Risk factors associated with prolonged intensive care unit stay following surgery for total anomalous pulmonary venous connection: a retrospective study.

BACKGROUND: Prolonged intensive care unit (ICU) stays consume medical resources and increase medical costs. This study identified risk factors associated with prolonged postoperative intensive care unit (ICU) stay in children with total anomalous pulmonary venous connection (TAPVC). METHODS: The medical records of 85 patients who underwent surgical repair of TAPVC were retrospectively analyzed. The patients were divided into prolonged-stay and standard-stay groups. The prolonged stay group included all patients who exceeded the 75th percentile of the ICU stay duration, and the standard stay group included all remaining patients. The effects of patient variables on ICU stay duration were investigated using univariate and logistic regression analyses. RESULTS: Patient median age was 41 (18-103) days, and median weight was 3.80 (3.30-5.35) kg.Postoperative duration of ICU stay was 11-68 days in the prolonged stay group (n = 23) and 2-10 days in the standard stay group (n = 62). Lower preoperative pulse oximetry saturation (SpO2), higher intraoperative plasma lactate levels, and prolonged postoperative mechanical ventilation were independent risk factors for prolonged ICU stay. Preoperative SpO2 < 88.5%, highest plasma lactate value > 4.15 mmol/L, and postoperative mechanical ventilation duration was longer than 53.5 h, were associated with increased risk of prolonged ICU stay. Young age, low body weight, subcardiac type, need for vasoactive drug support, emergency surgery, long anesthesia time, low SpO2 after anesthesia induction, long cardiopulmonary bypass (CPB) and aortic clamp times, high lactate level, low temperature, large volume of ultrafiltration during CPB, large amounts of chest drainage, large red blood cells (RBCs) and plasma transfusion, and postoperative cardiac dysfunction may be associated with prolonged ICU stay. CONCLUSIONS: Lower preoperative SpO2, higher intraoperative plasma lactate levels, and prolonged postoperative mechanical ventilation were independent risk factors for prolonged ICU stay in children with TAPVC. When SpO2 was lower than 88.5%, the highest plasma lactate value was more than 4.15 mmol/L, and the postoperative mechanical ventilator duration was longer than 53.5 h, the risk of prolonged ICU stay increased. Improved clinical management, including early diagnosis and timely surgical intervention to reduce hypoxia time and protect intraoperative cardiac function, may reduce ICU stay time.

Application of laryngeal mask airway anesthesia with preserved spontaneous breathing in children undergoing video-assisted thoracic surgery.

Purpose: To investigate the feasibility and safety of non-intubated general anesthesia with spontaneous breathing combined with paravertebral nerve blocks (PVNB) in young children undergoing video-assisted thoracic surgery (VATS) and to determine its significance for rapid recovery after pediatric thoracic surgery. Methods: The data of 46 children aged 6-36 months with an American Society of Anesthesiologists status of I-II who underwent elective VATS under general anesthesia were retrospectively analyzed. Of these patients, 25 underwent non-intubated general anesthesia with spontaneous breathing combined with PVNB (non-intubation group), and 21 received conventional intubated general anesthesia combined with local infiltration anesthesia (intubation group). The following perioperative parameters were compared between the two groups: heart rate (HR), mean arterial pressure, saturation of pulse oximetry (SpO2), partial pressure end-tidal carbon dioxide, time from the completion of the operation to extubation or removing laryngeal masks, time to first feeding after the operation, length of postoperative in-hospital stay, incidence of postoperative complications, and hospitalization expenses. Results: The operations were completed successfully in both groups. When the non-intubation group was compared with the intubation group, the minimal SpO2 level during the surgery was higher (93% vs. 88%, P < 0.001), which might indicate better oxygenation. There was no significant difference of the duration of surgery and intraoperative blood loss between two groups. Compared to the intubation group, the duration of anesthesia (P = 0.027), time from the completion of the operation to extubation (P < 0.001), time to the first feeding after surgery (P < 0.001), and length of postoperative in-hospital stay (P < 0.001) were significantly reduced in the non-intubation group. The incidence of postoperative complications was not significantly different. Conclusions: Non-intubated general anesthesia with spontaneous breathing combined with PVNB is safe and feasible in young children undergoing VATS and can promote rapid recovery in young children undergoing thoracoscopic surgery.

