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Article ; Online: Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non-COVID-19 Sepsis but Carries a Moderately Increased Risk of Death.

Sunden-Cullberg, Jonas

Hypertension (Dallas, Tex. : 1979)

2020 Volume 75, Issue 6, Page(s) e15–e16

MeSH term(s)	Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Intensive Care Units ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2 ; Sepsis
Chemical Substances	Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins
Keywords	covid19
Language	English
Publishing date	2020-04-10
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/HYPERTENSIONAHA.120.15178
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Article ; Online: Plasma calprotectin as an indicator of need of transfer to intensive care in patients with suspected sepsis at the emergency department.

Parke, Åsa / Unge, Christian / Yu, David / Sundén-Cullberg, Jonas / Strålin, Kristoffer

BMC emergency medicine

2023 Volume 23, Issue 1, Page(s) 16

Abstract: Background: Deciding whether to transfer patients with sepsis from the emergency department (ED) to intensive care units (ICUs) is challenging. We hypothesised that the new biomarker plasma calprotectin (p-calprotectin) could be used to aid the ... ...

Abstract	Background: Deciding whether to transfer patients with sepsis from the emergency department (ED) to intensive care units (ICUs) is challenging. We hypothesised that the new biomarker plasma calprotectin (p-calprotectin) could be used to aid the selection of patients for intensive care transfer, since it has been shown to be a promising tool for the determination of sepsis severity in critical care. Methods: This prospective study was performed on consecutive sepsis alert patients in the ED of Karolinska University Hospital Huddinge. The sepsis alert mandates clinical assessment and decisions regarding treatment, disposition, and level of care by physicians from the ED, the Department of Infectious Diseases, and the ICU. Blood sample analysis for C-reactive protein, procalcitonin, neutrophils, and lymphocytes was routinely performed. P-calprotectin was analysed from frozen plasma samples, using a specific turbidimetric assay. Results: Three-hundred fifty-one patients who triggered the sepsis alert were available for the study. Among 319 patients who were considered to have an infection, 66 patients (26%) were immediately transferred to the ICU or high-dependency unit (HDU), and 253 patients (74%) were transferred to ordinary wards. Median p-calprotectin was 2.2 mg/L (IQR 1.2-3.9 mg/L) for all patients with infection, it was 3.3 (IQR 1.6-5.2) for those transferred to ICU/HDU and 2.1 (IQR 1.1-3.5) for those transferred to ward units (p = 0.0001). Receiver operating characteristic curve analysis for transfer to the ICU/HDU showed superiority for p-calprotectin compared with procalcitonin and neutrophil-lymphocyte ratio, regarding both all sepsis alert cases and the patients with infection (p < 0.001 for all comparisons). The best p-calprotectin cut-off, 4.0 mg/L, showed a sensitivity of 42.5% and specificity of 83% for transfer to the ICU/HDU among patients with infection. Conclusions: In sepsis alert patients, p-calprotectin was significantly elevated in patients who were subject to immediate ICU/HDU transfer after assessment by a multidisciplinary team. P-calprotectin was superior to traditional biomarkers in predicting the need for transfer to the ICU/HDU.
MeSH term(s)	Humans ; Prospective Studies ; Procalcitonin ; Leukocyte L1 Antigen Complex ; Sepsis/diagnosis ; Sepsis/therapy ; Critical Care ; Intensive Care Units ; Emergency Service, Hospital ; Biomarkers
Chemical Substances	Procalcitonin ; Leukocyte L1 Antigen Complex ; Biomarkers
Language	English
Publishing date	2023-02-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2050431-7
ISSN	1471-227X ; 1471-227X
ISSN (online)	1471-227X
ISSN	1471-227X
DOI	10.1186/s12873-023-00785-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Prognostic significance of body temperature in the emergency department vs the ICU in Patients with severe sepsis or septic shock: A nationwide cohort study.

Inghammar, Malin / Sunden-Cullberg, Jonas

PloS one

2020 Volume 15, Issue 12, Page(s) e0243990

Abstract: Background: Increased body temperature in the Emergency Department (BT-ED) and the ICU (BT-ICU) is associated with lower mortality in patients with sepsis. Here, we compared how well BT-ED and BT-ICU predict mortality; investigated mortality in various ... ...

