 1.9 W52b−1.3 ± 1.9−1.0 ± 1.6−1.7 ± 2.1−1.2 ± 1.8−1.2 ± 1.8LDI, BLa,d32.8 ± 32.961.3 ± 73.593.8 ± 146.571.4 ± 118.599.6 ± 170.7 W52b,d−21.4 ± 37.1−42.1 ± 76.7−41.6 ± 89.3−56.5 ± 123.4−81.5 ± 173.0 BL, W52 mediand21.8, 7.428.3, 3.232.1, 20.028.6, 034.0, 5.6MDAe56.964.445.047.142.0PASI 100e54.044.443.947.535.0PASI 90e72.080.658.555.050.0PASI 75e82.094.482.975.067.5aBL mean ± SD.bMean change from BL ± SD.cPts with BL LEI ≥1 will be presented at EULAR.dPts with BL LDI ≥1 (n = 27, 21, 21, 19, 25) using nonresponder imputation.e% at W52Missing data not imputed.SD, standard deviation.Conclusion:TIL was well tolerated and improved joint and skin manifestations of PsA through W52.References:[1]Reich, et al.Lancet2017;390:276−88.[2]Taylor, et al.Arthritis Rheum2006;54:2665–73.Disclosure of Interests:Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Saima Chohan Employee of: Partner/physician at Arizona Arthritis and Rheumatology Associates, Ferran J García Fructuoso Grant/research support from: AbbVie, Eli Lilly, Gedeon Richter, MedImmune, Nichi-Iko, Pfizer, Sanofi-Aventis, Takeda, and UCB, Consultant of: AbbVie, Eli Lilly, Gedeon Richter, MedImmune, Nichi-Iko, Pfizer, Sanofi-Aventis, Takeda, and UCB, Speakers bureau: AbbVie, Eli Lilly, Gedeon Richter, MedImmune, Nichi-Iko, Pfizer, Sanofi-Aventis, Takeda, and UCB, Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Michael E Luggen Grant/research support from: AbbVie; Amgen; Eli Lilly; Genentech; Nichi-Iko; Novartis; Pfizer; R-Pharm; and Sun Pharmaceutical Industries, Inc., Consultant of: AbbVie; Amgen; Eli Lilly; Genentech; Nichi-Iko; Novartis; Pfizer; R-Pharm; and Sun Pharmaceutical Industries, Inc., Speakers bureau: AbbVie; Amgen; Eli Lilly; Genentech; Nichi-Iko; Novartis; Pfizer; R-Pharm; and Sun Pharmaceutical Industries, Inc., Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Siba P Raychaudhuri Grant/research support from: AbbVie; Janssen; Novartis, Pfizer; Sun Pharmaceutical Industries, Inc, Consultant of: Amgen; Eli Lilly; Janssen; Novartis and Pfizer, Richard C Chou Consultant of: Sun Pharmaceutical Industries, Inc, Alan M Mendelsohn Shareholder of: Johnson and Johnson, Employee of: Sun Pharmaceutical Industries, Inc, Stephen Rozzo Employee of: Sun Pharmaceutical Industries, Inc, Ana-Maria Orbai Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Consultant of: Eli Lilly; Janssen; Novartis; Pfizer; UCB. Ana-Maria Orbai was a private consultant or advisor for Sun Pharmaceutical Industries, Inc, not in her capacity as a Johns Hopkins faculty member and was not compensated for this service.

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Gottlieb, A. B., N. Mehta, A. Menter, A. M. Mendelsohn, S. Rozzo et M. Lebwohl. « AB0544 EFFICACY AND SAFETY OF TILDRAKIZUMAB IN PATIENTS WITH AND WITHOUT METABOLIC SYNDROME : 5-YEAR POOLED DATA FROM reSURFACE 1 AND reSURFACE 2 ». Annals of the Rheumatic Diseases 80, Suppl 1 (19 mai 2021) : 1304.2–1305. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1827.

