Feasibility of pleural and perilesional subcutaneous microdialysis to assess porcine experimental pulmonary contusion.

Background: Severe thoracic trauma affects 55% of patients with multiple traumatic injuries and may lead to acute lung injury or acute respiratory distress syndrome. Pulmonary trauma differs clinically and biologically from lung injury of other origins and carries a mortality rate of 10%. Treatment options are limited, and it is not possible to monitor the progression of lung injury with specific biomarkers. Microdialysis of pleural fluid may offer a viable entry to monitor the lung directly and specifically. Bronchial microdialysis has been described, but not pleural microdialysis. We therefore investigated the feasibility of microdialysis of pleural fluid, and its ability to detect pulmonary injury and inflammation in the pleural cavity after traumatic acute lung injury.Methods: 16 pigs (mean weight 64 kg) were randomized to groups "exposed with MD", receiving a focally severe pulmonary contusion and microdialysis (n = 7), "control with MD", receiving only microdialysis and no pulmonary contusion (n = 5), "normal no MD" receiving only anesthesia (n = 2) and "naïve no MD" (no instrumentation) (n = 2). Microdialysate from the pleura and the perilesional subcutis, plasma and bronchoalveolar lavage were collected for 5 hours.Results: Pleura lactate, plasma lactate and pleura lactate/pyruvate ratio increased in injured lungs (p < 0.05). Subcutis and plasma glucose increased after trauma (p < 0.05). Pleura glycerol increased although not reaching statistical significance. IL-6 and IL-8 were dissimilar in plasma, bronchoalveolar lavage and pleural fluid, while IL-1 did not differ. Neutrophils increased in bronchoalveolar lavage (p < 0.001) after trauma, and in pleural fluid, although not when the microdialysis catheter was omitted.Conclusion: Pleural microdialysis was technically feasible and detected signs of cellular injury and anaerobic metabolism after focally severe pulmonary contusion and may be of interest for future clinical applications. The microdialysis catheter triggered a recruitment of neutrophils to the pleura which needs to be elucidated further before taking the technique into clinical practice.

Transcatheter Arterial Embolization Compared With Surgery for Uncontrolled Peptic Ulcer Bleeding: A Population-based Cohort Study.

OBJECTIVE: To compare key outcomes after transcatheter arterial embolization (TAE) with conventional surgery for peptic ulcer bleeding when endoscopic intervention fails to achieve hemostasis. BACKGROUND: Mortality in peptic ulcer bleeding remains high, especially in patients who require surgical treatment. METHODS: A population-based cohort study in Stockholm, Sweden, in 2000 to 2014, assessing the main outcome all-cause mortality and the secondary outcomes re-bleeding, re-intervention, length of hospitalization, and complications, was conducted. Data were taken from well-maintained registries and medical records. Multivariable Cox-regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, ulcer history, comorbidity, and calendar period were considered. RESULTS: Included were 282 patients, 97 in the TAE group and 185 in the surgery group. Compared with the surgery group, the overall hazard of death was 34% decreased in the TAE group (adjusted HR 0.66, 95% CI 0.46-0.96). The corresponding HRs for mortality within 30 days, 90 days, 1 year, and 5 years were 0.70 (95% CI 0.37-1.35), 0.69 (95% CI 0.38-1.26), 0.88 (95% CI 0.53-1.47), and 0.67 (95% CI 0.45-1.00), respectively. The risk of re-bleeding was higher after TAE compared with surgery (HR 2.48, 95% CI 1.33-4.62). The median length of hospital stay was shorter in the TAE group-8 versus 16 days-acceleration factor 0.59 (95% CI 0.45-0.77) and the risk of complications was lower (8.3% vs 32.2%; P < 0.0001). CONCLUSIONS: This study indicates that TAE compares favorably with surgery regarding prognosis after refractory peptic ulcer bleeding, and the shorter length of hospital stay and fewer complications outweigh a higher risk of re-bleeding. TAE could be recommended as first-line treatment for these patients.

Surgeon-Performed Ultrasound in Diagnosing Acute Cholecystitis and Appendicitis.

