In vitro polymorphonuclear neutrophil function in surgical patients does not correlate with anergy but with "activating" processes such as sepsis or trauma

We studied 199 preoperative patients admitted for esophagogastric, gastric, colonic, or rectal resections, 132 patients with severe blunt trauma, 180 surgical intensive care unit patients with major sepsis, and 95 laboratory controls in order to clarify the role of polymorphonuclear neutrophil (PMN) adherence and chemotaxis to outcome. Patients were also stratified by the delayed-type hypersensitivity response to five ubiquitous antigens. PMN adherence and PMN chemotaxis were not different in preoperative reactive or anergic patients and were equal to the control values, whereas both reactive patients and anergic patients showed altered PMN function after trauma or sepsis. There was no difference in PMN adherence or chemotaxis between patients who died and those who lived. Multiple logistic regression analysis showed that patient age, delayed-type hypersensitivity, and admission serum albumin level, not PMN adherence or chemotaxis, were significantly related to septic mortality. We concluded that altered circulating PMN adherence and chemotaxis is seen in all patients after an "activation" event such as trauma or sepsis. This is a nonspecific immune alteration not related to specific immune events such as delayed-type hypersensitivity; it does not correlate with patient outcome and should not be used as a predictive variable.     

Heat-killed probiotic Lactobacillus plantarum affects the function of neutrophils but does not improve survival in murine burn injury

Probiotics have become of interest as therapeutics in trauma or sepsis-induced inflammation due to their ability to affects the immune response. However, their use is still under debate due to the potential risk of septicemia. Therefore, heat-killed probiotics offer a potential alternative, with recent research suggesting a comparable immunomodulating potential and increased safety. In a previous study, we demonstrated decreased mortality by administration of live Lactobacillus plantarum in a mouse burn-sepsis model. Neutrophils are an essential innate defense against pathogens. Therefore, our present study aims to understand the impact of heat-killed probiotic L. plantarum (HKLP) on neutrophil function. Utilizing an in vitro stimulation with HKLP and a burn-infection in vivo model, we determined that administration of HKLP induced significant release of granulocyte-colony stimulating factor (G-CSF) and stimulated the release of pro-and anti-inflammatory cytokines. HKLP had no impact on neutrophil function, such as phagocytosis, oxidative burst, and NETosis, but increased apoptosis and activated neutrophils. HKLP did not improve survival. Together, contrary to our hypothesis, heat-killed probiotics did not improve neutrophil function and survival outcome in a murine severe burn injury model.     

Immune function and the role of vaccination after splenic artery embolization for blunt splenic injury

The spleen is the most commonly injured solid organ following blunt abdominal trauma. Over recent decades, splenic artery embolization (SAE) has become the mainstay treatment for haemodynamically stable patients with high-grade blunt splenic trauma, with splenectomy the mainstay of treatment for unstable patients. Splenic function is complex but the spleen has an important role in immune function, particularly in protection against encapsulated bacteria. Established evidence suggests that following splenectomy immune function is impaired resulting in increased susceptibility to overwhelming post-splenectomy infection, however, immune function may be preserved following SAE. This review will discuss the current state of the literature on immune function following different treatments of blunt splenic injury, and the controversies surrounding what constitutes a quantitative test of splenic immune function.     

Isolated blunt chest injury leads to transient activation of circulating neutrophils

Introduction  

The acute respiratory distress syndrome (ARDS) is a severe and frequently seen complication in multi-trauma patients. ARDS is caused by an excessive innate immune response with a clear role for neutrophils. As ARDS is more frequently seen in trauma patients with chest injury, we investigated the influence of chest injury on the systemic neutrophil response and the development of ARDS.     

Opioids modulate human neutrophil and lymphocyte function: thermal injury alters plasma beta-endorphin levels

To investigate the role of opioids in the acquired immune dysfunctional state that occurs after burns or trauma, plasma beta-endorphin levels were measured serially in nine severely burned patients, and the effect of four different opioids on normal neutrophil and lymphocyte function was quantitated. The rationale for these studies is that the neuroendocrine system appears capable of interacting with and modulating immune function. The plasma levels of beta-endorphin increased to higher than normal during the first 36 hours after burn (15 versus 3.4 pmol/L, p less than 0.05) but quickly returned toward normal. Morphine had the most profound effect on in vitro neutrophil function; it decreased neutrophil chemotaxis but increased neutrophil bactericidal activity for Staphylococcus aureus, as well as resting and zymosan-stimulated oxygen consumption. Other opioids (naloxone, met-enkephalin, and beta-endorphin) had no direct effect on neutrophil chemotaxis or bactericidal activity. Both naloxone and met-enkephalin increased neutrophil oxygen consumption in a dose-dependent fashion, whereas beta-endorphin impaired neutrophil oxygen consumption. None of the opioids altered resting lymphocyte blastogenesis. The only opioid that impaired the ability of normal lymphocytes to respond to mitogen stimulation at physiologically relevant doses was beta-endorphin. These results, documenting that beta-endorphin levels are altered after thermal injury and that opioids can modulate normal neutrophil and lymphocyte function in vitro, support the concept that changes in neuroendocrine activity may occur and potentially alter immune function.     

