Guidelines 1 Aspleni (2024v1.1)
Rekommandationer for profylakse og vaccination ved aspleni. Denne vejledning dækker anbefalinger omhandlende vaccinationer, antibiotika profylakse og patientinformation om generelle forholdsregler for at beskytte personer med aspleni mod infektioner. Version 1.1, 11.06.2024. Ændringer siden version 1: Apexxnar er ændret til Prevenar 20 (og PCV13 til Prevenar 13). Prevenar 20 kan gives allerede fra 6 måneders alderen, hvorfor denne erstatter primær vaccination med PCV13 og PPV23. Erythrocyt morfologi er tilføjet som bilag. 2 Sepsis flowchart (2021)
Bilag med flowchart til vurdering og behandling af sepsis og septisk shock, se også infmed.dk/guidelines#sepsis_guidelines_(2021).pdf 3 Sepsis guidelines (2021)
Disse rekommandationer retter sig mod voksne indlagt med mistænkt sepsis og septisk shock. Se flowchart på infmed.dk/bilag#sepsis_flowchart_(2021).pdf På vegne af Dansk Selskab for Infektionsmedicin: Lars Skov Dalgaard, Michael Dalager, Christian Philip Fischer, Rikke Krogh-Madsen, Gitte Kronborg, Jannik Helweg Larsen, Stig Lønberg Nielsen, Christian Søborg, Lars Toft. Nye artikler 1 “Inhibitory immune checkpoints predict 7-day, in-hospital and 1-year mortality of internal medicine patients admitted with bacterial sepsis”
Journal of Infectious Diseases, 24.07.2024 Tilføjet 24.07.2024 Abstract Background Sepsis is a life-threatening syndrome with complex pathophysiology and great clinical heterogeneity which complicates the delivery of personalized therapies. Our goals were to demonstrate that some biomarkers identified as regulatory immune checkpoints in preclinical studies could 1)improve sepsis prognostication based on clinical variables and 2)guide the stratification of septic patients in subgroups with shared characteristics of immune response or survival outcomes.Methods We assayed the soluble counterparts of 12 biomarkers of immune response in 113 internal medicine patients with bacterial sepsis.Results IL-1 receptor-associated kinase M (IRAK-M) exhibited the highest hazard ratios (HRs) for increased 7-day (1.94 [1.17-3.20]) and 30-day mortality (1.61 [1.14-2.28]). HRs of IRAK-M and Galectin-1 for predicting 1-year mortality were 1.52 (1.20-1.92) and 1.64 (1.13-2.36), respectively. A prognostic model including IRAK-M, Galectin-1, and clinical variables (Charlson Comorbidty Index, multiple source of sepsis, and SOFA score) had high discrimination for death at 7 days and 30 days (area under the curve 0.90 [0.82-0.99]) and 0.86 [0.79-0.94], respectively). Patients with elevated serum levels of IRAK-M and Galectin-1 had clinical traits of immune suppression and low survival rates. None of the 12 biomarkers were independent predictors of 2-year mortality.Conclusions Two inhibitory immune checkpoint biomarkers (IRAK-M and Galectin-1) helped identify 3 distinct sepsis phenotypes with distinct prognoses. These biomarkers shed light on the interplay between immune dysfunction and prognosis in patients with bacterial sepsis and may prove to be useful prognostic markers, therapeutic targets, and biochemical markers for targeted enrollment in targeted therapeutic trials. Læs mere Tjek på PubMed2 [Seminar] Neonatal bacterial sepsis
Tobias Strunk, Eleanor J Molloy, Archita Mishra, Zulfiqar A Bhutta Lancet, 19.07.2024 Tilføjet 19.07.2024 Neonatal sepsis remains one of the key challenges of neonatal medicine, and together with preterm birth, causes almost 50% of all deaths globally for children younger than 5 years. Compared with advances achieved for other serious neonatal and early childhood conditions globally, progress in reducing neonatal sepsis has been much slower, especially in low-resource settings that have the highest burden of neonatal sepsis morbidity and mortality. By contrast to sepsis in older patients, there is no universally accepted neonatal sepsis definition. Læs mere Tjek på PubMed3 Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol
Ahlem Trifi, Sami Abdellatif, Asma Mehdi, Linda Messaoud, Eya Seghir, Nacef Mrad, Jalila Ben Khelil, Khaoula Ben Ismail, Takwa Merhaben, Hana Fradj, Amel Mokline, Amen Allah Messaadi, Hyem Khiari, Yasmin Garbaa, Nabiha Borsali Falfoul, Emna Ennouri, Radhouane Toumi, Mohamed Boussarsar, Oussama Jaoued, Souhail Atrous, Hassen Ben Ghezala, Nozha Brahmi, Insaf Trabelsi, Hatem Ghadhoune, Sabrine Bradaii, Mabrouk Bahloul, Rania Ammar, Fatma Medhioub Kaaniche PLoS One Infectious Diseases, 19.07.2024 Tilføjet 19.07.2024 by Ahlem Trifi, Sami Abdellatif, Asma Mehdi, Linda Messaoud, Eya Seghir, Nacef Mrad, Jalila Ben Khelil, Khaoula Ben Ismail, Takwa Merhaben, Hana Fradj, Amel Mokline, Amen Allah Messaadi, Hyem Khiari, Yasmin Garbaa, Nabiha Borsali Falfoul, Emna Ennouri, Radhouane Toumi, Mohamed Boussarsar, Oussama Jaoued, Souhail Atrous, Hassen Ben Ghezala, Nozha Brahmi, Insaf Trabelsi, Hatem Ghadhoune, Sabrine Bradaii, Mabrouk Bahloul, Rania Ammar, Fatma Medhioub Kaaniche One of the most important components of sepsis management