Spray-drying of PEI-/PPI-based nanoparticles for DNA or siRNA delivery.

Spray-drying of nucleic acid-based drugs designed for gene therapy or gene knockdown is associated with many advantages including storage stability and handling as well as the possibility of pulmonary application. The encapsulation of nucleic acids in nanoparticles prior to spray-drying is one strategy for obtaining efficient formulations. This, however, strongly relies on the definition of optimal nanoparticles, excipients and spray-drying conditions. Among polymeric nanoparticles, polyethylenimine (PEI)-based complexes with or without chemical modifications have been described previously as very efficient for gene or oligonucleotide delivery. The tyrosine-modification of linear or branched low molecular weight PEIs, or of polypropylenimine (PPI) dendrimers, has led to high complex stability, improved cell uptake and transfection efficacy as well as high biocompatibility. In this study, we identify optimal spray-drying conditions for PEI-based nanoparticles containing large plasmid DNA or small siRNAs, and further explore the spray-drying of nanoparticles containing chemically modified polymers. Poly(vinyl alcohol) (PVA), but not trehalose or lactose, is particularly well-suited as excipient, retaining or even enhancing transfection efficacies compared to fresh complexes. A big mesh size is critically important as well, while the variation of the spray-drying temperature plays a minor role. Upon spray-drying, microparticles in a ∼ 3.3 - 8.5 µm size range (laser granulometry) are obtained, dependent on the polymers. Upon their release from the spray-dried material, the nanoparticles show increased sizes and markedly altered zeta potentials as compared to their fresh counterparts. This may contribute to their high efficacy that is seen also after prolonged storage of the spray-dried material. We conclude that these spray-dried systems offer a great potential for the preparation of nucleic acid drug storage forms with facile reconstitution, as well as for their direct pulmonary application as dry powder.

A comparison of Simplified Acute Physiology Score II and Sepsis-related Organ Failure Assessment Score for prediction of mortality after Intensive Care Unit cardiac arrest.

BACKGROUND: This study investigates the predictive value and suitable cutoff values of the Sepsis-related Organ Failure Assessment Score (SOFA) and Simplified Acute Physiology Score II (SAPS-II) to predict mortality during or after Intensive Care Unit Cardiac Arrest (ICU-CA). METHODS: In this secondary analysis the ICU database of a German university hospital with five ICU was screened for all ICU-CA between 2016-2019. SOFA and SAPS-II were used for prediction of mortality during ICU-CA, hospital-stay and one-year-mortality. Receiver operating characteristic curves (ROC), area under the ROC (AUROC) and its confidence intervals were calculated. If the AUROC was significant and considered "acceptable," cutoff values were determined for SOFA and SAPS-II by Youden Index. Odds ratios and sensitivity, specificity, positive and negative predictive values were calculated for the cutoff values. RESULTS: A total of 114 (78 male; mean age: 72.8±12.5 years) ICU-CA were observed out of 14,264 ICU-admissions (incidence: 0.8%; 95% CI: 0.7-1.0%). 29.8% (N.=34; 95% CI: 21.6-39.1%) died during ICU-CA. SOFA and SAPS-II were not predictive for mortality during ICU-CA (P>0.05). Hospital-mortality was 78.1% (N.=89; 95% CI: 69.3-85.3%). SAPS-II (recorded within 24 hours before and after ICU-CA) indicated a better discrimination between survival and death during hospital stay than SOFA (AUROC: 0.81 [95% CI: 0.70-0.92] vs. 0.70 [95% CI: 0.58-0.83]). A SAPS-II-cutoff-value of 43.5 seems to be suitable for prognosis of hospital mortality after ICU-CA (specificity: 87.5%, sensitivity: 65.6%; SAPS-II>43.5: 87.5% died in hospital; SAPS-II<43.5: 65.6% survived; odds ratio:13.4 [95% CI: 3.25-54.9]). Also for 1-year-mortality (89.5%; 95% CI: 82.3-94.4) SAPS-II showed a better discrimination between survival and death than SOFA: AUROC: 0.78 (95% CI: 0.65-0.91) vs. 0.69 (95% CI: 0.52-0.87) with a cutoff value of the SAPS-II of 40.5 (specificity: 91.7%, sensitivity: 64.3%; SAPS-II>40.5: 96.4% died; SAPS-II<40.5: 42.3% survived; odd ratio: 19.8 [95% CI: 2.3-168.7]). CONCLUSIONS: Compared to SOFA, SAPS-II seems to be more suitable for prediction of hospital and 1-year-mortality after ICU-CA.

