Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers

Background: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods: Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Anagrelide in Essential Thrombocythemia: A Retrospective Analysis of 220 Patients. Session Type: Poster Session 646-III

This retrospective study analyses 220 patients with Essential Thrombocythemia (ET) treated with Anagrelide in 26 Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC). The patients, 81 males and 139 females, at diagnosis had a mean age of 39 years (13-40 years 55%; 41-60 years 35%; 61-82 years 10%) and showed a mean PLT count (109/L) of 1108, previous thrombosis (4.5%), previous hemorrhage (3%), disease related symptoms (20%), cardiovascular risk factors (32%) and splenomegaly (25%). At start of Anagrelide treatment the mean PLT count (109/L) was 907 (>1000 in 32%). The 68% of patients were receiving an antiplatelet treatment and the 74% received cytoreductive drugs (Alkylating agents and HU 17%, HU alone 20%, HU and IFN 21%, IFN alone 16%). The treatment with Anagrelide was started mainly because of the young age of patients, inefficacy and/or high dose required, toxicity and/or side effects of the other drugs and patient request. The mean daily Anagrelide dose from the baseline of 1.3 mg was increased to 1.5 mg after 1 month and to 1.8 mg since the 12th month. The most common side effects were cephalea/vertigo (24%), palpitation/tachycardia (24%), gastrointestinal (9%), asthenia (8%), oedema (5%). A transitory interruption of Anagrelide treatment was observed in 44/220 cases (20%) as a consequence of drug toxicity (3.7%), side effects (5%), no drug availability (4.5%), other causes (6.8%). A drug withdrawal was registered in 54/220 patients (24.5%) after a median treatment duration of 17 months when the mean Anagrelide dose was 1.8 mg/day and the mean PLT count was 665 x109/L), because of inefficacy (3%), toxicity (3%), side effects (9.5%), compliance loss (1%), no drug availability (3%),other causes (5%). The mean follow-up of all 220 patients was 21 months. The mean PLT count (109/L) from the baseline value of 907 decreased to 586, 505, 490, 458 and 449 after 1, 6, 12, 36 and 60 months, respectively. The mean WBC count (109/L) was 7.7 at the baseline and 9.2 after 60 months. The mean Hb level (g/dL) from the baseline of 13.2 decreased to 12.8 and 12.4 at months 6 and 60, respectively. Two minor hemorrhagic events (0.51/100 pt-yrs) and 3 major thrombotic events (0.77/100 pt-yrs) were observed during the follow-up. In this series of ET patients the treatment with the non-mutagenic Anagrelide has been confirmed to be effective and globally well tolerated. Nevertheless, new prospective studies are necessary to define the Anagrelide long-term toxicity, particularly in terms of thrombotic and/or hemorrhagic complications and anemia occurrence

Assessing the status of amphibian breeding sites in Italy: a national survey

The ecological status of 203 amphibian aquatic breeding sites, selected from the national database of the Societas Herpetologica Italica (SHI), was surveyed in the period 2008-2009 to assess their ecological status. Sites were randomly extracted, after stratification by the three biogeographical regions present in Italy, besides Sardinia and Sicily. The field surveys, conducted by professionals, amateurs and volunteers, showed that since 1979 about 11% of the sites were destroyed or no more suitable for the reproduction of amphibians that bred in the same site in the past. The percentage of destroyed or altered sites was 8%, both in the Mediterranean and Alpine biogeographical regions, and 15% in the Continental one. However, there were no statistical significant differences among the regions, suggesting that the rate of amphibian site loss was similar in different parts of Italy. This nation-wide monitoring project demonstrated that in Italy, during the last thirty years, a relevant proportion of amphibian breeding habitats has been destroyed or altered. The main cause of site alteration were land reclamation and water extraction

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientifc Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confrmed COVID19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non- Hodgkin lymphoma n=1084, myeloma n=684 and chronic lymphoid leukemia n=474) and myeloproliferative malignancies (mainly acute myeloid leukemia n=497 and myelodysplastic syndromes n=279). Severe/critical COVID-19 was observed in 63.8% of patients (n=2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate signifcantly decreased between the frst COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value<0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confrms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)