The Effect of Recruitment Maneuver on Static Lung Compliance in Patients Undergoing General Anesthesia for Laparoscopic Cholecystectomy: A Single-Centre Prospective Clinical Intervention Study.

Background and Objectives: The aim of this study was to examine whether the use of an alveolar recruitment maneuver (RM) leads to a significant increase in static lung compliance (Cstat) and an improvement in gas exchange in patients undergoing laparoscopic cholecystectomy. Material and Methods: A clinical prospective intervention study was conducted. Patients were divided into two groups according to their body mass index (BMI): normal-weight (group I) and pre-obese and obese grade I (group II). Lung mechanics were monitored (Cstat, dynamic compliance-Cdin, peak pressure-Ppeak, plateau pressure-Pplat, driving pressure-DP) alongside gas exchange, and hemodynamic changes (heart rate-HR, mean arterial pressure-MAP) at six time points: T1 (induction of anesthesia), T2 (formation of pneumoperitoneum), T3 (RM with a PEEP of 5 cm H2O), T4 (RM with a PEEP of 7 cm H2O), T5 (desufflation), and T6 (RM at the end). The RM was performed by increasing the peak pressure by +5 cm of H2O at an equal inspiration-to-expiration ratio (I/E = 1:1) and applying a PEEP of 5 and 7 cm of H2O. Results: Out of 96 patients, 33 belonged to group I and 63 to group II. An increase in Cstat values occurred after all three RMs. At each time point, the Cstat value was measured higher in group I than in group II. A higher increase in Cstat was observed in group II after the second and third RM. Cstat values were higher at the end of the surgical procedure compared to values after the induction of anesthesia. The RM led to a significant increase in PaO2 in both groups without changes in HR or MAP. Conclusions: During laparoscopic cholecystectomy, the application of RM leads to a significant increase in Cstat and an improvement in gas exchange. The prevention of atelectasis during anesthesia should be initiated immediately after the induction of anesthesia, using protective mechanical ventilation and RM.

Carob Extract (Ceratonia siliqua L.): Effects on Dyslipidemia and Obesity in a High-Fat Diet-Fed Rat Model.

Dyslipidemia and obesity are recognized as two of the major global health issues and main risk factors for coronary heart disease and cerebrovascular disease. In recent years, carob has shown certain antioxidant and anti-dyslipidemic potential. In this study, Wistar rats were fed with a standard and cholesterol-enriched diet and treated orally with carob extract and simvastatin for four weeks. After sacrifice, blood samples were collected for biochemical analysis, and liver tissue was taken for histological and immunohistochemical assessment. Weight gain was significantly higher in groups fed with cholesterol-fortified granules; total cholesterol was found to be significantly lower in the hypercholesterolemic groups treated with simvastatin and simvastatin/carob combined regimens compared with hypercholesterolemic animals treated with saline (p < 0.05). The same was true for low-density lipoprotein cholesterol and the LDL/HDL ratio (p < 0.05). Adiponectin was remarkably higher in animals treated with simvastatin compared to all other groups (p < 0.05). Leptin was significantly lower in groups treated with carob and simvastatin compared to the hypercholesterolemic group treated with saline (p < 0.05). Carob/simvastatin co-administration reduced hepatocyte damage and improved liver morphology. A study confirmed the anti-dyslipidemic, anti-obesity, and hepatoprotective potential of carob pulp alone or in combination with simvastatin in the treatment of high-fat diet-fed rats.

PERCUTANEOUS DILATATIONAL TRACHEOSTOMY IN COVID-19 PATIENTS IN THE COVID HOSPITAL INTENSIVE CARE UNIT: THE UNIVERSITY CLINICAL CENTER OF VOJVODINA EXPERIENCE.

Patients with acute respiratory distress syndrome due to COVID-19 require intensive care unit (ICU) admission with consecutive endotracheal intubation and invasive mechanical ventilation. In patients with long-term mechanical ventilation, percutaneous dilatational tracheostomy (PDT) may be considered. This retrospective analysis includes clinical data on patients treated at the ICUs of the COVID Hospital of the Clinical Center of Vojvodina in the period from September 3, 2021 to May 1, 2022, and underwent PDT. Patients were predominantly male (n=48; 65.8%). Weaning from mechanical ventilation was achieved in 31 (42.5%) and decannulation in 25 (34.2%) patients. The mean time from polymerase chain reaction SARS CoV-2 positivity until PDT was 15.59±6.85 days. The mean time of endotracheal intubation before the PDT procedure was 7.37±4.89 days. The mean weaning time from mechanical ventilation was 10.45±7.92 days. Twenty-five (34.2%) patients were decannulated at the mean time of 19.60±11.81 days. The complications were tracheostomy related bleeding (2 patients), pneumothorax (4 patients), subcutaneous emphysema (1 patient) and cricoid cartilage injury (1 patient). PDT is a simple, safe, and effective procedure performed in COVID-19 patients in the ICU.

Five-year surveillance and correlation of antibiotic consumption and resistance of Gram-negative bacteria at an intensive care unit in Serbia.

A surveillance study was performed in an intensive care unit in the largest tertiary health care center in Vojvodina, Serbia from 2014 to 2018. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days. Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated using cross-correlation analysis. An overall decrease in antibiotic utilization was observed. The prescription rates of piperacillin-tazobactam increased significantly, while consumption of 3rd and 4th generation cephalosporins and fluoroquinolones decreased. There were rising incidence densities of doripenem resistant Acinetobacter spp., piperacillin-tazobactam resistant Pseudomonas aeruginosa and carbapenem and colistin resistant Klebsiella pneumoniae. These results can serve as a basis for the development of antimicrobial stewardship strategies in the current setting.

