Pharmacologic prevention and therapy of postoperative paralytic ileus after gastrointestinal cancer surgery: systematic review and meta-analysis.

BACKGROUND: Postoperative paralytic ileus (POI) is a significant concern following gastrointestinal tumor surgery. Effective preventive and therapeutic strategies are crucial but remain elusive. Current evidence from randomized-controlled trials on pharmacological interventions for prevention or treatment of POI are systematically reviewed to guide clinical practice and future research. MATERIALS AND METHODS: Literature was systematically searched for prospective randomized-controlled trials testing pharmacological interventions for prevention or treatment of POI after gastrointestinal tumor surgery. Meta-analysis was performed using a random effects model to determine risk ratios and mean differences with 95% CI. Risk of bias and evidence quality were assessed. RESULTS: Results from 55 studies, involving 5078 patients who received experimental interventions, indicate that approaches of opioid-sparing analgesia, peripheral opioid antagonism, reduction of sympathetic hyperreactivity, and early use of laxatives effectively prevent POI. Perioperative oral Alvimopan or intravenous administration of Lidocaine or Dexmedetomidine, while safe regarding cardio-pulmonary complications, demonstrated effectiveness concerning various aspects of postoperative bowel recovery [Lidocaine: -5.97 (-7.20 to -4.74)h, P <0.0001; Dexmedetomidine: -13.00 (-24.87 to -1.14)h, P =0.03 for time to first defecation; Alvimopan: -15.33 (-21.22 to -9.44)h, P <0.0001 for time to GI-2 ] and length of hospitalization [Lidocaine: -0.67 (-1.24 to -0.09)d, P =0.02; Dexmedetomidine: -1.28 (-1.96 to -0.60)d, P =0.0002; Alvimopan: -0.58 (-0.84 to -0.32)d, P <0.0001] across wide ranges of evidence quality. Perioperative nonopioid analgesic use showed efficacy concerning bowel recovery as well as length of hospitalization [-1.29 (-1.95 to -0.62)d, P =0.0001]. Laxatives showed efficacy regarding bowel movements, but not food tolerance and hospitalization. Evidence supporting pharmacological treatment for clinically evident POI is limited. Results from one single study suggest that Neostigmine reduces time to flatus and accelerates bowel movements [-37.06 (-40.26 to -33.87)h, P <0.0001 and -42.97 (-47.60 to -38.35)h, P <0.0001, respectively] with low evidence quality. CONCLUSION: Current evidence concerning pharmacological prevention and treatment of POI following gastrointestinal tumor surgery is limited. Opioid-sparing concepts, reduction of sympathetic hyperreactivity, and laxatives should be implemented into multimodal perioperative approaches.

Outcomes of totally robotic Roux-en-Y gastric bypass in patients with BMI ≥ 50 kg/m2: can the robot level out "traditional" risk factors?

Roux-en-Y gastric bypass (RYGB) in patients with body mass index (BMI) ≥ 50 kg/m2 is a challenging procedure and BMI ≥ 50 kg/m2 has been identified as independent risk factor for postoperative complications and increased morbidity in previous studies. The objective of the present study was to assess whether a BMI ≥ 50 kg/m2 and various established risk factors maintain their significance in patients undergoing fully robotic RYGB (rRYGB). A single-center analysis of prospectively collected data of 113 consecutive patients undergoing standardized rRYGB with robotic stapling technique and hand-sewn gastrojejunostomy using the daVinci Xi system. Surgical outcomes were analyzed considering a number of individual perioperative risk factors including BMI ≥ 50 kg/m2. The mean BMI of the total cohort was 50.6 ± 5.5 kg/m2 and 63.7% of patients had a BMI ≥ 50 kg/m2. There were no major surgical and perioperative complications in patients with BMI ≥ 50 kg/m2 as well as in those with BMI < 50 kg/m2 after rRYGB. We identified female sex and surgeon experience but neither body weight, BMI, metabolic disorders, ASA nor EOSS scores as independent factors for shorter operation times (OT) in multivariate analyses. Complication rates and length of hospital stay (LOS) did not significantly differ between patients with potential risk factors and those without. rRYGB is a safe procedure in both, patients with BMI ≥ 50 kg/m2 and with BMI < 50 kg/m2. Higher body weight and BMI did affect neither OT nor LOS. A fully robotic approach for RYGB might help to overcome "traditional" risk factors identified in conventional laparoscopic bariatric surgery. However, larger and prospective studies are necessary to confirm these results.