Abstract	Background: Increased body temperature in the Emergency Department (BT-ED) and the ICU (BT-ICU) is associated with lower mortality in patients with sepsis. Here, we compared how well BT-ED and BT-ICU predict mortality; investigated mortality in various combinations of BT-ED and BT-ICU, and; compared degree of fever in the ED and ICU and associated quality of care. Methods: 2385 adults who were admitted to an ICU within 24 hours of ED arrival with severe sepsis or septic shock were included. Results: Thirty-day mortality was 23.6%. Median BT-ED and BT-ICU was 38.1 and 37.6°C. Crude mortality decreased more than 5% points per°C increase for both BT-ED and BT-ICU. Adjusted OR for mortality was 0.82/°C increase for BT-ED (0.76-0.88, p < 0.001), and 0.89 for BT-ICU (0.83-0.95, p<0.001). Patients who were at/below median temperature in both the ED and in the ICU had the highest mortality, 32%, and those with over median in the ED and at/below in the ICU had the lowest, 16%, (p<0.001). Women had 0.2°C lower median BT-ED (p = 0.03) and 0.3°C lower BT-ICU (p<0.0001) than men. Older patients had lower BT in the ICU, but not in the ED. Fever was associated with a higher rate of sepsis bundle achievement in the ED, but lower nurse workload in the ICU. Conclusions: BT-ED was more useful to prognosticate mortality than BT-ICU. Despite better prognosis in patients with elevated BT, fever was associated with higher quality of care in the ED. Future studies should assess how BT-ED can be used to improve triage of infected patients, assigning higher priority to patients with low-grade/no fever and vice versa. Patients with at/below median BT in both ED and ICU have the highest mortality and should receive special attention. Different BT according to sex and age also needs further study.
MeSH term(s)	Age Factors ; Aged ; Body Temperature ; Critical Care/methods ; Emergency Service, Hospital/statistics & numerical data ; Female ; Humans ; Intensive Care Units/statistics & numerical data ; Male ; Middle Aged ; Mortality/trends ; Predictive Value of Tests ; Sex Factors ; Shock, Septic/epidemiology ; Shock, Septic/mortality ; Shock, Septic/pathology
Language	English
Publishing date	2020-12-29
Publishing country	United States
Document type	Comparative Study ; Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0243990
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non-COVID-19 Sepsis but Carries a Moderately Increased Risk of Death

Sunden-Cullberg, Jonas

Hypertension

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #46141
Database	COVID19

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Article ; Online: Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non–COVID-19 Sepsis but Carries a Moderately Increased Risk of Death

Sunden-Cullberg, Jonas

Hypertension

2020 Volume 75, Issue 6

Keywords	Internal Medicine ; covid19
Language	English
Publisher	Ovid Technologies (Wolters Kluwer Health)
Publishing country	us
Document type	Article ; Online
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/hypertensionaha.120.15178
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prognostic significance of body temperature in the emergency department vs the ICU in Patients with severe sepsis or septic shock

Malin Inghammar / Jonas Sunden-Cullberg

PLoS ONE, Vol 15, Iss 12, p e

A nationwide cohort study.

2020 Volume 0243990

Abstract: Background Increased body temperature in the Emergency Department (BT-ED) and the ICU (BT-ICU) is associated with lower mortality in patients with sepsis. Here, we compared how well BT-ED and BT-ICU predict mortality; investigated mortality in various ... ...

