In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. ...Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased immediately and remained lower during the first 3.5 h after trauma, but increased after 24 h. Antagonizing TLR2 significantly decreased the phagocytizing activity of monocytes. Both, decreased percentage of activated as well as TLR2 expressing monocytes persisted as long as the reduced phagocytosis was observed. Moreover, neutralizing TLR2 led to a reduced capability of phagocytosis as well. Therefore, we assume that reduced TLR2 expression may be responsible for the decreased phagocytizing capacity of circulating monocytes in the early post-traumatic phase.
·Definitions for occult hypoperfusion in trauma (tOH) differ markedly in the literature.·The described impact of tOH on outcome differs between studies, and it´s role in trauma remains unclear.·A ...systematic review was performed to identify utilized criteria for tOH in recent literature.·The following definition for tOH is proposed: Lactate > 2 mmol/l or BE 〈-3 mmol/l plus SBP 〉 90 mmHg and PR < 120 bpm.
Occult hypoperfusion (OH) entails inadequate tissue oxygenation in the presence of normal vital signs. Numerous studies have demonstrated that this phenomenon is associated with impaired outcome and increased mortality, however definitions of OH differ between studies. The aim of the current study was to identify and evaluate the published definitions of the term `occult hypoperfusion` in trauma (tOH).
A review of literature was performed using the Medline database. The following MeSH terms have been used: occult hypoperfusion, severe trauma, polytrauma, resuscitation. Clinical studies on OH were included and utilized definitions have been compared. A predefined data-interpretation process was applied to create an integrative definition for tOH.
A total of 43 publications used the term OH. A definition of OH was provided in 16 manuscripts. A pooled mean number of participants of 729 (SD: 1158) was found per study. The majority of manuscripts combine multiple parameters for inadequate tissue oxygenation and normal vital signs to define OH in trauma. In 12 manuscripts, specific cut-off values for hemodynamic parameters (SBP/PR/UP) and in 11/16 papers exact metabolic thresholds (lactate/B.E) were defined. The following definition best integrates definitions in current literature: Lactate > 2 mmol/l or BE <-3 mmol/l (to define inadequate oxygenation) plus SBP > 90 mmHg and PR < 120 bpm (to define normal macroperfusion).
The current systematic review demonstrates that definitions of occult hypoperfusion in trauma differ in the literature. The following comprehensive definition for (tOH) is proposed: Lactate > 2 mmol/l or BE <-3 mmol/l plus SBP > 90 mmHg and PR < 120 bpm. This recommendation appears to represent current literature on tOH and may improve the identification of trauma patients at risk for OH and related complicated courses. Further validation studies are required to demonstrate the clinical role of tOH and the proposed definition.
We present an analysis of the molecular gas distributions in the 29 barred and 15 unbarred spirals in the BIMA CO (J= 1-0) Survey of Nearby Galaxies (SONG). For galaxies that are bright in CO, we ...confirm the conclusion by Sakamoto et al. that barred spirals have higher molecular gas concentrations in the central kiloparsec. The SONG sample also includes 27 galaxies below the CO brightness limit used by Sakamoto et al. Even in these less CO-bright galaxies we show that high central gas concentrations are more common in barred galaxies, consistent with radial inflow driven by the bar. However, there is a significant population of early-type (Sa-Sbc) barred spirals (6 of 19) that have no molecular gas detected in the nuclear region and have very little out to the bar corotation radius. This suggests that in barred galaxies with gas-deficient nuclear regions, the bar has already driven most of the gas within the bar corotation radius to the nuclear region, where it has been consumed by star formation. The median mass of nuclear molecular gas is over 4 times higher in early-type bars than in late-type (Sc-Sdm) bars. Since previous work has shown that the gas consumption rate is an order of magnitude higher in early-type bars, this implies that the early types have significantly higher bar-driven inflows. The lower accretion rates in late-type bars can probably be attributed to the known differences in bar structure between early and late types. Despite the evidence for bar-driven inflows in both early and late Hubble-type spirals, the data indicate that it is highly unlikely for a late-type galaxy to evolve into an early type via bar-induced gas inflow. Nonetheless, secular evolutionary processes are undoubtedly present, and pseudobulges are inevitable; evidence for pseudobulges is likely to be clearest in early-type galaxies because of their high gas inflow rates and higher star formation activity.
