• Catabolism
• Critically ill
• Endogenous substrate production
• Energy expenditure
• Rehabilitation phase
• Study design

• Humans
• Critical Illness/therapy
• Critical Care/methods
• Nutrition Therapy/methods
• Malnutrition/prevention & control
• Nutritional Support
• Energy Metabolism
• Energy Intake
• Nutritional Status

• Antibiotics
• Cost-effectiveness analysis
• Intensive care software
• Model-informed precision dosing
• Sepsis
• Septic shock

• ZonMW GGG 836041018 ZonMw

• Humans
• Male
• Female
• Child
• Child, Preschool
• Infant
• Adolescent
• Retrospective Studies
• Hospitalization/economics
• Hospitalization/statistics & numerical data
• Health Care Costs/statistics & numerical data
• Multiple Organ Failure/economics
• Multiple Organ Failure/therapy
• Multiple Organ Failure/epidemiology
• Infant, Newborn
• Patient Acceptance of Health Care/statistics & numerical data
• Health Resources/statistics & numerical data
• Health Resources/economics
• Emergency Service, Hospital/statistics & numerical data
• Emergency Service, Hospital/economics

• adult cardiac surgery
• mechanical circulatory support
• mortality
• multiorgan failure

• Humans
• Cardiac Surgical Procedures/trends
• Cardiac Surgical Procedures/mortality
• Male
• Retrospective Studies
• Female
• United States/epidemiology
• Middle Aged
• Aged
• Multiple Organ Failure/epidemiology
• Multiple Organ Failure/mortality
• Adult
• Postoperative Complications/epidemiology
• Hospital Mortality/trends
• Risk Factors
• Cohort Studies

• critical illness
• patient discharge
• hospital-to-home transition
• mental health
• cognition
• cardiovascular diseases
• intensive care units

• Humans
• Patient Discharge
• Critical Illness/psychology
• Intensive Care Units
• Critical Care/methods
• Survivors/psychology

• Mendelian randomization
• body mass index
• obesity
• sepsis
• waist circumstance

• Humans
• Genome-Wide Association Study
• Mendelian Randomization Analysis
• Obesity/complications
• Obesity/epidemiology
• Obesity/genetics
• Polymorphism, Single Nucleotide
• Reproducibility of Results
• Sepsis/epidemiology
• Sepsis/genetics

Early rehabilitation allows patients to better perform the activities of daily living after hospital discharge. A specialized physical therapist has been assigned as part of the early rehabilitation, but the effectiveness of the program remains unclear. We investigated how early rehabilitation provided by a specialized physical therapist affects ADL in patients with sepsis.

This was a retrospective cohort study. This study’s subjects were sepsis patients who entered the advanced emergency critical care center of Shinshu University Hospital between April 2014 and March 2020. Electronic medical records were reviewed to obtain information on demographic characteristics, severity score, primary source of infection, therapeutic medication, the number of days after hospital admittance until rehabilitation begins, length of hospital stay, discharge to home, and an assessment of daily living activities for each patient. The patients were divided into two groups based on whether they were treated before or after a specialized physical therapist had been hired by the advanced emergency critical care center.

Assigning a physical therapist to a patient significantly shortened the number of days until rehabilitation began. In a multivariable model, the strongest predictors of return to independent living after hospital discharge were (1) assigning a specialized physical therapist (odds ratio = 2.40; 95% confidence interval = 1.09–5.79; P = 0.050) and (2) the number of days until rehabilitation started (odds ratio = 0.24; 95% confidence interval = 0.08–0.76; P = 0.014).

Assigning a specialized physical therapist to sepsis patients at an advanced emergency critical care center significantly shortened the number of days until a patient can begin rehabilitation after hospital admittance and improved activities of daily living after hospital discharge.

Trial registration [University Hospital Medical Information Network Clinical Trials Registry, number UMIN000040570 (2020/5/28).]

