Association of endothelial and glycocalyx injury biomarkers with fluid administration, development of acute kidney injury, and 90-day mortality : data from the FINNAKI observational study

Abstract Background Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality. Results SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p  12 h from ICU admission (AKI>12 h). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI>12 h with OR (95% CI) of 12.71 (2.96–54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31–3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29–23.57], p < 0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44–4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67–11.79; p < 0.001) for 90-day mortality. Conclusions VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality

Associations between enteral nutrition and outcomes in the SUP ‐ ICU trial: Results of exploratory post hoc analyses

Background: Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological stress ulcer prophylaxis. We undertook post hoc analyses of the stress ulcer prophylaxis in the intensive care unit trial to assess for any associations and interactions between enteral nutrition and pantoprazole. Methods: Extended Cox models with time‐varying co‐variates and competing events were used to assess potential associations, adjusted for baseline severity of illness. Potential interactions between daily enteral nutrition and allocation to pantoprazole on outcomes were similarly assessed. Results: Enteral nutrition was associated with lower risk of clinically important gastrointestinal bleeding (cause‐specific hazard ratio [HR]: 0.29, 95% confidence interval: [CI] 0.19–0.44, p < .001), higher risk of pneumonia (HR: 1.44, 95% CI: 1.14–1.82, p = .003), and lower risk of all‐cause mortality (HR: 0.22, 95% CI: 0.18–0.27, p < .001). Enteral nutrition with allocation to pantoprazole was associated with a lower risk of mortality (HR: 0.27, 95% CI: 0.21–0.35, p < .001), similar to enteral nutrition with allocation to placebo (HR: 0.17, 95% CI: 0.13–0.23, p < .001). Allocation to pantoprazole with no enteral nutrition had little effect on mortality (HR: 0.83, 95% CI: 0.63–1.09, p = .179), whilst allocation to pantoprazole and receipt of enteral nutrition was mostly compatible with increased all‐cause mortality (HR: 1.27, 95% CI: 0.99–1.64, p = .061). The test of interaction between enteral nutrition and pantoprazole treatment allocation for all‐cause mortality was statistically significant (p = .024). Conclusions: Enteral nutrition was associated with an increased risk of pneumonia and a reduced risk of gastrointestinal bleeding. The interaction between pantoprazole and enteral nutrition suggesting an increased risk of mortality requires further study

Ketamiini ja kallonsisäinen paine : todellinen ongelma vai paljon melua tyhjästä

Ketamiinin käyttö ensihoidossa on lisääntynyt, sillä se ei lamaa hengitystä eikä verenkiertoa. Ketamiini saattaa kuitenkin nostaa kallonsisäistä painetta. Onko ketamiini turvallinen lääke ensihoidossa aivotapahtumapotilaita hoidettaessa? Kannattaako teho-osastolla aivotapahtumapotilaita lääkitä ketamiinilla?</p

Atypical teratoid/rhabdoid tumors (ATRTs) with SMARCA4 mutation are molecularly distinct from SMARCB1-deficient cases

Atypical teratoid/rhabdoid tumors (ATRTs) are very aggressive childhood malignancies of the central nervous system. The underlying genetic cause are inactivating bi-allelic mutations in SMARCB1 or (rarely) in SMARCA4. ATRT-SMARCA4 have been associated with a higher frequency of germline mutations, younger age, and an inferior prognosis in comparison to SMARCB1 mutated cases. Based on their DNA methylation profiles and transcriptomics, SMARCB1 mutated ATRTs have been divided into three distinct molecular subgroups: ATRT-TYR, ATRT-SHH, and ATRT-MYC. These subgroups differ in terms of age at diagnosis, tumor location, type of SMARCB1 alterations, and overall survival. ATRT-SMARCA4 are, however, less well understood, and it remains unknown, whether they belong to one of the described ATRT subgroups. Here, we examined 14 ATRT-SMARCA4 by global DNA methylation analyses. We show that they form a separate group segregating from SMARCB1 mutated ATRTs and from other SMARCA4-deficient tumors like small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) or SMARCA4 mutated extra-cranial malignant rhabdoid tumors. In contrast, medulloblastoma (MB) samples with heterozygous SMARCA4 mutations do not group separately, but with established MB subgroups. RNA sequencing of ATRT-SMARCA4 confirmed the clustering results based on DNA methylation profiling and displayed an absence of typical signature genes upregulated in SMARCB1 deleted ATRT. In summary, our results suggest that, in line with previous clinical observations, ATRT-SMARCA4 should be regarded as a distinct molecular subgroup

Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial

Background: Critically ill patients in the intensive care unit (ICU) are at risk of clinically important gastrointestinal bleeding, and acid suppressants are frequently used prophylactically. However, stress ulcer prophylaxis may increase the risk of serious adverse events and, additionally, the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low. The aim of the SUP-ICU trial is to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the ICU. We hypothesise that stress ulcer prophylaxis reduces the rate of gastrointestinal bleeding, but increases rates of nosocomial infections and myocardial ischaemia. The overall effect on mortality is unpredictable. Methods/design: The SUP-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomised, blinded, parallel-group trial of stress ulcer prophylaxis with a proton pump inhibitor versus placebo (saline) in 3350 acutely ill ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support in the 90-day period, serious adverse reactions, 1-year mortality, and health economic analyses. The sample size will enable us to detect a 20 % relative risk difference (5 % absolute risk difference) in 90-day mortality assuming a 25 % event rate with a risk of type I error of 5 % and power of 90 %. The trial will be externally monitored according to Good Clinical Practice standards. Interim analyses will be performed after 1650 and 2500 patients. Conclusion: The SUP-ICU trial will provide high-quality data on the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in critically ill adult patients admitted in the ICU

Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

PURPOSE: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P \u3c .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P \u3c .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD

Effects of stress ulcer prophylaxis in adult ICU patients receiving renal replacement therapy (Sup-Icu RENal, SIREN): Study protocol for a pre-planned observational study.

BACKGROUND Proton pump inhibitors are often used in critically ill patients to prevent gastrointestinal bleeding despite limited evidence for benefit. Patients with acute kidney injury requiring renal replacement therapy (RRT) are at high risk of gastrointestinal bleeding as (pre-)uremia induces coagulopathy through effects on platelets and coagulation cascades. No high-quality randomized clinical trials have previously assessed the benefits and harms of prophylactic proton pump inhibitor use in this high-risk population of adult critically ill patients. METHODS/DESIGN Among the 3350 patients included in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial-an investigator-initiated international randomized clinical trial on prophylactic proton pump inhibitor versus placebo in acutely admitted adult ICU patients at risk of gastrointestinal bleeding-we will compare the benefits and harms of prophylactic use of proton pump inhibitor in patients in need of RRT versus those not requiring this treatment. We will determine the proportion of patients with clinically important bleeding, the proportion of patients with adverse events including pneumonia, Clostridium difficile enteritis, or acute myocardial ischemia in the ICU, as well as transfusion requirements. Moreover, 90 day and 365 day mortality post-randomization will be investigated. As a secondary analysis, we will examine the association between acute kidney injury and RRT during ICU stay and gastrointestinal bleeding. DISCUSSION With the outlined predefined analysis, we will characterize the balance between the benefits and harms of stress ulcer prophylaxis in acutely admitted adult ICU patients in need of RRT, including the potential interaction of allocation to proton pump inhibitor versus placebo. TRIAL REGISTRATION ClinicalTrials.gov, NCT02718261 . Registered on 14 March 2016

MFA09 (MFA 2009)

Catalogue of a culminating student exhibition held at the Mildred Lane Kemper Art Museum in 2009. Content includes A new paradigm / Carmon Colangelo -- Evolving practices / Patricia Olynyk -- Stephanie Barenz -- Carolyn Dawn Bendel -- Jacob Cruzen -- Rachel Ann Dennis -- Bryan Eaton -- Maya Escobar -- Meredith Foster -- Morgan Gehris -- Gina Grafos -- Stephen Hoskins -- Amelia Jones -- Hye Young Kim -- Anne Lindberg -- Goran Maric -- Kelda Martensen -- Erica L. Millspaugh -- Carianne Noga -- Joel Parker -- Rebecca C. Potts -- Shannon Randol -- Elaine Rickles -- Michael Kenneth Smith -- Dan Solberg -- Natalie Toney -- Glenn Tramantano -- Kathryn Trout -- J. Taylor Wallace.https://openscholarship.wustl.edu/books/1006/thumbnail.jp