New Perianal Sepsis Risk Score Predicts Outcome of Elderly Patients with Perianal Abscesses.

Antibiotic therapy following surgical perianal abscess drainage is debated, but may be necessary for high-risk patients. Frailty has been shown to increase the risk of unfavorable outcomes in elderly surgical patients. This study aims to identify high-risk patients by retrospectively analyzing a single-center cohort and using a pretherapeutic score to predict the need for postoperative antibiotics and extended nursing care following perianal abscess drainage surgery. The perianal sepsis risk score was developed through univariable and multivariable analysis. Internal validation was assessed using the area under receiver-operating characteristic curve. Elderly, especially frail patients exhibited more severe perianal disease, higher frequency of antibiotic therapy, longer hospitalization, poorer clinical outcomes. Multivariable analysis revealed that scores in the 5-item modified frailty index, severity of local infection, and preoperative laboratory markers of infection independently predicted the need for prolonged hospitalization and anti-infective therapy after abscess drainage surgery. These factors were combined into the perianal sepsis risk score, which demonstrated better predictive accuracy for prolonged hospitalization and antibiotic therapy compared with chronological age or frailty status alone. Geriatric assessments are becoming increasingly important in clinical practice. The perianal sepsis risk score identifies high-risk patients before surgery, enabling early initiation of antibiotic therapy and allocation of additional nursing resources.

[Acute mesenteric ischemia-An overview and recommendations (S2k analogous) of the World Society of Emergency Surgery]. / Die akute Mesenterialischämie ­ eine Übersicht und Empfehlungen (S2k-analog) der World Society of Emergency Surgery.

Acute mesenteric ischemia is a severe illness, which if untreated, rapidly leads to a critical condition with sepsis, multiple organ failure and death in affected patients. The diagnosis and initiation of treatment of acute mesenteric ischemia should be performed as early and expeditiously as possible and follows the principle of the shortest possible time to reperfusion. Otherwise, the outcome of the patient rapidly deteriorates. The treatment algorithm should be adapted to the pathogenesis of the ischemia, the clinical condition and symptoms of the patients. With clinical signs of peritonitis, intestinal gangrene must be assumed and the abdomen should be surgically explored to detect and treat possible foci of sepsis at an early stage. The treatment of acute mesenteric ischemia should always be performed by an interdisciplinary team with all surgical and interventional options for intestinal revascularization as well as comprehensive intensive care medicine according to the standards of the Intestinal Stroke Center described in the literature. A short duration to revascularization and treatment in this interdisciplinary concept improves the outcome of patients with acute mesenteric ischemia. The World Society of Emergency Surgery provides expert consensus-based recommendations for the diagnosis and treatment of acute mesenteric ischemia; however, there is still a significant lack of broad high-quality evidence for this critical illness. Recommendations of the German specialist societies are urgently needed to ensure appropriate care, from the initial diagnostics to treatment and aftercare, for patients with suspected mesenteric ischemia in this country.

Pediatric trauma and emergency surgery: an international cross-sectional survey among WSES members.

