Evaluation of optimum classification measures used to define textbook outcome among patients undergoing curative-intent resection of gastric cancer.

BACKGROUND: Textbook outcome (TO) is a composite measure reflecting various aspects of services provided to patients with solid malignancies. We sought to evaluate the importance of various TO components previously proposed for gastric cancer. METHODS: Prospectively maintained electronic databases of 1,743 patients treated in two academic surgical centres were reviewed. Six candidate definitions of TO were evaluated based on their ability to accurately predict patients' prognosis by Cox proportional hazards modelling. RESULTS: TO definition combining 10 measures corresponding to complete tumour resection with an uneventful postoperative course showed the best goodness of fit by achieving the lowest values of Akaike (AIC) and Bayesian (BIC) information criteria and the best predictive performance based on the highest value of c-index. The overall median survival was significantly longer for patients with than without textbook outcome (69.0 vs 20.1 months, P < 0.001). TO maintained its prognostic value in a multivariate model controlling for age, sex, comorbidities, treatment, and tumour related variables and was associated with a 39% lower risk of death (HR 0.61, 95%CI 0.51 - 0.73, P < 0.001). Nine variables identified as predictors of TO were used to develop a nomogram showing very good correlation between the predicted and actual probability of achieving TO. The AUC of ROC obtained from the nomogram was 0.752 (95% CI 0.727 to 0.781). CONCLUSIONS: A uniform definition of textbook outcome provides clinically relevant prognostic information and could be used in quality improvement programs for gastric cancer patients.

Structure and function of the metagenomic plastic-degrading polyester hydrolase PHL7 bound to its product.

The recently discovered metagenomic-derived polyester hydrolase PHL7 is able to efficiently degrade amorphous polyethylene terephthalate (PET) in post-consumer plastic waste. We present the cocrystal structure of this hydrolase with its hydrolysis product terephthalic acid and elucidate the influence of 17 single mutations on the PET-hydrolytic activity and thermal stability of PHL7. The substrate-binding mode of terephthalic acid is similar to that of the thermophilic polyester hydrolase LCC and deviates from the mesophilic IsPETase. The subsite I modifications L93F and Q95Y, derived from LCC, increased the thermal stability, while exchange of H185S, derived from IsPETase, reduced the stability of PHL7. The subsite II residue H130 is suggested to represent an adaptation for high thermal stability, whereas L210 emerged as the main contributor to the observed high PET-hydrolytic activity. Variant L210T showed significantly higher activity, achieving a degradation rate of 20 µm h-1 with amorphous PET films.

Spine surgery in a state-of-the-art hybrid operating room: an experience of 1745 implanted pedicle screws in the thoracolumbar spine.

Hybrid-operating rooms (hybrid-OR) combine high-resolution 2D images and 3D-scans with the possibility of 3D-navigation and allow minimal invasive pedicle screw placement even in the upper thoracic spine. The disadvantage of high cost and increased radiation needs to be compensated with high accuracy and safety. The hybrid operating room consists of a floor-based flat-panel robotic C-arm with 3D-scan capability (Artis Zeego, Siemens; Germany) combined with navigation (BrainLAB Curve, BrainLAB; Germany). Through a minimally invasive incision, a Jamshidi needle was advanced through the pedicle and a K-wire was placed. If 2D image quality did not allow safe placement 3D-navigation was used to place the K-wire. Position was controlled through a 3D-Scan and corrected if necessary before screw placement. Postoperative CTs evaluated screw perforation grade with grade I when completely within the pedicle, II < 2 mm, III 2-4 mm, and IV > 4 mm outside the pedicle. Overall, 354 screws were placed in T1-T6, 746 in the lower thoracic spine T7-T12 and 645 in the L1-L5. Navigation was mainly used in upper thoracic spine cases (31 of 57). In 63 out of 326 cases K-wire was corrected after the 3D-Scan. Overall, 99.1% of the screws showed perforation less than 2 mm. Mean radiation was 13.3 ± 11.7 mSv and significantly higher in the upper thoracic spine and in navigated procedures. Despite higher costs and radiation, the hybrid-OR allows highest accuracy and therefore patient safety in minimal invasive pedicle screw placement in the thoracic and lumbar spine.