• Activities of Daily Living
• Humans
• Patient Discharge
• Physical Therapists
• Retrospective Studies
• Sepsis/therapy

• Japan Society for the Promotion of Science

Background: Survivors of sepsis often face long-term sequelae after intensive care treatment. Compared to the period of hospitalization, little is known about the ambulatory healthcare utilization in sepsis patients. The study evaluated healthcare utilization and associated costs of sepsis care including allied health professions after initial hospitalization. Methods: Secondary analysis was performed on data in 210 sepsis patients prospectively enrolled from nine intensive care study centers across Germany. Data was collected via structured surveys among their Primary care (Family-) physicians (PCPs) within the first month after discharge from ICU (baseline) and again at 6, 12 and 24 months after discharge, each relating to the period following the last survey. Costs were assessed by standardized cost unit rates from a health care system’s perspective. Changes in healthcare utilization and costs over time were calculated using the Wilcoxon rank-sum test. Results: Of the 210 patients enrolled, 146 (69.5%) patients completed the 24 months follow-up. In total, 109 patients were hospitalized within the first 6 months post-intensive care. Mean total direct costs per patient at 0–6 months were €17,531 (median: €6047), at 7–12 months €9029 (median: €3312), and at 13–24 months €18,703 (median: €12,828). The largest contributor to the total direct costs within the first 6 months was re-hospitalizations (€13,787 (median: €2965). After this first half year, we observed a significant decline in inpatient care costs for re-hospitalizations (p ≤ 0.001). PCPs were visited by more than 95% of patients over 24 months. Conclusions: Sepsis survivors have high health care utilization. Hospital readmissions are frequent and costly. Highest costs and hospitalizations were observed in more than half of patients within the first six months post-intensive care. Among all outpatient care providers, PCPs were consulted most frequently. Clinical impact: Sepsis survivors have a high healthcare utilization and related costs which persist after discharge from hospital. Within outpatient care, possible needs of sepsis survivors as physiotherapy or psychotherapy seem not to be met appropriately. Development of sepsis aftercare programs for early detection and treatment of complications should be prioritized.

• aftercare
• critical illness
• health care costs
• post-intensive care syndrome (PICS)
• primary care
• sepsis

• Cox proportion hazard model
• Nomogram
• Sepsis
• Survival

• Critical illness
• Frailty
• Geriatric rehabilitation
• ICU weakness
• Nutrition

• Germany/epidemiology
• Hospital Mortality
• Humans
• Intensive Care Units
• Retrospective Studies
• Sepsis
• Shock, Septic

• Cranial
• Elective Surgery
• Morbidity
• Outcomes
• Sepsis
• Spine

• Critical Care/economics
• Health Expenditures/statistics & numerical data
• Hospital Costs/statistics & numerical data
• Hospitalization/economics
• Humans
• Length of Stay/economics
• Longitudinal Studies
• Retrospective Studies
• Sepsis/economics
• Severity of Illness Index
• Taiwan

• Animals
• Male
• Mice
• Behavior, Animal
• Blood-Brain Barrier/metabolism
• Cognition Disorders/prevention & control
• Disease Models, Animal
• Gliosis/therapy
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/metabolism
• Prospective Studies
• Sepsis/therapy

• bacterial infection
• blood
• cytokines
• innate immunity
• phagocytes
• phagocytosis
• prothrombin

