Transition from a circular to a linear stapling protocol in laparoscopic Roux-en-Y gastric bypass surgery and its impact on quality of life: a 5-year outcome study.

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/m2, 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/m2, 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.

Shift of Neutrophils From Blood to Bone Marrow Upon Extensive Experimental Trauma Surgery.

Introduction: 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. Materials and Methods: 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. Results: All animals survived the interventions. A significant drop in circulating neutrophil counts from 9.3 to 3.2x106 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 CXCR4high-neutrophil subtype that was virtually absent at baseline. Conclusion: 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 CXCR4high-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.

Altered cell surface receptor dynamics and circulatory occurrence of neutrophils in a small animal fracture model.

INTRODUCTION: Excessive activation of the immune response after femoral fractures and fracture fixation is potentially associated with the development of systemic and local complications, particularly in multiple trauma patients. A dysregulated function of neutrophils, the most prevailing immune cells in circulation, has been discussed as a central pathophysiological background for these unfavourable post-traumatic courses. Our aim was to investigate alterations in activity and functionality as expressed by the cell surface receptor dynamics of circulatory neutrophils after femoral fracture and intramedullary stabilization. MATERIAL AND METHODS: After intramedullary stabilization, an isolated femur fracture was induced in 18 Sprague-Dawley rats. Animals were terminated at different time points, i.e. after 3 (n = 5, group 3d), 7 (n = 5, group 7d) and 14 (n = 5, Group 14d) days and grouped accordingly. Additionally, baseline measurements were performed in one control animal per study group (n = 3) after anaesthesia induction and termination, without prior intramedullary nailing and fracture induction. The numbers and cell surface expression of CD11b, CD11a, CD62 L, and CD49d of circulating neutrophils were compared between groups. RESULTS: Neutrophil numbers were significantly reduced at 3 days compared with baseline measurements (1.2 × 105 vs. 6.3 × 105 cells/mL, p < 0.01). By day 7, neutrophil counts significantly increased back to homeostatic levels (p < 0.05). At day 3, CD11b-expression was significantly reduced, whereas CD11a-expression was increased compared with the baseline measurements (p < 0.05). At day 7, the circulatory neutrophil pool exhibited a unique CD11bhigh/CD11ahigh-neutrophil subset showing a significantly increased co-expression of CD49d. The expression of CD62 L did not change significantly throughout the experiment compared with baseline measurements. CONCLUSIONS: This descriptive small animal fracture study is the first to show that an intramedullary stabilized femur fracture is associated with a temporary reduction in circulatory neutrophil count and concurrent changes in circulatory neutrophil function. Moreover, we demonstrated that the restoration to homeostatic neutrophil activation status occurs concomitantly with the appearance of a novel neutrophil subtype (CD11bhigh/CD11ahigh) in circulation. Our fundamental new findings of the changes in circulatory neutrophil count and functionality after trauma form an excellent basis for future studies to further elucidate the role of neutrophils as activators and regulators of different post-traumatic processes, potentially resulting in local (e.g., fracture healing disturbances) or systemic (e.g., MODS) complications. This might result in the development of specific therapies to reduce adverse outcomes after trauma.

Lessons learned from the mechanisms of posttraumatic inflammation extrapolated to the inflammatory response in COVID-19: a review.

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.

Comparative Analysis of the Regulatory T Cells Dynamics in Peripheral Blood in Human and Porcine Polytrauma.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model.

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.

Invasive surgery reduces infarct size and preserves cardiac function in a porcine model of myocardial infarction.

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.