Urine leaks in children sustaining blunt renal trauma.

BACKGROUND: Few consensus statements exist to guide the timely diagnosis and management of urine leaks in children sustaining blunt renal trauma (BRT). The aims of this study were to characterize kidney injuries among children who sustain BRT, evaluate risk factors for urine leaks, and describe the negative impact of urinoma on patient outcomes and resource consumption. METHODS: A retrospective review was performed of 347 patients, younger than 19 years, who presented with BRT to a single American College of Surgeons-verified Level I Pediatric Trauma Center between 2005 and 2020. Frequency of and risk factors for urine leak after BRT were evaluated, and impact on patient outcomes and resource utilization were analyzed. RESULTS: In total, 44 (12.7%) patients developed urine leaks, which exclusively presented among injury Grade 3 (n = 5; 11.4%), Grade 4 (n = 27; 61.4%), and Grade 5 (n = 12; 27.3%). A minority of urine leaks (n = 20; 45.5%) were discovered on presenting CT scan but all within 3 days. Kidney-specific operative procedures (nephrectomy, cystoscopy with J/ureteral stent, percutaneous nephrostomy) were more common among urine leak patients (n = 17; 38.6%) compared with patients without urine leaks (n = 3; 1.0%; p = 0.001). Patients with urine leak had more frequent febrile episodes during hospital stay (n = 24; 54.5%; p = 0.001) and showed increased overall 90-day readmission rates (n = 14; 33.3%; p < 0.001). Independent risk factors that associated with urine leak were higher grade (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.6-24.3; p < 0.001), upper-lateral quadrant injuries (OR, 2.9; 95% CI, 1.2-7.1; p = 0.02), and isolated BRT (OR, 2.6; 95% CI, 1.0-6.5; p = 0.04). CONCLUSION: In a large cohort of children sustaining BRT, urine leaks result in considerable morbidity, including more febrile episodes, greater 90-day readmission rates, and increased operative or image-guided procedures. This study is the first to examine the relationship between kidney quadrant injury and urine leaks. Higher grade (Grade 4-5) injury, upper lateral quadrant location, and isolated BRT were independently predictive of urine leaks. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Association of chest tube position with phrenic nerve palsy after neonatal and infant cardiac surgery.

BACKGROUND: Diaphragm paralysis (DP) complicates the postoperative course of neonates and infants undergoing cardiac surgery. Events causing DP remain poorly understood, and preventive strategies remain elusive. This retrospective cohort analysis aims to test the hypothesis that chest tubes in contact with the phrenic nerve in the pleural apex may cause pressure palsy. METHODS: In late 2018, the chest tube positioning strategy was changed so as to avoid a putative "danger zone" configuration, defined as (1) the chest tube looping apicomedially at the level of the second right intercostal space, and (2) wedging of chest tube tip against pericardium. A preintervention and postintervention analysis of 531 patients from 2012 to 2019 was performed to evaluate any association of chest tube position or duration in place with DP. Univariable and multivariable analyses were carried out, with significance set a priori at P < .05. RESULTS: The preintervention group comprised 488 patients, of whom 32 (6.6%) had RDP. The postintervention group comprised 43 patients, none of whom had DP. Multivariable analysis of the entire cohort revealed chest tube positioning in the danger zone as the only significant association with RDP (odds ratio, 4.22; 95% confidence interval, 1.57-11.33; P < .05). CONCLUSIONS: Chest tubes that occupy the right superior pleural space are associated with increased risk of DP.

Deformational brachycephaly: the clinical utility of the cranial index.

