Development of a New Method for Evaluating Heat-and-Moisture Exchanger Performance.

BACKGROUND: A model system described in International Organization for Standardization 9360 is the standard method for estimating the humidifying performance of heat-and-moisture exchangers (HMEs). However, there are no reliable bedside methods for evaluating the ongoing humidification performance of HMEs. Therefore, this study aimed to develop 2 clinically applicable methods for estimating the ongoing humidifying performance of HMEs and to evaluate their reliability in a model system. METHODS: Physiologically expired gas was simulated using a heated humidifier, and ventilation was delivered using a ventilator with constant flow through 3 different types of HMEs. Relative humidity (RH) was measured using a capacitive-type moisture sensor. Water content lost during expiration was calculated by integrating absolute humidity (AH), instantaneous gas flow measured at the expiratory outlet of the ventilator, and time. We also calculated the water content released and captured by the HMEs during tidal ventilation by integrating the difference in AH across the HMEs, instantaneous gas flow, and time. RESULTS: We found that the RH, temperature, and AH were almost constant on the expiratory outlet of the ventilator but rapidly varied near the HMEs. The water content lost by the 3 HMEs was associated with the manufacturer-reported values and inversely correlated with the calculated values of the water content exchanged by the HMEs. The water content released and captured by HMEs was closely correlated with the difference in HME weight measured at the end of inspiration and expiration; however, the water content captured by HMEs seemed to be overestimated. CONCLUSIONS: Our results demonstrated that our system was able to detect the differences in the performance of 3 models of HMEs and suggest that our method for calculating water loss is reliable for estimating the water retention performance of HMEs during mechanical ventilation, even in the presence of a constant flow.

Reading impairment after neonatal hypoglycemia with parieto-temporo-occipital injury without cortical blindness: A case report.

BACKGROUND: Perinatal brain injury may lead to later neurodevelopmental disorders, whose outcomes may vary due to neuroplasticity in young children. Recent neuroimaging studies have shown that the left parietotemporal area (which includes the left inferior parietal lobe) is associated with phonological awareness and decoding skills, which are essential skills for reading acquisition in children. However, the literature on the effect of perinatal cerebral injury on the development of phonological awareness or decoding ability in childhood is limited. CASE SUMMARY: We report the case of an 8-year-old boy who presented with reading difficulty following a perinatal injury in the parieto-temporal-occipital lobes. The patient was born at term and was treated for hypoglycemia and seizures during the neonatal period. Diffusion-weighted brain magnetic resonance imaging on postnatal day 4 revealed cortical and subcortical hyperintensities in the parieto-temporo-occipital lobe. At the age of 8 years, physical examination was unremarkable, aside from mild clumsiness. Despite occipital lobe injury, the patient had adequate visual acuity, normal eye movement, and no visual field defects. Full-scale intelligence quotient and verbal comprehension index on Wechsler Intelligence Scale for Children-Fourth Edition were 75 and 90, respectively. Further assessment revealed adequate recognition of Japanese Hiragana letters. However, he had significantly slower reading speed in the Hiragana reading test than control children. The phonological awareness test revealed significant errors (standard deviation +2.7) in the mora reversal task. CONCLUSION: Patients with perinatal brain injuries in the parietotemporal area require attention and may benefit from additional reading instructions.