Patients with severe infections and especially sepsis have a high in-hospital mortality, but even hospital survivors face long-term sequelae, decreased health-related quality of life, and high risk of death, suggesting a great need for specialized aftercare. However, data regarding a potential benefit of post-discharge rehabilitation in these patients are scarce. In this retrospective matched cohort study the claim data of a large German statutory health care insurer was analyzed. 83,974 hospital survivors having suffered from septic shock, sepsis, and severe infections within the years 2009–2016 were identified using an ICD abstraction strategy closely matched to the current Sepsis-3 definition. Cases were analyzed and compared with their matched pairs to determine their 5-year mortality and the impact of post-discharge rehabilitation. Five years after hospital discharge, mortality of initial hospital survivors were still increased after septic shock (HR_adj 2.03, 95%-CI 1.87 to 2.19; P<0.001), sepsis (HR_adj 1.73, 95%-CI 1.71 to 1.76; P<0.001), and also in survivors of severe infections without organ dysfunction (HR_adj 1.70, 95%-CI 1.65 to 1.74; P<0.001) compared to matched controls without infectious diseases. Strikingly, patients treated in rehabilitation facilities showed a significantly improved 5-year survival after suffering from sepsis or septic shock (HR_adj 0.81, 95%-CI 0.77 to 0.85; P<0.001) as well as severe infections without organ dysfunction (HR_adj 0.81, 95%-CI 0.73 to 0.90; P<0.001) compared to matched patients discharged to home or self-care. Long-term mortality and morbidity of hospital survivors are markedly increased after septic shock, sepsis and severe infections without organ dysfunction, but best 5-year survival was recorded in patients discharged to a rehabilitation facility in all three groups. Thus, our data suggest that specialized aftercare programs may help to improve long-term outcome in these patients and warrants more vigilance in future investigations.

• Aftercare/methods
• Aged
• Communicable Diseases/mortality
• Female
• Hospital Mortality
• Hospitals/statistics & numerical data
• Humans
• Male
• Patient Discharge/statistics & numerical data
• Quality of Life
• Retrospective Studies
• Sepsis/mortality
• Shock, Septic/mortality
• Survivors/statistics & numerical data

• Post-sepsis myocardial infarction
• Post-sepsis stroke
• Survival analysis

• Aged
• Aged, 80 and over
• Cardiovascular Diseases/epidemiology
• Cardiovascular Diseases/etiology
• Cardiovascular Diseases/mortality
• Female
• Humans
• Male
• Middle Aged
• Proportional Hazards Models
• Risk Factors
• Sepsis/complications
• Sepsis/epidemiology
• Sepsis/mortality
• Statistics, Nonparametric
• Survivors/statistics & numerical data
• Taiwan/epidemiology

• NSC 102-2314-B-002 -131 -MY3 Taiwan National Science Foundation Grant
• MOST 104-2314-B-002 -039 -MY3 Taiwan National Ministry of Science and Technology Grants
• MOST 105-2811-B-002-031 Taiwan National Ministry of Science and Technology Grants
• Taiwan National Science Foundation Grant
• Taiwan National Ministry of Science and Technology Grants

Introduction

Mortality from sepsis is decreasing in recent years owing to improved quality of care, targeted programs, and the implementation of sepsis bundles. This has led to an increased pool of sepsis survivors at risk of readmissions. Studies have shown that these sepsis readmissions are common and expensive. The factors associated with these readmissions remain elusive and have incited a lot of research in recent years. The 30-day sepsis readmission rate is increasingly being used as a quality metric for hospitals. A conducted a retrospective chart review analysis of patients admitted with sepsis to find factors affecting the 30-day readmissions of sepsis survivors.

Methods

Patients admitted to our hospital either on the medical-surgical floor or in the intensive care unit (ICU) with an administrative coding for sepsis between January 2014 to November 2015 were identified. A literature search, as well as expert opinion, was considered for the list of factors to be studied, including age, sex, residence on admission, length of stay, getting hemodialysis, hospitalization in the prior year, presence of acute kidney injury (AKI), source of sepsis, discharge disposition, receipt of red blood cell (RBC) products, and route of antibiotics on discharge. A univariate binary logistic regression analysis was performed to test the association between the above-mentioned variables and sepsis readmission. Variables with statistical significance in the univariate analysis were used to compute the multivariate regression analysis along, with adjusted OR and their 95% CI.

Results

A total of 1297 patients were identified with sepsis. Of these, 1068 patients met inclusion criteria. The readmission rate in our study population was 19.19%, and 52% of the readmissions were secondary to an infectious cause. After controlling for the effect of all the potential confounders, the factors that showed a positive association with readmissions were hospitalizations in the year prior to the index hospitalization and discharge to either nursing home or short-term rehab. The requirement of the intensive care unit was not associated with increased readmission. High hemoglobin on discharge was associated with a reduced chance of readmission.