Nomogram-Based Prognostic Evaluation of Gastric Cancer Patients with Low Counts of Examined Lymph Nodes Outperforms the Predictive Ability of the 7th and 8th Editions of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) staging system has limited accuracy in predicting survival of gastric cancer patients with inadequate counts of evaluated lymph nodes (LNs). We therefore aimed to develop a prognostic nomogram suitable for clinical applications in such cases. METHODS: A total of 1511 noncardia gastric cancer patients treated between 1990 and 2010 in the academic surgical center were reviewed to compare the 7th and 8th editions of the AJCC staging system. A nomogram was developed for the prediction of 5-year survival in patients with less than 16 LNs evaluated (n = 546). External validation was performed using datasets derived from the Polish Gastric Cancer Study Group (n = 668) and the SEER database (n = 11,225). RESULTS: The 8th edition of AJCC staging showed better overall discriminatory power compared to the previous version, but no improvement was found for patients with < 16 evaluated LNs. The developed nomogram had better concordance index (0.695) than the former (0.682) or latest (0.680) staging editions, including patients subject to neoadjuvant treatment, and calibration curves showed excellent agreement between the nomogram-predicted and actual survival. High discriminatory power was also demonstrated for both validation cohorts. Subsequently, the nomogram showed the best accuracy for the prediction of 5-year survival through the time-dependent ROC curve analysis in the training and validation cohorts. CONCLUSIONS: A clinically relevant nomogram was built for the prediction of 5-year survival in patients with inadequate numbers of LNs evaluated in surgical specimens. The predictive accuracy of the nomogram was validated in two Western populations.

Kidney Transplantation in Abernethy Malformation: A Case Report.

Abernethy malformation is a rare disorder defined by congenital portosystemic shunt. Advances in clinical imaging have led to increased identification of this anomaly, which has proven to be more common and more clinically diverse than previously assumed. Late presentations are not uncommon. We present a 35-year-old patient with type Ia Abernethy malformation and biopsy-confirmed mesangiocapillary glomerulonephritis who was referred for deceased donor kidney transplantation. After the diagnosis was confirmed, the patient remained stable and asymptomatic on a supervised low-protein, high-carbohydrate diet. The patient received the kidney transplant from a brain-dead donor with standard characteristics. The procedure was uneventful; no vascular or vesical abnormalities could be identified at the surgical site. Recovery was uneventful with excellent graft function. Unique issues with immunosuppression were identified. Pharmacologic adjustments accounting for congenital complete portosystemic shunting affecting liver first pass effect as well as multiple drug interactions were necessary and sufficient. Abernethy malformation may follow indolent course into adulthood and may be an unrelated finding in a patient with chronic kidney disease. Kidney transplantation proved to be feasible and safe in this young male with apparently efficient compensatory mechanisms.

Antarctic Polyester Hydrolases Degrade Aliphatic and Aromatic Polyesters at Moderate Temperatures.

Polyethylene terephthalate (PET) is one of the most widely used synthetic plastics in the packaging industry, and consequently has become one of the main components of plastic waste found in the environment. However, several microorganisms have been described to encode enzymes that catalyze the depolymerization of PET. While most known PET hydrolases are thermophilic and require reaction temperatures between 60°C and 70°C for an efficient hydrolysis of PET, a partial hydrolysis of amorphous PET at lower temperatures by the polyester hydrolase IsPETase from the mesophilic bacterium Ideonella sakaiensis has also been reported. We show that polyester hydrolases from the Antarctic bacteria Moraxella sp. strain TA144 (Mors1) and Oleispira antarctica RB-8 (OaCut) were able to hydrolyze the aliphatic polyester polycaprolactone as well as the aromatic polyester PET at a reaction temperature of 25°C. Mors1 caused a weight loss of amorphous PET films and thus constitutes a PET-degrading psychrophilic enzyme. Comparative modeling of Mors1 showed that the amino acid composition of its active site resembled both thermophilic and mesophilic PET hydrolases. Lastly, bioinformatic analysis of Antarctic metagenomic samples demonstrated that members of the Moraxellaceae family carry candidate genes coding for further potential psychrophilic PET hydrolases. IMPORTANCE A myriad of consumer products contains polyethylene terephthalate (PET), a plastic that has accumulated as waste in the environment due to its long-term stability and poor waste management. One promising solution is the enzymatic biodegradation of PET, with most known enzymes only catalyzing this process at high temperatures. Here, we bioinformatically identified and biochemically characterized an enzyme from an Antarctic organism that degrades PET at 25°C with similar efficiency to the few PET-degrading enzymes active at moderate temperatures. Reasoning that Antarctica harbors other PET-degrading enzymes, we analyzed available data from Antarctic metagenomic samples and successfully identified other potential enzymes. Our findings contribute to increasing the repertoire of known PET-degrading enzymes that are currently being considered as biocatalysts for the biological recycling of plastic waste.