Effect of transfusion on immune function in a traumatized animal model

Blood transfusions repeatedly have been shown to prolong allograft survival, probably by stimulating suppressor T lymphocytes. The effects of transfusions on immune function in traumatized patients has not previously been investigated. We investigated the effects of transfusions on the immune system using a burned rat model. The transfusions were found to have no effect on the white blood cell counts, differential cell count, or neutrophil migration and bactericidal index. Those animals that received transfusion did exhibit impaired cell-mediated immunity and macrophage migration. Blood transfusions seem to increase further the immunosuppression seen with trauma and surgery.     

Back to basics: validation of the admission systemic inflammatory response syndrome score in predicting outcome in trauma

BACKGROUND: We have previously documented that the admission systemic inflammatory response syndrome (SIRS) score, calculated with four variables-temperature, heart rate, neutrophil count, and respiratory rate-is a significant predictor of outcome in trauma (n = 4,887). The objective of this current study was to validate our previous findings in a larger trauma patient population, to analyze the predictive accuracy of the four individual components of the SIRS score (temperature, heart rate, neutrophil count, and respiratory rate), and to assess whether the admission SIRS score is an accurate predictor of intensive care unit (ICU) resource use in trauma. METHODS: Prospective data were collected on 9,539 patients admitted to a Level I trauma center over a 30-month period (January 1997-July 1999). Patients were stratified by age, sex, race, and Injury Severity Score (ISS). SIRS score was calculated at admission, and SIRS was defined as a SIRS score > or = 2. RESULTS: SIRS score was validated as a significant independent predictor of outcome in trauma by logistic regression analysis after controlling for age and ISS. Of the four SIRS variables, hypothermia (temperature < 36 degrees C) was the most significant predictor of mortality after controlling for age and ISS. Leukocytosis (neutrophil count > 12,000/mm3) was the most significant predictor of total hospital length of stay. SIRS scores of > or = 2 were increasingly predictive of mortality and ICU admission by logistic regression analysis (p < 0.001). CONCLUSION: These data provide further validation that an admission SIRS score of > or = 2 is a significant independent predictor of outcome and ICU resource use in trauma. Temperature (hypothermia) is the individual component of the SIRS score with the greatest predictive accuracy. SIRS score should be calculated on all trauma admissions.     

The prognostic value of liver tumor T cell infiltrates

Tumor infiltrating lymphocytes (TIL) have been demonstrated to predict oncologic outcomes following resection of primary intrahepatic neoplasms and metastatic liver tumors. Despite strong immunosuppressive factors within the intrahepatic space, TIL are frequently demonstrated in liver tumors. The presence of TIL within liver tumors provides evidence of a host immune response that may be protective, but often is rendered ineffective by tumor induced immune dysfunction. In this review, we discuss techniques involved in studying TIL and subsets of TIL commonly identified. We emphasize the unique nature of the intrahepatic milieu that promotes immunosuppression, and how liver TIL and TIL ratios can be used as indicators of prognosis. Several types of primary and metastatic liver tumors are considered to highlight the similarities and important differences in TIL responses, which likely reflect how intrahepatic immunity is influenced by tumor biology. The studies we discuss indicate that tumor infiltration by suppressor cells and expression of immunoinhibitory molecules by TIL limits the anti-tumor immune function of effector T cells. Most patients fail to mount an adequate immune response to liver tumors, which provides compelling rationale for clinical study of immunotherapy for intrahepatic neoplasms.     

