Pathological findings associated with the updated European Society of Cardiology 2022 guidelines for preoperative cardiac testing: an observational cohort modelling study.

BACKGROUND: In 2022, the European Society of Cardiology updated guidelines for preoperative evaluation. The aims of this study were to quantify: (1) the impact of the updated recommendations on the yield of pathological findings compared with the previous guidelines published in 2014; (2) the impact of preoperative B-type natriuretic peptide (NT-proBNP) use for risk estimation on the yield of pathological findings; and (3) the association between 2022 guideline adherence and outcomes. METHODS: This was a secondary analysis of MET-REPAIR, an international, prospective observational cohort study (NCT03016936). Primary endpoints were reduced ejection fraction (EF<40%), stress-induced ischaemia, and major adverse cardiovascular events (MACE). The explanatory variables were class of recommendations for transthoracic echocardiography (TTE), stress imaging, and guideline adherence. We conducted second-order Monte Carlo simulations and multivariable regression. RESULTS: In total, 15,529 patients (39% female, median age 72 [inter-quartile range: 67-78] yr) were included. The 2022 update changed the recommendation for preoperative TTE in 39.7% patients, and for preoperative stress imaging in 12.9% patients. The update resulted in missing 1 EF <40% every 3 fewer conducted TTE, and in 4 additional stress imaging per 1 additionally detected ischaemia events. For cardiac stress testing, four more investigations were performed for every 1 additionally detected ischaemia episodes. Use of NT-proBNP did not improve the yield of pathological findings. Multivariable regression analysis failed to find an association between adherence to the updated guidelines and MACE. CONCLUSIONS: The 2022 update for preoperative cardiac testing resulted in a relevant increase in tests receiving a stronger recommendation. The updated recommendations for TTE did not improve the yield of pathological cardiac testing.

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia.

Apart from being a significant line of defense in the host defense system, neutrophils have many immunological functions. Although there are not many publications that accurately present the functions of neutrophils in relation to oncological pathology, their activity and implications have been studied a lot recently. This review aims to extensively describe neutrophils functions'; their clinical implications, especially in tumor pathology; the value of clinical markers related to neutrophils; and the implications of neutrophils in onco-anesthesia. This review also aims to describe current evidence on the influence of anesthetic drugs on neutrophils' functions and their potential influence on perioperative outcomes.

The Effect of Different Anesthetic Techniques on Proliferation, Apoptosis, and Gene Expression in Colon Cancer Cells: A Pilot In Vitro Study.

BACKGROUND: Colorectal cancer is highly common and causes high mortality rates. Treatment for colorectal cancer is multidisciplinary, but in most cases the main option remains surgery. Intriguingly, in recent years, a number of studies have shown that a patient's postoperative outcome may be influenced by certain anesthetic drugs. Our main objective was to compare the effect of propofol-total intravenous anesthesia (TIVA) with sevoflurane anesthesia and to investigate the potential role of intravenous lidocaine on colon cancer cell functions. We tested the effects of serum from colorectal cancer patients undergoing TIVA vs. sevoflurane anesthesia with or without lidocaine on HCT 116 cell lines; on proliferation, apoptosis, migration, and cell cycles; and on cancer-related gene expressions. METHODS: 60 patients who were scheduled for colorectal cancer surgery were randomized into four different groups (two groups with TIVA and two groups with sevoflurane anesthesia with or without intravenous lidocaine). Blood samples were collected at the start and at the end of surgery. HCT 116 cells were exposed to the patients' serum. RESULTS: 15 patients were included in each of the study groups. We did not find any significant difference on cell viability or apoptosis between the study groups. However, there was an increased apoptosis in propofol groups, but this result was not statistically significant. A significant increase in the expression profile of the TP53 gene in the propofol group was registered (p = 0.029), while in the other study groups, no significant differences were reported. BCL2 and CASP3 expressions increased in the sevoflurane-lidocaine group without statistical significance. CONCLUSIONS: In our study, serum from patients receiving different anesthetic techniques did not significantly influence the apoptosis, migration, and cell cycle of HCT-116 colorectal carcinoma cells. Viability was also not significantly influenced by the anesthetic technique, except the sevoflurane-lidocaine group where it was increased. The gene expression of TP53 was significantly increased in the propofol group, which is consistent with the results of similar in vitro studies and may be one of the mechanisms by which anesthetic agents may influence the biology of cancer cells. Further studies that investigate the effects of propofol and lidocaine in different plasma concentrations on different colon cancer cell lines and assess the impacts of these findings on the clinical outcome are much needed.

