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The aim of this study was to compare the estimated glomerular filtration rate (eGFR) from serum creatinine (eGFRcrea) and cystatin C (eGFRcys) in patients with elevated serum trough levels of gentamicin before the next planned dose during treatment in the intensive care unit (ICU).

Pancreatic cancer (PDAC) has a poor prognosis despite surgical removal and adjuvant therapy. Additionally, the effects of postoperative analgesia with morphine and piritramide on survival among PDAC patients are unknown, as are their interactions with opioid/cannabinoid receptor gene expressions in PDAC tissue. Cancer-specific survival data for 71 PDAC patients who underwent radical surgery followed by postoperative analgesia with morphine ( n = 48) or piritramide ( n = 23) were therefore analyzed in conjunction with opioid/cannabinoid receptor gene expressions in the patients' tumors. Receptor gene expressions were determined using the quantitative real-time polymerase chain reaction. Patients receiving morphine had significantly longer cancer-specific survival (CSS) than those receiving piritramide postoperative analgesia (median 22.4 vs. 15 months; p = 0.038). This finding was supported by multivariate modelling ( p < 0.001). The morphine and piritramide groups had similar morphine equipotent doses, receptor expression, and baseline characteristics. The opioid/cannabinoid receptor gene expression was analyzed in a group of 130 pancreatic cancer patients. Of the studied receptors, high cannabinoid receptor 2 (CB2) and opioid growth factor receptor (OGFR) gene expressions have a positive influence on the length of overall survival (OS; p = 0.029, resp. p = 0.01). Conversely, high delta opioid receptor gene expression shortened OS ( p = 0.043). Multivariate modelling indicated that high CB2 and OGFR expression improved OS (HR = 0.538, p = 0.011, resp. HR = 0.435, p = 0.001), while high OPRD receptor expression shortened OS (HR = 2.264, p = 0.002). Morphine analgesia, CB2, and OGFR cancer tissue gene expression thus improved CSS resp. OS after radical PDAC surgery, whereas delta opioid receptor expression shortened OS.

Background: Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet., Methods: We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development., Discussion: The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies., Trial Registration Number: NCT03700411, registration date: October 3, 2018., Study Status: recruiting., (© 2023. The Author(s).)

Aim: The aim of this review article is to summarize current knowledge about the role of cannabinoids and cannabinoid receptors in tumor disease modulation and to evaluate comprehensively the use of cannabinoids in cancer patients., Method: According to the PRISMA protocol, we have included data from a total of 105 articles., Results: Cannabinoids affect cancer progression by three mechanisms. The most important mechanism is the stimulation of autophagy and affecting the signaling pathways leading to apoptosis. The most important mechanism of this process is the accumulation of ceramide. Cannabinoids also stimulate apoptosis by mechanisms independent of autophagy. Other mechanisms by which cannabinoids affect tumor growth are inhibition of tumor angiogenesis, invasiveness, metastasis, and the modulation of the anti-tumor immune response., Conclusion: In addition to the symptomatic therapy of cancer patients, the antitumor effects of cannabinoids (whether in monotherapy or in combination with other cancer therapies) have promising potential in the treatment of cancer patients. More clinical trials are needed to demonstrate the antitumor effect of cannabinoids (Tab. 1, Fig. 1, Ref. 167).

Background: Hospital-acquired pneumonia (HAP) is associated with high mortality. In Central Europe, there is a dearth of information on the prevalence and treatment of HAP. This project was aimed at collecting multicenter epidemiological data on patients with HAP in the Czech Republic and comparing them with supraregional data., Methods: This prospective, multicenter, observational study processed data from a database supported by a Czech Ministry of Health grant project. Included were all consecutive patients aged 18 and over who were admitted to participating intensive care units (ICUs) between 1 May 2013 and 31 December 2014 and met the inclusion criterion of having HAP. The primary endpoint was to analyze the relationships between 30-day mortality (during the stay in or after discharge from ICUs) and the microbiological etiological agent and adequacy of initial empirical antibiotic therapy in HAP patients., Results: The group dataset contained data on 330 enrolled patients. The final validated dataset involved 214 patients, 168 males (78.5%) and 46 females (21.5%), from whom 278 valid lower airway samples were obtained. The mean patient age was 59.9 years. The mean APACHE II score at admission was 21. Community-acquired pneumonia was identified in 13 patients and HAP in 201 patients, of whom 26 (12.1%) had early-onset and 175 (81.8%) had late-onset HAP. Twenty-two bacterial species were identified as etiologic agents but only six of them exceeded a frequency of detection of 5% (Klebsiella pneumoniae 20.4%, Pseudomonas aeruginosa 20.0%, Escherichia coli 10.8%, Enterobacter spp. 8.1%, Staphylococcus aureus 6.2% and Burkholderia cepacia complex 5.8%). Patients infected with Staphylococcus aureus had significantly higher rates of early-onset HAP than those with other etiologic agents. The overall 30-day mortality rate for HAP was 29.9%, with 19.2% mortality for early-onset HAP and 31.4% mortality for late-onset HAP. Patients with late-onset HAP receiving adequate initial empirical antibiotic therapy had statistically significantly lower 30-day mortality than those receiving inadequate initial antibiotic therapy (23.8% vs 42.9%). Patients with ventilator-associated pneumonia (VAP) had significantly higher mortality than those who developed HAP with no association with mechanical ventilation (34.6% vs 12.7%). Patients having VAP treated with adequate initial antibiotic therapy had lower 30-day mortality than those receiving inadequate therapy (27.2% vs 44.8%)., Conclusions: The present study was the first to collect multicenter data on the epidemiology of HAP in the Central European Region, with respect to the incidence of etiologic agents causing HAP. It was concerned with relationships between 30-day patient mortality and the type of HAP, etiologic agent and adequacy of initial empirical antibiotic therapy.