BACKGROUND: In contrast to adults, the situation for pediatric trauma care from an international point of view and the global management of severely injured children remain rather unclear. The current study investigates structural management of pediatric trauma in centers of different trauma levels as well as experiences with pediatric trauma management around the world. METHODS: A web-survey had been distributed to the global mailing list of the World Society of Emergency Surgery from 10/2021-03/2022, investigating characteristics of respondents and affiliated hospitals, case-load of pediatric trauma patients, capacities and infrastructure for critical care in children, trauma team composition, clinical work-up and individual experiences with pediatric trauma management in response to patients´ age. The collaboration group was subdivided regarding sizes of affiliated hospitals to allow comparisons concerning hospital volumes. Comparable results were conducted to statistical analysis. RESULTS: A total of 133 participants from 34 countries, i.e. 5 continents responded to the survey. They were most commonly affiliated with larger hospitals (> 500 beds in 72.9%) and with level I or II trauma centers (82.0%), respectively. 74.4% of hospitals offer unrestricted pediatric medical care, but only 63.2% and 42.9% of the participants had sufficient experiences with trauma care in children ≤ 10 and ≤ 5 years of age (p = 0.0014). This situation is aggravated in participants from smaller hospitals (p < 0.01). With regard to hospital size (≤ 500 versus > 500 in-hospital beds), larger hospitals were more likely affiliated with advanced trauma centers, more elaborated pediatric intensive care infrastructure (p < 0.0001), treated children at all ages more frequently (p = 0.0938) and have higher case-loads of severely injured children < 12 years of age (p = 0.0009). Therefore, the majority of larger hospitals reserve either pediatric surgery departments or board-certified pediatric surgeons (p < 0.0001) and in-hospital trauma management is conducted more multi-disciplinarily. However, the majority of respondents does not feel prepared for treatment of severe pediatric trauma and call for special educational and practical training courses (overall: 80.2% and 64.3%, respectively). CONCLUSIONS: Multi-professional management of pediatric trauma and individual experiences with severely injured children depend on volumes, level of trauma centers and infrastructure of the hospital. However, respondents from hospitals at all levels of trauma care complain about an alarming lack of knowledge on pediatric trauma management.

Establishing robotic bariatric surgery at an academic tertiary hospital: a learning curve analysis for totally robotic Roux-en-Y gastric bypass.

The use of robotic systems in bariatric surgery has constantly increased over the last years. However, beside its technical advantages in morbidly obese patients the conclusive role of robotics in bariatric and metabolic surgery is still under controversial debate. This is an analysis of prospectively collected data of consecutive patients undergoing fully robotic Roux-en-Y gastric bypasses (TR-RYGB) during the first year after implementation of a robotic bariatric program at a tertiary university hospital. All patients were operated by a previously untrained robotic but experienced laparoscopic bariatric surgeon using the daVinci Xi system (Intuitive Surgical, Sarl). Data recording included patient characteristics, operative and functional outcomes, complications and learning curves for surgeon and assistants. In total, 80 patients underwent primary or revisional robotic bariatric surgery. Seventy-two patients (90%) received a TR-RYGB. There were no major complications, re-interventions or readmissions. The overall complication rate was 2.5% (Clavien-Dindo grade I and II). The overall operation time was 140.7 ± 24.6 min and decreased significantly from the first to the last decade of procedures (procedure 1-10: 171.2 ± 26.3 min versus procedure 63-72: 116.0 ± 10.9 min, p < 0.0001). A stabilization of the learning curve was observed after 30 procedures for the surgeon and after five procedures for the bedside assistant. With immediate effect, TR-RYGB is a safe procedure with low complication rates for an experienced laparoscopic bariatric surgeon without prior robotic skills. Learning curves are steep and operation times can be effectively decreased by increasing the experience of the surgeon.

Perioperative statin medication impairs pulmonary outcome after abdomino-thoracic esophagectomy.

BACKGROUND: Although surgery is the curative option of choice for patients with locally advanced esophageal cancer, morbidity, especially the rate of pulmonary complications, and consequently mortality of patients undergoing abdomino-thoracic esophagectomy remain unacceptably high. Causes for developing post-esophagectomy pulmonary complications are trauma to the lung and thoracic cavity as well as systemic inflammatory response. Statins are known to influence inflammatory pathways, but whether perioperative statin medication impacts on inflammatory response and pulmonary complication development after esophagectomy had not been investigated, yet. METHODS: Retrospective analysis and propensity score matching of patients, who either received perioperative statin medication [statin( +)] or not [statin( -)], with regard to respiratory impairment (PaO2/FiO2 < 300 mmHg), pneumonia development, and inflammatory serum markers after abdomino-thoracic esophagectomy. RESULTS: Seventy-eight patients who underwent abdomino-thoracic esophagectomy for cancer were included into propensity score pair-matched analysis [statin( +): n = 26 and statin( -): n = 52]. Although no differences were seen in postoperative inflammatory serum markers, C-reactive protein values correlated significantly with the development of pneumonia beyond postoperative day 3 in statin( -) patients. This effect was attenuated under statin medication. No difference was seen in cumulative incidences of respiratory impairment; however, significantly higher rate (65.4% versus 38.5%, p = 0.0317, OR 3.022, 95% CI 1.165-7.892) and higher cumulative incidence (p = 0.0468) of postoperative pneumonia were seen in statin( +) patients, resulting in slightly longer postoperative stay on intensive care unit (p = 0.0612) as well as significantly prolonged postoperative in-hospital stay (p = 0.0185). CONCLUSIONS: Development of pulmonary complications after abdomino-thoracic esophagectomy is multifactorial but frequent. The establishment of preventive measures into the perioperative clinical routine is mandatory for an improved patient outcome. Perioperative medication with statins might influence pneumonia development in the highly vulnerable lung after abdomino-thoracic esophagectomy. Perioperative interruption of statin medication might be beneficial in appropriate patients; however, further clinical trials and translational studies are needed to prove this hypothesis.

