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BACKGROUND: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. METHODS: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. FINDINGS: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p

BACKGROUND: COVID-19 prediction models based on clinical characteristics, routine biochemistry and imaging, have been developed, but little is known on proteomic markers reflecting the molecular pathophysiology of disease progression. METHODS: The multicentre (six European study sites) Prospective Validation of a Proteomic Urine Test for Early and Accurate Prognosis of Critical Course Complications in Patients with SARS-CoV-2 Infection Study (Crit-COV-U) is recruiting consecutive patients (≥ 18 years) with PCR-confirmed SARS-CoV-2 infection. A urinary proteomic biomarker (COV50) developed by capillary-electrophoresis-mass spectrometry (CE-MS) technology, comprising 50 sequenced peptides and identifying the parental proteins, was evaluated in 228 patients (derivation cohort) with replication in 99 patients (validation cohort). Death and progression along the World Health Organization (WHO) Clinical Progression Scale were assessed up to 21 days after the initial PCR test. Statistical methods included logistic regression, receiver operating curve (ROC) analysis and comparison of the area under the curve (AUC). FINDINGS: In the derivation cohort, 23 patients died, and 48 developed worse WHO scores. The odds ratios (OR) for death per 1 standard deviation (SD) increment in COV50 were 3·52 (95% CI, 2·02-6·13, p

Background: \ud Microalbuminuria is an early sign of kidney disease in people with diabetes and indicates increased risk of cardiovascular disease. We tested whether a urinary proteomic risk classifier (CKD273) score was associated with development of microalbuminuria and whether progression to microalbuminuria could be prevented with the mineralocorticoid receptor antagonist spironolactone.\ud \ud Methods: \ud In this multicentre, prospective, observational study with embedded randomised controlled trial (PRIORITY), we recruited people with type 2 diabetes, normal urinary albumin excretion, and preserved renal function from 15 specialist centres in ten European countries. All participants (observational cohort) were tested with the CKD273 classifier and classified as high risk (CKD273 classifier score >0·154) or low risk (≤0·154). Participants who were classified as high risk were entered into a randomised controlled trial and randomly assigned (1:1), by use of an interactive web-response system, to receive spironolactone 25 mg once daily or matched placebo (trial cohort). The primary endpoint was development of confirmed microalbuminuria in all individuals with available data (observational cohort). Secondary endpoints included reduction in incidence of microalbuminuria with spironolactone (trial cohort, intention-to-treat population) and association between CKD273 risk score and measures of impaired renal function based on estimated glomerular filtration rate (eGFR; observational cohort). Adverse events (particularly gynaecomastia and hyperkalaemia) and serious adverse events were recorded for the intention-to-treat population (trial cohort). This study is registered with the EU Clinical Trials Register (EudraCT 20120-004523-4) and ClinicalTrials.gov (NCT02040441) and is completed.\ud \ud Findings: \ud Between March 25, 2014, and Sept 30, 2018, we enrolled and followed-up 1775 participants (observational cohort), 1559 (88%) of 1775 participants had a low-risk urinary proteomic pattern and 216 (12%) had a high-risk pattern, of whom 209 were included in the trial cohort and assigned to spironolactone (n=102) or placebo (n=107). The overall median follow-up time was 2·51 years (IQR 2·0–3·0). Progression to microalbuminuria was seen in 61 (28%) of 216 high-risk participants and 139 (9%) of 1559 low-risk participants (hazard ratio [HR] 2·48, 95% CI 1·80–3·42; p

This open-label, multicentre phase I/II study determined the maximum tolerated dose (MTD), safety and efficacy of clofarabine administered with cytarabine and idarubicin in newly diagnosed acute myeloid leukaemia (AML) patients lacking favourable genetic aberrations. The MTD was 30 mg/m2 clofarabine for patients below and above 60 years. The most frequently reported grade 3-4 non-haematological adverse events were infectious and gastrointestinal toxicities. Complete remission (CR)/CR with incomplete recovery rate was 67%. Allogeneic haematopoietic cell transplantation in first remission was feasible in a high proportion of younger AML patients and probably contributed to the favourable outcome compared to historical controls.