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Background:Patients with psoriasis and metabolic syndrome (MetS) may have reduced absolute Psoriasis Area and Severity Index (PASI) response and long-term drug survival. Tildrakizumab is approved for the treatment of moderate to severe plaque psoriasis in the US, EU, Australia, and Japan. Efficacy and safety of tildrakizumab were previously shown to be comparable in patients with vs without MetS after 1 and 3 years of treatment.1Objectives:This post hoc analysis of pooled data from reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) assessed tildrakizumab efficacy and safety through up to 5 years of treatment in patients with psoriasis with and without MetS.Methods:reSURFACE 1 and 2 were 3-part, double-blind, randomized controlled phase 3 trials with long-term extensions evaluating tildrakizumab 100 or 200 mg monotherapy at Weeks 0, 4, and every 12 weeks thereafter in adults with moderate to severe plaque psoriasis.2 Patients who achieved ≥50% improvement from baseline PASI score (PASI 50 response) at both week 28 and at the end of the phase 3 studies could enter the long-term extension studies continuing the same dose of tildrakizumab.1 This post hoc analysis reports results from a pooled data analysis through up to 5 years of tildrakizumab exposure from patients with and without MetS by National Cholesterol Education Program-Adult Treatment Panel III criteria who continuously received the same dose of tildrakizumab throughout the base studies and entered the long-term extensions. Efficacy was assessed as change from baseline PASI score; missing data were handled using multiple imputation. Safety was assessed from exposure adjusted incidence rates of serious adverse events (SAEs) and treatment-emergent AEs of special interest.Results:Analyses included 70/265 patients with/without MetS receiving tildrakizumab 100 mg and 64/241 patients with/without MetS receiving tildrakizumab 200 mg. Median percentage change from baseline PASI score is shown in Figure 1. Among patients with/without MetS receiving tildrakizumab 100 mg, 78.6%/87.9% achieved PASI 75, 57.1%/63.8% achieved PASI 90, and 25.7%/32.5% achieved PASI 100 response at week 244; the PASI 75, PASI 90, and PASI 100 response rates at week 244 in patients with/without MetS receiving tildrakizumab 200 mg were 76.6%/85.1%, 46.9%/61.4%, and 26.6%/36.5%, respectively. Safety outcomes over the 5-year extension period were consistent with the known safety profile of tildrakizumab. Rates of SAEs were <8.5 per 100 patient-years among all patients, and there were no new safety signals in patients with vs without MetS (Table 1).Table 1.SAEs and TEAEs of special interest by MetS status through up to 5 years of tildrakizumab exposureTIL 100 mgTIL 200 mgWithout MetSWithMetSWithout MetSWithMetSn = 265n = 70n = 241n = 64n (EAIR per 100 PY)1149.1 PY304.1 PY1057.1 PY287.6 PYSAEs53 (4.61)22 (7.23)52 (4.92)24 (8.35)TEAEs of special interest24 (2.09)6 (1.97)27 (2.55)15 (5.22)Infections and infestations10 (0.87)2 (0.66)13 (1.23)6 (2.09)Malignanciesa5 (0.44)1 (0.33)4 (0.38)3 (1.04)Nonmelanoma skin cancer3 (0.26)1 (0.33)6 (0.57)1 (0.35)Confirmed extended MACE3 (0.26)1 (0.33)3 (0.28)3 (1.04)Drug hypersensitivity2 (0.17)1 (0.33)1 (0.09)2 (0.70)Melanoma skin cancer2 (0.17)000Injection site reactionsb1 (0.09)000Incidence rates reported as events per 100 PY.aExcluding nonmelanoma and melanoma skin cancer.bNot considered of special interest in the extension study.AE, adverse event; EAIR, exposure adjusted incidence rate; MACE, major adverse cardiovascular events; MetS, metabolic syndrome; PY, patient-years; SAE, serious AE; TEAE, treatment-emergent AE; TIL, tildrakizumab.Conclusion:The efficacy and safety of tildrakizumab were maintained in patients with and without MetS following 5 years of treatment.References:[1]Lebwohl, M et al. JAAD. 2020;S0190-9622(20)32637-2.[2]Reich K, et al. Lancet. 2017;390:276–88.Disclosure of Interests:Alice B Gottlieb Shareholder of: Xbiotech (only stock options, which she has not used)., Consultant of: Anaptyps Bio, Avotres Therapeutics; Beiersdorf; Boehringer Ingelheim; Bristol-Myers Squibb Co.; Eli Lilly; Janssen; LEO Pharma; Novartis; Sun Pharmaceutical Industries, Inc.; UCB; and Xbiotech, Grant/research support from: Boehringer Ingelheim; Janssen; Novartis; Sun Pharmaceutical Industries, Inc.; UCB; and Xbiotech., Nehal Mehta Grant/research support from: Grants to the NIH from AbbVie, Celgene, Janssen, and Novartis., Employee of: Full-time employee of the US government., Alan Menter Speakers bureau: AbbVie, Abbott Labs, Amgen, Anacor, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, LEO Pharma, Merck & Co., Novartis, Sienna, and UCB., Consultant of: AbbVie, Abbott Labs, Amgen, Anacor, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, LEO Pharma, Merck & Co., Novartis, Sienna, and UCB., Grant/research support from: AbbVie, Abbott Labs, Amgen, Anacor, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, LEO Pharma, Merck & Co., Novartis, Sienna, and UCB., Alan M Mendelsohn Shareholder of: Has individual shares in Johnson and Johnson, and as part of retirement account/mutual funds, Employee of: Sun Pharmaceutical Industries, Inc., Stephen Rozzo Employee of: Sun Pharmaceutical Industries, Inc., Mark Lebwohl Consultant of: Aditum Bio; Allergan; Almirall; Arcutis; Avotres Therapeutics; BirchBioMed, Inc.; BMD Skincare; Boehringer Ingelheim; Bristol-Myers Squibb; Cara Therapeutics; Castle Biosciences; Corrona; Dermavant Sciences; Evelo; Facilitate International Dermatologic Education; Foundation for Research and Education in Dermatology; Inozyme Pharma; Kyowa Kirin; LEO Pharma; Meiji Seika Pharma; Menlo; Mitsubishi; Neuroderm; Pfizer; Promius/Dr. Reddy’s Laboratories; Serono; Theravance; and Verrica., Grant/research support from: AbbVie; Amgen; Arcutis; Boehringer Ingelheim; Dermavant; Eli Lilly; Incyte; Janssen Research & Development, LLC; LEO Pharma; Ortho Dermatologics; Pfizer; and UCB.