Abstract	Background Increased body temperature in the Emergency Department (BT-ED) and the ICU (BT-ICU) is associated with lower mortality in patients with sepsis. Here, we compared how well BT-ED and BT-ICU predict mortality; investigated mortality in various combinations of BT-ED and BT-ICU, and; compared degree of fever in the ED and ICU and associated quality of care. Methods 2385 adults who were admitted to an ICU within 24 hours of ED arrival with severe sepsis or septic shock were included. Results Thirty-day mortality was 23.6%. Median BT-ED and BT-ICU was 38.1 and 37.6°C. Crude mortality decreased more than 5% points per°C increase for both BT-ED and BT-ICU. Adjusted OR for mortality was 0.82/°C increase for BT-ED (0.76-0.88, p < 0.001), and 0.89 for BT-ICU (0.83-0.95, p<0.001). Patients who were at/below median temperature in both the ED and in the ICU had the highest mortality, 32%, and those with over median in the ED and at/below in the ICU had the lowest, 16%, (p<0.001). Women had 0.2°C lower median BT-ED (p = 0.03) and 0.3°C lower BT-ICU (p<0.0001) than men. Older patients had lower BT in the ICU, but not in the ED. Fever was associated with a higher rate of sepsis bundle achievement in the ED, but lower nurse workload in the ICU. Conclusions BT-ED was more useful to prognosticate mortality than BT-ICU. Despite better prognosis in patients with elevated BT, fever was associated with higher quality of care in the ED. Future studies should assess how BT-ED can be used to improve triage of infected patients, assigning higher priority to patients with low-grade/no fever and vice versa. Patients with at/below median BT in both ED and ICU have the highest mortality and should receive special attention. Different BT according to sex and age also needs further study.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correlation of clinical sepsis definitions with microbiological characteristics in patients admitted through a sepsis alert system; a prospective cohort study.

Yu, David / Unger, David / Unge, Christian / Parke, Åsa / Sundén-Cullberg, Jonas / Strålin, Kristoffer / Özenci, Volkan

Annals of clinical microbiology and antimicrobials

2022 Volume 21, Issue 1, Page(s) 7

Abstract: Background: Sepsis was recently redefined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. With this redefinition (Sepsis-3), clinical and microbiological characteristics of patients with sepsis may differ ... ...

Abstract	Background: Sepsis was recently redefined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. With this redefinition (Sepsis-3), clinical and microbiological characteristics of patients with sepsis may differ from the patients fulfilling the previous definition (Sepsis-2). Purpose: To describe differences in clinical and microbiological characteristics of sepsis episodes between Sepsis-3 and Sepsis-2. The secondary aim was to compare blood culture outcomes between episodes fulfilling Sepsis-3 and Sepsis-2 criteria, respectively. Methods: A prospective study design was used to include patients presenting with clinically suspected sepsis in the emergency department. Six blood culture bottles were collected from each patient. Blood cultures were described as having clinically relevant growth, contaminant growth, or no growth. Clinical and laboratory data were collected from medical records and the laboratory information system. Results: The analysis included 514 episodes. There were 357/514 (79.5%) Sepsis-3 and 411/514 (80.0%) Sepsis-2 episodes. In total, 341/514 (66.3%) episodes fulfilled both Sepsis-3 and Sepsis-2 criteria. Blood cultures were positive for clinically relevant growth in 130/357 (36.1%) and 145/411 (35.3%) episodes in Sepsis-3 and Sepsis-2, respectively. Other clinical and microbiological characteristics did not differ between Sepsis-3 and Sepsis-2. Conclusions: A high proportion of patients included through a sepsis alert system fulfilled both Sepsis-3 and Sepsis-2 criteria. The performance of blood cultures in detection of microorganisms was poor and were similar in Sepsis-3 and Sepsis-2 patients.
MeSH term(s)	Aged ; Aged, 80 and over ; Communicable Diseases ; Emergency Service, Hospital/statistics & numerical data ; Female ; Hospital Mortality ; Hospitalization/statistics & numerical data ; Humans ; Infections/mortality ; Male ; Middle Aged ; Prospective Studies ; Sepsis/diagnosis ; Sepsis/microbiology ; Sepsis/mortality
Language	English
Publishing date	2022-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2097873-X
ISSN	1476-0711 ; 1476-0711
ISSN (online)	1476-0711
ISSN	1476-0711
DOI	10.1186/s12941-022-00498-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Sex-based differences in ED management of critically ill patients with sepsis: a nationwide cohort study.

Sunden-Cullberg, Jonas / Nilsson, Anton / Inghammar, Malin

Intensive care medicine

2020 Volume 46, Issue 4, Page(s) 727–736

Abstract: Purpose: To compare management and outcomes for critically ill women and men with sepsis in the emergency medical services (EMS), the emergency department (ED) and the ICU.: Methods: We used two prospectively compiled Swedish national quality ... ...

