The neuroprotective effect of mesenchymal stem cells in colistin-induced neurotoxicity.

Colistin is an effective antibiotic against multidrug-resistant gram-negative bacterial infections; however, neurotoxic effects are fundamental dose-limiting factors for this treatment. Stem cell therapy is a promising method for treating neuronal diseases. Multipotent mesenchymal stromal cells (MSC) represent a promising source for regenerative medicine. Identification of neuroprotective agents that can be co-administered with colistin has the potential to allow the clinical application of this essential drug. This study was conducted to assess the potential protective effects of MSC, against colistin-induced neurotoxicity, and the possible mechanisms underlying any effect. Forty adult female albino rats were randomly classified into four equal groups; the control group, the MSC-treated group (A single dose of 1 × 106/mL MSCs through the tail vein), the colistin-treated group (36 mg/kg/d colistin was given for 7 d) and the colistin and MSC treated group (36 mg/kg/d colistin was administered for 7 d, and 1 × 106/mL MSCs). Colistin administration significantly increased GFAP, NGF, Beclin-1, IL-6, and TNF-α immunreactivity intensity. MSC administration in colistin-treated rats partially restored each of these markers. Histopathological changes in brain tissues were also alleviated by MSC co-treatment. Our study reveals a critical role of inflammation, autophagy, and apoptosis in colistin-induced neurotoxicity and showed that they were markedly ameliorated by MSC co-administration. Therefore, MSC could represent a promising agent for prevention of colistin-induced neurotoxicity.

Does chest compression during cardiopulmonary resuscitation provide sufficient cerebral oxygenation?

Background/aim: Some of the patients suffering from cardiac arrest (CA) remain in a chronic unconscious state in intensive care units (ICUs). The primary aim of this study was to evaluate the efficacy of chest compression (CC) on cerebral oxygenation during cardiopulmonary resuscitation (CPR). As a secondary goal, we attempted to determine the effects of regional cerebral oxygen saturation (rSO2) values on consciousness and the survival rate using the Full Outline of Unresponsiveness (FOUR) scoring method. Materials and methods: This observational preliminary study was carried out with 20 patients with CA who were hospitalized in ICUs. The rSO2 values measured by near-infrared spectroscopy were recorded during CA. FOUR scoring was used to determine the neurological status, severity of disease, and degree of organ dysfunction in survivors. Results: Return of spontaneous circulation (ROSC) was gained in 8 (40%) of 20 patients. Maximum rSO2 values were higher in survivors than in nonsurvivors (P = 0.005). The mean FOUR score before CA was 11.50 ± 0.8 in survivors, whereas this value was 7.87 ± 0.7 for 1 week after ROSC (P < 0.0001). There was a significant positive correlation between the minimum and mean rSO2 values and the mean 1-week FOUR scores in survivors (r = 0.811, r = 0.771 and P = 0.015, P = 0.025, respectively). Conclusion: Our results suggest that the maximum rSO2 values affect ROSC while the minimum and mean rSO2 values affect the post-cardiac arrest neurological outcome.

The effect of mouth prop on endotracheal tube intracuff pressure in children during dental rehabilitation under general anaesthesia.

Although the endotracheal tube (ETT) cuff may be associated with tracheal morbidity, cuffed tubes may reduce the aspiration risk in oral procedures. Dentists must use a mouth prop to facilitate oral visualization and to protect the oral soft tissues during dental rehabilitation under general anaesthesia (DRGA). The aim of this study was to evaluate the effect of mouth prop on endotracheal tube intracuff pressure in children during DRGA. Two-hundred and three ASA I-II patients, <18 years of age (mean: 5.3 ± 2.4 years) were included in the prospective observational study whose comprehensive dental treatment was performed under general anaesthesia. Following the induction of general anaesthesia, placement of a cuffed endotracheal tube which was an appropriate size for children was fixed. The intracuff pressure was measured intermittently after the intubation (baseline) (T0), immediately after the mouth prop (T1), 30 min after the mouth prop (T2), after taking out the mouth prop (T3) and just before extubation (T4). The mean intracuff pressure was 28.3 ± 2.01 cm H2O at T0. The mean intracuff pressure significantly increased at T1 (30.8 ± 2.7) and T2 (29.6 ± 3.7) compared to T0 (P < 0.001). No significant differences were observed between the duration of the procedure and intracuff pressure or postoperative complications (P > 0.05). Cough, sore throat and nausea were observed in 4, 1 and 5 patients, respectively. Because a mouth prop may increase the intracuff pressure of ETT, strict measurement and readjustment of cuff pressures should be employed when used in children during DRGA.