Low Carbon Footprint Recycling of Post-Consumer PET Plastic with a Metagenomic Polyester Hydrolase.

Earth is flooded with plastics and the need for sustainable recycling strategies for polymers has become increasingly urgent. Enzyme-based hydrolysis of post-consumer plastic is an emerging strategy for closed-loop recycling of polyethylene terephthalate (PET). The polyester hydrolase PHL7, isolated from a compost metagenome, completely hydrolyzes amorphous PET films, releasing 91 mg of terephthalic acid per hour and mg of enzyme. Vertical scanning interferometry shows degradation rates of the PET film of 6.8 µm h-1 . Structural analysis indicates the importance of leucine at position 210 for the extraordinarily high PET-hydrolyzing activity of PHL7. Within 24 h, 0.6 mgenzyme gPET -1 completely degrades post-consumer thermoform PET packaging in an aqueous buffer at 70 °C without any energy-intensive pretreatments. Terephthalic acid recovered from the enzymatic hydrolysate is then used to synthesize virgin PET, demonstrating the potential of polyester hydrolases as catalysts in sustainable PET recycling processes with a low carbon footprint.

Accuracy of screw stabilization of the dorsal pelvic ring using a hybrid operating room: 5 Year experience in a level 1 trauma center.

INTRODUCTION: Accuracy for screw placement in the dorsal pelvic ring can be enhanced using intraoperative 3D navigation. Advances in intraoperative imaging lead to benefits for pelvic surgery. New c-arms are equipped with flat panel detectors, which have a larger detector and assure higher image quality with accompanying dose reduction. A hybrid OR is defined by a fixed imaging system in an operating room providing the benefit of the surgical environment in combination with advanced intraoperative imaging. Aim of our investigation was to analyze the accuracy of navigated sacroiliac (SI) and transsacral transiliac (TSTI) screws in the dorsal pelvic ring, which were implanted with a hybrid OR in the first five years of use. MATERIAL AND METHODS: All percutaneous SI or TSTI screws implanted in the hybrid OR using intraoperative navigation in the first 5 years of utilization (between June 2012 to June 2017) were included. Intraoperative 3D-scans and postoperative computed tomography were examined for screw perforation. RESULTS: 210 SI and TSTI screws were implanted in 187 patients using intraoperative navigation in the hybrid-OR. 90.6 % of SI screws showed no cortical perforation. 6,3 % had a grade 1, 2.4 % a grade 2 and 0.8 % a grade 3 perforation. In 80.7 % of TSTI screws no perforation and in 13.3 % a grade 1 perforation was detected. 3.6 % showed a grade 2 and 2.4 % a grade 3 perforation. No significant difference between both screw types regarding the grade of cortical perforation could be seen. No significant relation between perforation rate and year of operation could be detected. CONCLUSION: Intraoperative navigation in a hybrid OR ensures a high accuracy for SI screws. Due to the large field of view and high image quality TSTI screws can be safely implanted in S1 and S2. Utilization of a hybrid-OR is accompanied with a steep learning curve.

Differentiating between micronucleus dose-responses induced by whole cigarette smoke solutions with Benchmark Dose potency ranking.

