Management of Sepsis would greatly benefit from the incorporation of simple and informative new biomarkers in clinical practice. Ideally, a sepsis biomarker should segregate infected from non-infected patients, provide information about prognosis and organ-specific damage, and be accessible to most healthcare services. The immature platelet fraction (IPF) and immature reticulocyte fraction (IRF) are new analytical parameters of the complete blood count, that have been studied as biomarkers of several inflammatory conditions. Recently, a study performed in critically-ill patients suggested that IPF could be a more accurate sepsis biomarker than C-reactive protein (CRP) and procalcitonin. In this retrospective study we evaluated the performance of IPF and IRF as biomarkers of sepsis diagnosis and severity. 41 patients admitted to two intensive care units were evaluated, 12 of which with severe sepsis or septic shock, and 11 with non-complicated sepsis. Significantly higher IPF levels were observed in patients with severe sepsis/ septic shock. IPF correlated with sepsis severity scores and presented the highest diagnostic accuracy for the presence of sepsis of all studied clinical and laboratory parameters. No significant differences were observed in IRF levels. Our results suggest that IPF levels could be used as a biomarker of sepsis diagnosis and severity.

To describe the experience in a recently created ocular graft-versus-host disease unit in a tertiary hospital and to detail ocular surface features and complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective study included all patients who underwent allo-HSCT, with or without chronic GVHD and were being monitored in the Hematopoietic Stem Cell Transplantation Unit in the UNICAMP Clinical Hospital (Campinas, Sao Paulo, Brazil) from 2015 to 2020. Patients were concomitantly evaluated by hematology and ophthalmology teams of the Ocular GVHD Unit. Hematologists performed a comprehensive systemic evaluation searching and grading mouth, skin, lungs, gastrointestinal tract, liver and genitalia GVHD. While ophthalmologists evaluated ocular symptoms through specific questionnaire (Ocular Surface Disease Index—OSDI) and a protocol of distinct ocular surface parameters for dry eye disease (1) and ocular complications, which encompassed meniscometry, non-invasive tear break-up time (NITBUT) measurement, conjunctival hyperemia quantification, meibography, fluorescein and lissamine staining and Schirmer’s test. Patients were diagnosed with chronic GVHD using the National Institutes of Health (NIH) Consensus Criteria for Chronic Graft-versus-Host Disease. The International Chronic Ocular GVHD Consensus Group (ICOGCG) score was obtained at the onset of ocular disease presentation or afterwards. A total of 82 patients underwent allo-HSCT (97.6% full matched and 2.4% haploidentical), mainly for cases of leukemia and 73.2% had chronic GVHD. Mean onset time for chronic GVHD was 232 ± 7.75 days. The mouth, skin, and eyes were the main organs involved (63%, 50%, and 48%, respectively). Symptom scores and all ocular surface parameters differ in patients with and without chronic GVHD and along different timepoints of the follow-up. Ocular complications mostly involved were severe DED and meibomian gland dysfunction, conjunctival scarring, cataract and infections resulting in keratitis and corneal perforation. As therapeutic strategies, 73% patients received preservative-free lubricants, 27% autologous serum, 48% topical steroids, 27% oral tetracycline derivatives, 22% mucolytic eye drops and 3 patients needed bandage contact lens. Ocular GVHD is a complex and challenging disease with varied manifestations, resulting in a broad range of ocular test endpoints, and inconsistent treatment responses. The main ocular presentations were dry eye, meibomian gland dysfunction and cataracts. The therapeutic approach often involves topical steroids and autologous serum tears. It is important to monitor these patients closely, so the ocular GVHD Unit may improve the care, providing prompt identification of ocular manifestations and faster treatment of complications.

Background: We hypothesized that one single episode of acute kidney injury (AKI) reduces long-term survival compared with no acute kidney injury (No AKI) following recovery from critical illness. Materials and methods: A prospective cohort of 2,010 patients admitted to the ICU between 2000 and 2009 at a provincial referral hospital was followed to determine whether AKI influences long-term survival. Results: Of the 1,844 eligible patients, 18.4% had AKI stage 1, 12.1% had stage 2, 26.5% had stage 3, and 43.0% had No AKI, using the KDIGO classification. The mean and median follow-up time was 8.1 and 8.7 years. The 28-day, 1-year, 5-year and 10-year survival rates were 59.6%, 44.9%, 37.4%, and 33.4%, in patients with any AKI (stage 1, stage 2, stage 3), which was significantly worse compared with the critically ill patients with no AKI at any time (P < 0.01). The adjusted 10-year mortality risk associated with AKI was 1.44 (95% CI = 1.2 to 1.7) among 28-day survivors. Patients who had mild AKI (stage 1) had significantly worse survival at 28 days, 1 year, 3 years, 5 years and 10 years compared with No AKI (P < 0.01) (Figure 1A). Patients with sepsis and AKI who survived 28 days had significantly poorer 5-year and 10-year survival compared with nonseptic AKI (P < 0.01) (Figure 1B). Conclusions: Patients with one episode of mild (stage 1) AKI have significantly lower survival rates over 10 years than critically ill patients without AKI. The causes and mechanisms of this association warrant further careful study. Close medical follow-up of these patients may be warranted and mechanistic research required understanding how AKI influences distant events.