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Paoli, Matilde. « Sull'uso di mentre invece ». XXI, 2022/2 (aprile-giugno), n^o 21 (20 juin 2008). http://dx.doi.org/10.35948/2532-9006/2022.19776.

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Molti utenti tra cui Gianluca Arrigoni da Assemini, Cristina Esposito da Rozzano, Claudio Reale da Palermo, Giuseppe Discalzo da Reano ci chiedono se sia corretto usare mentre invece e Maria Lenigno di Cagliari ci scrive: "Invito sempre i miei alunni a non usare insieme mentre e invece, che hanno uguale funzione avversativa e ritengo scorretta al pari di ma però, ma loro rimangono perplessi, perché è un'espressione assai usata e sentita".

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Gallizzi, G., S. Crivellari, A. Roveta, A. Muzio, S. Zai, G. Taverna, A. Aurelio et al. « Mesotelioma pleurico sarcomatoide : analisi clinico-patologica e di sopravvivenza di una serie di 80 casi, studio retrospettivo multicentrico ». Working Paper of Public Health 4, n^o 1 (15 juin 2015). http://dx.doi.org/10.4081/wpph.2015.6707.

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Introduzione: Il mesotelioma pleurico maligno è una patologia rara, ma con incidenza non trascurabile nelle aree inquinate da amianto. L’istotipo sarcomatoide (SMPM) è caratterizzato da una prognosi particolarmente infausta. Metodologia: Sono state analizzate le caratteristiche e gli outcome clinici di 80 pazienti affetti da SMPM seguiti presso gli Ospedali di Alessandria, Casale Monferrato, Rozzano, Padova. Risultati: Dopo la prima linea chemioterapica è stata osservata risposta parziale (PR) in 2 pazienti (2,5%), stabilità di malattia (SD) in 32 pazienti (40%), progressione di malattia (PD) in 25 pazienti (31%), malattia non valutabile per 21 pazienti (26%). Il time to progression (TTP) è risultato 3.5 mesi; l’overall survival (OS) è stata 7.8 mesi. L’OS dei pazienti che avevano ricevuto pemetrexed è risultata 7.5 mesi vs 8.9 mesi dei pazienti sottoposti a chemioterapia senza pemetrexed (p>0,05). Conclusione: I dati confermano come l’istotipo sarcomatoide abbia una prognosi peggiore rispetto all’epitelioide, con una minor sopravvivenza e una scarsa risposta ai trattamenti. In particolare la chemioterapia standard non ha mostrato efficacia, sottolineando la necessità di altre prospettive terapeutiche nell’ambito di studi clinici incentrati sui nuovi target biomolecolari.