Microbial H2 Consumption by a Formation Fluid from a Natural Gas Field at High-Pressure Conditions Relevant for Underground H2 Storage.

Underground hydrogen storage (UHS) has been proposed as one option for storage of excess energy from renewable sources. Depleted gas reservoirs appear suitable, but at the same time, they may be environments with potentially high microbial abundances and activities. Hydrogen (H2) is one of the most energetic substrates in such environments, and many microorganisms are able to oxidize H2, potentially leading to loss of H2 or other unwanted reactions like production of, e.g., H2S, clogging, or corrosion. This study addressed the potential of H2 consumption by naturally abundant microorganisms in formation fluid from a gas field at near in situ pressure and temperature conditions. Microbial H2 consumption was evident at ambient and 100 bar and tolerated pressure variations reflecting cycles of H2 storage. Temperature strongly influenced the activity with higher activity at 30 °C but lower activity at 60 °C. The activity was sulfate-dependent, and sulfide was produced. The microbial community composition changed during H2 consumption with an increase in sulfate-reducing prokaryotes (SRP). Thus, the presence of an SRP-containing, H2-consuming microbial community with activity at UHS-relevant pressure and temperature conditions was shown and should be taken into account when planning UHS at this and other sites.

Women's Perception of Transgastric and Transvaginal Natural Orifice Transluminal Endoscopic Surgery (NOTES) - Impact of Medical Education, Stage of Life and Cross-Cultural Aspects.

Introduction: Despite that NOTES produces at least matchable clinical long-term results when compared to laparoscopy, still a restraint within the medical community and among patients is evident. Consequently, it might be meaningful to evaluate factors of patient's NOTES perception to promote its acceptance. NOTES is still quite novel and questionnaires regarding its perception by the public is still lacking even so in the Middle East. Aim of our survey is to investigate the viewpoint of female healthcare staff on NOTES. Materials and Methods: A total of 350 questionnaires along with written information about Minimally Invasive Surgery and NOTES were distributed among the female staff in a Tertiary-care Hospital in Abu Dhabi, 257 were returned completely anonymously and voluntarily and entered into a database with a response rate of 73%. We surveyed factors like religion, medical background, age as well as history of previous laparoscopy, endoscopy, birth and other aspects that may impact a woman's perception of both transgastric and transvaginal NOTES for cholecystectomy and ovariectomy, respectively. Results: Univariate analyses revealed the majority of Muslim women to be more receptive to NOTES as a choice of surgical technique for cholecystectomy and for ovariectomy, respectively, when compared to Christians and Hindus. However, when compared to Muslims, Christian and Hindu groups had a larger share of medical professions. Women with a medical background would opt significantly less for NOTES. Among younger women, NOTES cholecystectomy was refused due to anxiety concerning future pregnancies and sexual dysfunction. Multinomial logistic regression analysis determined medical background and with independent predictive value for the overall choice of interventional technique (p<0.001). Marital status played a significant role only in the comparison of laparoscopy vs transgastric NOTES when performing cholecystectomy and ovariectomy (p<0.01). Conclusion: In this first study emanating from the Middle East, medical education and partly life stage rather than cross-cultural differences seem to influence NOTES perception in women.

Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance.

OBJECTIVE: Human white adipose tissue (AT) is a metabolically active organ with distinct depot-specific functions. Despite their locations close to the gastrointestinal tract, mesenteric AT and epiploic AT (epiAT) have only scarcely been investigated. Here, we aim to characterise these ATs in-depth and estimate their contribution to alterations in whole-body metabolism. DESIGN: Mesenteric, epiploic, omental and abdominal subcutaneous ATs were collected from 70 patients with obesity undergoing Roux-en-Y gastric bypass surgery. The metabolically well-characterised cohort included nine subjects with insulin sensitive (IS) obesity, whose AT samples were analysed in a multiomics approach, including methylome, transcriptome and proteome along with samples from subjects with insulin resistance (IR) matched for age, sex and body mass index (n=9). Findings implying differences between AT depots in these subgroups were validated in the entire cohort (n=70) by quantitative real-time PCR. RESULTS: While mesenteric AT exhibited signatures similar to those found in the omental depot, epiAT was distinct from all other studied fat depots. Multiomics allowed clear discrimination between the IS and IR states in all tissues. The highest discriminatory power between IS and IR was seen in epiAT, where profound differences in the regulation of developmental, metabolic and inflammatory pathways were observed. Gene expression levels of key molecules involved in AT function, metabolic homeostasis and inflammation revealed significant depot-specific differences with epiAT showing the highest expression levels. CONCLUSION: Multi-omics epiAT signatures reflect systemic IR and obesity subphenotypes distinct from other fat depots. Our data suggest a previously unrecognised role of human epiploic fat in the context of obesity, impaired insulin sensitivity and related diseases.

