Vibeke Lind Jørgensen

Bio: Vibeke Lind Jørgensen is an academic researcher from University of Copenhagen. The author has contributed to research in topics: Medicine & Mechanical ventilation. The author has an hindex of 9, co-authored 18 publications receiving 368 citations. Previous affiliations of Vibeke Lind Jørgensen include Copenhagen University Hospital & Herlev Hospital.

Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis.

Abstract: Background and aims: Expression of inducible nitric oxide synthase (iNOS) is greatly upregulated in the colonic mucosa of patients with collagenous and ulcerative colitis. As the transcription factor nuclear factor κB (NFκB) is a major inducer of iNOS gene expression, we compared activation and transcriptional activity of NFκB in colonic mucosal biopsies from these patients. Patients: Eight patients with collagenous colitis, six with relapsing ulcerative colitis, and eight with uninflamed bowel were studied. Methods: NFκB DNA binding activity was assessed by electrophoretic mobility shift assay and inhibitor of NFκB (IκB) kinase (IKK) activity by immunocomplex kinase assay. In vivo recruitment of NFκB to the iNOS promoter was determined by chromatin immunoprecipitation analysis and transcriptional activity by NFκB gene expression profiling arrays. Cells showing NFκB activation were identified by immunohistochemistry. Results: In collagenous and ulcerative colitis, as opposed to uninflamed bowel, IKKβ activity and strong NFκB DNA binding gave rise to activation of identical NFκB subunits and recruitment of transcriptionally active p65 to the iNOS promoter. In collagenous colitis, activated NFκB was observed only in epithelial cells while up to 10% of lamina propria macrophages showed activation in ulcerative colitis. Conclusions: In collagenous and ulcerative colitis, colonic mucosal NFκB is activated and recruited to the iNOS promoter in vivo via an IKKβ mediated pathway. As collagenous colitis is not associated with tissue injury, these data challenge the prevailing view that activation of NFκB per se mediates tissue injury. Our results suggest that downstream inflammatory reactions leading to tissue damage originate in lamina propria immune cells, as increased NFκB activity in collagenous colitis was localised solely in epithelial cells, but present also in macrophages in ulcerative colitis.

Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial.

Abstract: Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.

Characteristics, interventions and longer-term outcomes of COVID-19 ICU patients in Denmark - a nationwide, observational study.

Abstract: Background Most data on intensive care unit (ICU) patients with COVID-19 originate in selected populations from stressed healthcare systems with shorter term follow-up. We present characteristics, interventions and longer term outcomes of the entire, unselected cohort of all ICU patients with COVID-19 in Denmark where the ICU capacity was not exceeded. Methods We identified all patients with SARS-CoV-2 admitted to any Danish ICU from 10 March to 19 May 2020 and registered demographics, chronic comorbidities, use of organ support, length of stay, and vital status from patient files. Risk factors for death were analyzed using adjusted Cox regression analysis. Results There were 323 ICU patients with confirmed COVID-19. Median age was 68 years, 74% were men, 50% had hypertension, 21% diabetes, and 20% chronic pulmonary disease; 29% had no chronic comorbidity. Invasive mechanical ventilation was used in 82%, vasopressors in 83%, renal replacement therapy in 26%, and extra corporeal membrane oxygenation in 8%. ICU stay was median 13 days (IQR 6-22) and hospital stay 19 days (11-30). Median follow-up was 79 days. At end of follow-up, 118 had died (37%), 15 (4%) were still in hospital hereof 4 in ICU as of 16 June 2020. Risk factors for mortality included male gender, age, chronic pulmonary disease, active cancer, and number of co-morbidities. Conclusions In this nationwide, population-based cohort of ICU patients with COVID-19, longer term survival was high despite high age and substantial use of organ support. Male gender, age, and chronic co-morbidities, in particular chronic pulmonary disease, were associated with increased risk of death.

Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial.

Abstract: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI −0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.

Increased colorectal permeability in patients with severe sepsis and septic shock

Abstract: Objective To develop a method for the assessment of colorectal permeability in septic patients.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis.

Abstract: Background MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterised the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis.

Delirium in Older Persons: Advances in Diagnosis and Treatment.

Abstract: Importance Delirium is defined as an acute disorder of attention and cognition. It is a common, serious, and often fatal condition among older patients. Although often underrecognized, delirium has serious adverse effects on the individual’s function and quality of life, as well as broad societal effects with substantial health care costs. Objective To summarize the current state of the art in diagnosis and treatment of delirium and to highlight critical areas for future research to advance the field. Evidence Review Search of Ovid MEDLINE, Embase, and the Cochrane Library for the past 6 years, from January 1, 2011, until March 16, 2017, using a combination of controlled vocabulary and keyword terms. Since delirium is more prevalent in older adults, the focus was on studies in elderly populations; studies based solely in the intensive care unit (ICU) and non–English-language articles were excluded. Findings Of 127 articles included, 25 were clinical trials, 42 cohort studies, 5 systematic reviews and meta-analyses, and 55 were other categories. A total of 11 616 patients were represented in the treatment studies. Advances in diagnosis have included the development of brief screening tools with high sensitivity and specificity, such as the 3-Minute Diagnostic Assessment; 4 A’s Test; and proxy-based measures such as the Family Confusion Assessment Method. Measures of severity, such as the Confusion Assessment Method–Severity Score, can aid in monitoring response to treatment, risk stratification, and assessing prognosis. Nonpharmacologic approaches focused on risk factors such as immobility, functional decline, visual or hearing impairment, dehydration, and sleep deprivation are effective for delirium prevention and also are recommended for delirium treatment. Current recommendations for pharmacologic treatment of delirium, based on recent reviews of the evidence, recommend reserving use of antipsychotics and other sedating medications for treatment of severe agitation that poses risk to patient or staff safety or threatens interruption of essential medical therapies. Conclusions and Relevance Advances in diagnosis can improve recognition and risk stratification of delirium. Prevention of delirium using nonpharmacologic approaches is documented to be effective, while pharmacologic prevention and treatment of delirium remains controversial.