Mu-Opioid Receptor 1 and C-Reactive Protein Single Nucleotide Polymorphisms as Biomarkers of Pain Intensity and Opioid Consumption.

Children constitute a special group in pain therapy. Single nucleotide polymorphisms that are associated with differences in postoperative, inflammatory pain perception and opioid requirement are the A118G SNP in the mu-opioid receptor 1 (OPRM1) gene and the rs1205 CRP. This study aimed to determine connection between OPRM1 and rs1205 CRP SNPs in pediatric patients postoperatively and pain intensity, the opioid dose needed to control pain after scoliosis correction, and other clinical aspects. Genotypes of rs1205 CRP and OPRM1 polymorphisms in a sample of 31 patients were specified, and statistical analysis was performed in terms of age, genotype frequency, pain assessment, sufentanil flow, post-anesthesia care unit stay, and the use of coanalgesics. The frequency of A/A and A/G genotypes in the OPRM1 gene was in line with 1000Genomes data for the European population. Patients from the AG group of OPRM1 SNP more frequently required coanalgesics for adequate pain control; however, it was of weak statistical significance. Other parameters measured in the study were not statistically significant in relation to OPRM1 and CRP polymorphisms. The effect of SNPs on postoperative pain management and opioid therapy in children was not confirmed by this study. An expansion of the study sample and other opioid-related SNPs is required.

Opioid Therapy and Implications for Oxidative Balance: A Clinical Study of Total Oxidative Capacity (TOC) and Total Antioxidative Capacity (TAC).

BACKGROUND: Opioids are used in pharmacotherapy for chronic pain. The phenomenon of their influence on the oxidative-antioxidant balance is poorly understood. Additionally, little is known about the oxidative status in patients receiving chronic opioid noncancer pain therapy. METHODS: The primary goal was to explore oxidative status using the total oxidative capacity (TOC) and total antioxidative capacity (TAC) in patients with chronic lower back pain (LBP) treated with opioids. The secondary task was to present the risk factors connected with the duration of therapy or anthropometric parameters. Plasma TOC and TAC were analyzed in the study group (n = 28), i.e., patients with chronic LBP treated with opioids, and in the control group (n = 11), i.e., healthy volunteers. RESULTS: The TAC was significantly lower in the study group compared to the control group (p < 0.05), while the TOC did not differ significantly. A statistically lower TOC for buprenorphine compared to oxycodone (p = 0.019) and tramadol (p = 0.036) was observed. The TOC did not differ between tramadol and oxycodone. The highest TAC was described for oxycodone, while the TAC for buprenorphine and tramadol was significantly lower in comparison with oxycodone (p = 0.007 and p = 0.016). The TOC/TAC ratio was higher in patients with nicotinism in both groups. CONCLUSIONS: Patients receiving chronic opioid therapy presented a lower antioxidative capacity. There were differences in opioid-induced oxidative imbalance, which is very important clinically. Nicotinism increases the oxidative-antioxidative imbalance. The least oxidative capacity was associated with buprenorphine, while oxycodone showed the greatest antioxidant activity. The most favorable TOC/TAC ratio was observed for buprenorphine. It is suggested that buprenorphine or oxycodone has the best profile, and there is no correlation with the duration of opioid therapy or the opioid dose. However, all opioid substances can potentially enhance the oxidative-antioxidative status.

Plasma Brain-Derived Neurotrophic Factor and Opioid Therapy: Results of Pilot Cross-Sectional Study.

