Chronic Lung Allograft Dysfunction (CLAD), manifesting as Bronchiolitis Obliterans Syndrome (BOS) or Restrictive Allograft Syndrome (RAS), is the main reason for adverse long-term outcome after Lung ...Transplantation (LTX). Until now, no specific biomarkers exist to differentiate between CLAD phenotypes. Therefore, we sought to find suitable cytokines to distinguish between BOS, RAS and Azithromycin Responsive Allograft Dysfunction (ARAD); and reveal potential similarities or differences to end-stage fibrotic diseases. We observed significantly increased Lipocalin-2 serum concentrations in RAS compared to BOS patients. In addition, in RAS patients immunohistochemistry revealed Lipocalin-2 expression in bronchial epithelium and alveolar walls. Patients with ARAD showed significantly lower Activin-A serum concentrations compared to Stable-LTX and BOS patients. Further, increased serum concentrations of Lipocalin-2 and Activin-A were predictors of worse freedom-from-CLAD in Stable-LTX patients. These biomarkers serve as promising serum biomarkers for CLAD prediction and seem suitable for implementation in clinical practice.
ICU (intensive care unit) patients are exposed to nutritional risks such as swallowing problems and delayed gastric emptying. A previous ICU stay may affect nutritional support upon transfer to the ...ward. The aim was to study the use of enteral (EN), parenteral nutrition (PN), and oral nutritional supplements (ONS) in ward patients with and without a previous ICU stay, also referred to as post- and non-ICU patients. In total, 136,667 adult patients from the nutritionDay audit 2010–2019 were included. A previous ICU stay was defined as an ICU stay during the current hospitalisation before nutritionDay. About 10% of all patients were post-ICU patients. Post-ICU patients were more frequently exposed to risk factors such as a BMI < 18.5 kg/m2, weight loss, decreased mobility, fair or poor health status, less eating and a longer hospital length of stay before nDay. Two main results were shown. First, both post- and non-ICU patients were inadequately fed: About two thirds of patients eating less than half a meal did not receive EN, PN, or ONS. Second, post-ICU patients had a 1.3 to 2.0 higher chance to receive EN, PN, or ONS compared to non-ICU patients in multivariable models, accounting for sex, age, BMI, weight change, mobility, health status, amount eaten on nutritionDay, hospital length of stay, and surgical status. Based on these results, two future goals are suggested to improve nutritional support on the ward: first, insufficient eating should trigger nutritional therapy in both post- and non-ICU patients; second, medical caregivers should not neglect nutritional support in non-ICU patients.
•sST2, HSP and hsCRP in plasma are increased in chronic stable heart failure patients.•sST2, HSP27 and hsCRP are associated with worse outcome in chronic heart failure.•sST2, HSP27 and hsCRP are not ...associated with LVEF, kidney function and smoking.
The inflammatory markers sST2, HSP27 and hsCRP have already been identified as prognostic markers in chronic heart failure (HF). Though individual biomarkers have proven their value in mortality risk prediction, the role of a multimarker strategy needs further evaluation.
This is an exploratory reanalysis in chronic HF patients. Plasma HSP27, sST2 and hsCRP in outpatients with chronic HF were analysed. Patients were followed for a minimum of twelve months for the endpoint cardiovascular mortality and unplanned HF associated hospitalisation (=event). 15 year overall mortality was assessed retrospectively. The prognostic impact was assessed using a Cox proportional hazard model.
113 chronic HF patients were included. Median follow up time was 614 days and 37 patients (32.7%) experienced an event. A Kaplan-Meier analysis revealed that patients with increased sST2, HSP27 and hsCRP levels have significantly worse prognosis (p < 0.001). The use of a three-biomarker combination was superior in an independent risk prediction of an event (one high vs. two high: HR = 4.5, 95% CI: 1.3–15.5, p = 0.018; and one high vs. all high: HR = 9.8, 95% CI: 2.8–34.3, p < 0.001) as shown in a multivariable cox proportional hazard model. However, the biomarker panel did not predict 15 year overall mortality, in contrast to elevated HSP27 levels (p = 0.012).
The combination of all three markers is an independent predictor of cardiovascular death and unplanned HF associated hospitalisation but not overall mortality. Our findings suggest that adding those markers in combination to well established risk assessment parameters may improve risk stratification.
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Data on anesthetic proceedings during cardiac implantable electronic device (CIED) implant procedures are scarce and it remains unclear whether anesthetic care is still required in ...selected patients.
In this retrospective, single center study we assessed the prevalence of intraoperative anesthetic management comprising anesthetic standby, sedation or general anesthesia as well as anesthetic and procedural complications. We analyzed pre-existing and perioperative risk factors related to procedure-related adverse outcome such as perioperative cardiopulmonary resuscitation (CPR) and 30-day mortality in a uni- and multivariable analysis.
In total, PM and ICD insertion were performed in up to 85% and 58% under anesthetic standby, with an increasing tendency over time.
