Prediction of a Difficult Airway Using the ARNE Score and Flexible Laryngoscopy in Patients with Laryngeal Pathology.

Background and Objectives: The ARNE score was developed for the prediction of a difficult airway for both general and ear, nose and throat (ENT) surgery with a universal cut-off value. We tested the accuracy of this score in the case of laryngeal surgery and provided an insight into its effects in combination with flexible laryngoscopy. Materials and Methods: This prospective pilot clinical study included 100 patients who were being scheduled for microscopic laryngeal surgery. We calculated the ARNE score for every patient, and flexible laryngoscopy was provided preoperative. Difficult intubation was assessed according to the intubation difficulty score (IDS). Results: A total of 33% patients had difficult intubation according to the IDS. The ARNE score showed limited accuracy for the prediction of difficult intubation in laryngology with p < 0.0001 and an AUC of 0.784. Flexible laryngoscopy also showed limitations when used as an independent parameter with p < 0.0001 and an AUC of 0.766. We defined a new cut-off value of 15.50 for laryngology, according to the AUC. After the patients were divided into two groups, according to the new cut-off value and provided cut-off value, the AUC improved to 0.707 from 0.619, respectively. Flexible laryngoscopy improved the prediction model of the ARNE score to an AUC of 0.882 and of the new cut-off value to an AUC of 0.833. Conclusions: It is recommended to use flexible laryngoscopy together with the ARNE score in difficult airway prediction in patients with laryngeal pathology. Also, the universally recommended cut-off value of 11 cannot be effectively used in laryngology, and a new cut-off value of 15.50 is recommended.

Enhanced antimicrobial properties and bioactivity of 3D-printed titanium scaffolds by multilayer bioceramic coating for large bone defects.

The restoration of large bone defects caused by trauma, tumor resection, or infection is a major clinical problem in orthopedics and dentistry because postoperative infections, corrosion, and limited osteointegration of metal implants can lead to loosening of the implant. The aim of this study was to improve the surface properties of a 3D-printed (electron beam melting) Ti6Al4V-based macroporous scaffold by multilayer coating with bioactive silicate glasses (BAGs) and hydroxyapatite doped with a silver (AgHAP) or AgHAP additionally sonochemically modified with ZnO (ZnO-AgHAP). The coated scaffolds AgHAP_BAGs_Ti and ZnO-AgHAP_BAGs_Ti enhanced cytocompatibility in L929 and MRC5 cell lines and expressed bioactivity in simulated body fluid. A lower release of vanadium ions in coated samples compared to bare Ti scaffold indicates decreased dissolution of Ti alloy in coated samples. The coated samples reduced growth ofEscherichia coliandStaphylococcus aureusfor 4-6 orders of magnitude. Therefore, the 3D-printed Ti-based scaffolds coated with BAGs and (ZnO-)AgHAP have great potential for application as a multifunctional implant with antibacterial properties for the restoration of defects in load-bearing bones.

Macrophages, the main marker in biocompatibility evaluation of new hydrogels after subcutaneous implantation in rats.

Biocompatibility of materials is one of the most important conditions for their successful application in tissue regeneration and repair. Cell-surface interactions stimulate adhesion and activation of macrophages whose acquaintance can assist in designing novel biomaterials that promote favorable macrophage-biomaterial surface interactions for clinical application. This study is designed to determine the distribution and number of macrophages as a means of biocompatibility evaluation of two newly synthesized materials [silver/poly(vinyl alcohol) (Ag/PVA) and silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) nanocomposite hydrogels] in vivo, with approval of the Ethics Committee of the Faculty of Veterinary Medicine, University of Belgrade. Macrophages and giant cells were analyzed in tissue sections stained by routine H&E and immunohistochemical methods (CD68+). Statistical relevance was determined in the statistical software package SPSS 20 (IBM corp). The results of the study in terms of the number of giant cells localized around the implant showed that their number was highest on the seventh postoperative day (p.o.d.) in the group implanted with Ag/PVA hydrogels, and on the 30th p.o.d. in the group implanted with Ag/PVA/Gr. Interestingly, the number of macrophages measured in the capsular and pericapsular space was highest in the group implanted with the commercial Suprasorb© material. The increased macrophage number, registered around the Ag/PVA/Gr implant on 60th p.o.d. indicates that the addition of graphene can, in a specific way, modulate different biological responses of tissues in the process of wound healing, regeneration, and integration.

In silico development of anesthetics based on barbiturate and thiobarbiturate inhibition of GABAA.