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Legrottaglie, Emanuela Filomena, Laura Balia, Fabrizio Ivo Camesasca, Jose Luis Vallejo-Garcia, Giovanni Fossati, Riccardo Vinciguerra, Pietro Rosetta et Paolo Vinciguerra. « Management of an ophthalmology department during COVID-19 pandemic in Milan, Italy ». European Journal of Ophthalmology, 22 septembre 2020, 112067212096033. http://dx.doi.org/10.1177/1120672120960334.

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Purpose: Spreading from China, COVID-19 pandemic reached Italy, the first massively involved western nation. At the beginning of March, 2020 in Northern Italy a complete lockdown of activities was imposed. Access to all healthcare providers, was halted for patients with elective problems. We present the management experience of the Humanitas Clinical and Research Center Ophthalmology Department in Rozzano, Milan, Italy, during the lockdown. Methods: Containment measures were taken to reduce viral transmission and identify infected patients. All planned visits were canceled but for those not deferrable. Social distancing was introduced reducing number of visits per hour. Minor surgery for progressive pathologies was continued. As the lockdown prolonged, we reorganized patient care. All canceled cases were evaluated by electronic medical records analysis and telephonic triage, to identify, recall, and visit patients at risk of vision loss. Results: From March 9, to April 30, 2020 we performed a total of 930 visits and 612 exams. Some visits ( n = 698) and exams ( n = 160) were deemed as necessary for continuity of care and performed as planned. Among the remaining 1283 canceled appointments, after evaluation 144 visits and 32 instrumental exams were classified as urgent and rapidly rescheduled. Performed surgical activities were limited to corneal collagen cross linking ( n = 39) and intravitreal injections ( n = 91), compared to 34 and 94, respectively, in the same period of 2019. Conclusion: In-office activities deemed not deferrable were performed safely. The recall service was highly appreciated by all patients. No patient or staff member reported symptoms of COVID-19.

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« Epidermal growth factor receptor (EGFR) expression on NSCLC is not useful to predict response to ZD1839 therapy : Preliminary results of the Istituto Clinico Humanitas, Rozzano, Milano ». European Journal of Cancer 38 (novembre 2002) : S58. http://dx.doi.org/10.1016/s0959-8049(02)80833-4.

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Ricchitelli, S. « 533 IMPACT OF LOCAL MICROBIOME ON THE ONSET OF ESOPHAGEAL ADENOCARCINOMA FOR THE DEVELOPMENT OF A STRATEGY FOR PREVENTION AND TREATMENT ». Diseases of the Esophagus 33, Supplement_1 (septembre 2020). http://dx.doi.org/10.1093/dote/doaa087.141.

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Abstract Esophageal adenocarcinoma (EAC) is one of the most aggressive gastrointestinal tumor. High mortality is due to difficulties in diagnosis at an early stage and to its biological aggressive features. Little is know about the association between esophageal microbiome dysbiosis and EAC pathogenesis. The aim of the study is the identification of a specific esophageal local microbiota that can be related to the pathogenesis and to the onset of EAC Methods We investigated the resident microbiome in 38 biopsies from Tumoral (T) and Non-Tumoral (NT) tissues obtained from 19 patients submitted to distal-EAC, cardiac-EAC, ESCC resection in Upper GI Surgery Division, Humanitas Research Hospital (Rozzano, Milano). We have analyzed the microbiota in biopsies obtained from EAC Tumoral tissues (T) and Non-Tumoral tissues (NT). After genomic DNA extraction the V3V4-hypervariable regions of the 16S-rRNA bacterial gene were amplified and sequenced on MiSeq Illumina sequencer. The Bioinformatic Data Analysis has been perfomed using the CLC Genomic Workbench. Results Alpha diversity analysis showed an increased microbial species richness in Esophageal Squamo-Cellular Carcinoma (ESCC) respect to distal/cardiac EAC and tissues without metaplasia. PERMANOVA statistical analysis was applied to estimate Beta Diversity significance. Bray-Curtis index showed a statistically significant different microbiome composition when comparing both cardiac and distal EAC versus ESCC (p-value 0.022 and 0.010 respectively) and when comparing samples with and without metaplasia. Relative abundances analysis obtained after the comparison of distal EAC, cardiac EAC and ESCC identified specific bacterial species in each group. Streptococcus genus is present only in cardiac EAC, Helicobacter pylori only in distal EAC. Conclusion Our study evidenced an increased microbial species richness in samples deriving from ESCC compared to EAC and samples without metaplasia. A significant difference was found comparing EAC with ESCC or with/without metaplasia tissues, mirroring a reduced biodiversity in EAC and metaplasia. We speculated a generalized alteration of the local microbiome from healthy to diseased tissue, characterized by certain bacterial strains that developed through the creation of a chronic inflammatory milieu that triggers the carcinogenic cascade.