Urban injuries in Tehran: demography of trauma patients and evaluation of trauma care

Trauma now attracts more attention than ever before as a major cause of death and disability in developed and developing countries. To describe the characteristics and outcome of injuries in our environment, and to identify and discuss possible preventative and management protocols that may also be adopted in developing countries, we designed a prospective study on all trauma patients consecutively attending three emergency departments over a period of 1 year in Tehran, Iran.Among the total of 58013 patients studied, workers were the most vulnerable occupational group and deserve special preventative measures. The high frequency of traffic (especially pedestrian) accidents suggests that considerable progress is required in preventing these injuries.Our hospitalized patients were comparable with patients in the Major Trauma Outcome Study (m=0.890), and the z (-15.485) and w (-2.447) statistics showed an unsatisfactory quality of care, which may partly be due to less usage of ambulances, the long time of transportation to hospital, frequent referrals between centres, and delayed and inadequate resuscitation by the emergency services. Based on our findings and the fact that the positive effect of trauma systems on outcome has been well documented, we suggest that an integrated trauma system be established in Tehran to improve the quality of trauma care.     

Structure, function, and levels of neutrophil elastase after laparoscopic cholecystectomy

Neutrophil elastase is a neutral proteinase present mainly in the azurophilic granules of segmented granulocytes, the main cells involved in the inflammatory response reaction. In our study we attempted to determine whether an enzyme such as neutrophil elastase produced by polymorpho-nuclear leukocytes could be an indicator capable of determining the degree of surgical trauma, comparing two surgical approaches, namely, laparoscopic cholecystectomy and open cholecystectomy. Plasma neutrophil elastase was determined photometrically, using an immune-activation immunoassay, in 66 patients (32 patients underwent open cholecystectomy and 34 laparoscopic cholecystectomy) 1 day before surgery and 1, 3, 6 and 12 days after surgery. We established a reference range for elastase by measuring the serum elastase concentration in 48 healthy control patients. A significant increase (p < 0.05) in plasma neutrophil elastase levels was observed on days 1, 3 and 6 after surgery in patients undergoing open cholecystectomy, whereas the levels of the enzyme were almost stable in patients undergoing laparoscopic cholecystectomy. We recorded two cases (6.2%) of respiratory tract infections in the "open" group. Neutrophil elastase is a good indicator for discriminating the severity of the surgical trauma, which is certainly more severe in laparotomy than in laparascopic cholecystectomy. Peripheral leukocyte function seems to be better preserved after laparoscopic surgery than after laparotomy.     

The effects of estrogen on various organs: therapeutic approach for sepsis, trauma, and reperfusion injury. Part 2: liver, intestine, spleen, and kidney

Several clinical studies show a gender dimorphism of immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. However, there are conflicting reports on the role of gender in outcomes. Animal studies of shock, trauma, and sepsis have confirmed that alterations in immune and organ functions are more markedly depressed in adult males and in ovariectomized and aged females. In this review, we discuss the effect of estrogen on liver, intestinal, splenic, and renal functions in an experimental model of sepsis, trauma, and reperfusion injury. To establish the role of gender in the outcome of these patients, more studies in clinical and experimental settings are required to determine whether gender-specific responses are global across the injuries or are observed in specific injury situations. Studies are also needed to delineate underlying mechanisms responsible for differences between males and females. The findings gained from the experimental studies will help in designing innovative therapeutic approaches for the treatment of sepsis, trauma, and reperfusion injury patients.     

The value of trauma registries

Trauma registries are databases that document acute care delivered to patients hospitalised with injuries. They are designed to provide information that can be used to improve the efficiency and quality of trauma care. Indeed, the combination of trauma registry data at regional or national levels can produce very large databases that allow unprecedented opportunities for the evaluation of patient outcomes and inter-hospital comparisons. However, the creation and upkeep of trauma registries requires a substantial investment of money, time and effort, data quality is an important challenge and aggregated trauma data sets rarely represent a population-based sample of trauma. In addition, trauma hospitalisations are already routinely documented in administrative hospital discharge databases. The present review aims to provide evidence that trauma registry data can be used to improve the care dispensed to victims of injury in ways that could not be achieved with information from administrative databases alone. In addition, we will define the structure and purpose of contemporary trauma registries, acknowledge their limitations, and discuss possible ways to make them more useful.     