Drug resistant bacteria in perianal abscesses are frequent and relevant.

Perianal abscesses are frequent diseases in general surgery. Principles of standard patient care are surgical drainage with exploration and concomitant treatment of fistula. Antiinfective therapy is frequently applied in cases of severe local disease and perianal sepsis. However, the role of microbiologic testing of purulence from perianal abscesses is disputed and the knowledge concerning bacteriology and bacterial resistances is very limited. A retrospective cohort study was performed of consecutive patients (≥ 12 years of age) from a tertiary care hospital, who underwent surgical treatment for perianal abscess from 01/2008 to 12/2019. Subdividing the cohort into three groups regarding microbiological testing results: no microbiological testing of purulence (No_Swab, n = 456), no detection of drug resistant bacteria [DR(-), n = 141] or detection of bacteria with acquired drug resistances from purulence [DR(+), n = 220]. Group comparisons were performed using Kruskall-Wallis test and, if applicable, followed by Dunn´s multiple comparisons test for continuous variables or Fishers exact or Pearson's X2 test for categorical data. Fistula persistence was estimated by Kaplan Meier and compared between the groups using Log rank test. Corralation analysis between perioperative outcome parameters and bacteriology was performed using Spearman´s rho rank correlation. Higher pretherapeutic C-reactive protein (p < 0.0001) and white blood cell count (p < 0.0001), higher rates of supralevatoric or pararectal abscesses (p = 0.0062) and of complicated fistula-in-ano requiring drainage procedure during index surgery (p < 0.0001) reflect more severe diseases in DR(+) patients. The necessity of antibiotic therapy (p < 0.0001), change of antibiotic regimen upon microbiologic testing results (p = 0.0001) and the rate of re-debridements during short-term follow-up (p = 0.0001) were the highest, the duration until definitive fistula repair was the longest in DR(+) patients (p = 0.0061). Escherichia coli, Bacteroides, Streptococcus and Staphylococcus species with acquired drug resistances were detected frequently. High rates of resistances against everyday antibiotics, including perioperative antibiotic prophylaxis were alarming. In conclusion, the knowledge about individual bacteriology is relevant in cases of complex and severe local disease, including locally advanced infection with extended soft tissue affection and perianal sepsis, signs of systemic inflammatory response as well as the need of re-do surgery for local debridements during short-term and fistula repair during long-term follow-up. Higher rates of acquired antibiotic resistances are to be expected in patients with more severe diseases.

Right colectomy from open to robotic - a single-center experience with functional outcomes in a learning-curve setting.