Risk assessment for major adverse cardiovascular events after noncardiac surgery using self-reported functional capacity: international prospective cohort study.

BACKGROUND: Guidelines endorse self-reported functional capacity for preoperative cardiovascular assessment, although evidence for its predictive value is inconsistent. We hypothesised that self-reported effort tolerance improves prediction of major adverse cardiovascular events (MACEs) after noncardiac surgery. METHODS: This is an international prospective cohort study (June 2017 to April 2020) in patients undergoing elective noncardiac surgery at elevated cardiovascular risk. Exposures were (i) questionnaire-estimated effort tolerance in metabolic equivalents (METs), (ii) number of floors climbed without resting, (iii) self-perceived cardiopulmonary fitness compared with peers, and (iv) level of regularly performed physical activity. The primary endpoint was in-hospital MACE consisting of cardiovascular mortality, non-fatal cardiac arrest, acute myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care or resulting in a prolongation of stay on ICU/intermediate care (≥24 h). Mixed-effects logistic regression models were calculated. RESULTS: In this study, 274 (1.8%) of 15 406 patients experienced MACE. Loss of follow-up was 2%. All self-reported functional capacity measures were independently associated with MACE but did not improve discrimination (area under the curve of receiver operating characteristic [ROC AUC]) over an internal clinical risk model (ROC AUCbaseline 0.74 [0.71-0.77], ROC AUCbaseline+4METs 0.74 [0.71-0.77], ROC AUCbaseline+floors climbed 0.75 [0.71-0.78], AUCbaseline+fitnessvspeers 0.74 [0.71-0.77], and AUCbaseline+physical activity 0.75 [0.72-0.78]). CONCLUSIONS: Assessment of self-reported functional capacity expressed in METs or using the other measures assessed here did not improve prognostic accuracy compared with clinical risk factors. Caution is needed in the use of self-reported functional capacity to guide clinical decisions resulting from risk assessment in patients undergoing noncardiac surgery. CLINICAL TRIAL REGISTRATION: NCT03016936.

Induced Wettability Switch in Thin Films of Conductive Polymer Coatings Exhibiting Hydrophobic/Hydrophilic Interactions.

The hydrophobic/hydrophilic character of some conductive polymer (CP) coatings can be switched in the function of the working conditions of these adaptive materials. We studied the influence of electrical stimuli and intrinsic physical characteristics (nature of the polymerizable core, dopants, the droplet dimension and physical properties, surface roughness, etc.) on the CP wettability. A simulation strategy was developed for determining the contact angle (CA) of a liquid droplet on a CP layer with roughness. The method was tested for new reported CP composites, but with new dopants. The results indicate that the influences on the material wettability are correlated, and in practice, modification of more than one parameter converges to a wanted behavior of the material. E.g., the CP porous film of poly(3-hexylthiophene) (P3HT) + [6,6]-phenyl-C61-butyricacid-methyl-ester (PCBM) changes its wettability at voltages of up to 26 V, but if doping ions are inserted and the roughness geometry is modified, the voltage decreases twice. Our multi-parametrical study points out that the polymer wettability type is driven by the voltage, but this effect is tuned differently by each internal parameter. The thin films' effect and the dopants (in-situ and ex-situ) significantly decrease the actuation voltage. We also illustrated that the wettability type does not change for specific sets of parameters.