Objective: The neurotoxic effect of opioid has not been thoroughly described. No studies have been conducted to explain the effect of opioids in chronic non-cancer pain therapy on the neurotrophic factors level. Due to the ability to cross the blood-brain barrier, it seems the determination of serum Brain-derived neurotrophic factor (BDNF) concentration is a reliable presentation of the concentration in the central nervous system. The aim of the study was to explore the changes of plasma BDNF concentration during long-term opioid therapy.Methods: The study group included 28 patients with chronic low back pain treated with opioid therapy buprenorphine (n=10), tramadol (n=8), oxycodone (n=6), morphine (n=3), fentanyl (n=1). The control group included 11 patients. Measurements of plasma BDNF concentrations were performed, and information about opioid therapy were recorded (age, sex, opioid substance type, daily dose and the duration of opioid therapy). Data were analyzed using nonparametric tests.Results: The median BDNF level in the study group was significantly lower (2.73 ng/mL) than that in the control group (5.04 ng/mL, P<0.05). BDNF levels did not differ among groups based on the type of opioid substance used, but the lowest median value was observed for tramadol (2.62 ng/mL), and the highest median value was observed for buprenorphine (2.73 ng/mL). The widest minimum-maximum ranges of BDNF for oxycodone were noted, minimum 1.23 ng/mL and maximum 4.57 ng/mL, respectively. BDNF concentrations were correlated with age in the tramadol group and with the duration of opioid therapy in the buprenorphine group.Conclusion: Chronic opioid therapy for noncancer pain induces specific changes in the BDNF concentration. Tramadol and buprenorphine exerted an important effect on BDNF levels in the examined patients. The BDNF level depends on duration of opioid therapy with buprenorphine, and age in tramadol therapy.

Invitation to participate in a multi-center study for validation of cerebral computed tomography angiography and computed tomography perfusion in the determination of cerebral circulatory arrest during brain death/death by neurological criteria diagnosis procedure in paediatric population below 12 years of age.

We would like to invite paediatric intensive care units (PICU) to join our multi-center trial concerning patient population < 12 y/o and aiming at: • validation of computed tomography angiography (CTA)/computed tomography perfusion (CTP) tests for brain death/death by neurological criteria (BD/DNC) diagnosis procedures, • validation of duplex Doppler insonation of extracranial segments of the internal cerebral arteries and the vertebral arteries for choosing an optimal time for CTA/CTP testing.

Effect of body mass index and rocuronium on serum tryptase concentration during volatile general anesthesia: an observational study.

OBJECTIVE: Female sex, body mass index (BMI), and neuromuscular blocking agents are risk factors of perioperative hypersensitivity reactions. This study aimed to investigate the effect of rocuronium on serum tryptase concentrations during general anesthesia in overweight and obese women. METHODS: The study was conducted in two groups: Group I (n=66) underwent volatile anesthesia with rocuronium and group II (n=60) underwent volatile anesthesia without any muscle relaxant. Serum tryptase concentration (STC) measurements were performed at baseline (STC 0) and postoperatively (STC 1). ClinicalTrials.gov: NCT04035707 RESULTS: The highest median value of STC 0 was seen in obese patients (3.44 µg L-1) and it was significantly higher than in overweight (p=0.01) and underweight patients (p=0.03). The maximum STC 0 was observed in overweight patients (20.4 µg L-1). In group I, STC 0 in obese patients presented the highest median value (4.49 µg L-1), and was significantly higher than in overweight patients (p=0.03), and had significantly higher STC 1 than patients with normal BMI (p=0.04). STC 0 and STC 1 in overweight and obese female patients did not differ significantly between groups. STC 1 did not correlate with rocuronium doses. In group I, BMI positively correlated with the duration of rocuronium infusion (rho=0.37) and STC 1 positively correlated with BMI (rho=0.32). CONCLUSION: Excess weight and obesity predispose to higher preoperative serum tryptase values. Postoperative STC is not linked to rocuronium doses. BMI is the main determinant factor of STC during combined volatile general anesthesia.

Palliative care for people living with cardiac disease.

