Background:No specific recommendations are available regarding the intensive care management of critically ill acute ischemic stroke (AIS) patients, and questions remain regarding optimal ventilatory, hemodynamic and general ICU therapeutic targets in this population. We performed an international survey to investigate intensive care unit (ICU) admission criteria and management of AIS patients.Methods: An electronic questionnaire including 25 items divided into 3 sections was available on the European Society of Intensive Care Medicine (ESICM) website between 1 st November 2019 and 30 th March 2020 and advertised through the Neurointensive Care (NIC) section newsletter. This survey was emailed directly to the NIC members and was endorsed by the ESICM.Results: There were 214 respondents from 198 centers, with response rate of 16,5% of total membership (214/1296). In most centers (67%), the number of AIS patients admitted to respondents' hospitals in 2019 was between 100 and 300, and, among them, fewer than 50 required ICU admission per hospital. The most widely accepted indication for ICU admission criteria was a requirement for intubation and mechanical ventilation. A standard protocol for arterial blood pressure (ABP) management was utilized by 88 (58%) of the respondents. For patients eligible for iv thrombolysis, the most common ABP target was < 185/110 mmHg (n=77 [51%]), while for patients undergoing mechanical thrombectomy it was < 160/90 mmHg (n=79 [54%]). The preferred drug for reducing ABP was labetalol (n=84 [55,6%]). Other frequently used therapeutic targets included: blood glucose 140-180 mg/dl (n=65 [43%]) maintained with intravenous insulin infusion in most institutions (n=110 [72,4%]); enteral feeding initiated within 2-3 days from stroke onset (n=142 [93,4%]); oxygen saturation (SpO2) >95% (n=80 [53%]), and tidal volume 6-8 ml/kg of predicted body weight (n=135 [89%]). Conclusions:The ICU management of AIS, including therapeutic targets and clinical practice strategies, importantly varies between centers. Our findings may be helpful to define future studies and create a research agenda regarding the ICU therapeutic targets for AIS patients.

Background The majority of myelodysplastic syndrome (MDS), primary myelofibrosis (MPN) and aplastic anemia (AA) patients during the course of the disease develops a symptomatic anemia requiring transfusions of packed red blood cells (PRBC), each of them containing approximately 200 mg of elementary iron. Because of the fact that human beings are unable to actively eliminate iron from the body, secondary emosiderosis yet becomes evident when body iron content is above 7-14 grams, an amount easily reached after receiving as few as 15-30 PRCB units.From a pathophysiologic point of view, long-term transfusion therapy is certainly the most important cause of iron overload (IOL) in these patients; nevertheless, others mechanism account for this phenomenon, and in particular the role of the ineffective erythropoiesis.Deferasirox (DSX) is the principal option currently available for iron chelation therapy in the management of IOL due to transfusion dependent anemia. DSX is also a potent NF-kB inhibitor, and this effect may explain in part the phenomenon of hematological improvements reported in different clinical trials and in case reports. Materials and Methods We analyzed 21 patients,16 male and 5 female, with transfusion dependent anemia and with a transfusional history of almost 10 packed PRBC, treated with DSX from 1 February 2013 to 1 February 2014. Median age was 80 years (65-88). 