Safety of primary nasotracheal intubation in the pediatric intensive care unit (PICU).

Background: Nasal tracheal intubation (TI) represents a minority of all TI in the pediatric intensive care unit (PICU). The risks and benefits of nasal TI are not well quantified. As such, safety and descriptive data regarding this practice are warranted. Methods: We evaluated the association between TI route and safety outcomes in a prospectively collected quality improvement database (National Emergency Airway Registry for Children: NEAR4KIDS) from 2013 to 2020. The primary outcome was severe desaturation (SpO2 > 20% from baseline) and/or severe adverse TI-associated events (TIAEs), using NEAR4KIDS definitions. To balance patient, provider, and practice covariates, we utilized propensity score (PS) matching to compare the outcomes of nasal vs. oral TI. Results: A total of 22,741 TIs [nasal 870 (3.8%), oral 21,871 (96.2%)] were reported from 60 PICUs. Infants were represented in higher proportion in the nasal TI than the oral TI (75.9%, vs 46.2%), as well as children with cardiac conditions (46.9% vs. 14.4%), both p < 0.001. Severe desaturation or severe TIAE occurred in 23.7% of nasal and 22.5% of oral TI (non-adjusted p = 0.408). With PS matching, the prevalence of severe desaturation and or severe adverse TIAEs was 23.6% of nasal vs. 19.8% of oral TI (absolute difference 3.8%, 95% confidence interval (CI): - 0.07, 7.7%), p = 0.055. First attempt success rate was 72.1% of nasal TI versus 69.2% of oral TI, p = 0.072. With PS matching, the success rate was not different between two groups (nasal 72.2% vs. oral 71.5%, p = 0.759). Conclusion: In this large international prospective cohort study, the risk of severe peri-intubation complications was not significantly higher. Nasal TI is used in a minority of TI in PICUs, with substantial differences in patient, provider, and practice compared to oral TI.A prospective multicenter trial may be warranted to address the potential selection bias and to confirm the safety of nasal TI.

Ketamine Use in the Intubation of Critically Ill Children with Neurological Indications: A Multicenter Retrospective Analysis.

BACKGROUND: Ketamine has traditionally been avoided for tracheal intubations (TIs) in patients with acute neurological conditions. We evaluate its current usage pattern in these patients and any associated adverse events. METHODS: We conducted a retrospective observational cohort study of critically ill children undergoing TI for neurological indications in 53 international pediatric intensive care units and emergency departments. We screened all intubations from 2014 to 2020 entered into the multicenter National Emergency Airway Registry for Children (NEAR4KIDS) registry database. Patients were included if they were under the age of 18 years and underwent TI for a primary neurological indication. Usage patterns and reported periprocedural composite adverse outcomes (hypoxemia < 80%, hypotension/hypertension, cardiac arrest, and dysrhythmia) were noted. RESULTS: Of 21,562 TIs, 2,073 (9.6%) were performed for a primary neurological indication, including 190 for traumatic brain injury/trauma. Patients received ketamine in 495 TIs (23.9%), which increased from 10% in 2014 to 41% in 2020 (p < 0.001). Ketamine use was associated with a coindication of respiratory failure, difficult airway history, and use of vagolytic agents, apneic oxygenation, and video laryngoscopy. Composite adverse outcomes were reported in 289 (13.9%) Tis and were more common in the ketamine group (17.0% vs. 13.0%, p = 0.026). After adjusting for location, patient age and codiagnoses, the presence of respiratory failure and shock, difficult airway history, provider demographics, intubating device, and the use of apneic oxygenation, vagolytic agents, and neuromuscular blockade, ketamine use was not significantly associated with increased composite adverse outcomes (adjusted odds ratio 1.34, 95% confidence interval CI 0.99-1.81, p = 0.057). This paucity of association remained even when only neurotrauma intubations were considered (10.6% vs. 7.7%, p = 0.528). CONCLUSIONS: This retrospective cohort study did not demonstrate an association between procedural ketamine use and increased risk of peri-intubation hypoxemia and hemodynamic instability in patients intubated for neurological indications.

