Aims To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. Methods and results We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). Conclusion Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.

ADAMTS-13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2012; 10: 1556-65.Summary. Background: Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening disease. Of surviving patients, 45% develops an exacerbation or a late recurrence. Severe ADAMTS-13 deficiency, both during the acute episode and remission, is a well-established predictor of recurrence. The predictive value of anti-ADAMTS-13 antibodies, their inhibitory activity and Ig class subtype for disease recurrence is still to be established. Objectives: To analyze ADAMTS-13-related biomarkers (ADAMTS-13 and anti-ADAMTS-13 immunoglobulins, classes and subclasses) and their potential relationship with prognosis. Patients/Methods: In 115 patients with TTP, we assessed the association between levels of these biomarkers and the severity of acute episodes; we analysed also the hazard ratio (HR) and 95% confidence interval (CI) of recurrence in association with biomarkers levels retrieved at the previous acute episode or during remission, using Cox regression models. Results: During the acute phase, higher IgA, IgG1 and IgG3 titers showed the strongest association with acute episode severity. In the survival analyzes, the only biomarker significantly associated with a high hazard of recurrence after an acute episode was the presence of IgG. Conversly, low ADAMTS-13 activity or antigen levels (< 10%), the presence of ADAMTS-13 inhibitor or IgG during remission were all significantly associated with a higher hazard of recurrence. Conclusions: Both the Ig class and subclass are of predictive value for acute episode severity in patients with TTP. Although markers that could predict the risk of recurrence in the acute phase are limited, a thorough assessment of ADAMTS-13-related parameters during remission is warranted.

No abstract

A 66-year-old woman with posttraumatic anoxic coma after diffuse cerebral fat embolism had continuous alternating-side myoclonic jerks. Usually, this kind of myoclonic status epilepticus (SE) occurs in newborn infants. We postulate the unusual combination of diffuse cerebral anoxia plus commissural fiber damage as a possible explanation.

Background: It has been reported a slow progression of hepatitis B in patients undergoing maintenance dialysis, and a role of dialysis session per se has been suggested. The aim of the present study is to evaluate the kinetics of the hepatitis B viral load (HBV DNA) in serum during haemodialysis sessions using a highly sensitive technique; the role of interferon-α in lowering HBV viral load in such patients was also investigated. Methods: HBV DNA was determined in 24 HBsAg positive patients on maintenance hemodialysis immediately before and after a 4-hour hemodialysis session, the same measurements were repeated 48 and 72 hours later. HBV DNA quantitation was performed by a novel RealTime PCR assay. Serum IFN-α levels were tested in parallel in a subset of HD sessions (n=40) by ELISA. Results: 20 (83%) HBsAg positive patients had detectable HBV DNA in serum. Positive status for HBV DNA in serum was not predicted by demographic, clinical or biochemical parameters. HBV load decreased in many patients after hemodialysis sessions 5.92 log₁₀ IU/mL (95% CI, 5.34 to 6.28 log₁₀ IU/mL) vs. 4.79 log₁₀ IU/mL (95% CI, 4.23 to 6.15 log₁₀ IU/mL) (P=0.02). A significant relationship between mean HBV DNA levels before dialysis and percentage reduction of HBV DNA during HD sessions occurred [F-test=5.41, rho (least squares)=0.307]. Increase of serum IFN-α levels was found in a minority (3/40=7%) of HD sessions. Conclusions: Hemodialysis procedure gives reduction of HBV load in HBsAg chronic carriers; no relationship with IFN-α activity during HD sessions was found. The kinetics of HBV viremia in HD procedures could explain the low viral load which is typically observed in these patients. Further studies to identify the mechanisms responsible for reduction of HBV viremia during HD procedures are under way.

Background: An urgent need exists for an early detection of cases with a high-risk of SARS-CoV-2 infection, particularly in high-flow and -risk settings, such as emergency departments (EDs). The aim of this work is to develop and validate a predictive model for the evaluation of SARS-CoV-2 infection risk, with the rationale of using this tool to manage ED patients. Methods: A retrospective study was performed by cross-sectionally reviewing the electronical case records of patients admitted to Niguarda Hospital or referred to its ED in the period 15 March to 24 April 2020. Derivation sample was composed of non-random inpatients hospitalized on 24 April and admitted before 22 April 2020. Validation sample was composed of consecutive patients who visited the ED between 15 and 25 March 2020. The association between the dichotomic outcome and each predictor was explored by univariate analysis with logistic regression models. Results: A total of 113 patients in the derivation sample and 419 in the validation sample were analyzed. History of fever, elder age and low oxygen saturation showed to be significant predictors of SARS-CoV-2 infection. The neutrophil count improves the discriminative ability of the model, even if its calibration and usefulness in terms of diagnosis is unclear. Conclusion: The discriminatory ability of the identified models makes the overall performance suboptimal; their implementation to calculate the individual risk of infection should not be used without additional investigations. However, they could be useful to evaluate the spatial allocation of patients while awaiting the result of the nasopharyngeal swab.