The inhibition of GABAA can be used in general anesthesia. Although, barbiturates and thiobarbiturates are used in anesthesia, the mechanism of their action hasn't been established. QSAR modeling is a wieldy used technique in these cases and this study presents the QSAR modeling for a group of barbiturates and thiobarbiturates with determined anesthetic activity. Developed QSAR models were based on conformation independent and 2D descriptors as well as field contribution. As descriptors used for developing conformation independent QSAR models, (SMILES) notation and local invariants of the molecular graph were used. Monte Carlo optimization method was applied for building QSAR models for two defined activities. Methodology for developing QSAR models capable of dealing with the small dataset that integrates dataset curation, "exhaustive" double cross-validation and a set of optimal model selection techniques including consensus predictions was used. Two-dimensional descriptors with definite physicochemical meaning were used and modeling was done with the application of both partial least squares and multiple linear regression models with three latent variables related to simple and interpretable 2D descriptors. Different statistical methods, including novel method - the index of ideality of correlation, were used to test the quality of the developed models, especially robustness and predictability and all obtained results were good. In this study, obtained results indicate that there is a very good correlation between all developed models. Molecular fragments that account for the increase/decrease of a studied activity were defined and further used for the computer-aided design of new compounds as potential anesthetics.

Pre and postoperative risk management: the role of scores and biomarkers.

PURPOSE OF REVIEW: The goal of risk prediction is to identify high-risk patients who will benefit from further preoperative evaluation. Clinical scores and biomarkers are very well established tools for risk prediction but their accuracy remains a controversial issue. RECENT FINDINGS: Current guidelines recommend one of the risk tools for preoperative cardiac risk assessment: American College of Surgeons National Surgical Quality Improvement Program (NSQIP) calculator or Revised Cardiac Risk Index. Although not as easy to use as risk scores, risk models are more accurate and can predict individual patient risk more precisely. A step forward in risk estimation was performed by introducing new risk models developed from the American College of Surgeons NSQIP database - NSQIP surgical risk calculator and Myocardial Infarction or Cardiac Arrest index. Although biomarkers, especially in cardiac risk assessment, are already present in current European and American guidelines, this use is still controversial. Novel biomarkers: microRNAs, heart-type fatty acid-binding protein and mid-regional proadrenomedullin, can be used as new potential biomarkers in clinical practice. Also some of the experimental biomarkers have not yet been introduced into clinical practice, preliminary results are encouraging. SUMMARY: Different risk indices and biomarkers might lead to varying risk estimates. However, the importance of clinical judgment in risk assessment should not be underestimated.

Caffeic acid phenethyl ester attenuates changes in pancreatic tissue damage biomarkers induced by cisplatin.

Application of cisplatin (CP) for the treatment of different cancers is known to cause pancreatitis through an increase in reactive oxygen species production and promotion of inflammation. Caffeic acid phenethyl ester (CAPE), the main activity carrier of propolis extracts, was previously found to possess numerous beneficial properties. This study aims to determine for the first time the potential of CAPE in preventing CP-induced pancreatic tissue damage by studying the changes occurring on both biochemical and microscopic levels. The levels of serum α-amylase and a panel of pancreatic tissue biomarkers related to tissue injury (reduced glutathione, xanthine oxidase, malondialdehyde, and protein carbonylated concentration) and inflammation (myeloperoxidase, nitric oxide, and umor necrosis factor alpha) were studied in male Wistar rats treated with either CP alone or with CP and CAPE. Additionally, microscopic analysis of pancreatic tissue would be conducted as well. Application of CAPE together with CP statistically significantly prevented the disturbance in all here-studied pancreatic tissue damage and inflammation-related biomarkers. The changes in pancreas biochemical status was followed by morphological disturbance. The results of the present study suggest that CAPE could act as a protective agent in pancreatic damage that arises after CP application.

Cardiac biomarkers improve prediction performance of the combination of American Society of Anesthesiologists physical status classification and Americal College of Surgeons National Surgical Quality Improvement Program calculator for postoperative mortality in elderly patients: a pilot study.

