Retransplanting a previously transplanted kidney: A safe strategy in times of organ shortage?

BACKGROUND: The shortage of organs for transplantation remains a global problem. The retransplantation of a previously transplanted kidney might be a possibility to expand the pool of donors. We provide our experience with the successful reuse of transplanted kidneys in the Eurotransplant region. METHODS: A query in the Eurotransplant database was performed between January 1, 1995 and December 31, 2015, to find kidney donors who themselves had previously received a kidney graft. RESULTS: Nine out of a total of 68,554 allocated kidneys had previously been transplanted. Four of these kidneys were transplanted once again. The mean interval between the first transplant and retransplantation was 1689±1682 days (SD; range 55-5,333 days). At the time of the first transplantation the mean serum creatinine of the donors was 1.0 mg/dl (.6-1.3 mg/dl) and at the second transplantation 1.4 mg/dl (.8-1.5 mg/dl). The mean graft survival in the first recipient was 50 months (2-110 months) and in the second recipient 111 months (40-215 months). CONCLUSION: Transplantation of a previously transplanted kidney may successfully be performed with well-preserved graft function and long-term graft survival, even if the first transplantation was performed a long time ago. Such organs should be considered even for younger recipients in carefully selected cases.

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.

Activation of Humoral Immunity during the Pathogenesis of Experimental Chronic Lung Allograft Dysfunction.

Alloreactive and autoreactive antibodies have been associated with the development of chronic lung allograft dysfunction (CLAD), but their pathogenic role is disputed. Orthotopic left lung transplantation was performed in the Fischer-344 to Lewis rat strain combination followed by the application of ciclosporine for 10 days. Four weeks after transplantation, lipopolysaccharide (LPS) was instilled into the trachea. Lungs were harvested before (postoperative day 28) and after LPS application (postoperative days 29, 33, 40, and 90) for histopathological, immunohistochemical, and Western blot analyses. Recipient serum was collected to investigate circulating antibodies. Lung allografts were more strongly infiltrated by B cells and deposits of immunoglobulin G and M were more prominent in allografts compared to right native lungs or isografts and increased in response to LPS instillation. LPS induced the secretion of autoreactive antibodies into the circulation of allograft and isograft recipients, while alloreactive antibodies were only rarely detected. Infiltration of B cells and accumulation of immunoglobulin, which is observed in allografts treated with LPS but not isografts or native lungs, might contribute to the pathogenesis of experimental CLAD. However, the LPS-induced appearance of circulating autoreactive antibodies does not seem to be related to CLAD, because it is observed in both, isograft and allograft recipients.

Progranulin serum levels and gene expression in subcutaneous vs visceral adipose tissue of severely obese patients undergoing bariatric surgery.

BACKGROUND: Progranulin represents an adipokine putatively mediating insulin resistance and inflammation. Data in humans are sparse, and the source of circulating progranulin in obesity is unknown. OBJECTIVES: Serum progranulin concentrations and subcutaneous (sc) as well as visceral (vis) adipose tissue (AT) progranulin expression were quantified in a large cohort of patients with obesity undergoing bariatric surgery (BS) (n = 153) or a low-calorie diet (LCD) (n = 121). COHORTS AND METHODS: Paired serum and AT mRNA samples were obtained from patients with severe obesity undergoing BS (ROBS cohort; Research in Obesity and Bariatric Surgery). Serum progranulin was measured by ELISA in both cohorts, and AT mRNA expression was analysed by quantitative real-time PCR in bariatric patients. RESULTS: There was no gender-specific effect in serum progranulin or AT progranulin expression. Importantly, circulating progranulin was independent from adipose tissue gene expression in paired samples. sc AT progranulin expression was higher than in vis AT (P = 0.027), and there was a positive correlation between sc AT and vis AT gene expression (P < 0.001; r = +0.34). Serum progranulin strongly and rapidly increased after BS within 3 days and remained elevated up to 12 months. Serum progranulin was strongly correlated with serum CTRP-3 levels. CONCLUSIONS: The present study provides detailed progranulin gene expression data in sc and vis AT in a large, prospective and observational cohort of patients with severe obesity. Serum progranulin concentrations are not predicted by sc or vis AT progranulin gene expression. Thus, AT seems not to be the main source of circulating progranulin levels in obesity.

