PRIOR EXPOSURE TO IMMUNOSUPPRESSIVE AGENTS AND COMORBIDITIES ARE ASSOCIATED WITH WORSE OUTCOMES OF SARS-COV2 INFECTION IN PH-NEG CHRONIC MYELOPROLIFERATIVE NEOPLASMS: RESULTS OF EPICOVIDEHA SURVEY

Background: Philadelphia-negatie chronic myeloproliferatie neoplasms (MPN) typically incur high rates of thrombosis and infections and cytoreductie drugs may modulate such risks. Aims: The present analysis aims at assessing the seerity and outcomes of MPN facing coronairus disease 2019 (COVID-19). Hence, we aimed to assess the impact of immunosuppressie agents and comorbidity burden in COVID- 19 outcome. Methods: The EPICOVIDEHA registry is an online surey (www.clinicalsureys.net) that has collected since April 2020 until January 2022 5,445 cases of COVID-19 in indiiduals with baseline haematological malignancies (Salmanton-García et al, 2021 Hemasphere) The surey is promoted by the European Hematology Association - Infectious Diseases Working Party (EHA-IDWP) and has been approed centrally by the Institutional Reiew Board and Ethics Committee of Fondazione Policlinico Uniersitario A. Gemelli - IRCCS - Uniersità Cattolica del Sacro Cuore, Rome, Italy (Study ID: 3226). Results: Oerall, 308 patients (5.6%) with MPN were obsered for a median of 102 days (IQR: 21-223, range 22-97) after COVID-19 diagnosis. Median age at infection was 69 years (IQR: 58-77, range 22-97) and at least one comorbidity was reported from most of the indiiduals (62.6%, n = 193). A large portion of patients had a history of cardiopathy (n=109, 35.4%), diabetes (n=40, 15.9%), or chronic pulmonary disease (n=44, 14.3%). Myelofibrosis (MF) (n=140, 45.4%) was the most prealent baseline malignancy, with 18 MF patients (12.9%) reporting 3 or more comorbidities. Out of the whole cohort, 72 patients (42.8% of MF) receied immunosuppressige therapies including steroids, immunomodulatory drugs (IMiDs) or JAK-inhibitors. Hospitalization and consecutie admission to intensie care unit was required for 187 (60.7%) and 45 (24%) patients, respectiely. At multiariate logistic regression, Hospital admission was predicted by age >70 years (OR 2.809;95% CI 1.651-4.779), exposure to immunosuppressie therapies (OR 2.802;95% CI 1.5380-5.103) and comorbidity burden. During the study follow-up (median 101 days;range 21-222) 84 patients deceased after a median time of 14 days (IQR: 8-49, range 0-457) since COVID-19 diagnosis. The fatality rate (FR) decreased from 40.3% (50 out of 124) in the first two quarters of year 2020 to 15.8% (3 out of 19) in the first two quarters of year 2021 (p<0.05). Death was principally attributable to COVID-19 in 58 patients (69.0%) and contributable by COVID-19 in 15 (17.9%). FR was particularly high (54 out of 140, 38.6%) in MF patients and in patients receiing immunosuppressie agents (32 out of 86, 37%). Moreoer, FR increased from 13.0% in indiiduals with no comorbidity to 36.0% and 62.1% in those with >2 or >3 comorbidities, respectiely. More specifically, three comorbidities independently increased the FR: chronic cardiopathy (HR 1.653;95%CI 1.017-2.687), chronic pulmonary disease (HR 1.847;95% CI 1.097-3.109), and diabetes mellitus (HR 1.712;95% CI 1.006-2.914). A heay comorbidity burden, namely 3 or more comorbidities (HR 2.956;95% CI 1.403-6.227), adanced age, namely >70 years (HR .809;95% CI 1.651-4.779), myelofibrosis (HR 2.501;95% CI 1.384-4.519), and ICU admission (HR 2.669;95% CI 1.641-4.342) independently predicted FR. (MF) (n=140, 45.4%) was the most prealent baseline malignancy, with 18 MF patients (12.9%) reporting 3 or more comorbidities. Out of the whole cohort, 72 patients (42.8% of MF) receied immunosuppressige therapies including steroids, immunomodulatory drugs (IMiDs) or JAK-inhibitors. Hospitalization and consecutie admission to intensie care unit was required for 187 (60.7%) and 45 (24%) patients, respectiely. At multiariate logistic regression, Hospital admission was predicted by age >70 years (OR 2.809;95% CI 1.651-4.779), exposure to immunosuppressie therapies (OR 2.802;95% CI 1.5380-5.103) and comorbidity burden. During the study follow-up (median 101 days;range 21-222) 84 patients deceased after a median time of 14 days (IQR: 8-49, range 0-457) since COVID-19 diagnosis. The fatality rate (FR) dec eased from 40.3% (50 out of 124) in the first two quarters of year 2020 to 15.8% (3 out of 19) in the first two quarters of year 2021 (p<0.05). Death was principally attributable to COVID-19 in 58 patients (69.0%) and contributable by COVID-19 in 15 (17.9%). FR was particularly high (54 out of 140, 38.6%) in MF patients and in patients receiing immunosuppressie agents (32 out of 86, 37%). Moreoer, FR increased from 13.0% in indiiduals with no comorbidity to 36.0% and 62.1% in those with >2 or >3 comorbidities, respectiely. More specifically, three comorbidities independently increased the FR: chronic cardiopathy (HR 1.653;95%CI 1.017-2.687), chronic pulmonary disease (HR 1.847;95% CI 1.097-3.109), and diabetes mellitus (HR 1.712;95% CI 1.006-2.914). A heay comorbidity burden, namely 3 or more comorbidities (HR 2.956;95% CI 1.403-6.227), adanced age, namely >70 years (HR .809;95% CI 1.651-4.779), myelofibrosis (HR 2.501;95% CI 1.384-4.519), and ICU admission (HR 2.669;95% CI 1.641-4.342) independently predicted FR. Summary/Conclusion: COVID-19 infection led to a particularly dismal outcome in patients exposed to immunosuppressie agents and in those with chronic heart or pulmonary diseases, or diabetes. These data allow to tailor future strategies for preenting seere COVID-19 in MPN patients. (Table Presented).