Practice of oxygen use in anesthesiology - a survey of the European Society of Anaesthesiology and Intensive Care.

BACKGROUND: Oxygen is one of the most commonly used drugs by anesthesiologists. The World Health Organization (WHO) gave recommendations regarding perioperative oxygen administration, but the practice of oxygen use in anesthesia, critical emergency, and intensive care medicine remains unclear. METHODS: We conducted an online survey among members of the European Society of Anaesthesiology and Intensive Care (ESAIC). The questionnaire consisted of 46 queries appraising the perioperative period, emergency medicine and in the intensive care, knowledge about current recommendations by the WHO, oxygen toxicity, and devices for supplemental oxygen therapy. RESULTS: Seven hundred ninety-eight ESAIC members (2.1% of all ESAIC members) completed the survey. Most respondents were board-certified and worked in hospitals with > 500 beds. The majority affirmed that they do not use specific protocols for oxygen administration. WHO recommendations are unknown to 42% of respondents, known but not followed by 14%, and known and followed by 24% of them. Respondents prefer inspiratory oxygen fraction (FiO2) ≥80% during induction and emergence from anesthesia, but intraoperatively < 60% for maintenance, and higher FiO2 in patients with diseased than non-diseased lungs. Postoperative oxygen therapy is prescribed more commonly according to peripheral oxygen saturation (SpO2), but shortage of devices still limits monitoring. When monitoring is used, SpO2 ≤ 95% is often targeted. In critical emergency medicine, oxygen is used frequently in patients aged ≥80 years, or presenting with respiratory distress, chronic obstructive pulmonary disease, myocardial infarction, and stroke. In the intensive care unit, oxygen is mostly targeted at 96%, especially in patients with pulmonary diseases. CONCLUSIONS: The current practice of perioperative oxygen therapy among respondents does not follow WHO recommendations or current evidence, and access to postoperative monitoring devices impairs the individualization of oxygen therapy. Further research and additional teaching about use of oxygen are necessary.

Postoperative Analgesia after Laparoscopic Cholecystectomy - Prospective, Randomized, Double Blind, Control Trial.

In this prospective, randomized, double blind control trial we aim to investigate which of the most used analgesic techniques after laparoscopic cholecystectomy is the most efficient. Methods: This study included 81 patients that were randomly distributed into 3 groups using a computer-generated random number which was enclosed in a sealed envelope: group A (control) received classic multimodal iv opioid analgesia, group B received Tap block in oblique subcostal approach (OSTAP) and group C received local anesthetic infiltration of the trocar insertion sites (LAI). The primary outcome of this trial was to evaluate the efficacy of each analgetic technique by measuring VAS pain scores. Secondary outcome included intraoperative opioid requirement and the opioid consumption in the first 24h postoperatively. Intraoperative parameters and outcome data were recorded by an anesthesiologist who was blinded to the study groups. Results: We analyzed a total of 75 patients. For the primary outcome variable, VAS pain scores at rest were significantly reduced in OSTAP group at each time point assessed in the first 24 hours after surgery compared with LAI group and IV opioid analgesia group (p 0.001). Intraoperative fentanyl consumption and 24h pethidine consumption were also significantly reduced in TAP block group compared with LAI group and IV opioid analgesia group (p 0.001). Conclusions: Our study showed that OSTAP block is a more efficient analgesia technique compared with IV opioid analgesia and with local anesthetic infiltration of trocar sites after laparoscopic cholecystectomy surgery. This trial was registered at www.clinicaltrials.gov (NCT02707250).

Perioperative Management of Patients with Pancreatic Cancer - the ERAS Protocols.