Stress hormones modulate neutrophil and lymphocyte activity in vitro

There is increasing evidence that stress hormones and neurotransmitters may represent an information channel between the immune, endocrine, and central nervous systems. The goal of this investigation was to determine the in vitro effect of selected stress hormones on neutrophil and lymphocyte function using leukocytes from healthy volunteers. The following hormones were tested using a complete dose response curve including dosages within the physiological range; cortisol, epinephrine, norepinephrine, and glucagon. Cortisol did not affect neutrophil function, but did suppress lymphocyte blastogenesis. The catecholamines, epinephrine, and norepinephrine inhibited only neutrophil chemotaxis, while glucagon impaired both neutrophil chemotactic and bactericidal activity. When the individual hormones were combined into hormone cocktails, the inhibitory effect of both epinephrine and glucagon on neutrophil function was lost, while the inhibitory effect of cortisol on lymphocyte blastogenesis was greatly reduced. In fact, incubation of neutrophils in the stress hormone cocktail resulted in the neutrophils becoming hypermetabolic. Although the in vitro effects of these hormones on neutrophil and lymphocyte function do not fully correlate with the in vivo effect of trauma on immune function, these studies do support the general concept that the stress hormones may represent a link between the immune and endocrine systems.     

Blunt trauma-induced upper extremity vascular injuries

Penetrating vascular injury which is associated with a satisfactory response to treatment occurs more commonly than blunt injury in the upper limb. Blunt trauma is a complex entity with associated soft tissue and skeletal injuries that may determine outcome irrespective of successful vascular repair. We reviewed 50 patients with upper limb vascular injury of which 43 were due to blunt trauma and seven to penetrating trauma. All patients with penetrating trauma had a good result without loss of limb function. Eight amputations and residual poor limb function in ten patients confirm the poor results of blunt injury. Associated nerve damage, responsible for nine of the ten poorly functioning limbs, is the most important determinant of outcome in limbs surviving the peri-traumatic period.     

Use of prokinetic agents in hospitalised adult patients: A scoping review

Background

Gastrointestinal motility is important for adequate uptake of fluids and nutrition but is often impaired in hospitalised patients. Prokinetic agents enhance gastrointestinal motility and are prescribed for many hospitalised patients. In this scoping review, we aimed to systematically describe the body of evidence on the use of prokinetic agents in hospitalised patients. We hypothesised, that the body of evidence would be limited and derive from heterogeneous populations.

Methods

We conducted this scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews statement. We searched Medline, Embase, Epistemonikos and the Cochrane Library for studies assessing the use of prokinetic agents on any indication and outcome in adult hospitalised patients. We used a modified version of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence.

Results

We included 102 studies with a total of 8830 patients. Eighty-six studies were clinical trials (84%), and 52 (60%) of these were conducted in the intensive care unit, with feeding intolerance as the main indication. In the non-intensive care setting the indications were wider; most studies assessed use of prokinetic agents before gastroscopy to improve visualisation. The most studied prokinetic agent was metoclopramide (49% of studies) followed by erythromycin (31%). In total 147 outcomes were assessed with only 67% of the included studies assessing patient-centred outcomes, and with gastric emptying as the most frequently reported outcome. Overall, the data provided no firm evidence on the balance between the desirable and undesirable effects of prokinetic agents.

Conclusions

In this scoping review, we found that the studies addressing prokinetic agents in hospitalised adults had considerable variations in indications, drugs and outcomes assessed, and that the certainty of evidence was judged to be low to very low.     

The systemic inflammatory response induced by trauma is reflected by multiple phenotypes of blood neutrophils

Secondary morbidity and mortality after trauma are mainly due to a dysfunctional immune system. Severe injury can trigger a systemic inflammatory response, which is characterised by pre-activation or priming of neutrophils in peripheral blood. Signals initiated as result of local tissue damage can further activate these neutrophils leading to post-injury inflammatory complications. Additional trauma caused by surgical intervention can worsen the inflammatory response, thereby increasing the risk of these inflammatory complications. Limiting surgical procedures through damage control principles can reduce the risk of secondary morbidity.

Inflammatory complications after injury cannot adequately be predicted using the current anatomical and physiological-based scoring systems. In this review we propose a methodology focussing on the activation state of the systemic inflammatory response with focus on neutrophils to aid in the risk assessment of secondary morbidity after trauma. Neutrophils are essential effector cells during the post-injury systemic inflammatory response. Neutrophils differentially express an array of surface receptors by which the cells can respond and adapt to changing environmental signals. The determination of specific expression profiles of neutrophil receptors can aid in phenotyping and quantifying the systemic inflammatory response. This article reviews the application of these specific signatures of neutrophil receptors as a consequence of severe injury.     

Measuring spine fracture outcomes: common scales and checklists

Introduction

Although outcome instruments have been used extensively in spine surgical research, few studies at present specifically address their use in investigations regarding spine trauma. In this review we provide a summary of the outcome instruments used most frequently in spine trauma research, identify the unique challenges of studying outcomes of spine trauma patients, and propose an integrated approach that may be beneficial for future studies.