Background: Patients with significant medical and social problems resulting from impaired perfusion of the upper limbs caused by micro- or macro-angiopathy are now frequent in clinical practice. Vasospastic disease of the upper limbs of combined origin is a difficult condition to treat by conservative methods and therapeutic strategies are usually multidisciplinary. In addition to standard pharmacotherapy, treatment may involve regional anaesthesia, thoracoscopic or radiofrequency sympathectomy and surgical treatment of defects, including plastic surgery., Methods: This paper describes our successful work in the treatment of upper limb critical ischemia using radiofrequency upper thoracic sympathectomy., Results: In three case reports we present the results of radiofrequency thermolysis applied to treat patients with chronic defects of the hand and fingers. These patients were diagnosed with upper limb critical ischemia of combined origin, standard conservative treatment methods failed and surgical intervention was originally not indicated, however, radiofrequency thermolysis proved to be beneficial., Conclusions: Radiofrequency thoracic sympathectomy could improve peripheral perfusion of the upper limbs and thereby contribute to healing of chronic defects, reduction of pain and improvement in the quality of life of the patients.

Aims: To compare the pharmacodynamics of 0.6 mg kg(-1) rocuronium in young and older patients of both genders during total intravenous anesthesia., Methods: Following local ethics committee approval and informed consent, patients scheduled for surgery under total intravenous anesthesia (propofol/sufentanil) were divided into 4 study groups: 37 males aged 20-40, 40 males aged 60-75 yrs, 43 females aged 20-40 and 38 females aged 60-75 yrs. Neuromuscular block following rocuronium (0.6 mg kg(-1)) was monitored: train-of-four [TOF] stimulation of the ulnar nerve at 15-s intervals, EMG of the adductor pollicis muscle. The onset time (from application of rocuronium to maximum depression of T(1)), clinical duration (from application to 25% recovery of T(1)), and time to full spontaneous recovery (from application to TOF-ratio ≥ 0.9) were determined for each patient. The Kruskal-Wallis test was used to compare differences between groups; P<0.05 was considered statistically significant., Results: The onset time (median [interquartile range]) in the respective groups was 90 [80-110](BCD), 135 [116-165](AC), 75 [60-90](ABD), and 120 [90-146](AC) seconds. The clinical duration was 30 [25-42](BCD), 58 [53-67](AD), 50 [40-65](AD), and 85 [70-90](ABC) min. Interval to full spontaneous recovery was 59 [51-67](BCD), 102 [75-106](A), 76 [66-91](AD), and 128 [94-137](AC) min. ((A)P<0.05 vs. young males, (B)P<0.05 vs. elderly males, (C)P<0.05 vs. young females, (D)P<0.05 vs. elderly females)., Conclusion: Females and older patients were more sensitive to rocuronium.