Shewanella putrefaciens, a rare human pathogen: A review from a clinical perspective.

Shewanella putrefaciens is a gramnegative, facultatively anaerobic, rod shaped bacterium. It belongs to the class of the Gammaproteobacteria and was first described in 1931. S. putrefaciens is part of the marine microflora and especially present in moderate and warm climates. The bacterium is a rare oppurtonistic human pathogen associated mainly with intra-abdominal as well as skin and soft tissue infections. However, it has also been reported in association with more severe diseases such as pneumonia, intracerebral and ocular infections and endocarditis. In these cases the clinical courses are often associated with underlying, predisposing diseases and risk factors. For successful treatment of S. putrefaciens, a combination of appropriate local therapy, e.g. surgical treatment or drainage, and antibiotic therapy should be performed. Since multiple resistances to antibiotics are described, the results of the antimicrobial susceptibility testing must be considered for effective therapy as well. Furthermore, a main challenge in clinical practice is the accurate microbiological identification, and especially the correct differentiation between S. putrefaciens and S. algae. Under certain circumstances, Shewanella-infections can have severe, sometimes even fatal consequences. Therefore, we decided to present the current state of knowledge as well as further aspects with regard to future diagnostics, therapy and research.

Technical aspects of paediatric robotic pancreatic enucleation based on a case of an insulinoma.

BACKGROUND: Insulinomas are rare insulin-producing pancreatic neuroendocrine tumours leading to severe episodes of hypoglycaemia. Surgery is the predominant curative therapy. METHODS: We report here the first paediatric case of an insulinoma of the pancreatic body resected completely robotically under ultrasound guidance in a 10-year-old male with multiple endocrine neoplasia type 1. The port set-up was adapted for the narrowed dimensions of the paediatric peritoneal space. We comment on technical key steps for the organ-preserving procedure that was performed in close proximity to critical anatomic structures, with supporting video. Preoperative diagnostics, including endoscopic ultrasound, to determine surgical management are highlighted. RESULTS: Following an uneventful post-operative course, the boy was discharged on day 11 with normalised glucose-metabolism. A pseudocyst developing after 4 weeks was treated with endoscopic stenting. CONCLUSIONS: The applicability of a robotic surgical system in limited space conditions such as found in the paediatric abdominal cavity is demonstrated here for pancreatic surgery.

Severe drug-induced liver injury caused by levetiracetam - A case report and review of the literature.

Levetiracetam (LEV) is a broad-spectrum, second-generation anti-seizure medication, which has quickly become one of the most commonly prescribed drugs for people with epielpsy due to its good tolerability, rapid up-dosing capability, with both parenteral and enteral routes of administration. Considering the frequent prescriptions and predominant excretion by the kidney with minimal hepatic metabolism, severe liver injury is very rarely a complication associated with LEV. An analysis of this reported case and further published cases was performed with respect to indication, relevant previous liver diseases, concomitant medication, and both the dosage as well as the duration of LEV when drug-induced liver injury (DILI) was noted. DILI occurs after a few days to a maximum of five months after initiation of therapy with LEV and, in the worst case, may require liver transplantation or result in death. Monitoring of serum transaminase values may be helpful. Discontinuing LEV is the first therapeutic measure. In addition, immunosuppression with cortisone can be considered for serious cases.

Grave thoraco-intestinal complication secondary to an undetected traumatic rupture of the diaphragm: a case report.