is hemodynamic restoration. If the target mean arterial pressure (MAP) is not obtained, the first recommendation is for volume expansion, and the second is for norepinephrine (NE). We describe the methodology of a randomized multicenter trial aiming to assess the hypothesis that low-dose NE given early in adult patients with sepsis will provide better control of shock within 6 hours from therapy starting compared to standard care. This trial includes ICU septic patients in whom MAP decrease below 65 mmHg to be randomized into 2 groups: early NE-group versus standard care-group. The patient’s attending clinician will determine how much volume expansion is necessary to meet the target of a MAP > 65 mm Hg. If this target not achieved, after at least 30 ml/kg and guided by the available indices of fluid responsiveness, NE will be used in a usual way. The latter must follow a consensual schedule elaborated by the investigating centers. Parameters to be taken at inclusion and at H6 are: lactates, cardiac ultrasound parameters (stroke volume (SV), cardiac output (CO), E/E’ ratio), and P/F ratio. MAP and diuresis are recorded hourly. Our primary outcome is the shock control defined as a composite criterion (MAP > 65 mm Hg for 2 consecutive measurements and urinary output > 0.5 ml/kg/h for 2 consecutive hours) within 6 hours. Secondary outcomes: Decrease in serum lactate> 10% from baseline within 6 hours, the received fluid volume within 6 hours, variation of CO and E/E’, and 28 days-Mortality. The study is ongoing and aims to include at least 100 patients per arm. This study is likely to contribute to support the indication of early initiation of NE with the aim to restrict fluid intake in septic patients. (ClinicalTrials.gov ID: NCT05836272). Læs mere Tjek på PubMed4 Analyzing the molecular mechanism of Scutellaria Radix in the treatment of sepsis using RNA sequencing
BMC Infectious Diseases, 17.07.2024 Tilføjet 17.07.2024 Abstract Background Sepsis is a life-threatening organ dysfunction, which seriously threatens human health. The clinical and experimental results have confirmed that Traditional Chinese medicine (TCM), such as Scutellariae Radix, has anti-inflammatory effects. This provides a new idea for the treatment of sepsis. This study systematically analyzed the mechanism of Scutellariae Radix treatment in sepsis based on network pharmacology, RNA sequencing and molecular docking. Methods Gene expression analysis was performed using Bulk RNA sequencing on sepsis patients and healthy volunteers. After quality control of the results, the differentially expressed genes (DEGs) were analyzed. The active ingredients and targets of Scutellariae Radix were identified using The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Ontology (GO) and Protein-Protein Interaction (PPI) analysis were performed for disease-drug intersection targets. With the help of GEO database, Survival analysis and Meta-analysis was performed on the cross-targets to evaluate the prognostic value and screen the core targets. Subsequently, single-cell RNA sequencing was used to determine where the core targets are located within the cell. Finally, in this study, molecular docking experiments were performed to further clarify the interrelationship between the active components of Scutellariae Radix and the corresponding targets. Results There were 72 active ingredients of Scutellariae Radix, and 50 common targets of drug and disease. GO and PPI analysis showed that the intersection targets were mainly involved in response to chemical stress, response to oxygen levels, response to drug, regulation of immune system process. Survival analysis showed that PRKCD, EGLN1 and CFLAR were positively correlated with sepsis prognosis. Meta-analysis found that the three genes were highly expressed in sepsis survivor, while lowly in non-survivor. PRKCD was mostly found in Macrophages, while EGLN1 and CFLAR were widely expressed in immune cells. The active ingredient Apigenin regulates CFLAR expression, Baicalein regulates EGLN1 expression, and Wogonin regulates PRKCD expression. Molecular docking studies confrmed that the three active components of astragalus have good binding activities with their corresponding targets. Conclusions Apigenin, Baicalein and Wogonin, important active components of Scutellaria Radix, produce anti-sepsis effects by regulating the expression of their targets CFLAR, EGLN1 and PRKCD. Læs mere Tjek på PubMed5 One-year survival of patients admitted for sepsis to intensive care units in Colombia