Background: Pancreatic cancer represents the fifth leading cause of death in industrialized countries. The prognosis is reserved, surgical resection being the only curative treatment, but the complications associated bear important impact on the patients survival, prognosis, and quality of life. The ERAS protocols come to meet these shortcomings for enhanced recovery after major pancreatic resections. Material and method: A systematic review was performed following the guidelines outlined by The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Original articles published in the online databases Pubmed (Medline), Embase and Cochrane since 2017 until 2022 were screened after using specific keywords. Results: A total of 252 studies was obtained by searching through online databases. Following the exclusion criteria, we included 7 studies in the systematic review. Conclusions: The ERAS protocols are safe to be applied in the common practice. They are efficient in the perioperative management of patients undergoing pancreatic resections. They can further decrease hospitalization stay, promote better recovery of gastrointestinal function, and speed up postoperative recovery.

Oleogel Formulations for the Topical Delivery of Betulin and Lupeol in Skin Injuries-Preparation, Physicochemical Characterization, and Pharmaco-Toxicological Evaluation.

The skin integrity is essential due to its pivotal role as a biological barrier against external noxious factors. Pentacyclic triterpenes stand as valuable plant-derived natural compounds in the treatment of skin injuries due to their anti-inflammatory, antioxidant, antimicrobial, and healing properties. Consequently, the primary aim of the current investigation was the development as well as the physicochemical and pharmaco-toxicological characterization of betulin- and lupeol-based oleogels (Bet OG and Lup OG) for topical application in skin injuries. The results revealed suitable pH as well as organoleptic, rheological, and textural properties. The penetration and permeation of Bet and Lup oleogels through porcine ear skin as well as the retention of both oleogels in the skin were demonstrated through ex vivo studies. In vitro, Bet OG and Lup OG showed good biocompatibility on HaCaT human immortalized cells. Moreover, Bet OG exerted a potent wound-healing property by stimulating the migration of the HaCaT cells. The in ovo results demonstrated the non-irritative potential of the developed formulations. Additionally, the undertaken in vivo investigation indicated a positive effect of oleogels treatment on skin parameters by increasing skin hydration and decreasing erythema. In conclusion, oleogel formulations are ideal for the local delivery of betulin and lupeol in skin disorders.

Neutrophil extracellular trapping and angiogenesis biomarkers after intravenous or inhalation anaesthesia with or without intravenous lidocaine for breast cancer surgery: a prospective, randomised trial.

BACKGROUND: Experimental and, retrospective, clinical data indicate that anaesthetic technique might influence the risk of metastasis after cancer surgery. Neutrophil extracellular trapping (NETosis) is an immunological mechanism strongly linked with increased metastatic risk. Similarly, vascular endothelial growth factor A is linked to angiogenesis implicated in recurrence. Therefore, we investigated the effect of four anaesthetic techniques on NETosis and angiogenic factors expression in women undergoing breast cancer resection. METHODS: Women (n=120) undergoing primary breast tumour resection were randomly assigned to receive one of four anaesthetics: sevoflurane (S), sevoflurane plus i.v. lidocaine (SL), propofol (P), and propofol plus i.v. lidocaine (PL). Venous blood was collected before induction and 20-28 h after operation. Neutrophil myeloperoxidase and citrullinated histone H3, biomarkers of NETosis, and biomarkers of angiogenesis were measured by enzyme-linked immunosorbent assay. RESULTS: Patient characteristic data and perioperative management did not differ between study groups. The anaesthetic technique including lidocaine decreased expression of citrullinated histone H3 compared with no lidocaine (109 [23] vs 125 [22] ng ml-1, P=0.01 for SL and S and 98 [14] vs 130 [32] mg ml-1, P=0.007, for PL and P, respectively). Similarly, myeloperoxidase was decreased by lidocaine (8.5 [3.4] vs 10.8 [1.8] ng ml-1, P=0.03 for SL and S and 8.6 [3.1] vs 11.6 [2.5] ng ml-1, P=0.01 for PL and P, respectively). Lidocaine also decreased expression of matrix metalloproteinase 3 (MMP3) but not MMP9, whichever anaesthetic was used. Vascular endothelial growth factor A concentrations were not significantly influenced by the anaesthetic technique. CONCLUSIONS: I.V. perioperative lidocaine decreased postoperative expression of NETosis and MMP3, regardless of general anaesthetic technique. This supports the hypothesis that i.v. lidocaine during cancer surgery of curative intent might reduce recurrence. CLINICAL TRIAL REGISTRATION: NCT02839668.