BACKGROUND: Diaphragmatic lesions as a result of blunt or penetrating trauma are challenging to detect in the initial trauma setting. This is especially true when diaphragmatic trauma is part of a polytrauma. Complications of undetected diaphragmatic defects with incarcerating bowel are rare, but as in our patient can be serious. CASE PRESENTATION: A 57-year-old female presented to the Emergency Room of our Hospital in a critical condition with 3 days of increasing abdominal pain. The initial clinical examination showed peritonism with tinkling peristaltic bowel sounds of mechanical obstruction. A thoraco-abdominal CT scan demonstrated colon prolapsed through the left diaphragmatic center with a large sero-pneumothorax under tension. As the patient was hemodynamically increasingly unstable with developing septic shock, an emergency laparotomy was performed. After retraction of the left colon, which had herniated through a defect of the tendinous center of the left diaphragm and was perforated due to transmural ischemia, large amounts of feces and gas discharged from the left thorax. A left hemicolectomy resulting in a Hartmann-type procedure was performed. A fully established pleural empyema required meticulous debridement and lavage conducted via the 7-10 cm in diameter phrenic opening followed by a diaphragmatic defect reconstruction. Due to pneumonia and recurring pleural empyema redo-debridement of the left pleural space via thoracotomy were required. The patient was discharged on day 56. A thorough history of possible trauma revealed a bicycle-fall trauma 7 months prior to this hospitalization with a surgically stabilized fracture of the left femur and conservatively treated fractures of ribs 3-9 on the left side. CONCLUSION: This is the first report on a primarily established empyema at the time of first surgical intervention for feco-pneumothorax secondary to delayed diagnosed diaphragmatic rupture following abdomino-thoracic blunt trauma with colic perforation into the pleural space, requiring repetitive surgical debridement in order to control local and systemic sepsis. Thorough investigation should always be undertaken in cases of blunt abdominal and thoracic trauma to exclude diaphragmatic injury in order to avoid post-traumatic complications.

Hepatic Vasculopathy and Regenerative Responses of the Liver in Fatal Cases of COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects the nasopharynx and lungs and causes coronavirus disease-2019 (COVID-19). It may impact the heart, brain, kidney, and liver.1 Although functional impairment of the liver has been correlated with worse clinical outcomes, little is known about the pathophysiology of hepatic injury and repair in COVID-19.2,3 Histologic evaluation has been limited to small numbers of COVID-19 cases with no control subjects2,4 and demonstrated largely heterogeneous patterns of pathology.2,3.

Isolation and Characterization of Two Novel Colorectal Cancer Cell Lines, Containing a Subpopulation with Potential Stem-Like Properties: Treatment Options by MYC/NMYC Inhibition.

Cancer stem cells (CSC) are crucial mediators of cancer relapse. Here, we isolated two primary human colorectal cancer cell lines derived from a rectal neuroendocrine carcinoma (BKZ-2) and a colorectal adenocarcinoma (BKZ-3), both containing subpopulations with potential stem-like properties. Protein expression of CSC-markers prominin-1 and CD44 antigen was significantly higher for BKZ-2 and BKZ-3 in comparison to well-established colon carcinoma cell lines. High sphere-formation capacity further confirmed the existence of a subpopulation with potential stem-like phenotype. Epithelial-mesenchymal transition markers as well as immune checkpoint ligands were expressed more pronounced in BKZ-2. Both cell populations demonstrated N-myc proto-oncogene (NMYC) copy number gain. Myc proto-oncogene (MYC)/NMYC activity inhibitor all-trans retinoic acid (ATRA) significantly reduced the number of tumor spheres for both and the volume of BKZ-2 spheres. In contrast, the sphere volume of ATRA-treated BKZ-3 was increased, and only BKZ-2 cell proliferation was reduced in monolayer culture. Treatment with KJ-Pyr-9, a specific inhibitor of MYC/NMYC-myc-associated factor X interaction, decreased survival by the induction of apoptosis of both. In summary, here, we present the novel colorectal cancer cell lines BKZ-2 and BKZ-3 as promising cellular in vitro models for colorectal carcinomas and identify the MYC/NMYC molecular pathway involved in CSC-induced carcinogenesis with relevant therapeutic potential.

Platelets Boost Recruitment of CD133+ Bone Marrow Stem Cells to Endothelium and the Rodent Liver-The Role of P-Selectin/PSGL-1 Interactions.

