Transversus abdominis plane block with different bupivacaine concentrations in children undergoing unilateral inguinal hernia repair: a single-blind randomized clinical trial.

BACKGROUND: Current knowledge on the ideal local anesthetic concentration for the ultrasound-guided transversus abdominis plane block (TAPB) in pediatrics is scarce. The purpose of this study is to compare the efficacy of US-guided TAPB at two different concentrations of bupivacaine in pediatrics undergoing unilateral inguinal hernia repair. METHODS: After random allocation, 74 children aged 1-8 were randomized to receive US-guided TAPB by using 1 mg.kg- 1 bupivacaine as either 0,25% (0,4 ml.kg- 1) (Group 1) or 0,125% (0,8 ml.kg- 1) (Group 2) concentration. All blocks were performed under general anesthesia, immediately after the induction, unilaterally with a lateral approach. All subjects received intravenous 15 mg/kg paracetamol 0.15 mg/kg dexamethasone and 0.1 mg/kg ondansetron intraoperatively. The primary outcome was the efficacy which is assessed by postoperative FLACC behavioral pain assessment score at 15', 30', 45', 1 h, 2 h, 6 h, and 24 h. The secondary outcomes were to assess the total dose of rescue analgesic consumption, length of hospital stay, the incidence of side effects, complications and satisfaction levels of the patients' parents and the surgeons. RESULTS: Sixty-four children were recruited for the study. Postoperative pain scores were equal between the two groups. There was no need for a rescue analgesic in any group after the postoperative 6thhour. No local or systemic complication or side effect related to anesthesia or surgery was reported. CONCLUSION: TAPB using 1 mg.kg- 1 bupivacaine administered as either high volume/low concentration or low volume/high concentration was providing both adequate analgesia and no side effects. TRIAL REGISTRATION: This trial was retrospectively registered at Clinicaltrals.gov , NCT04202367 .

Lipid parameters, doses and blood levels of calcineurin inhibitors in renal transplant patients.

The calcineurin inhibitors (CNIs) [cyclosporin A (CsA) and tacrolimus (Tac)] are currently the most widely prescribed drugs for maintenance of immunosuppression after renal transplantation. These immunosuppressants are associated with side effects such as hyperlipidemia. We evaluated the differential effects of different CNIs on serum lipid parameters in renal transplant patients. Moreover, the aim of this study is to investigate the relationships between doses and blood levels of CNIs, and blood levels of CNIs and lipid parameters retrospectively. Two groups of 98 non-diabetic renal transplant patients, each treated with different CNIs, were studied: group A (n = 50, mean age: 31 ± 10 years), CsA, mycophenolate mofetil/azathioprin, steroid; group B (I = 48, mean age: 34 ± 12 years), Tac, mycophenolate mofetil/azathioprin, steroid. In renal transplant patients, CNIs blood levels and doses were examined at 1, 3, 6, 9, and 12 months after transplantation. Biochemical laboratory parameters including plasma lipids [total-cholesterol (CHOL), low-density lipoprotein (LDL)-CHOL, high-density lipoprotein (HDL)-CHOL, and triglycerides (TG)], CNI levels and doses were examined at 1, 3, 6, 9, and 12 months after transplantation. None of the patients received anti-lipidemic drugs during the study period. Blood levels of CNIs were detectable in all whole-blood samples by Cloned- Enzyme-Donor Immunoassay (CEDIA). The relationship between CNIs blood levels and CHOL, (LDL)-CHOL, HDL-CHOL, TG were evaluated. The mean serum CHOL levels and LDL-CHOL levels of patients in group A were found significantly higher than the patients in group B during the 12 month of follow up (p < 0.05). There was no significant difference in TG and HDL-CHOL plasma levels between group A and group B (p > 0.005). In group A the daily dose of CsA was significantly correlated with the mean blood levels of CsA at the 1st and 3rd months (r = 0.387, p = 0.005; r = 0.386, p = 0.006), respectively. In group A, the daily dose of CsA was significantly correlated with the mean serum TG levels during the 12 month of follow up (r = 0.420, p = 0.003). In group B, the daily dose of Tac was significantly correlated with the mean blood level of Tac (r = 0.335, p = 0.020) at the 1st month. No correlation was found between mean Tac blood levels and lipid parameters during the 12-month of follow up (p > 0.05). Significant positive correlation was observed between the CsA blood levels and LDL-CHOL levels (r = 0.338, p = 0.027) at the 3rd month. In the renal transplant patients with well functioning grafts, CsA therapy is associated with increased CHOL and LDL-CHOL ratio which represents an increased atherogenic risk tended to be associated with CsA. Serum LDL-CHOL levels may be effected by blood CsA levels.