Indefinite cytomegalovirus prophylaxis with valganciclovir after lung transplantation.

Human cytomegalovirus (HCMV) infections and reactivations are common after lung transplantation and are associated with the development of bronchiolitis obliterans syndrome. Against this background, temporary HCMV prophylaxis is an established standard regimen after lung transplantation in most centers. However, the optimal duration of prophylaxis is unclear. We conducted a retrospective two-center study to determine the efficacy of indefinite lifelong HCMV prophylaxis with oral valganciclovir in a cohort of 133 lung transplant recipients with a mean follow-up time of approximately 5 years. During the follow-up period, HCMV DNA was detected in 22 recipients (16.5%). In one case, HCMV pneumonitis developed after prophylaxis had been terminated. We observed a beneficial safety profile and tolerability in our cohort, as the majority of patients still received valganciclovir after a 1- and 3-year observation period, respectively. Compared to the literature, these data indicate a beneficial effect of extended valganciclovir prophylaxis with an acceptable safety profile.

Antibiotic-treated acute appendicitis-reception in social media.

PURPOSE: Social media, especially Twitter®, is becoming increasingly important for medical topics. Systematic analyses of the content of these tweets are rare. To date, no analysis of the reception of antibiotic/non-operative-treated acute appendicitis on Twitter® has been performed. METHODS: Tweets with the content "appendicitis," "appendix," and "appendectomy" from December 31, 2010, to September 27, 2017, were recorded. Further analysis was performed by secondary search strings related to antibiotic-treated acute appendicitis. Subsequent systematic analysis of content, author groups, and followers was performed. RESULTS: Out of 22,962 analyzed tweets, 3400 were applicable on all search strings, and 349 dealt meaningfully with antibiotic-treated acute appendicitis. 47.9% of the tweets were published by individuals, of which non-surgical consultants comprised the largest group. The tweets published by organizations and institutions were mostly published by publishing platforms. Half of the tweets were neutral, with an overall positive trend for antibiotic-treated acute appendicitis, but significant differences were noted among the authors. The number of followers showed a wide range, with an considerable numeric impact. CONCLUSION: The scientific discussion of antibiotic-treated acute appendicitis is reflected on Twitter®. Overall, antibiotic-treated acute appendicitis is presented in a neutral and differentiated manner on Twitter®, but this picture is exclusively derived from assessment of a variety of tweets. Individual tweets are partially undifferentiated in content and misrepresent antibiotic-treated acute appendicitis. In addition, content and intentions are significantly author dependent. Scientists should therefore use Twitter® to make sound medical information heard. If this policy is not implemented, the importance of inadequate and incorrect information transfer is indirectly increased.

Expression of neuropeptide Y and its receptors Y1 and Y2 in pancreatic intraepithelial neoplasia and invasive pancreatic cancer in a transgenic mouse model and human samples of pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most dismal of human malignancies. Neuropeptides have shown to be implicated in angiogenesis, tumor growth, and formation of distant metastases in various solid tumors. In the present study, we used a genetically engineered mouse model of pancreatic cancer to evaluate the impact of neuropeptide Y (NPY) and its receptors 1 (Y1) and 2 (Y2) in preneoplastic lesions and pancreatic cancer as a potential target with antiproliferative properties. In addition, human PDAC tissue was analyzed. MATERIALS AND METHODS: By interbreeding conditional LsL-Trp53R172H,LsL-KrasG12D and Pdx1-Cre strains, we obtained LsL-KrasG12D;LsL-Trp53R172H;Pdx1-Cre(KPC), LsL-KrasG12D;Pdx1-Cre(KP) and control mice (n = 8 each). Mice were then followed in a longitudinal study for 3 to 6 mo. Pancreata were analyzed in regard to pancreatic intraepithelial neoplasia (PanIN) lesions and invasive carcinoma. Corresponding sections were then assessed by immunohistochemistry and quantitative polymerase chain reaction for NPY, Y1 and Y2 expression in murine and human samples. RESULTS: NPY and Y1 expressions were detected in human and murine pancreatic samples, but expression levels were similar in neoplastic and non-neoplastic tissue. Y2 revealed a significant increase of expression in the transgenic mouse model in PanIN lesions and pancreatic cancer compared to control. This holds also true for human samples of pancreatic cancer. Immunohistochemistry of Y2 in murine and human samples of PanINs and pancreatic carcinoma revealed an increased expression in PanIN lesions and pancreatic cancer. CONCLUSIONS: Y2 is strongly overexpressed in pancreatic cancer and may modulate angiogenesis.