Hemodynamic response related to the Airway Scope versus the Macintosh laryngoscope: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: It is important to reduce the hemodynamic response during tracheal intubation. We performed a systematic review and meta-analysis of the Airway Scope and Macintosh laryngoscope to determine whether they reduce the hemodynamic responses of heart rate (HR) and mean blood pressure (MBP) after tracheal intubation under general anesthesia. METHODS: We performed a comprehensive literature search of electronic databases for clinical trials comparing hemodynamic response to tracheal intubation. The primary aim of our meta-analyst is to determine if the Airway Scope reduces hemodynamic responses (HR and mean MBP) 60 seconds after tracheal intubation compared to the Macintosh laryngoscope. We expressed pooled differences in hemodynamic responses between the 2 devices as weighted mean differences with 95% confidence intervals. We conducted trial sequential analysis. Secondarily, we investigated the ability of the Airway Scope and Macintosh laryngoscope to reduce hemodynamic responses at 120 seconds, 180 seconds, and 300 seconds after tracheal intubation. RESULTS: We identified clinical trials comparing hemodynamic response via a comprehensive literature search. Of 185 articles found in the search, we selected 8. In comparison to the Macintosh laryngoscope, the Airway Scope significantly reduced HR and MBP at 60 seconds after tracheal intubation (HR; weighted mean difference = -7.29; 95% confidence interval, -10.9 to -3.62; P < .0001; I2 = 57%, MBP; weighted mean difference = -11.5; 95% confidence interval, -20.4 to -2.65; P = .01; I2 = 91%). At the secondary outcome, the Airway Scope significantly reduced the fluctuation of HR after 120 seconds and 180 seconds of tracheal intubation. However, the Airway Scope did not significantly reduce MBP 120 seconds, 180 seconds, and 300 seconds after tracheal intubation. Trial sequential analysis suggested that the total sample size reached the required information size for heart rate. CONCLUSIONS: Our finding suggested that the Airway Scope attenuated hemodynamic responses at 60 seconds after tracheal intubation in comparison with that of the Macintosh laryngoscope. However, the MBP sample size is small and further research is needed.

Effects of volume-targeted pressure-controlled inverse ratio ventilation on functional residual capacity and dead space in obese patients undergoing robot-assisted laparoscopic radical prostatectomy.

Background: The effect of inverse inspiration:expiration (I:E) ratio on functional residual capacity (FRC) during pneumoperitoneum is unclear. We hypothesised that volume-targeted pressure-controlled inverse ratio ventilation (vtPC-IRV) would increase FRC by increasing the level of auto-PEEP in low respiratory compliance situations. Methods: During robot-assisted laparoscopic radical prostatectomy, 20 obese patients were sequentially ventilated with four different settings for 30 min in each setting: (1) control, I:E ratio of 1:2 and baseline airway pressure (BAP) of 5 cm H2O; (2) IRV2, I:E ratio of 2:1 and BAP off; (3) IRV3, I:E ratio of 3:1 and BAP off; and (4) IRV4, I:E ratio of 4:1 and BAP off. The changes in FRC were identified and compared among these settings. Results: The FRC significantly increased as the I:E ratio increased. The FRC values expressed as median (inter-quartile range) during control, IRV2, IRV3, and IRV4 were 1149 (898-1386), 1485 (1018-1717), 1602 (1209-1775), and 1757 (1337-1955) ml, respectively. Auto-PEEP increased significantly as the I:E ratio increased and correlated with FRC (rho=0.303; P=0.006). Shunt and physiological dead space were significantly lower in all IRV groups than in the control group; however, there were no significant differences among the IRV groups. Conclusions: vtPC-IRV with shortened expiratory time and increased auto-PEEP effectively increases FRC during robot-assisted laparoscopic radical prostatectomy in obese patients. FRC increases progressively as the I:E ratio increases from 1:2 to 4:1; however, an I:E ratio higher than 2:1 does not further improve the dead space. Clinical trial registration: UMIN000038989.

Effectiveness of lacosamide in children and young adults previously treated with other sodium channel blockers.

PURPOSE: This multicenter study examined the effectiveness and tolerability of lacosamide (LCM) for children and young adults with epilepsy, particularly in patients who had previously been treated with other sodium channel blockers (SCBs) and the difference in effectiveness and tolerability when using other concomitant SCBs. METHODS: We retrospectively studied the clinical information of patients aged <30 years given LCM to treat epilepsy. The effectiveness and adverse events (AEs) of LCM and the other SCBs were investigated. Factors related to the effectiveness and AEs of LCM, such as the number of antiepileptic drugs (AEDs) tried before LCM and concomitantly used SCBs, were also studied. RESULTS: We enrolled 112 patients (median age = 11 years). One year after starting LCM, 29% of the patients were seizure free, and 50% had a ≥50% seizure reduction. Of the patients, 17% experienced AEs, the most common being somnolence. A ≥50% seizure reduction was observed for LCM in 30% of patients in whom other SCBs had not been effective. Lacosamide produced a ≥50% seizure reduction in 35% of the patients taking one concomitant SCB. By contrast, no patients had ≥50% seizure reduction, and 33% developed AEs, when LCM was administered concomitantly with two SCBs. CONCLUSIONS: Lacosamide was effective in 30% of children and young adults in whom other SCBs had not been effective. The effectiveness of LCM may differ from that of other SCBs, and it is worth trying in patients with epilepsy resistant to other AEDs.