Purpose
Surgical technique in bariatric surgery has been refined over the past decades. This study analysed the effect of changing the stapling protocol on the quality of life (QoL) at a midterm ...follow-up.
Methods
The retrospective cohort study included patients undergoing Roux-en-Y gastric bypass between June 2012 and March 2016. Patients were stratified into the circular stapling protocol (CSP, n = 117) or the linear stapling protocol (LSP, n = 118). QoL was quantified by the Moorehead score at 12, 24 and 60 months. Multivariate testing was used to identify confounders.
Results
The age was 42.8 ± 11.5 years and the body mass index (BMI) was 43.8 ± 6.2 kg/m
2
, with no baseline intergroup differences. Overall baseline Moorehead score was 0.42 ± 1.1 and improved in both groups after 12 months (1.97 ± 0.74,
p
< 0.001), 24 months (1.86 ± 0.79,
p
< 0.001) and 60 months (1.71 ± 0.9,
p
< 0.001). LSP was associated with improved Moorehead score after 60 months (odds ratio OR 1.251, 95% confidence interval CI 1.06–1.48,
p
= 0.010). Overall, a drop of mean BMI occurred and this effect lasted throughout the observation period (− 12.48 kg/m
2
,
p
< 0.001). More profound BMI reduction was further positively associated with Moorehead scores after 24 and after 60 months (OR 0.97,
p
= 0.028; OR 0.96,
p
= 0.007). Complications, rehospitalisations and reoperations were more frequent in the CSP group (50% vs 23.7%,
p
< 0.001; 39.7% vs 22.9%,
p
= 0.009; 37.1% vs 18.6%,
p
= 0.003).
Conclusion
The CSP and LSP achieve a long-lasting increase in QoL, although the LSP is associated with fewer complications, persistent weight loss and improved Moorehead score. Therefore, the LSP might be considered the favourable protocol in Roux-en-Y gastric bypass.
Up to 20% of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients develop severe inflammatory complications with diffuse pulmonary inflammation, reflecting acute respiratory distress ...syndrome (ARDS). A similar clinical profile occurs in severe trauma cases. This review compares pathophysiological and therapeutic principles of severely injured trauma patients and severe coronavirus disease 2019 (COVID-19). The development of sequential organ failure in trauma parallels deterioration seen in severe COVID-19. Based on established pathophysiological models in the field of trauma, two complementary pathways of disease progression into severe COVID-19 have been identified. Furthermore, the transition from local contained disease into systemic and remote inflammation has been addressed. More specifically, the traumatology concept of sequential insults ('hits') resulting in immune dysregulation, is applied to COVID-19 disease progression modelling. Finally, similarities in post-insult humoral and cellular immune responses to severe trauma and severe COVID-19 are described. To minimize additional 'hits' to COVID-19 patients, we suggest postponing all elective surgery in endemic areas. Based on traumatology experience, we propose that immunoprotective protocols including lung protective ventilation, optimal thrombosis prophylaxis, secondary infection prevention and calculated antibiotic therapy are likely also beneficial in the treatment of SARS-CoV-2 infections. Finally, rising SARS-CoV-2 infection and mortality rates mandate exploration of out-of-the box treatment concepts, including experimental therapies designed for trauma care.
Severely injured patients experience substantial immunological stress in the aftermath of traumatic insult, which often results in systemic immune dysregulation. Regulatory T cells (Treg) play a key ...role in the suppression of the immune response and in the maintenance of immunological homeostasis. Little is known about their presence and dynamics in blood after trauma, and nothing is known about Treg in the porcine polytrauma model. Here, we assessed different subsets of Treg in trauma patients (TP) and compared those to either healthy volunteers (HV) or data from porcine polytrauma.