PURPOSE: Right colectomy (RC) is a frequently performed procedure. Beneath standard conventional open surgery (COS), various minimally invasive techniques had been introduced. Several advantages had recently been described for robotic approaches over COS or conventional laparoscopy. Nevertheless, novel minimally invasive techniques require continuous benchmarking against standard COS to gain maximum patient safety. Bowel dysfunction is a frequent problem after RC. Together with general complication rates postoperative bowel recovery are used as surrogate parameters for postoperative patient outcome in this study. METHODS: Retrospective, 10-year single-center analysis of consecutive patients who underwent sequentially either COS (n = 22), robotic-assisted (ECA: n = 39), or total robotic surgery (ICA: n = 56) for oncologic RC was performed. RESULTS: The conversion from robotic to open surgery rate was low (overall: 3.2%). Slightly longer duration of surgery had been observed during the early phase after introduction of the robotic program to RC (ECA versus COS, p = 0.044), but not anymore thereafter (versus ICA). No differences were observed in oncologic parameters including rates of tumor-negative margins, lymph node-positive patients, and lymph node yield during mesocolic excision. Both robotic approaches are beneficial regarding postoperative complication rates, especially wound infections, and shorter length of in-hospital stay compared with COS. The duration until first postoperative stool is the shortest after ICA (COS: 4 [2-8] days, ECA: 3 [1-6] days, ICA: 3 [1-5] days, p = 0.0004). Regression analyses reveal neither a longer duration of surgery nor the extent of mesocolic excision, but the degree of minimally invasiveness and postoperative systemic inflammation contribute to postoperative bowel dysfunction, which prolongs postoperative in-hospital stay significantly. CONCLUSION: The current study reflects the institutional learning curve of oncologic RC during implementation of robotic surgery from robotic-assisted to total robotic approach without compromises in oncologic results and patient safety. However, the total robotic approach is beneficial regarding postoperative bowel recovery and general patient outcome.

Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members.

BACKGROUND: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. METHODS: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. RESULTS: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. CONCLUSIONS: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years.

Frailty in elderly patients with acute appendicitis.

PURPOSE: Acute appendicitis in the elderly is becoming increasingly recognized for its often severe course. For various elective and urgent operations in older patients, frailty is a risk factor for poor outcomes. However, there is a lack of data on frailty in elderly patients with acute appendicitis. METHODS: Patients over 65 years old who underwent surgery for acute appendicitis in three hospitals between January 2015 and September 2020 were assessed with the Hospital Frailty Risk Score (HFRS) and the modified Frailty Index (mFI). Outcomes of interest, including morbidity, mortality, and length of stay, were recorded. RESULTS: While frailty can be measured with both tests, the mFI has better applicability and takes significantly less time to implement compared to the HFRS (21.6 s vs. 80.3 s, p < 0.0001) while providing the same information value. Patients who exhibited frailty according to either assessment had a significantly higher rate of milder (OR 5.85/2.87, p < 0.0001/0.009) and serious (OR 4.92/3.61, p < 0.011/0.029) complications, more admissions to the intensive care unit (OR 5.16/7.36, p < 0.0001), and an almost doubled length of stay (12.7 days vs. 6.6 days, p < 0.005). Up to 31% of these patients required institutional care after discharge, which is significantly more than those without frailty (p < 0.0001). Furthermore, the mortality rate in frail patients was significantly elevated to 17%, compared to less than 1% in non-frail patients (p = 0.018). CONCLUSION: In elderly patients, frailty is a significant risk factor for negative outcomes. Frailty can be assessed more quickly and reliably with the mFI compared to the HFRS.

Appendicitis during the COVID-19 lockdown: results of a multicenter analysis in Germany.

PURPOSE: The COVID-19 pandemic has transformed medical care worldwide. General surgery has been affected in elective procedures, yet the implications for emergency surgery are unclear. The current study analyzes the effect of the COVID-19 lockdown in spring 2020 on appendicitis treatment in Germany. METHODS: Hospitals that provided emergency surgical care during the COVID-19 lockdown were invited to participate. All patients diagnosed with appendicitis during the lockdown period (10 weeks) and, as a comparison group, patients from the same period in 2019 were analyzed. Clinical and laboratory parameters, intraoperative and pathological findings, and postoperative outcomes were analyzed. RESULTS: A total of 1915 appendectomies from 41 surgical departments in Germany were included. Compared to 2019 the number of appendectomies decreased by 13.5% (1.027 to 888, p=0.003) during the first 2020 COVID-19 lockdown. The delay between the onset of symptoms and medical consultation was substantially longer in the COVID-19 risk group and for the elderly. The rate of complicated appendicitis increased (58.2 to 64.4%), while the absolute number of complicated appendicitis decreased from 597 to 569, (p=0.012). The rate of negative appendectomies decreased significantly (6.7 to 4.6%; p=0.012). Overall postoperative morbidity and mortality, however, did not change. CONCLUSION: The COVID-19 lockdown had significant effects on abdominal emergency surgery in Germany. These seem to result from a stricter selection and a longer waiting time between the onset of symptoms and medical consultation for risk patients. However, the standard of emergency surgical care in Germany was maintained.