The correlation of results of panel reactive antibody, identification, and single antigen beads in detection of anti-HLA antibodies: Istanbul Faculty of Medicine, tissue typing laboratory experience.

BACKGROUND: We have performed a retrospective analysis of anti-HLA class I MHC and class II MHC antibodies measured using a single antigen bead (SAB) assay and a panel reactive antibody (PRA) assay. MATERIAL AND METHODS: A group of 256 patients with end-stage renal disease (ESRD) was tested for anti-HLA antibodies in the tissue typing laboratory between 2017 and 2020. In the cohort, the serum samples of patients waiting for transplantation were tested. Both the PRA and SAB tests of these patients were analyzed using the Luminex (Immucor) method. The threshold of positivity was accepted as median fluorescence intensities (MFI) ≥1000 for PRA screening and MFI ≥750 for SAB screening. RESULTS: Overall, antibodies to HLA antigens were detected in 202 (78.9%) out of 256 patients in the PRA study. Antibodies against both class I/II antigens were detected only in 15.6% of these patients, whereas antibodies against only against class I HLA in 31.3% and only against class II HLA in 32.0%. By comparison, the SAB study found that 66.8% of patients were positive for HLA antigens. Furthermore, donor-specific antibodies (DSA) were detected in 52.0% of PRA-positive patients and 52.6% of SAB-positive patients. It was shown that 168 patients (83.2%) out of 202 PRA-positive patients were found to be SAB-positive. In addition, 51 patients negative in the SAB assay (94.4%) were also negative in the PRA assay. Statistical analysis established a significant correlation between the PRA and SAB positivity (p > 0.001). It was also shown that MFI ≥3000 PRA positivity for class I HLA antigens (p = 0.049) and MFI ≥5000 PRA positivity for class II antigens (p < 0.001) correlated with the SAB positivity in patients. CONCLUSION: Our results showed the importance of both PRA and SAB assays to define the status of sensitization in patients.

The association of HLA-DRB1 alleles and MBL2 gene variant in pediatric acute lymphoblastic leukemia patients.

INTRODUCTION: Epidemiologic studies on pediatric acute lymphoblastic leukemias (ALL) have been conducted to evaluate the possible risk factors including genetic, infectious and environmental factors with the objective of idenfying the etiology. Mannose-binding lectin 2 (MBL2) plays an important role in first-line immune defense. HLA DRB1 alleles play a role in presentation of peptides to T cells and in activation of the adaptive immune response. OBJECTIVE: In our study, we aimed to investigate both the MBL2 gene variant and HLA-DRB1 alleles in pediatric ALL patients. MATERIALS: In this study, 86 high-risk ALL patients and 100 controls were included. Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (PCR-RFLP) and PCR-sequence specific primer (SSP) methods were used for detection of polymorphism of the MBL2 and HLA-DRB1 alleles, respectively. RESULTS: The frequency of the MBL2 AB genotype was lower in female ALL patients, compared to male ALL patients (p = 0.034). An association was found between the MBL2 BB genotype and DRB1*07 and among patients with the MBL2 BB genotype; those who also carried the DRB1*07 and *04 alleles were significantly higher than those without the DRB1*07 and *04 alleles. (p = 0.048, p = 0.022, respectively). CONCLUSION: This is the first study suggesting that the MBL2 BB genotype in association with the DRB1*07 or co-inheritance of the HLA-DRB1*04 and HLA DRB1*07 may have an impact on the etiopathogenesis of the disease.

Correlation of Luminex-Based Single Antigen Based Results With Complement-Dependent Cytotoxicity Crossmatch and Flow Cytometry Crossmatch Results: A Single-Center Experience From Istanbul.