Aberrant serotonergic signaling contributes to the hyperexcitability of CA1 pyramidal neurons in a mouse model of Alzheimer's disease.

Hyperactivity of pyramidal neurons (PNs) in CA1 is an early event in Alzheimer's disease. However, factors accounting for the hyperactivity of CA1 PNs remain to be completely investigated. In the present study, we report that the serotonergic signaling is abnormal in the hippocampus of hAPP-J20 mice. Interestingly, chemogenetic activation of serotonin (5-hydroxytryptamine; 5-HT) neurons in the median raphe nucleus (MRN) attenuates the activity of CA1 PNs in hAPP-J20 mice by regulating the intrinsic properties or inhibitory synaptic transmission of CA1 PNs through 5-HT3aR and/or 5-HT1aR. Furthermore, activating MRN 5-HT neurons improves memory in hAPP-J20 mice, and this effect is mediated by 5-HT3aR and 5-HT1aR. Direct activation of 5-HT3aR and 5-HT1aR with their selective agonists also improves the memory of hAPP-J20 mice. Together, we identify the impaired 5-HT/5-HT3aR and/or 5-HT/5-HT1aR signaling as pathways contributing to the hyperexcitability of CA1 PNs and the impaired cognition in hAPP-J20 mice.

Modulating adult neurogenesis affects synaptic plasticity and cognitive functions in mouse models of Alzheimer's disease.

New neurons are abnormal in the adult hippocampus of Alzheimer's disease (AD) mouse models. The effects of modulating adult neurogenesis on AD pathogenesis differ from study to study. We reported recently that ablation of adult neural stem cells (aNSCs) was associated with improved memory in AD models. Here, we found that long-term potentiation (LTP) was improved in the hippocampus of APP/PS1 mice after ablation of aNSCs. This effect was confirmed in hAPP-J20 mice, a second AD mouse model. On the other hand, we found that exposure to enriched environment (EE) dramatically increased the number of DCX+ neurons, promoted dendritic growth, and affected the location of newborn neurons in the dentate gyrus of APP/PS1 mice, and EE exposure significantly ameliorated memory deficits in APP/PS1 mice. Together, our data suggest that both inhibiting abnormal adult neurogenesis and enhancing healthy adult neurogenesis could be beneficial for AD, and they are not mutually exclusive.

Ablating Adult Neural Stem Cells Improves Synaptic and Cognitive Functions in Alzheimer Models.

Adult neurogenesis is impaired in the hippocampus of patients with Alzheimer disease (AD) as well as AD models. However, it is far from clear how modulating adult neurogenesis affects AD neuropathology. We confirm that adult hippocampal neurogenesis is impaired in two AD models. Surprisingly, however, cognitive functions are improved in AD models after ablating adult neural stem cells (aNSCs). Ablation of aNSCs does not affect the levels of amyloid ß but restores the normal synaptic transmission in the dentate gyrus (DG) granule cells of AD models. Furthermore, calbindin depletion in the DG of AD mice is ameliorated after aNSC ablation, and knocking down calbindin abolishes the effects of aNSC ablation on synaptic and cognitive functions of AD mice. Together, our data suggest that cognitive functions of AD mice are improved after aNSC ablation, which is associated with the restoration of synaptic transmission in the DG granule cells with calbindin as an important mediator.

Effect of nalbuphine on rocuronium injection pain.

Objective: Rocuronium-associated intravenous injection pain occurs frequently in children during induction of anesthesia. The aim of this study was to systematically evaluate the benefits of nalbuphine in patients with rocuronium-associated injection pain. Methods: Ninety children undergoing tonsillectomy and adenoidectomy in our hospital between October 2019 and September 2020 were randomly divided into the following groups, with 30 patients per group: control group (group C), lidocaine group (group L), and nalbuphine group (group N). Routine 0.1 mg/kg midazolam and 2 mg/kg propofol were injected intravenously. After sedation, children in group C, group L, and group N were administered an intravenous injection of saline, lidocaine (10 mg/mL), or nalbuphine hydrochloride (2 mg/mL), respectively, at a dosage of 0.1 mL/kg. Intravenous injection of rocuronium stock solution (0.6 mg/kg) was administered 2 minutes later. Pain was evaluated using Ambeshs 4-pointscale. The incidence of rocuronium injection pain was compared among the three groups, and postoperative adverse reactions, such as drowsiness, bradycardia, hypotension, and respiratory depression, were evaluated. Results: The incidence of injection pain among children in group N was significantly lower than that in group C and group L (p<0.05). The incidence of drowsiness in group N was significantly higher than that in the other groups (p<0.05). The incidences of hypotension, bradycardia, and respiratory depression were not significantly different among the three groups (p>0.05). Conclusions: Intravenous nalbuphine during induction of anesthesia effectively prevented rocuronium-associated injection pain in children. Drowsiness is a complication.