BACKGROUND: The use of ultrasound (US) outside the radiology department has increased the last decades, but large studies assessing the quality of bedside US are still lacking. This study evaluates surgeon-performed US (SPUS) and radiologist-performed US (RPUS) with respect to biliary disease and appendicitis. METHODS: Between October 2011 and November 2012, 300 adult patients, with a referral for an abdominal US, were prospectively enrolled in the study and examined by a radiologist as well as a surgeon. The surgeons had undergone a 4-week-long US education. US findings of the surgeon and of the radiologist were compared to final diagnosis, set by an independent external observer going through each patient's chart. RESULTS: Among 183 patients with suspected biliary disease, 74 had gallstones and 21 had acute cholecystitis. SPUS and RPUS diagnosed gallstones with a sensitivity of 87.1 versus 97.3%. Specificity was 96.0 versus 98.9%, and the accuracy 92.3 versus 98.2%. The sensitivity, specificity and accuracy for acute cholecystitis by SPUS and RPUS were: 60.0 versus 80.0%, 98.6 versus 97.8% and 93.9 versus 95.6%, respectively. Among 58 patients with suspected appendicitis, 15 had the disease. The sensitivity, specificity and accuracy for appendicitis by SPUS and RPUS were: 53.3 versus 73.3%, 89.7 versus 93.3% and 77.3 versus 86.7%, respectively. CONCLUSION: SPUS is reliable in diagnosing gallstones. Diagnosing cholecystitis and appendicitis with US is more challenging for both surgeons and radiologists. TRIAL REGISTRATION NUMBER: The study was registered at clinicaltrials.gov. Registration number: NCT02469935.

Impact of postoperative complications on the risk for chronic groin pain after open inguinal hernia repair.

BACKGROUND: Chronic pain is common after inguinal hernia repair and has become one of the most important outcome measures for this procedure. The purpose of this study was to determine whether or not there is a relationship between specific postoperative complications and risk for chronic pain after open inguinal hernia repair. METHODS: A prospective cohort study was designed in which participants responded to the Inguinal Pain Questionnaire regarding postoperative groin pain 8 years after inguinal hernia repair. Responses to the questionnaire were matched with data from a previous study regarding reported postoperative complications after open inguinal hernia repair. Participants were recruited originally from the Swedish Hernia Register. Response rate was 82.4% (952/1,155). The primary outcome was chronic pain in the operated groin at follow-up. Grading of pain was performed using the Inguinal Pain Questionnaire. RESULTS: A total of 170 patients (17.9%) reported groin pain and 29 patients (3.0%) reported severe groin pain. The risk for developing chronic groin pain was greater in patients with severe pain in the preoperative or immediate postoperative period (odds ratio 2.09; 95% confidence interval 1.28-3.41). Risk for chronic pain decreased for every 1-year increase in age at the time of operation (odds ratio 0.99, 95% confidence interval 0.98-1.00). CONCLUSION: Both preoperative pain and pain in the immediate postoperative period are strong risk factors for chronic groin pain. Risk factor patterns should be considered before operative repair of presumed symptomatic inguinal hernias. The problem of postoperative pain must be addressed regarding both pre-emptive and postoperative analgesia.

Accuracy of Surgeon-Performed Ultrasound in Detecting Gallstones: A Validation Study.

BACKGROUND: Symptomatic gallstone disease is a common diagnosis in patients with abdominal pain. Ultrasound is considered the gold standard method to identify gallstones. Today the examination may be performed bedside by the treating clinician. Bedside ultrasound could provide a safe and time-saving diagnostic resource for surgeons evaluating patients with suspected symptomatic gallstones; however, large validation studies of the accuracy and reliability are lacking. The aim of this study was to prospectively investigate the accuracy of surgeon-performed ultrasound for the detection of gallstones. METHODS: Between October 2011 and November 2012, 179 adult patients, with an acute or elective referral for an abdominal ultrasound examination, were examined with a right upper quadrant ultrasound scan by a radiologist as well as a surgeon. The surgeons had undergone a four-week-long ultrasound education before participating in the study. Ultrasound findings of the surgeon were compared to those of the radiologist, using radiologist-performed ultrasound as reference standard. RESULTS: Surgeon-performed ultrasound agreed with radiologist findings in 169 of 179 patients regarding the detection of gallstones, providing an accuracy of 94 %. The sensitivity was 88 % (67/76), specificity 99 % (102/103), positive predictive value 99 % (67/68), and negative predictive value 92 % (102/111). Agreement between the diagnosis set by the radiologists and the surgeons was high: Cohen's Kappa coefficient = 0.88. CONCLUSIONS: Ultrasound-trained surgeons may accurately diagnose gallstones using ultrasound and reach a high level of agreement with radiologists.

Cellular High-Energy Cavitation Trauma - Description of a Novel In Vitro Trauma Model in Three Different Cell Types.