BMC Infectious Diseases, 17.07.2024 Tilføjet 17.07.2024 Abstract Background Sepsis is a frequent cause of admission to intensive care units (ICUs). High mortality rates are estimated globally, and in our country, few studies have reported one-year survival. The objective of this study is to determine one-year survival in patients with sepsis admitted to the ICU in Colombia, compared with the survival of patients admitted for other conditions. Methods Retrospective cohort study using administrative databases from the Ministry of Health of Colombia. One-year survival and the adjusted hazard ratio for survival, adjusted for comorbidities included in the Charlson Index, were determined using a Cox proportional hazards model for patients admitted for other causes as well as for those admitted for sepsis. This was then compared with an inverse propensity score weighting model. Results A total of 116.407 patients were initially admitted to the ICUs, with 12.056 (10.36%) diagnosed with sepsis. Within the first year, 4.428 (36.73%) patients died due to sepsis. Age and male gender were associated with an increased risk of death from sepsis, and the covariates associated with one-year mortality were as follows: age over 80 years with HR 9.91 (95% CI: 9.22–10.65), renal disease with HR 3.16 (95% CI: 3.03–3.29), primary tumoral disease with HR 2.07 (95% CI: 1.92–2.23), liver disease with HR 2.27 (95% CI: 2.07–2.50), and metastatic solid tumor with HR 2.03 (95% CI: 1.92–2.15). Conclusion This study revealed a high one-year sepsis mortality rate in the population, associated with variables such as age over 80 years, the presence of renal disease, liver disease, connective tissue diseases, and cancer. Men exhibited higher mortality compared to women. Læs mere Tjek på PubMed6 Analyzing the molecular mechanism of Scutellaria Radix in the treatment of sepsis using RNA sequencing
BMC Infectious Diseases, 13.07.2024 Tilføjet 13.07.2024 Abstract Background Sepsis is a life-threatening organ dysfunction, which seriously threatens human health. The clinical and experimental results have confirmed that Traditional Chinese medicine (TCM), such as Scutellariae Radix, has anti-inflammatory effects. This provides a new idea for the treatment of sepsis. This study systematically analyzed the mechanism of Scutellariae Radix treatment in sepsis based on network pharmacology, RNA sequencing and molecular docking. Methods Gene expression analysis was performed using Bulk RNA sequencing on sepsis patients and healthy volunteers. After quality control of the results, the differentially expressed genes (DEGs) were analyzed. The active ingredients and targets of Scutellariae Radix were identified using The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Ontology (GO) and Protein-Protein Interaction (PPI) analysis were performed for disease-drug intersection targets. With the help of GEO database, Survival analysis and Meta-analysis was performed on the cross-targets to evaluate the prognostic value and screen the core targets. Subsequently, single-cell RNA sequencing was used to determine where the core targets are located within the cell. Finally, in this study, molecular docking experiments were performed to further clarify the interrelationship between the active components of Scutellariae Radix and the corresponding targets. Results There were 72 active ingredients of Scutellariae Radix, and 50 common targets of drug and disease. GO and PPI analysis showed that the intersection targets were mainly involved in response to chemical stress, response to oxygen levels, response to drug, regulation of immune system process. Survival analysis showed that PRKCD, EGLN1 and CFLAR were positively correlated with sepsis prognosis. Meta-analysis found that the three genes were highly expressed in sepsis survivor, while lowly in non-survivor. PRKCD was mostly found in Macrophages, while EGLN1 and CFLAR were widely expressed in immune cells. The active ingredient Apigenin regulates CFLAR expression, Baicalein regulates EGLN1 expression, and Wogonin regulates PRKCD expression. Molecular docking studies confrmed that the three active components of astragalus have good binding activities with their corresponding targets. Conclusions Apigenin, Baicalein and Wogonin, important active components of Scutellaria Radix, produce anti-sepsis effects by regulating the expression of their targets CFLAR, EGLN1 and PRKCD. Læs mere Tjek på PubMed7 One-year survival of patients admitted for sepsis to intensive care units in Colombia
BMC Infectious Diseases, 10.07.2024 Tilføjet 10.07.2024 Abstract Background Sepsis is a frequent cause of admission to intensive care units (ICUs). High mortality rates are estimated globally, and in our country, few studies have reported one-year survival. The objective of this study is to determine one-year survival in patients with sepsis admitted to the ICU in Colombia, compared with the survival of patients admitted for other conditions. Methods Retrospective cohort study using administrative databases from the Ministry of Health of Colombia. One-year survival and the adjusted hazard ratio for survival, adjusted for comorbidities included in the Charlson Index, were determined using a Cox proportional hazards model for patients admitted for other causes as well as for those admitted for sepsis. This was then compared with an inverse propensity