Many cardiovascular diseases lead to heart failure, which is a progressive syndrome causing significant distress and limiting the quality of life, despite optimal cardiologic treatment. It is estimated that about 26 000 people in Poland suffer from advanced heart failure, and this number is growing. That is why palliative care (PC) dedicated to people living with end­stage cardiac diseases should be urgently implemented in Poland. Well­organized PC may not only relieve symptoms and improve quality of life in people living with cardiac diseases not responding to treatment but also support patients and their families during the dying process. Palliative care in patients with cardiac diseases should be continued during the end-of-life period. It should be implemented regardless of prognosis, and adjusted to patients' needs. Two approaches to PC are presented in this expert opinion. The first one (generic) is provided by all medical professionals incorporating PC principles into the usual patient care. The second approach, namely, specialized PC, is ensured by a multiprofessional team or at least a PC specialist who received appropriate training in PC. The model of needs-based (not prognosis-based) implementation of PC is discussed in this paper. Symptom control, support in decision-making, and sensitive, open communication are considered integral elements of PC interventions. Medical professionals developing PC in Poland should think about groups of patients with special needs like those with valvular heart disease, grown­up congenital heart disease, and pulmonary arterial hypertension, as well as elderly people. This consensus document presents main recommendations for future PC organization in Poland. Among others, we suggest changing the Polish National Health Fund reimbursement rules regarding PC and improving cardiologist education on PC.

Cardiac Surgery is Associated with Biomarker Evidence of Neuronal Damage.

BACKGROUND: Anesthesia and surgery is commonly associated with central nervous system sequelae and cognitive symptoms, which may be caused by neuronal injury. Neuronal injury can be monitored by plasma concentrations of the neuronal biomarkers tau and neurofilament light protein (NFL). Currently, there are no studies examining whether neuronal injury varies between surgical procedures. OBJECTIVE: Our aim was to investigate if neuronal damage is more frequent after cardiac than after otolaryngeal surgery, as estimated by tau and NFL concentrations in plasma. METHODS: Blood samples were drawn before, during, and after surgery and concentrations of tau, NFL, Aß40, and Aß42 were measured in 25 patients undergoing cardiac surgery (9 off-pump and 16 on-pump) and 26 patients undergoing otolaryngeal surgery. RESULTS: Tau increased during surgery (1752%, p = 0.0001) and NFL rose seven days post-surgery (1090%, p < 0.0001) in patients undergoing cardiac surgery; even more in patients on-pump than off-pump. No changes were observed in patients undergoing otolaryngeal surgery and only minor fluctuations were observed for Aß40 and Aß42. CONCLUSION: Cardiac surgery is associated with neuronal injury, which is aggravated by extracorporeal circulation. Analyses of NFL and tau in blood may guide development of surgical procedures to minimize neuronal damage, and may also be used in longitudinal clinical studies to assess the relationship of surgery with future neurocognitive impairment or dementia.

Effect of body mass index and rocuronium on serum tryptase concentration during volatile general anesthesia: an observational study

OBJECTIVE: Female sex, body mass index (BMI), and neuromuscular blocking agents are risk factors of perioperative hypersensitivity reactions. This study aimed to investigate the effect of rocuronium on serum tryptase concentrations during general anesthesia in overweight and obese women. METHODS: The study was conducted in two groups: Group I (n=66) underwent volatile anesthesia with rocuronium and group II (n=60) underwent volatile anesthesia without any muscle relaxant. Serum tryptase concentration (STC) measurements were performed at baseline (STC 0) and postoperatively (STC 1). ClinicalTrials.gov: NCT04035707 RESULTS: The highest median value of STC 0 was seen in obese patients (3.44 μg L-1) and it was significantly higher than in overweight (p=0.01) and underweight patients (p=0.03). The maximum STC 0 was observed in overweight patients (20.4 μg L-1). In group I, STC 0 in obese patients presented the highest median value (4.49 μg L-1), and was significantly higher than in overweight patients (p=0.03), and had significantly higher STC 1 than patients with normal BMI (p=0.04). STC 0 and STC 1 in overweight and obese female patients did not differ significantly between groups. STC 1 did not correlate with rocuronium doses. In group I, BMI positively correlated with the duration of rocuronium infusion (rho=0.37) and STC 1 positively correlated with BMI (rho=0.32). CONCLUSION: Excess weight and obesity predispose to higher preoperative serum tryptase values. Postoperative STC is not linked to rocuronium doses. BMI is the main determinant factor of STC during combined volatile general anesthesia.