Peripheral blood was withdrawn from 20 TP with injury severity score (ISS) ≥16 at the admittance to the emergency department (ED), and subsequently on day 1 and at day 3. Ten HV were included as controls (ctrl). The porcine polytrauma model consisted of a femur fracture, liver laceration, lung contusion, and hemorrhagic shock resulting in an ISS of 27. After polytrauma, the animals underwent resuscitation and surgical fracture fixation. Blood samples were withdrawn before and immediately after trauma, 24 and 72 h later. Different subsets of Treg, CD4
CD25
, CD4
CD25
FoxP3
, CD4
CD25
CD127
, and CD4
CD25
CD127
FoxP3
were characterized by flow cytometry.
Absolute cell counts of leukocytes were significantly increasing after trauma, and again decreasing in the follow-up in human and porcine samples. The proportion of human Treg in the peripheral blood of TP admitted to the ED was lower when compared to HV. Their numbers did not recover until 72 h after trauma. Comparable data were found for all subsets. The situation in the porcine trauma model was comparable with the clinical data. In porcine peripheral blood before trauma, we could identify Treg with the typical immunophenotype (CD4
CD25
CD127
), which were virtually absent immediately after trauma. Similar to the human situation, most of these cells expressed FoxP3, as assessed by intracellular FACS stain.
Despite minor percental differences in the recovery of Treg populations after trauma, our findings show a comparable decrease of Treg early after polytrauma, and strengthen the immunological significance of the porcine polytrauma model. Furthermore, the Treg subpopulation CD4
CD25
CD127
was characterized in porcine samples.
Background
Revision surgeries in patients with failed gastric banding including band removal are increasingly necessary. However, long-term outcomes after band removal alone are unsatisfactory due to ...weight regain and limited improvement in quality of life. This study aimed to report mid-term quality of life outcomes after gastric band removal and single-stage conversion to Roux-en-Y gastric bypass.
Methods
Data of 108 patients who underwent conversion surgery from 2011 to 2017 were extracted from a prospective database and retrospectively analyzed. During follow-up visits, physical and laboratory data as well as quality of life questionnaires were obtained.
Results
Postoperative mean Moorehead score increased significantly after 1 year (1.62 ± 0.86,
p
< 0.001) and after 5 years (1.55 ± 0.84,
p
< 0.001) compared to baseline values (0.72 ± 1.1). The mean follow-up time was 53 months. Moorehead scores at 1, 2, and 5 years postoperative were available in 75% (
n
= 81), 71% (
n
= 77), and 42% (
n
= 45) of cases, respectively. Mixed ANOVA analysis showed a significantly superior increase in Moorehead score in males (
p
= 0.024). No other significant predictors were identified. Lasting BMI reduction (− 4.6 to 33.0 ± 6.7 kg/m
2
,
p
< 0.001) and weight loss (− 12.9% (− 13.6 kg),
p
< 0.001) 5 years after conversion surgery were seen. Postoperative complications occurred in 35% (
n
= 38) of patients with a re-operation rate of 30.5% (
n
= 33).
Conclusion
The current study shows that band removal with single-stage gastric bypass in patients with failed gastric banding leads to a lasting improvement in quality of life and may be the rescue procedure of choice in this setting.
Reperfusion injury following myocardial infarction (MI) increases infarct size (IS) and deteriorates cardiac function. Cardioprotective strategies in large animal MI models often failed in clinical ...trials, suggesting translational failure. Experimentally, MI is induced artificially and the effect of the experimental procedures may influence outcome and thus clinical applicability. The aim of this study was to investigate if invasive surgery, as in the common open chest MI model affects IS and cardiac function. Twenty female landrace pigs were subjected to MI by transluminal balloon occlusion. In 10 of 20 pigs, balloon occlusion was preceded by invasive surgery (medial sternotomy). After 72 hrs, pigs were subjected to echocardiography and Evans blue/triphenyl tetrazoliumchloride double staining to determine IS and area at risk. Quantification of IS showed a significant IS reduction in the open chest group compared to the closed chest group (IS versus area at risk: 50.9 ± 5.4% versus 69.9 ± 3.4%, P = 0.007). End systolic LV volume and LV ejection fraction measured by echocardiography at follow‐up differed significantly between both groups (51 ± 5 ml versus 65 ± 3 ml, P = 0.033; 47.5 ± 2.6% versus 38.8 ± 1.2%, P = 0.005). The inflammatory response in the damaged myocardium did not differ between groups. This study indicates that invasive surgery reduces IS and preserves cardiac function in a porcine MI model. Future studies need to elucidate the effect of infarct induction technique on the efficacy of pharmacological therapies in large animal cardioprotection studies.