score weighting model. Results A total of 116.407 patients were initially admitted to the ICUs, with 12.056 (10.36%) diagnosed with sepsis. Within the first year, 4.428 (36.73%) patients died due to sepsis. Age and male gender were associated with an increased risk of death from sepsis, and the covariates associated with one-year mortality were as follows: age over 80 years with HR 9.91 (95% CI: 9.22–10.65), renal disease with HR 3.16 (95% CI: 3.03–3.29), primary tumoral disease with HR 2.07 (95% CI: 1.92–2.23), liver disease with HR 2.27 (95% CI: 2.07–2.50), and metastatic solid tumor with HR 2.03 (95% CI: 1.92–2.15). Conclusion This study revealed a high one-year sepsis mortality rate in the population, associated with variables such as age over 80 years, the presence of renal disease, liver disease, connective tissue diseases, and cancer. Men exhibited higher mortality compared to women. Læs mere Tjek på PubMed8 Benefits and Harms of Procalcitonin- or C-Reactive Protein-Guided Antimicrobial Discontinuation in Critically Ill Adults With Sepsis: A Systematic Review and Network Meta-Analysis
Kubo, Kenji; Sakuraya, Masaaki; Sugimoto, Hiroshi; Takahashi, Nozomi; Kano, Ken-ichi; Yoshimura, Jumpei; Egi, Moritoki; Kondo, Yutaka Critical Care Medicine, 9.07.2024 Tilføjet 9.07.2024 Objectives: In sepsis treatment, antibiotics are crucial, but overuse risks development of antibiotic resistance. Recent guidelines recommended the use of procalcitonin to guide antibiotic cessation, but solid evidence is insufficient. Recently, concerns were raised that this strategy would increase recurrence. Additionally, optimal protocol or difference from the commonly used C-reactive protein (CRP) are uncertain. We aimed to compare the effectiveness and safety of procalcitonin- or CRP-guided antibiotic cessation strategies with standard of care in sepsis. Data Sources: A systematic search of PubMed, Embase, CENTRAL, Igaku Chuo Zasshi, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform. Study Selection: Randomized controlled trials involving adults with sepsis in intensive care. Data Extraction: A systematic review with network meta-analyses was performed. The Grading of Recommendations, Assessments, Developments, and Evaluation method was used to assess certainty. Data Synthesis: Eighteen studies involving 5023 participants were included. Procalcitonin-guided and CRP-guided strategies shortened antibiotic treatment (–1.89 days [95% CI, –2.30 to –1.47], –2.56 days [95% CI, –4.21 to –0.91]) with low- to moderate-certainty evidence. In procalcitonin-guided strategies, this benefit was consistent even in subsets with shorter baseline antimicrobial duration (7–10 d) or in Sepsis-3, and more pronounced in procalcitonin cutoff of “0.5 μg/L and 80% reduction.” No benefit was observed when monitoring frequency was less than half of the initial 10 days. Procalcitonin-guided strategies lowered mortality (–27 per 1000 participants [95% CI, –45 to –7]) and this was pronounced in Sepsis-3, but CRP-guided strategies led to no difference in mortality. Recurrence did not increase significantly with either strategy (very low to low certainty). Conclusions: In sepsis, procalcitonin- or CRP-guided antibiotic discontinuation strategies may be beneficial and safe. In particular, the usefulness of procalcitonin guidance for current Sepsis-3, where antimicrobials are used for more than 7 days, was supported. Well-designed studies are needed focusing on monitoring protocol and recurrence. Læs mere Tjek på PubMed9 Failure to Rescue as a Quality Measure in Sepsis
Journal of the American Medical Association, 8.07.2024 Tilføjet 8.07.2024 This Viewpoint discusses the limitations of current tools to improve sepsis outcomes and proposes that these tools be supplemented with “failure to rescue,” a systems-level approach for recognizing and addressing complications and managing sepsis throughout the hospitalization period. Læs mere Tjek på PubMed10 Development and external validation of machine learning-based models to predict patients with cellulitis developing sepsis during hospitalisation
Chen, X., Hu, L., Yu, R. BMJ Open, 5.07.2024 Tilføjet 5.07.2024 ObjectiveCellulitis is the most common cause of skin-related hospitalisations, and the mortality of patients with sepsis remains high. Some stratification models have been developed, but their performance in external validation has been unsatisfactory. This study was designed to develop and compare different models for predicting patients with cellulitis developing sepsis during hospitalisation. DesignThis is a retrospective cohort study. SettingThis study included both the development and the external-validation phases from two independent large cohorts internationally. Participants and methodsA total of 6695 patients with cellulitis in the Medical Information Mart for Intensive care (MIMIC)-IV database were used to develop models with different machine-learning algorithms. The best models were