Recommendation about the perioperative prevention of infection to healthcare workers and the anesthesia management of children with SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely and persistently over 100 countries. New challenges have occurred in the perioperative management of airway and anesthesia in children diagnosed with SARS-CoV-2 infection. According to current publications and to our own experiences in anesthesia management for cases with SARS-CoV-2 suspected, we reviewed concerns about the perioperative prevention of SARS-CoV-2 to medical staff and the anesthesia strategy to the patient.

Effect of inguinal hernia on the thickness and blood flow of spermatic cord in boys.

Objective: To evaluate the effect of inguinal hernia (IH) on the spermatic cord using spermatic cord ultrasonography (SCU). Methods: From January 2016 to January 2017, boys with IH who received SCU at the start of open herniorrhaphy (OH) were enrolled in this study. The age and weight at SCU, width of the spermatic cord (SC-W), peak systolic velocity (PSV) in the spermatic artery (SA-PSV) and velocity in the pampiniform plexus (PP-V), and the interval between the initial and the second OH in boys with metachronous inguinal hernia (MIH) were recorded, and the relationship among them was studied. Boys with unilateral IH comprised the IH group, and boys with MIH comprised the MIH group. Boys with polydactylism served as the control. One-way analysis of variance tested the differences among groups. Spearman's r tested the relationship between SC-W in the MIH group and the interval. Results: A total of 80 boys were enrolled in this study (IH group 29, MIH group 26, and control group 25). SA-PSV and PP-V in the hernia side were faster and slower than the control, respectively. There was no significant difference in PP-V and SA-PSV of the treated side in the MIH group and in the control group. After herniorrhaphy, SC-W was tapered down to normal size. SC-W, SA-PSV, and PP-V in the treated side were all highly correlated to the interval in a curvilinear manner. Conclusion: PSV was positively correlated with SC-W in boys with IH, and PP-V was negatively correlated; herniorrhaphy could reverse the impairment.

Early Activation of Astrocytes does not Affect Amyloid Plaque Load in an Animal Model of Alzheimer's Disease.

Astrocytes are closely associated with Alzheimer's disease (AD). However, their precise roles in AD pathogenesis remain controversial. One of the reasons behind the different results reported by different groups might be that astrocytes were targeted at different stages of disease progression. In this study, by crossing hAPP (human amyloid precursor protein)-J20 mice with a line of GFAP-TK mice, we found that astrocytes were activated specifically at an early stage of AD before the occurrence of amyloid plaques, while microglia were not affected by this crossing. Activation of astrocytes at the age of 3-5 months did not affect the proteolytic processing of hAPP and amyloid plaque loads in the brains of hAPP-J20 mice. Our data suggest that early activation of astrocytes does not affect the deposition of amyloid ß in an animal model of AD.

Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease.

Accumulation of amyloid ß (Aß) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aß interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aß-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aß detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aß-induced synaptic and cognitive dysfunctions without affecting Aß levels.

Enhanced Expression of Markers for Astrocytes in the Brain of a Line of GFAP-TK Transgenic Mice.