Conclusions

Readmissions after sepsis hospitalization are common and mostly caused by infections. Several factors associated with index sepsis hospitalization can be associated with readmissions. Some of these factors are modifiable and more research is needed to see if these readmissions can be prevented.

• 30 day readmission
• predictors of readmission
• sepsis

Alpha-lipoic acid (ALA) reportedly has protective effects against sepsis, which is a leading cause of mortality worldwide and is associated with multiple organ dysfunction. The present study aimed to investigate further the possible action mechanisms of ALA. Male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP) in order to establish a sepsis model. The rats received an oral gavage of 200 mg/kg ALA or saline immediately after surgery. The heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximum rising and lowering rates of left ventricular pressure (±dp/dt) were examined for assessing the cardiac function. Blood urea nitrogen (BUN) and serum creatinine levels were assessed for evaluating renal function. Neutrophil gelatinase-associated lipocalin (NAGL) was examined for reflecting acute renal injury. Histopathological alterations of the small intestine were examined by hematoxylin-eosin staining. The ultrastructure of the small intestine and kidney was observed under electron microscopy. The levels of autophagy- and inflammation-associated proteins were determined via western blot analysis. The binding of nuclear factor-kappa B (NF-κB) to DNA was tested via an electrophoretic mobility shift assay. Cell apoptosis was examined using TUNEL staining. ALA treatment improved the survival rate, restored the loss of body weight and pro-inflammatory cytokines production in the serum of CLP-induced septic rats. ALA improved the cardiac and renal functions, downregulated the expression levels of interleukin-1β, tumor necrosis factor-α, and inducible nitric oxide synthase in the myocardium and small intestine of septic rats. ALA treatment also inactivated the NF-κB signaling pathway in the small intestine. An examination of autophagy showed that ALA increased the LC3II/I ratio, upregulated Atg5, Atg7, and beclin-1 and downregulated p62 protein levels in the myocardium, kidney, and small intestine of septic rats, and further promoted autophagosome accumulation in the kidney and small intestine. In addition, ALA could also reduce cell apoptosis in myocardium, kidney and small intestine tissues. These effects can be completely or party inhibited by 3-MA. Our findings suggest that autophagy enhancing may contribute to the organ protective effect of ALA in septic rats.

• alpha-lipoic acid
• autophagy
• inflammation
• rats
• sepsis

• epidemiology
• sepsis
• septic shock
• severe sepsis
• taiwan

• Adolescent
• Adult
• Aged
• Female
• Hospitalization/statistics & numerical data
• Humans
• Incidence
• Male
• Medical Records
• Mortality
• Respiratory Insufficiency/epidemiology
• Respiratory Insufficiency/mortality
• Retrospective Studies
• Sepsis/epidemiology
• Sepsis/mortality
• Severity of Illness Index
• Taiwan/epidemiology

• Emergency Service, Hospital/statistics & numerical data
• Hospital Mortality
• Humans
• Intensive Care Units/statistics & numerical data
• Multiple Organ Failure/etiology
• Multiple Organ Failure/pathology
• Prognosis
• Sepsis/complications
• Sepsis/pathology

• This study was funded by grant Fundamental Research Grant Scheme (FRGS/1/2014/SKK01/UKM/03/3), Prototype Research Grant Scheme (PRGS/1/2017/STG05/UKM/03/1) from the Ministry of Higher Education, Malaysia and Fundamental Fund, FF-2018-015 from Faculty of Medicine, Universiti Kebangsaan Malaysia.

• fli-1
• pericytes
• sepsis
• vascular leak

• Animals
• Cecum
• Cells, Cultured
• Disease Models, Animal
• Gene Expression Regulation
• Inflammation/metabolism
• Ligation
• Lipopolysaccharides
• Lung/cytology
• Mice
• Mice, Knockout
• Pericytes/physiology
• Proto-Oncogene Protein c-fli-1/metabolism
• Pyroptosis
• Sepsis/immunology
• Sepsis/metabolism
• Up-Regulation