selected and then externally validated in 2506 patients with cellulitis from the YiduCloud database of our university. The performances and robustness of selected models were further compared in the external-validation group by area under the curve (AUC), diagnostic accuracy, sensitivity, specificity and diagnostic OR. Primary outcome measuresThe primary outcome of interest in this study was the development based on the Sepsis-3.0 criteria during hospitalisation. ResultsPatient characteristics were significantly different between the two groups. In internal validation, XGBoost was the best model, with an AUC of 0.780, and AdaBoost was the worst model, with an AUC of 0.585. In external validation, the AUC of the artificial neural network (ANN) model was the highest, 0.830, while the AUC of the logistic regression (LR) model was the lowest, 0.792. The AUC values changed less in the boosting and ANN models than in the LR model when variables were deleted. ConclusionsBoosting and neural network models performed slightly better than the LR model and were more robust in complex clinical situations. The results could provide a tool for clinicians to detect hospitalised patients with cellulitis developing sepsis early. Læs mere Tjek på PubMed11 A secondary abdominal aorta-duodenal fistula accompanied with acquired Immune Deficiency Syndrome presented with recurrent sepsis: a case report
BMC Infectious Diseases, 5.07.2024 Tilføjet 5.07.2024 Abstract Background Abdominal aorta-duodenal fistulas are rare abnormal communications between the abdominal aorta and duodenum. Secondary abdominal aorta-duodenal fistulas often result from endovascular surgery for aneurysms and can present as severe late complications. Case presentation A 50-year-old male patient underwent endovascular reconstruction for an infrarenal abdominal aortic pseudoaneurysm. Prior to the operation, he was diagnosed with Acquired Immune Deficiency Syndrome and Syphilis. Two years later, he was readmitted with lower extremity pain and fever. Blood cultures grew Enterococcus faecium, Salmonella, and Streptococcus anginosus. Sepsis was successfully treated with comprehensive anti-infective therapy. He was readmitted 6 months later, with blood cultures growing Enterococcus faecium and Escherichia coli. Although computed tomography did not show contrast agent leakage, we suspected an abdominal aorta-duodenal fistula. Esophagogastroduodenoscopy confirmed this suspicion. The patient underwent in situ abdominal aortic repair and received long-term antibiotic therapy. He remained symptom-free during a year and a half of follow-up. Conclusions This case suggests that recurrent infections with non-typhoidal Salmonella and gut bacteria may be an initial clue to secondary abdominal aorta-duodenal fistula. Læs mere Tjek på PubMed12 A secondary abdominal aorta-duodenal fistula accompanied with acquired Immune Deficiency Syndrome presented with recurrent sepsis: a case report
BMC Infectious Diseases, 4.07.2024 Tilføjet 4.07.2024 Abstract Background Abdominal aorta-duodenal fistulas are rare abnormal communications between the abdominal aorta and duodenum. Secondary abdominal aorta-duodenal fistulas often result from endovascular surgery for aneurysms and can present as severe late complications. Case presentation A 50-year-old male patient underwent endovascular reconstruction for an infrarenal abdominal aortic pseudoaneurysm. Prior to the operation, he was diagnosed with Acquired Immune Deficiency Syndrome and Syphilis. Two years later, he was readmitted with lower extremity pain and fever. Blood cultures grew Enterococcus faecium, Salmonella, and Streptococcus anginosus. Sepsis was successfully treated with comprehensive anti-infective therapy. He was readmitted 6 months later, with blood cultures growing Enterococcus faecium and Escherichia coli. Although computed tomography did not show contrast agent leakage, we suspected an abdominal aorta-duodenal fistula. Esophagogastroduodenoscopy confirmed this suspicion. The patient underwent in situ abdominal aortic repair and received long-term antibiotic therapy. He remained symptom-free during a year and a half of follow-up. Conclusions This case suggests that recurrent infections with non-typhoidal Salmonella and gut bacteria may be an initial clue to secondary abdominal aorta-duodenal fistula. Læs mere Tjek på PubMed13 Predictive value of the dynamics of absolute lymphocyte counts for 90-day mortality in ICU sepsis patients: a retrospective big data study