Intubation practice and outcomes among pediatric emergency departments: A report from National Emergency Airway Registry for Children (NEAR4KIDS).

BACKGROUND: Tracheal intubation (TI) practice across pediatric emergency departments (EDs) has not been comprehensively reported. We aim to describe TI practice and outcomes in pediatric EDs in contrast to those in intensive are units (ICUs) and use the data to identify quality improvement targets. METHODS: Consecutive TI encounters from pediatric EDs and ICUs in the National Emergency Airway Registry for Children (NEAR4KIDS) database from 2015 to 2018 were analyzed for patient, provider, and practice characteristics and outcomes: adverse TI-associated events (TIAEs), oxygen desaturation (SpO2 < 80%), and procedural success. A multivariable model identified factors associated with TIAEs in the ED. RESULTS: A total of 756 TIs in 13 pediatric EDs and 12,512 TIs in 51 pediatric/cardiac ICUs were reported. Median (interquartile range [IQR]) patient age for ED TIs was higher (32 [7-108] months) than that for ICU TIs (15 [3-91] months; p < 0.001). Proportion of TIs for respiratory decompensation (52% of ED vs. 64% ICU), shock (26% vs. 14%), and neurologic deterioration (30% vs. 11%) also differed by location. Limited neck mobility was reported more often in the ED (16% vs. 6%). TIs in the ED were performed more often via video laryngoscopy (64% vs. 29%). Adverse TIAE rates (15.6% ED, 14% ICU; absolute difference = 1.6%, 95% confidence interval [CI] = -1.1 to 4.2; p = 0.23) and severe TIAE rates (5.4% ED, 5.8% ICU; absolute difference = -0.3%, 95% CI = -2.0 to 1.3; p = 0.68) were not different. Oxygen desaturation was less commonly reported in ED TIs (13.6%) than ICU TIs (17%, absolute difference = -3.4%, 95% CI = -5.9 to -0.8; p = 0.016). Among ED TIs, shock as an indication (adjusted odds ratio [aOR] = 2.15, 95% CI = 1.26 to 3.65) and limited mouth opening (aOR = 1.74, 95% CI = 1.04 to 2.93) were independently associated with TIAEs. CONCLUSIONS: While TI characteristics vary between pediatric EDs and ICUs, outcomes are similar. Shock and limited mouth opening were independently associated with adverse TI events in the ED.

Urgent need to strengthen school health in Asia and the Pacific islands.

In Asia and the Pacific island region, strengthening of school health activities and measures is urgently recommended to deal with the impact of the increasing risk of potential school closures due to continuation of the coronavirus disease 2019 (COVID-19) pandemic in 2021. As the incidence of COVID-19 in 2020 was relatively low in these regions, many of the countries were able to avoid prolonged school closures. However, even if vaccination is expanded in the future and the pandemic tends to come to an end, the risk of SARS-CoV-2 variants spreading among children will also increase, and the possibility of having to close schools again will also increase.

Analysis of the presence or absence of atrophy of the subgenual and subcallosal cingulate cortices using voxel-based morphometry on MRI is useful to select prescriptions for patients with depressive symptoms.