Protective loop ileostomy increases the risk for prolonged postoperative paralytic ileus after open oncologic rectal resection.

PURPOSE: Postoperative gut dysmotility is a physiologic and frequent temporary reaction after major abdominal surgery. If paralysis merges into a prolonged ileus state, it causes significant morbidity and subsequently worse outcome and discomfort for the patients. Pathophysiology of pathologic prolonged postoperative paralytic ileus remains multifactorial. METHODS: We present a retrospective single-center analysis of patients, who underwent a primary open oncologic anterior rectal resection with primary anastomosis with or without defunctioning loop ileostomy during a 43-month period of observation. Primary endpoint was the rate of prolonged postoperative paralytic ileus, defined by the intravenous administration of neostigmine. Confounders for regression analysis were assessed by univariate analysis and correlations between confounders were examined. Odds ratio for prolonged postoperative paralytic ileus in patients with defunctioning loop ileostomy was estimated by a logistic regression model. RESULTS: Of 101 patients (62 male), 62 (61.39%) received defunctioning loop ileostomy. In univariate analysis, male gender and patients with ileostomy showed more frequently prolonged paralysis by tendency (both p = 0.07). Logistic regression analysis proves the influence of a defunctioning ileostomy on the development of prolonged postoperative paralytic ileus after oncologic rectal resection (p = 0.047). Odds ratio for prolonged postoperative paralytic ileus in patients with ileostomy was 4.96 [95% CI 1.02-24.03]. CONCLUSIONS: Although the construction of defunctioning loop ileostomies during rectal resection is a safe, uncomplicated surgical procedure, they can cause significant postoperative morbidity for the patients. High fluid and electrolyte loss are well-known complications, but herewith we raise the evidence for prolonged gut paralysis in patients with defunctioning loop ileostomy.

Thoracotomy versus video-assisted thoracoscopic surgery (VATS) in stage III empyema-an analysis of 217 consecutive patients.

BACKGROUND: Pleural empyema is an infectious disease of the chest cavity, with a high morbidity and mortality. According to the American Thoracic Society, pleural empyema gets graduated into three stages, with surgery being indicated in intermediate stage II and chronic stage III. Evidence for the feasibility of a minimally-invasive video-assisted thoracoscopic approach in stage III empyema for pulmonary decortication is still little. METHODS: Retrospective single-center analysis of patients conducted to surgery for chronic stage III pleural empyema from 05/2002 to 04/2014 either by video-assisted thoracoscopic surgery (VATS, n = 110) or conventional open surgery by thoracotomy (n = 107). Multiple regression analysis and propensity score matching was used to evaluate the influence of operation technique (thoracotomy versus VATS) on the length of post-operative hospitalization. RESULTS: Operation time was longer in the thoracotomy-group (p = 0.0207). Conversion rate from VATS to open surgery by thoracotomy was 4.5%. Post-operative complication- (61 patients in thoracotomy- and 55 patients in VATS-group), recurrence- (3 patients in thoracotomy- and 5 in VATS-group) and mortality-rates (6.5% in thoracotomy- and 9.5% in VATS-group) did not differ between both groups; the length of (post-operative) stay at intensive care unit was longer in the VATS-group (p = 0.0023). Duration of chest tube drainage and prolonged air leak rate were similar among both groups, leading to a similar overall and post-operative length of hospital stay in both groups. Adjusted to clinically and statistically relevant confounders, multiple regression analysis showed an influence of the surgical technique on length of post-operative stay after pair matching of the patients (n = 84 in each group) by propensity score (B = - 0.179 for thoracotomy = 0 and VATS = 1, p = 0.032) leading to a reduction of 0.836 days after a VATS-approach compared to thoracotomy. CONCLUSIONS: VATS in late stage (III) pleural empyema is feasible and safe. The decrease in post-operative hospitalization demonstrated by adjusted multiple regression analysis may indicate the minimally-invasive approach being safe, more tolerable for patients, and more effective.