Chen, D., Zhou, K., Tian, R., Wang, R., Zhou, Z. BMJ Open, 3.07.2024 Tilføjet 3.07.2024 ObjectivesThe objective of the study was to assess the clinical predictive value of the dynamics of absolute lymphocyte count (ALC) for 90-day all-cause mortality in sepsis patients in intensive care unit (ICU). DesignRetrospective cohort study using big data. SettingThis study was conducted using the Medical Information Mart for Intensive Care IV database V.2.0 database. Primary and secondary outcome measuresThe primary outcome was 90-day all-cause mortality. ParticipantsPatients were included if they were diagnosed with sepsis on the first day of ICU admission. Exclusion criteria were ICU stay under 24 hours; the absence of lymphocyte count on the first day; extremely high lymphocyte count (>10x109/L); history of haematolymphatic tumours, bone marrow or solid organ transplants; survival time under 72 hours and previous ICU admissions. The analysis ultimately included 17 329 sepsis patients. ResultsThe ALC in the non-survivors group was lower on days 1, 3, 5 and 7 after admission (p Læs mere Tjek på PubMed14 Albumin Versus Balanced Crystalloid for the Early Resuscitation of Sepsis: An Open Parallel-Group Randomized Feasibility Trial. The ABC-Sepsis Trial
Gray, Alasdair J.; Oatey, Katherine; Grahamslaw, Julia; Irvine, Sîan; Cafferkey, John; Kennel, Titouan; Norrie, John; Walsh, Tim; Lone, Nazir; Horner, Daniel; Appelboam, Andy; Hall, Peter; Skipworth, Richard J. E.; Bell, Derek; Rooney, Kevin; Shankar-Hari, Manu; Corfield, Alasdair R.; on behalf of the Albumin, Balanced, and Crystalloid-Sepsis (ABC-Sepsis) Investigators Critical Care Medicine, 1.07.2024 Tilføjet 1.07.2024 Objectives: International guidelines recommend IV crystalloid as the primary fluid for sepsis resuscitation, with 5% human albumin solution (HAS) as the second line. However, it is unclear which fluid has superior clinical effectiveness. We conducted a trial to assess the feasibility of delivering a randomized controlled trial comparing balanced crystalloid against 5% HAS as sole early resuscitation fluid in patients with sepsis presenting to hospital. Design: Multicenter, open, parallel-group randomized feasibility trial. Setting: Emergency departments (EDs) in 15 U.K. National Health Service (NHS) hospitals. Patients: Adult patients with sepsis and a National Early Warning Score 2 greater than or equal to five requiring IV fluids withing one hour of randomization. Interventions: IV fluid resuscitation with balanced crystalloid or 5% HAS for the first 6 hours following randomization. Measurements and Main Results: Primary feasibility outcomes were recruitment rate and 30-day mortality. We successfully recruited 301 participants over 12 months. Mean (sd) age was 69 years (± 16 yr), and 151 (50%) were male. From 1303 participants screened; 502 participants were potentially eligible and 300 randomized to receive trial intervention with greater than 95% of participants receiving the intervention. The median number of participants per site was 19 (range, 1–63). Thirty-day mortality was 17.9% (n = 53). Thirty-one participants died (21.1%) within 30 days in the 5% HAS arm, compared with 22 participants (14.8%) in the crystalloid arm (adjusted odds ratio, 1.50; 95% CIs, 0.84–2.83). Conclusions: Our results suggest it is feasible to recruit critically ill patients to a fluid resuscitation trial in U.K. EDs using 5% HAS as a primary resuscitation fluid. There was lower mortality in the balanced crystalloid arm. Given these findings, a definitive trial is likely to be deliverable, but the point estimates suggest such a trial would be unlikely to demonstrate a significant benefit from using 5% HAS as a primary resuscitation fluid in sepsis. Læs mere Tjek på PubMed15 Understanding maternal sepsis risk factors and bacterial etiology: A case control study protocol
Kelly Thompson, Duy Pham Thanh, Jane E. Hirst, Mark Woodward, Hai Pham Thanh, Huong Tran Thi Lien, Kiet Tao Tuan, Binh Le Thanh, Evelyne Kestelyn, Thuan Dang Trong, Katie Harris, Linh Nguyen Thi My, Hien Vu Thi Minh, Tuyen Ha Thanh, Thanh Le Quang, Louise Thwaites PLoS One Infectious Diseases, 26.06.2024 Tilføjet 26.06.2024 by Kelly Thompson, Duy Pham Thanh, Jane E. Hirst, Mark Woodward, Hai Pham Thanh, Huong Tran Thi Lien, Kiet Tao Tuan, Binh Le Thanh, Evelyne Kestelyn, Thuan Dang Trong, Katie Harris, Linh Nguyen Thi My, Hien Vu Thi Minh, Tuyen Ha Thanh, Thanh Le Quang, Louise Thwaites Introduction Maternal disorders are the third leading cause of sepsis globally, accounting for 5.7 million (12%) cases in 2017. There are increasing concerns about the emergence of antimicrobial resistance (AMR) in bacteria commonly causing maternal sepsis. Our aim is to describe the protocol for a clinical and microbiology laboratory study to understand risk factors for and the bacterial etiology of maternal sepsis in a tertiary Obstetrics and Gynaecology Hospital. Methods This case-control study aims to recruit 100 cases and 200 controls at Tu Du Hospital in Ho Chi Minh City, Vietnam, which had approximately 55,000 births in 2022. Women aged ≥ 18 years and ≥ 28 weeks gestation having a singleton birth will be eligible for inclusion as cases or controls, unless they have an uncomplicated localised or chronic infection, or an infection with SARS-CoV-2. Cases will include pregnant or recently pregnant women with sepsis recognised between the onset of labour and/or time