BACKGROUND: Our previous research has shown American Society of Anaesthesiologists physical status classification (ASA) score and Americal College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator to have the most accuracy in the prediction of postoperative mortality. AIMS: The aim of our research was to define the most reliable combination of cardiac biomarkers with ASA and ACS NSQIP. METHODS: We have included a total of 78 patients. ASA score has been determined in standard fashion, while we used the available interactive calculator for the ACS NSQIP score. Biomarkers BIRC5, H-FABP, and hsCRP have been measured in specialized laboratories. RESULTS: All of the deceased patients had survivin (BIRC5) > 4.00 pg/ml, higher values of H-FABP and hsCRP and higher estimated levels of ASA and ACS NSQIP (P = 0.0001). ASA and ACS NSQIP alone had AUC of, respectively, 0.669 and 0.813. The combination of ASA and ACS NSQIP had AUC = 0.841. Combination of hsCRP with the two risk scores had AUC = 0.926 (95% CI 0.853-1.000, P < 0.0001). If we add three cardiac biomarkers to this model, we get AUC as high as 0.941 (95% CI 0.876-1.000, P < 0.0001). The correction of statistical models with comorbidities (CIRS-G score) did not change the accuracy of prediction models that we have provided. DISCUSSION: Addition of ACS NSQIP and biomarkers adds to the accuracy of ASA score, which has already been proved by other authors. CONCLUSION: Cardiac biomarker hsCRP can be used as the most reliable cardiac biomarker; however, the "multimarker approach" adds the most to the accuracy of the combination of clinical risk scores.

Clinical Utility of Survivin (BIRC5), Novel Cardiac Biomarker, as a Prognostic Tool Compared to High-sensitivity C-reactive Protein, Heart-type Fatty Acid Binding Protein and Revised Lee Score in Elderly Patients Scheduled for Major Non-cardiac Surgery: A Prospective Pilot Study.

BACKGROUND: Recent studies indicate that survivin (BIRC5) is sensitive to the existence of previous ischemic heart disease, since it is activated in the process of tissue repair and angiogenesis. The aim of this study was to determine the potential of survivin (BIRC5) as a new cardiac biomarker in the preoperative assessment of cardiovascular risk in comparison with clinically accepted cardiac biomarkers and one of the relevant clinical risk scores. METHODS: We included 79 patients, female (41) and male (38), with the mean age of 71.35±6.89. Inclusion criteria: extensive non-cardiac surgery, general anesthesia, age >55 and at least one of the selected cardiovascular risk factors (hypertension, diabetes mellitus, hyperlipidemia, smoking and positive family history). Exclusion criteria: emergency surgical procedures and inability to understand and sign an informed consent. Blood sampling was performed 7 days prior surgery and levels of survivin (BIRC5), hsCRP and H-FABP were measured. RESULTS: Revised Lee score was assessed based on data found in patients' history. Levels of survivin (BIRC5) were higher in deceased patients (P<0.05). It showed AUC=0.807 (95% CI, P<0.0005, 0.698-0.917), greater than both H-FABP and revised Lee index, and it increases the mortality prediction when used together with both biomarkers and revised Lee score. The determined cut-off value was 4 pg/mL and 92.86% of deceased patients had an increased level of survivin (BIRC5), (P=0.005). CONCLUSIONS: Survivin (BIRC5) is a potential cardiac biomarker even in elderly patients without tumor, but it cannot be used independently. Further studies with a greater number of patients are needed.

Enhanced Recovery after Vascular Surgery.

The beginnings of the enhanced recovery after surgery (ERAS) program were first developed for patients in colorectal surgery, and after it was established as the standard of care in this surgical field, it began to be applied in many others surgical areas. This is multimodal, evidence-based approach program and includes simultaneous optimization of preoperative status of patients, adequate selection of surgical procedure and postoperative management. The aim of this program is to reduce complications, the length of hospital stay and to improve the patients outcome. Over the past decades, special attention was directed to the postoperative management in vascular surgery, especially after major vascular surgery because of the great risk of multiorgan failure, such as: respiratory failure, myocardial infarction, hemodynamic instability, coagulopathy, renal failure, neurological disorders, and intra-abdominal complications. Although a lot of effort was put into it, there is no unique acceptable program for ERAS in this surgical field, and there is still a need to point out the factors responsible for postoperative outcomes of these patients. So far, it is known that special attention should be paid to already existing diseases, type and the duration of the surgical intervention, hemodynamic and fluid management, nutrition, pain management, and early mobilization of patients.

Enhanced Recovery in Thoracic Surgery: A Review.

The main goal of enhanced recovery program after thoracic surgery is to minimize stress response, reduce postoperative pulmonary complications, and improve patient outcome, which will in addition decrease hospital stay and reduce hospital costs. As minimally invasive technique, video-assisted thoracoscopic surgery represents an important element of enhanced recovery program in thoracic surgery. Anesthetic management during preoperative, intraoperative and postoperative period is essential for the enhanced recovery. In the era of enhanced recovery protocols, non-intubated thoracoscopic procedures present a step forward. This article focuses on the key elements of the enhanced recovery program in thoracic surgery. Having reviewed recent literature, the authors highlight potential procedures and techniques that might be incorporated into the program.