Changes in dead space components during pressure-controlled inverse ratio ventilation: A secondary analysis of a randomized trial.

BACKGROUND: We previously reported that there were no differences between the lung-protective actions of pressure-controlled inverse ratio ventilation and volume control ventilation based on the changes in serum cytokine levels. Dead space represents a ventilation-perfusion mismatch, and can enable us to understand the heterogeneity and elapsed time changes in ventilation-perfusion mismatch. METHODS: This study was a secondary analysis of a randomized controlled trial of patients who underwent robot-assisted laparoscopic radical prostatectomy. The inspiratory to expiratory ratio was adjusted individually by observing the expiratory flow-time wave in the pressure-controlled inverse ratio ventilation group (n = 14) and was set to 1:2 in the volume-control ventilation group (n = 13). Using volumetric capnography, the physiological dead space was divided into three dead space components: airway, alveolar, and shunt dead space. The influence of pressure-controlled inverse ratio ventilation and time factor on the changes in each dead space component rate was analyzed using the Mann-Whitney U test and Wilcoxon's signed rank test. RESULTS: The physiological dead space and shunt dead space rate were decreased in the pressure-controlled inverse ratio ventilation group compared with those in the volume control ventilation group (p < 0.001 and p = 0.003, respectively), and both dead space rates increased with time in both groups. The airway dead space rate increased with time, but the difference between the groups was not significant. There were no significant changes in the alveolar dead space rate. CONCLUSIONS: Pressure-controlled inverse ratio ventilation reduced the physiological dead space rate, suggesting an improvement in the total ventilation/perfusion mismatch due to improved inflation of the alveoli affected by heterogeneous expansion disorder without hyperinflation of the normal alveoli. However, the shunt dead space rate increased with time, suggesting that atelectasis developed with time in both groups.

Risks of ACTH therapy for West syndrome following BCG vaccination.

OBJECTIVE: Bacille de Calmette et Guérin (BCG) is a live vaccine for tuberculosis that is administered to all infants in Japan. Adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS) causes immunosuppression and may result in BCG infection after BCG vaccination. We evaluated the safety of ACTH therapy initiated shortly after BCG vaccination. METHODS: We analyzed patients with WS who received ACTH therapy between 2005 and 2018. We evaluated the interval between BCG and ACTH therapy, and the rate of BCG infection during and after ACTH therapy, by retrospective chart review. RESULTS: Seventy-nine patients were included in the analysis. Twenty-three patients received ACTH therapy prior to BCG vaccination. For the remaining 56 patients, the median interval between BCG vaccination and the start of ACTH therapy (BCG-ACTH interval) was 91.5 (range 14-280) days. The BCG-ACTH interval was shorter in patients with unknown than in those with known etiologies. It was <8 weeks in 13 patients (10 with unknown and 3 with known etiologies). The minimum BCG-ACTH interval was 14 days. Six patients with epileptic spasms received BCG vaccinations because physicians did not recognize their seizures. None of the patients developed BCG infection. CONCLUSION: No patients who received ACTH therapy after BCG, even at an interval of 8 weeks, developed BCG infection. The timing of ACTH therapy initiation should be based on the risk of BCG-related adverse events and the adverse effects of any delay.

Comparison of polyurethane tracheal tube cuffs and conventional polyvinyl chloride tube cuff for prevention of ventilator-associated pneumonia: A systematic review with meta-analysis.

BACKGROUND: The aim of this meta-analysis with trial sequential analysis (TSA) was to evaluate the effect of a polyurethane (PU) tracheal tube cuff on the prevention of ventilator-associated pneumonia (VAP). METHODS: We performed a systematic search using the MEDLINE database through PubMed, Cochrane Central Register of Controlled Trial, SCOPUS, and Web of Science.Randomized controlled trials comparing the incidence of VAP and clinically relevant outcomes between PU cuff tubes and polyvinyl chloride (PVC) cuff tubes in adult patients. Two authors independently extracted study details, patient characteristics, and clinical outcomes such as incidence of VAP, bacterial colonization of tracheal aspirate, duration of mechanical ventilation, ICU stay, and ICU mortality. RESULTS: From 309 studies identified as potentially eligible, six studies with 1226 patients were included in this meta-analysis. All studies compared the incidence of VAP between PU cuffs and PVC cuffs. Use of a PU cuff was not associated with a reduction in VAP incidence (RR = 0.68; 95% CI, 0.45-1.03) with significant statistical heterogeneity (I2 = 65%). The quality of evidence was "very low." According to the TSA, the actual sample size was only 15.8% of the target sample size, and the cumulative Z score did not cross the trial sequential monitoring boundary for benefit. No positive impact was reported for the other relevant outcomes for PU cuffs. CONCLUSIONS: The use of a PU cuff for mechanical ventilation did not prevent VAP. Further trials with a low risk of bias need to be performed.