of delivery/cessation of pregnancy for up to 42 days post-partum. Sepsis will be defined as suspected or confirmed infection with an obstetrically modified Sequential Organ Failure Assessment score of ≥ 2, treatment with intravenous antimicrobials and requested cultures of any bodily fluid. Controls will be matched by age, location, parity, mode of delivery and gestational age. Primary and secondary outcomes are risk factors associated with the development of maternal sepsis, the frequency of adverse outcomes due to maternal sepsis, bacterial etiology and AMR profiles of cases and controls. Discussion This study will improve understanding of the epidemiology and clinical implications of maternal sepsis management including the presence of AMR in women giving birth in Vietnam. It will help us to determine whether women in this setting are receiving optimal care and to identify opportunities for improvement. Læs mere Tjek på PubMed16 Activation of the MAPK network provides a survival advantage during the course of COVID-19-induced sepsis: a real-world evidence analysis of a multicenter COVID-19 Sepsis Cohort
Infection, 24.06.2024 Tilføjet 24.06.2024 Abstract Purpose There is evidence that lower activity of the RAF/MEK/ERK network is associated with positive outcomes in mild and moderate courses of COVID-19. The effect of this cascade in COVID-19 sepsis is still undetermined. Therefore, we tested the hypothesis that activity of the RAF/MEK/ERK network in COVID-19-induced sepsis is associated with an impact on 30-day survival. Methods We used biomaterial from 81 prospectively recruited patients from the multicentric CovidDataNet.NRW-study cohort (German clinical trial registry: DRKS00026184) with their collected medical history, vital signs, laboratory parameters, microbiological findings and patient outcome. ERK activity was measured by evaluating ERK phosphorylation using a Proximity Ligation Assay. Results An increased ERK activity at 4 days after diagnosis of COVID-19-induced sepsis was associated with a more than threefold increased chance of survival in an adjusted Cox regression model. ERK activity was independent of other confounders such as Charlson Comorbidity Index or SOFA score (HR 0.28, 95% CI 0.10–0.84, p = 0.02). Conclusion High activity of the RAF/MEK/ERK network during the course of COVID-19 sepsis is a protective factor and may indicate recovery of the immune system. Further studies are needed to confirm these results. Læs mere Tjek på PubMed17 The causal relationship between blood cell indices and 28-day mortality in sepsis: a retrospective study and bidirectional Mendelian randomization analysis
BMC Infectious Diseases, 23.06.2024 Tilføjet 23.06.2024 Abstract Background Despite emerging evidence linking blood cell indices (BCIs) to sepsis mortality, the inconsistency of observational studies obscures the clarity of these associations. This study aims to clarify the causal influence of BCIs on 28-day mortality rates in sepsis patients. Methods Utilizing univariable and multivariable Mendelian randomization (MR) analyses, we examined the impact of BCIs on sepsis mortality by analyzing data from extensive genome-wide association studies. The inverse-variance weighted (IVW) method was our primary analytic tool, complemented by several robustness checks to mitigate pleiotropy, including weighted median, mode-based estimates, MR-Egger regression, and MR-PRESSO. Subsequently, we conducted a retrospective study to further explore the correlation between platelet indices and 28-day mortality of sepsis using real-world data. Results Our findings highlight a significant causal relationship between platelet distribution width (PDW) and 28-day mortality in sepsis, with the univariable Mendelian randomization approach yielding an odds ratio of 1.12 (95% CI, 1.06–1.26; P Læs mere Tjek på PubMed18 Determinants of puerperal sepsis among postpartum women: a case-control study in East Shoa Zone public hospitals, Central Ethiopia
Oyato, B. T., Debele, T., Edosa, D., Abasimel, H. Z., Awol, M., Kebede, E. T., Gezahagn, A., Desta, A. A., Alemu, F. T., Asfaw, S. B. BMJ Open, 22.06.2024 Tilføjet 22.06.2024 ObjectiveTo identify determinants of puerperal sepsis among postpartum women attending East Shoa Zone public hospitals, Central Ethiopia, 2023. Design and settingAn institutional-based, unmatched case–control study was conducted from 19 June 2023 to 4 September 2023, in East Shoa Zone public hospitals. Participants495 postpartum women (100 cases and 395 controls) were selected using systematic sampling techniques. Data were collected through face-to-face interviews and from medical charts using a pretested, structured questionnaire. The AOR with its corresponding 95% CI was used to identify determinant variables. Findings were presented in texts and tables. Outcome measuresThe medical charts of participants were reviewed to identify those who had developed puerperal sepsis. ResultsAnaemia (AOR 6.05; 