Adsorptive therapies in sepsis and inflammation: description of the various adsorptive techniques and their failure to improve outcomes.

Blood purification as an adjunctive therapy has been studied for several decades. In this review, we will focus on the most recent studies, particularly on adsorption techniques. These include hemofilters with adsorptive membranes, both endotoxin-specific and non-specific. In addition, we will discuss sorbents that target endotoxins, as well as devices that non-selectively capture viruses and bacteria. For each technique, we will also explore the reasons why blood purification methods have thus far failed to improve survival. Conventionally, reasons for the lack of success in blood purification techniques have been attributed to the need for better patient stratification through bedside measurements of interleukins and endotoxins. The choice of assay is also crucial, with endotoxin activity assays being preferable to other forms of limulus amoebocyte lysate assays. Another critical factor is timing, as administering blood purification at the wrong moment can potentially harm the patient. Mechanistic studies are still lacking for most devices, leaving us to treat patients blindly, except in endotoxin cases. In the context of viruses, especially COVID-19, we require a deeper understanding of the complexities involved in viral replication, as this could significantly impact the efficacy of blood purification techniques. The failures highlighted for each device should be viewed as potential areas for improvement. Despite the challenges, we remain hopeful that these techniques will eventually succeed and prove beneficial in the future.

Lung Transplant Recipients Immunogenicity after Heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA Vaccination.

(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 vaccine. A subset of 32 patients received a booster dose of BNT162b2 mRNA vaccine 18 weeks after the second dose. (3) Results: Two-doses of ChAdOx1 nCoV-19 induced poor immunogenicity with 7.2% seropositivity at day 180 and low neutralizing capacities. The BNT162b2 mRNA vaccine induced significant increases in IgG titers with means of 197.8 binding antibody units per milliliter (BAU/mL) (95% CI 0-491.4) and neutralizing antibodies, with means of 76.6 AU/mL (95% CI 0-159.6). At day 238, 32.2% of LTRs seroconverted after the booster dose. Seroneutralization capacities against Delta and Omicron variants were found in only 13 and 9 LTRs, respectively. Mycophenolate mofetil and high-dose corticosteroids were associated with a weak serological response. (4) Conclusions: The immunogenicity of a two-dose ChAdOx1 nCoV-19 vaccine regimen was very poor in LTRs, but was significantly enhanced after the booster dose in one-third of LTRs. In immunocompromised individuals, the administration of a fourth dose may be considered to increase the immune response against SARS-CoV-2.

Adherence to quality indicators for ST-elevation myocardial infarction and its relation to mortality: a hospital network analysis from the Belgian STEMI database.

AIMS: To assess the adherence to established quality indicators (QIs) for ST-elevation myocardial infarction (STEMI) at the hospital-network level and its relation to outcome. METHODS AND RESULTS: The data of 7774 STEMI patients admitted to 32 STEMI networks during the period 2014-18 were extracted from the Belgian STEMI database. Five QIs [primary percutaneous coronary intervention use, diagnosis-to-balloon time (DiaTB) <90 min, door-to-balloon time (DoTB) <60 min, P2Y12 inhibitor and statin prescription at discharge, and a composite QI score ranging from 0 to 10] were correlated with in-hospital mortality adjusted for differences in baseline risk profile (TIMI risk score). The median composite QI score was 6.5 [interquartile range (IQR) 6-8]. The most important gaps in quality adherence were related to time delays: the recommended DiaTB and DoTB times across the different networks were achieved in 68% (IQR 53-71) and 67% (IQR 50-78), respectively. Quality adherence was better in networks taking care of more high-risk STEMI patients. The median in-hospital mortality among the STEMI networks was 6.4% (IQR 4.1-7.9%). There was a significant independent inverse correlation between the composite QI score and in-hospital mortality (partial correlation coefficient: -0.45, P = 0.013). Stepwise regression analysis revealed that among the individual QIs, prolonged DiaTB was the most important independent outcome predictor. CONCLUSION: Among established STEMI networks, the time delay between diagnosis and treatment was the most variable and the most relevant prognostic QI, underscoring the importance of assessing quality of care throughout the whole network.

Impact of COVID-19-related public containment measures on the ST elevation myocardial infarction epidemic in Belgium: a nationwide, serial, cross-sectional study.

