Airway oscillometry parameters in baseline lung allograft dysfunction: Associations from a multicenter study.

BACKGROUND: Baseline lung allograft dysfunction (BLAD), the failure to achieve ≥80%-predicted spirometry after lung transplant (LTx), is associated with impaired survival. Physiologic abnormalities in BLAD are poorly understood. Airway oscillometry measures respiratory system mechanics and may provide insight into understanding the mechanisms of BLAD. OBJECTIVES: This study aims to describe and measure the association between airway oscillometry parameters [Reactance (Xrs5, Ax), Resistance (Rrs5, Rrs5-19)] (1) stable LTx recipients, comparing those with normal spirometry and those with BLAD; and (2) in recipients with chronic lung allograft dysfunction (CLAD), comparing those with normal baseline spirometry and those with BLAD. METHODS: A multi-center cross-sectional study was performed including bilateral LTx between January 2020 and June 2021. Participants performed concurrent airway oscillometry and spirometry. Multivariable logistic regression was performed to measure the association between oscillometry parameters and BLAD. RESULTS: A total of 404 LTx recipients performed oscillometry and 253 were included for analysis. Stable allograft function was confirmed in 149 (50.2%) recipients (92 (61.7%) achieving normal spirometry and 57 (38.3%) with BLAD). Among stable LTx recipients, lower Xrs5 Z-Score (aOR 0.50 95% CI 0.37-0.76, p = 0.001) was independently associated with BLAD. CLAD was present in 104 (35.0%) recipients. Among recipients with CLAD, lower Xrs5 Z-Score (aOR 0.73 95% CI 0.56-0.95, p = 0.02) was associated with BLAD. CONCLUSIONS: Oscillometry provides novel physiologic insights into mechanisms of BLAD. The independent association between Xrs5 and BLAD, in both stable recipients and those with CLAD suggests that respiratory mechanics, in particular abnormal elastance, is an important physiologic feature. Further longitudinal studies are needed to understand the trajectory of oscillometry parameters in relation to allograft outcomes.

Limited recovery from post-acute sequelae of SARS-CoV-2 at 8 months in a prospective cohort.

In a longitudinal cohort, a significant proportion of patients had persistent symptoms 8 months after initial #COVID19 infection. There was no significant improvement in symptoms or health-related quality of life between 4- and 8-month assessments. https://bit.ly/2Wtb7IX.

The identification of a subgroup of children with traumatic subarachnoid hemorrhage at low risk of neuroworsening.

OBJECTIVEPediatric traumatic subarachnoid hemorrhage (tSAH) often results in intensive care unit (ICU) admission, the performance of additional diagnostic studies, and ICU-level therapeutic interventions to identify and prevent episodes of neuroworsening.METHODSData prospectively collected in an institutionally specific trauma registry between 2006 and 2015 were supplemented with a retrospective chart review of children admitted with isolated traumatic subarachnoid hemorrhage (tSAH) and an admission Glasgow Coma Scale (GCS) score of 13-15. Risk of blunt cerebrovascular injury (BCVI) was calculated using the BCVI clinical prediction score.RESULTSThree hundred seventeen of 10,395 pediatric trauma patients were admitted with tSAH. Of the 317 patients with tSAH, 51 children (16%, 23 female, 28 male) were identified with isolated tSAH without midline shift on neuroimaging and a GCS score of 13-15 at presentation. The median patient age was 4 years (range 18 days to 15 years). Seven had modified Fisher grade 3 tSAH; the remainder had grade 1 tSAH. Twenty-six patients (51%) had associated skull fractures; 4 involved the petrous temporal bone and 1 the carotid canal. Thirty-nine (76.5%) were admitted to the ICU and 12 (23.5%) to the surgical ward. Four had an elevated BCVI score. Eight underwent CT angiography; no vascular injuries were identified. Nine patients received an imaging-associated general anesthetic. Five received hypertonic saline in the ICU. Patients with a modified Fisher grade 1 tSAH had a significantly shorter ICU stay as compared to modified Fisher grade 3 tSAH (1.1 vs 2.5 days, p = 0.029). Neuroworsening was not observed in any child.CONCLUSIONSChildren with isolated tSAH without midline shift and a GCS score of 13-15 at presentation appear to have minimal risk of neuroworsening despite the findings in some children of skull fractures, elevated modified Fisher grade, and elevated BCVI score. In this subgroup of children with tSAH, routine ICU-level care and additional diagnostic imaging may not be necessary for all patients. Children with modified Fisher grade 1 tSAH may be particularly unlikely to require ICU-level admission. Benefits to identifying a subgroup of children at low risk of neuroworsening include improvement in healthcare efficiency as well as decreased utilization of unnecessary and potentially morbid interventions, including exposure to ionizing radiation and general anesthesia.

Do corticosteroids play a role in the management of traumatic brain injury?

Neuroprotective strategies for the medical management of traumatic brain injury (TBI) have been elusive. While laboratory studies provide a conceptual framework for the potential efficacy of corticosteroids in this context, clinical trials testing this hypothesis have yielded no convincing evidence of clinical benefit. Here, we review the five key randomized control trials (RCTs) that have examined this issue. Based on the proposed primary endpoints of these RCTs, the five RCTs consistently showed that corticosteroids do not confer significant benefit in the TBI population.

Impact of medical academic genealogy on publication patterns: An analysis of the literature for surgical resection in brain tumor patients.