Overall, Cardiopulmonary resuscitation (CPR) was required in 59 patients. Acute heart failure (AHF) was the only independent pre-existing risk factor for CPR and for 30-day mortality. Sedation and general anesthesia had a significantly increased odds ratio for CPR compared to anesthetic standby. The risk for CPR significantly decreased during the study period.
Over the years anesthetic practice during CIED implant procedures shifted from mixed anesthetic proceedings to mainly standby duties. The prevalence of complications and emergency measures is low, however not uncommon. Accordingly, the presence of an anesthesiologist should be further guaranteed when sedatives were titrated and in AHF patients. However, in patients receiving local anesthetic infiltration only, it seems safe to perform CIED implant procedures without anesthetic standby.
After major surgery, longitudinal changes in resting energy expenditure (REE) as well as imbalances in oxygen delivery (DO2) and distribution and processing (VO2) may occur due to dynamic metabolic ...requirements, an impaired macro- and microcirculatory flow and mitochondrial dysfunction. However, the longitudinal pattern of these parameters in critically ill patients who die during hospitalization remains unknown. Therefore, we analyzed in 566 patients who received a pulmonary artery catheter (PAC) their REE, DO2, VO2 and oxygen extraction ratio (O2ER) continuously in survivors and non-survivors over the first 7 days post cardiac surgery, calculated the percent increase in the measured compared with the calculated REE and investigated the impact of a reduced REE on 30-day, 1-year and 6-year mortality in a uni- and multivariate model. Only in survivors was there a statistically significant transition from a negative to a positive energy balance from day 0 until day 1 (Day 0: −3% (−18, 14) to day 1: 5% (−9, 21); p < 0.001). Furthermore, non-survivors had significantly decreased DO2 during the first 4 days and reduced O2ER from day 2 until day 6. Additionally, a lower REE was significantly associated with a worse survival at 30 days, 1 year and 6 years (p = 0.009, p < 0.0001 and p = 0.012, respectively). Non-survivors seemed to be unable to metabolically adapt from the early (previously called the ‘ebb’) phase to the later ‘flow’ phase. DO2 reduction was more pronounced during the first three days whereas O2ER was markedly lower during the following four days, suggesting a switch from a predominantly limited oxygen supply to prolonged mitochondrial dysfunction. The association between a reduced REE and mortality further emphasizes the importance of REE monitoring.
Reduced oxygen consumption (VO
), either due to insufficient oxygen delivery (DO
), microcirculatory hypoperfusion and/or mitochondrial dysfunction, has an impact on the adverse short- and long-term ...survival of patients after cardiac surgery. However, it is still unclear whether VO
remains an efficient predictive marker in a population in which cardiac output (CO) and consequently DO
is determined by a left ventricular assist device (LVAD). We enrolled 93 consecutive patients who received an LVAD with a pulmonary artery catheter in place to monitor CO and venous oxygen saturation. VO
and DO
of in-hospital survivors and non-survivors were calculated over the first 4 days. Furthermore, we plotted receiver-operating curves (ROC) and performed a cox-regression analysis. VO
predicted in-hospital, 1- and 6-year survival with the highest area under the curve of 0.77 (95%CI: 0.6-0.9;
= 0.0004). A cut-off value of 210 mL/min VO
stratified patients regarding mortality with a sensitivity of 70% and a specificity of 81%. Reduced VO
was an independent predictor for in-hospital, 1- and 6-year mortality with a hazard ratio of 5.1 (
= 0.006), 3.2 (
= 0.003) and 1.9 (
= 0.0021). In non-survivors, VO
was significantly lower within the first 3 days (
= 0.010,
< 0.001,
< 0.001 and
= 0.015); DO
was reduced on days 2 and 3 (
= 0.007 and
= 0.003). In LVAD patients, impaired VO
impacts short- and long-term outcomes. Perioperative and intensive care medicine must, therefore, shift their focus from solely guaranteeing sufficient oxygen supply to restoring microcirculatory perfusion and mitochondrial functioning.
Background:
To the best of our knowledge, a strategic approach to define the contents of structured clinical documentation tools for both clinical routine patient care and research purposes has not ...been reported so far, although electronic health record will become more and more structured and detailed in the future.
Objective:
To achieve an interdisciplinary consensus on a checklist to be considered for the preparation of disease- and situation-specific clinical documentation tools.
Methods:
A 2-round Delphi consensus-based process was conducted both with 19 physicians of different disciplines and 14 students from Austria, Switzerland, and Germany. Agreement was defined as 80% or more positive votes of the participants.
Results:
The participants agreed that a working group should be set up for the development of structured disease- or situation-specific documentation tools (97% agreement). The final checklist included 4 recommendations concerning the setup of the working group, 12 content-related recommendations, and 3 general and technical recommendations (mean agreement standard deviation = 97.4% 4.0%, ranging from 84.2% to 100.0%).
Discussion and Conclusion:
In the future, disease- and situation-specific structured documentation tools will provide an important bridge between registries and electronic health records. Clinical documentation tools defined according to this Delphi consensus-based checklist will provide data for registries while serving as high-quality data acquisition tools in routine clinical care.