Recently developed PCR systems offer online-monitoring of amplification and allow simple and reliable DNA quantification. We have used the LightCycler system to develop a simple and rapid method for direct identification of female carriers of deletions and duplications in the dystrophin gene. The challenge resides in the ability to identify the presence of a deleted or duplicated allele over the background contributed by the normal allele. Quantification is based on the determination of the ratio between potentially deleted/duplicated dystrophin exons and non-deleted/-duplicated reference exons using the unspecific dsDNA-dye SYBRgreen I. In a retrospective study, we evaluated our method in female relatives of DMD/BMD patients with known carrier status by comparative analysis of deleted or duplicated versus non-deleted/-duplicated exons. Carrier status was accurately attributed in 100% of cases, the mean ratios being 0.52±0.12 for deletion carriers (expected value: 0.5) and 1.56±0.18 for duplication carriers (expected value: 1.5) vs. 1.022±0.17 for non-carriers (expected value: 1.0). The method proved to be simple, rapid, reliable, and cost-effective. It may be used for direct determination of deletions/duplications in potential DMD/BMD carriers and may easily be adapted for other genetic conditions involving deletions and duplications. Hum Mutat 23:385-391, 2004 © 2004 Wiley-Liss, Inc.

Background: Clofarabine is a second-generation purine nucleoside analogue, which has shown synergistic activity with cytarabine. We determined the maximum tolerated dose (MTD, primary endpoint), safety and efficacy (secondary endpoints) of clofarabine in combination with cytarabine and idarubicin in newly diagnosed acute myeloid leukemia (AML) patients with high-risk for induction failure stratified in two age groups (< 60 years and ≥ 60 years). Methods: In this prospective, open-label, multicenter phase I/II study (EudraCT 2010-021719-18, CIARA trial), newly diagnosed AML patients with high risk of induction failure (NPM1 wildtype, FLT3-ITD negative), who were eligible for intensive chemotherapy, received two induction courses (cytarabine 750 mg/m2 d1-5, idarubicin 7.5 mg/m2 in patients Results: Forty-two patients with de novo (n=32) or secondary (n=10) AML were included. Median age was 58.5 years (range 28-73, 24 patients < 60 years, 18 patients ≥ 60 years). Intermediate/adverse risk cytogenetics were found in 22 and 12 patients, respectively (karyotype missing in 8 patients). All patients received induction 1, 27 (64%) received induction 2; 4 (10%) patients died during induction courses 1 or 2. Eight patients developed a dose-limiting toxicity (6 patients with grade 3/4 non-hematologic toxicity and 3 patients with grade 4/5 hematologic toxicity) and the MTD was determined at 30 mg/m2 clofarabine for both age cohorts (younger patients: 2 of 6 patients with DLT at 35 mg/m2, no DLT at 30 mg/m2 (n=9); older patients: 4 of 6 patients with DLT at 35 mg/m2 in the extension phase, no DLT at 30 mg/m2 (n=3). The most frequent grade 3-5 non-hematologic adverse events were febrile neutropenia, sepsis, increased liver enzymes, pneumonia, decreased appetite and diarrhea occurring in 55, 24, 21, 21, 10 and 10% of patients. The median time to neutrophils ≥0.5/nl and platelets ≥50/nl after induction 1 was 25 and 24 days, respectively. Sixteen patients (38%) proceeded to allogeneic HCT in first CR and 8 (19%) received at least one course of high-dose cytarabine consolidation. Complete remission (CR) or CR with incomplete recovery (CRi) was achieved in 67%. After a median follow up of 2.2 years the 2-year overall survival (OS) was 56% and the 2-year event-free survival was 38% (median EFS 11.4 months). Compared to a matched historical control of 197 younger AML patients (SHG 0199 trial, Schlenk et al. NEJM 2008), the CR rate was 79% in the 24 younger CIARA patients compared to 66% in the control cohort (P=.18), and 2-year OS was higher for CIARA than for control patients (74% vs 49%, P=.021, Figure A). The allogeneic HCT rate in first CR (CR1) was higher in younger CIARA compared to younger control patients (58% vs 27%, P=.002). The CR rate in older CIARA patients was 50% compared to 36% in a historical control of 191 older patients, who were selected using the same genetic inclusion criteria as for CIARA patients (HD98B trial, Schlenk et al. Haematologica 2009, P=.23). Two-year OS in older patients was similar between CIARA and control patients (33% vs 17%, P=.31, Figure B). The allogeneic HCT rate in CR1 was 11% vs 2% in CIARA vs control patients (P=.029). Conclusion: Clofarabine can be safely administered at 30 mg/m2 in combination with cytarabine and idarubicin in younger and older newly diagnosed AML patients. Allogeneic HCT in CR1 was feasible in a high proportion of younger AML patients and likely contributed to the favorable outcome compared to historical control patients. Figure Overall survival in younger and older AML patients of the CIARA trial compared to historical controls. Figure. Overall survival in younger and older AML patients of the CIARA trial compared to historical controls. Disclosures Krauter: Genzyme: Research Funding. Schlenk:Amgen: Research Funding; Pfizer: Honoraria, Research Funding. Paschka:Novartis: Consultancy; Medupdate GmbH: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer Pharma GmbH: Honoraria; Celgene: Honoraria; ASTEX Pharmaceuticals: Consultancy. Lübbert:Ratiopharm: Other: Study drug valproic acid; Celgene: Other: Travel Funding; Janssen-Cilag: Other: Travel Funding, Research Funding. Janning:Teva: Honoraria. Becker:BMS: Honoraria; Novartis: Honoraria. Heuser:Tetralogic: Research Funding; Novartis: Consultancy, Research Funding; Celgene: Honoraria; Pfizer: Research Funding; Bayer Pharma AG: Research Funding; BerGenBio: Research Funding; Karyopharm Therapeutics Inc: Research Funding.