Purpose: Extreme lateral interbody fusion (XLIF) is a method for stabilization of the lumbar spine. Intraoperatively, the surgeon identifies the lumbar nerve roots with a stimulator to prevent their injury. The objective of this study was to determine the extent to which shallow rocuronium-induced neuromuscular block must be intraoperatively reversed for reliable identification of nerve roots., Methods: General anesthesia (midazolam-propofol-sufentanil-oxygen/air/sevoflurane-rocuronium) was administered to all patients. Train-of-four (TOF) stimulation of the ulnar nerve at 15-s intervals and electromyographic response of the adductor pollicis muscle were used. During operation, the surgeon stimulated the lumbar nerve roots (5-10 mA) to identify their course. At the appearance of two twitches to the TOF stimuli, sugammadex (2 mg/kg) or neostigmine (0.04 mg/kg) was administered. When the response to nerve root stimulation appeared, the TOF ratio was recorded., Results: When the response to nerve root stimulation with 10 mA became detectable, the median (range) TOF ratios were 0.67 (0.50-0.81) and 0.65 (0.42-0.71) after sugammadex and neostigmine, respectively. Similarly, TOF ratios at the first detectable response to stimulation with 5 mA were 0.88 (0.67-0.93) and 0.83 (0.61-0.93). After sugammadex and neostigmine, the respective intervals until TOF ratio ≥0.90 were 2.0 (0.8-3.3) and 15.9 (7.3-28.8) min., Conclusion: Intraoperative reversal of shallow rocuronium-induced block with either sugammadex or neostigmine is an efficient method. For reliable detection of lumbar nerve roots with a stimulating current of 10 mA, the block should be reversed to a TOF ratio of at least 0.70. For a current intensity of 5 mA, the TOF ratio should reach 0.90.

Aim: To determine the inter-observer reproducibility of 15 tests used for predicting difficult tracheal intubation (DI)., Material and Methods: Following local ethics committee approval and informed consent, 101 volunteers were examined by two assessors using 15 tests for predicting DI. The two assessors who were blinded to the results of the other, examined each volunteer independently. Cohen's kappa (κ) or first-order agreement coefficient (AC1) were used to measure agreement between assessor ratings on a qualitative scale. Agreement between two quantitative outcomes was described using the intraclass correlation coefficient (ICC) and Pearson's (PCC) or Spearman's (SCC) correlation coefficients. The following interpretation of the coefficients was used: poor (< 0.20), fair (0.21-0.40), satisfactory (0.41-0.60), good (0.61-0.80), and excellent (0.81-1.00)., Results: Respective coefficients of inter-rater agreement and correlation coefficients were determined for the following parameters: pathologies associated with DI (κ=0.662, AC1=0.990), clinical impression (κ=-0.013, AC1=0.969), modified Mallampati test (κ=0.503, AC1=0.861), upper lip bite test (κ=0.370, AC1=0.897), temporo-mandibular joint movement (κ=0.088, AC1=0.797), max. anteroflexion of C-spine (ICC=0.136, SCC=0.391), max. retroflexion of C-spine (ICC=0.020, SCC=0.284), mandibular length (ICC=0.301, SCC=0.553), neck circumference (ICC=0.832, SCC=0.928), hyo-mental distance (ICC=0.378, SCC=0.472), thyro-mental distance (ICC=-0.002, PCC=0.265), sternomental distance (ICC=0.674, PCC=0.815), and finally, inter-incisor gap (ICC=0.695, PCC=0.785). Two tests (positive history of DI and retrogenia), were excluded from calculation because no positive cases were found., Conclusion: Best inter-rater agreement was found for the assessment of neck circumference while the highest discrepancies between raters were in goniometrically-measured mobility of the C-spine. Many of the pre-operative airway tests had only fair inter-observer reproducibility. This may be one reason why models for predicting difficult intubation are not universally reliable.

Aim: To determine the accuracy of the modified Mallampati test for predicting difficult tracheal intubation., Design: A cross-sectional, clinical, observational, non-blinded study. A quality analysis of anesthetic care., Setting: Operating theatres and department of anesthesiology in a university hospital., Material and Methods: Following the local ethics committee approval and patients' informed consent to anesthesia, all adult patients (> 18 yrs) presenting for any type of non-emergency surgical procedures under general anesthesia requiring endotracheal intubation were enrolled. Prior to anesthesia, Samsoon and Young's modification of the Mallampati test (modified Mallampati test) was performed. Following induction, the anesthesiologist described the laryngoscopic view using the Cormack-Lehane scale. Classes 3 or 4 of the modified Mallampati test were considered a predictor of difficult intubation. Grades 3 or 4 of the Cormack-Lehane classification of the laryngoscopic view were defined as impaired glottic exposure. The sensitivity, specificity, positive and negative predictive value, relative risk, likelihood ratio and accuracy of the modified Mallampati test were calculated on 2x2 contingency tables., Results: Of the total 1,518 patients enrolled, 48 had difficult intubation (3.2%). We failed to detect as many as 35.4% patients in whom glottis exposure during direct laryngoscopy was inadequate (sensitivity 0.646). Compared to the original article by Mallampati, we found lower specificity (0.824 vs. 0.995), lower positive predictive value (0.107 vs. 0.933), higher negative predictive value (0.986 vs. 0.928), lower likelihood ratio (3.68 vs. 91.0) and accuracy (0.819 vs. 0.929)., Conclusion: When used as a single examination, the modified Mallampati test is of limited value in predicting difficult intubation.