ß-Nicotinamide Adenine Dinucleotide (ß-NAD) Inhibits ATP-Dependent IL-1ß Release from Human Monocytic Cells.

While interleukin-1ß (IL-1ß) is a potent pro-inflammatory cytokine essential for host defense, high systemic levels cause life-threatening inflammatory syndromes. ATP, a stimulus of IL-1ß maturation, is released from damaged cells along with ß-nicotinamide adenine dinucleotide (ß-NAD). Here, we tested the hypothesis that ß-NAD controls ATP-signaling and, hence, IL-1ß release. Lipopolysaccharide-primed monocytic U937 cells and primary human mononuclear leukocytes were stimulated with 2'(3')-O-(4-benzoyl-benzoyl)ATP trieethylammonium salt (BzATP), a P2X7 receptor agonist, in the presence or absence of ß-NAD. IL-1ß was measured in cell culture supernatants. The roles of P2Y receptors, nicotinic acetylcholine receptors (nAChRs), and Ca2+-independent phospholipase A2 (iPLA2ß, PLA2G6) were investigated using specific inhibitors and gene-silencing. Exogenous ß-NAD signaled via P2Y receptors and dose-dependently (IC50 = 15 µM) suppressed the BzATP-induced IL-1ß release. Signaling involved iPLA2ß, release of a soluble mediator, and nAChR subunit α9. Patch-clamp experiments revealed that ß-NAD inhibited BzATP-induced ion currents. In conclusion, we describe a novel triple membrane-passing signaling cascade triggered by extracellular ß-NAD that suppresses ATP-induced release of IL-1ß by monocytic cells. This cascade links activation of P2Y receptors to non-canonical metabotropic functions of nAChRs that inhibit P2X7 receptor function. The biomedical relevance of this mechanism might be the control of trauma-associated systemic inflammation.

Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1ß Release by Pulmonary Epithelial Cells.

Phosphocholine-modified bacterial cell wall components are virulence factors enabling immune evasion and permanent colonization of the mammalian host, by mechanisms that are poorly understood. Recently, we demonstrated that free phosphocholine (PC) and PC-modified lipooligosaccharides (PC-LOS) from Haemophilus influenzae, an opportunistic pathogen of the upper and lower airways, function as unconventional nicotinic agonists and efficiently inhibit the ATP-induced release of monocytic IL-1ß. We hypothesize that H. influenzae PC-LOS exert similar effects on pulmonary epithelial cells and on the complex lung tissue. The human lung carcinoma-derived epithelial cell lines A549 and Calu-3 were primed with lipopolysaccharide from Escherichia coli followed by stimulation with ATP in the presence or absence of PC or PC-LOS or LOS devoid of PC. The involvement of nicotinic acetylcholine receptors was tested using specific antagonists. We demonstrate that PC and PC-LOS efficiently inhibit ATP-mediated IL-1ß release by A549 and Calu-3 cells via nicotinic acetylcholine receptors containing subunits α7, α9, and/or α10. Primed precision-cut lung slices behaved similarly. We conclude that H. influenzae hijacked an endogenous anti-inflammatory cholinergic control mechanism of the lung to evade innate immune responses of the host. These findings may pave the way towards a host-centered antibiotic treatment of chronic airway infections with H. influenzae.

Surfactant inhibits ATP-induced release of interleukin-1ß via nicotinic acetylcholine receptors.