Significance of IL-6 Deficiency in Recognition Memory in Young Adult and Aged Mice.

Chronic peripheral elevation of interleukin 6 (IL-6) in humans is associated with cognitive deficits. 4- and 24-month-old IL-6-deficient C57BL/6J (IL-6KO) and reference wild-type (WT) mice were tested in an object recognition test. Discrimination ratios and recognition indexes were significantly lower in 4-month-old IL-6KO and in 24-month-old WT mice vs 4-month-old WT animals. Their discrimination ratios had negative values and recognition indexes were below 50% indicating inability to differentiate the novel from the familiar object after 1-hour delay. In 24-month-old IL-6KO mice recognition index reached 53.17% indicating that their recognition memory was not worsened with age in comparison with younger IL-6-deficient animals. Results of holeboard and elevated plus maze indicated that this effect was memory specific. Inborn IL-6 deficiency attenuated recognition memory in 4-month-old mice and did not altered recognition memory in aged animals. IL-6 signalling may constitute a target for development of the protection against memory disturbances connected with IL-6 overexpression.

Candesartan prevents impairment of recall caused by repeated stress in rats.

RATIONALE: Deleterious effects of psychological stress on memory are increasingly important. Overexpression of the AT(1) angiotensin receptors in brain has been found to participate in several negative effects of chronic stress including hypertension and a cognitive impairment. OBJECTIVE: In this study, we searched for the protective effects the AT(1) angiotensin receptor blockade with candesartan against the adverse effects of repeated stress on recall of aversively and appetitively motivated behaviours in rats. METHODS: Two groups of male Wistar rats were repeatedly stressed by keeping them daily (2 h/21 days) in tight plastic tubes. The subjects of the group 1 received candesartan (0.1 mg/kg, orally) each day before the stressing procedure. The rats of the group 2 received vehicle. Another two groups of rats (3 and 4) receiving candesartan and vehicle, respectively, were appropriately handled but not stressed. Next day, after ending the repeated stress procedure, all rats were tested in two cognitive paradigms: inhibitory avoidance (IA) and object recognition (OR). RESULTS: Stressed animals displayed decreased recall of the IA behaviour (p < 0.01) and decreased OR (p < 0.05). These effects were not seen in the animals stressed and concomitantly treated with candesartan. The auxiliary tests designed to control for the possible unspecific contribution of motor (open field) and emotional (elevated "plus" maze) effects of the experimental procedures to results of the cognitive tests showed no such contribution. CONCLUSION: These data strongly suggest that the AT(1) angiotensin receptor blockade effectively counteracts deleterious effects of stress on recall of aversively and appetitively motivated memories in rats.

Risk factors of neurological complications in cardiac surgery.