B-CELL MALIGNANCIES TREATED WITH TARGETED DRUGS AND SARS-COV-2 INFECTION. A EUROPEAN HEMATOLOGY ASSOCIATION SURVEY (EPICOVIDEHA)

Background: Patients with lymphoproliferatie diseases (LPD) appear particularly ulnerable to SARS-CoV-2 infection, partly because of the effects of the anti-neoplastic regimens (chemotherapy, signaling pathway inhibitors, and monoclonal antibodies) on the immune system. The real impact of COVID-19 on the life expectancy of patients with different subtypes of lymphoma and targeted treatment is still unknown. Aims: The aim of this study is to describe and analyse the outcome of COVID-19 patients with underlying LPD treated with targeted drugs such as monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, niolumab or pembrolizumab), BTK inhibitors (ibrutinib, acalabrutinib), PI3K inhibitors (idelalisib), BCL2 inhibitors (enetoclax) and IMIDs, (lenalidomide). Methods: The surey was supported by EPICOVIDEHA registry. Adult patients with baseline CLL or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between January 2020 and January 2022 were selected. Results: The study included 368 patients (CLL n=205, 55.7%;NHL n=163, 44.3%) treated with targeted drugs (Table 1). Median follow-up was 70.5 days (range 19-159). Most used targeted drugs were ITKs (51.1%), anti-CD20 other than rituximab (16%), BCL2 inhibitors (7.3%) and lenalidomide (7.9%). Of note, only 16.0% of the patients were accinated with 2 or more doses of accine at the onset of COVID-19. Pulmonary symptoms were present at diagnosis in 244 patients (66.2%). Seere COVID-19 was obsered in 47.8 % patients while 21.7% were admitted to to intensie care unit (ICU), being 55 (26.8%) CLL patients and 25 (15.3%) NHL patients. More comorbidities were reported in patients with seere-critical COVID-19 compared to those with mild- asymptomatic infection (p=0.002). This difference was releant in patients with chronic heart diseases (p=0.005). Oerall, 134 patients (36.4%) died. Primary cause of death was COVID-19 in 92 patients (68.7%), LPD in 14 patients (10.4%), and a combination of both in 28 patients (20.9%).Mortality was 24.2% (89/368) at day 30 and 34.5%(127/368) at day 200. After a Cox multiariable regression age >75 years (p<0.001, HR 1.030), actie malignancy (p=0.011, HR 1.574) and admission to ICU (p<0.00, HR 4.624) were obsered as risk factors. Surial in patients admitted to ICU was 33.7% (LLC 38.1%, NHL 24%). Mortality rate decreased depending on accination status, being 34.2% in not accinated patients, 15.9-18% with one or two doses, decreasing to 9.7% in patients with booster dose (p<0.001). There was no difference in OS in NLH s CLL patients (p=0.344), nor in ITKs s no ITKs treated patients (p=0.987). Additionally, mortality rate dropped from the first semester 2020 (41.3%) to last semester 2021 (25%). Summary/Conclusion: - Our results confirm that patients with B--mallignancies treatted with targeted drugs hae a high risk off seere infection (47.8%) and mortality (36.4%) from COVID-19. - Pressence of comorbidities,, especially heart disease,, is a risk factor for seere COVIID--19 infection in ourr series. - Age >75 years,, actie mallignancy att COVIID--19 onset and ICU admission were mortality risk factors. - COVIID--19 acination was a protectie factor for mortality,, een iin this popullation wiitth humorall immunity impairment. - The learning cure in the management of the infection throughout the pandemiic and the deelopmentt off COVIID--19 treatments showed benefit in this partticullarlly ullnerablle popullation? (Table Presented).

