Атипичный гемолитико-уремический синдром (аГУС)-орфанное заболевание из группы тромботических микроангиопатий, которое при естественном течении характеризуется неблагоприятным прогнозом, нередко с развитием синдрома полиорганной недостаточности уже в дебюте болезни� Важная роль в междисциплинарной команде специалистов, принимающих участие в лечении таких пациентов, принадлежит врачам анестезиологам-реаниматологам� Однако в силу редкости заболевания и сходства его симптомов с симптомами целого ряда других заболеваний и состояний, в том числе сепсиса и синдрома диссеминированного внутрисосудистого свертывания, диагностика аГУС часто запаздывает, а специфическое лечение из-за этого начинается несвоевременно� Целью данной статьи является представление основных понятий, относящихся к проблеме тромботических микроангиопатий, и обсуждение актуальных вопросов дифференциальной диагностики аГУС в отделениях реанимации и интенсивной терапии на примере двух клинических наблюдений� Ключевые слова: тромботическая микроангиопатия, атипичный гемолитико-уремический синдром, сепсис, синдром диссеминированного внутрисосудистого свертывания Для цитирования: Козловская Н� Л�, Галстян Г� М�, Степанюк В� Н� Сложные вопросы диагностики атипичного гемолитико-уремического синдрома в отделении реанимации и интенсивной терапии // Вестник анестезиологии и реаниматологии�-2019�-Т� 16, № 4�-С� 65-76�

Background: Patients (pts) with hematologic disease are at increased risk of severe SARS-CoV-2 infection. Recent observations reported poor outcomes of COVID-19 in pts with various cancer types and higher mortality rates compared with the general population. However, currently available data on COVID-19 in pts with hematologic disease are limited. Methods: CHRONOS19 registry is an observational prospective cohort study with the primary objective to evaluate the treatment outcomes in adult pts (age 18 or older) with hematologic disease and COVID-19. Secondary objectives are to describe severity and complications of COVID-19 and course of hematologic disease in SARS-CoV-2 infected pts, and to explore importance of various factors for disease severity and mortality. Pts with laboratory-confirmed or suspected (based on clinical symptoms and/or CT) COVID-19 were eligible for enrollment. Data were collected on a web platform and managed in a de-identified manner. Physicians from 8 hematology clinical centers and hospitals from all over Russia (Moscow, Ulan-Ude, Saransk, Vladimir, Nizhniy Novgorod, Kazan) participate in this study. Pts are followed for 30 days (ds) after COVID-19 diagnosis and up to 6 months (mos) for hematologic disease outcomes and overall survival assessment. The results of the first follow-up are presented in this interim analysis. Results: As of July 30, 2020, 184 pts were enrolled (females/males [n(%)]: 80(44%)/104 (56%); median [range] age: 55 [18-83] years. Disease type (malignant/non-malignant [n(%)]): 164(89%)/20(11%), including AML 36(20%), ALL 16(9%), MDS 5(2%), APL 5(2%), MM 38(21%), HL 4(2%), NHL 38(21%), MPN 9(5%), CLL 13(7%), others 20(11%). Concomitant diseases were in 95(52%) pts: cardiovascular 56(59%), pulmonary 6(6%), hepatic 6(6%) or renal 5(5%), diabetes 17(18%), obesity 4(4%), other 16(17%). 176 patients were evaluable for the primary outcome assessment with a median follow-up of 41(1-125) ds. Thirty-day all-cause mortality was 23% (41 pts died). Death due to COVID-19 complications occurred in 34 (83%) pts, 7(17%) pts died due to progression of hematologic disease. Fifty (28%) pts experienced COVID-19 complications, the most common were pneumonia in 125 (71%) pts, respiratory failure in 82(47%) pts, ARDS in 11(6%) pts, cytokine release syndrome in 15(9%) pts, multiple organ failure in 10(6%) pts, sepsis in 6(3%) pts, and pulmonary bleeding in 1(0,6%). Specific anti-COVID-19 treatment was given to 117 pts(67%) pts: most common first-line treatment was hydroxichloroquine+azithromycin in 84(72%) pts, azithromycin monotherapy in 27(23%) pts, other drugs in 6(5%) pts; second-line treatment comprised lopinavir+ritonavir in 38 pts, tocilizumab in 29 pts, umifenovir in 5 pts, baricitinib in 5 pts, canakinumab in 1pt, sarilumab in 1 pt. The rate of ICU admissions was 27%(47 pts), among them only 11(23%) pts survived, 36(20%) pts required mechanical ventilation, only 2(5.5%) pts survived. Eighty-eight(50%) pts received anticoagulants. With regard to the blood disease, treatment delays occurred in 101(57%) pts with a median 4 weeks, 6(3%) pts required change of treatment. At the first follow-up (30 ds) the rate of relapse / progression of hematologic disease was 16 of 151 evaluable pts (10.6%). Thirty-day overall survival was 75%. At the data cutoff, median overall survival was not reached. Antibody detection was performed in 70 pts: 53(76%) pts had IgG SARS-CoV-2 antibodies. Among factors possibly associated with poor survival were: stage of COVID-19 1(n=41) - 91,8%/ 2(n=75) - 90%/ 3(n=36) - 56,5%/ 4(n=22) - 13,6% (p<0,0001), concomitant diseases (n=93/81): 59,5% vs. 87% (p=0,0001), transfusion dependence (n=65/104): 58,1% vs. 81,8% (p=0,0007), prior steroid therapy (n=73/90): 64,6% vs. 82% (p=0,019), older age (<60 (n=108)/≥60 (n=68) years): 80% vs. 60% (p=0,048). Sex, disease type, myelotoxic agranulocytosis, and prior hematopoietic stem cell transplantation were not associated with worse outcomes. Data on the longer follow-up (90 and 180 ds) will be presented. Conclusions: Patients with hematologic disease and SARS-CoV-2 infection have high 30-day all-cause mortality predominantly due to COVID-19 complications. Stage of COVID-19, concomitant diseases, transfusion dependence, prior steroid therapy, and older age were associated with poor outcomes. Disclosures Shuvaev: Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. OffLabel Disclosure: hydroxichloroquine, azithromycin, lopinavir+ritonavir, tocilizumab, umifenovir, baricitinib, canakinumab, sarilumab for COVID-19 treatment

reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. carbon dioxide 30 [27][28][29][30][31][32][33][34][35] mmHg and median temperature 37.1 [36.8-37.3]°C. After removal of artefacts, the mean monitoring time was 22 h08 (8 h54). All patients had impaired cerebral autoregulation during their monitoring time. The mean IAR index was 17 (9.5) %. During H 0 H 6 and H 18 H 24 , the majority of our patients; respectively 53 and 71 % had an IAR index > 10 %. Conclusion According to our data, patients with septic shock had impaired cerebral autoregulation within the first 24 hours of their admission in the ICU. In our patients, we described a variability of distribution of impaired autoregulation according to time. ReferencesSchramm P, Klein KU, Falkenberg L, et al. Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium. Crit Care 2012; 16: R181. Aries MJH, Czosnyka M, Budohoski KP, et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit. Care Med. 2012.

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Background Acute myeloid leukemia (AML) in older adults is a biologically and clinically distinct entity. These patients often have comorbidities, and their treatment must be chosen with caution. In AML patients over 60y old, cure rates are under 10% even after intensive chemotherapy (CT). Aim To compare the efficacy of different therapeutic approaches in elderly AML-pts treated in NRCH. Methods From 2002 till 2019, NRCH has conducted a prospective non-randomized study which included 80 AML-patients 60-81y (Me - 67y): 60-65 yy (n=53) and >65y (n=27); M/F - 35/45; de novo AML n=61 (76,25%), AML from MDS - n=13 (16,25%), «secondary» AML - n=6 (7,5%); cytogenetic risk: favorable n=1 (1,25%), intermediate n=49 (61,25%), poor n=30 (37,5%). The patients were stratified to different treatment approaches according to age. Patients 60-70y (n=40) mostly received 1-2 induction cycles 7+3 (ARA-C 100 mg/m2 bid; Dauno - 45-60 mg/m2 ), then 2 consolidation cycles 7+3 (Dauno - 45 mg/m2) and 2 years maintenance (5+5 with 6-MP). Patients >70y (n=22) were usually treated with 1-2 induction and 2 consolidation cycles of low dose Ara-C (LDAC) (10 mg/m2 sc bid, 28-days) and 3 years maintenance with 21-28-days LDAC. In some cases, fit patients over the age of 70y have got 7+3 (n=5) and some younger with comorbidities - LDAC (n=13). The analysis was done in May 2019. We evaluated treatment outcome according to age, cytogenetics and type of CT. Results The CR rate in the whole group of elderly AML-pts was 57,5% (46/80) with a median CR-duration - 10 mon (1-138 mon), early death - 16,25% (13/80) and resistance - 26,25% (21/80) with no major differences in the two age cohorts (<>70y). In order to assess of the efficacy of two chemotherapy options we have compared 7+3 and LDAC in patients aged 60-65 and older. In patients aged 60-65 CR-rate was higher -75% (21/28) after 7+3 vs 50% (2/4) after LDAC, with less resistant forms - 7% (2/28) vs 25% (1/4), respectively. In > 65y group CR-rate was identical in pts after 7+3 (47%, 8/17) and after LDAC (55%, 17/31) with similar numbers of resistant forms: 41% vs 29%. Early death rate did not differ among the groups. There was statistically higher CR-rate and lower resistant forms on 7+3 in pts aged 60-65 compared to older pts. - 75% vs 47% (p<0.05) and 7% vs 41% (<0.005) (Tab.1). Long-term results in the whole cohort of elderly patients were as follows: 1-y OS - 46%, DFS - 52,2%, 5-y ОS - 13%, DFS - 9% with high relapse rate (70%) development, mostly with early occurrence (Me - 12.8 mon). The median survival was statistically longer in patients aged 60-65y (n=32) comparing to older ones (n=48) - 15.4 vs 8 mon, respectively (p=0.0542), but DFS was equal (Fig.1). Higher incidence (87% vs 74%) and earlier relapse development (12 vs 16 mon) were registered in the group with poor cytogenetics comparing to favorable/intermediate (p=0,022). We didn't observe significant difference in long-term outcome of AML-pts older or younger 70y. Standard LDAC duration is 10-14 days, twice less than we used in our study. A landmark-analysis (from day 30 of induction) has shown that, if the 1st course-duration was less than 28 days, the median survival was shorter - 5,9 mo in comparison with 14,9 mo in pts with 28-days LDAC (p=0.12). The efficacy of 28-days LDAC was very similar to 7+3, mainly in patients aged 66 and older (Fig.2). Conclusion The outcome in elderly AML-patients is determined by age (more or less 65y) and the group of cytogenetic prognosis (poor vs favorable/intermediate). Intensive induction (7+3) is more preferable in patients aged 60-65 y as it produced the higher CR-rate and less resistant forms, results that are comparable to younger AML-patients. In patients older than 65y - CR-rate after 7+3 or 28-day LDAC was identical, and 28-days LDAC may become the choice of treatment for patients older than 65y. However long-term results are generally poor so new therapeutic strategies for elderly AML-patients are highly needed. Disclosures No relevant conflicts of interest to declare.