AIMS: The current study assessed the impact of COVID-19-related public containment measures (i.e. lockdown) on the ST elevation myocardial infarction (STEMI) epidemic in Belgium. METHODS AND RESULTS: Clinical characteristics, reperfusion therapy modalities, COVID-19 status and in-hospital mortality of consecutive STEMI patients who were admitted to Belgian hospitals for percutaneous coronary intervention (PCI) were recorded during a three-week period starting at the beginning of the lockdown period on 13 March 2020. Similar data were collected for the same time period for 2017-2019. An evaluation of air quality revealed a 32% decrease in ambient NO2 concentrations during lockdown (19.5 µg/m³ versus 13.2 µg/m³, p < .001). During the three-week period, there were 188 STEMI patients admitted for PCI during the lockdown versus an average 254 STEMI patients before the lockdown period (incidence rate ratio = 0.74, p = .001). Reperfusion strategy was predominantly primary PCI in both time periods (96% versus 95%). However, there was a significant delay in treatment during the lockdown period, with more late presentations (>12 h after onset of pain) (14% versus 7.6%, p = .04) and with longer door-to-balloon times (median of 45 versus 39 min, p = .02). Although the in-hospital mortality between the two periods was comparable (5.9% versus 6.7%), 5 of the 7 (71%) COVID-19-positive STEMI patients died. CONCLUSION: The present study revealed a 26% reduction in STEMI admissions and a delay in treatment of STEMI patients. Less exposure to external STEMI triggers (such as ambient air pollution) and/or reluctance to seek medical care are possible explanations of this observation.

Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant - a historical prospective study.

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO2 /FiO2  ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized.

Lung allocation score: the Eurotransplant model versus the revised US model - a cross-sectional study.

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET.

Quality assessment in Belgian ST elevation myocardial infarction patients: results from the Belgian STEMI database.

The present report describes the quality of care, including in hospital mortality for more than 22.000 STEMI patients admitted in 60 Belgian hospitals for the period 2008-2016. We found a strong increase in the use of primary PCI over time, particularly for patients that were admitted first in a non-PCI capable hospital, reaching a penetration rate of >95%. The transition of thrombolysis to transfer for pPCI in the setting of a STEMI network was, however, associated with an increase of the proportion of patients with prolonged (>120 min) diagnosis-to-balloon time (from 16 to 22%), suggesting still suboptimal interhospital transfer. The in-hospital mortality of the total study population was 6.5%. For non-cardiac arrest patients in-hospital mortality decreased from 5.1% to 3.7%, while it increased for cardiac arrest patients from 29 to 37%. The observation that quality indicators (QI's), such as modalities and timing of reperfusion therapy, were associated with lower levels of mortality, underscores the potential of QIs for STEMI to improve care and reduce unwarranted variation and premature death from STEMI.

Mode of admission and its effect on adherence to reperfusion therapy guidelines in Belgian STEMI patients.

OBJECTIVES: Emergency medical services play a key role in the recognition and treatment of ST-segment elevation myocardial infarction (STEMI). This study evaluates the effect of emergency medical services use on adherence to reperfusion therapy guidelines in Belgian STEMI patients and on in-hospital mortality. METHODS: The mode of admission with against without emergency medical services was associated with baseline risk profile, reperfusion modalities and in-hospital mortality in 5692 consecutive STEMI patients from 2012 to 2014. RESULTS: A total of 3896 STEMI patients (68%) were transported to the hospital by emergency medical services, and 1796 patients (32%) arrived at the hospital using their own transport (self-referral). Emergency medical services patients were older than self-referral patients (64 vs. 62 years) and more frequently presented with cardiac arrest (14% vs. 5%) and with cardiogenic shock (10% vs. 4%). Emergency medical services patients received primary percutaneous coronary intervention more often (95% vs. 91%, P<0.0001) and more frequently within 90 minutes (72% vs. 65%, P<0.001). Moreover, the time interval between symptom onset and reperfusion therapy was shorter in the emergency medical services group (median of 195 vs. 255 minutes, P<0.001). Crude in-hospital mortality was higher in the emergency medical services group (7.7% vs. 3.8%, P<0.0001) and was mainly driven by the high prevalence of cardiogenic shock and cardiac arrest in the emergency medical services group. After adjustment, the impact on mortality was no longer significantly different. CONCLUSION: Emergency medical services are used by two-thirds of Belgian STEMI patients and are associated with a better adherence to STEMI reperfusion guidelines. These data favour the use of emergency medical services as the preferred transfer system for patients with chest pain suspicious for STEMI.