Association of early-onset epileptic encephalopathy with involuntary movements - Case series and literature review.

Epileptic-dyskinetic encephalopathies are rare epilepsies characterized by early-onset epileptic encephalopathies (EOEEs) with involuntary movement. Herein, we investigated the impact of gene variants in epileptic-dyskinetic encephalopathies. Four independent patients from four families who exhibited involuntary movements were recruited from Tokyo Metropolitan Neurological Hospital. The inclusion criteria were as follows: onset within 1 year after birth, frequent seizures, severe developmental delay and accompanying involuntary movements. We detected four genetic mutations, including STXBP1, GNAO1, CYFIP2, and SCN8A variants. The involuntary movements were drug-resistant. However, pallidal electrocoagulation followed by gabapentin were partially effective in treating chorea and ballismus of the extremities in patients with GNAO1 variants, and perampanel partially suppressed seizures and involuntary movements in one patient with a SCN8A variant. Movement disorders are common to many neurodevelopmental disorders, including a variety of EOEEs. Although we could not establish a definitive correlation using genetic variants in patients with EOEE and movement disorders, involuntary movements in patients with EOEEs may be a key diagnostic finding. The usage of genetic variants could prove beneficial in the future as more patients are investigated with epileptic-dyskinetic encephalopathies.

MRI findings in children with congenital cytomegalovirus infection retrospectively diagnosed with dried umbilical cord.

PURPOSE: Brain MRI provides important information about suspected congenital CMV infection in neonatally underdiagnosed children. This study aimed to describe MRI findings in children in whom congenital CMV infection was not suspected during the neonatal period and was proven retrospectively. METHODS: We enrolled 31 children referred to the pediatric neurology clinic with neurological symptoms who were proven to have congenital CMV infection based on dried umbilical cord samples. Upon diagnosis, MR and CT images were assessed using the van der Knaap scoring system integrated with additional variables. Two investigators independently assessed all images. RESULTS: The age at diagnosis was < 12 months in 14, 12-24 months in 11, and > 24 months in 6 patients. The initial symptom triggering clinic referral was delayed development in 22, seizure in 5, deafness in 3, and hemiplegia in 1 patient. Of the 31 children, 30 had a white matter (WM) abnormality predominant in the deep WM of the parietal lobe (n = 25). Anterior temporal lesions were observed in 21 children. Cortical lesions were observed in 7 children, suggestive of polymicrogyria. No child had cerebellar or brainstem abnormalities. Brain CT was performed in 22 of 31 children, and 11 showed punctate cerebral calcification in the periventricular and/or deep WM. CONCLUSION: Patients with congenital CMV infection with delayed neurological symptoms show a relatively uniform pattern of parietal-dominant multifocal WM lesions and anterior temporal lesions, with or without polymicrogyria.

Lung-protective properties of expiratory flow-initiated pressure-controlled inverse ratio ventilation: A randomised controlled trial.