An evaluation of the redox state in professional scuba divers.

Taking into consideration limited data regarding molecular interactions during and after diving, this investigation was intended to determine the oxidative status of divers before and after scuba diving by monitoring the oxidative status parameters. The prevalence study included a group of 32 male professional police scuba divers, 32 ± 5.1 years old. The examination took place twice: in a resting state before scuba diving and immediately after the dive (to 30 meters for 30 minutes). The oxidative status of the scuba divers was determined by measuring levels of the following oxidative stress markers: the index of lipid peroxidation (measured as TBARS), nitrites (NO2-), superoxide anion radical (O2*-), hydrogen peroxide (H2O2), superoxide dismutase (SOD) and catalase (CAT). Statistically significant increases in levels of NO2- and TBARS were observed after the dive, while there were no statistically relevant changes in levels of O2*-, H2O2, SOD and CAT. Our results have shown that a dive with these characteristics only slightly disturbs redox homeostasis, without serious intermolecular changes that can lead to prominent oxidative stress.

Anaphylaxis on Graft Reperfusion during Orthotopic Liver Transplantation: A Case Study.

INTRODUCTION: Hemodynamic instability is a common occurrence during liver transplantation (LT). Hypotension and hemodynamic instability during graft reperfusion are most commonly consequences of the postreperfusion syndrome (PRS). CASE OUTLINE: In this report, we present a case of severe cardiovascular collapse leading to cardiac arrest which occurred in the course of graft reperfusion during LT. Persistent hypotension, non-responsive to regular measures such as volume filling and the use of vasopressors, yielded the question of whether other mechanisms were involved in causing it. Diffuse redness of the face and body, swelling of the face, lips and tongue with tongue prolapse, accompanied with severe cardiovascular collapse indicated that it was an anaphylactic reaction. This caused a dilemma as to what instigated the reaction. The trigger may have been the pharmacological substance administered during the graft reperfusion, or the one administered immediately prior to the reperfusion.The substances in question would most likely be either the University of Wisconsin preservation solution (UW), which was administered during the reperfusion, or Hepatect, which the patient received immediately prior to reperfusion. CONCLUSION: The clinical syndrome resulting from degranulation of mast cells and basophils in anaphylaxis is very similar to the PRS in LT. Clinical features play the most important role in establishing a timely diagnosis and early treatment of anaphylaxis. Swift administration of epinephrine reduces the chances of a fatal outcome. Better information on both donor and recipient can improve the efficiency of therapy and prophylaxis for anaphylaxis.

Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms.

OBJECTIVE: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied. MATERIALS AND METHODS: Three modified-release formulations of aminophylline consisted of Carbopol® 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin(®) 350, tablets Purdue Frederic, Canada (R-II). RESULTS: Calculated release rate constants and the ƒ2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher Tmax, was found in the rabbits, dosed with F-II (12.00 h), F-III (10.50 h), and R-II (15.00 h) formulation. The highest Cmax (9.22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58 mg/L) and R-II (4.18 mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L). DISCUSSION AND CONCLUSION: The results demonstrated a good correlation of Level A (r(2) = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.

An investigation into effects of in vitro test condition on the release properties of theophylline from HPMC matrices using factorial design.

The purpose of this study was to investigate the effect of various in vitro test conditions, on the release properties of theophylline (TP) from aminophylline (AP) matrices based on different hydroxypropylmethylcellulose (HPMC) ratio and viscosity grades. The general full factorial experimental design 3 x 3 x 3 was used, based on three independent variables: applied in vitro test (X1), HPMC/drug ratio (X2) and polymer viscosity grade (X3). The drug release percent at 2h (Y(2h)), 4h (Y(4h)) and 8 h (Y(8h)) and time for 50% of TP release from matrices (Y(T50%)) were response variables. Three in vitro tests were used: test 1 and test 4 (theophylline extended-release capsules, USP 30) and half-change method. According to factorial design analyses, in vitro test was the most significant factor influencing mechanism and amount of drug release. For half change method erosion was the predominant mechanism indicating case - II transport, while for test 1 the release mechanism were followed by both diffusion and erosion. The lowest release exponent n values, obtained from Ritger-Pepass equation, for test 4 indicate diffusion process inclining from Fickian diffusion to anomalous transport. Therefore, it is in the stage of development, useful to consider the influence of various in vitro test conditions on the formulation, in order to choose an optimal test for the purpose of future drug release examination.

Application of mixture experimental design in the formulation and optimization of matrix tablets containing carbomer and hydroxy-propylmethylcellulose.

Using mixture experimental design, the effect of carbomer (Carbopol((R)) 971P NF) and hydroxypropylmethylcellulose (Methocel((R)) K100M or Methocel((R)) K4M) combination on the release profile and on the mechanism of drug liberation from matrix tablet was investigated. The numerical optimization procedure was also applied to establish and obtain formulation with desired drug release. The amount of TP released, release rate and mechanism varied with carbomer ratio in total matrix and HPMC viscosity. Increasing carbomer fractions led to a decrease in drug release. Anomalous diffusion was found in all matrices containing carbomer, while Case - II transport was predominant for tablet based on HPMC only. The predicted and obtained profiles for optimized formulations showed similarity. Those results indicate that Simplex Lattice Mixture experimental design and numerical optimization procedure can be applied during development to obtain sustained release matrix formulation with desired release profile.