• R01 GM130653 NIGMS NIH HHS
• R01 GM113995 NIGMS NIH HHS
• K23 HL135263 NHLBI NIH HHS
• R01 HL133751 NHLBI NIH HHS
• UL1 TR001450 NCATS NIH HHS

• cost
• incidence
• mortality
• postsepsis syndrome
• severe sepsis

• Cancer
• Emergency Department

• Calories
• Enteral nutrition
• Lean body mass
• Lipids
• Parenteral nutrition
• Protein

Increase in mortality and in recurrent infections in the year following ICU discharge continues in survivors of septic shock, even after total clinical recovery from the initial septic event and its complications. This supports the hypothesis that sepsis could induce persistent long-term immune dysfunctions. To date, there is almost no data on ICU discharge and long-term evolution of sepsis-induced immunosuppression in septic shock survivors. The aim of this study was to assess the persistence of sepsis-induced immunosuppression by measuring expression of human leukocyte antigen DR on monocytes (mHLA-DR), CD4+ T cells, and regulatory T cells (Treg) at ICU discharge and 6 months after ICU discharge in patients admitted to the ICU for septic shock.

In this prospective observational study, septic shock survivors with no preexisting immune suppression or treatment interfering with the immune system were included. mHLA-DR, CD4+ T cells, and Treg expression were assessed on day 1–2, 3–4, and 6–8 after ICU admission, at ICU discharge, and 6 months after ICU discharge.

A total of 40 patients were enrolled during their ICU stay: 21 males (52.5%) and 19 females, median age 68 years (IQR 58–77), median SOFA score on day 1–2 was 8 (IQR 7–9), and median ICU length of stay was 11 days (IQR 7–24). Among these 40 patients, 33 were studied at ICU discharge and 15 were disposed for blood sampling 6 months after ICU discharge. On day 1–2, mHLA-DR expression was abnormally low for all patients [median 4212 (IQR 2640–6047) AB/C] and remained abnormally low at ICU discharge for 75% of them [median 10,281 (IQR 7719–13,035) AB/C]. On day 3–4, 46% of patients presented CD4+ lymphopenia [median 515 (IQR 343–724) mm⁻³] versus 34% at ICU discharge [median 642 (IQR 459–846) mm⁻³]. Among patients with a 6-month blood sample, normal values of mHLA-DR were found for all patients [median 32,616 (IQR 24,918–38,738) AB/C] except for one and only another one presented CD4+ lymphopenia.

While immune alterations persist at ICU discharge, there is, at cellular level, no persistent immune alterations among septic shock survivors analyzed 6 months after ICU discharge.

• CD4+ T cells
• HLA-DR
• Immune system
• Immunology
• Immunosuppression
• Regulatory T cells
• Sepsis

• catalase
• coenzyme Q10
• electron transport chain
• glutathione
• methylmalonic acid
• methylmalonic acidemia
• mitochondria
• nitric oxide synthase
• nitrosative stress
• oxidative stress
• peroxisome
• phenylketonuria
• reactive nitrogen species
• reactive oxygen species
• sepsis
• superoxide dismutase

• Autophagy
• DADLE
• Myocardial injury
• Sepsis

Nutrition guidelines recommendations differ on the use of parenteral nutrition (PN), and existing clinical trial data are inconclusive. Our recent observational data show that amounts of energy/protein received early in the intensive care unit (ICU) affect patient mortality, particularly for inadequate nutrition intake in patients with body mass indices (BMIs) of <25 or >35. Thus, we hypothesized increased nutrition delivery via supplemental PN (SPN) + enteral nutrition (EN) to underweight and obese ICU patients would improve 60-day survival and quality of life (QoL) versus usual care (EN alone).

In this multicenter, randomized, controlled pilot trial completed in 11 centers across four countries, adult ICU patients with acute respiratory failure expected to require mechanical ventilation for >72 hours and with a BMI of <25 or ≥35 were randomized to receive EN alone or SPN + EN to reach 100% of their prescribed nutrition goal for 7 days after randomization. The primary aim of this pilot trial was to achieve a 30% improvement in nutrition delivery.