New classification of donation after circulatory death donors definitions and terminology.

In the face of a crisis in organ donation, the transplant community are increasingly utilizing donation after circulatory death (DCD) donors. Over the last 10 years, with the increasing usage of DCD donors, we have seen the introduction in a number of new terms and definitions. We report the results of the 6th International Conference in Organ Donation held in Paris in 2013 and report a consensus agreement of an established expert European Working Group on the definitions and terminology regarding DCD donation, including refinement of the Maastricht definitions. This document forms part of a special series where recommendations are presented for uncontrolled and controlled DCD donation and organ specific guidelines for kidney, pancreas, liver and lung transplantation. An expert panel formed a consensus on definitions and terms aiming to establish consistent usage of terms in DCD donation.

Gender, TIMI risk score and in-hospital mortality in STEMI patients undergoing primary PCI: results from the Belgian STEMI registry.

AIMS: The relationship between the predictive performance of the TIMI risk score for STEMI and gender has not been evaluated in the setting of primary PCI (pPCI). Here, we compared in-hospital mortality and predictive performance of the TIMI risk score between Belgian women and men undergoing pPCI. METHODS AND RESULTS: In-hospital mortality was analysed in 8,073 (1,920 [23.8%] female and 6,153 [76.2%] male patients) consecutive pPCI-treated STEMI patients, included in the prospective, observational Belgian STEMI registry (January 2007 to February 2011). A multivariable logistic regression model, including TIMI risk score variables and gender, evaluated differences in in-hospital mortality between men and women. The predictive performance of the TIMI risk score according to gender was evaluated in terms of discrimination and calibration. Mortality rates for TIMI scores in women and men were compared. Female patients were older, had more comorbidities and longer ischaemic times. Crude in-hospital mortality was 10.1% in women vs. 4.9% in men (OR 2.2; 95% CI: 1.82-2.66, p<0.001). When adjusting for TIMI risk score variables, mortality remained higher in women (OR 1.47, 95% CI: 1.15-1.87, p=0.002). The TIMI risk score provided a good predictive discrimination and calibration in women as well as in men (c-statistic=0.84 [95% CI: 0.809-0.866], goodness-of-fit p=0.53 and c-statistic=0.89 [95% CI: 0.873-0.907], goodness-of-fit p=0.13, respectively), but mortality prediction for TIMI scores was better in men (p=0.02 for TIMI score x gender interaction). CONCLUSIONS: In the Belgian STEMI registry, pPCI-treated women had a higher in-hospital mortality rate even after correcting for TIMI risk score variables. The TIMI risk score was effective in predicting in-hospital mortality but performed slightly better in men. The database was registered with clinicaltrials.gov (NCT00727623).

Transcranial doppler assessment of cerebral perfusion in critically ill septic patients: a pilot study.

BACKGROUND: The aim of this study is to evaluate the feasibility and efficacy of Transcranial Doppler (TCD) in assessing cerebral perfusion changes in septic patients. METHODS: Using TCD, we measured the mean velocity in the middle cerebral artery (VmMCA, cm/sec) and calculated the pulsatility index (PI), resistance index (RI) and cerebral blood flow index (CBFi = 10*MAP/1.47(PI)) on the first day of patients' admission or on the first day of sepsis development; measurements were repeated on the second day. Sepsis was defined according to standard criteria. RESULTS: Forty-one patients without any known neurologic deficit treated in our 24-bed Critical Care Unit were assessed (Sepsis Group = 20, Control Group = 21). Examination was feasible in 91% of septic and 85% of non-septic patients (p = 0.89). No difference was found between the two groups in mean age, mean arterial pressure (MAP) or APACHE II score. The pCO2 values were higher in septic patients (46 ± 12 vs. 39 ± 4 mmHg p < 0.01). No statistically significant higher values of VmMCA were found in septic patients (110 ± 34 cm/sec vs. 99 ± 28 cm/sec p = 0.17). Higher values of PI and RI were found in septic patients (1.15 ± 0.25 vs. 0.98 ± 0.16 p < 0.01, 0.64 ± 0.08 vs. 0.59 ± 0.06 p < 0.01, respectively). No statistically significant lower values of CBFi were found in septic patients (497 ± 116 vs. 548 ± 110 p = 0.06). CONCLUSIONS: Our results suggest cerebral vasoconstriction in septic compared to non-septic patients. TCD is an efficient and feasible exam to evaluate changes in cerebral perfusion during sepsis.