The mechanisms involved in traumatic brain injury have yet to be fully characterized. One mechanism that, especially in high-energy trauma, could be of importance is cavitation. Cavitation can be described as a process of vaporization, bubble generation, and bubble implosion as a result of a decrease and subsequent increase in pressure. Cavitation as an injury mechanism is difficult to visualize and model due to its short duration and limited spatial distribution. One strategy to analyze the cellular response of cavitation is to employ suitable in vitro models. The flyer-plate model is an in vitro high-energy trauma model that includes cavitation as a trauma mechanism. A copper fragment is accelerated by means of a laser, hits the bottom of a cell culture well causing cavitation, and shock waves inside the well and cell medium. We have found the flyer-plate model to be efficient, reproducible, and easy to control. In this study, we have used the model to analyze the cellular response to microcavitation in SH-SY5Y neuroblastoma, Caco-2, and C6 glioma cell lines. Mitotic activity in neuroblastoma and glioma was investigated with BrdU staining, and cell numbers were calculated using automated time-lapse imaging. We found variations between cell types and between different zones surrounding the lesion with these methods. It was also shown that the injured cell cultures released S-100B in a dose-dependent manner. Using gene expression microarray, a number of gene families of potential interest were found to be strongly, but differently regulated in neuroblastoma and glioma at 24 h post trauma. The data from the gene expression arrays may be used to identify new candidates for biomarkers in cavitation trauma. We conclude that our model is useful for studies of trauma in vitro and that it could be applied in future treatment studies.

Risk Factors for Marginal Ulcer After Gastric Bypass Surgery for Obesity: A Population-based Cohort Study.

OBJECTIVE: This study aimed to assess risk factors for developing marginal ulcer (MU) after gastric bypass (GBP) surgery for obesity. BACKGROUND: MU is a common and potentially serious complication of GBP surgery, little is known about its etiology. METHODS: This population-based cohort study of GBP in 2006-2011 evaluated MU in relation to diabetes, hyperlipidemia, hypertension, chronic obstructive pulmonary disease (COPD), ulcer history, use of proton pump inhibitors (PPIs), aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective serotonin reuptake inhibitors (SSRIs). Multivariable Cox proportional hazard regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for confounding. RESULTS: Among 20,294 GBP patients, diabetes and peptic ulcer history entailed statistically significantly increased risk of MU (HR = 1.26, 95% CI 1.03-1.55 and HR  =  2.70, 95% CI 1.81-4.03), although hyperlipidemia, hypertension, and COPD did not. PPI users had an increased HR of MU (HR  =  1.37, 95% CI 1.17-1.60). Aspirin and NSAID consumption less than or equal to median entailed decreased HRs of MU (HR  =  0.56, 95% CI 0.37-0.86 and HR  =  0.30, 95% CI 0.24-0.38), although aspirin and NSAID users more than median had an increased risk and no association with MU, respectively (HR  =  1.90, 95% CI 1.41-2.58 and HR  =  0.90, 95% CI 0.76-1.87). The use of SSRI less than or equal to median had a decreased risk of MU (HR  =  0.50, 95% CI 0.37-0.67), although use more than median entailed increased HR (HR  =  1.26, 95% CI 1.01-1.56). CONCLUSIONS: Diabetes and peptic ulcer history seem to be risk factors for MU, but not hyperlipidemia, hypertension, or COPD. Limited doses of aspirin, NSAIDs, and SSRIs might not increase the risk, although higher doses of aspirin do. The association with PPI could be due to confounding by indication.

Minimal versus definitive surgery in managing peptic ulcer bleeding: a population-based cohort study.

OBJECTIVE: To compare radical surgery with a minimal approach for peptic ulcer bleeding in relation to survival. DESIGN: A Swedish nationwide population-based cohort study from 1987-2008 compared survival after minimal surgery and definitive surgery. The cohort was also stratified into calendar year before and after the year 2000 for subgroup analyses. Data were collected from the Swedish Patient Register. The two surgical groups were matched based on the propensity score to mimic a randomized trial design. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounders. RESULTS: 4,163 patients were included. There were no differences in survival in patients who underwent definitive surgical procedures compared to those who underwent minimal surgery for a bleeding peptic ulcer during the full study period. Using minimal surgery group as the reference, the HRs for death in the definitive surgery group within 30 days, 90 days, 1 year, and 5 years were 0.87 (95% CI 0.72-1.05), 0.93 (0.80-1.09), 1.00 (95% CI 0.87-1.14), and 1.05 (95% CI 0.95-1.16), respectively. The corresponding HRs during the calendar period after the year 2000 were 1.05 (95% CI 0.65-1.69), 1.18 (95% CI 0.81-1.73), 1.17 (0.84-1.62), and 1.27 (95% CI 0.99-1.63), respectively. CONCLUSION: This study found no worse overall survival after minimal surgery compared to more extensive surgery for refractory peptic ulcer bleeding, and indicated better long-term survival in the minimal surgery group during the more recent study period. A minimal approach is probably sufficient in most cases.

Shock wave trauma leads to inflammatory response and morphological activation in macrophage cell lines, but does not induce iNOS or NO synthesis.