Molecular Diagnostic of Prostate Cancer From Body Fluids Using Methylation-Specific PCR (MS-PCR) Method.

BACKGROUND: Worldwide prostate cancer (PCa) represents the 2nd leading cause of cancer related deaths among men. Currently, the screening for early detection of PCa is based on determination of serum prostate-specific antigen (PSA) levels. But this biomarker presents some disadvantages related to its specificity and sensitivity. In our study, we want to determine if methylation levels of the glutathione S-transferase P1 (GSTP1) gene could be used as a new biomarker for the early detection of PCa and to distinguish between malignant and benign pros-tatic lesions. METHODS: To determine the methylation levels of the GSTP1 gene, 31 men with histopathological diagnosis of prostate adenocarcinoma and 34 men with the histopathological diagnosis of benign prostatic hyperplasia (BPH) as controls were included in the study group. The genomic DNA was extracted from urine samples. We analyzed the methylation levels of the GSTP1 gene by methylation-specific polymerase chain reaction (MS-PCR) method. RESULTS: In prostate cancer patients 27 of 31 (87%) presented hypermethylated levels of the GSTP1 gene, whereas 4 of 34 (11.8%) BPH patients had hypermethylated levels of the GSTP1 gene. Further, in the case of these four patients a second biopsy was done, which confirmed the diagnosis of prostate adenocarcinoma. Using the receiver operating curve (ROC), we obtained a specificity of 87% and a sensitivity of 98% for the GSTP1 gene. CONCLUSIONS: We can conclude that GSTP1 represents a new molecular biomarker which can aid in early detection of PCa and be used to discriminate between benign and malignant prostatic lesions from body fluids by noninvasive methods.

Determinants of procedural pain intensity in the intensive care unit. The Europain® study.

RATIONALE: Intensive care unit (ICU) patients undergo several diagnostic and therapeutic procedures every day. The prevalence, intensity, and risk factors of pain related to these procedures are not well known. OBJECTIVES: To assess self-reported procedural pain intensity versus baseline pain, examine pain intensity differences across procedures, and identify risk factors for procedural pain intensity. METHODS: Prospective, cross-sectional, multicenter, multinational study of pain intensity associated with 12 procedures. Data were obtained from 3,851 patients who underwent 4,812 procedures in 192 ICUs in 28 countries. MEASUREMENTS AND MAIN RESULTS: Pain intensity on a 0-10 numeric rating scale increased significantly from baseline pain during all procedures (P < 0.001). Chest tube removal, wound drain removal, and arterial line insertion were the three most painful procedures, with median pain scores of 5 (3-7), 4.5 (2-7), and 4 (2-6), respectively. By multivariate analysis, risk factors independently associated with greater procedural pain intensity were the specific procedure; opioid administration specifically for the procedure; preprocedural pain intensity; preprocedural pain distress; intensity of the worst pain on the same day, before the procedure; and procedure not performed by a nurse. A significant ICU effect was observed, with no visible effect of country because of its absorption by the ICU effect. Some of the risk factors became nonsignificant when each procedure was examined separately. CONCLUSIONS: Knowledge of risk factors for greater procedural pain intensity identified in this study may help clinicians select interventions that are needed to minimize procedural pain. Clinical trial registered with www.clinicaltrials.gov (NCT 01070082).

The effect of anaesthetic management on neutrophil gelatinase associated lipocalin (NGAL) levels after robotic surgical oncology.