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Trancuccio, Alessandro, Andrea Mazzanti, Deni Kukavica, Carlo Arnò, Matteo Sturla, Maira Marino, Raffaela Bloise, Carlo Napolitano, Lorenzo Monti et Silvia G. Priori. « 764 Prevalence and clinical implications of cardiac involvement in individuals with paucisymptomatic SARS-CoV-2 infection ». European Heart Journal Supplements 23, Supplement_G (1 décembre 2021). http://dx.doi.org/10.1093/eurheartj/suab135.046.

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Abstract Aims Myocardial involvement has been reported in SARS-CoV-2 infection, especially in hospitalized patients during the acute phase of the disease. However, the exact prevalence and the clinical implications of cardiac involvement in young individuals with paucisymptomatic SARS-CoV-2 infection are debated. Methods and results We gathered data on 100 young patients with previous paucisymptomatic SARS-CoV-2 infection, not undergoing hospitalization and without previous diagnosis of structural heart disease, who underwent cardiological evaluation in our clinic at IRCCS ICS Maugeri (Pavia, Italy). Results were validated in an external cohort of 28 patients who underwent cardiac magnetic resonance (MRI) at Humanitas Research Hospital (Rozzano, Italy). The study population included 100 patients with previous paucisymptomatic SARS-CoV-2 infection: 60 (60%) males; median age 36 years (IQR: 22–50 years); median time after SARS-CoV-2 infection 181 days (IQR: 76–218 days). At the cardiological evaluation, 31/100 (31%) of patients referred cardiological symptoms, including dyspnoea, palpitations, chest pain or syncope. Overall, 26/100 (26%) patients showed on or more of the following instrumental alterations at first level assessment: 4/100 (4%) increase of TnI; 7/100 (7%) electrocardiographic abnormalities, 12/100 (12%) ventricular arrhythmias, and 11/100 (11%) echocardiographic abnormalities. Of 32 patients who underwent cardiac MRI, myocardial involvement was detected in 6/32 (19%) patients (Figure 1), similarly to what was observed in the validation cohort [54% males; median age 47 years (IQR: 26–55 years); myocardial involvement at MRI 4/28, 14%]. Furthermore, the proportion of patients with myocardial involvement was significantly higher in patients with first-level cardiac alterations (6/18, 28%) as compared with patients without cardiac alterations at first-level examination (0/14, 0%, P = 0.024). When analysing possible predictors for the occurrence of cardiac involvement at the MRI, documentation of ventricular arrhythmias at Holter ECG or exercise test was associated with an 87-fold higher probability of cardiac involvement at the MRI (OR: 87.3; 95% CI: 4.0–1914.3; P < 0.001). Conclusions Around 15–20% of patients with paucisymptomatic SARS-CoV-2 infection exhibit cardiac involvement documented at the cardiac MRI after a mean of 6 months from the onset of the disease. The presence of instrumental alterations detected with first level diagnostic tests, and in particular the documentation of ventricular arrhythmias at the 24 h-Holter ECG or at the exercise stress test, is a powerful predictor of myocardial involvement.

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Tomasoni, Francesco. « LUDWIG FEUERBACH : L’UOMO E LA SUA ALIMENTAZIONE ». Revista Dialectus - Revista de Filosofia, n^o 12 (30 juillet 2018). http://dx.doi.org/10.30611/2018n12id33204.