OBJECTIVE: The incidence of deformational brachycephaly has risen since the "Back to Sleep" movement in 1992 by the American Academy of Pediatrics. Brachycephaly prevalence and understanding the dynamic nature of the pediatric skull have not been explored in relation to the cranial index (CI). The objective of the study was to determine the prevalence of brachycephaly, via the CI, with respect to time. METHODS: The authors conducted a retrospective review of 1499 patients ≤ 19 years of age who presented for trauma evaluation with a negative CT scan for trauma (absence of bleed) in 2018. The CI was calculated using CT at the lateral-most point of the parietal bone (cephalic width), and the distance from the glabella to the opisthocranion (cephalic length). Brachycephaly was defined as a CI ≥ 90%. RESULTS: The mean CI was 82.6, with an average patient age of 6.8 years. The prevalence of deformational brachycephaly steadily decreased from 27% to 4% from birth to > 2 years of life. The mean CI was statistically different between ages < 12 months, 12-24 months, and > 24 months (F[2,1496] = 124.058, p < 0.0005). A simple linear regression was calculated to predict the CI based on age; the CI was found to decrease by 0.038 each month. A significant regression equation was found (F[1,1497] = 296.846, p < 0.0005), with an R2 of 0.140. CONCLUSIONS: The incidence of deformational brachycephaly is common in infants but decreases as the child progresses through early childhood. Clinicians can expect a significant decrease in mean CI at 12 and 24 months. Additionally, these regression models show that clinicians can expect continued improvement throughout childhood.

Management of Suprasellar Arachnoid Cysts in Children: A Systematic Literature Review Highlighting Modern Endoscopic Approaches.

OBJECTIVE: Suprasellar arachnoid cysts are a rare but important pediatric neurosurgical pathology with unknown ideal management. They have been previously managed with techniques including open craniotomy with microsurgical fenestration, cystoperitoneal shunting, endoscopic ventriculocystostomy, and endoscopic ventriculocystocisternostomy (VCC), without a consistent consensus on the best surgical approach. We present an overview of the literature on surgical management of suprasellar arachnoid cysts. METHODS: A literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted for all articles evaluating treatment modalities for suprasellar arachnoid cysts, using PubMed, OVID, and Web of Science. RESULTS: Twenty-five articles on management of suprasellar arachnoid cysts in children were identified. Few published studies exist that examine different types of surgical management across a single institution. The majority of studies reported best clinical outcomes in patients treated with endoscopic approaches when compared with microsurgical fenestration or cystoperitoneal shunting, reporting lower rates of infection, shunt dependence, and need for revision in addition to better resolution of clinical symptoms. Furthermore, most studies argue that VCC is superior to ventriculocystostomy, offering better long-term improvement of clinical symptoms and lower rates of failure. CONCLUSIONS: This study examines the current literature on suprasellar arachnoid cyst surgical management to conclude that an endoscopic approach in comparison with other approaches has the best outcomes. Of the endoscopic options available, VCC provides patients with the best long-term resolution of symptoms and the lowest need for revision. These findings should be further investigated with larger multicenter studies to further compare different surgical techniques and outcomes.

Chiari type I malformation: role of the Chiari Severity Index and Chicago Chiari Outcome Scale.

OBJECTIVE: The authors aimed to determine whether the Chiari Severity Index (CSI), and other clinical variables, can be used as a predictor of postoperative outcomes for Chiari type I malformation (CM-I) using the modified Chicago Chiari Outcome Scale (mCCOS) as the postoperative measure. METHODS: The cohort included patients 18 years of age and younger who were treated for CM-I between 2010 and 2015 who had at least 12 months of clinical and radiographic follow-up. CSI grades were assigned using preoperative clinical and neuroimaging data. Clinical, radiographic, and operative data were obtained from medical records. Kruskal-Wallis tests and Spearman correlations were conducted to assess for differences among CSI grades. Linear and ordinal regressions were conducted to evaluate predictors of the mCCOS and its components. Statistical significance was set a priori at p < 0.05. RESULTS: A total of 65 patients were included in the final cohort. The average age at the time of surgery and the mean mCCOS score were 9.8 ± 4.9 years and 10.4 ± 1.4, respectively. There were no significant differences in the mean mCCOS scores or CSI grades. Pre- and postoperative syrinx sizes were similar across the total patient cohort with median sizes of 7.4 and 3.7 mm, respectively. After controlling for age at the time of surgery, whether duraplasty and/or arachnoid dissection was performed, CSI preoperative score did not predict postoperative mCCOS score. No clinical variable could predict total mCCOS score. When the mCCOS was broken down into 3 subcomponents (pain, non-pain, and complications), only one relationship was identified. Those patients who presented with no headache had a statistically significant decrease in their pain (neck pain, shoulder pain, or dysesthesia in the upper extremities) as measured by the pain component of the mCCOS (χ2 [2, n = 20] = 6.43, p = 0.04). All other preclinical predictors, including CSI grades, were nonsignificant in demonstrating correlations to the mCCOS subcomponents. CONCLUSIONS: CSI grade was not found to be a marker of surgical outcome as measured by the mCCOS in this study. There were no correlations between the clinical variables and covariates investigated with the mCCOS. The lack of variation in mCCOS scores across this cohort may suggest that the mCCOS is not adequate for detecting differences in postsurgical outcomes. Further investigation is warranted to make this determination.