PURPOSE: The main objective of this study was to compare the effect of two anaesthetic techniques (general vs combined) on plasma levels of NGAL (Neutrophil Gelatinase Associated Lipocalin) after robotic urogenital oncosurgery. The secondary objective was to correlate NGAL levels with the incidence of acute kidney injury (AKI). METHODS: This was a longitudinal prospective study. Forty patients were included and randomized in 2 groups: group C (N=16 cases; combined general-epidural anesthesia) and group G (N=24 cases; control group with general anesthesia). Demographic data, Charlson Comorbidity Index, Apache II, SOFA and ASA scores were similar in both groups. Serum creatinine was determined preoperatively and every 24 hrs for 4 postoperative days to identify AKI according to RIFLE and AKIN criteria. Serum NGAL was determined at 6 and 12 hrs after induction of anesthesia. RESULTS: Serum creatinine increased at 24 hrs postoperatively in both groups as compared to baseline, but significant changes were registered only in the G group (p(control) = 0.004). Serum NGAL increased significantly in both groups as compared with baseline levels (pcase=0.0034 vs p(control)=0.0001). The incidence of AKI was 12.50% (95% CI 0.4-34) in the C group and 37.50% (95% CI 17-58) in the G group (p=0.0909), respectively. CONCLUSION: Impaired renal function and AKI occurred in robot-assisted laparoscopic urogenital oncosurgery under both general and combined anaesthesia. The incidence of AKI was lower in patients undergoing combined anesthesia compared to general anaesthesia after robotic urogenital oncosurgery but the difference did not reach statistical significance. However, plasma levels of NGAL were significantly increased at 6 and 12 hrs in the general anaesthesia group as compared with combined anaesthesia. NGAL may be a better marker in detecting postoperative acute kidney injury. Further studies are needed.

The influence of a prophylactic dose of dexamethasone for postoperative nausea and vomiting on plasma interleukin concentrations after laparoscopic cholecystectomy: a randomised trial.

BACKGROUND: Little is known about the effects of small doses of dexamethasone used for the prophylaxis of postoperative nausea and vomiting on the innate host response. OBJECTIVES: We studied the influence of dexamethasone 4 mg on the perioperative plasma concentrations of interleukins after laparoscopic cholecystectomy. We hypothesised that there would be differences in pro-inflammatory interleukin concentrations in patients who received dexamethasone. DESIGN: A randomised controlled study. SETTING: University hospital. PATIENTS: Forty-six patients undergoing laparoscopic cholecystectomy under total intravenous anaesthesia were allocated randomly into one of two study groups; 42 patients completed the study. INTERVENTIONS: Patients in group 1 (dexamethasone, n = 22) received dexamethasone 4 mg and group 2 (n = 20) acted as controls. MAIN OUTCOME MEASURES: Plasma levels of tumour necrosis factor alpha and interleukins 1ß, 6, 8, 10 and 13 were measured before anaesthesia, before surgery and 2 and 24 h after surgery. The frequency and number of episodes of postoperative nausea and vomiting were recorded. RESULTS: Areas under the curve of the percentage variation of interleukins 6 and 8 were significantly lower in the dexamethasone group. There were no significant differences between groups in the areas under the curve for tumour necrosis factor alpha and interleukins 1ß, 10 and 13. The greatest variation in interleukin concentrations was 2 h postoperatively, when the concentration of interleukin 6 was greater in the control group, whereas the concentration of interleukin 10 was higher in the dexamethasone group. Twenty-four hours after surgery, only the concentration of interleukin 6 remained significantly increased in both groups (P = 0.001 and P = 0.002, respectively). There were no significant differences between groups in respect of postoperative nausea and vomiting. CONCLUSION: Prophylactic dexamethasone given before laparoscopic cholecystectomy produced a significant decrease in concentrations of interleukins 6 and 8. Further studies are needed to investigate the clinical implications of these findings.

