A randomised comparison between Cobra PLA and classic laryngeal mask airway and laryngeal tube during mechanical ventilation for general anaesthesia

BACKGROUND: The aim of this study was to compare ventilation parameters during mechanical ventilation using Laryngeal Mask Airway (LMA), Laryngeal Tube (LT), and Peri-Laryngeal Airway Cobra (PLA).METHODS: In a prospective, randomised controlled trial, 90 patients undergoing general anaesthesia for elective surgery were divided into three subgroups. The settings of controlled ventilation were: oxygen 50%, air 50%, sevoflurane 1.5–2.0%, TV 7 mL kg–1, RR 10 breath min–1, inspiratory/expiratory ratio 1:2 and FGF 3 L min–1. The number of attempts, time taken to insert the device, airway pressure (peak airway pressure, plateau airway pressure), air leak (inspiratory and expiratory volume difference), and dynamic compliance were measured. The timepoints for collecting data were after successful insertion of the device, and after ten, 20, 30 and 50 mins of ventilation. The presence of visible blood traces, patients’ assessment of their throat soreness, dysphonia and dysphagia were noted postoperatively.RESULTS: The success rates at first insertion were 90% and 80% and 90%, while time for insertion was 5 sec and 21.94 sec and 5.24 sec in the Cobra PLA, LMA and LT groups respectively. Ventilation pressures during procedure were highest in the LT group, where compliance was lowest compared to the Cobra PLA and LMA groups. The air leak was similar in all the groups. 30% vs. 40% vs. 10% of devices had positive blood traces; 20% vs. 40% vs. 30% of patients suffered from a sore throat; and 30% vs. 30% and 30% of patients suffered from dysphagia in the Cobra PLA, LMA and LT groups respectively.CONCLUSION: The differences were small, but Cobra PLA seemed to be slightly superior in terms of the measured parameters.BACKGROUND: The aim of this study was to compare ventilation parameters during mechanical ventilation using Laryngeal Mask Airway (LMA), Laryngeal Tube (LT), and Peri-Laryngeal Airway Cobra (PLA).METHODS: In a prospective, randomised controlled trial, 90 patients undergoing general anaesthesia for elective surgery were divided into three subgroups. The settings of controlled ventilation were: oxygen 50%, air 50%, sevoflurane 1.5–2.0%, TV 7 mL kg–1, RR 10 breath min–1, inspiratory/expiratory ratio 1:2 and FGF 3 L min–1. The number of attempts, time taken to insert the device, airway pressure (peak airway pressure, plateau airway pressure), air leak (inspiratory and expiratory volume difference), and dynamic compliance were measured. The timepoints for collecting data were after successful insertion of the device, and after ten, 20, 30 and 50 mins of ventilation. The presence of visible blood traces, patients’ assessment of their throat soreness, dysphonia and dysphagia were noted postoperatively.RESULTS: The success rates at first insertion were 90% and 80% and 90%, while time for insertion was 5 sec and 21.94 sec and 5.24 sec in the Cobra PLA, LMA and LT groups respectively. Ventilation pressures during procedure were highest in the LT group, where compliance was lowest compared to the Cobra PLA and LMA groups. The air leak was similar in all the groups. 30% vs. 40% vs. 10% of devices had positive blood traces; 20% vs. 40% vs. 30% of patients suffered from a sore throat; and 30% vs. 30% and 30% of patients suffered from dysphagia in the Cobra PLA, LMA and LT groups respectively.CONCLUSION: The differences were small, but Cobra PLA seemed to be slightly superior in terms of the measured parameters.