Methods

We reviewed the use of outcome instruments applicable to spine trauma research, including generic health measures, inventories of back-specific function, pain scales, health related quality of life (HRQOL) instruments, and radiographic determinants of outcome.

Results

Several inventories have been utilised to measure clinical outcomes following spinal trauma. Excluding measures of neurological function (e.g. ASIA motor score), none have been specifically validated for use with spine fractures. The SF-36, RMDQ, and ODI are amongst the most commonly used instruments. Importantly, the use of validated functional outcome measures in spine trauma research is hampered by the fact that the pre-morbid state of patients who sustain spine trauma may not be accurately represented by normative values established for the general population. The VAS is used most frequently to assess degree of neck and back pain. Most studies have relied on non-validated measures to determine radiographic results of treatment, although more elegant radiographic metrics exist.

Conclusions

Functional outcome measurement of traumatically injured spine patients is challenging because available generic and spine-specific instruments were not designed for or validated in this population. Furthermore, no single inventory is capable of capturing global data necessary to evaluate results following these injuries. Investigations seeking to quantify outcomes following spine trauma should consider the use of a combination of existing surveys in a complementary fashion that should include a generic health survey, a measure of back-specific function, and determinants of bodily pain and work-related disability.     

Early proximal row carpectomy after severe carpal trauma

Complex fracture dislocations of the wrist often result in post-traumatic arthrosis. In these cases, patients can experience severe pain and loss of function of the wrist and as a result many of them end up having a total arthrodesis. In trying to avoid the disadvantages of a total arthrodesis, alternative treatment strategies have been investigated, amongst which proximal row carpectomy (PRC). Basic conditions for a good outcome of PRC are an intact cartilage of the lunate fossa of the distal radius and an intact surface of the head of the capitate for the new radiocapitate joint (, schematic drawing post-PRC). Also, an intact (volar) radioscaphocapitate (RSC) ligament is necessary because it plays an essential role in stabilizing the new joint and preventing volar dislocation and ulnar translocation of the distal carpal row. Acute post-traumatic PRC can be indicated, but is rarely reported in literature. In this article, we present four patients whom we have treated with early PRC after severe trauma of the wrist. Three patients had a good outcome. In the patient with the bad outcome, the before-mentioned prerequisites were not met, which is discussed.     

CXCL5 Drives Neutrophil Recruitment in TH17-Mediated GN

Neutrophil trafficking to sites of inflammation is essential for the defense against bacterial and fungal infections, but also contributes to tissue damage in T_H17-mediated autoimmunity. This process is regulated by chemokines, which often show an overlapping expression pattern and function in pathogen- and autoimmune-induced inflammatory reactions. Using a murine model of crescentic GN, we show that the pathogenic T_H17/IL-17 immune response induces chemokine (C-X-C motif) ligand 5 (CXCL5) expression in kidney tubular cells, which recruits destructive neutrophils that contribute to renal tissue injury. By contrast, CXCL5 was dispensable for neutrophil recruitment and effective bacterial clearance in a murine model of acute bacterial pyelonephritis. In line with these findings, CXCL5 expression was highly upregulated in the kidneys of patients with ANCA-associated crescentic GN as opposed to patients with acute bacterial pyelonephritis. Our data therefore identify CXCL5 as a potential therapeutic target for the restriction of pathogenic neutrophil infiltration in T_H17-mediated autoimmune diseases while leaving intact the neutrophil function in protective immunity against invading pathogens.     

Safety and efficacy of vena cava filters in trauma patients

Pulmonary embolism (PE), due to its sudden onset, notoriously difficult diagnosis, unpredictable nature and often fatal outcome, remains one of the most feared complications in surgical practice. Trauma patients with multisystem injuries, extremity or pelvic fractures and head or spinal cord injuries often pose a significant dilemma for the surgeon because of the inability to use conventional measures such as anticoagulation therapy and compression devices. On the other hand, the incidence of deep vein thrombosis (DVT) is high among trauma patients and the attendant risk of PE is an important cause of morbidity and mortality. Inferior vena cava (IVC) interruption by placement of diverse filtering devices has evolved over the past three decades. With the use of these devices, the risk of PE has been reduced dramatically. However, variable rates of complications are reported from their use. In this study, we review all the available data on IVC filter placement in trauma patients and we discuss the potential complications of IVC filters in order to understand better the risk/benefit ratio of their use.