In total, 125 patients were enrolled. Over the first 7 post-randomization ICU days, patients in the SPN + EN arm had a 26% increase in delivered calories and protein, whereas patients in the EN-alone arm had a 22% increase (both p < 0.001). Surgical ICU patients received poorer EN nutrition delivery and had a significantly greater increase in calorie and protein delivery when receiving SPN versus medical ICU patients. SPN proved feasible to deliver with our prescribed protocol. In this pilot trial, no significant outcome differences were observed between groups, including no difference in infection risk. Potential, although statistically insignificant, trends of reduced hospital mortality and improved discharge functional outcomes and QoL outcomes in the SPN + EN group versus the EN-alone group were observed.

Provision of SPN + EN significantly increased calorie/protein delivery over the first week of ICU residence versus EN alone. This was achieved with no increased infection risk. Given feasibility and consistent encouraging trends in hospital mortality, QoL, and functional endpoints, a full-scale trial of SPN powered to assess these clinical outcome endpoints in high-nutritional-risk ICU patients is indicated—potentially focusing on the more poorly EN-fed surgical ICU setting.

NCT01206166

The online version of this article (doi:10.1186/s13054-017-1736-8) contains supplementary material, which is available to authorized users.

• Calorie delivery
• Critical care
• Intensive care
• Malnutrition
• Parenteral Nutrition
• Protein
• Quality of life

Our aim in the present study was to assess the mortality impact of hospital-acquired post-operative sepsis up to 1 year after hospital discharge among adult non-short-stay elective surgical patients.

We conducted a population-based, retrospective cohort study of all elective surgical patients admitted to 82 public acute hospitals between 1 January 2007 and 31 December 2012 in New South Wales, Australia. All adult elective surgical admission patients who stayed in hospital for ≥4 days and survived to discharge after post-operative sepsis were identified using the Admitted Patient Data Collection records linked with the Registry of Births, Deaths, and Marriages. We assessed post-discharge mortality rates at 30 days, 60 days, 90 days and 1 year and compared them with those of patients without post-operative sepsis.

We studied 144,503 survivors to discharge. Of these, 1857 (1.3%) had experienced post-operative sepsis. Their post-discharge mortality rates at 30 days, 60 days, 90 days and 1 year were 4.6%, 6.7%, 8.1% and 13.5% (vs 0.7%, 1.2%, 1.5% and 3.8% in the non-sepsis cohort), respectively (P < 0.0001 for all). After adjustment for patient and hospital characteristics, post-operative sepsis remained independently associated with a higher mortality risk (30-day mortality HR 2.75, 95% CI 2.14–3.53; 60-day mortality HR 2.45, 95% CI 1.94–3.10; 90-day mortality HR 2.31, 95% CI 1.85–2.87; 1-year mortality HR 1.71, 95% CI 1.46–2.00). Being older than 75 years of age (HR 3.50, 95% CI 1.56–7.87) and presence of severe/very severe co-morbidities as defined by Charlson co-morbidity index (severe vs normal HR 2.05, 95% CI 1.45–2.89; very severe vs normal HR 2.17, 95% CI 1.49–3.17) were the only other significant independent predictors of increased 1-year mortality.

Among elective surgical patients, post-operative sepsis is independently associated with increased post-discharge mortality up to 1 year after hospital discharge. This risk is particularly high in the first month, in older age patients and in the presence of severe/very severe co-morbidities. This high-risk population can be targeted for interventions.

The online version of this article (doi:10.1186/s13054-016-1596-7) contains supplementary material, which is available to authorized users.

In addition to acute hospital mortality, sepsis is associated with higher risk of death following hospital discharge. We assessed the strength of epidemiological evidence supporting a causal link between sepsis and mortality after hospital discharge by systematically evaluating the available literature for strength of association, bias, and techniques to address confounding.

We searched Medline and Embase using the following ‘mp’ terms, MESH headings and combinations thereof - sepsis, septic shock, septicemia, outcome. Studies published since 1992 where one-year post-acute mortality in adult survivors of acute sepsis could be calculated were included. Two authors independently selected studies and extracted data using predefined criteria and data extraction forms to assess risk of bias, confounding, and causality. The difference in proportion between cumulative one-year mortality and acute mortality was defined as post-acute mortality. Meta-analysis was done by sepsis definition categories with post-acute mortality as the primary outcome.