Interleukin (IL)-1ß is a potent pro-inflammatory cytokine of innate immunity involved in host defense. High systemic IL-1ß levels, however, cause life-threatening inflammatory diseases, including systemic inflammatory response syndrome. In response to various danger signals, the pro-form of IL-1ß is synthesized and stays in the cytoplasm unless a second signal, such as extracellular ATP, activates the inflammasome, which enables processing and release of mature IL-1ß. As pulmonary surfactant is known for its anti-inflammatory properties, we hypothesize that surfactant inhibits ATP-induced release of IL-1ß. Lipopolysaccharide-primed monocytic U937 cells were stimulated with an ATP analog in the presence of natural or synthetic surfactant composed of recombinant surfactant protein (rSP)-C, palmitoylphosphatidylglycerol, and dipalmitoylphosphatidylcholine (DPPC). Both surfactant preparations dose-dependently inhibited IL-1ß release from U937 cells. DPPC was the active constituent of surfactant, whereas rSP-C and palmitoylphosphatidylglycerol were inactive. DPPC was also effective in primary mononuclear leukocytes isolated from human blood. Experiments with nicotinic antagonists, siRNA technology, and patch-clamp experiments suggested that stimulation of nicotinic acetylcholine receptors (nAChRs) containing subunit α9 results in a complete inhibition of the ion channel function of ATP receptor, P2X7. In conclusion, the surfactant constituent, DPPC, efficiently inhibits ATP-induced inflammasome activation and maturation of IL-1ß in human monocytes by a mechanism involving nAChRs.

The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III trial of the German AIO/CAO-V/CAOGI.

BACKGROUND: Historical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases. METHODS: This is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled. DISCUSSION: If the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention. TRIAL REGISTRATION: The article reports of a health care intervention on human participants and is registered on October 12, 2015 under ClinicalTrials.gov Identifier: NCT02578368 ; EudraCT: 2014-002665-30.

Plasma DNA and RNA differentially impact coagulation during abdominal sepsis-an explorative study.

BACKGROUND: Cell-free DNA (cfDNA) and extracellular RNA (exRNA) are both suspected to activate coagulation cascades in sepsis. Therefore, our study investigated the influence of plasmatic nucleic acids on coagulation in septic patients in comparison to patients after major abdominal surgery. MATERIALS AND METHODS: A total of 15 patients with sepsis, 10 postoperative patients, and 10 healthy volunteers were included in this longitudinal study. Blood was collected at sepsis onset and after surgery respectively, as well as after 24, 72 and 168 h. Levels of cfDNA and exRNA were measured by quantitative probe-based polymerase chain reaction. In addition, thromboelastography for coagulation as well as thromboaggregometry for platelet function was conducted. RESULTS: Both cfDNA and exRNA were elevated in patients with sepsis compared with postoperative patients and healthy volunteers. While higher exRNA levels correlated with a faster clotting time and more stable clots, cfDNA correlated with a shorter clotting time but also less fibrinolysis. In addition, higher cfDNA seems to be associated with kidney dysfunction as well as with general markers of cell damage (lactate dehydrogenase and lactate). CONCLUSIONS: Both nucleic acid species might be associated with different effects on coagulation during sepsis, with an overall procoagulatory influence. For this reason, individualized therapeutic approaches in patients suffering from coagulation-associated organ dysfunction might be feasible.

Phosphocholine-Modified Macromolecules and Canonical Nicotinic Agonists Inhibit ATP-Induced IL-1ß Release.

IL-1ß is a potent proinflammatory cytokine of the innate immune system that is involved in host defense against infection. However, increased production of IL-1ß plays a pathogenic role in various inflammatory diseases, such as rheumatoid arthritis, gout, sepsis, stroke, and transplant rejection. To prevent detrimental collateral damage, IL-1ß release is tightly controlled and typically requires two consecutive danger signals. LPS from Gram-negative bacteria is a prototypical first signal inducing pro-IL-1ß synthesis, whereas extracellular ATP is a typical second signal sensed by the ATP receptor P2X7 that triggers activation of the NLRP3-containing inflammasome, proteolytic cleavage of pro-IL-1ß by caspase-1, and release of mature IL-1ß. Mechanisms controlling IL-1ß release, even in the presence of both danger signals, are needed to protect from collateral damage and are of therapeutic interest. In this article, we show that acetylcholine, choline, phosphocholine, phosphocholine-modified LPS from Haemophilus influenzae, and phosphocholine-modified protein efficiently inhibit ATP-mediated IL-1ß release in human and rat monocytes via nicotinic acetylcholine receptors containing subunits α7, α9, and/or α10. Of note, we identify receptors for phosphocholine-modified macromolecules that are synthesized by microbes and eukaryotic parasites and are well-known modulators of the immune system. Our data suggest that an endogenous anti-inflammatory cholinergic control mechanism effectively controls ATP-mediated release of IL-1ß and that the same mechanism is used by symbionts and misused by parasites to evade innate immune responses of the host.