PROSPECTIVE MULTICENTRIC STUDY ON INFECTIOUS COMPLICATIONS AND CLINICAL OUTCOME IN 230 UNFIT AML PATIENTS TREATED IN FIRST-LINE WITH HYPOMETHYLATING AGENTS ALONE OR IN COMBINATION WITH VENETOCLAX

Background: The hypomethylating agents (HMAs) are an important therapeutic option for older patients (pts) with AML and have become the backbone for combination regimens (eg, with Venetoclax). However, there are very limited real-life prospective studies regarding clinical outcome of these pts, including infectious complications and infection related mortality (IRM) during treatment. Aims: To investigate the infectious complications and clinical outcome in AML patients treated with HMAs± Venetoclax (V) outside of clinical trials. Methods: The recruitment of this prospective multicentric study (CE-Id-study:2908) has been completed on December 31, 2020. We enrolled 230 AML pts with a median age of 75 years (range 25-94);157 pts (68%) had >2 relevant comorbidities. Of the 230 cases, 132 (57%) received a first-line therapy with a combination of HMAs+V while 98 (43%) were treated with HMAs monotherapy (azacitidine or decitabine). A total of 1550 cycles of HMAs have been administered (680/1550 with HMAs+V). Results: The best response achieved, with HMAs treatment, was: CR in 44% of cases (57,6% with HMAs+V and 25,5% with HMAs alone, P=0,0001), PR in 17% and SD in 14% of cases (ORR 61%;72% in HMAS+V and 46% in HMAs alone, P=0,0007). The microbiological or radiological proven infectious complications (almost one) occurred in 160/230 (70%) of pts, mainly pneumonia (in 42% of pts) and/or bacteremia/sepsis (one or more events in 29% of pts). Febrile neutropenia (one or more episodes) occurred in 38% of pts and 14 cases of Covid-19 (6%) were reported. After a median follow-up of 9 months (1-24) from the start of HMAs therapy, 144 (63%) pts died and 86 (37%) were alive. The 1 yr OS probability was 46% with a median OS of 10,3 months (11 months in HMAs+V and 9 months in HMAs alone;P=ns). The primary causes of death were: progression of AML (42%), Infection (26%-37/144), Infection+AML (24%), other causes (8%). The IRM was 26% and 19/144 (13%) pts died of infectious complication while in CR/PR (16 in HMAs+V group and only 3 in HMAs group;P=0,005). Data on antibiotic prophylaxis, hospitalization, drugdoses modulation, are available and analyzed in this study. Summary/Conclusion: The results of this real-life, multicentric, prospective study, confirm a higher CR rate in pts treated with HMAs+V compared to HMAs alone (P=0,0001). However, we found a high rate of infectious complications and IRM (26%) with a higher infection related deaths in patients in CR/PR who were treated with HMAs+V (P=0,005). Findings from this study highlight the critical relevance of infection prevention in reducing infectious mortality, which adversely impacts the OS of this frail AML population.