Addition of biomarker panel improves prediction performance of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator for cardiac risk assessment of elderly patients preparing for major non-cardiac surgery: a pilot study.

BACKGROUND: Number of elderly patients subjected to extensive surgical procedures in the presence of cardiovascular morbidities is increasing every year. Therefore, there is a need to make preoperative diagnostics more accurate. AIMS: To evaluate the usefulness of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator as a predictive tool in preoperative assessment of cardiovascular risk in elderly patients. METHODS: This prospective pilot study included 78 patients who were being prepared for extensive non-cardiac surgeries under general anaesthesia. Their data have been processed on the interactive ACS NSQIP calculator. Blood sampling has been performed 7 days prior to surgery, and serum has been separated. Clinical, novel, and experimental biomarkers [hsCRP, H-FABP, and Survivin (BIRC5)] have been measured in specialized laboratories. RESULTS: Mean age of included patients was 71.35 ± 6.89 years. In the case of heart complications and mortality prediction, hsCRP and ACS NSQIP showed the highest specificity and sensitivity with AUC, respectively, 0.869 and 0.813 for heart complications and 0.883 and 0.813 for mortality. When combined with individual biomarkers AUC of ACS NSQIP raised, but if we combined all three biomarkers with ACS NSQIP, AUC reached as much as 0.920 for heart complications and 0.939 for mortality. DISCUSSION: ACS NSQIP proved to reduce inaccuracy in preoperative assessment, but it cannot be used independently, which has already been proved by other authors. CONCLUSIONS: Our results indicate that ACS NSQIP represents an accurate tool for preoperative assessment of elderly patients, especially if combined with cardiac biomarkers.

Addition of clinical risk scores improves prediction performance of American Society of Anesthesiologists (ASA) physical status classification for postoperative mortality in older patients: a pilot study.

PURPOSE: Many methods for preoperative risk stratifications used in everyday practice do not take into account all of the comorbidities and complex physiological status of older patients. Therefore, anaesthesiologists and surgeons must consider multiple ways of preoperative diagnostics. Determining which of the preoperative clinical risk scores [Revised Lee score, the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator and Surgical Outcome Risk Tool (SORT)] best improves routinely used American Society of Anaesthesiologists (ASA) physical status classification. METHODS: The prospective pilot study included 78 patients who were being prepared for extensive non-cardiac surgeries under general anaesthesia. Preoperatively, anaesthesiologist determined ASA score according to guidelines. Then, the data of patients have been processed on the interactive calculators of Revised Lee score, ACS NSQIP and SORT. RESULTS: Mean age of included patients was 71.4 ± 6.9 years. When it comes to postoperative mortality prediction, three risk scores (ASA, ACS NSQIP and SORT) have been statistically significant, respectively, P = 0.016, P < 0.0001, P < 0.0001. Results showed that AUC being higher in ACS NSQIP and SORT (0.813; 0.797). Out of all three additional risk scores, ACS NSQIP showed to add the most to the specificity and sensitivity of ASA score, with combined AUC = 0.841. CONCLUSIONS: ACS NSQIP and SORT increase the accuracy of ASA score. Revised Lee score cannot be considered a good indicator of postoperative mortality risk since it is primarily the score which indicates risk for cardiovascular complications. Further studies, with a greater number of patients, are needed.

Clinical indices and biomarkers for perioperative cardiac risk stratification: an update.

European Society of Cardiology (ESC)/ European Society of Anesthesiology (ESA) highlighted that anesthesiologist has a leading role in perioperative cardiovascular assessment and management in the year of 2014. During cardiovascular assessment one can rely on cooperation of multidisciplinary specialists like: other anesthesiologists, cardiologists and surgeons. For the purpose of precise systematization and decision making the Lee Score or NSQUIP database can be used besides the traditionally used ASA Score. Additional help is provided with specific palette of cardiac biomarkers like: cardiac troponins T, cardiac troponins I, C-reactive protein, N-terminal pro-brain natriuretic peptide, brain natriuretic peptide, etc. Biomarkers are considered to represent a foundation of evidence based medicine and they help anesthesiologists in the decision-making process. They increase the chance to achieve the best clinical outcome for each patient. An ideal biomarker does not exist and therefore new research are currently being conducted with the aim to find and declare more specific biomarkers like heart-type fatty acid-binding protein, micro RNA, PAMP and high sensitivity troponins T.

The role of kinesitherapy and electrotherapeutic procedures in non-operative management of patients with intermittent claudications.