20 patients (95%) have almost a comorbidity, 7 of them (30%) have more than 3 comorbidities. Heart disease was the most common comorbidity. At baseline median creatinine clearance was 76 ml/min; in 12 patients was < 60ml/min but >40 ml/min, according to NCCN Guidelines. All patients (16 MDS, 3 MPN, 1 AA, 1 hemolytic anemia) were evaluated for IOL by serum ferritin (SF), while only 7 with RM T2*.Median SF at baseline was 1750 μg/L and median PRBC was 32.The starting dose of DSX was 10 mg/kg/day; the dosage should be adjusted up to 20–30 mg/kg/daily according to the transfusional regimen, SF and IOL, if tolerated. Objectives To observe safety, tolerability, and efficacy of iron chelation therapy with DSX in older patients with transfusion dependent anemia. Results The SF decreased of 50% and 66% after 3 and 6 months respectively. The SF was normalized (SF<500 μg/L) in 5 patients (24%) after six months. The IOL occurred also in patients with a short transfusional history, inferior to 10 packed red blood cells, and SF <1000 μg/L. That was more evident in MDS patients especially in RARS. The median dose tolerated of DSX was 20 mg/kg/daily.The drug related adverse events (AE) was evaluated by the Common Terminology Criteria for Adverse Events (CTCAE versione 4.02). The severe adverse events (SAE) occurred in 10%.The most Common AE were diarrhea, nausea, upper abdominal pain, serum creatinine increase and rash. Hematologic response according to IWG criteria 2006 with DSX were observed in 17% of patients and was more frequent in MPN than MDS, independently from IOL. Conclusion DSX has shown high efficacy in a variety of iron overloaded patients with different anemias. Appropriate patient selection and regular clinical multidisciplinary evaluation of comorbidity and concomitant therapy remains a critical components of successful ther­apy, combined with carefull monitoring for both adverse effects and clinical efficacy, in order to derive the most benefit from a carefully imple­mented chelation strategy.In our cohort improvement of erythropoiesis was marginal. This might be due to the very small patient group analyzed. Disclosures No relevant conflicts of interest to declare.

Introduction: Potential detrimental effects of hyperoxemia on outcomes have been reported in critically ill patients. Little evidence exists on the effects of hyperoxygenation and hyperoxemia on cerebral physiology. The primary aim of this study is to assess the effect of hyperoxygenation and hyperoxemia on cerebral autoregulation in acute brain injured patients. We further evaluated potential links between hyperoxemia, cerebral oxygenation and intracranial pressure (ICP).Methods: This is a single center, observational, prospective study. Acute brain injured patients [traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH)] undergoing multimodal brain monitoring through a software platform (ICM+) were included. Multimodal monitoring consisted of invasive ICP, arterial blood pressure (ABP) and near infrared spectrometry (NIRS). Derived parameters of ICP and ABP monitoring included the pressure reactivity index (PRx) to assess cerebral autoregulation. ICP, PRx, and NIRS-derived parameters (cerebral regional saturation of oxygen, changes in concentration of regional oxy- and deoxy-hemoglobin), were evaluated at baseline and after 10 min of hyperoxygenation with a fraction of inspired oxygen (FiO2) of 100% using repeated measures t-test or paired Wilcoxon signed-rank test. Continuous variables are reported as median (interquartile range).Results: Twenty-five patients were included. The median age was 64.7 years (45.9–73.2), and 60% were male. Thirteen patients (52%) were admitted for TBI, 7 (28%) for SAH, and 5 (20%) patients for ICH. The median value of systemic oxygenation (partial pressure of oxygen-PaO2) significantly increased after FiO2 test, from 97 (90–101) mm Hg to 197 (189–202) mm Hg, p &lt; 0.0001. After FiO2 test, no changes were observed in PRx values (from 0.21 (0.10–0.43) to 0.22 (0.15–0.36), p = 0.68), nor in ICP values (from 13.42 (9.12–17.34) mm Hg to 13.34 (8.85–17.56) mm Hg, p = 0.90). All NIRS-derived parameters reacted positively to hyperoxygenation as expected. Changes in systemic oxygenation and the arterial component of cerebral oxygenation were significantly correlated (respectively ΔPaO2 and ΔO2Hbi; r = 0.49 (95% CI = 0.17–0.80).Conclusion: Short-term hyperoxygenation does not seem to critically affect cerebral autoregulation.

