Insights into treatment of complex Crohn's perianal fistulas.

Complex perianal fistula is a common complication of Crohn's disease (CD) which leads to negative impact on patient's quality of life. Successful management of the disease requires a multidisciplinary approach, including a gastroenterologist and a colorectal surgeon, applying combined surgical and medical therapy. One of frequently practiced surgical procedures is seton placement in the fistula tract, which is used to control perianal sepsis and drain the fistula, while preventing recurrent abscess formation.Darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Following approval of darvadstrocel, the INSPIRE registry is being conducted in order to evaluate long-term safety and effectiveness of the drug on a large, heterogenous population.An online expert meeting was held from March 20 to March 30, 2023, which provided relevant insights into the decision-making process regarding seton use and obtained feedback on the first experiences with darvadstrocel. The aim of this article is to present the perspectives from gastroenterologists and colorectal surgeons practicing in Czechia, Hungary, Israel, Lithuania, Serbia, and Slovenia in topics such as diagnosis and treatment options for patients with complex Crohn's perianal fistulas (CPF), specifically focusing on the use of setons and darvadstrocel.During this virtual session, unavailability of comprehensive data on safety and efficacy of available treatment procedures was emphasized as an important obstacle towards development of standardized recommendations and improvement of outcomes in treatment of (CPF). Furthermore, achieving consensus in seton use, duration of its placement, and frequency of change is recognized as one of CPF treatments major challenges. Despite these issues, it is important to promote better understanding and treatment of complex perianal fistulas in order to improve the quality of life of those affected by this condition.

Remodeling of extracellular matrix of the lamina propria in the uninvolved human rectal mucosa 10 and 20 cm away from the malignant tumor.

In recent years, it has been demonstrated that malignancy arises and advances through the molecular interplay between tumor cells and non-malignant elements of the tumor stroma, that is, fibroblasts and extracellular matrix. However, in contrast to the mounting evidence about the role of tumor stroma in the genesis and progression of the malignant disease, there are very few data regarding the uninvolved stromal tissue in the remote surrounding of the tumor. Using the objective morphometric approach in patients with adenocarcinoma, we demonstrate the remodeling of extracellular matrix of the lamina propria in the uninvolved rectal mucosa 10 and 20 cm away from the neoplasm. We show that the representation of basic extracellular matrix constituents (reticular and collagen fibers and ground substance) is decreased. Also, the diameter of empty spaces that appear within the extracellular matrix of the lamina propria is increased. These spaces do not represent the blood or lymphatic vessel elements. Very likely, they reflect the development of tissue edema in the remote, uninvolved lamina propria of the mucosa in patients with the malignant tumor of the rectum. We hypothesize that the remodeling of extracellular matrix in lamina propria of the rectal mucosa may increase its stiffness, modulating the mechano-signal transduction, and thus promote the progression of the malignant disease.

[Awareness detection in anaesthesia during otorhino-maxillofacial surgery using bispectral index-monitoring technology].

INTRODUCTION: Awareness is characterized by intraoperative presence of consciousness and recollecting of the events occurring during general anaesthesia. The study was aimed at detecting awareness during general anaesthesia in otorhino-maxillofacial procedure. METHODS: The study is a part of a prospective, phase IV academic study carried out at the Department for Otorhinolaringology, Clinical Centre of Serbia, and Maxillofacial Surgery. The study was approved by the Ethics Committee of the Clinical Centre of Serbia and performed in accordance with European Union Clinical Trials Directive. The evaluation included 40 patients (T-propofol and E-sevofluran group) subjected to different surgical procedures (American Society ofAnesthesiologists I-III). Depth of anaesthesia was monitored during surgical procedures according to the hemodynamic parameters (blood pressure, pulse, oxygen saturation, electrocardiography, capnometry). Bispectral index monitoring was applied; however, the insight into the obtained bispectral index values was possible only after the completion of the surgery when the comparison with hemodynamic values was performed. Modified Brice interview was postoperatively applied to the patients in whom awareness was suspected. RESULTS: Based on the hemodynamic parameter values obtained in 40 anesthetized patients, no cases of awareness were expected. After the completion of the surgical procedures, the recorded graphic and numeric bispectral index values obtained in the course of anaesthesia were analyzed. Higher bispectral index values (BIS > 60) were recorded in 1 T-group patient. CONCLUSION: It is possible to miss an awareness episode without using bispectral index technology monitoring during general anaesthesia in otorhinolaryngology and maxillofacial surgery. Bispectral index monitoring should be the clinical standard in general anaesthesia.

[Anesthetic dose correction in hospital pharmacology using bispectral index monitoring technology].

INTRODUCTION: Modern hospital pharmacology insists on assessing each patient's individual characteristics because of their influence on drug pharmacokinetics and pharmacodynamic effect. The study was aimed at evaluating anesthetic doses in patients with benign larynx tumors treated by general endotracheal anesthesia during endoscopic surgery procedures. MATERIAL AND METHODS: The study is a part of a prospective, phase IV, academic study carried out at the Clinical Center of Serbia. The evaluation included 30 patients, who were divided into two groups: Group A - 10 patients, anesthetized with standard recommended anesthetic doses. The insight into the obtained bispectral index values was possible only after completion of the surgery. Group B consisted of 20 patients, anesthetized with anesthetic doses corrected according to bispectral index monitoring values. RESULTS: The average duration of waking up in group A and B was 120.0 +/- 10.0 sec and B 70.0 +/- 9.0 sec, respectively, (p<0.01). When compared with group A the corrected induction anesthetic doses, corrected maintenance doses and anesthetic total consumption were lower in group B by 25% (p<0.01), 15% (p<0.01) and 25% (p<0.01), respectively. CONCLUSION: It is possible to overdose anesthetic drug during surgery without using bispectral index technology monitoring during general anesthesia in otorhinolaryngology maxillofacial surgery. Bispectral index monitoring should be the clinical standard in general anesthesia.