We previously demonstrated that clinical administration of mobilized CD133+ bone marrow stem cells (BMSC) accelerates hepatic regeneration. Here, we investigated the potential of platelets to modulate CD133+BMSC homing to hepatic endothelial cells and sequestration to warm ischemic livers. Modulatory effects of platelets on the adhesion of CD133+BMSC to human and mouse liver-sinusoidal- and micro- endothelial cells (EC) respectively were evaluated in in vitro co-culture systems. CD133+BMSC adhesion to all types of EC were increased in the presence of platelets under shear stress. This platelet effect was mostly diminished by antagonization of P-selectin and its ligand P-Selectin-Glyco-Ligand-1 (PSGL-1). Inhibition of PECAM-1 as well as SDF-1 receptor CXCR4 had no such effect. In a model of the isolated reperfused rat liver subsequent to warm ischemia, the co-infusion of platelets augmented CD133+BMSC homing to the injured liver with heightened transmigration towards the extra sinusoidal space when compared to perfusion conditions without platelets. Extravascular co-localization of CD133+BMSC with hepatocytes was confirmed by confocal microscopy. We demonstrated an enhancing effect of platelets on CD133+BMSC homing to and transmigrating along hepatic EC putatively depending on PSGL-1 and P-selectin. Our insights suggest a new mechanism of platelets to augment stem cell dependent hepatic repair.

Impact of ASA-score, age and learning curve on early outcome in the initiation phase of an oncological robotic colorectal program.

The ASA score is known to be an independent predictor of complications and mortality following colorectal surgery. We evaluated early outcome in the initiation phase of a robotic oncological colorectal resection program in dependence of comorbidity and learning curve. 43 consecutive colorectal cancer patients (median age: 74 years) who underwent robotic surgery were firstly analysed defined by physical status (group A = ASA1 + 2; group B = ASA3). Secondly, outcome was evaluated relating to surgery date (group E: early phase; group L: late phase). There were no differences among groups A and B with regard to gender, BMI, skin-to-skin operative times (STS), N- and M-status, hospital-stay as well as overall rate of complications according to Dindo-Clavien and no one-year mortality. GroupA when compared to group B demonstrated significantly lower mean age (65.5 years ± 11.4 years vs 75.8 years ± 8.9 years), T-stage and ICU-stay. When separately analyzed for patients age ICU-stay was comparable (> 75 years vs. < 75 years). Group E and L demonstrated comparable characteristics and early outcome except more frequent lymphatic fistulas in group E. STS was reduced in group L compared to group E. Beyond learning curve aspects in our series, we could demonstrate that patient's physical condition according to ASA rather than age may have an impact on early outcome in the initial phase of a robotic oncological colorectal program.

[Base Rate of Probable Malingering and its Indicators in the Assessment of Mental Disorders - Retrospective Analysis of a Sample of Forensic Psychological Evaluations]. / Prävalenz nicht-authentischer Beschwerdenbilder und Indikatoren in der Begutachtung psychischer und psychosomatischer Störungen ­ retrospektive Analyse einer Begutachtungsstichprobe.

PURPOSE: Estimation of a base rate of malingering in accordance with changes of the complexity of assessment in a sample of forensic psychological evaluations. METHODS: We performed a retrospective analysis of 1175 psychological evaluations over the course of 16 years (2000-2015). RESULTS: With the use of increasingly complex methods, inconsistencies are reported more frequently and a higher rate of feigning (47,2%) in symptom validity testing is noted. However, the overall rate of malingering is only 15,8%. A uniform multi-methods approach guarantees that there does not develop any bias in the assessment across evaluators. CONCLUSION: The revealed rate of malingering matches recent reviews that call into question estimations which had yielded substantially higher rates. Symptom validity tests serve as an important decision-making tool for psychological evaluators. For the overall assessment, however, other possible inconsistencies are taken into account.

A standardized suprapubic bottom-to-up approach in robotic right colectomy: technical and oncological advances for complete mesocolic excision (CME).