Zmiany parametrów morfologicznych krwi w pierwszych dniach leczenia kwasicy ketonowej u dzieci z cukrzycą typu 1

Background. Diabetic ketoacidosis (DKA) is a life-threatening complication of newly diagnosed type 1 diabetes (T1DM) and is associated with severe dehydration. The aim of the study was to evaluate the changes in hematological parameters (RBC, Hct, Hb, MCV, PLT, WBC) and their correlations with acidosis level and dehydration during ketoacidosis treatment. Methods. The study group consisted of 262 children with newly diagnosed type 1 diabetes. Clinical data were collected from hospital discharge charts. Data considering hematological parameters were collected from two timepoints: first at admission and second up to 6 days since admission. Results. Ketoacidosis was present in 76 patients (29.01%). The DKA group had significantly higher values of baseline RBC (p = 0.0026), Hct (p = 0.0019), Hb (p = 0.0235), PLT (p = 0.0427) and WBC count (p < 0.0001) vs. patients without DKA. Interestingly, baseline MCV level was similar between the groups (p = 0.9869). During the first days of diabetes treatment, all hematological parameters such as RBC, Hct, Hb, PLT and WBC significantly decreased in both groups (all p values < 0.0001), while MCV significantly increased after treatment (p < 0.0001). However, the latter was evident only in no-DKA group. Changes in all hematological parameters correlated positively with pH (all R > 0.3 and all p values < 0.05) in DKA group but not in no-DKA group. However, weak, positive correlations at the margin of statistical significance with pH were observed for changes in PLT (p = 0.0609) and WBC (p = 0.0811) in no-DKA group. Conclusion. Monitoring dynamics of hematological parameters at T1DM diagnosis may be useful in esti­mating patients’ hydration status.Wstęp: Kwasica ketonowa (ang. DKA) jest zagrażającym życiu powikłaniem nowo rozpoznanej cukrzycy typu 1 (T1DM) wiążącym się z ciężkim odwodnieniem pacjenta. Cel: Celem pracy była ocena zmian parametrów morfologicznych krwi (RBC, Hct, Hb, MCV, PLT, WBC) i ich korelacji ze stopniem zakwaszenia oraz odwodnienia organizmu podczas leczenia kwasicy ketonowej. Metody: Grupa badana składała się z 262 dzieci z nowo zdiagnozowaną cukrzycą typu 1. Dane kliniczne zostały zebrane z kart wypisów ze szpitala. Dane dotyczące parametrów morfologicznych krwi zostały zebrane z dwóch punktów czasowych: pierwszego przy przyjęciu a drugiego do 6 dni od przyjęcia. Wyniki: Kwasica ketonowa występowała u 76 pacjentów (29,01%). Grupa DKA miała istotnie wyższe wartości wyjściowe RBC (p=0.0026), Hct (p=0,0019), Hb (p=0,0235), PLT (p=0,0427) i WBC (

Zmiany parametrów morfologicznych krwi w pierwszych dniach leczenia kwasicy ketonowej u dzieci z cukrzycą typu 1

Wstęp. Kwasica ketonowa (DKA) jest zagrażającym życiu powikłaniem nowo rozpoznanej cukrzycy typu 1 (T1DM) wiążącym się z ciężkim odwodnieniem chorego. Celem pracy była ocena zmian parametrów morfologicznych krwi [liczba erytrocytów (RBC), hematokryt (Hct), stężenie hemoglobiny (Hb), średnia objętość krwinki (MCV), liczba płytek krwi (PLT), liczba leukocytów (WBC)] i ich korelacji z ciężkością kwasicy oraz stopniem odwodnienia podczas leczenia kwasicy ketonowej. Metody. Grupa badana składała się z 262 dzieci z nowo rozpoznaną cukrzycą typu 1. Dane kliniczne uzyskano z kart wypisów ze szpitala. Dane dotyczące parame­trów morfologicznych krwi zostały zebrane z dwóch punktów czasowych: pierwszego przy przyjęciu, a drugiego — do 6 dni od przyjęcia do szpitala. Wyniki. Kwasica ketonowa występowała u 76 chorych (29,01%). W grupie DKA stwierdzono istotnie wyższe wartości wyjściowe RBC (p = 0,0026), Hct (p = 0,0019), Hb (p = 0,0235), PLT (p = 0,0427) i WBC (p < 0,0001) w porównaniu z pacjentami bez DKA. Co ciekawe, wyjściowe wartości MCV były podobne w obu grupach (p = 0,9869). W pierwszych dniach leczenia cukrzycy wszystkie parametry morfologiczne krwi, takie jak RBC, Hct, Hb, PLT i WBC, zmniejszyły się istotnie w obu gru­pach (wszystkie wartości p < 0,0001), natomiast warość MCV istotnie wzrosła po leczeniu tylko w grupie bez DKA. Zmiany wszystkich parametrów morfolo­gicznych krwi korelowały dodatnio z pH (wszystkie R > 0,3 i p < 0,05) tylko w grupie z DKA. Jednak w grupie bez DKA zaobserwowano słabą dodatnią korelację na pograniczu istotności statystycznej pomiędzy pH a zmianą PLT (p = 0,0609) oraz zmianą WBC (p = 0,0811). Wnioski. Monitorowanie zmian parametrów morfo­logicznych krwi u chorych z nowo rozpoznaną T1DM może być przydatne w ocenie ich stanu nawodnienia