BACKGROUND: Experimental CNS trauma results in post-traumatic inflammation for which microglia and macrophages are vital. Experimental brain contusion entails iNOS synthesis and formation of free radicals, NO and peroxynitrite. Shock wave trauma can be used as a model of high-energy trauma in cell culture. It is known that shock wave trauma causes sub-lytic injury and inflammatory activation in endothelial cells. Mechanical disruption of red blood cells can induce iNOS synthesis in experimental systems. However, it is not known whether trauma can induce activation and iNOS synthesis in inflammatory cell lines with microglial or macrophage lineage. We studied the response and activation in two macrophage cell lines and the consequence for iNOS and NO formation after shock wave trauma. METHODS: Two macrophage cell lines from rat (NR8383) and mouse (RAW264.7) were exposed to shock wave trauma by the Flyer Plate method. The cellular response was investigated by Affymetrix gene arrays. Cell survival and morphological activation was monitored for 24 h in a Cell-IQ live cell imaging system. iNOS induction and NO synthesis were analyzed by Western blot, in cell Western IR-immunofluorescence, and Griess nitrite assay. RESULTS: Morphological signs of activation were detected in both macrophage cell lines. The activation of RAW264.7 was statistically significant (p < 0.05), but activation of NR8383 did not pass the threshold of statistical significance alpha (p > 0.05). The growth rate of idle cells was unaffected and growth arrest was not seen. Trauma did not result in iNOS synthesis or NO induction. Gene array analyses showed high enrichment for inflammatory response, G-protein coupled signaling, detection of stimulus and chemotaxis. Shock wave trauma combined with low LPS stimulation instead led to high enrichment in apoptosis, IL-8 signaling, mitosis and DNA-related activities. LPS/IFN-É£ stimulation caused iNOS and NO induction and morphological activation in both cell lines. CONCLUSIONS: Shock wave trauma by the Flyer Plate method caused an inflammatory response and morphological signs of activation in two macrophage cell lines, while iNOS induction appeared to require humoral signaling by LPS/IFN-É£. Our findings indicated that direct energy transfer by trauma can activate macrophages directly without humoral mediators, which comprises a novel activation mechanism of macrophages.

Patient factors influencing the effect of surgeon-performed ultrasound on the acute abdomen.

PURPOSE: To evaluate the effect of surgeon-performed ultrasound on acute abdomen in specific patient subgroups regarding the diagnostic accuracy and further management. METHODS: Eight hundred patients attending the emergency department at Stockholm South General Hospital, Sweden, for abdominal pain, were randomized to either receive or not receive surgeon-performed ultrasound as a complement to routine management. Patients were divided into subgroups based on patient characteristics, symptoms or first preliminary diagnosis set at the emergency department before randomization. Outcomes measured were diagnostic accuracy, admission rate and requests for further examinations. Timing of surgery was evaluated for patients with peritonitis. RESULTS: Increased diagnostic accuracy was seen in patients with body mass index > 25, elevated C-reactive protein, peritonitis, age 30-59 years and/or upper abdominal pain. Decreased need for further examinations and/or fewer admissions were seen in all groups except in patients with a preliminary diagnosis of appendicitis. Among patients with non-specific abdominal pain, admission frequency was decreased with 14% when ultrasound was used (P = 0.007). Among patients with peritonitis, requiring surgery, 61% in the ultrasound group were admitted for surgery directly from the emergency department compared to 19% in the control group. CONCLUSION: In different ways, surgeon-performed ultrasound is helpful for the majority of patients admitted to the emergency department for abdominal pain. Taking into account other shown benefits and the lack of adverse effects, we find the method worth consideration for routine implementation.

Mechanisms of shock wave induced endothelial cell injury.

BACKGROUND AND OBJECTIVES: Medical procedures, for example, laser angioplasty and extracorporeal lithotripsy as well as high-energy trauma expose human tissues to shock waves (SWs) that may cause tissue injury. The mechanisms for this injury, often affecting blood vessel walls, are poorly understood. Here we sought to assess the role of two suggested factors, viz., cavitation or reactive oxygen species (ROS). STUDY DESIGN/MATERIALS AND METHODS: A laser driven flyer-plate model was used to expose human umbilical cord vein endothelial cell (HUVEC) monolayers to SWs or to SWs plus cavitation (SWC). Cell injury was quantified with morphometry, trypan blue staining, and release of (51)Cr from labeled HUVECs. RESULTS: HUVECs, exposed to SWs only, could not be distinguished from controls in morphological appearance or ability to exclude trypan blue. Yet, release of (51)Cr, indicated a significant cell injury (P < 0.05). HUVEC cultures exposed to SWC, exhibited cell detachment and cell membrane damage detectable with trypan blue. Release of (51)Cr was fourfold compared to SW samples (P < 0.01). Signs of cell injury were evident at 15 minutes and did not change over the next 4 hours. No protective effects of ROS scavengers were demonstrated. CONCLUSIONS: Independent of ROS, SWC generated an immediate cell injury, which can explain, for example, vessel wall perturbation described in relation to SW treatments and trauma.