Impact of the SARS-CoV-2 pandemic on emergency surgery services-a multi-national survey among WSES members.

BACKGROUND: The SARS-CoV-2 pandemic is a major challenge for health care services worldwide. It's impact on oncologic therapies and elective surgery has been described recently, and the literature provides guidelines regarding appropriate elective patient treatment during the pandemic. However, the impact of SARS-CoV-2 pandemic on emergency surgery services has been poorly investigated up to now. METHODS: A 17-item web survey had been distributed to emergency surgeons in June 2020 around the world, investigating the impact of SARS-CoV-2 pandemic on patients and septic diseases both requiring emergency surgery and the time-to-intervention in emergency surgery routine, as well as experiences with surgery in COVID-19 patients. RESULTS: Ninety-eight collaborators from 31 countries responded to the survey. The majority (65.3%) estimated the impact of the SARS-CoV-2 pandemic on emergency surgical patient care as being strong or very strong. Due to the pandemic, 87.8% reported a decrease in the total number of patients undergoing emergency surgery and approximately 25% estimated a delay of more than 2 h in the time-to-diagnosis and another 2 h in the time-to-intervention. Fifty percent make structural problems with in-hospital logistics (e.g. transport of patients, closed normal wards etc.) mainly responsible for delayed emergency surgery and the frequent need (56.1%) for a triage of emergency surgical patients. 56.1% of the collaborators observed more severe septic abdominal diseases during the pandemic, especially for perforated appendicitis and severe septic cholecystitis (41.8% and 40.2%, respectively). 62.2% had experiences with surgery in COVID-19-infected patients. CONCLUSIONS: The results of The WSES COVID-19 emergency surgery survey are alarming. The combination of an estimated decrease in numbers of emergency surgical patients and an observed increase in more severe septic diseases may be a result of the fear of patients from infection with COVID-19 and a consecutive delayed hospital admission and diagnosis. A critical delay in time-to-diagnosis and time-to-intervention may be a result of changes in in-hospital logistics and operating room as well as intensive care capacities. Both reflect the potentially harmful impact of SARS-CoV-2 pandemic on emergency surgery services.

Amyloid Beta Peptide (Aß1-42) Reverses the Cholinergic Control of Monocytic IL-1ß Release.

Amyloid-ß peptide (Aß1-42), the cleavage product of the evolutionary highly conserved amyloid precursor protein, presumably plays a pathogenic role in Alzheimer's disease. Aß1-42 can induce the secretion of the pro-inflammatory cytokine intereukin-1ß (IL-1ß) in immune cells within and out of the nervous system. Known interaction partners of Aß1-42 are α7 nicotinic acetylcholine receptors (nAChRs). The physiological functions of Aß1-42 are, however, not fully understood. Recently, we identified a cholinergic mechanism that controls monocytic release of IL-1ß by canonical and non-canonical agonists of nAChRs containing subunits α7, α9, and/or α10. Here, we tested the hypothesis that Aß1-42 modulates this inhibitory cholinergic mechanism. Lipopolysaccharide-primed monocytic U937 cells and human mononuclear leukocytes were stimulated with the P2X7 receptor agonist 2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate triethylammonium salt (BzATP) in the presence or absence of nAChR agonists and Aß1-42. IL-1ß concentrations were measured in the supernatant. Aß1-42 dose-dependently (IC50 = 2.54 µM) reversed the inhibitory effect of canonical and non-canonical nicotinic agonists on BzATP-mediated IL-1ß-release by monocytic cells, whereas reverse Aß42-1 was ineffective. In conclusion, we discovered a novel pro-inflammatory Aß1-42 function that enables monocytic IL-1ß release in the presence of nAChR agonists. These findings provide evidence for a novel physiological function of Aß1-42 in the context of sterile systemic inflammation.