BACKROUND: Several studies have demonstrated a direct correlation between lymph node yield and survival after colectomy for cancer. Complete mesocolic excision (CME) in right colectomy (RC) reduces local recurrence but is technically demanding. Here we report our early single center experience with robotic right colectomy comparing our standardized bottom-to-up (BTU) approach of robotic RC with CME and central vessel ligation (CVL) facilitated by a suprapubic access with the "classical" medial-to-lateral (MTL) strategy. METHODS: A 4-step BTU approach of robotic RC guided by embryonal planes in the process of retrocolic mobilization with suprapubic port placement was performed in the BTU-group (n = 24; all with intention to treat cancer). In step 1 CME was initiated with caudolateral mobilization of the right colon guided by the fascia of Toldt across the duodenum and up to the Trunk of Henle. Subsequently, dissection was performed BTU right of the middle supramesenteric vessels with central ileocolic vessel ligation in step 2. Subsequent to separation of the transverse retromesenteric space and completion of mobilization the hepatic flexure in step 3, the transverse mesocolon was then transected right of the middle colic vessels in step 4. An extracorporeal side to side anastomosis was performed. We compared the outcome of the BTU-group with a MTL-group (n = 7). RESULTS: Patient characteristics like age, gender, BMI, comorbidity (ASA) and M-status were comparable among groups. There was no conversion. Overall complication rate was 35.5%. We experienced no anastomoses insufficiency, grade Dindo/Clavien III/IV complication or mortality in this study. Type I and II complications and surgical characteristics incl. OR-time, ICU- and hospital-stay were comparable between the two groups. However, the lymph node yield was superior in the BTU-group (mean 40.2 ± 17.1) when compared with the MTL-group (16,3 nodes ±8.5; p <  0,001). CONCLUSIONS: Compared to the classical MTL approach, robotic suprapubic BTU RC changes from a search of the layers bordering the oncological dissection to a consequent utilization of the planes as a retro-mesocolic guide during CME. The BTU strategy could bear the potential to increase the lymph node yield. Robotic systems may provide the technical requirements to combine advantages of both open and minimally invasive RC.

CD133+ bone marrow stem cells (BMSC) control platelet activation - Role of ectoNTPDase-1 (CD39).

BACKGROUND: We previously demonstrated CD133+ bone marrow stem cells (BMSC) to promote hepatic proliferation for liver regeneration. Here, we evaluated the capacity of CD133+BMSC to utilize platelets for homing to vasculature and concomitant controlling their aggregability upon ADP stimulation. METHODS: CD133+BMSC and platelets were co-cultured along micro endothelial cells under variable flow conditions and tested for homing levels along vasculature. Aggregometry and FACS analysis were utilized to evaluate platelet reactivity following co-incubation ±â€¯CD133+BMSC. RT-PCR and FACS analyses served to characterize ADP degrading ectonucleoside triphosphate diphosphohydrolase-1 (ectoNTPDase-1/CD39) expression on various cell types. RESULTS: Platelets attracted human CD133+BMSC to autologous micro endothelium under shear stress unaffected by ADP stimulation. However, CD133+BMSC inhibited ADP-mediated platelet activation and aggregation. Latter was dependent on ectoNTPDase-1 expression levels. Platelet aggregatory control was increased with CD133+BMSC compared to CD133+PHSC. Different effects of those stem cell subtypes positively correlated with their FACS-detected expression levels of ectoNTPDase-1. CONCLUSION: We provide evidence that CD133+BMSC are capable of controlling ADP-dependent platelet aggregation and activation by direct interaction dependent on cellular expression of ectoNTPDase-1. Whether different capacities of BMSC modulate platelet-depending thrombogenicity at sites of regeneration impact effectiveness and adverse event profiles of regenerative treatment requires further evaluation.

Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications.

OBJECTIVES: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size. DESIGNS: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre. RESULTS: A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis. CONCLUSIONS: This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients. TRIAL REGISTRATION NUMBER: DRKS00007768; Pre-results.

Dorsal Track Control (DTC): A Modified Surgical Technique for Atraumatic Handling of the Distal Esophagus in Esophagojejunostomy.

Surgical therapy for adenocarcinoma of the esophagogastric junction II requires distal esophagectomy, in which a transhiatal management of the lower esophagus is critical. The 'dorsal track control' (DTC) maneuver presented here facilitates the atraumatic handling of the distal esophagus, in preparation for a circular-stapled esophagojejunostomy. It is based on a ventral semicircular incision in the distal esophagus, with an intact dorsal wall for traction control of the esophagus. The maneuver facilitates the proper placement of the purse-string suture, up to its tying (around the anvil), thus minimizing the manipulation of the remaining esophagus. Furthermore, the dorsally-exposed inner wall surface of the ventrally-opened esophagus serves as a guiding chute that eases anvil insertion into the esophageal lumen. We performed this novel technique in 21 cases, enabling a safe anastomosis up to 10 cm proximal to the Z-line. No anastomotic insufficiency was observed. The DTC technique improves high transhiatal esophagojejunostomy.