Pediatric cranial deformations: demographic associations.

OBJECTIVE: No study has established a relationship between cranial deformations and demographic factors. While the connection between the Back to Sleep campaign and cranial deformation has been outlined, considerations toward cultural or anthropological differences should also be investigated. METHODS: The authors conducted a retrospective review of 1499 patients (age range 2 months to less than 19 years) who presented for possible trauma in 2018 and had a negative CT scan. The cranial vault asymmetry index (CVAI) and cranial index (CI) were used to evaluate potential cranial deformations. The cohort was evaluated for differences between sex, race, and ethnicity among 1) all patients and 2) patients within the clinical treatment window (2-24 months of age). Patients categorized as "other" and those for whom data were missing were excluded from analysis. RESULTS: In the CVAI cohort with available data (n = 1499, although data were missing for each variable), 800 (56.7%) of 1411 patients were male, 1024 (79%) of 1304 patients were Caucasian, 253 (19.4%) of 1304 patients were African American, and 127 (10.3%) of 1236 patients were of Hispanic/Latin American descent. The mean CVAI values were significantly different between sex (p < 0.001) and race (p < 0.001). However, only race was associated with differences in positional posterior plagiocephaly (PPP) diagnosis (p < 0.001). There was no significant difference in CVAI measurements for ethnicity (p = 0.968). Of the 520 patients in the treatment window cohort, 307 (59%) were male. Of the 421 patients with data for race, 334 were Caucasian and 80 were African American; 47 of the 483 patients with ethnicity data were of Hispanic/Latin American descent. There were no differences between mean CVAI values for sex (p = 0.404) or ethnicity (p = 0.600). There were significant differences between the mean CVAI values for Caucasian and African American patients (p < 0.001) and rate of PPP diagnosis (p = 0.02). In the CI cohort with available data (n = 1429, although data were missing for each variable), 849 (56.8%) of 1494 patients were male, 1007 (67.4%) of 1283 were Caucasian, 248 (16.6%) of 1283 were African American, and 138 patients with ethnicity data (n = 1320) of Hispanic/Latin American descent. Within the clinical treatment window cohort with available data, 373 (59.2%) of 630 patients were male, 403 were Caucasian (81.9%), 84 were African American (17.1%), and 55 (10.5%) of 528 patients were of Hispanic/Latin American descent. The mean CI values were not significantly different between sexes (p = 0.450) in either cohort. However, there were significant differences between CI measurements for Caucasian and African American patients (p < 0.001) as well as patients of Hispanic/Latin American descent (p < 0.001) in both cohorts. CONCLUSIONS: The authors found no significant associations between cranial deformations and sex. However, significant differences exist between Caucasian and African American patients as well as patients with Hispanic/Latin American heritage. These findings suggest cultural or anthropological influences on defining skull deformations. Further investigation into the factors contributing to these differences should be undertaken.

Positional posterior plagiocephaly: a single-center review.