Transcriptome Analysis of Cells Exposed to Actinomycin D and Nutlin-3a Reveals New Candidate p53-Target Genes and Indicates That CHIR-98014 Is an Important Inhibitor of p53 Activity

Co-treatment with actinomycin D and nutlin-3a (A + N) strongly activates p53. Previously we reported that CHIR-98014 (GSK-3 kinase inhibitor), acting in cells exposed to A + N, prevents activation of TREM2-an innate immunity and p53-regulated gene associated with Alzheimer’s disease. In order to find novel candidate p53-target genes and genes regulated by CHIR-98014, we performed RNA-Seq of control A549 cells and the cells exposed to A + N, A + N with CHIR-98014 or to CHIR-98014. We validated the data for selected genes using RT-PCR and/or Western blotting. Using CRISPR/Cas9 technology we generated p53-deficient cells. These tools enabled us to identify dozens of candidate p53-regulated genes. We confirmed that p53 participates in upregulation of BLNK, APOE and IRF1. BLNK assists in activation of immune cells, APOE codes for apolipoprotein associated with Alzheimer’s disease and IRF1 is activated by interferon gamma and regulates expression of antiviral genes. CHIR-98014 prevented or inhibited the upregulation of a fraction of genes stimulated by A + N. Downregulation of GSK-3 did not mimic the activity of CHIR-98014. Our data generate the hypothesis, that an unidentified kinase inhibited by CHIR-98014, participates in modification of p53 and enables it to activate a subset of its target genes, e.g., the ones associated with innate immunity

Elevated level of lysophosphatidic acid among patients with HNF1B mutations and its role in RCAD syndrome : a multiomic study

INTRODUCTION: Patients with hepatocyte nuclear factor-1 beta (HNF1B) mutations present a variable phenotype with two main symptoms: maturity onset diabetes of the young (MODY) and polycystic kidney disease (PKD). OBJECTIVES: Identification of serum metabolites specific for HNF1Bmut and evaluation of their role in disease pathogenesis. METHODS: We recruited patients with HNF1Bmut (N = 10), HNF1Amut (N = 10), PKD: non-dialyzed and dialyzed (N = 8 and N = 13); and healthy controls (N = 12). Serum fingerprinting was performed by LC-QTOF-MS. Selected metabolite was validated by ELISA (enzyme-linked immunosorbent assay) measurements and then biologically connected with HNF1B by in silico analysis. HepG2 were stimulated with lysophosphatidic acid (LPA) and HNF1B gene was knocked down (kd) by small interfering RNA. Transcriptomic analysis with microarrays and western blot measurements were performed. RESULTS: Serum levels of six metabolites including: arachidonic acid, hydroxyeicosatetraenoic acid, linoleamide and three LPA (18:1, 18:2 and 20:4), had AUC (the area under the curve) > 0.9 (HNF1Bmut vs comparative groups). The increased level of LPA was confirmed by ELISA measurements. In HepG2(HNF1Bkd) cells LPA stimulation lead to downregulation of many pathways associated with cell cycle, lipid metabolism, and upregulation of steroid hormone metabolism and Wnt signaling. Also, increased intracellular protein level of autotaxin was detected in the cells. GSK-3alpha/beta protein level and its phosphorylated ratio were differentially affected by LPA stimulation in HNF1Bkd and control cells. CONCLUSIONS: LPA is elevated in sera of patients with HNF1Bmut. LPA contributes to the pathogenesis of HNF1B-MODY by affecting Wnt/GSK-3 signaling. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11306-022-01873-z