Inter-hospital variation in length of hospital stay after ST-elevation myocardial infarction: results from the Belgian STEMI registry.

OBJECTIVE: The aim of this paper was to assess the determinants of and variations in length of hospital stay (LOS) in Belgium after ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Data on LOS were collected from 2079 STEMI patients who were discharged alive from 33 Belgian hospitals (21 with PCI facilities) during 2010-201 1. Early discharge was defined as hospital discharge within 4 days after admission, and the hospitals were clustered according to their LOS for low-risk patients. Determinants of LOS were calculated by means of a negative binomial regression model. LOS was, on average, 6.5 days with a median of 5 days (IQR 4). Baseline risk profiles and reperfusion treatment explained only 13% of the LOS variation. Additional analysis revealed major in-hospital variations independent of the case mix of patients. For comparable baseline risk profiles, the average LOS in a cluster of 11 hospitals with short discharge policies was 5.3 + 5.6 days, with an early discharge rate of 58%, while in the cluster of 11 hospitals with long discharge policies, the average LOS was 7.9 + 8.5 days with an early discharge rate of 22% (P <0.0001). Among the clustered hospitals, there were no differences with regard to logistics (PCI facility, academic affiliation) or volume of STEMI patients. The 1-month mortality rate was less than 0.5% in the different clusters of hospitals (p = NS). CONCLUSIONS: Length of hospital stay is not only determined by baseline risk profiles of patients but is also highly dependent on hospital discharge policy, which seems to be unrelated to medical or logistical factors.

Reperfusion therapy and mortality in octogenarian STEMI patients: results from the Belgian STEMI registry.

BACKGROUND: Treatment strategies and outcome of ST-elevation myocardial infarction (STEMI) have been mainly studied in middle-aged patients. With increasing lifetime expectancy, the proportion of octogenarians will substantially increase. We aimed to evaluate whether the benefit of currently recommended reperfusion strategies is maintained in octogenarians. METHODS: Reperfusion therapy and in-hospital mortality were evaluated in 1,092 octogenarians and compared with 7,984 STEMI patients <80 years old based on data from the prospective Belgian STEMI registry. RESULTS: The octogenarian STEMI group had more cardiovascular comorbidities, contained more female patients and presented more frequently with cardiac failure (Killip class >1, 40 vs. 20 %) compared with their younger counterparts (all p < 0.05). Although the rate of thrombolysis was similar (9.2 vs. 9.9 %) between both groups, a conservative approach was chosen more frequently (13.8 vs. 4.7 %), while PCI was performed less frequently (76.9 vs. 85.4 %) in octogenarians (p < 0.001). Moreover, ischemic time and door-to-needle/balloon time were longer for octogenarians. In-hospital mortality for octogenarians was 17.8 vs. 5.5 % in the younger group [adjusted OR 2.43(1.92-3.08)]. In haemodynamically stable octogenarians, PCI seemed to improve outcome compared with thrombolysis or conservative treatment (5.7 vs. 12.7 vs. 8.5 %, p = 0.09). In octogenarians with cardiac failure, in-hospital mortality was extremely high independent of the chosen reperfusion therapy (34.6 vs. 31.6 vs. 36.3 %, p = 0.88). CONCLUSIONS: In-hospital mortality in octogenarian STEMI patients was high and related to a high prevalence of cardiac failure. Less PCI was performed in the octogenarian group compared with the younger patients, although mortality benefit of PCI was maintained in haemodynamically stable octogenarians.

Renal dysfunction in STEMI-patients undergoing primary angioplasty: higher prevalence but equal prognostic impact in female patients; an observational cohort study from the Belgian STEMI registry.