Imaging findings and management of diaphragmatic mesothelial cysts in children.

BACKGROUND: Diaphragmatic mesothelial cysts are rare benign congenital lesions with typical imaging findings. OBJECTIVE: To present imaging and treatment outcomes in 30 children with diaphragmatic mesothelial cyst. MATERIALS AND METHODS: We conducted a retrospective chart review and recorded demographic data, imaging findings, treatment and US follow-up results, initial and final volume of the cysts and length of follow-up period for each case of diaphragmatic mesothelial cyst in a specialist hospital. RESULTS: The study included 30 children (16 girls, age range 1-17 years, mean age 7.9 years) diagnosed with diaphragmatic mesothelial cyst between January 2010 and December 2015. Imaging findings included thin-walled bilobulated or oval-shape cysts located between the diaphragm and right lobe of the liver. Treatment consisted of percutaneous drainage in 17 children and was successful in all. Cysts disappeared completely in 12 of these 17 children (70.5%, 95% confidence interval [CI] 44-90%). Mean volume reduction was 98%. No complication or mortality was seen. The other 13 children were followed with US without treatment. In 4 of these 13 children (30.8%, 95% CI 9-61%), cysts spontaneously decreased in size. No cyst increased in size. CONCLUSION: In children with typical imaging findings, percutaneous drainage appears safe and effective when treatment is deemed necessary.

Comparison of the myotoxic effects of levobupivacaine, bupivacaine, and ropivacaine: an electron microscopic study.

The aim of this study was to investigate the myotoxic effects of bupivacaine, ropivacaine, and levobupivacaine which were applied intramuscularly to rat skeletal muscle. Forty Wistar-Albino rats were divided into four groups. In the study, .5% bupivacaine (Group B), .5% ropivacaine (Group R), .5% levobupivacaine (Group L), or .9% normal saline (Group SF) was applied intramuscularly to the right gastrocnemius muscle of rats. The rats in each group were sacrificed on the second day after injection. Sections of muscle samples were stained with hematoxylin-eosin for light microscopic investigation and prepared for the evaluation of ultrastructural changes in the subcellular level with transmission electron microscopy. All three local anesthetic agents caused qualitatively similar skeletal muscle damage. The most observed muscle damage was in Group B, muscle damage of Group R was less than that of Group B, and the least damage was seen in Group L quantitatively. Electron microscopic examination of each group that caused cellular damage was qualitatively similar. The most subcellular damage was observed in the group receiving bupivacaine, less was seen in the ropivacaine group, and the least was observed in the levobupivacaine group. The results indicated that bupivacaine caused more myotoxic damage than the other two agents in the skeletal muscle of rats and that levobupivacaine caused less myotoxic damage than both bupivacaine and ropivacaine at the cell and tissue levels.

The effects of dexmedetomidine on early stage renal functions in pediatric patients undergoing cardiac angiography using non-ionic contrast media: a double-blind, randomized clinical trial.

BACKGROUND: In this study we aimed to investigate the effects of dexmedetomidine on early stage renal function in pediatric patients undergoing cardiac angiography. METHODS: 60 pediatric patients between 6 and 72 months of age undergoing cardiac angiography were included in the study. Patients were divided into two groups. The patients in both groups were administered 1 mg · kg(-1) ketamine, 1 mg · kg(-1) propofol as bolus and followed by 1 mg · kg(-1) · h(-1) ketamine and 50 µg · kg(-1) · min(-1) propofol infusion. Additionally, a loading dose of 1 µg · kg(-1) dexmedetomidine given over 10 min followed by 0.5 µg · kg(-1) · h(-1) dexmedetomidine infusion to patients in group D. The patients were evaluated for NGAL, creatinine, renin, endothelin-1, TAS and TOS blood levels before the procedure and 6th and 24th h after the procedure. pRIFLE criteria were used to define CIN and its incidence in the study. RESULTS: According to pRIFLE criteria contrast-induced acute kidney injury developed in 3 (10%) of the patients in group D and 11 (36.7%) of the patients in group C (P = 0.029, risk ratio = 0.27; 95% CI: 0.084-0.88). In patients who developed CIN, Endothelin-1 levels in groups C and D were significantly higher than baseline levels at 6th, 24th and 6th h, respectively. Renin levels were significantly increased at 6th and 24 th( ) h in patients with CIN in both groups. CONCLUSIONS: Dexmedetomidine may be beneficial in protecting against contrast-induced nephropathy during pediatric angiography by preventing the elevation of vasoconstrictor agents such as plasma endothelin-1 and renin.

Sedation for paediatric transcatheter atrial septal defect closure: comparison of two sedation protocols.