BACKGROUND: Expiratory flow-initiated pressure-controlled inverse ratio ventilation (EF-initiated PC-IRV) reduces physiological dead space. We hypothesised that EF-initiated PC-IRV would be lung protective compared with volume-controlled ventilation (VCV). METHODS: Twenty-eight men undergoing robot-assisted laparoscopic radical prostatectomy were enrolled in this randomised controlled trial. The EF-initiated PC-IRV group (n = 14) used pressure-controlled ventilation with the volume guaranteed mode. The inspiratory to expiratory (I:E) ratio was individually adjusted by observing the expiratory flow-time wave. The VCV group (n = 14) used the volume control mode with a 1:2 I:E ratio. The Mann-Whitney U test was used to compare differences in the serum cytokine levels. RESULTS: There were no significant differences in serum IL-6 between the EF-initiated PC-IRV (median 34 pg ml-1 (IQR 20.5 to 63.5)) and VCV (31 pg ml-1 (24.5 to 59)) groups (P = 0.84). The physiological dead space rate (physiological dead space/expired tidal volume) was significantly reduced in the EF-initiated PC-IRV group as compared with that in the VCV group (0.31 ± 0.06 vs 0.4 ± 0.07; P<0.001). The physiological dead space rate was negatively correlated with the forced vital capacity (% predicted) in the VCV group (r = -0.85, P<0.001), but not in the EF-initiated PC-IRV group (r = 0.15, P = 0.62). Two patients in the VCV group had permissive hypercapnia with low forced vital capacity (% predicted). CONCLUSIONS: There were no differences in the lung-protective properties between the two ventilatory strategies. However, EF-initiated PC-IRV reduced physiological dead space rate; thus, it may be useful for reducing the ventilatory volume that is necessary to maintain normocapnia in patients with low forced vital capacity (% predicted) during robot-assisted laparoscopic radical prostatectomy.

Use of the GlideScope does not lower the hemodynamic response to tracheal intubation more than the Macintosh laryngoscope: a systematic review and meta-analysis.

BACKGROUND: It is presently unclear whether the hemodynamic response to intubation is less marked with indirect laryngoscopy using the GlideScope (GlideScope) than with direct laryngoscopy using the Macintosh laryngoscope. Thus, the aim of this study was to determine whether using the GlideScope lowers the hemodynamic response to tracheal intubation more than using the Macintosh laryngoscope. METHODS: We performed a comprehensive literature search of electronic databases for clinical trials comparing hemodynamic response to tracheal intubation. The primary aim was to determine whether the heart rate (HR) and mean blood pressure (MBP) 60 s after tracheal intubation with the GlideScope were lower than after intubation with the Macintosh laryngoscope. We expressed pooled differences in HR and MBP between the devices as the weighted mean difference with 95% confidence interval and also performed trial sequential analysis (TSA). Second, we examined whether use of the GlideScope resulted in lower post-intubation hemodynamic responses at 120, 180, and 300 s compared with use of the Macintosh laryngoscope. For sensitivity analysis, we used a multivariate random effects model that accounted for within-study correlation of the longitudinal data. RESULTS: The literature search identified 13 articles. HR and MBP at 60 seconds post-intubation was not significantly lower with the GlideScope than with the Macintosh (HR vs MBP: weighted mean difference = 0.22 vs 2.56; 95% confidence interval -3.43 to 3.88 vs -0.82 to 5.93; P = .90 vs 0.14; I = 77% vs 63%: Cochran Q, 52.7 vs 27.2). Use of the GlideScope was not associated with a significantly lower HR or MBP at 120, 180, or 300 s post-intubation. TSA indicated that the total sample size was over the futility boundary for HR and MBP. Sensitivity analysis indicated no significant association between use of the GlideScope and a lower HR or MBP at any measurement point. CONCLUSIONS: Compared with the Macintosh laryngoscope, the GlideScope did not lower the hemodynamic response after tracheal intubation. Sensitivity analysis results supported this finding, and the results of TSA suggest that the total sample size exceeded the TSA monitoring boundary for HR and MBP.

Development of central retinal artery occlusion accompanied by choroidal folds in a patient with antineutrophil cytoplasmic antibody-associated vasculitis: A case report.

RATIONALE: We report a case of central retinal artery occlusion (CRAO) accompanied by choroidal folds in a patient positive for myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA). PATIENT CONCERNS: The study involved a 67-year-old female patient who presented at the Department of Ophthalmology, Osaka Medical College, Takatsuki-City, Osaka, Japan on October 24, 2016 after becoming aware of a sudden decrease of visual acuity (VA) in her right eye. Other than suffering with scleritis 6-months previous, there was no obvious past history. DIAGNOSIS: Upon examination, the VA in her right eye was hand motion, and the anterior segment of that eye showed thinning of the superior sclera. Macular edema in the inner retina and cherry red spots were observed in the ocular fundus, and optical coherence tomography (OCT) findings showed hyperreflectivity of the inner retina and choroidal folds. Fluorescein angiography (FA) examination of the fundus showed scattered areas of no retinal perfusion, and indocyanine green angiography (IA) findings of the fundus indicated a possible choroidal circulatory disturbance in her right eye. Blood test findings revealed the patient to be positive for MPO-ANCA. Based on the above findings, the patient was diagnosed with CRAO and choroidal circulatory disturbance due to ANCA-associated vasculitis. INTERVENTIONS: For treatment, steroid semi-pulse therapy was initiated. OUTCOMES: Post treatment initiation, the fundus features and choroidal folds gradually improved, and her VA slightly improved to 0.08. LESSONS: Based on the FA, IA, and OCT findings, the present case was considered to have CRAO accompanied by choroidal circulatory disturbance due to ANCA-associated vasculitis, a rare disease that may be complicated by choroidal circulatory disturbances.