Newborn Care Poster Presentation Purpose for the Program The purpose of the program was to improve mother and newborn outcomes on multiple key measures through the integration of multiple best practice models into a community hospital setting. Proposed Change The proposed change involved identification and cultivation of nurse-led teams to successfully deploy and manage the integration of these practice models into the existing culture and practice setting. Implementation involved a well-staged sequential 4-year roll-out of five integrated best practice models. The setting was Catholic Health Services at St. Catherine of Siena Medical Center community hospital. Implementation, Outcomes, and Evaluation The outcomes of interest were measures of quality and perception of transition care during delivery, frequency counts of continuous skin-to-skin contact, frequency of rooming-in, quality and perception of nonseparation of mother and infant from delivery to discharge, and frequency of breastfeeding exclusivity. Formative and summative evaluation of the program's structure and processes, and patient and staff outcomes were required to ensure continual attention to the effect of the implementation and subsequent revision of methods. Quantitative and qualitative outcomes of multiple sources were examined for triangulation of evidence to drive program success. We modified our model of practice from traditional postpartum/nursery care to a couplet care model promoting nonseparation of mother and infant from delivery to discharge. With these programmatic changes in our culture of care came staff resistance, which warranted education, support, and reward. Staff was provided with ongoing education, including didactic training, staff-driven cross-training, modeling of care, shared governance, competencies, and new evaluation tools to foster accountability. Policies were updated to support these changes. The maternity education line was increased from part-time to full-time and the lactation consultant staff line became an education position. Implications for Nursing Practice We discovered that a major change in programmatic culture of care takes a great deal of education, time, and patience. Budgeting is also a consideration. It is better to make small changes that include staff for buy-in and to reward each victory. We identified the need to slow our change process by taking baby steps and implementing in phases. Collecting data and surveys are excellent tools to promote staff accountability and ensure that patients’ needs are being met. A dedicated transition nurse to initiate biological harmony and adjustment to parenthood promotes best care and practice. Finally, a team approach, which includes staff and management, is essential to support success.

In einer prospektiven, randomisierten, kontrollierten Studie mit 100 Patienten wurde die Wirksamkeit prophylaktischer Mezlocillin-Gaben in der elektiven Kolonchirurgie untersucht. 52 Patienten waren in der Behandlungsgruppe, 48 dienten der Kontrolle. Beide Kollektive waren nach Randomisierung in bezug auf Alter, Geschlecht, Erkrankungen und Operationsarten vergleichbar. Praoperativ wurden 2 g Mezlocillin i. v. gegeben, danach 2 g achtstundlich bis zum funften postoperativen Tag. Bei 20 Patienten wurden die Mezlocillin-Konzentrationen in Serum und Geweben bestimmt und zu den MHK der Kontaminationsflora und der postoperativ isolierten Erreger in Beziehung gesetzt. In der Mezlocillin-Gruppe wurde eine signifikante Senkung der Haufigkeit intraabdominaler Komplikationen, Peritonitiden, Harnwegsinfektionen und Wundinfektionen (10%), verglichen mit der Kontrollgruppe (46%), gefunden. Die durchschnittliche postoperative Liegezeit verkurzte sich signifikant von 23 Tagen in der Kontroll- auf 19 Tage in der Mezlocillin-Gruppe. Die Analyse der bakteriologischen Ergebnisse ergab keinen Anhalt fur eine Selektionierung von Keimen durch die systemische Antibiotikaprophylaxe. Es wurden keine Nebenwirkungen im Zusammenhang mit der Mezlocillin-Prophylaxe beobachtet.