BACKGROUND: Postoperative complications are integral to cardiac surgery. The most serious ones are stroke, which develops in about 7.5% of the patients, and postoperative encephalopathy, which affects 10-30% of the patients. According to bibliographical data, the number of complications is increasing. AIM: To analyse the risk factors and the types of neurological complications in patients undergoing heart surgery. METHODS: We assessed retrospectively 323 consecutive patients undergoing surgery at the Department of Cardiac Surgery, University Teaching Hospital, Medical University of Bialystok, Poland, between July 2007 and June 2008. Group 1 comprised patients without neurological complications (n = 287; 89%) and Group 2 consisted of patients with neurological complications (n = 36; 11%). Our analysis included the following: preoperative status (age, sex, co-morbidities), intraoperative course (surgery type, duration of cardiopulmonary bypass [CPB], duration of aortic cross-clamping, types of medications administered, necessity of reinfusion from the cardiotomy reservoir and the necessity of tranexamic acid infusion) and the postoperative course (time to regaining consciousness, duration of mechanical ventilation, development of complications, types of complications). The results were then analysed statistically: arithmetic means and standard deviations were calculated for quantitative variables and the quantitative and percentage distributions were calculated for qualitative variables. The between- group comparisons of the quantitative variables were carried out using the t-Student test, while the qualitative variables were compared using the χ(2) test. The variables that proved significant in the univariate comparisons were included in the multivariate model. Regression analysis was the final step of the analysis of the risk factors for neurological complications. Based on the analysis of the ROC curve we calculated the cutoff values for the continuous variables. We calculated odds ratios with their 95% confidence intervals. P values of less than 0.05 were considered statistically significant. RESULTS: Among the 36 patients in Group 2, postoperative encephalopathy developed in 22 patients, transient ischaemic attacks in 7 patients, ischaemic stroke in 6 patients (associated with right hemisphere damage in 3 patients and with left hemisphere damage in 3 patients) and haemorrhagic stroke in 1 patient (right hemisphere). Early mortality was 5% with 2 (0.69%) patients dying in Group 1 and 14 (38.9%) in Group 2. Univariate analysis revealed that the preoperative risk factors of neurological complications were: age >68 years (with a cutoff value of 58.5 years), a history of stroke with paresis, atrial fibrillation (AF) and a euroSCORE of >6 (with a cutoff value of 4.5). The peri- and postoperative risk factors included: surgery type (complex coronary and valvular surgeries aortic valve surgeries), duration of CPB of >142 min, duration of aortic crossclamping of >88 min, mean perfusion pressure during CPB of <70 mm Hg, haemodilution manifested by a haematocrit (HCT) of <28%, perfusate supply, time to regaining consciousness of >14.5 h and duration of artificial ventilation of >30.5 h. Multivariate analysis revealed the following factors to increase the risk of neurological complications: long duration of ventilation, a history of stroke with paresis, AF, low HCT values and long duration of aortic cross-clamping. The Nagelkerke R2 coefficient of determination was 0.636, the sensitivity was 74.36%, the specificity was 97.545% and the accuracy was 94.74%. CONCLUSIONS: In patients undergoing heart surgery, the independent risk factors of neurological complications in the first 30 days include: long duration of ventilation, a history of stroke with paresis, AF, haemodilution manifested by an HCT of <28% and long duration of aortic cross-clamping. Neurological complications are associated with high postoperative mortality.

[Apicoaortic valved conduit as an alternative method of surgical treatment of aortic stenosis - a case report]. / Wszczepienie protezy zaopatrzonej w zastawke pomiedzy koniuszkiem lewej komory a aorta zstepujaca jako alternatywna metoda operacji zwezenia zastawki aortalnej - opis przypadku.

A case of a 73-year-old patient with critical aortic stenosis, porcelain aorta and occluded femoral arteries is presented. We performed apico-aortic valved conduit (A-AVC) without cardiopulmonary bypass (CPB). Hegar dilator inserted through the apex into the left ventricle allowed anastomosis of dacron tube to the apex. Valved conduit was anastomosed to the descending aorta. Both tubes were connected. Before the operation, maximal gradient through the valve was 95, after operation dropped to 33 mmHg. This method of apical anastomosis allowed to perform A-AVC without CPB in a patient with extremely high peri-operative risk while using CPB.

[The effect of enalapril and captopril on emotional processes in hypertensive patients]. / Wplyw enalaprilu i kaptoprilu na procesy emocjonalne u pacjentów z nadcisnieniem tetniczym.

This study was aimed at the estimation of influence of enalapril and captopril on emotional processes in hypertensive patients. Hypertensive subjects evaluated before introducing drug treatment and normotensive persons comprised the control groups. All groups were examined with the psychological methods (BDI, HSC, Raven's Matric test). In BDI, there were no significant differences between the groups in the total score and particular factors as well. In HSC, there were significant differences in the total ratings between untreated hypertensive subjects and the normotensive group (p < 0.05). The depression/anxiety profile was the main contributing factor being itself significantly different (p < 0.05) in those groups. Enalapril and captopril reversed the negative behavioural changes caused by hypertension only moderately with no statistical significance. There were no alterations in intellectual abilities tested by the Raven's Matric test in any group examined. In conclusion, significant negative emotional effects of high blood pressure are only partly reversed by the antihypertensive doses of enalapril and captopril.