GFAP-TK mice are widely used in studies on neurogenesis and reactive astrocytes. Previous studies reported that GCV treatment in GFAP-TK mice resulted in reduced neurogenesis and deletion of proliferating GFAP-expressing astrocytes without affecting mature GFAP-expressing astrocytes. In the present study, we found that GFAP- and vimentin-expressing astrocytes were dramatically increased in the cortex and hippocampus with or without GCV treatment in a line of GFAP-TK mice (Jackson Laboratory, Stock No. 005698), while the neurons and microglia were not affected. In a second line of GFAP-TK mice (MMRRC, Stock No. 037351-UNC) generated in Dr. Heather Cameron's laboratory in NIH, however, no difference in GFAP and vimentin expression was found in both hippocampus and cortex, regardless of GCV treatment or not. Furthermore, enhanced expression of aquaporin 4 (AQP4) was found in the cortex and hippocampus of the GFAP-TK mice from Jackson lab but not in the brain of GFAP-TK mice from NIH. Our data suggested that we should be careful to select different lines of GFAP-TK mice to study adult neurogenesis or reactive astrocytes.

Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesis via the brain-derived neurotrophic factor pathway.

Efr3 is a newly identified plasma membrane protein and plays an important role in the phosphoinositide metabolism on the plasma membrane. However, although it is highly expressed in the brain, the functional significance of Efr3 in the brain is not clear. In the present study, we generated Efr3af/f mice and then crossed them with Nestin-Cre mice to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. We found that brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology. Moreover, the brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling pathway was significantly enhanced in the hippocampus of Efr3a-deficient mice, as reflected by increased expression of BDNF, TrkB, and the downstream molecules, including phospho-MAPK and phospho-Akt. Furthermore, the number of TUNEL+ cells was decreased in the subgranular zone of dentate gyrus in Efr3a-deficient mice compared with that of control mice. Our data suggest that brain-specific deletion of Efr3a could promote adult hippocampal neurogenesis, presumably by upregulating the expression of BDNF and its receptor, TrkB, and therefore provide new insight into the roles of Efr3 in the brain.-Qian, Q., Liu, Q., Zhou, D., Pan, H., Liu, Z., He, F., Ji, S., Wang, D., Bao, W., Liu, X., Liu, Z., Zhang, H., Zhang, X., Zhang, L., Wang, M., Xu, Y., Huang, F., Luo, B., Sun B. Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesis via the brain-derived neurotrophic factor pathway.

Amyloid ß Is Not the Major Factor Accounting for Impaired Adult Hippocampal Neurogenesis in Mice Overexpressing Amyloid Precursor Protein.

Adult hippocampal neurogenesis was impaired in several Alzheimer's disease models overexpressing mutant human amyloid precursor protein (hAPP). However, the effects of wild-type hAPP on adult neurogenesis and whether the impaired adult hippocampal neurogenesis was caused by amyloid ß (Aß) or APP remained unclear. Here, we found that neurogenesis was impaired in the dentate gyrus (DG) of adult mice overexpressing wild-type hAPP (hAPP-I5) compared with controls. However, the adult hippocampal neurogenesis was more severely impaired in hAPP-I5 than that in hAPP-J20 mice, which express similar levels of hAPP mRNA but much higher levels of Aß. Furthermore, reducing Aß levels did not affect the number of doublecortin-positive cells in the DG of hAPP-J20 mice. Our results suggested that hAPP was more likely an important factor inhibiting adult neurogenesis, and Aß was not the major factor affecting neurogenesis in the adult hippocampus of hAPP mice.

Effects of Heart Bypass Surgery on Plasma Aß40 and Aß42 Levels in Infants and Young Children.

Accumulation of ß-amyloid (Aß) plaques is a pathological hallmark of Alzheimer disease. Aß levels in animals and adults were reported to be associated with postoperative cognitive dysfunction (POCD). Our goal was to determine the plasma levels of Aß in infants and young children after cardiac surgery with cardiopulmonary bypass (CPB).Forty-two infants and young children aged from 1 to 35 months undergoing cardiac surgery with general anesthetics were prospectively enrolled from January to June 2014 at a tertiary medical center. Perioperative plasma samples were obtained, and Aß42 and Aß40 levels were measured using ELISA. Other clinical characteristics of the patients were also recorded.Plasma levels of Aß42 and Aß40 decreased dramatically 2 hours after surgery and remained significantly lower 6 hours after operation. Baseline Aß42 level correlated significantly with surgical intensive care unit (SICU) length of stay (LOS) and was an independent predictor for SICU LOS on multivariate analysis.Cardiac surgery with CPB decreases plasma Aß levels. Plasma levels of Aß42 and Aß40 might be used as novel biomarkers for predicting outcomes in the patient population.