Background: HSCT has greatly improved the prognosis of patients affected by hematological malignancies leading to more long-term survivors. However, long-term survivors are at increased risk of developing complications; cardiovascular complications are relatively rare but, on the other hand, it seems quite common to develop cardiovascular risk factors like: arterial hypertension (AH), diabetes, dyslipidemia. Aims of the study: to observe the incidence and outcome of patients developing cardiovascular risk factors (CVRF) and cardiovascular events (CVE) after allo-HSCT, eventually identifying patient and HSCT-related risk factors for CVE (CVE predictors). Materials and methods: We retrospectively analyzed 300 patients undergoing allo-HSCT from January 2006 to December 2009. Patients were considered long-term survivors and suitable for the analysis if they were alive at 2 years after HSCT. Following variables were recorded: diagnosis, sex, age at time of HSCT, comorbidities and pre-existing risk factors, BMI, previous chemotherapy with anthracyclines, donor type, disease status at time of HSCT, conditioning regimens with or without total body irradiation (TBI), onset of acute or chronic graft versus host disease (aGVHD and cGvHD), treatment with high doses corticosteroids after HSCT. We observed incidence and outcome of early (within 2 years) and late (after 2 years) CVRF and CVE in long-term survivors; CVE were divided in non-serious (grade1-2) and serious (grade 3-4) if they required or not hospitalization. Dichothomius variables were compared with Chi-Square test or Fisher's exact test. Continuous variables were compared with Student's T-Test. Median Follow-Up duration was estimated with Kaplan Meier reverse survival method. Multiple linear regression models were built for multivariate analysis of CVE incidence. A two-sided p value <0.05 (<0.02 for multivariate analysis) was considered statistically significant. Results: 4 of 300 patients died of acute heart failure within 2 years from HSCT. 149 patients were alive at least 2 years after HSCT, and 125 patients (83%) were alive at the time of last follow-up, with a median follow-up of 2384 days (range 722-3098) and a median age of 40 years (range 15-72). Overall crude mortality was 24/ 149 (17%), of whom 16 patients dying of disease recurrence (66%) and 8 patients (34%) dying due to non-relapse causes (Non Relapse Mortality, NRM). Non-serious CVE were observed in 42 patients (28%), whereas serious CVE were reported in 23 cases (15%; 5 acute coronary syndrome, 4 heart failure, 5 cardiac arrythmias, 5 cerebrovascular events, 2 aortic aneurism, 2 pericarditis), with 11 patients experiencing both. Regarding CVRF, post-HSCT AH was observed in 62 patients (42%), dyslipidemia in 124 pts (83%), diabetes in 29 pts (19%). In univariate analysis older age was associated with a higher risk of developing late diabetes (p 0.025), early and late AH (p<0.001), any CVE (p=0.04). cGVHD was associated with a higher risk of early AH (p 0.018), while aGVHD, advanced disease at HSCT and use of high dose of corticosteroids were associated with serious CVE (respectively p=0.039,p=0.025,p=<0.0001). In multivariate analysis, Event Free Survival (EFS) for any CVE was lower in case of older age (p=0.01), acute and chronic GvHD (p=0.010, p=0.006), pre-existing AH (p=0.001) and smoke abuse (p=0.01), reduced intensity conditioning regimens (p=0.03), and high dose corticosteroids treatment (p=0.001). Furthermore, serious CVE were associated with male sex, reduced intensity conditioning regimen, use of TBI within conditioning regimens, older age, and pre-existing AH (respectively p=0.006, p=0.026, p=0.002, p=0.009, p=0.038). Older age was also associated with the development of late AH (p=0.001) and late diabetes (p=0.025) Conclusions: Older allo-HSCT patients have an higher risk of developing any CVE and any CVRF than age-matched non-hematologic population; interestingly, prolonged treatment with high dose steroids also seems to play a role. CVE do not show nowadays a high impact on survival since they seems to be an uncommon complication of HSCT. Furthermore an increasing number of late CVRF has been observed, possibly leading to late cardiovascular events in the future and should therefore be monitored. Disclosures No relevant conflicts of interest to declare.