BACKGROUND: This study aimed to retrospectively investigate the correlation of mean Class I donor-specific antibody (DSA) intensity values detected in Luminex-based techniques with the results of complement-dependent cytotoxicity crossmatch (CDC-XM) and flow cytometry crossmatch (FC-XM) results. METHODS: A total of 335 patients with kidney failure and their living donors whose CDC-XM, FC-XM, and single antigen based (SAB) tests were studied between 2018 and 2020 for transplant preparation from living donor candidates were included in the study. Patients were divided into 4 groups according to their mean fluorescence intensity (MFI) values of SAB assay. RESULTS: Anti-HLA antibodies (class I and/or class II) were detected using SAB in 91.6% patients included in the study (MFI >1000). Class I DSA was positive in 34.8% of patients with anti-HLA antibodies. When CDC-XM and FC-XM results were evaluated in the 4 groups separated according to MFI values, 3 patients with DSA MFI <1000 had negative CDC-XM and T-B-FC-XM results. Of 32 patients with DSA-MFI between 1000 and 3000, 93.75% (n = 30) had T-B-FC-XM or CDC-XM-negative results, and 6.25% (n = 2) had B-FC-XM-positive results. The CDC-XM, T, and B-FC-XM were negative in all 17 patients with DSA-MFI between 3000 and 5000. Our results showed that MFI >5834 DSA values were significantly correlated with positive T-FC-XM (P < .001), and MFI >6016 values were significantly correlated with positive CDC-XM (P = .002). In addition, MFI values >5000 were associated with both CDC-XM and FC-XM in our study. CONCLUSIONS: The MFI values >5000 correlated with both CDC-XM and FC-XM.

Can serum soluble urokinase plasminogen activator receptor be an effective biomarker in comparing the inflammatory response between laparoscopic and open appendectomy?

Introduction: The inflammatory response after laparoscopy and laparotomy has been compared in studies in adults, but only a few studies have compared the immune response between laparoscopy and laparotomy in children. Aim: To compare open and laparoscopic appendectomies regarding a new biomarker, suPAR, to evaluate the inflammatory response. Material and methods: Patients between 3 and 17 years of age who were admitted to the pediatric surgery department and scheduled for appendectomy due to appendicitis were enrolled in the investigation. The patients were randomized to receive either laparoscopic (n = 20) or conventional open appendectomy (n = 20). The primary outcome was a change in preoperative and postoperative suPAR levels. The secondary outcomes were the white blood cell count, lymphocytes, neutrophils, platelets, C-reactive protein level, appendix diameter, symptoms, symptom duration, surgical complications, operative time, rescue analgesics, hospital stay, and family satisfaction. Results: The mean age of the patients undergoing laparoscopic appendectomy was 10.55 ±2.743 (3-17) years. The mean age of the patients undergoing open appendectomy was 11.40 ±3.515 (3-17) years. A statistically significant difference was found when the postoperative suPAR values between the two groups were compared (p = 0.048). The operative time and hospital stay in the laparoscopic group were significantly shorter than those in the open group (p = 0.001, p = 0.047). Conclusions: Laparoscopic appendectomy is associated with a shorter operative time, a shorter hospital stay, and a smaller inflammatory response caused by surgical stress than open appendectomy. suPAR is an effective marker for comparing postoperative inflammatory stress between open and closed appendectomies.

Quadratus Lumborum Block with Laparoscopic Assisted Catheter Placement Technique in Donor Nephrectomy: A Preliminary Report.

Quadratus lumborum block (QLB) is a new fascial plane block that may be helpful for laparoscopic surgeries. In this present study, we aim to evaluate the analgesic efficacy of QLB in laparoscopic living related donor nephrectomy (LLRDN) applied continuously via a catheter that was placed under laparoscopic vision by the surgeon. Following the approval of the Clinical Research Ethics Committee of Istanbul University, Istanbul Medical Faculty (2019/1552), 9 study (Group QLB) and 26 control (Group M) patients that underwent LLRDN were enrolled in this retrospective study. All donors underwent left nephrectomy via transperitoneal laparoscopic approach. An epidural catheter was placed between the QL and psoas major (PM) fascial plane intraoperatively by the surgeon under laparoscopic direct vision, and bupivacaine 0.25% 20 mL was injected through the catheter. After the operation, for group QLB, we used a continuous infusion of bupivacaine 0.1% 7 mL/h over 24 hours. Group M patients received intravenous morphine patient controlled analgesia for 24 hours, postoperatively. Pain scores, total morphine consumption, and complications during the first 24 hours after surgery were recorded. During the first postoperative 24 hours, morphine requirement decreased by more than 70% in Group QLB (Group QLB: 5.11 ± 1.16 mg vs Group M: 16.8 ± 7.1 mg) (P < .0001). Postoperative Numeric Rating Scale (NRS) values at the 45th minute and first hour were both significantly lower in Group QLB than Group M (P < .01). This preliminary report showed that QL catheter placement technique provides good postoperative analgesia in patients undergoing LLRDN. However, further randomized controlled studies with extended patient numbers are required to test the efficacy of the technic.