The influence of total intravenous anaesthesia and isoflurane anaesthesia on plasma interleukin-6 and interleukin-10 concentrations after colorectal surgery for cancer: a randomised controlled trial.

BACKGROUND: Although it has been demonstrated that both surgery and anaesthesia induce immune suppression, it remains unclear whether there are differences between anaesthetic techniques in inducing immune suppression in cancer patients. OBJECTIVE: The aim of this present study was to compare the effects of total intravenous anaesthesia (TIVA) and isoflurane anaesthesia on plasma concentrations of interleukins IL-6 and IL-10 in patients undergoing surgery for colorectal cancer. DESIGN: A randomised, controlled, open-label study. SETTING: University hospital. PATIENTS: Seventy patients undergoing open colorectal surgery with tumour resection were randomised prospectively into one of two groups; 60 patients completed the study. INTERVENTIONS: Group 1 (n = 30) received TIVA and group 2 (n = 30) received isoflurane. Propofol infusion rate and inspired concentration of isoflurane were titrated to achieve bispectral index values of 40 to 55. MAIN OUTCOME MEASURES: Plasma concentrations of IL-6 and IL-10 were measured preoperatively, before surgical incision and at 2 and 24 h postoperatively. The area under the curve (AUC) for IL-6 and IL-10 over 24 h and plasma interleukin concentrations at each time point were compared between the groups. RESULTS: Median (range) AUC for IL-6 was 4657 (1219 to 8427) pg h ml in the TIVA group and 5349 (839 to 8126) pg h ml in the isoflurane group. For IL-10, AUC was 1165 (344 to 5258) pg h ml in the TIVA group and 1405 (463 to 8161) pg h ml in the isoflurane group. When comparing interleukin concentrations between study groups at different time intervals, there were no significant differences in plasma concentrations of IL-6 or IL-10. Intragroup comparisons revealed that IL-6 and IL-10 concentrations were significantly increased 2 and 24 h postoperatively in both groups when compared with their baseline values (P < 0.01 and P < 0.01 at 2 and 24 h for the TIVA group and isoflurane group, respectively). CONCLUSION: We found no significant differences between the effects of TIVA and isoflurane anaesthesia on plasma concentrations of IL-6 and IL-10 after colorectal cancer surgery during the first 24 h postoperatively. Further studies are needed to determine differences in long-term outcome of these patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01902849. The study was registered retrospectively.

The Hydractinia echinata test-system. III: Structure-toxicity relationship study of some azo-, azo-anilide, and diazonium salt derivatives.

Structure-toxicity relationships for a series of 75 azo and azo-anilide dyes and five diazonium salts were developed using Hydractinia echinata (H. echinata) as model species. In addition, based on these relationships, predictions for 58 other azo-dyes were made. The experimental results showed that the measured effectiveness Mlog(1/MRC50) does not depend on the number of azo groups or the ones corresponding to metobolites, but it is influenced by the number of anilide groups, as well as by the substituents' positions within molecules. The conformational analysis pointed out the intramolecular hydrogen bonds, especially the simple tautomerization of quinoidic (STOH) or aminoidic (STNH2) type. The effectiveness is strongly influenced by the "push-pull" electronic effect, specific to two hydroxy or amino groups separated by an azo moiety (double alternate tautomery, (DAT), to the -COOH or -SO3H groups which are located in ortho or para position with respect to the azo group. The levels of the lipophylic/hydrophilic, electronic and steric equilibriums, pointed out by the Mlog(1/MRC50) values, enabled the calculation of their average values Clog(1/MRC50) ("Köln model"), characteristic to one derivative class (class isotoxicity). The azo group reduction and the hydrolysis of the amido/peptidic group are two concurrent enzymatic reactions, which occur with different reaction rates and mechanisms. The products of the partial biodegradation are aromatic amines. No additive or synergic effects are noticed among them.