OBJECTIVE: The authors sought to assess the prevalence and severity of positional posterior plagiocephaly (PPP) in the pediatric population at a tertiary care center. METHODS: The authors conducted a retrospective review of 1429 consecutive patients aged 2 months to 18 years who presented with head trauma and a negative CT scan in 2018. The cohort was stratified by age. The cranial vault asymmetry index (CVAI) was calculated at the superior orbital rim. Asymmetry was categorized according to the following CVAI scores: mild (3.5%-7%), moderate (7%-12%), and severe (> 12%). Patients were grouped by age to assess PPP at different stages of head development: group 1, 2-5 months; group 2, 6-11 months; group 3, 12-23 months; group 4: 2-4 years; group 5, 5-8 years; group 6, 9-12 years; and group 7, 13-18 years. Patients with a history of shunted hydrocephalus, craniosynostosis, skull surgery, or radiographic evidence of intracranial trauma were excluded. RESULTS: The overall cohort prevalence of PPP was 24.8% (354 patients). PPP prevalence was higher among younger patients from groups 1-3 (40.4%, 33.5%, and 0.8%, respectively). There was a continued decline in PPP by age in groups 4-7 (26.4%, 20%, 20%, and 10.8%, respectively). Mild cranial vault asymmetry was noted most often (78.0%, 276 patients), followed by moderate (19.5%, 69 patients) and severe (2.5%, 9 patients). There were no patients in group 6 or 7 with severe PPP. CONCLUSIONS: PPP is prevalent in pediatric populations and most commonly presents as a case of mild asymmetry. Although there was an overall decline of PPP prevalence with increasing age, moderate asymmetry was seen in all age groups. No patients in the cohort had severe asymmetry that persisted into adolescence.

Diverse Effects on M1 Signaling and Adverse Effect Liability within a Series of M1 Ago-PAMs.

Both historical clinical and recent preclinical data suggest that the M1 muscarinic acetylcholine receptor is an exciting target for the treatment of Alzheimer's disease and the cognitive and negative symptom clusters in schizophrenia; however, early drug discovery efforts targeting the orthosteric binding site have failed to afford selective M1 activation. Efforts then shifted to focus on selective activation of M1 via either allosteric agonists or positive allosteric modulators (PAMs). While M1 PAMs have robust efficacy in rodent models, some chemotypes can induce cholinergic adverse effects (AEs) that could limit their clinical utility. Here, we report studies aimed at understanding the subtle structural and pharmacological nuances that differentiate efficacy from adverse effect liability within an indole-based series of M1 ago-PAMs. Our data demonstrate that closely related M1 PAMs can display striking differences in their in vivo activities, especially their propensities to induce adverse effects. We report the discovery of a novel PAM in this series that is devoid of observable adverse effect liability. Interestingly, the molecular pharmacology profile of this novel PAM is similar to that of a representative M1 PAM that induces severe AEs. For instance, both compounds are potent ago-PAMs that demonstrate significant interaction with the orthosteric site (either bitopic or negative cooperativity). However, there are subtle differences in efficacies of the compounds at potentiating M1 responses, agonist potencies, and abilities to induce receptor internalization. While these differences may contribute to the differential in vivo profiles of these compounds, the in vitro differences are relatively subtle and highlight the complexities of allosteric modulators and the need to focus on in vivo phenotypic screening to identify safe and effective M1 PAMs.

Discovery and SAR of a novel series of potent, CNS penetrant M4 PAMs based on a non-enolizable ketone core: Challenges in disposition.

This Letter describes the chemical optimization of a novel series of M4 PAMs based on a non-enolizable ketone core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent, selective and CNS penetrant; however, the compound was highly cleared in vitro and in vivo. SAR provided analogs for which M4 PAM potency and CNS exposure were maintained; yet, clearance remained high. Metabolite identification studies demonstrated that this series was subject to rapid, and near quantitative, reductive metabolism to the corresponding secondary alcohol metabolite that was devoid of M4 PAM activity.