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.

Introduction: Sepsis in febrile neutropenia (FN) is a life threatening condition, and a health problem of increasing proportions. Although multiple organ dysfunction syndrome (MODS) frequently precedes death in patients with sepsis, the ultimate mechanisms responsible for organ dysfunction and tissue damage in sepsis are yet to be determined. Currently, tissue damage is attributed to an exacerbated response of the immune and hemostatic systems, mediated by endothelial cells, platelets and neutrophils. Of note, recent evidence demonstrated that neutrophils, platelets and fibrin participate in this response by mediating neutrophil extracellular traps (NET) formation, and promoting the hemostatic containment of infectious foci. In animal models, down-regulation of NET formation, coagulation and platelet activation are usually associated with deficiencies in pathogen clearance. Unfortunately, activation of hemostasis and NET formation could potentially contribute to tissue damage by a process called "immunethrombosis". Although the increase of sepsis severity in patients with severe neutropenia is well described, the mechanisms of sepsis-associated tissue damage in the context of severe neutropenia/thrombocytopenia are yet to be determined. Methods: In order to investigate the mechanisms of tissue damage in the context of severe neutropenia/thrombocytopenia, we compiled clinical data from two different prospective sepsis cohorts (A, neutropenic; n=129; and B, non-neutropenic; n=30) followed at our Institution. In addition, we reviewed histopathological data from 16 autopsies of individuals with hematological malignancies and septic shock from our institution (cohort C; n=16). H&E-stained slides from liver, kidneys and lungs were systematically analyzed by one investigator, and reviewed by 2 experienced pathologists, all of them blind to the presence or absence of neutropenia and thrombocytopenia. In each organ, we characterized (as present or absent) three main organic lesions: thrombi in microvessels, microorganism colonies, and inflammatory infiltrate (mononuclear and polymorphonuclear). Inflammation was graded as weak or intense, and only considered when there was no neoplastic infiltration. Results: Median ages of patients from cohorts A and B were respectively 46.0 years (13-78), and 59.4 years (22-85); P<0.0001. In cohort A, neutrophil counts were < 100/mcl in 55.8% of patients and between 100-500/mcl in 42.6%. Platelet counts were also lower in cohort A (30,126 vs 213,933/mcl; P<0.0001). Median SOFA scores (at admission) were 4 (0-15) and 5 (0-17); P=0.3 in neutropenic and non-neutropenic patients respectively, and sepsis-related mortality was 22.5% and 10.3% in the same groups (P=0.19). Among patients with a higher SOFA score, mortality was higher in neutropenic patients (100% vs 33.3%; p=0.04). The frequencies of clinically-evident infection foci were 60% in cohort A and 100% in cohort B (P=0.0001). In contrast, positive blood cultures were present in 38% of neutropenic, but in only 3.3% of non-neutropenic patients (P<0.0001). The autopsy-based study included 10 patients with lymphoma and 6 with acute leukemia. The cause of death was septic shock in all of them, and three patients presented severe neutropenia (<500/mcl). The main histological findings are shown in table 1. The only neutropenic patient with microthrombi presented AML-M3 and leukostasis. Using H&E staining, no bacterial colonies were found in any slide. Conclusions: as expected, septic patients with severe neutropenia presented a worse outcome compared to non-neutropenic patients in our cohort. In addition, the lower frequency of clinically-defined infectious foci, coupled with a strikingly higher frequency of positive blood cultures, suggest that severe neutropenia and thrombocytopenia could impair pathogen containment and clearance. Severe neutropenia/thrombocytopenia was compatible with inflammatory infiltrates and microvascular thrombosis in lungs, although the latter was only observed in a patient with leukostasis and promyelocityc acute leukemia. Table 1. Histological findings in autopsies of neutropenic and non-neutropenic patients Microthrombi Inflammation (weak/intense) Lungs Kidney Liver Lungs Kidney Liver Neutropenic 33% 33% 0% 50%/50% 0%/0% 0%/0% Non-neutropenic 56.25% 25% 6.25% 70%/20% 34%/9% 67%/0% Disclosures No relevant conflicts of interest to declare.