Blood Levels of Free-Circulating Mitochondrial DNA in Septic Shock and Postsurgical Systemic Inflammation and Its Influence on Coagulation: A Secondary Analysis of a Prospective Observational Study.

Major surgery is regularly associated with clinical signs of systemic inflammation, which potentially affects the rapid identification of sepsis. Therefore, this secondary analysis of an observational study aims to determine whether NADH dehydrogenase 1 (ND1) mitochondrial DNA (mtDNA) could be used as a potential biomarker for the discrimination between septic shock and postsurgical systemic inflammation. Overall, 80 patients were included (septic shock (n = 20), cardiac artery bypass grafting (CABG, n = 20), major abdominal surgery (MAS, n = 20), and matched controls (CTRL, n = 20)). Quantitative PCR was performed to measure ND1 mtDNA. Thromboelastography was used to analyze the coagulatory system. Free-circulating ND1 mtDNA levels were significantly higher in septic shock patients compared to patients suffering from post-surgical inflammation ({copies/µL}: CTRL: 1208 (668-2685); septic shock: 3823 (2170-7318); CABG: 1272 (417-2720); and MAS: 1356 (694-2845); CTRL vs. septic shock: p < 0.001; septic shock vs. CABG: p < 0.001; septic shock vs. MAS: p = 0.006; CABG vs. MAS: p = 0.01). ND1 mtDNA levels in CABG patients showed a strong positive correlation with fibrinogen (correlation coefficient [r]= 0.57, p < 0.001) and fibrinogen-dependent thromboelastographic assays (maximum clot firmness, EXTEM: r = 0.35, p = 0.01; INTEM: r = 0.31, p = 0.02; FIBTEM: r = 0.46, p < 0.001). In conclusion, plasma levels of free-circulating ND1 mtDNA were increased in septic shock patients and were discriminative between sepsis and surgery-induced inflammation. Furthermore, this study showed an association between ND1 mtDNA and a fibrinogen-dependent pro-coagulatory shift in cardiac surgical patients.

Early Respiratory Impairment and Pneumonia after Hybrid Laparoscopically Assisted Esophagectomy-A Comparison with the Open Approach.

Patients undergoing esophageal cancer surgery are at high risk of developing severe pulmonary complications. Beneficial effects of minimally invasive esophagectomy had been discussed recently, but the incidence of perioperative respiratory impairment remains unclear. This is a retrospective single-center cohort study of patients, who underwent open (OE) or laparoscopically assisted, hybrid minimally invasive abdomino-thoracic esophagectomy (LAE) for cancer regarding respiratory impairment (PaO2/FiO2 ratio (P/FR) < 300 mmHg) and pneumonia. No differences were observed in the cumulative incidence of reduced P/FR between OE and LAE patients. Of note, until postoperative day (POD) 2, P/FR did not differ among both groups. Thereafter, the rate of patients with respiratory impairment was higher after OE on POD 3, 5, and 10 (p ≤ 0.05) and tended being higher on POD 7 and 9 (p ≤ 0.1). Although the duration of LAE procedure was slightly longer (total: p = 0.07, thoracic part: p = 0.004), the duration of surgery (Spearman's rank correlation coefficient (rsp) = -0.267, p = 0.006), especially of laparotomy (rsp = -0.242, p = 0.01) correlated inversely with respiratory impairment on POD 3 after OE. Pneumonia occurred on POD 5 (1-25) and 8.5 (3-14) after OE and LAE, respectively, with the highest incidence after OE (p = 0.01). In conclusion, respiratory impairment and pulmonary complications occur frequently after esophagectomy. Although early respiratory impairment is independent of the surgical approach, postoperative pneumonia rate is reduced after LAE.

Nonoperative Antibiotic Treatment of Appendicitis in Adults: A Survey among Clinically Active Surgeons.