AIM: This study aimed to compare the effects of dexmedetomidine-propofol and ketamine-propofol sedation on haemodynamic stability, immobility, and recovery time in children who underwent transcatheter closure of atrial septal defects. METHODS: In all, 46 children scheduled for transcatheter closure of atrial septal defects (n = 46) were included. The dexmedetomidine-propofol group (n = 23) received dexmedetomidine (1 µg/kg) and propofol (1 mg/kg) for induction, followed by dexmedetomidine (0.5 µg/kg/hour) and propofol (100 µg/kg/minute) for maintenance. The ketamine-propofol group (n = 23) received ketamine (1 mg/kg) and propofol (1 mg/kg) for induction, followed by ketamine (1 mg/kg) and propofol (100 µg/kg/minute) for maintenance. RESULTS: In all, 11 patients in the dexmedetomidine group (47.8%) and one patient (4.3%) in the ketamine group demonstrated a decrease ≥20% from the baseline in mean arterial pressure (p = 0.01). Heart rates decreased ≥20% from the baseline value in 10 patients (43.4%) in the dexmedetomidine group and three patients (13%) in the ketamine group (p = 0.047). Heart rate values were observed to be lower in the dexmedetomidine group throughout the procedure after the first 10 minutes. The number of patients requiring additional propofol was higher in the dexmedetomidine group (p = 0.01). The recovery times were similar in the two groups--15.86 ± 6.50 minutes in the dexmedetomidine group and 19.65 ± 8.19 minutes in the ketamine group; p = 0.09. CONCLUSION: The ketamine-propofol combination was less likely to induce haemodynamic instability, with no significant change in recovery times, compared with the dexmedetomidine-propofol combination. The ketamine-propofol combination provided good conditions for the intervention.

Long-Term Immunogenicity and Safety of a Homologous Third Dose Booster Vaccination with TURKOVAC: Phase 2 Clinical Study Findings with 32-Week Post-Booster Follow-Up.

Vaccine-induced immunity wanes over time and warrants booster doses. We investigated the long-term (32 weeks) immunogenicity and safety of a third, homologous, open-label booster dose of TURKOVAC, administered 12 weeks after completion of the primary series in a randomized, controlled, double-blind, phase 2 study. Forty-two participants included in the analysis were evaluated for neutralizing antibodies (NAbs) (with microneutralization (MNT50) and focus reduction (FRNT50) tests), SARS-CoV-2 S1 RBD (Spike S1 Receptor Binding Domain), and whole SARS-CoV-2 (with ELISA) IgGs on the day of booster injection and at weeks 1, 2, 4, 8, 16, 24, and 32 thereafter. Antibody titers increased significantly from week 1 and remained higher than the pre-booster titers until at least week 4 (week 8 for whole SARS-CoV-2) (p < 0.05 for all). Seroconversion (titers ≥ 4-fold compared with pre-immune status) persisted 16 weeks (MNT50: 6-fold; FRNT50: 5.4-fold) for NAbs and 32 weeks for S1 RBD (7.9-fold) and whole SARS-CoV-2 (9.4-fold) IgGs. Nine participants (20.9%) tested positive for SARS-CoV-2 RT-PCR between weeks 8 and 32 of booster vaccination; none of them were hospitalized or died. These findings suggest that boosting with TURKOVAC can provide effective protection against COVID-19 for at least 8 weeks and reduce the severity of the disease.

The effect of playing music and mother's voice to children on sedation level and requirement during pediatric magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging examinations frequently cause anxiety and fear in children. The objective of this study was to investigate the effects of listening to music sound, the mother's voice, and sound isolation on the depth of sedation and need for sedatives in pediatric patients who would undergo MRI. METHODS: Ninety pediatric patients aged 3 to 12 years who were planned for imaging in the MRI unit were randomly assigned to isolation group (Group I), musical sound group (Group II), and mother's voice group (Group III). We evaluated patients' anxiety and sedation levels via the Observer's Assessment of Alertness/Sedation (OAA/S) RESULTS: Heart rate, oxygen saturation, OAA/S, and Ramsey scores during the procedure were not significantly different among the groups (p>0.05). The mean amount of propofol and total propofol consumption was statistically lower in the mother's voice group than in the isolation and music sound groups (p<0.001). Mean propofol amount and total propofol consumption were not significantly different in isolation and music sound groups (p>0.05). No difference was found between the groups regarding the time it took for the patients' Modified Aldrete score to reach 9 (p>0.05). CONCLUSIONS: In pediatric patients, listening to the mother's voice during MRI decreased the total sedative requirement consumed without increasing the depth of sedation.