Hippocampal diffusion abnormality after febrile status epilepticus is related to subsequent epilepsy.

OBJECTIVE: To assess hippocampal signal changes on diffusion-weighted imaging (DWI) during the acute period after febrile status epilepticus (FSE) and to examine the relationship between DWI and subsequent epilepsy. METHODS: A prospective, multicenter study of children with a first episode of FSE was performed. The patients underwent magnetic resonance imaging (MRI) within 3 days of FSE, and signal intensity was evaluated on DWI. Electroencephalography studies within 3 days of FSE were also assessed. Nine to 13 years after FSE, information on subsequent epilepsy was obtained. RESULTS: Twenty-two children with FSE were evaluated. DWI showed unilateral hippocampal hyperintensity in six patients (27%). Three of six patients with hippocampal hyperintensity had ipsilateral thalamic hyperintensity. On EEG within 3 days of FSE, five of six patients with hippocampal hyperintensity had ipsilateral focal slowing, spikes, or attenuation. Nine to 13 years later, the outcomes could be determined in five patients with hippocampal hyperintensity and in 10 without. All 5 patients with hippocampal hyperintensity had hippocampal atrophy and developed focal epilepsy, whereas only 1 of 10 patients without hippocampal hyperintensity developed epilepsy (P = 0.002). Ictal semiology was concordant with temporal lobe seizures in all patients. Ipsilateral temporal epileptiform abnormalities were seen on EEG in four of five at last follow-up. SIGNIFICANCE: Acute DWI hippocampal hyperintensity was seen in 27% of patients with FSE. Acute DWI hyperintensity suggests cytotoxic edema caused by prolonged seizure activity. Hippocampal DWI hyperintensity is related to mesial temporal lobe epilepsy and can be a target of neuroprotective treatments to prevent the onset of epilepsy.

De novo PHACTR1 mutations in West syndrome and their pathophysiological effects.

Trio-based whole exome sequencing identified two de novo heterozygous missense mutations [c.1449T > C/p.(Leu500Pro) and c.1436A > T/p.(Asn479Ile)] in PHACTR1, encoding a molecule critical for the regulation of protein phosphatase 1 (PP1) and the actin cytoskeleton, in unrelated Japanese individuals with West syndrome (infantile spasms with intellectual disability). We then examined the role of Phactr1 in the development of mouse cerebral cortex and the pathophysiological significance of these two mutations and others [c.1561C > T/p.(Arg521Cys) and c.1553T > A/p.(Ile518Asn)], which had been reported in undiagnosed patients with intellectual disability. Immunoprecipitation analyses revealed that actin-binding activity of PHACTR1 was impaired by the p.Leu500Pro, p.Asn479Ile and p.Ile518Asn mutations while the p.Arg521Cys mutation exhibited impaired binding to PP1. Acute knockdown of mouse Phactr1 using in utero electroporation caused defects in cortical neuron migration during corticogenesis, which were rescued by an RNAi-resistant PHACTR1 but not by the four mutants. Experiments using knockdown combined with expression mutants, aimed to mimic the effects of the heterozygous mutations under conditions of haploinsufficiency, suggested a dominant negative effect of the mutant allele. As for dendritic development in vivo, only the p.Arg521Cys mutant was determined to have dominant negative effects, because the three other mutants appeared to be degraded with these experimental conditions. Electrophysiological analyses revealed abnormal synaptic properties in Phactr1-deficient excitatory cortical neurons. Our data show that the PHACTR1 mutations may cause morphological and functional defects in cortical neurons during brain development, which is likely to be related to the pathophysiology of West syndrome and other neurodevelopmental disorders.