Abstract	Purpose: To compare management and outcomes for critically ill women and men with sepsis in the emergency medical services (EMS), the emergency department (ED) and the ICU. Methods: We used two prospectively compiled Swedish national quality registers, the National Quality Sepsis Registry and the Swedish Intensive Care Registry to identify a nationwide cohort of 2720 adults admitted to an ICU within 24 h of arrival to any of 32 EDs, with a diagnosis of severe sepsis or septic shock between 2008 and 2015. Results: Patients were 44.5% female. In the EMS, a higher fraction of men had all vital signs recorded-54.4 vs 49.9% (p = 0.02) and received IV fluids and oxygen-40.0 vs 34.8% (p = 0.02). In the ED, men had completed 1-h sepsis bundles in 41.5% of cases compared to 30.0% in women (p < 0.001), and shorter time to antibiotics-65 (IQR 30-136) vs 87 min (IQR 39-172) (p = 0.0001). There was no significant difference between men and women regarding ICU nursing workload, mechanical ventilation or ICU length of stay. In severity-adjusted multivariable analysis, OR for women achieving a completed sepsis bundle, compared to men was 0.64 (CI 0.51-0.81). Thirty-day mortality was 25.0% for women and 23.1% for men (p = 0.24). Adjusted OR for female death was 1.28 (CI 1.00-1.64), but the increased mortality was not mediated by differential bundle completion. Conclusions: Women and men with severe sepsis or septic shock received differential care in the ED, but this did not explain higher odds of death in women.
MeSH term(s)	Adult ; Cohort Studies ; Critical Illness ; Emergency Service, Hospital ; Female ; Hospital Mortality ; Humans ; Length of Stay ; Male ; Retrospective Studies ; Sepsis/epidemiology ; Sepsis/therapy ; Shock, Septic/therapy ; Sweden/epidemiology
Language	English
Publishing date	2020-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	80387-x
ISSN	1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
ISSN (online)	1432-1238
ISSN	0340-0964 ; 0342-4642 ; 0935-1701
DOI	10.1007/s00134-019-05910-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1089: Show issues

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Article ; Online: Plasma concentrations of secretory leukocyte protease inhibitor (SLPI) differ depending on etiology and severity in community-onset bloodstream infection.

Lange, Anna / Cajander, Sara / Magnuson, Anders / Sundén-Cullberg, Jonas / Strålin, Kristoffer / Hultgren, Olof

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology

2019 Volume 38, Issue 8, Page(s) 1425–1434

Abstract: The severity of bloodstream infections (BSI) depends on pathogen, source, and host factors. Secretory leukocyte protease inhibitor (SLPI) counteracts tissue damage, balances inflammation, and is increased in pneumonia and sepsis. We aimed to evaluate ... ...

Abstract	The severity of bloodstream infections (BSI) depends on pathogen, source, and host factors. Secretory leukocyte protease inhibitor (SLPI) counteracts tissue damage, balances inflammation, and is increased in pneumonia and sepsis. We aimed to evaluate whether SLPI production differs depending on etiology, disease severity, and sex in BSI and to correlate SLPI with markers of inflammation and immunosuppression. Of the adult patients with BSI, 109 were included and sampled repeatedly, from hospital admission through day 28. Controls (blood donors) were sampled twice. SLPI in plasma was measured with enzyme-linked immunosorbent assay (ELISA) technique. Streptococcus pneumoniae and Staphylococcus aureus etiology were associated with higher SLPI than Escherichia coli on days 1-2 and 3. On day 1-2, subjects with sepsis had higher SLPI concentrations than those with non-septic BSI. Pneumonia was associated with higher SLPI than a non-pulmonary source of infection. SLPI co-varied with inflammatory markers. SLPI concentrations did not differ with regard to sex in the full cohort, but men with pneumonia had higher SLPI than women on day 1-2. S. pneumoniae and S. aureus BSI were associated with higher SLPI, when compared to E. coli. Severity and pneumonia, as well as male sex in the pneumonia sub-cohort, were factors independently associated with higher SLPI.
MeSH term(s)	Aged ; Aged, 80 and over ; Bacteremia/diagnosis ; Bacteremia/microbiology ; Biomarkers/blood ; Escherichia coli ; Escherichia coli Infections/diagnosis ; Female ; Humans ; Inflammation ; Male ; Middle Aged ; Pneumococcal Infections/diagnosis ; Pneumonia, Bacterial/diagnosis ; Pneumonia, Bacterial/microbiology ; Prospective Studies ; Secretory Leukocyte Peptidase Inhibitor/blood ; Severity of Illness Index ; Sex Factors ; Staphylococcal Infections/diagnosis ; Staphylococcus aureus ; Streptococcus pneumoniae
Chemical Substances	Biomarkers ; SLPI protein, human ; Secretory Leukocyte Peptidase Inhibitor
Language	English
Publishing date	2019-05-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	603155-9
ISSN	1435-4373 ; 0934-9723 ; 0722-2211
ISSN (online)	1435-4373
ISSN	0934-9723 ; 0722-2211
DOI	10.1007/s10096-019-03567-2
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Zs.A 1732: Show issues