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Nel 2015 si è svolto a Milano l’Expo, una manifestazione fieristica dal titolo “Nutrire il pianeta. Energia per la vita” che in 184 giorni e con 145 nazioni partecipanti, fra cui ovviamente il Brasile, ha avuto 21 milioni di visitatori. Sull’onda di questo evento è tornato di attualità il celebre motto di Feuerbach: «L’uomo è (ist) ciò che mangia (isst)». Nella lingua tedesca l’assonanza fra le terze persone del verbo essere e del verbo mangiare è evidente e suggerisce una stretta relazione fra essere e mangiare. Non a caso i critici dell’epoca vi videro un’espressione di rozzo materialismo, che poteva essere avvicinata alla frase di Karl Vogt: «I pensieri stanno press’a poco nel medesimo rapporto col cervello, come la bile al fegato o l’urina alle reni». Vogt era ben consapevole di usare un’espressione «in un certo senso rozza», ma intendeva dire che «tutte le attività psichiche» erano «solo funzioni della sostanza cerebrale» [...]

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« First Performances ». Tempo, n^o 203 (janvier 1998) : 21–28. http://dx.doi.org/10.1017/s0040298200049494.

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Henze's Ninth Symphony Christoph SchlürenHenze's ‘Venus and Adonis’ at the Proms Guy RickardsJames Dillon's ‘Blitzschlag’ Rachel Beckles WillsonJames Macmillan: ‘Raising Sparks’ Ronald WeitzmanSalzburg Festival 1: Ligeti and Greenaway George NewmanSalzburg Festival 2: Matthias Pintscher Christoph SchlürenSchwantner's Percussion Concerto Bret Johnson‘Il rozzo martello’ and the ISM Congress Malcolm Miller

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Maráczi, K., et É. Baracsi. « The examination of the broadleaf evergreen ornamental shrub species in Keszthely ». International Journal of Horticultural Science 16, n^o 5 (6 septembre 2010). http://dx.doi.org/10.31421/ijhs/16/5/929.

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The examination of production possibilities of woody ornamental shrubs (originating from warmer regions than our country) commenced with the financial support of the INTERREG IIIA Slovenia – Hungary – Croatia programme at the Department of Horticulture of the University of Pannonia’s Georgikon Faculty in spring 2007. Our examinations focused on the appearance of species in our country as well as on their frost resistance abilities. The species participating in the experiment are as follows: Abelia grandiflora, Aucuba japonica ’Rozzanie’, Calycanthus floridus, Cotoneaster franchettii, Elaeagnus pungens ’MaculataAurea’, Ilex cornuta, Ligustrum sinense, Ligustrum texanum, Nandina domestica, Osmanthus heterophyllus, Perovskia atriplicifolia, Phyllyrea angustifolia, Photinia fraseri ’Red Robin’, Prunus lusitanica, Sarcococca hoockeriana, Spartium junceum, Teucrium fruticans, Viburnum cinnamonifolium, Viburnum tinus.

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« Cover Picture : Paint resin. © Edward Rozzo/Corbis Digital Stock (Chem. Eng. Technol. 8/2007) ». Chemical Engineering & ; Technology 30, n^o 8 (août 2007) : NA. http://dx.doi.org/10.1002/ceat.200790037.

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Rachayu, Fauziyah Fitriyanti, Sabar Warsini et Sylvia Rozza. « ANALISIS FAKTOR YANG MEMPENGARUHI PERENCANAAN PAJAK PADA PERUSAHAAN MANUFAKTUR YANG TERDAFTAR DI BURSA EFEK INDONESIA ». account 7, n^o 2 (21 décembre 2020). http://dx.doi.org/10.32722/acc.v7i2.3553.