Dose-response modeling of in vitro micronucleus test (IVMNT) data was evaluated to determine if the approach has value in discriminating among different tobacco products. Micronucleus responses were generated in L5178Y/Tk+/- mouse lymphoma cells and TK6 human lymphoblastoid cells from a series of whole smoke solutions (WSSs) expected to have different levels of genotoxicity based on differences in their machine-generated smoke constituents. Eight WSSs were prepared by machine smoking different numbers (20 or 60) of two commercial cigarettes (Marlboro Silver or Red) under International Standardization Organization (ISO) or Health Canada Intense (HCI) smoking machine regimens and tested in the two cell lines with and without rat liver S9 activation. The S9-mediated IVMNT dose-response data from the WSSs were evaluated with PROAST software and Benchmark Doses (BMDs) and their upper and lower confidence intervals (CIs) were generated. IVMNT data differed based on the number and type of cigarettes smoked and smoking machine regimen. The IVMNT responses produced in mouse lymphoma cells generally were greater than in TK6 cells, but the ability of the two cell types to differentiate between WSSs was similar. The results indicate that BMD potency ranking was useful for differentiating between IVMNT responses.

Clinical characteristics and outcome of patients over 60 years with Hodgkin lymphoma treated in Switzerland.

Hodgkin lymphoma (HL) in older patients appears to be a different disease compared with younger patients with historically lower survival rates. This is related to a variety of factors, including increased treatment-related toxicity, the presence of comorbidities, and biologic differences. In order to better assess the clinical characteristics, treatment strategies, and outcome of this particular population, we conducted a population-based, retrospective analysis including 269 patients with HL older than 60 years (median age 71 years, range 60-94), treated between 2000 and 2017 in 15 referral centers across Switzerland. Primary endpoints were overall survival (OS), progression-free survival (PFS), and cause-specific survival (CSS). The vast majority of patients were treated with curative intent, either with a combined modality approach (chemotherapy followed by radiation therapy) or with systemic therapy. At a median follow-up of 6.6 years (95% confidence interval [CI], 6.0-7.6), 5-year PFS was 52.2% (95% CI, 46.0-59.2), 5-year OS was 62.5% (95% CI, 56.4-69.2), and 5-year CSS was 85.1.8% (95% CI, 80.3-90.1) for the entire cohort. A significant difference in terms of CSS was observed for patients older than 71 years in comparison to patients aged 60-70 years (hazard ratio 2.6, 1.3-5.0, p = 0.005). Bleomycin-induced lung toxicity (BLT) was documented in 26 patients (17.7%) out of the 147 patients exposed to this compound and was more frequent in patients older than 71 years (15/60, 25%). Outcome of HL pts older than 71 years appeared to decrease substantially in comparison to the younger counterpart. Treatment-related toxicities appeared to be relevant, in particular, BLT. New, potentially less toxic strategies need to be investigated in prospective clinical trials in this particular frail population.

Cement augmentation of the proximal femur nail antirotation: is it safe?

BACKGROUND: Cement augmentation of the proximal femur nail antirotation (PFNA; Fa. DePuy Synthes) showed good biomechanical and clinical results regarding increased stability and functional outcome [Linden et al. in J Orthop Res 24:2230-2237, 2006;Kammerlander et al. in Injury 49:1436-1444, 2018;]. Cement-associated complications are well known in orthopedic procedures like hip arthroplasty, vertebra- and kyphoplasty. This study investigates outcome and safety of augmentation of the proximal femur nail blade. MATERIALS AND METHODS: The retrospective review of the 299 patients (mean age 80 ± 13 years; 205 women and 94 men) focused on perioperative complications after augmentation which was performed with Traumacem V+ Cement (Fa. DePuy Synthes) in 152 cases. The decision for augmentation of the blade was made by the attending surgeon and based on the factors age, bone quality, and fracture pattern. Primary outcome measures were changes in blood pressure, heart rate or oxygen saturation, and the number of needed vasoactive drugs during augmentation. Secondary outcome measures where the rate of cement leakage into the joint, mechanical failure, and perioperative complications like pulmonary embolism, stroke, or heart attack. RESULTS: In 152 augmented cases, no leakage of cement into the joint could be detected. No signs of mechanical failure like cut-out of the blade were seen after 6 weeks and 3 months. Also, augmentation did not show a higher rate of mortality or postoperative complications like stroke, heart attack, embolism, or infection. 57 of 152 augmented cases received an intraoperative intervention with vasoactive medication at the time of augmentation either prophylactically or because of a blood pressure fall. Out of the non-augmented cases, 21 of 147 needed vasoactive medication in the second half of the operation. The difference between these groups was significant (p < 0.05). In the cases without an intervention, there was a significant blood pressure fall of about 8 ± 7.4 mmHg during the augmentation (p < 0.001). Still, none of the augmented cases showed a change in heart rate or oxygen saturation. CONCLUSION: The augmentation of the PFNA blade proved to be a safe procedure. Cement augmentation will not increase postoperative complications or mortality. The risk for leakage of cement into the joint is low and mechanical cut-out might be prevented. The decision for augmentation should be made carefully and always be declared loud and in advance to allow the anesthetist to prepare, because blood pressure changes can occur.