Proceedings of the VI National Meeting of the Italian Group of Paleopathology (GIPaleo)

The presence of numerous scientific contributions in the program is certainly demonstrative of the fact that research in the field of paleopathology and anthropology has not stopped since the beginning of Covid-19. Furthermore, the same emergency that we are still partially feeling, has pushed our community scientific research to question itself more intensely in connection to the epidemic relationship and measures that repeatedly led to profound transformations in the societies of the past from different points of view: demographic, economic, social and the history buried under the bioarchaeological strata is today more capable than ever to show this connection. It can do this by bringing to light the paleodemographic data that is obtained from the study of human remains. Today we will listen to many paleopathological stories and among these I am very happy to also present ours. Twenty years ago, the University of Insubria started a collaboration with the Archaeological Superintendence of Lombardy for the study of osteological remains found mostly during emergency archaeology recoveries. These experiences led us to reach those bioarchaeological sites again with the aim of extracting all those cemetery layers that remained there because they were not subjected at that time by building reclamation interventions. Returning to those sites that in the past brought to light fragmentary anthropological data means allowing oneself the possibility of obtaining new palaeodemographic and palaeopathological data which are decisive for reconstructing the demographic and epidemiological history of the populations of the past. These new interventions led us to create an operational model that immediately intended to underline the importance of an evident continuity between the archaeological recovery and the anthropological study of the finds through the setting up of physical anthropology and paleopathology laboratories directly on the sites of the finds. All this in harmony with the final design of the projects or the museumization of bioarchaeological sites in their complexity aimed at enhancing cultural tourist routes in the area. In this regard, I would like to thank the community foundation of Varese and the Cariplo foundation for supporting our current initiatives. These include the project financed by the emblematic provincial tender and which has as its final objective the enhancement of three bioarchaeological sites in Valcuvia: the medieval sites of San Biagio in Cittiglio, Sant’Agostino in Caravate, and the modern crypt of the church of the Convent of Azzio. Today, our Research Centre works in Piedmont in different sites in the province of Vercelli and Alessandria. Aware of the importance of a physical anthropological approach in the field, our young Centre goes beyond the continental borders to reach Eritrea, the ancient city of Adulis, because it is in dissecting the taphonomic events and the funeral actions that will make it possible to identify the funerary ritual adopted by the ancient populations. The operational model of paleopathological research, which gradually enriches itself thanks to the multidisciplinary nature of the interventions and thanks to the individual experiences in the field, is thus continuously transferred and adapted to other anthropological contexts that retain potential both in terms of investigative and enhancement of the bioarchaeological heritage. Through the musealization of the sites it is also possible to acquire an attractive force towards all those potentially bioarchaeological areas but which today are in conditions of neglect because they are marginal with respect to the conventionally understood cultural tourist good. And we all know how important it is to transfer the study data even outside the academic context because making this aspect of archaeology, the truly human one, usable too, cannot fail to arouse a strong awareness of our past. We also know how much more we will have to work, following in the footsteps of the professors who started this path, to ensure that the d sciplines of paleopathology and physical anthropology arrive within all those degree courses still discovered today by these teachings to heal an important lack: knowing the human past from a physical and pathological point of view allows us to understand the evolutionary path of some pathologies, especially those of infectious nature. If my title of the speech “Paleopathology and osteoarchaeology in the province of Varese” does not respond to what is being said today, it is because my feeling about paleopathology and osteoarchaeology in the province of Varese is understood as that of carrying out research, what I could feel everywhere, through the operational model, the enthusiasm for paleopathological research and of course the people I am lucky enough to work with. The Morgagni Museum of Pathological Anatomy of the University of Padua preserves a wide series of pathological specimens, mostly from the second half of the 19th century and the early 20th century. The Museum was recently renewed, as the result of an intervention of enhancement of the museum and cultural heritage of the University of Padua and its Medical School, being also testimony to the history and evolution of human pathology and past population lifestyle. In the collection of the Morgagni Museum there are several specimens affected by atherosclerotic lesions. Atherosclerosis is characterized by a chronic inflammatory disease in which different factors are involved, such as lipoproteins, immune cells and endothelial damage. The main clinical syndromes related to atherosclerosis are angina pectoris, acute myocardial infarction, transient ischemic attack, cerebral stroke, intermittent claudication, aortic aneurysm and nephro-vascular hypertension. Atherosclerosis was believed to be a modern disease, related almost exclusively to age and current lifestyle. The cases from the Morgagni Museum are therefore useful for studying the presence of the atherosclerosis in a recent past population. In the collection there were identified six atherosclerotic cases: an atherosclerotic aneurysm of the ascending aorta: the specimen highlights the left ventricular outflow tract and the aortic root. There is a severe atherosclerosis of the ascending aorta with saccular aneurysm including a large thrombus;a syphilitic aortitis complicated by atherosclerosis: the finding highlights the left ventricular outflow tract and aortic root. It is possible to note the intima of the ascending aorta with ulcer-calcific atherosclerotic plaques and “tree-bark” whitish areas;an atherosclerotic aneurysm of the abdominal aorta: abdominal aorta with saccular atherosclerotic aneurysm, proximal to the iliac bifurcation;a case of aortic atherosclerosis: aorta with severe atherosclerosis complicated by calcification and thrombosis;a case of aortic atherosclerosis: massive dissemination of atheromatous-calcific plaques;a case of aortic atherosclerosis with parietal thrombi: widespread presence of plaques along the aortic wall. Thanks to this collection, it is possible to notice the spread of pathology on an atheromatous basis in the recent past populations. Moreover, current paleopathological investigations on ancient populations mummified remains also showed traces of atherosclerotic lesions in both sexes and different ages. It is therefore possible to support a ubiquitous diffusion in space and time of this complex multifactorial pathology which has so far considered to be almost an exclusive prerogative of old age and current lifestyle. The Morgagni Museum of Pathological Anatomy of the University of Padua, founded by Lodovico Brunetti (1813-1899) in the 1860s, gathers important pathological specimens mainly from the 19th century. Among them, there is a very peculiar preparation: it consists of a dried head representing a case of argyria dating back to 1873. The specimen is preserved in a sealed jar, all the skin has a blue-gray coloration with white-blonde hair and beard. The eyes are not preserved, but since the ocular cavities remain open, it is possible to presume that origin lly there were glass eyes. Two glass sticks are inserted inside the mouth to show that also tongue and gums have the same blue-gray pigmentation as the face. The upper teeth are strongly eroded. Argyria is a rare disease caused by chronic absorption of products with a high silver content, which surpass body’s renal and hepatic excretory capacities, leading to silver granules being deposited in the skin and its appendages, mucosae and internal organs. It is characterized by blue-gray or black staining of the skin and mucous membranes. Our case was first mentioned in 1862 as a syphilitic man who was treating himself with some caustic silver nitrate, the so called “infernal stone”, since 1840s. According to him, this medicament cured the syphilis, but turned him into a “graphite man”. The patient died in 1873 of an intestinal infection, most likely related to the prolonged ingestion of the silver nitrate. This case was described as “spectacular” by Austrian dermatologist Isidor Neumann (1832-1906), who studied a sample of the tongue of the specimen sent by Brunetti. In fact, Brunetti performed the autopsy on the body of the individual and prepared also a plaster cast of the head along with the sample for Neumann. Thus, we can assume Brunetti was also the one who preserved the original head, taxidermizing it (so-called stuffed head preparation) in order to preserve the skin color, because his famous tannisation method would not maintained the original characteristics. Human taxidermy is quite rare, and it is limited to a few cases in the 19th century. Moreover, there are just a few known human stuffed heads in the world, making the Paduan specimen particularly unique both for the pathology and the technique used for the preparation.