OBJECTIVE: We objectively evaluated the presence or absence of atrophy of the subgenual anterior cingulate cortex (sgACC) and the subcallosal anterior cingulate cortex (scACC), using new voxel-based morphometry (VBM) software employing Statistical Parametric Mapping software v8 and diffeomorphic anatomic registration through an exponentiated lie algebra. We prepared a database covering young-mature adulthood and investigated the clinical usefulness of the evaluation. SUBJECTS AND METHODS: One hundred seven patients with major depressive disorder (MDD), 74 patients with bipolar disorder (BD), and 240 healthy control subjects underwent 1.5T magnetic resonance imaging scanning. Using new VBM software and databases covering young-mature adults and the elderly, target volumes of interest were set in the sgACC and scACC, four indicators (severity, extent, ratio, and whole-brain extent) were determined, and the presence or absence of atrophy of the sgACC and scACC was evaluated on the basis of the indicators. In addition, the relationships between the presence or absence of atrophy of the sgACC and scACC and performance of diagnosing MDD and BD and therapeutic drugs were investigated. RESULTS: It was clarified that the disease is likely to be MDD when atrophy is detected in the sgACC, and likely to be BD when no atrophy is detected in the sgACC but is detected in the scACC. Regarding the relationship with therapeutic drugs, it was clarified that, when atrophy is detected in both the sgACC and the scACC, concomitant administration of mood stabilizers and atypical antipsychotics acting as dopamine-system stabilizers is necessary in many cases. CONCLUSION: VBM on magnetic resonance imaging enabled automatic analysis of atrophy in the sgACC and scACC, and findings obtained by this procedure are useful not only for differentiation of MDD and BD patients but also for selection of prescriptions.

Usefulness of visual evaluation of the anterior thalamic radiation by diffusion tensor tractography for differentiating between Alzheimer's disease and elderly major depressive disorder patients.

BACKGROUND AND OBJECTIVE: Many surveys of neural integrity of the cerebral white matter with psychiatric diseases on diffusion tensor imaging have recently been performed, but these mainly utilize fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) values, and the results were inconsistent and not fully applied clinically. In this study, we investigated the possibility of differentiating between Alzheimer's disease (AD) and elderly major depressive disorder (MDD) patients in whom early-stage symptoms are difficult to diagnose, by visually evaluating cerebral nerve fascicles utilizing diffusion tensor tractography. We also measured and evaluated FA and ADC values at the same time. SUBJECTS AND METHODS: The subjects included 13 AD patients (age: 69.5 ± 5.1 years), 19 MDD patients (65.8 ± 5.7 years), and 22 healthy control (HC) subjects (67.4 ± 4.8 years). Images were acquired using a 1.5T magnetic resonance imaging device and analyzed by diffusion tensor tractography analysis software. RESULTS: Depiction of the anterior thalamic radiation (ATR) tended to be poor in AD patients unlike in MDD patients and HC subjects. The FA values in the left superior longitudinal fasciculus and fornix (FX) in AD patients were significantly different from those in MDD patients and HC subjects. The ADC values in the bilateral ATR and left superior and inferior longitudinal fasciculi, left inferior fronto-occipital fasciculus, and FX in AD patients were significantly different from those in MDD patients and HC subjects. CONCLUSION: Visual evaluation of the ATR in combination with the FA values of the left superior longitudinal fasciculus and FX and ADC values of the bilateral ATR, left superior and inferior longitudinal fasciculi, left inferior fronto-occipital fasciculus, and FX is useful for differentiating between AD and MDD patients, which further suggests that it may become a useful auxiliary diagnostic tool.

Identification of atrophy of the subgenual anterior cingulate cortex, in particular the subcallosal area, as an effective auxiliary means of diagnosis for major depressive disorder.

BACKGROUND: Despite being a very common psychiatric disorder, physicians often have difficulty making a diagnosis of major depressive disorder (MDD) because, without established diagnostic criteria, they have to depend on interviews with patients and observation to assess psychiatric symptoms. However, previous researchers have reported that magnetic resonance imaging (MRI) scans identify morphological changes in the brains of patients with MDD, which inspired us to hypothesize that assessment of local changes in the brain using voxel-based morphometry would serve as an auxiliary diagnostic method for MDD. Therefore, we focused on the VSRAD(®) plus (voxel-based specific regional analysis system for Alzheimer's disease), a diagnostic support system for use in early Alzheimer's disease, which allowed us to identify regional atrophy in the brain easily based on images obtained from MRI scans. METHODS: The subjects were 75 patients with MDD, 15 with bipolar disorder, and 30 healthy subjects, aged 54-82 years. First, 1.5 T MRI equipment was used to scan three-dimensional T(1)-weighted images for the individual subjects, and the imaged data were analyzed by VSRAD advance (voxel-based morphometric software developed for diagnosis of early Alzheimer's disease). The efficacy of the equipment for diagnosis of MDD was evaluated based on the distribution of atrophy in the subgenual anterior cingulate cortex (sACC) on the z-score map obtained. RESULTS: No significant difference in atrophy was noted between the left and right sACCs. The VSRAD advance used in the present study was more effective than the VSRAD plus for diagnosis of MDD, with a sensitivity of 90.7%, specificity of 86.7%, accuracy of 89.5%, a positive predictive value of 94.4%, and a negative predictive value of 78.8%. In particular, atrophy was observed in the subcallosal area of the sACC. CONCLUSION: The identification of atrophy in the sACC, in particular of the subcallosal area, with the use of updated voxel-based morphometric software proved to be effective as an auxiliary diagnostic method for MDD.