Impact of oral anticoagulation on proximal femur fractures treated within 24 h - A retrospective chart review.

BACKGROUND: About one third of all patients with proximal femur fractures take oral anticoagulation like aspirin (ASS), direct platelet aggregation inhibitors like Clopidogrel and Ticagrelor (PAI), vitamin-K-antagonists like Warfarin (VKA) and direct oral anticoagulants like Rivaroxaban, Dabigatran and Apixaban (DOAC). The management and timing of fracture stabilization of these patients is a rising challenge in orthopedic trauma. Our objective was to determine the effect of oral anticoagulation on patients with proximal femur fractures, which received a proximal femur nail antirotation (PFNA) within 24 h after trauma. MATERIAL AND METHODS: A retrospective chart review of 327 patients (mean age 80 ± 13 years; 223 women and 104 men) with sub- or intertrochanteric fractures between January 2013 and December 2017 was performed. All patients underwent surgery in the first 24 h after admission. Solely patients without or with only one type of oral anticoagulation were included. There were 74 patients with ASS, 30 with PAI, 52 with DOAC and 25 with VKA medication. All patients taking VKA received high dose Vitamin K or coagulation factors to normalize INR prior to surgery. Primary outcome measures were transfusion rate and pre- and postoperative hemoglobin (Hb) difference. Secondary outcome measures were mortality and complications like infection, hematoma and acute cardiovascular events. RESULTS: Patients undergoing treatment with DOAC had a 3.4-fold increased risk for intraoperative blood transfusion. The risk for blood transfusion for patients taking ASS, PAI or VKA did no differ from the control group. Patients without an intraoperative blood transfusion on oral anticoagulation showed no increase in pre- and postoperative Hb-difference compared with controls. Anticoagulation showed no significant effect on complication rates and mortality in patients operated within the first 24 h. CONCLUSION: Early surgical care of proximal femur fractures is safe even in patients with anticoagulant medication. All patients should be preoperatively prepared for possibly intraoperative transfusion, especially patients on DOAC.

[Dysphagia in cervical spine diseases]. / Dysphagie bei Erkrankungen der Halswirbelsäule.

Dysphagia is a common symptom and can be indicative of a variety of heterogeneous diseases. "Classical" diseases of the head and neck region, such as acute tonsillitis, peritonsillar abscesses, diverticula, and benign or malignant tumors are common causes of dysphagia. However, it can also occur in the context of neurological diseases, e.g., as a result of stroke or as an age-related phenomenon (presbyphagia). Pathologies of the cervical spine can also be a cause of dysphagia. In this context, congenital or acquired diseases, inflammatory or degenerative processes, cervical spine surgery, and (malignant) masses of the cervical spine should be taken into account. Particular dysphagia with a positive history of previous operative interventions on the cervical spine or symptoms such as chronic back pain and trauma should give rise to consideration of a cervical spine-related cause.

Radiation exposure for the surgical team in a hybrid-operating room.