C-MAC videolaryngoscope versus Macintosh laryngoscope for tracheal intubation: A systematic review and meta-analysis with trial sequential analysis.

STUDY OBJECTIVE: The C-MAC laryngoscope (C-MAC) is a videolaryngoscope that uses a modified Macintosh blade. Although several anecdotal reports exist, it remains unclear whether the C-MAC is superior to the Macintosh laryngoscope for tracheal intubation in the adult population. DESIGN: Systematic review, meta-analysis. SETTING: Operating room, intensive care unit. MEASUREMENTS: For inclusion in our analysis, studies had to be prospective randomised trials which compared the C-MAC with the Macintosh laryngoscope for tracheal intubation in the adult population. Data on success rates, intubation time, glottic visualisation and incidence of external laryngeal manipulations (ELM) during tracheal intubation were extracted from the identified studies. In subgroup analysis, we separated those parameters to assess the influence of the airway condition (normal or difficult) and laryngoscopists (novice or experienced). We conducted a trial sequential analysis (TSA). MAIN RESULTS: Sixteen articles with 18 trials met the inclusion criteria. The C-MAC provided better glottic visualisation compared to the Macintosh (RR, 1.08; 95% CI, 1.03-1.14). TSA corrected the CI to 1.01-1.19; thus, total sample size reached the required information size (RIS). Success rates and intubation time did not differ significantly between the laryngoscopes. TSA showed that total sample size reached the RIS for success rates. The TSA Z curve surpassed the futility boundary. The C-MAC required less ELM compared to the Macintosh (RR, 0.83; 95% CI, 0.72-0.96). TSA corrected the CI to 0.67-1.03; 52.3% of the RIS was achieved. In difficult airways, the C-MAC showed superior success rates, glottic visualisation, and less ELM compared to the Macintosh. Among experienced laryngoscopists, the C-MAC offered better glottic visualisation with less ELM than the Macintosh. CONCLUSIONS: The C-MAC provided better glottic visualisation and less ELM (GRADE: Very Low or Moderate), with improved success rates, glottic visualisation, and less ELM in difficult airways.

Is hiragana decoding impaired in children with periventricular leukomalacia?

BACKGROUND: There are few studies on hiragana reading skill and phonological awareness in Japanese schoolchildren with periventricular leukomalacia (PVL). METHODS: Three seven-year-old children with PVL who had no intellectual disabilities or dysarthria were recruited. Their perinatal information, brain magnetic resonance image (MRI) at term equivalent age, accompanying neurodevelopmental disorders, ophthalmologic features, Kaufman Assessment Battery for Children (K-ABC), a hiragana reading test (four tasks), and a phonological awareness task (mora reversal tasks) were analyzed. RESULTS: Patient (Pt) 1 and pt2 were male. Pt2 and pt3 were siblings of triplets. Their gestational age was 28 or 32 weeks, and their birth weights were 1196, 1554, and 1848 g, respectively. Their brain MRI revealed cystic or non-cystic periventricular white matter injury involving the deep white matter at the trigone of both lateral ventricles. Pt1 had attention-deficit/hyperactivity disorder and pt3 had pervasive developmental disorder not otherwise specified. All patients had strabismus with spared best-corrected visual acuity. Scores of Reading/Decoding in K-ABC ranged from 89 to 99. As for the single mora reading task or the non-word reading task in the kana reading test, Z scores of their reading time ranged from 2.3 to 5.9 compared to control children. Pt1 and pt3 made significant errors in the mora reversal task of three-mora words, whereas all patients could answer all words correctly in the mora reversal task of two-mora words. CONCLUSION: All children showed significantly prolonged reading time despite their adequate letter recognition. Two patients showed delayed phonological awareness. It was suggested that hiragana decoding impairment due to subcortical and/or cortical injury related to PVL affected their reading ability.

A patient with a GNAO1 mutation with decreased spontaneous movements, hypotonia, and dystonic features.