95% CI 2.57 to 14.26), undernourishment (AOR 4.43; 95% CI 1.96 to 10.01), gestational diabetes mellitus (AOR 3.26; 95% CI 1.22 to 8.74), postpartum haemorrhage (AOR 3.17; 95% CI 1.28 to 7.87), obstructed labour (AOR 2.76; 95% CI 1.17 to 6.52), multiparity (AOR 2.54; 95% CI 1.17 to 5.50), placenta previa (AOR 2.27; 95% CI 1.11 to 4.67) and vaginal examination ≥5 times (AOR 2.19; 95% CI 1.05 to 4.54) were the independent determinants of puerperal sepsis in this study. ConclusionThis study found that gestational diabetes mellitus, anaemia, undernourishment, placenta previa, obstructed labour, postpartum haemorrhage and five or more per-vaginal examinations during labour were the determinants of puerperal sepsis. Therefore, it is recommended that obstetric care providers strictly adhere to guidelines on the number of vaginal exams that should be performed throughout labour and that they perform these exams using the appropriate infection-prevention techniques. In addition, they should provide comprehensive health education on nutrition during pregnancy and postnatal periods and the importance of iron supplements. Læs mere Tjek på PubMed19 Activation of the MAPK network provides a survival advantage during the course of COVID-19-induced sepsis: a real-world evidence analysis of a multicenter COVID-19 Sepsis Cohort
Infection, 20.06.2024 Tilføjet 20.06.2024 Abstract Purpose There is evidence that lower activity of the RAF/MEK/ERK network is associated with positive outcomes in mild and moderate courses of COVID-19. The effect of this cascade in COVID-19 sepsis is still undetermined. Therefore, we tested the hypothesis that activity of the RAF/MEK/ERK network in COVID-19-induced sepsis is associated with an impact on 30-day survival. Methods We used biomaterial from 81 prospectively recruited patients from the multicentric CovidDataNet.NRW-study cohort (German clinical trial registry: DRKS00026184) with their collected medical history, vital signs, laboratory parameters, microbiological findings and patient outcome. ERK activity was measured by evaluating ERK phosphorylation using a Proximity Ligation Assay. Results An increased ERK activity at 4 days after diagnosis of COVID-19-induced sepsis was associated with a more than threefold increased chance of survival in an adjusted Cox regression model. ERK activity was independent of other confounders such as Charlson Comorbidity Index or SOFA score (HR 0.28, 95% CI 0.10–0.84, p = 0.02). Conclusion High activity of the RAF/MEK/ERK network during the course of COVID-19 sepsis is a protective factor and may indicate recovery of the immune system. Further studies are needed to confirm these results. Læs mere Tjek på PubMed20 Sepsis caused by Phytobacter diazotrophicus complicated with galactosemia type 1 in China: a case report
BMC Infectious Diseases, 20.06.2024 Tilføjet 20.06.2024 Abstract Background Phytobacter diazotrophicus (P. diazotrophicus) is an opportunistic pathogen that causes nosocomial outbreaks and sepsis. However, there are no reports of P. diazotrophicus isolated from human blood in China. Case presentation A 27-day-old female infant was admitted to our hospital with fever and high bilirubin levels. The clinical features included jaundice, abnormal coagulation, cholestasis, fever, convulsions, weak muscle tension, sucking weakness, ascites, abnormal tyrosine metabolism, cerebral oedema, abnormal liver function, clavicle fracture, and haemolytic anaemia. The strain isolated from the patient’s blood was identified as P. diazotrophicus by whole-genome sequencing (WGS). Galactosemia type 1 (GALAC1) was diagnosed using whole-exome sequencing (WES). Based on drug sensitivity results, 10 days of anti-infective treatment with meropenem combined with lactose-free milk powder improved symptoms. Conclusion P. diazotrophicus was successfully identified in a patient with neonatal sepsis combined with galactosemia. Galactosemia may be an important factor in neonatal sepsis. This case further expands our understanding of the clinical characteristics of GALAC1. Læs mere Tjek på PubMed |
Ph.d. forsvar ved Andreas Arnholdt Pedersen
Emil Aarestrup auditorium, Odense Universityhospital (og online)
Torsdag d. 8. august
Ph.d. forsvar ved Nichlas Hovmand
Fredag d. 23. august
Medical Artificial Intelligence Toolbox (MAIT) seminar 2024
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Onsdag d. 28. august
Nordic Society of Clinical Microbiology and Infectious Diseases (NSCMID) annual meeting 2024
Oslo, Norge
Torsdag d. 29. august
European Respiratory Society (ERS) Congress 2024
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Lørdag d. 7. september
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BMJ Open
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Udvalgt og kommenteret af Professor Lars Østergaard
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Udvalgt og kommenteret af Professor Niels Obel
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