Life skills training to promote health and well-being at school: an evaluation

Background In educational settings, health promotion refers to a whole-school approach to help individuals realize their potential, cope with the everyday stresses of life, work productively and fruitfully, and contribute to their community. In these regards, it is essential to enhance a vast repertoire of knowledge, skills, attitudes, and values, a narrower set of psychosocial skills (Life Skills - LS). The Local Health Unit of Palermo, the Centre of Training and the National Institute of Health (ISS) developed the project “Life Skills and resilience: effective strategies to promote health at school”. Objectives The project's general aim was to provide headteachers and teachers with methodologies and tools to develop and promote LS in educational settings. Through the participatory approach, training was structured in 5 modules of 16 hours each. The training activities began in October 2019 and ended online due to the Covid-19 emergency in July 2020. The evaluation plan provides the assessment of learning, satisfaction, monitoring and assessment of attitudes and behaviours using a validated questionnaire. The aim was to identify improvements in relationships inside and outside the school context and increase self-efficacy and job satisfaction among teachers. Data analysis is currently being processed. Results 169 Teachers, 12 Healthcare workers attended the training. The preliminary results show that: i. there is an improvement in relationships between colleagues, students and parents;ii. there is a slight improvement in the perceived self-efficacy in managing negative emotions;iii. there is an improvement in the personal and collective effectiveness perceived in the school environment and job satisfaction. Conclusions The project was designed for implementing sustainable interventions. The advent of COVID-19 has allowed further reflection on the usefulness of this approach for promoting resilience and protective factors and managing the consequences of the pandemic. Key messages The training improved personal and professional skills on design and methods to apply LS. The use of qualitative/quantitative assessment made it possible to illustrate the entire training process.