We report on a 4-year-old girl with a de novo GNAO1 mutation who had neurological findings, including decreased spontaneous movements, hypotonia, and dystonic features. She was referred to our hospital because of delayed psychomotor development. She showed hypotonia and decreased spontaneous movements. Voluntary movements of the limbs were more frequent in the lower extremities than in the upper extremities. Occasional dyskinetic features, such as awkward hand/foot posturing and grimacing, were seen during the voluntary movements. Serum metabolic screening, head magnetic resonance imaging, and electroencephalography were unremarkable. Whole-exome sequencing revealed a de novo mutation in the patient's GNAO1 gene, c.709 G > A (p.E237K). We calculated the free-energy change using the FoldX Suite to evaluate the impact of the E237K mutation. The FoldX calculations showed an increased free-energy change in the active state of the GNAO1 protein, indicating that the E237K mutation destabilizes the active state complexes. No seizures, chorea, tremor, or myoclonia, which are frequently reported in patients with GNAO1 mutations, were observed as of the last follow up. Our patient will improve the understanding of early neurological features in patients with GNAO1 mutations.

Supraglottic airway device versus a channeled or non-channeled blade-type videolaryngoscope for accidental extubation in the prone position: A randomized crossover manikin study.

BACKGROUND: It is very rare but challenging to perform emergency airway management for accidental extubation in a patient whose head and neck are fixed in the prone position when urgently turning the patient to the supine position would be unsafe. The authors hypothesized that tracheal intubation with a videolaryngoscope would allow effective airway rescue in this situation compared with a supraglottic airway device and designed a randomized crossover manikin study to test this hypothesis. METHODS: The authors compared airway rescue performances of the 3 devices-the ProSeal laryngeal mask airway (PLMA; Teleflex Medical, Westmeath, Ireland) as a reference; the Pentax AWS (AWS; Nihon Kohden, Tokyo, Japan) as a channeled blade-type videolaryngoscope; and the McGRATH videolaryngoscope (McGRATH; Medtronic, Minneapolis, MN) as a nonchanneled blade type in a manikin fixed to the operating table in the prone position. Twenty-one anesthesiologists performed airway management on the prone manikin with the 3 devices, and the time required for intubation/ventilation and the success rates were recorded. RESULTS: The median (range) intubation/ventilation times with the PLMA, AWS, and McGRATH were 24.5 (13.5-89.5) s, 29.9 (17.1-79.8) s, and 46.7 (21.9-211.7) s, respectively. There was no significant difference in intubation/ventilation times between the PLMA and AWS. The AWS permitted significantly faster tracheal intubation than did the McGRATH (P = 0.006). The success rates with the PLMA (100%) and AWS (100%) were significantly greater than that with the McGRATH (71.4%). Airway management performance of the PLMA and AWS was comparable between devices and better than that of the McGRATH in the prone position. CONCLUSIONS: Considering that tracheal intubation can provide a more secure airway and more stable ventilation than the PLMA, re-intubation with a channeled blade-type videolaryngoscope such as the AWS may be a useful method of airway rescue for accidental extubation in patients in the prone position.

Distinctive facies, macrocephaly, and developmental delay are signs of a PTEN mutation in childhood.

BACKGROUND: Germline mutations of the PTEN gene are responsible for several PTEN hamartoma tumor syndromes. They are also implicated as a cause of macrocephaly and mild to severe developmental delay, regardless of the presence or absence of hamartomas in childhood. Nevertheless, because of limited information, the clinical features present during childhood in patients with a PTEN mutation are yet to be elucidated. METHODS: PTEN mutations were investigated by multiplex targeted sequencing of genomic DNA from 33 children with increased head circumference (>+2 SD) and developmental delay. The clinical features of all the patients with a PTEN mutation were abstracted by dysmorphologists. RESULTS: We have identified six children with a PTEN mutation. Clinical dissection of these six patients, in addition to patient reports in the literature, revealed distinctive facial features that included frontal bossing, dolichocephaly, horizontal eyebrows, and a depressed nasal bridge. Macrocephaly (+3.2 to +6.0 SD) was noticeable compared to their height (-0.8 to +2.1 SD), and the difference in the SD value of head circumference and height was more than 3 SD in all patients. CONCLUSION: The presence of distinctive facies, extreme macrocephaly with normal to mildly high stature, and developmental delay may be useful for identifying patients with a PTEN mutation in childhood. Early identification of patients with a PTEN mutation would help uncover the natural course of tumor development in this group of individuals who have a possible predisposition to cancer, and be important for the development of an optimal surveillance strategy.