BACKGROUND: Mortality in female patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary angioplasty (pPCI) is higher than in men. We examined gender differences in the prevalence and prognostic performance of renal dysfunction at admission in this setting. METHODS: A multicenter retrospective sub-analysis of the Belgian STEMI-registry identified 1,638 patients (20.6% women, 79.4% men) treated with pPCI in 8 tertiary care hospitals (January 2007-February 2011). The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. Main outcome measure was in-hospital mortality. RESULTS: More women than men suffered from renal dysfunction at admission (42.3% vs. 25.3%, p < 0.001). Mortality in women was doubled as compared to men (9.5 vs. 4.7%, OR (95% CI) = 2.12 (1.36-3.32), p<0.001). In-hospital mortality for men and women with vs. without renal dysfunction was much higher (10.7 and 15.3 vs. 2.3 and 2.4%, p < 0.001). In a multivariable regression analysis, adjusting for age, gender, peripheral artery disease (PAD), coronary artery disease (CAD), hypertension, diabetes and low body weight (<67 kg), female gender was associated with renal dysfunction at admission (OR (95% CI) 1.65 (1.20-2.25), p = 0.002). In a multivariable model including TIMI risk score and renal dysfunction, renal dysfunction was an independent predictor of in-hospital mortality in both men (OR (95% CI) = 2.39 (1.27-4.51), p = 0.007) and women (OR (95% CI) = 4.03 (1.26-12.92), p = 0.02), with a comparable impact for men and women (p for interaction = 0.69). CONCLUSIONS: Female gender was independently associated with renal dysfunction at admission in pPCI treated patients. Renal dysfunction was equally associated with higher in-hospital mortality in both men and women.

STEMI mortality in community hospitals versus PCI-capable hospitals: results from a nationwide STEMI network programme.

AIMS: Reports examining local ST elevation myocardial infarction (STEMI) networks focused mainly on percutaneous coronary intervention (PCI)-related time issues and outcomes. To validate the concept of STEMI networks in a real-world context, more data are needed on management and outcome of an unselected community based STEMI population. METHODS AND RESULTS: The current study evaluated reperfusion strategies and in-hospital mortality in 8500 unselected STEMI patients admitted to 47 community hospitals (n=3053) and 25 PCI-capable hospitals (n=5447) in the context of a nationwide STEMI network programme that started in 2007 in Belgium. The distance between the hub and spoke hospitals ranged from 2.2 to 47 km (median 15 km). A propensity score was used to adjust for differences in baseline characteristics. Reperfusion strategy was significantly different with a predominant use of primary PCI (pPCI) in PCI-capable hospitals (93%), compared to a mixed use of pPCI (71%) and thrombolysis (20%) in community hospitals. A door-to-balloon time <120 min was achieved in 83% of community hospitals and in 91% of PCI-capable hospitals (p<0.0001). In-hospital mortality was 7.0% in community hospitals versus 6.7% in PCI-capable hospitals with an adjusted odds ratio of 1.1 (95% confidence interval: 0.8-1.4). Between the periods 2007-2008 and 2009-2010, the pPCI rate in community hospitals increased from 60% to 80%, whereas the proportion of conservatively managed patients decreased from 11.1% to 7.9%. CONCLUSION: In a STEMI network with >70% use of pPCI, in-hospital mortality was comparable between community hospitals and PCI-capable hospitals. Participation in the STEMI network programme was associated with an increased adherence to reperfusion guidelines over time.

Methadone and lung transplants.

OBJECTIVES: The aim of this article is to better understand the role of the liaison psychiatrist regarding the pulmonary pre-transplantation assessment for a patient treated by methadone. METHOD: At the beginning, we collected data concerning the different habits of patients requiring pulmonary transplantation. Through a literature review, we studied the possible guidelines related to this subject, the effects of methadone, the side-effects explaining the psychiatrist's concerns. Finally, this problem is involved in the bio-psycho-social model to underline the influence of methadone on post-operative prognosis. RESULTS: In our database, only 4.3% of patients were treated by methadone. However, this addiction is one of the most important stressors for psychiatrists and involves a great deal of multidisciplinary staff time. There are absolutely no guidelines on this topic. Due to the action of methadone, the pulmonary, cardiac, urologic, drug and immune side effects are more understandable. Thanks to clinical labels, we are able to handle this dual problem. Different parameters are considered such as patient's history, drug addiction, deterioration of physical condition, possible surgery and its consequences, choice of treatment to better estimate the post-operative prognosis. CONCLUSION: Until now, there is nor indication or contra-indication regarding the duration of treatment by methadone for patients requiring pulmonary transplantation. The main advantage is the patient's stabilization by minimizing possible relapses. This advantage is to compare the following major inconvenience: increased confusional risk, delicate management of the post-operative pain, negative impact on the immunity. The support, a double psychoeducation and the patient's decision making are to be encouraged.