BACKGROUND: As a result of well-publicized studies, the nonsurgical antibiotic therapy of uncomplicated acute appendicitis has been propagated since 2006. A final assessment regarding efficiency and long-term results is not possible; however, nonoperative therapy of acute appendicitis is actually being discussed more diversely and receives a lot of attention. It is still unknown how far this therapy has found its way into everyday clinical care. METHODS: An online questionnaire was sent to 1,400 randomly selected specialists for general/visceral surgery in Germany. Representativeness was achieved by a preselection according to the geographical origin and the care level of the hospitals. RESULTS: 14% of surgeons stated that they methodically treat appendicitis conservatively. 38.1% do so in exceptional cases, while 48.8% reject this therapy. For methodically use, sonography or computed tomography is demanded beforehand. Nonoperative therapy is performed more often in metropolitan areas and maximum-care/university hospitals. Patients' request for antibiotic therapy is an important factor for conservative treatment. The main argument against this therapy is "medical doubts." 26% of the surgeons would treat their own appendicitis conservatively. There are distinct associations between the application of conservative therapy, satisfaction with it, and expectations about future development. The response rate was 19.9%. CONCLUSION: The nonoperative antibiotic therapy of appendicitis is part of clinical practice in Germany. There are differences in preconditions as well as in the acceptance of this therapeutic option with a high proportion of general rejection.

Ivor Lewis esophagectomy patients are particularly vulnerable to respiratory impairment - a comparison to major lung resection.

Pulmonary complications and a poor clinical outcome are common in response to transthoracic esophagectomy, but their etiology is not well understood. Clinical observation suggests that patients undergoing pulmonary resection, a surgical intervention with similarities to the thoracic part of esophagectomy, fare much better, but this has not been investigated in detail. A retrospective single-center analysis of 181 consecutive patients after right-sided thoracotomy for either Ivor Lewis esophagectomy (n = 83) or major pulmonary resection (n = 98) was performed. An oxygenation index <300 mm Hg was used to indicate respiratory impairment. When starting surgery, respiratory impairment was seen more frequently in patients undergoing major pulmonary resection compared to esophagectomy patients (p = 0.009). On postoperative days one to ten, however, esophagectomy caused higher rates of respiratory impairment (p < 0.05) resulting in a higher cumulative incidence of postoperative respiratory impairment for patients after esophagectomy (p < 0.001). Accordingly, esophagectomy patients were characterized by longer ventilation times (p < 0.0001), intensive care unit and total postoperative hospital stays (both p < 0.0001). In conclusion, the postoperative clinical course including respiratory impairment after Ivor Lewis esophagectomy is significantly worse than that after major pulmonary resection. A detailed investigation of the underlying causes is required to improve the outcome of esophagectomy.

Lung decortication in phase III pleural empyema by video-assisted thoracoscopic surgery (VATS)-results of a learning curve study.

BACKGROUND: Pleural empyema (PE) is a devastating disease with a high morbidity and mortality. According to the American Thoracic Society it is graduated into three phases and surgery is indicated in intermediate phase II and organized phase III. In the latter, open decortication of the lung via thoracotomy is the gold standard whereas the evidence for feasibility and safety of a minimally-invasive video-assisted thoracoscopic approach is still poor. METHODS: Retrospective single-center analysis of patients undergoing surgery for phase III PE from 02/2011 to 03/2015 [n=138, including n=130 VATS approach (n=3 of them with bilateral disease) and n=8 open approach]. The learning curve was assessed by grouping those 127 patients with unilateral disease who underwent a video-assisted thoracoscopic approach into two groups: VATS-1 (03/2011 to 06/2012, n=43) and VATS-2 (06/2012 to 03/2015, n=84). RESULTS: ASA-scores (P=0.0279) and rate of pre-operative drainage therapy (P=0.0534) were higher in VATS-2 patients. Operating times were longer in VATS-1 (P=0.0308), intra-operative complication as well as conversion to open surgery rates did both not differ. Rates of post-operative vasoconstrictive therapy (P=0.0191) and prolonged mechanical ventilation (P=0.0560) were both higher in VATS-2, however, post-operative length of stay (LOS) at intensive care unit, overall post-operative LOS and post-operative complication rate were similar in both groups. CONCLUSIONS: Video-assisted thoracoscopic surgery is feasible for evacuation and decortication in late phase III PE. A learning curve of approximately 40 cases is sufficient to gain procedure-specific surgical skills and thus reduce the operating times sufficiently.