Can Direct-Acting Antiviral Treatment Change the Immunologic Risk Profile in Patients Infected with Hepatitis C Virus Who Are on the Cadaveric Waiting List?

BACKGROUND: In patients with hepatitis C virus (HCV) infection, the activation of the immune system by the virus or viral proteins leads to the production of numerous autoantibodies and clinical manifestations. The objectives of this study were to investigate the relationship between HCV and anti-HLA antibodies, as well as the effect of viremia on the antibody response and of direct-acting antivirals (DAAs) on anti-HLA antibody persistence in patients on the waiting list for a cadaveric kidney transplant. METHODS: A total of 395 patients from the cadaveric renal transplant waiting list were included in the study. The patients were grouped according to the presence of HCV infection, and patients with HCV positivity were further divided into a spontaneous clearance group and a persistent group. Anti-HLA antibodies were examined before and after treatment of the patients in the persistent group. The One Lambda Luminex method (Thermo Fisher Scientific, Waltham, MA, United States) was used to assess both HLA class I and II alleles and the anti-HLA antibody profile. RESULTS: Anti-HLA class I and II antibodies were detected in 48.2% and 55.1%, respectively, of the patients infected with HCV and in 21.8% and 20.4%, respectively, of the patients who were not infected. The level of anti-HLA A3, A11, B72, B52, Cw6, Cw16, DR3, and DQ4 antibodies was significantly higher in the patients infected with HCV. There was no statistically significant difference in class I and II antibody titration between the HCV-infected spontaneous clearance group and the persistent group (class I mean fluorescence intensity [MFI] ± SD: 13,583 ± 6224, 13,450 ± 9540, P = .808; Class II MFI ± SD: 13,000 ± 8673, 8440 ± 8302, P = .317, respectively). There was no significant difference in the class I and class II anti-HLA antibody profile and titration in the persistent group after treatment with DAAs (P > .05). CONCLUSIONS: The results of this study demonstrated that hepatitis C DAA treatment did not change the anti-HLA antibody profile and titration.

Comparing the Effects of Combined General/Epidural Anaesthesia and General Anaesthesia on Serum Cytokine Levels in Radical Cystectomy.

OBJECTIVE: Surgical stress combined with general anaesthesia (GA) suppresses the immune system and leads to cancer cell growth and premature metastasis in major oncological interventions. Epidural analgesia decreases the need for inhalation agents and opioids during surgery by suppressing sympathetic and neuroendocrine responses in the postoperative period. This study aimed to compare the effects of combined general/epidural anaesthesia (GEA)+patient-controlled epidural analgesia (PCEA) and GA+IV patient-controlled analgesia (PCA) on serum tumour necrosis factor-alpha TNF-α), interleukin-1 beta (IL-1ß) and interferon-gamma (IFN-γ) levels in patients undergoing radical cystectomy. METHODS: Sixty-five patients were enrolled in this prospective study. Patients were randomly enrolled to the GEA group, i.e., combined GEA+ PCEA (0.1% bupivacaine+1 µg mL-1 fentanyl), and the GA group, namely combined GA+IV PCA (0.03 mg mL-1 morphine). To evaluate the cytokine response, blood samples were collected at preoperative, postoperative 1st and 24th hours. RESULTS: There was no statistically significant difference in serum TNF-α, IL-1ß and IFN-γ levels between groups GA and GEA at preoperative and postoperative 1st hour and 24th hour. Total remifentanil consumption was significantly lower and length of hospital stay was significantly shorter in the GEA group than in the GA group (p<0.05). CONCLUSION: There is no difference between two anaesthesia methods in terms of serum cytokine levels; however, combined GEA+PCEA technique appeared to be superior to GA+IV PCA because of lower intraoperative narcotic analgesic consumption and shorter hospital stay.