Patients responded to different treatments regardless of ADAMTS13 activity, requiring less PEs with larger volume exchanges.

2532 Background: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease characterized by acute episodes of thrombocytopenia and microangiopathic hemolytic anemia due to disseminated microvascular thrombosis. Up to 40% of patients with TTP who survive the first acute disease episode develop one or more recurrent episodes. The severe deficiency of the von Willebrand factor (VWF) cleaving protease ADAMTS13 in plasma and the presence of anti-ADAMTS13 autoantibodies during both acute presentation and disease remission are associated with increased risk for recurrence. However, additional markers are needed for an accurate prediction of the risk for recurrent disease. Anti-ADAMTS13 autoantibodies of different immunoglobulin (Ig) subclass, specificity and mechanisms of action have been described in patients with the autoimmune form of TTP. We sought to determine the relationships between anti-ADAMTS13 Ig subclasses and risk for recurrence in a large cohort of TTP patients. Patients and methods: TTP was defined using commonly accepted criteria (microangiopathic hemolytic anemia, thrombocytopenia and exclusion of alternative explanation for the disease symptoms). Anti-ADAMTS13 IgM, IgA, IgG and IgG1, IgG2, IgG3 and IgG4 subclasses were measured by ELISA in plasma samples obtained from a total of 115 patients with TTP referred to the Milan TTP registry. Plasma samples had been collected during acute disease presentation (n=60), disease remission (n=92) or both (n=37). ADAMTS13 activity and inhibitor were also measured. The levels of different Ig subclasses were compared between two groups of patients with or without recurrence during follow-up. Patients with a follow-up <24 months were excluded from analysis. Statistical analysis was performed using random effect linear regression models. Results: TTP patients had a median follow-up of 64 months (range 0–399). A total of 11 patients (9.5% of all patients) were followed-up for less than 24 months and excluded from further analysis. Of patients with a follow-up >24 months, 53 (50%) developed recurrences, whereas 51 did not. Recurrences occurred at a median of 24 months (45 days to 11 years) after the first episode and were more common in the first three years (n=35, 67%). Comparison of anti-ADAMTS13 Ig subclasses measured during acute disease presentation in TTP patients with recurrence and in patients without recurrence revealed lower levels of IgA (0.017 vs 0.243, p=0.05), IgG1 (0.076 vs 0.234, p=0.01) and IgG3 (0.126 vs 0.385, p=0.002) in recurrent patients, whereas IgG4 were higher in recurrent TTP (0.712 vs 0.289, p<0.0005). Notably, levels of IgA (random effect, p=0.018), IgG1 (random effect, p=0.005) and IgG3 (random effect, p=0.006) were also associated with lower platelet counts at presentation of acute TTP and IgG3 levels were associated with the number of plasma exchange procedures performed until remission/death. In TTP patients during remission lower levels of ADAMTS13 antigen (49.3 vs 69.5 p<0.0005) and activity (41.4 vs 75.5 p<0.0005) as well as high levels of anti-ADAMTS13 total IgG (21.93 vs 5.13 p=0.007) were confirmed to be predictors of recurrent disease. Other Ig subclasses, measured during remission were not associated with a history of recurrent TTP. The logistic analysis showed an odds of relapse of 4.2 (range 1.5–12 p=0.008) at remission in patients with reduced ADAMTS13 and of 4.4 (range 1.7–11.3; p=0.002) in patients with high levels of IgG, but not in the acute phase. Conclusions: Low values of ADAMTS13 and anti-ADAMTS13 autoantibodies showed and association with a fourfold increase of recurrency risk, while the same result is not confirmed for the acute phase. Anti-ADAMTS13 IgA, IgG1, 3 and 4 subclasses, measured at acute TTP presentation, showed association with recurrent disease in a retrospective cohort study of TTP patients. Ig subclass measurement might be useful to improve recurrence risk prediction in patients with TTP. Disclosures: No relevant conflicts of interest to declare.