Background and Objectives: Percutaneous radiofrequency (RF) thoracic sympathectomy is an alternative method to surgical procedures for the treatment of acral ischemia in Raynaud phenomenon. The procedure is indicated if conservative therapy fails to provide sufficient relief. The aim of this study was to compare classic T2 and T3 RF thermolesioning with a less invasive procedure at the level of T2 only., Methods: Fifty adult patients, American Society of Anesthesiologists (ASA) classification I to III, were randomly assigned to 1 of 2 groups. T2 and T3 thoracic RF thermolesion was performed in 1 group, whereas T2 thermolesion with local application of 0.5 mL of 6% phenol was delivered in the second group. Changes in cold perception, pain, and quality of life were assessed using a questionnaire. Blood circulation in the upper extremity was evaluated using infrared thermography. Patients were observed for a period of 3 months., Results: A significant decrease in pain according to visual analog scale (P < 0.001), increase in peripheral temperature in the upper extremities (P < 0.001), and improvement in quality of life were observed in both groups of patients after the procedure. Susceptibility to cold-provoked vasospasm was not significantly affected in either group. There was no significant difference between the 2 groups in any parameter apart from the duration of the procedure., Conclusions: Thoracic RF upper sympathectomy is an effective method in the treatment of resistant forms of Raynaud phenomenon. A single-shot procedure at the level of T2 may be preferable because of the shorter procedure duration of this technique.

Background: Continuous paravertebral block (PVB) has been successfully used for postoperative analgesia in children. However, data regarding the efficacy of a single injection technique for major renal surgery are still lacking., Methods: Following the ethics committee approval and parent informed consent, 24 children (median 10.3 months; range: 2.9-26.8) undergoing major renal surgery were included in a prospective observational pilot study. Following a standardized general anesthetic the patients were administered a single injection low thoracic PVB (loss-of-resistance technique; 0.5 ml.kg(-1) of levobupivacaine 2.5 mg.ml(-1) with epinephrine 5 mug.ml(-1)) at the end of surgery. Postoperative pain was assessed by Face, Legs, Activity, Cry, Consolability (FLACC) score at predetermined time points and in case of apparent patients' discomfort during the first 12 postoperative hours. The duration of postoperative analgesia was defined as the interval between PVB and the first supplemental administration of a rescue opioid analgesic. The incidence of complications and postoperative vomiting (POV) was also recorded., Results: A successful PVB was achieved in 23/24 patients (95.8%). The median duration of the block was 600 min (range: 180-720 min) with 10 children not requiring any supplemental analgesia during the 12-h observation period. Vascular puncture was observed in 2/24 children (8.3%) and POV occurred in 4/24 children (16.7%). All complications were considered minor and did not influence recovery., Conclusions: Single injection PVB provided clinically relevant postoperative analgesia in children undergoing major renal surgery.

Aims: To assess the influence of gender on the course of rocuronium-induced neuromuscular block following a single bolus dose of 2 x ED(95) (0.6 mg kg(-1))., Methods: Following the ethics committee approval and informed consent, 245 patients (121 men, 124 women) scheduled for elective general surgery under TIVA with muscle relaxation were studied. After rocuronium 0.6 mg kg(-1), the onset time for maximal depression of T(1), clinical duration until 25 % recovery and recovery index (T(1) from 25 to 75 %) were determined with TOF-Watch SX accelerometric monitor. The data for male and female groups were compared with appropriate statistical tests (Student's unpaired t-test, Mann-Whitney Rank Sum Test and Fisher's exact test)., Results: Men were significantly larger (p < 0.001) and heavier (p < 0.05) than women, but the body mass index was comparable (ns). The onset time was shorter in females [92.5 (SD 14.2) vs. 104.7 (12.2) s, p < 0.0001]. Clinical duration was increased in females [43.1 (7.9) vs. 31.3 (5.5) min; p < 0.0001], while the recovery index was identical in both groups [14.7 (5.0) min in females and 14.8 (4.0) min in males; ns]., Conclusions: Women are more sensitive than men to the dose 0.6 mg kg(-1) of rocuronium. Under the study conditions described, the onset time was shortened and the clinical duration increased in female patients. This suggests that the routine dose of rocuronium should be reduced in women.