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ANALISIS FAKTOR YANG MEMPENGARUHI PERENCANAAN PAJAK PADA PERUSAHAAN MANUFAKTURYANG TERDAFTAR DI BURSA EFEK INDONESIA Fauziyah Fitriyanti Rachayu fauziyahfrachayu@gmail.com Sabar Warsini sabar.warsini@akuntansi.pnj.ac.id Sylvia Rozza sylvia_rozza@yahoo.com ABSTRACTThis research aims to examine and analyse factors that are affecting tax planning oncompanies using effective tax rate as the indicator. The said factors are firm size, leverage, inventory intensity, profitability, and foreign income of a company. The sample of this study were 47 listedmanufacturing companies in Indonesia Stock Exchange (BEI) from the year 2014 to 2018. The tools used in this analysis were data panel regression, t test, F test, and the coefficient of determination. The result of this study shows that partially, firm size and profitability have positive effect on tax planning, while leverage and foreign income have negative effect. On the other hand, the result of this study also shows that inventory intensity doesn’t have any significant effect on tax planning. Moreover, the result of this study shows that the said factors simultaneously affected tax planning. Keywords: Tax Planning, Firm Size, Leverage, Inventory Intensity, Profitability, Foreign Income ABSTRAKPenelitian ini menguji dan menganalisis faktor-faktor yang dapat mempengaruhiperencanaan pajak perusahaan dengan indikator tarif pajak efektif. Faktor-faktor yang dimaksudadalah ukuran perusahaan, tingkat utang, intensitas persediaan, tingkat profitabilitas, serta pendapatan luar negeri suatu perusahaan. Sampel pada penelitian ini adalah 47 perusahaan manufaktur yang terdaftar pada Bursa Efek Indonesia pada tahun 2014-2018. Alat analisis yang digunakan adalah regresi data panel, uji t, uji f dan koefisien determinasi. Hasil penelitian menunjukkan bahwa secara parsial ukuran perusahaan dan tingkat profitabilitas perusahaan memiliki pengaruh signifikan positif terhadap perencanaan pajak, sedangkan tingkat utang dan pendapatan luar negeri memiliki pengaruh signifikan negatif terhadap perencanaan pajak perusahaan. Di sisi lain, hasil penelitian menunjukkan bahwa intensitas persediaan tidak memiliki pengaruh yang signifikan terhadap perencanaan pajak. Selain itu, hasil penelitian juga menunjukkan bahwa faktor-faktor tersebut berpengaruh secara simultan. Kata kunci: Perencanaan Pajak, Ukuran Perusahaan, Tingkat Utang, Intensitas Persediaan, TingkatProfitabilitas, Pendapatan Luar Negeri

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Araujo, Andre Vieira de Freitas, et Diná Marques Pereira Araújo. « Fundamentos da Biblioteconomia moderna em Gabriel Naudé : notas transversais pela lente episteme da bibliografia e da bibliofilia ». Pesquisa Brasileira em Ciência da Informação e Biblioteconomia 14, n^o 1 (19 février 2019). http://dx.doi.org/10.22478/ufpb.1981-0695.2019v14n1.44423.

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Reflexão preliminar acerca dos fundamentos da Biblioteconomia Moderna em Gabriel Naudé (1600-1653) sob a perspectiva da Bibliografia e Bibliofilia. A partir de abordagem histórico-bibliográfica, apresenta a paisagem histórico-cultural de Naudé e os contextos de concepção de Advis pour dresser une bibliothèque (1627). Discute a dimensão bibliográfica de Advis perante a seleção e ordem libraria. Sob a perspectiva da Bibliografia, identifica que: 1) Naudé define os critérios e as motivações culturais para se formar uma biblioteca pautada em um cânon bibliográfico em consonância com a paisagem cultural de sua época (BALSAMO, 1998); 2) Naudé faz recomendações de ordem libraria que se expressam por meio da classificação que propõe em disciplinas: Teologia, Medicina, Direito, História, Filosofia, Matemática e Humanidades e suas subdivisões; 3) Advis não é um guia biblioteconômico e nem mesmo tem seus eixos teóricos vinculados aos aspectos biblioteconômicos e organizacionais, mas seu foco está na atenção e na preocupação em relação à constituição de coleção de livros por meio de estratégias bibliográficas voltadas à coleta, seleção e aquisiçãolibraria (SERRAI; SABBA, 2005). Para além de sua dimensão bibliográfica, Advis caracteriza-se, essencialmente, enquanto um tratado da Bibliofilia para a Bibliofilia no qual são detalhadas as recomendações para a formação de uma biblioteca para o bibliófilo (MALCLÈS, 1956; ROZZO, 1995). Neste horizonte, Advis é um construto da Bibliografia e Bibliofilia. Os impactos do pensamento de Naudé e de seu Advis - pela lente da Bibliografia e da Bibliofilia - podem ser evidenciados pela organização e pelo planejamento de coleções librariae patrimoniais e, sobretudo, pela ideologia a favor de uma conduta singular das práticas de formação de bibliotecas naquele momento histórico - o que requer uma leitura temporal do tratado naudeano sem o canonizarmos. Essas são, de fato, as grandes contribuições de Naudé e de seu Advis para a Biblioteconomia Moderna, na medida em que perpassam não apenas por aspectos formativos de uma biblioteca, mas também pelos elementos culturais e epistêmicos que sustentam a construção da instituição biblioteca e, consequentemente, do campo biblioteconômico.Palavras-chave: Advis pour dresser une bibliothèque (1627). Bibliofilia. Bibliografia. Biblioteconomia Moderna - Fundamentos. Gabriel Naudé (1600-1653). Link: https://rbbd.febab.org.br/rbbd/article/view/1180/1060