Systemic blood flow in patients on extracorporeal assist devices is frequently not or only minimally pulsatile. Loss of pulsatile brain perfusion, however, has been implicated in neurological ...complications. Furthermore, the adverse effects of absent pulsatility on the cerebral microcirculation are modulated similarly as CO
vasoreactivity in resistance vessels. During support with an extracorporeal assist device swings in arterial carbon dioxide partial pressures (PaCO
) that determine cerebral oxygen delivery are not uncommon-especially when CO
is eliminated by the respirator as well as via the gas exchanger of an extracorporeal membrane oxygenation machine. We, therefore, investigated whether non-pulsatile flow affects cerebrovascular CO
reactivity (CVR) and regional brain oxygenation (rSO
).
In this prospective, single-centre case-control trial, we studied 32 patients undergoing elective cardiac surgery. Blood flow velocity in the middle cerebral artery (MCAv) as well as rSO
was determined during step changes of PaCO
between 30, 40, and 50 mmHg. Measurements were conducted on cardiopulmonary bypass during non-pulsatile and postoperatively under pulsatile blood flow at comparable test conditions. Corresponding changes of CVR and concomitant rSO
alterations were determined for each flow mode. Each patient served as her own control.
MCAv was generally lower during hypocapnia than during normocapnia and hypercapnia (p < 0.0001). However, the MCAv/PaCO
slope during non-pulsatile flow was 14.4 cm/s/mmHg CI 11.8-16.9 and 10.4 cm/s/mmHg CI 7.9-13.0 after return of pulsatility (p = 0.03). During hypocapnia, non-pulsatile CVR (4.3 ± 1.7%/mmHg) was higher than pulsatile CVR (3.1 ± 1.3%/mmHg, p = 0.01). Independent of the flow mode, we observed a decline in rSO2 during hypocapnia and a corresponding rise during hypercapnia (p < 0.0001). However, the relationship between ΔrSO
and ΔMCAv was less pronounced during non-pulsatile flow.
Non-pulsatile perfusion is associated with enhanced cerebrovascular CVR resulting in greater relative decreases of cerebral blood flow during hypocapnia. Heterogenic microvascular perfusion may account for the attenuated ΔrSO
/ΔMCAv slope. Potential hazards related to this altered regulation of cerebral perfusion still need to be assessed.
The study was retrospectively registered on October 30, 2018, with Clinical Trial.gov (NCT03732651).
The investigation of biomarkers associated with undesired outcome following lung transplantation (LuTX) is essential for a better understanding of the underlying pathophysiology, an earlier ...identification of susceptible recipients and the development of targeted therapeutic options. We therefore determined the longitudinal perioperative course of putative cytokines related to neutrophil activation (chemokine CC motif ligand 4 (CCL-4), interleukin (IL)-23 and Lipocalin 2 (LCN2)) and a cytokine that has been implicated in graft-versus-host disease (Follistatin-like 1 (FSTL1)) in 42 consecutive patients undergoing LuTX. We plotted receiver-operating curves (ROC) to assess the predictive power of the measured cytokines for short-term outcomes namely primary graft dysfunction (PGD), early complications requiring extracorporeal membrane oxygenation (ECMO), and a high postoperative sequential organ failure assessment (SOFA). All cytokines increased immediately after surgery. ROC analyses determined significant associations between CCL4 and a high SOFA score (area under the curve (AUC) 0.74 (95%CI:0.5−0.9; p < 0.05), between LCN2 and postoperative ECMO support (AUC 0.73 (95%CI:0.5−0.9; p < 0.05), and between FSTL1 and PGD (AUC 0.70 (95%CI:0.5−0.9; p < 0.05). The serum concentrations of the neutrophil-derived cytokines LCN2 and CCL4 as well as FSTL1 were all related to poor outcome after LuTX. The specific predictive power, however, still has to be assessed in larger trials. The potential role of FSTL1 as a biomarker in the development of PGD could be of great interest particularly since this protein appears to play a crucial role in allograft tolerance.
Measuring skeletal muscle area (SMA) at the third lumbar vertebra level (L3) using computed tomography (CT) is increasingly popular for diagnosing low muscle mass. The aim was to describe the effect ...of the CT L3 cut-off choice on the prevalence of low muscle mass in medical and surgical patients. Two hundred inpatients, who underwent an abdominal CT scan for any reason, were included. Skeletal muscle area (SMA) was measured according to Hounsfield units on a single CT scan at the L3 level. First, we calculated sex-specific cut-offs, adjusted for height or BMI and set at mean or mean-2 SD in our population. Second, we applied published cut-offs, which differed in statistical calculation and adjustment for body stature and age. Statistical calculation of the cut-off led to a prevalence of approximately 50 vs. 1% when cut-offs were set at mean vs. mean-2 SD in our population. Prevalence varied between 5 and 86% when published cut-offs were applied (p < 0.001). The adjustment of the cut-off for the same body stature variable led to similar prevalence distribution patterns across age and BMI classes. The cut-off choice highly influenced prevalence of low muscle mass and prevalence distribution across age and BMI classes.
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