Diagnosis of depression by MRI scans with the use of VSRAD - a promising auxiliary means of diagnosis: a report of 10 years research.

OBJECTIVES: This study was designed to evaluate the usefulness of assessing subgenual anterior cingulate cortex (sACC) volume reduction by magnetic resonance imaging (MRI) as an objective auxiliary means of diagnosis of depression. The study was additionally designed to analyze the association of sACC volume reduction with the effectiveness of treatments for depression and other diseases presenting with similar symptoms, and to examine the possibility of using sACC volume reduction in the distinction between depression and bipolar disorder and determining optimum medication for these conditions. METHODS: Three-dimensional T1-weighted sagittal images, taken with Achieva 1.5T NOVA (Philips), were analyzed with VSRAD plus(®) to evaluate a reduction in sACC volume. The finding from this analysis was compared with the clinical data, including the longitudinal course follow-up data based on the treatment algorithm. SUBJECTS: The study involved 88 patients aged over 54 who received MRI during 2010, ie, 71 patients with major depressive disorder (MDD), 11 patients bipolar disorder, and 6 patients in whom the initial diagnosis (MDD) was later modified. Thirty-three normal individuals served as controls. RESULTS: sACC volume reduction was noted in 66 of the 71 patients receiving treatment of MDD, with sensitivity of 93%, specificity of 85%, and accuracy of 90%. In the 66 patients diagnosed as having MDD and exhibiting sACC volume reduction, the disease showed remission in response to treatment with antidepressants, but medication needed to be continued after achievement of remission. In cases initially diagnosed as having MDD but not exhibiting sACC volume reduction, the necessity of modifying the diagnosis was considered. Typical cases of bipolar disorder did not exhibit sACC volume reduction. CONCLUSION: That patients receiving treatment of MDD often showed reduction in sACC volume suggests the usefulness of this parameter as an objective auxiliary means of diagnosis for MDD.

Genetic variant of the Renin-Angiotensin system and diabetes influences blood pressure response to Angiotensin receptor blockers.

OBJECTIVE Recent studies have proven the favorable effects of angiotensin receptor blockers (ARBs) on cardiovascular and renal disorders. However, determinants of the response to ARBs remain unclear. We substantiated the hypothesis that genetic variants of the renin-angiotensin system (RAS) have significant impacts on the response to ARBs. RESEARCH DESIGN AND METHODS Subjects comprised 231 consecutively enrolled hypertensive individuals including 45 type 2 diabetic subjects. Five genetic variants of the RAS, i.e., renin (REN) C-5312T, ACE insertion/deletion, angiotensinogen M235T, angiotensin II type 1 receptor A1166C, and angiotensin II type 2 receptor C3123A were assayed by PCR and restriction fragment-length polymorphism. A dose of 40-160 mg/day of valsartan was administered for 3 months as a monotherapy. RESULTS Changes in diastolic blood pressure significantly differed between genotypes of REN C-5312T: 10.7-mmHg reduction (from 95.9 +/- 12.9 to 85.2 +/- 11.4) in CC versus 7.0-mmHg reduction (from 94.7 +/- 14.0 to 87.7 +/- 12.6) in CT/TT (P = 0.02 for interactive effects of valsartan and genotype). Responder rates also differed between the genotypes: 72.8% in CC versus 58.0% in CT/TT (P = 0.03). Univariate analysis indicated a significant association of response to valsartan with blood pressure, diabetes, plasma aldosterone concentration, and CC homozygotes of REN C-5312T. Finally, multiple logistic regression analysis revealed that systolic blood pressure, CC homozygotes of REN C-5312T, and diabetes were independent predictors for responders with odds ratios (95% CI) of 2.49 (1.41-4.42), 2.03 (1.10-3.74), and 0.48 (0.24-0.96), respectively. CONCLUSIONS This study provides strong support that a genetic variant of REN C-5312T and diabetes contribute to the effects of ARBs and are independent predictors for responder. Thus, in treatment of hypertension with ARBs, a new possibility for personalized medicine has been shown.