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« Preface ». IOP Conference Series : Earth and Environmental Science 914, n^o 1 (1 novembre 2021) : 011001. http://dx.doi.org/10.1088/1755-1315/914/1/011001.

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Abstract The International Conference 2021 (INAFOR 2021 Stream 2) was held on 7-8 September 2021 in a virtual format via zoom meetings due to the COVID-19 pandemic situation. It was conducted virtually to align with the biannual agenda of The 6th International Conference of Indonesia Forestry and Environment Researchers (INAFOR), which previously was carried out by The Agency for Standardization of Environment and Forestry Instruments, Ministry of Environment of Forestry, Indonesia. This is the first international conference hosted by The Center for Standardization of Sustainable Forest Management Instruments, Bogor, West Java, Indonesia. This conference was an important medium for sharing information and experiences and encouraging collaboration in sustainable forest management. The theme “Managing Forest and Natural Resources, Meeting Sustainable and Friendly Use”, strategically supports Indonesia’s commitment to Net Sink Forestry and Land Use (FoLU) 2030. The INAFOR 2021 Stream 2 was attended by approximately 750 participants, invitees, keynote speakers, scientists, and academicians from Indonesia, South Korea, the Netherland and Australia. The conference took place with a plenary session featuring six Keynote Speakers that presented exciting and practical information relevant to the theme. Also, a parallel session was divided into 12 separate zoom spaces according to the topics and number of participants. The presenters had ten minutes to present their papers and followed by interactive and engaging discussion. This proceeding presents 78 papers of research results on various topics, including biodiversity conservation, livelihoods, climate resilience, timber, and non-timber forest products. Those valuable pieces of information and recommendations can be modalities and references for the preparation and development of standards for sustainable forest management instruments and the development of science, technology, and innovation. Thank you. Dr. Wening Sri Wulandari Acting Director of Center for Standardization of Sustainable Forest Management Instruments Scientific Committee Prof. (Ris.) Dr. Sri Suharti; Prof. (Ris.) Dr. Pratiwi; Prof. (Ris.) Dr. Hendra Gunawan; Prof. (Ris.) Dr. Maman Turjaman; Prof. (Ris.) Dr. Haruni Krisnawati; Prof. (Ris). Dr. R. Garsetiasih; Prof. (Ris). Dr. Murniati; Prof. (Ris). Dr. Nina Mindawati; Prof. (Ris). Chairil Anwar Siregar; Prof. (Ris). Dr. Gustan Pari; Prof. (Ris). Dr. AYPBC Widyatmoko; Prof. (Ris). Dr. Liliana Baskorowati ; Asep Hidayat, Ph.D.; Henti Hendalastuti Rachmat, Ph.D.; Krisdianto, Ph.D.; Jamaludin Malik, Ph.D.; Dr. Neo Endra Lelana; Dr. Rozza Tri Kwatrina; Dr. Budi Hadi Narendra; Dr. Wa Ode Muliastuty Arsyad; Dr. Rizki Maharani; Dr. Arif Nirsatmanto; Dr. Dede Sudrajat; Denny, S. Hut., M.P.; Rinaldi Imanuddin, S.Hut., M.Si.; Irma Yeni, S.P., M.Sc.; Drs. Bugi Sumirat, M.Phil.

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