Stage-directed therapy of pleural empyema.

PURPOSE: Intensivists and surgeons are often confronted with critically ill patients suffering from pleural empyema. Due to it' s multifactorial pathogenesis and etiology, medicals should be sensitized to recognize the different stages of the disease. Besides a whole bundle of different established classification systems, the progress of pleural effusions can be subdivided into the early exudative, the intermediate fibropurulent and the late organized phase according to the classification of the American Thoracic Society. RESULTS: Rapid diagnosis of pleura empyema is essential for patients' survival. Due to the importance of stage-adapted therapeutic decisions, different classification systems were established. Depending on the stage of pleural empyema, both antimicrobial and interventional approaches are indicated. For organized empyema, minimally invasive and open thoracic surgery are gold standard. Surgery is based on the three therapeutic columns: removal of pleural fluid, debridement and decortication. In general, therapy must be intended stage-directed following multidisciplinary concepts including surgeons, intensivists, anesthesiologists, physiotherapists and antibiotic stewards. Despite an established therapeutic algorithm is presented in this review, there is still a lack of randomized, prospective studies to evaluate potential benefits of minimally invasive (versus open) surgery for end-stage empyema or of catheter-directed intrathoracic fibrinolysis (versus minimally invasive surgery) for intermediate-stage pleural empyema. Any delay in adequate therapy results in an increased morbidity and mortality. CONCLUSION: The aim of this article is to review current treatment standards for different phases of adult thoracic empyema from an interdisciplinary point of view.

Application of Continuous Wound-Infusion Catheters in Lung Transplantation: A Retrospective Data Analysis.

Background Lung transplantation is the only treatment option for many patients with end-stage pulmonary disease. Therefore, postthoracotomy pain therapy is of vital interest. Thoracic epidural analgesia (EPI) is the "gold standard" for postthoracotomy pain, but especially in lung transplantation contraindications, and potential infectious complications limit its advantages. Under these circumstances surgically placed postthoracotomy catheter-assisted continuous paravertebral intercostal nerve block (PVB) could be of advantage. Methods We performed a retrospective cohort study of patients who underwent lung transplantation between 2005 and 2012. Groups were defined according to the type of postoperative pain therapy: PVB, EPI, and SYS (systemic analgesia). Total 44 patients were eligible. Results Postoperative opioid requirement of the PVB and EPI group was comparable and less than that of the SYS group. Patients of the PVB group were weaned earlier from mechanical ventilation after lung transplantation. Conclusion The potency of postoperative pain therapy of EPI and PVB seemed to be comparable and superior to SYS. Considering the risks and benefits, PVB could be a better choice than EPI for postthoracotomy pain therapy, especially in lung transplantation.

Chemokines (CCL3, CCL4, and CCL5) Inhibit ATP-Induced Release of IL-1ß by Monocytic Cells.