The literature search identified 11,156 records, of which 59 studies met our inclusion criteria and 43 studies reported post-acute mortality. In patients who survived an index sepsis admission, the post-acute mortality was 16.1 % (95 % CI 14.1, 18.1 %) with significant heterogeneity (p < 0.001), on random effects meta-analysis. In studies reporting non-sepsis control arm comparisons, sepsis was not consistently associated with a higher hazard ratio for post-acute mortality. The additional hazard associated with sepsis was greatest when compared to the general population. Older age, male sex, and presence of comorbidities were commonly reported independent predictors of post-acute mortality in sepsis survivors, challenging the causality relationship. Sensitivity analyses for post-acute mortality were consistent with primary analysis.

Epidemiologic criteria for a causal relationship between sepsis and post-acute mortality were not consistently observed. Additional epidemiologic studies with recent patient level data that address the pre-illness trajectory, confounding, and varying control groups are needed to estimate sepsis-attributable additional risk and modifiable risk factors to design interventional trials.

The online version of this article (doi:10.1186/s13054-016-1276-7) contains supplementary material, which is available to authorized users.

• Bias
• Causality
• Confounding factors (epidemiology)
• Mortality
• Sepsis

Long-lasting impairment of the immune system is believed to be the underlying reason for delayed deaths after surviving sepsis. We tested the hypothesis of persisting changes to the immune system in survivors of sepsis for the first time.

In our prospective, cross-sectional pilot study, eight former patients who survived catecholamine-dependent sepsis and eight control individuals matched for age, sex, diabetes and renal insufficiency were enrolled. Each participant completed a questionnaire concerning morbidities, medications and infection history. Peripheral blood was collected for determination of i) immune cell subsets (CD4⁺, CD8⁺ T cells; CD25⁺ CD127^- regulatory T cells; CD14⁺ monocytes), ii) cell surface receptor expression (PD-1, BTLA, TLR2, TLR4, TLR5, Dectin-1, PD-1 L), iii) HLA-DR expression, and iv) cytokine secretion (IL-6, IL10, TNF-α, IFN-γ) of whole blood stimulated with either α-CD3/28, LPS or zymosan.

After surviving sepsis, former patients presented with increased numbers of clinical apparent infections, including those typically associated with an impaired immune system. Standard inflammatory markers indicated a low-level inflammatory situation in former sepsis patients. CD8⁺ cell surface receptor as well as monocytic HLA-DR density measurements showed no major differences between the groups, while CD4⁺ T cells tended towards two opposed mechanisms of negative immune cell regulation via PD-1 and BTLA. Moreover, the post-sepsis group showed alterations in monocyte surface expression of distinct pattern recognition receptors; most pronouncedly seen in a decrease of TLR5 expression. Cytokine secretion in response to important activators of both the innate (LPS, zymosan) and the adaptive immune system (α-CD3/28) seemed to be weakened in former septic patients.

Cytokine secretion as a reaction to different activators of the immune system seemed to be comprehensively impaired in survivors of sepsis. Among others, this could be based on trends in the downregulation of distinct cell surface receptors. Based on our results, the conduct of larger validation studies seems feasible, aiming to characterize alterations and to find potential therapeutic targets to engage.

• Immune system
• Immunocompromised
• Immunology
• Sepsis

• Administrative Data
• Diagnosis Validation
• International Classification of Disease
• Patient Care/Classification
• Sepsis

• Aged
• Algorithms
• Canada
• Clinical Coding/standards
• Databases, Factual
• Female
• Hospitalization
• Humans
• Intensive Care Units/organization & administration
• International Classification of Diseases
• Male
• Medical Records/standards
• Middle Aged
• Patient Discharge
• Sensitivity and Specificity
• Sepsis/diagnosis
• Severity of Illness Index
• Tertiary Care Centers

• Canadian Institutes of Health Research