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Background: Immune paralysis can be defined as a hypoinflammatory state associated with the incapacity of the immune system to release proinflammatory mediators despite the clearance of pathogens by antimicrobials. Persistent immune paralysis leads to failure to eradicate primary infections with a substantial increase in the risk of multiorgan dysfunction and mortality. The state of immune paralysis is caused mainly by the diminished ability of monocytes to release proinflammatory cytokines in response to endotoxin. This phenomenon is known as endotoxin tolerance. This study aimed to assess the role of dexmedetomidine in modifying immune paralysis in septic shock patients., Methods: Twenty-four patients with septic shock were randomized into two groups of 12 patients. A continuous intravenous infusion of dexmedetomidine started at 0.15 µg kg -1  hr -1 and adjusted by 0.15 µg kg -1  h -1 to a maximum of 0.75 µg kg -1  h -1 (10 ml h -1 ), while midazolam was started at 1 mg h -1 (2 mL hr -1 ) and adjusted by 1 mg h -1 to a maximum of 5 mg h -1 (10 mL h -1 ). All infusions were adjusted by increments of 2 mL/hr -1 to maintain blinding. Serum levels of CD42a+/CD14+, HLADR+/CD14+, CRP, IL-6, IL-10 and TNF-α were measured at baseline (T1), 12 h (T2), and 24 h (T3)., Results: Treatment with dexmedetomidine yielded no significant difference in CD42a+/CD14+, HLADR+/CD14, CD24b-MFI, HLADR-MFI, IL6 and TREM1 at all time points when compared with midazolam treatment. There was no significant difference in TLR levels between the two groups. Cardiac output in the dexmedetomidine group showed a significant decrease at 6, 12 and 24 h (P = 0.033, 0.021, and 0.005, respectively) compared with that in the midazolam group., Conclusion: Our results indicated that dexmedetomidine did not affect CD42a+/CD14+ and HLA-DR+/CD14+ expression in septic patients. Furthermore, cytokine production and inflammatory biomarkers did not change with dexmedetomidine infusion. Trial registration Clinical trial.gov registry (NCT03989609) on June 14, 2019, https://register., Clinicaltrials: gov ., (© 2023. European Society of Intensive Care Medicine and Springer Nature Switzerland AG.)

Background: Noninvasive measurement of blood hemoglobin could save time and decrease the risk of anemia and infection. The accuracy of CO-oximetry-derived noninvasive hemoglobin (Sp-Hb) had been evaluated in pediatric population; however, its accuracy in children with congenital heart disease has not been studied till date. We evaluated the accuracy of Sp-Hb in relation to laboratory-measured hemoglobin (Lab-Hb) in children with congenital heart disease., Methods: This prospective observational study included children with congenital heart disease undergoing procedural intervention. Sp-Hb measurements were obtained using Radical-7 Masimo pulse CO-oximeter and were compared against simultaneous Lab-Hb measurements obtained from the arterial line. Children were divided in cyanotic and acyanotic, and separate analysis was performed for each group. The values of both measurements were analyzed using Spearman's correlation coefficient and Bland-Altman analysis. Correlation was performed between Sp-Hb and Lab-Hb bias and each of arterial oxygen saturation and perfusion index., Results: One-hundred and eleven pairs of readings were obtained from 65 children. The median (quartiles) age and weight of the children were 1 (1.2-4) years and 11 (8-17) kg, respectively. There was moderate correlation between Lab-Hb and Sp-Hb with a correlation coefficient (95% confidence interval [CI]) of 0.75 (0.63-0.83) in acyanotic children and 0.62 (0.37-0.79) in cyanotic children. The mean bias (95% limits of agreements) was -0.4 g/dL (-2.4 to 1.6 g/dL) and 1 g/dL (-2.7 to 4.6 g/dL) in acyanotic and cyanotic children, respectively. The mean bias between Sp-Hb and Lab-Hb showed a weak negative correlation with oxygen saturation (r [95% CI]): (-0.36 [-0.51--0.18]), and a weak positive correlation with the perfusion index (r [95% CI]): (0.19 [0.01-0.37])., Conclusion: The large bias and the wide limits of agreement between Sp-Hb and Lab-Hb denote that Masimo-derived Sp-Hb is not accurate in children with congenital heart disease especially in the cyanotic group; the error in Sp-Hb increases when oxygen saturation decreases., (© 2020 John Wiley & Sons Ltd.)