[Costs of anesthetics and other drugs in anesthesia].

INTRODUCTION: Drugs are real and transparent costs of treatment, which are subject to constant monitoring and changes. The study was aimed at measuring and analyzing consumption of anesthetics and other drugs in anesthesia in the Clinical Centre of Serbia. MATERIAL AND METHODS: This paper is part of a five-year (2005-2009), academic, pharmacoeconomic retrospective-prospective study (the 4th phase). We calculated the costs of anesthetics and other drugs in all anesthetized patients at the Institute of Anesthesia and Reanimation, Clinical Center of Serbia in 2006. The data, obtained from the Clinical Centre of Serbia Database, were analyzed by descriptive statistical methods using computer program Microsoft Office Excel 2003 and the Statistical Package for the Social Sciences (SPSS) for Windows. RESULTS: The amount of money spent for the application of 33,187 general and 16,394 local anesthesia and 20,614 anesthesiology procedures was 83,322,046.36 RSD (Euros 1,054,705.4), which was 5.93% of the funds allocated for all drugs used at the Clinical Center of Serbia. Of the total fund for drugs, 57.8% was spent for anesthetics (local anesthetics 1.20%) and muscle relaxants, whereas 42.2% was spent for other drugs in anesthesia. The highest amount was spent at the Emergency Center (35.8%), then at the Cardio-surgery (11.9%) and the Neurosurgery (10.9%) because of the large number and length of surgical interventions. CONCLUSION: There is no space for rationalizing the costs of anesthetics and other drugs in anesthesia.

[Radiotherapeutical chromosomal aberrations in laryngeal cancer patients]. / Radioterapijska ostecenja hromozoma kod karcinoma larinksa.

INTRODUCTION: The authors present the results of cytogenetic analysis of 21 patients with laryngeal carcinomas diagnosed and treated in the period 1995-2000 at the Institute of Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia and Clinical Center of Novi Sad. MATERIAL AND METHODS: The patients were specially monitored and the material was analyzed at the Institute of Human Genetics of the School of Medicine in Belgrade as well as in the Laboratory for Radiological Protection of the Institute of Occupational and Radiological Health "Dr Dragomir Karajovic" in Belgrade. RESULTS: The incidence of chromosomal aberrations and incidence of exchange of material between sister chromatids were observed in the preparation of the metaphasic lymphocyte chromosomes of the peripheral blood obtained in the culture. Structural aberrations were found on the chromosomes in the form of breakups, rings, translocations and dicentrics as early as after a single exposure of patients to tumor radiation dose of 2 Gy in the field sized 5x7. Out of the total number of 35 cultivated blood samples obtained from 13 patients, 21 were successfully cultivated and they were proved to contain chromosomal aberrations. Some of the peripheral blood samples failed to show cell growth in vitro due to the lethal cell damages in vivo. DISCUSSION: We have concluded that the number of structural aberrations cannot be used as a biological measure of the absorbed ionizing radiation dose. The presence of aberrations per se is indicative of the mutagenic effect of the ionizing radiation, which was also confirmed in our series on the original model by cultivation of the peripheral blood lymphocytes in the culture of the cells of the volunteer donors upon in vitro radiation. Using the method of bromdeoxyuridylreductase, the increased incidence of SCE as a mutagenic effect was registered. CONCLUSION: It has been concluded that the increase of absorbed radiation dose in vitro leads to prolonged duration of cell cycle in the same conditions, which proves cytostatic effect of radiation. Further fundamental studies are required for clinical implementation of the findings.

Antibiotic consumption monitoring at the Institute of Otorhinolaryngology and Maxillofacial Surgery--Clinical Center of Serbia in 2001-2003.

BACKGROUND: At the Clinical Center of Serbia (CCS), which includes 21 Institutes and 6 Centers, approximately 10% of the total annual budgetary funds is spent on the drugs. During the studied period, it was estimated that 0.5% of the above amount has been spent at the Institute for Otorhinolaryngology and Maxillofacial surgery (Institute for ORL and MFS), Clinical Center of Serbia. The aim of this study was to find out if these antibiotics had been used rationally by the monitoring of antibiotics in relation to the number of inpatients, and by the 5 most frequent diagnoses. METHODS: The authors monitored the three-year consumption of antibiotics for inhospital treated patients during the period 2001-2003. Data were obtained from the itemized quarterly report on the consumption by the Central Pharmacy of the CCS. RESULTS: The results were statistically analyzed and presented in percentages and Defined Daily Dosages (DDD) for each group of the antibiotics. The results were analyzed in accordance with the World Health Organization Recommendations and the Guidelines. CONCLUSION: The authors concluded that antibiotics were adequately used at the Institute for ORL and MFS-CCS. The most commonly used antibiotics for gram-positive infections were those from the penicillin and cephalosporin groups. According to the international trends and recommendations, the selected therapy was rational and the antibiotics consumption was cut down during the observed three-year period. It was a true confirmation that the recommendations for the rational antibiotics consumption had been fruitful (produced good results).