TNF-α-308 G/A variant may be associated with bipolar disorder in a Turkish population

ABSTRACT Background: Tumor necrosis factor alpha (TNF-α) is a proinflammatory multifunctional cytokine produced by macrophages. A dysregulation of the immune system contribute to the pathogenesis of bipolar disorder (BD). In this study, we aimed to investigate the relationship between the TNF-α gene -308G/A promoter variant and the risk of BD. Methods: A total of 104 BD patients and 94 healthy controls were enrolled in the study. Genomic DNA was isolated and TNF-α -308G/A variant was analyzed using PCR-RFLP method. Results: TNF-α -308G/A variant GG genotype and G allele were more prevalent in BD patients compared to the controls (p = 0.002 and p = 0.017, respectively). The patients carrying GG genotype had a 5.927-fold higher risk of developing BD. Then, we divided patients into two groups as smokers and non-smokers. TNF-α -308G/A variant GA genotype was higher in non-smoker BD patients than smoker patients (p = 0.027). We found that TNF-α -308G/A AA genotype and A allele increased in smoker patients compared to non-smoker patients (p = 0.008, p = 0.002, respectively). Discussion: Our results provided evidence that TNF-α -308G/A variant may contribute to development of BD in a Turkish cohort. In addition, this variant plays a relevant role in the smoker status of BD.

Effect of monoamine oxidase B A644G variant on nicotine dependence and/or schizophrenia risk

Abstract Objectives Schizophrenia (Sch) is a severe and chronic mental illness. Smoking prevalence is higher in patients with Sch than general population. We aimed to investigate the effects of MAOB gene A644G variant on nicotine dependence (ND) and Sch+ND risk in Turkish population and to evaluate by bioinformatic analysis. Methods Present study included 161 individuals with ND, 223 patients with Sch+ND, and 96 non-smoker controls. MAOB A644G variant was analyzed using PCR-RFLP method. As the MAOB gene is located on the X chromosome, each gender was analysed separately. Results The total distributions of AA, AG and GG genotypes of MAOB gene A644G were 44.7%, 22.4% and 32.9% in the ND group, 45.3%, 25.1% and 29.6% in the Sch+ND group and, 44.8, 22.9% and 32.3% in non-smoker controls. No significant differences were observed between groups for the MAOB A644G genotype and allele frequencies when female group compared to male group (p > 0.05). Examination of disease associations of SNPs from each miRNA gene region in GWAS databases yielded results for aging, bipolar disorder, autoimmune, and neurological diseases. Discussion Our results indicate that the MAOB gene A644G variant is not associated with ND and/or Sch susceptibility in the Turkish population.

Long-Term Effects of Antibodies against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year after Renal Transplantation.

OBJECTIVE: In this study, we aimed to investigate the incidence, dynamics and profiles of human leukocyte antigen (HLA)-directed antibodies developed after transplantation and their impact on graft rejection and outcome in kidney recipients. STUDY DESIGN: Prospective follow-up study. MATERIAL AND METHODS: A total of 56 kidney recipients were monitored at 1(st), 6(th) and 12(th) months for the development of anti-HLA antibodies using bead based flow-cytometry assays (Flow PRA tests). RESULTS: In 21 (37.5%) patients, panel reactive antibodies (PRA) was positive after transplantation, however, in 35 (62.5%) patients PRA was found negative. Twelve (57.1%) patients with post-transplantation HLA-reactive antibodies [PRA (+)] and 8 (22.9%) patients with no detectable alloantibodies [PRA (-)] were developed allograft rejection (p=0.010). In the PRA positive patient group the rates of early period infection and delayed graft function (DGF) were higher than the PRA negative patient group. Serum creatinine levels of PRA positive group at 6. and 12. months after transplantation were significantly higher than the PRA negative group (p=0.015 and p=0.048, respectively). The rejection rates of patients who had class I and II HLA antibodies were significantly higher than the patients who had either class I or II HLA antibodies (p=0.011). Acute rejection rates were significantly higher in patients who had class I and II HLA antibodies at the first month (p=0.007). CONCLUSION: Higher occurrence of rejection episodes in PRA positive group may show the importance of anti-HLA antibody monitoring using Flow-PRA after renal transplantation as a prognostic marker in terms of graft survival.