Synergistic expression of angiotensin-converting enzyme (ACE) and ACE2 in human renal tissue and confounding effects of hypertension on the ACE to ACE2 ratio.

Angiotensin-converting enzyme (ACE) 2, a newly emerging component of the renin-angiotensin system, is presumed to be a counterregulator against ACE in generating and degrading angiotensin II. It remains to be elucidated how mRNA levels of these two genes are quantitatively regulated in the kidney and also what kind of clinicopathological characteristics could influence the gene expressions in humans. Seventy-eight cases of biopsy-proven renal conditions were examined in detail. Total RNA from a small part of each renal cortical biopsy specimen was reverse transcribed, and the resultant cDNA was amplified for ACE, ACE2, and glyceraldehyde-3-phosphate dehydrogenase with a real-time PCR system. Then we investigated the relationship between clinicopathological variables and mRNA levels adjusted for glyceraldehyde-3-phosphate dehydrogenase. Statistically significant correlation was not observed between any clinicopathological variables and either of the gene expressions by pairwise comparison. However, a strong correlation was observed between the gene expressions of ACE and those of ACE2. Moreover, the ACE to ACE2 ratio was significantly higher in subjects with hypertension (HT) than that in subjects without HT. Whereas parameters of renal function, e.g. urinary protein excretion (UPE) and creatinine clearance (Ccr), are not significantly related to the ACE to ACE2 ratio as a whole, the HT status may reflect disease-induced deterioration of renal function. That is, UPE and Ccr of subjects with HT are significantly different from those without HT, in which a significant correlation is also observed between UPE and Ccr. Finally, stepwise regression analysis further revealed that only the HT status is an independent confounding determinant of the ACE to ACE2 ratio among the variables tested. Our data suggest that ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension. Thus, ACE2 may exert pivotal effects on cardiovascular and renal conditions.

Tissue gene expression of renin-angiotensin system in human type 2 diabetic nephropathy.

OBJECTIVE: Recent studies have proved that blockade of the renin-angiotensin system (RAS) retards the progression of diabetic nephropathy, whereas hyporeninemia is known as a typical state in diabetic subjects. The purpose of this study is to determine whether expression levels of RAS differ between nondiabetic and diabetic renal tissues with accurate quantitative method. RESEARCH DESIGN AND METHODS: Subjects were 66 nondiabetic and 8 diabetic patients with biopsy-proven renal diseases. The eight diabetic subjects suffered from type 2 diabetes with overt proteinuria. Renal histology revealed typical diffuse or nodular lesions with linear IgG deposit on immunofluorescent staining and thickened basement membrane on electronic microscopy. Total RNA from a small part of the renal cortical biopsy specimens was reverse-transcribed, and the resultant cDNA was amplified for new major components of RAS (i.e., renin, renin receptor, angiotensinogen, ACE, ACE2, angiotensin II type 1 receptor, and angiotensin II type 2 receptor) and measured. RESULTS: Among these components, a significant upregulation was observed in the ACE gene in diabetic renal tissue. CONCLUSIONS: The results suggest that renal tissue RAS might be activated in the respect that ACE gene expression is upregulated in spite of a tendency to low renin expression in type 2 diabetic nephropathy.