PURPOSE: To examine the effects of physical therapy (kinesitherapy and electrotherapeutic procedures) on the course of peripheral arterial occlusive disease by monitoring the changes in values of claudication distance and ankle-brachial indexes. METHODS: Prospective randomized study included 47 patients with peripheral arterial occlusive disease manifested by intermittent claudications associated with ankle-brachial indexes values ranging from 0.5 to 0.9. Patients from the first group (25 pts) were treated with medicamentous therapy, walking exercises beyond the pain threshold, dynamic low-burden kinesi exercises and electrotherapeutic ageneses (interference therapy, diadynamic therapy, and electromagnetic field), while the second group of patients (22 pts) was treated with "conventional" non-operative treatment - medicamentous therapy and walking exercises. The values of newly established absolute claudication distance and ankle-brachial indexes were measured. FINDINGS: Significant increase of absolute claudication distance in both groups of patients was registered, independently of therapeutic protocol applied (p < 0.001), as well as the increase in the claudication distance interval in the physical therapy group. There was no significant increase in ankle-brachial indexes values in both groups of patients. CONCLUSION: Methods of physical therapy presented valuable supplement in non-operative treatment of peripheral arterial occlusive disease patients, improving their functional ability and thus postponing surgical treatment. However, further investigations including larger number of patients are needed.

Peripartum Cardiomyopathy in Intensive Care Unit: An Update.

Peripartum cardiomyopathy (PPCM) is a systolic heart failure that occurs during the last month of pregnancy or within 5 months after delivery. It is an uncommon disease of unknown etiopathogenesis and has a very high rate of maternal mortality. Because of similarity between symptoms of PPCM and physiological discomforts during pregnancy, the early diagnosis of PPCM presents a major challenge. Since hemodynamic changes during PPCM can vitally jeopardize the mother and the fetus, patients with severe forms of PPCM require a multidisciplinary approach in intensive care units. This review summarizes the current state of knowledge about the diagnosis, monitoring, and the treatment of PPCM. Having reviewed the recent researches, it gives insight into the new treatment strategies of this rare disease.

Beyond the Limits: Clinical Utility of Novel Cardiac Biomarkers.

Preoperative assessment of cardiovascular risk is essential when it comes to extensive noncardiac surgery procedures. Therefore, accurate and timely diagnosis of myocyte damage is vital. In modern medical practice it is believed that the so-called "multimarker" approach is the most appropriate and most accurate, but new research points out that there are novel biomarkers which could be used independently. Studies that evaluate miRNA, H-FABP, and MR-PAMP give encouraging results. When it comes to miRNA clinical studies show high statistical significance, especially in the case of acute myocardial infarction (P = 0.001). Statistical significance of P = 0.007 was found in acute coronary syndrome, when H-FABP was measured. Biochemical marker MR-PAMP showed statistical significance of P < 0.0001 in most clinical studies.

Characterization of deciduous teeth stem cells isolated from crown dental pulp.

BACKGROUND/AIM: The last decade has been profoundly marked by persistent attempts to use ex vivo expanded and manipulated mesenchymal stem cells (MSCs), as a tool in different types of regenerative therapy. In the present study we described immunophenotype and the proliferative and differentiation potential of cells isolated from pulp remnants of exfoliated deciduous teeth in the final phase of root resorption. METHODS: The initial adherent cell population from five donors was obtained by the outgrowth method. Colony forming unit-fibroblast (CFU-F) assay was performed in passage one. Cell expansion was performed until passage three and all tests were done until passage eight. Cells were labeled for early mesenchymal stem cells markers and analysis have been done using flow cytometry. The proliferative potential was assessed by cell counting in defined time points and population doubling time was calculated. Commercial media were used to induce osteoblastic, chondrogenic and adipogenic differentiation. Cytology and histology methods were used for analysis of differentiated cell morphology and extracellular matrix characteristics. RESULTS: According to immunophenotype analyses all undifferentiated cells were positive for the mesenchymal stem cell markers: CD29 and CD73. Some cells expressed CD146 and CD106. The hematopoietic cell marker, CD34, was not detected. In passage one, incidence of CFU-F was 4.7 +/- 0.5/100. Population doubling time did not change significantly during cell subcultivation and was in average 25 h. After induction of differentiation, the multicolony derived cell population had a tri-lineage differentiation potential, since mineralized matrix, cartilage-like tissue and adipocytes were successfully formed after three weeks of incubation. CONCLUSION: Altogether, these data suggest that remnants of deciduous teeth dental pulp contained cell populations with mesenchymal stem cell-like features, with a high proliferation and tri-lineage differentiation potential and that these cultures are suitable for further in vitro evaluation of cell based therapies.