Chemokines and ATP are among the mediators of inflammatory sites that can enter the circulation via damaged blood vessels. The main function of chemokines is leukocyte mobilization, and ATP typically triggers inflammasome assembly. IL-1ß, a potent inflammasome-dependent cytokine of innate immunity, is essential for pathogen defense. However, excessive IL-1ß may cause life-threatening systemic inflammation. Here, we hypothesize that chemokines control ATP-dependent secretion of monocytic IL-1ß. Lipopolysaccharide-primed human monocytic U937 cells were stimulated with the P2X7 agonist BzATP for 30 min to induce IL-1ß release. CCL3, CCL4, and CCL5 dose dependently inhibited BzATP-stimulated release of IL-1ß, whereas CXCL16 was ineffective. The effect of CCL3 was confirmed for primary mononuclear leukocytes. It was blunted after silencing CCR1 or calcium-independent phospholipase A2 (iPLA2) by siRNA and was sensitive to antagonists of nicotinic acetylcholine receptors containing subunits α7 and α9. U937 cells secreted small factors in response to CCL3 that mediated the inhibition of IL-1ß release. We suggest that CCL chemokines inhibit ATP-induced release of IL-1ß from U937 cells by a triple-membrane-passing mechanism involving CCR, iPLA2, release of small mediators, and nicotinic acetylcholine receptor subunits α7 and α9. We speculate that whenever chemokines and ATP enter the circulation concomitantly, systemic release of IL-1ß is minimized.

Anatomic lung resections for benign pulmonary diseases by video-assisted thoracoscopic surgery (VATS).

PURPOSE: Based on increasing evidence of its benefits regarding perioperative and oncologic outcome, video-assisted thoracoscopic surgery (VATS) has gained increasing acceptance in the surgical treatment of early stage non-small cell lung cancer (NSCLC). However, the evidence for a VATS approach in anatomic lung resection for benign pulmonary diseases is still limited. METHODS: Between March 2011 and May 2014, data from 33 and 63 patients who received VATS anatomic lung resection for benign diseases (VATS-B) and early stage NSCLC (VATS-N), respectively, were analyzed retrospectively. For subgroup analyses, VATS-B was subdivided by operation time and underlying diseases. Subgroups were compared to VATS-N. RESULTS: Three patients from VATS-B and four from VATS-N experienced conversion to open surgery. Causes of conversion in VATS-B were intraoperative complications, whereas conversions in VATS-N were elective for oncological concerns (p < 0.05). Operation time and duration of postoperative mechanical ventilation were longer by tendency; postoperative stay on intensive care unit and chest tube duration were significantly longer in VATS-B. Subgroup analyses showed a longer operation time as a predictor for worse perioperative outcome regarding postoperative mechanical ventilation, postoperative stay on intensive care unit, chest tube duration, and length of hospital stay. Patients with longer operation time suffered from more postoperative complications. Differences in perioperative outcome data were not significantly dependent on the underlying benign diseases compared to VATS-N. CONCLUSIONS: VATS is feasible and safe in anatomic lung resection for benign pulmonary diseases. Not the underlying disease, but a longer operation time is a factor for worse postoperative outcome.

Video-assisted thoracoscopic anatomic lung resections in Germany-a nationwide survey.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) is an accepted alternative to thoracotomy for anatomic lung resection (AR) and literature suggests benefits over the conventional open approach. However, it's routine clinical application is still low and varies within different countries. METHODS: Nationwide survey among thoracic surgical units in Germany, evaluating the departmental structure, volume of the VATS program, experience with VATS-AR (lobectomies and other-than-lobectomies-anatomic-resections), surgical technique and learning curve data. RESULTS: Response rate among the 269 surgical units practicing thoracic surgery in Germany was 84.4 % (n = 227). One hundred twenty-two (53.7 %) units do have experience with any type of VATS-AR. The majority of units started the VATS program only within the last 5 years and 17.2 % (n = 21) of the units have performed more than 100 procedures by now. In 2013, 78.7 % of the units performed less than 25 % of their institutional AR via a VATS approach. Indications for VATS-AR were non-small cell lung cancer in 93.4 % (up to UICC-stage IA, IB, IIA, IIB, IIIA in 7 %, 22.8 %, 33.3 %, 17.5 %, 7 %, respectively), benign diseases in 57.4 %, and pulmonary metastases in 50.8 %. 43.4 % of the departments had experience with extended VATS-AR and 28.7 % performed VATS-AR after induction-therapy. CONCLUSIONS: Every second thoracic surgical unit in Germany does have experience in VATS-AR though only about 20 % of them perform it routinely and also in extended procedures.