In continuation of our previous work on the design and synthesis of topoisomerase II (Topo II) inhibitors and DNA intercalators, a new series of quinoxaline derivatives were designed and synthesized. The synthesized compounds were evaluated for their cytotoxic activities against a panel of three cancer cell lines (Hep G-2, Hep-2, and Caco-2). Compounds 18b, 19b, 23, 25b, and 26 showed strong potencies against all tested cell lines with IC 50 values ranging from 0.26 ± 0.1 to 2.91 ± 0.1 µM, comparable with those of doxorubicin (IC 50 values ranging from 0.65 ± 0.1 to 0.81 ± 0.1 µM). The most active compounds were further evaluated for their Topo II inhibitory activities and DNA intercalating affinities. Compounds 19b and 19c exhibited high activities against Topo II (IC 50 = 0.97 ± 0.1 and 1.10 ± 0.1 µM, respectively) and bound the DNA at concentrations of 43.51 ± 2.0 and 49.11 ± 1.8 µM, respectively, whereas compound 28b exhibited a significant affinity to bind the DNA with an IC 50 value of 37.06 ± 1.8 µM. Moreover, apoptosis and cell-cycle tests of the most promising compound 19b were carried out. It was found that 19b can significantly induce apoptosis in Hep G-2 cells. It has revealed cell-cycle arrest at the G2/M phase. Moreover, compound 19b downregulated the Bcl-2 levels, indicating its potential to enhance apoptosis. Furthermore, molecular docking studies were carried out against the DNA-Topo II complex to examine the binding patterns of the synthesized compounds., (© 2019 Deutsche Pharmazeutische Gesellschaft.)

Deregulation of many kinases is directly linked to cancer development and the tyrosine kinase family is one of the most important targets in current cancer therapy regimens. In this study, we have designed and synthesized a series of thieno[2,3-d]pyrimidine derivatives as an EGFR and HER2 tyrosine kinase inhibitors. All the synthesized compounds were evaluated in vitro for their inhibitory activities against EGFR WT ; and the most active compounds that showed promising IC 50 values against EGFR WT were tested in vitro for their inhibitory activities against mutant EGFR T790M and HER2 kinases. Moreover, the antitumor activities of these compounds were tested against four cancer cell lines (HepG2, HCT-116, MCF-7 and A431). Compounds 13g, 13h and 13k exhibited the highest activities against the examined cell lines with IC 50 values ranging from 7.592 ± 0.32 to 16.006 ± 0.58 µM comparable to that of erlotinib (IC 50 ranging from 4.99 ± 0.09 to 13.914 ± 0.36 µM). Furthermore, the most potent antitumor agent (13k) was selected for further studies to determine its effect on the cell cycle progression and apoptosis in MCF-7 cell line. The results indicated that this compound arrests G 2 /M phase of the cell cycle and it is a good apoptotic agent. Finally, molecular docking studies showed a good binding pattern of the synthesized compounds with the prospective target, EGFR WT and EGFR T790M ., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Caudal block is the most commonly used regional anesthetic technique in pediatric surgeries; different additives have been used for better and safer outcome., Aim: The aim of this study is to compare the combination of dexamethasone and dexmedetomidine as adjuvants to bupivacaine versus using each agent solely with bupivacaine in pediatric caudal block as regards their efficiency in pain relief (the duration of postoperative analgesia, first time to request analgesia, and modified objective pain score [MOPS])., Study Design: This was a prospective, double-blinded, randomized study., Patients and Methods: Patients and Methods: Sixty-three children scheduled for hypospadias surgery wererandomized into three groupsaccording to the adjuvant drug added to caudal bupivacaine : Group I (n = 21): dexamethasone 0.1 mg/kg + 0.5 mg/kg bupivacaine 0.25%, Group II (n = 21): dexmedetomidine0.01 μg/kg + 0.5 mg/kg bupivacaine 0.25% and Group III (n = 21): dexamethasone 0.1 mg/kg + dexmedetomidine 0.01 μg/kg + 0.5 mg/kgbupivacaine 0.25%. Intraoperative and postoperative hemodynamics were recorded. In postoperative anesthesia care unit and then the ward, MOPS and sedation score were recorded at 30 min and 1, 2, 3, 6 and 12 h. Further, the time of first analgesic request and side effects were recorded., Statistical Analysis: Categorical data were presented as frequencies (%) and analyzed using Chi-square test. Continuous data were presented as mean (standard deviation) and median (quartiles). Continuous data were analyzed using one-way analysis of variance for single measures and two-way mixed model for repeated measures. Kaplan-Meier analysis was performed for the duration of analgesia., Results: In Group III, MOPS was lower than Groups I and II at the study times. Further, Group III had prolonged time for first request of analgesic. Sedation scores were prolonged in Group III and Group II than in Group I. There was a reduction in heart rates in Group III more than Group I and Group II but with no significant difference. However, there was a significant reduction in mean arterial blood pressure 30 min intraoperatively and postoperatively in Group III as compared to Groups I and II., Conclusion: The addition of combined dexmedetomidine at a dose of 1 μg/kg and dexamethasone 0.1 mg/kg to caudal bupivacaine seemed to be an attractive alternative to each drug if used alone with more prolonged analgesia and almost no adverse effects., Competing Interests: There are no conflicts of interest.