Dendritic/antigen presenting cell mediated provision of T-cell receptor gamma delta (TCRγδ) expressing cells contributes to improving antileukemic reactions ex vivo

T-cell receptor gamma delta (TCRγδ) expressing T-cells are known to mediate an MHC-independent immune response and could therefore qualify for immune therapies. We examined the influence of dendritic cells(DC)/antigen presenting cell (APC) generated from blast-containing whole blood (WB) samples from AML and MDS patients on the provision of (leukemia-specific) TCRγδ expressing T-cells after mixed lymphocyte culture (MLC). Kit-M (granulocyte-macrophage colony-stimulating factor (GM-CSF) + prostaglandin E1 (PGE1)) or Kit-I (GM-CSF + Picibanil) were used to generate leukemia derived APC/DC (DCleu)from WB, which were subsequently used to stimulate T-cell enriched MLC. Immune cell composition and functionality were analysed using degranulation- (DEG), intracellular cytokine- (INTCYT) and cytotoxicity fluorolysis- (CTX) assays. Flow cytometry was used for cell quantification. We found increased frequencies of APCs/DCs and their subtypes after Kit-treatment of healthy and patients´ WB compared to control, as well as an increased stimulation and activation of several types of immune reactive cells after MLC. Higher frequencies of TCRγδ expressing leukemia-specific degranulation and intracellularly cytokine producing T-cells were found. The effect of Kit-M-treatment on frequencies of TCRγδ expressing cells and their degranulation could be correlated with the Kit-M-mediated blast lysis compared to control. We also found higher frequencies of TCRγδ expressing T-cells in AML patients´ samples with an achieved remission (compared to blast persistence) after induction chemotherapy. This might point to APC/DC-mediated effects resulting in the provision of leukemia-specific TCRγδ expressing T-cells: Moreover a quantification of TCRγδ expressing T-cells might contribute to predict prognosis of AML/MDS patients

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The Effect of High-Dose Insulin Analog Initiation Therapy on Lipid Peroxidation Products and Oxidative Stress Markers in Type 2 Diabetic Patients

Effect of high-dose insulin analog initiation therapy was evaluated on lipid peroxidation and oxidative stress markers in type 2 diabetes mellitus (T2DM). Twenty-four T2DM patients with HbA1c levels above 10% despite ongoing therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs. Glycemic profiles were determined over 72 hours by Continuous Glucose Monitoring System (CGMS), and blood/urine samples were collected at 24 and 72 hours. Insulin analog plus metformin treatment significantly reduced glucose variability. Plasma and urine lipid peroxidation were markedly decreased following insulin analog plus metformin treatment. No correlation existed between glucose variability and levels of plasma and urine oxidative stress markers. Likewise, changes in mean blood glucose from baseline to end point showed no significant correlation with changes in markers of oxidative stress. On the contrary, decreased levels of oxidative stress markers following treatment with insulin analogs were significantly correlated with mean blood glucose levels. In conclusion, insulin plus metformin resulted in a significant reduction in oxidative stress markers compared with oral hypoglycemic agents alone. Data from this study suggests that insulin analogs irrespective of changes in blood glucose exert inhibitory effects on free radical formation

The Effect of Distance Education Play Activities on the Motor Skills of Children with Down Syndrome

This study aimed to investigate the effect of an adapted play activities module on the motor skills of children with Down Syndrome (DS) through distance education. The participants were twenty children (10 boys and 10 girls), aged 4-7 years, with DS, and living in Denizli. The average age of children with DS was 5.25 +/- 1.02 years. In the study, the activity program consisting of games and exercises were adapted from the MEB Play Activities Module and was applied for 60 minutes, 2 days a week for 12 weeks through distance education by forming 2 different study groups. Before and after the adapted exercise program, the pretest and posttest motor skill measurements of the children were assessed through the Bruininks-Oseretsky Motor Competence Test Short Form (BOT-2 SF). There was no significant difference between the mean scores of all subtests and total scores of the BOT-2 SF in boys and girls with DS (p>0.05). However, in terms of age variable, there was a significant difference in favor of children with DS in the 6-7 age group in BOT-2 SF total scores and fine motor accuracy, dexterity and strength subtests (p0.05). In the study, a significant difference was found between the pre-test and post-test total and sub -test scores of the BOT-2 SF of children with DS (p0.05). The results of the study showed that the activity program consisting of games and exercises given through distance education improved the motor skills of children with DS

Clinical indicators that influence a clinician’s decision to start L-thyroxine treatment in prematurity with transient hypothyroxinemia

Abstract Background Transient hypothyroxinemia of prematurity (THOP) is defined as a low level of circulating thyroxine (T4), despite low or normal thyroid-stimulating hormone (TSH) levels. Aims: We aimed to evaluate the incidence of THOP, the clinical and laboratory findings of preterm infants with this condition and the levothyroxine (L-T4) treatment. Methods Preterm infants (n = 181) delivered at 24–34 weeks of gestation were evaluated by their thyroid function tests that were performed between the 10th and 20th days of postnatal life and interpreted according to the gestational age (GA) references. Clinical and laboratory characteristics of the patients with THOP and normal thyroid function tests were compared. Patients with THOP and treated with L-T4 were compared with the ones who were not regarding laboratory, and clinical characteristics. Results Incidence of hypothyroxinemia of prematurity was 45.8% (n = 83). Euthyroidism, primary hypothyroidism, and subclinical hypothyroidism were diagnosed in 47.5% (n = 86), 5% (n = 9) and 1.7% (n = 3) of the patients, respectively. Mean birth weight (BW) and GA were significantly lower in the hypothyroxinemia group than in the euthyroid group (p < 0.001). L-T4 was started in 43% (n = 36) of the patients with THOP. Treatment initiation rate was 44.4% (n = 16) in 24–27 wk, 41.6% (n = 15) in 28–30 wk, and 13.8% (n = 5) in 31–34 wk. As the GA increased, the incidence of THOP and the rate of treatment initiation decreased (p < 0.001). The lowest free thyroxine (FT4) cut-off value was 0.72 ng/dl in the treated group. In addition, incidences of vancomycin + amikacin, caffeine, dopamine treatments, RDS, IVH, BPD, central catheter, FFP transfusion, and ventilator support were higher in the treated group (P < 0.05). Conclusion This study revealed that prevalence of THOP increased as the GA and BW decreased. As the GA decreased, THOP patients requiring L-T4 treatment increased. Additionally, association with comorbid diseases increased the requirement of treatment

The Correlation of Cord Arterial Blood Gas Analysis Results and Apgar Scores in Term Infants Without Fetal Distress

Objective: This study aimed to evaluate the necessity of cord arterial blood gas analysis in cases without fetal distress and normal Apgar score