Production and persistence of specific antibodies in COVID-19 patients with hematologic malignancies: role of rituximab.

The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.

Safety and efficacy of the “carmen” regimen, a new dose-dense short-term therapy in patients with aggressive B-cell lymphoma and myc rearrangement

Introduction: Patients (pts) with aggressive B-cell lymphoma and MYC rearrangement exhibits poor outcome after R-CHOP treatment. In the last decade, these pts were treated with a new dose-dense, short-term therapy termed “CARMEN”, at several Italian Centers. Excellent efficacy and safety profile have been reported in HIV/AIDS pts with high-risk Burkitt lymphoma (BL) [Ferreri et al. BJH 2021], but its efficacy in pts with high-grade B-cell lymphoma with MYC rearrangement (HGBCL) remains to be defined. Herein, we report a retrospective series of consecutive pts with BL or HGBCL treated with CARMEN regimen. Methods: Either HIV-negative and HIV-positive pts aged 18-80 years with BL or HGBCL and MYC rearrangement positive by FISH were treated with CARMEN regimen, which includes a single 36-day induction course of sequential doses of cyclophosphamide, vincristine, rituximab, methotrexate, VP16, and doxorubicin plus intrathecal chemotherapy, followed by consolidation with HD-cytarabine ± cisplatin. Pts who did not achieve complete remission (CR) after induction received BEAM/ASCT after consolidation. Results: 63 pts (22 HGBCL;41 BL) received the CARMEN regimen (Table). Treatment was well tolerated: 56 (89%) pts completed the induction, and 55 (87%) completed the consolidation. G4 hematological toxicity during induction was neutropenia in 48 (76%) pts, thrombocytopenia in 24 (38%) and anemia in 7 (11%), which were recorded after consolidation in 34 (62%), 38 (69%) and 1 (2%) pt, respectively. G4 non hematological toxicity was uncommon: mucositis in 4 (6%) pts and tumor lysis syndrome in 1 (2%) during induction, and heart failure and bleeding in 1 (2%) pt each after consolidation. G4 infections were recorded in 4 (6%) pts during induction and in 2 (3%) after consolidation. Induction and consolidation doses were reduced in 6 (9%) and 4 (7%) pts, respectively. Seven HGBCL and 9 BL pts received ASCT, with expected tolerability. 4 HGBCL and 2 BL pts died of toxicity (sepsis in 4;respiratory failure;COVID-19), with a TRM of 9%. After induction, 18 (82%) HGBCL and 37 (90%) BL pts achieved a response, which was CR in 10 (45%) and 26 (63%) pts, respectively. After the whole treatment, 15 (68%) HGBCL pts and 32 (78%) BL pts achieved a CR, and, at a median follow-up of 54 (2-131) months, 15 (100%) HGBCL and 29 (91%) BL pts remain relapse-free, with a 5-yr PFS of 67% and 70%, respectively. 15 HGBCL and 32 BL pts are alive, with a 5-yr OS of 66% and 77%, respectively. HIV seropositivity did not modify outcome. Age and LDH level were independently associated with OS. Conclusions: With the limitations of a retrospective series, this study shows that CARMEN is a safe and active treatment both in HIVnegative and-positive pts with HGBCL and MYC rearrangement and BL. Survival figures in HGBCL pts compare favorably with results reported with R-CHOP or analogous, and are similar to those achieved in BL pts.

Violence against women in the Covid-19 pandemic: A review of the literature and a call for shared strategies to tackle health and social emergencies.

The aim of this article was to conduct a rapid critical review of the literature about the relationship between violence against women (VAW) and the current COVID-19 pandemic. After the screening process, a total of 42 articles were considered. Our review confirmed that the "stay at home" policies to contrast the pandemic have increased the problem of VAW, creating a "shadow pandemic within the pandemic", as it was called by the United Nations. However, rigorous studies estimating the relationship between VAW and COVID-19 pandemic are scarce; most of the articles are commentaries, letters, editorials, and most of the published data derives from social media, internet, anecdotal evidence and helplines reports. Health care systems should promote further investigations into the relation between VAW and COVID-19, to identify creative solutions to provide clinical care and forensic services for victims of VAW.