Hybrid-operating rooms enable the surgeon to acquire intraoperative high-resolution 2- and 3D images and use them for navigation. The radiation dose of the operating personal and the patient remains the major concern. In 9 months, 109 pelvic and spine cases were performed using a hybrid operating room. Radiation dose of the surgeon and the assisting nurse was recorded using real-time dosimeters. Lower radiation doses for the main surgeon in navigated dorsal instrumentations of the thoracic spine were recorded. Standing between the C-arm during screw placement increased the radiation dose sixfold. Lumbar dorsal instrumentation showed a similar radiation dose compared to the previous studies in traditional operating room settings. The use of a hybrid-operating room for dorsal spine instrumentation showed no increase in radiation dose compared to traditional settings. Intraoperative navigation can help to reduce the radiation dosage for the operating personnel.

Author Correction: Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.

Change history: In this Letter, author M. Akhlaghi should be associated with affiliation (2) rather than (3). This error has been corrected online.

Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.

Galaxies are surrounded by large reservoirs of gas, mostly hydrogen, that are fed by inflows from the intergalactic medium and by outflows from galactic winds. Absorption-line measurements along the lines of sight to bright and rare background quasars indicate that this circumgalactic medium extends far beyond the starlight seen in galaxies, but very little is known about its spatial distribution. The Lyman-α transition of atomic hydrogen at a wavelength of 121.6 nanometres is an important tracer of warm (about 104 kelvin) gas in and around galaxies, especially at cosmological redshifts greater than about 1.6 at which the spectral line becomes observable from the ground. Tracing cosmic hydrogen through its Lyman-α emission has been a long-standing goal of observational astrophysics1-3, but the extremely low surface brightness of the spatially extended emission is a formidable obstacle. A new window into circumgalactic environments was recently opened by the discovery of ubiquitous extended Lyman-α emission from hydrogen around high-redshift galaxies4,5. Such measurements were previously limited to especially favourable systems6-8 or to the use of massive statistical averaging9,10 because of the faintness of this emission. Here we report observations of low-surface-brightness Lyman-α emission surrounding faint galaxies at redshifts between 3 and 6. We find that the projected sky coverage approaches 100 per cent. The corresponding rate of incidence (the mean number of Lyman-α emitters penetrated by any arbitrary line of sight) is well above unity and similar to the incidence rate of high-column-density absorbers frequently detected in the spectra of distant quasars11-14. This similarity suggests that most circumgalactic atomic hydrogen at these redshifts has now been detected in emission.

Correction to: Radiation exposure for intraoperative 3D scans in a hybrid operating room: how to reduce radiation exposure for the surgical team.

The original version of this article unfortunately contained a mistake. In abstract, results section should read.

Radiation exposure for intraoperative 3D scans in a hybrid operating room: how to reduce radiation exposure for the surgical team.

BACKGROUND: Hybrid operating rooms are used in different fields of surgery. In orthopedic surgery, the possibility of a 3D scan of difficult anatomical regions (spine, pelvis) showed promising results not only in navigated screw placement. The associated exposure to radiation raises questions regarding potential risks for the operating room personal and the patient. The present study focuses on scatter radiation during 3D scans in a hybrid operating room, the adjacent rooms, and methods to reduce radiation exposure. MATERIAL AND METHODS: [Formula: see text] i2 dosimeters were used to measure scatter radiation during 3D scans of different anatomical regions in different distances and heights in a hybrid operating room. The 3D scans were performed with a floor-based flat-panel robotic C-arm with 3D scan capability (Artis Zeego, Siemens; Germany). The 3D scans were performed using a human cadaver. The 3D scans were performed using a standard and a dose reduction protocol (DRP). RESULTS: The highest scatter radiation was measured during 3D scans of the pelvis on the side of the surgical assistant (39.5 µSv in height of 1 m) compared to the side of the main surgeon (23 µSv in height of 1 m). Scatter radiation was less on the position of the scrub nurse (6.8 µSv in height of 1 m) and during 3D scans of the other anatomical regions. The radiation dosage was about 66% less with the DRP. Low values of scatter radiation were measured behind a radiation protection wall and with open doors in the adjacent rooms. CONCLUSION: While performing a scan scatter radiation was measured everywhere in the operating room especially during 3D scans of the pelvic girdle. Therefore, settings with lower dosage should be used whenever possible. Personnel should stand behind a radiation safety wall or leave the operating room and close the doors. For this study, six behavioral rules to avoid radiation in a hybrid operating room were established.