Safety and immunogenicity of an inactivated whole virion SARS-CoV-2 vaccine, TURKOVAC, in healthy adults: Interim results from randomised, double-blind, placebo-controlled phase 1 and 2 trials.

BACKGROUND: Development of safe and effective vaccine options is crucial to the success of fight against COVID-19 pandemic. Herein, we report interim safety and immunogenicity findings of the phase 1&2 trials of ERUCoV-VAC, an inactivated whole virion SARS-CoV-2 vaccine. METHODS: Double-blind, randomised, single centre, phase 1 and 2 trials included SARS-CoV-2 seronegative healthy adults aged 18-55 years (18-64 in phase 2). All participants, except the first 4 in phase 1 who received ERUCoV-VAC 3 µg or 6 µg unblinded and monitored for 7 days for safety purposes, were assigned to receive two intramuscular doses of ERUCoV-VAC 3 µg or 6 µg (an inactivated vaccine containing alhydrogel as adjuvant) or placebo 21 days apart (28 days in phase 2) according to computer-generated randomisation schemes. Both trials are registered at ClinicalTrials.gov (phase 1, NCT04691947 and phase 2, NCT04824391). RESULTS: Forty-four participants (3 µg [n:17], 6 µg [n:17], placebo [n:10]) in phase 1 and 250 (3 µg [n:100], 6 µg [n:100], placebo [n:50]) in phase 2 received ≥1 dose. In phase 1 trial, 25 adverse events AEs (80 % mild) occured in 15 participants (34.1 %) until day 43. There was no dose-response relationship noted in safety events in ERUCoV-VAC recipients (p = 0.4905). Pain at injection site was the most common AE (9/44;20.5 %). Both doses of ERUCoV-VAC 3 µg and 6 µg groups were comparable in inducing SARS-CoV-2 wild-type neutralising antibody (MNT50): GMTs (95 %CI) were 8.3 (6.4-10.3) vs. 8.6 (7.0-10.2) at day 43 (p = 0.7357) and 9.7 (6.0-13.4) vs. 10.8 (8.8-12.8) at day 60 (p = 0.8644), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wild-type neutralising antibody GMTs (95 %CI) were 8.4 (6.3-10.5) vs. 9.0 (7.2-10.8) at day 43 (p = 0.5393) and 11.0 (7.0-14.9) vs. 12.3 (10.3-14.5) at day 60 (p = 0.8578). Neutralising antibody seroconversion rates (95 %CI) were 86.7 % (59.5-98.3) vs 94.1 % (71.3-99.8) at day 43 (p = 0.8727) and 92.8 % (66.1-99.8) vs. 100 % (79.4-100.0) at day 60 (p = 0.8873), in ERUCoV-VAC 3 µg and 6 µg groups, respectively. In phase 2 trial, 268 AEs, (67.2 % moderate in severity) occured in 153 (61.2 %) participants. The most common local and systemic AEs were pain at injection site (23 events in 21 [8.4 %] subjects) and headache (56 events in 47 [18.8 %] subjects), respectively. Pain at injection site was the only AE with a significantly higher frequency in the ERUCoV-VAC groups than in the placebo arm in the phase 2 study (p = 0.0322). ERUCoV-VAC groups were comparable in frequency of AEs (p = 0.4587). ERUCoV-VAC 3 µg and 6 µg groups were comparable neutralising antibody (MNT50): GMTs (95 %CI) were 30.0 (37.9-22.0) vs. 34.9 (47.6-22.1) at day 43 (p = 0.0666) and 34.2 (23.8-44.5) and 39.6 (22.7-58.0) at day 60, (p = 0.2166), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wildtype neutralising antibody GMTs were 28.9 (20.0-37.7) and 30.1 (18.5-41.6) at day 43 (p = 0.3366) and 34.2 (23.8-44.5) and 39.6 (22.7-58.0) at day 60 (p = 0.8777). Neutralising antibody seroconversion rates (95 %CI) were 95.7 % (91.4-99.8) vs. 98.9 % (96.9-100.0) at day 43 (p = 0.8710) and 96.6 % (92.8-100.0) vs 98.9 % (96.7-100.0) at day 60 (p = 0.9129) in ERUCoV-VAC 3 µg and 6 µg groups, respectively. CONCLUSIONS: Two-dose regimens of ERUCoV-VAC 3 µg and 6 µg 28 days both had an acceptable safety and tolerability profile and elicited comparable neutralising antibody responses and seroconversion rates exceeding 95 % at day 43 and 60 after the first vaccination. Data availability Data will be made available on request.