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Article ; Online: Soluble B and T Lymphocyte Attenuator Correlates to Disease Severity in Sepsis and High Levels Are Associated with an Increased Risk of Mortality.

Lange, Anna / Sundén-Cullberg, Jonas / Magnuson, Anders / Hultgren, Olof

PloS one

2017 Volume 12, Issue 1, Page(s) e0169176

Abstract: Introduction and aims: B- and T-lymphocyte Attenuator (BTLA), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. In the present study of ICU-treated patients we ...

Abstract	Introduction and aims: B- and T-lymphocyte Attenuator (BTLA), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. In the present study of ICU-treated patients we measured plasma concentrations of their soluble isoforms, with the aim to evaluate their potential as sepsis biomarkers and utility as prognostic indicators. Methods: 101 patients with sepsis, 28 patients with non-infectious critical illness (ICU controls) and 31 blood donors (healthy controls, HC) were included in the study. Plasma concentrations of soluble BTLA (sBTLA), CTLA-4 (sCTLA-4) and PD-1 (sPD-1) were measured with ELISA in serial blood samples. Comparisons were made with Mann-Whitney U test and correlations were assessed with Spearman's Rank correlation test. Cox proportional hazard models, with sBTLA and sPD-1 as fixed and sBTLA as time-varying covariates, were used to determine association with 28-day mortality. Results: sBTLA levels were significantly higher in the sepsis cohort (median 14 ng/mL, IQR 8-29) compared to ICU controls (9 ng/mL, IQR 5-26, p = 0.048) and HC (2.9 ng/mL, IQR 0.9-9.1, p<0.01), and correlated to SOFA score. sBTLA levels were higher in 28 day sepsis non-survivors than in survivors (baseline median 28 ng/mL, IQR 13-41 vs 13 ng/mL, IQR 8-23, p = 0.04). After adjustment for age and comorbidities, the relative risk of 28 day mortality was nearly 5-fold higher in sepsis patients with a baseline sBTLA > 21 ng/mL, compared to those with a level below this threshold. sBTLA was even more associated with mortality in the time-varying analysis. sPD-1 levels were lower in the sepsis cohort compared to HC but not compared to ICU controls and were not associated with mortality. sCTLA-4 was detectable in only one subject. Conclusion: Plasma concentrations of soluble BTLA were increased early in sepsis/septic shock and correlated to severity of disease. A baseline concentration >21ng/mL was associated with a poor prognosis.
MeSH term(s)	Aged ; Biomarkers/blood ; CTLA-4 Antigen/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunocompromised Host/immunology ; Male ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/blood ; Receptors, Immunologic/blood ; Sepsis/blood ; Sepsis/immunology ; Sepsis/mortality ; Shock, Septic/blood ; Shock, Septic/immunology ; Shock, Septic/mortality
Chemical Substances	BTLA protein, human ; Biomarkers ; CTLA-4 Antigen ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Receptors, Immunologic
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0169176
Database	MEDical Literature Analysis and Retrieval System OnLINE

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