Myocardial infarction (MI) induces an inflammatory response in which neutrophils fulfill a prominent role. Mean neutrophil volume (MNV) represents the average size of the circulating neutrophil ...population. Our goal was to determine the effect of MI on MNV and investigate the mechanisms behind MNV elevation. MNV of 84 MI patients was compared with the MNV of 209 stable angina patients and correlated to simultaneously measured CK levels. Fourteen pigs were subjected to temporary coronary balloon occlusion and blood was sampled at multiple time points to measure MNV. Echocardiography was performed followed by ex vivo infarct size assessment after 72 h. MNV was higher in MI patients compared to stable angina patients (602 SD26 AU vs. 580 SD20 AU,
p
< 0.0001) and correlated with simultaneously measured CK levels (
R
= 0.357,
p
< 0.0001). In pigs, MNV was elevated post-MI (451 SD11 AU vs. 469 SD12 AU),
p
< 0.0001). MNV correlated with infarct size (
R
= 0.705,
p
= 0.007) and inversely correlated with left ventricular ejection fraction (
R
= −0.718,
p
= 0.009). Cell sorting revealed an increased presence of banded neutrophils after MI, which have a higher MNV compared to mature neutrophils post-MI (495 SD14 AU vs. 478 SD11 AU,
p
= 0.012). MNV from coronary sinus blood was higher than MNV of neutrophils from simultaneously sampled arterial blood (463 SD7.6 AU vs. 461 SD8.6 AU,
p
= 0.013) post-MI. The current study shows MNV is elevated and reflects cardiac damage post-MI. MNV increases due to altered neutrophil composition and systemic neutrophil activation. MNV may be an interesting parameter for prognostic assessment in MI and provide new insights into pathological innate immune responses evoked by ischemia–reperfusion.
Extensive trauma surgery evokes an immediate cellular immune response including altered circulatory neutrophil numbers. The concurrent bone marrow (BM) response however is currently unclear. We ...hypothesize that these BM changes include (1) a relative reduction of the bone marrow neutrophil fraction and (2) increasing heterogeneity of the bone marrow neutrophil pool due to (3) the appearance of aged/returning neutrophils from circulation into the BM-compartment.
Eight pigs were included in a standardized extensive trauma surgery model. Blood and bone marrow samples were collected at baseline and after 3 hours of ongoing trauma surgery. Leukocyte and subtype counts and cell surface receptor expression levels were studied by flow cytometry.
All animals survived the interventions. A significant drop in circulating neutrophil counts from 9.3 to 3.2x10
cells/ml (P=0.001) occurred after intervention, whereas circulatory neutrophil cell surface expression of CD11b increased. The concurrent bone marrow response included an increase of the BM neutrophil fraction from 63 ± 3 to 71 ± 3 percent (P<0.05). Simultaneously, the BM neutrophil pool became increasingly mature with a relative increase of a CXCR4
-neutrophil subtype that was virtually absent at baseline.
The current study shows a shift in composition of the BM neutrophil pool during extensive trauma surgery that was associated with a relatively circulatory neutropenia. More specifically, under these conditions BM neutrophils were more mature than under homeostatic conditions and a CXCR4
-neutrophil subset became overrepresented possibly reflecting remigration of aged neutrophils to the BM. These findings may contribute to the development of novel interventions aimed to modify the trauma-induced immune response in the BM.
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