"Academic genealogy" refers to the linking of scientists and scholars based on their dissertation supervisors. We propose that this concept can be applied to medical training and that this "medical academic genealogy" may influence the landscape of the peer-reviewed literature. We performed a comprehensive PubMed search to identify US authors who have contributed peer-reviewed articles on a neurosurgery topic that remains controversial: the value of maximal resection for high-grade gliomas (HGGs). Training information for each key author (defined as the first or last author of an article) was collected (eg, author's medical school, residency, and fellowship training). Authors were recursively linked to faculty mentors to form genealogies. Correlations between genealogy and publication result were examined. Our search identified 108 articles with 160 unique key authors. Authors who were members of 2 genealogies (14% of key authors) contributed to 38% of all articles. If an article contained an authorship contribution from the first genealogy, its results were more likely to support maximal resection (log odds ratio = 2.74, p < 0.028) relative to articles without such contribution. In contrast, if an article contained an authorship contribution from the second genealogy, it was less likely to support maximal resection (log odds ratio = -1.74, p < 0.026). We conclude that the literature on surgical resection for HGGs is influenced by medical academic genealogies, and that articles contributed by authors of select genealogies share common results. These findings have important implications for the interpretation of scientific literature, design of medical training, and health care policy.

Progression of traumatic intracerebral hemorrhage: a prospective observational study.

ABSTRACT Preliminary evidence has shown that intracerebral hemorrhages, either spontaneous (sICH) or traumatic (tICH) often expand over time. An association between hemorrhage expansion and clinical outcomes has been described for sICH. The intent of this prospective, observational study was to characterize the temporal profile of hemorrhage progression, as measured by serial computed tomography (CT) scanning, with the aim of better understanding the natural course of hemorrhage progression in tICH. There was also a desire to document the baseline adverse event (AE) profile in this patient group. An important motive for performing this study was to set the stage for subsequent studies that will examine the role of a new systemic hemostatic agent in tICH. Subjects were enrolled if they had tICH lesions of at least 2 mL on a baseline CT scan obtained within 6 h of a head injury. CT scans were repeated at 24 and 72 h. Clinical outcomes and pre-defined AEs were documented. The data showed that 51% of the subjects demonstrated an increase in tICH volume, and that most of the increase occurred early. In addition, larger hematomas exhibited the greatest expansion. Thromboembolic complications were identified in 13% of subjects. This study demonstrates that tICH expansion between the baseline and 24-h CT scans occurred in approximately half of the subjects. The earlier after injury that the initial CT scan is obtained, the greater is the likelihood that the hematoma will expand on subsequent scans. The time frame during which hemorrhagic expansion occurs provides an opportunity for early intervention to limit a process with adverse prognostic implications.

Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial.

OBJECTIVE: Intracerebral hemorrhages, whether spontaneous or traumatic (tICH), often expand, and an association has been described between hemorrhage expansion and worse clinical outcomes. Recombinant factor VIIa (rFVIIa) is a hemostatic agent that has been shown to limit hemorrhage expansion and which, therefore, could potentially reduce morbidity and mortality in tICH. This first prospective, randomized, placebo-controlled, dose-escalation study evaluated the safety and preliminary effectiveness of rFVIIa to limit tICH progression. METHODS: Patients were enrolled if they had tICH lesions of at least 2 ml on a baseline computed tomographic scan obtained within 6 hours of injury. rFVIIa or placebo was administered within 2.5 hours of the baseline computed tomographic scan but no later than 7 hours after injury. Computed tomographic scans were repeated at 24 and 72 hours. Five escalating dose tiers were evaluated (40, 80, 120, 160, and 200 microg/kg rFVIIa). Clinical evaluations and adverse events were recorded until Day 15. RESULTS: No significant differences were detected in mortality rate or number and type of adverse events among treatment groups. Asymptomatic deep vein thrombosis, detected on routinely performed ultrasound at Day 3, was observed more frequently in the combined rFVIIa treatment group (placebo, 3%; rFVIIa, 8%; not significant). A nonsignificant trend for rFVIIa dose-response to limit tICH volume increase was observed (placebo, 21.0 ml; rFVIIa, 10.1 ml). CONCLUSION: In this first prospective study of rFVIIa in tICH, there appeared to be less hematoma progression in rFVIIa-treated patients (80-200 microg/kg) compared with that seen in placebo treated patients. The potential significance of this biological effect on clinical outcomes and the significance of the somewhat higher incidence of ultrasound-detected deep vein thromboses in the rFVIIa-treated group need to be examined in a larger prospective randomized clinical trial.

Development of spontaneous intracranial hypotension concurrent with grade IV mobilization of the cervical and thoracic spine: a case report.

Spontaneous intracranial hypotension (SIH) has been clinically defined as the development of severe orthostatic headaches caused by an acute cerebrospinal fluid (CSF) leak. Typically, intracranial hypotension occurs as a complication of lumbar puncture, but recent reports have identified cases caused by minor trauma. We report a case of SIH secondary to a dural tear caused by a cervical and thoracic spine mobilization. A 32-year-old woman with SIH presented with severe positional headaches with associated hearing loss and C6-8 nerve root distribution weakness. CSF opening pressure was less than 5cmH(2)O and showed no abnormalities in white blood cell count. Cranial, cervical, and thoracic magnetic resonance imaging revealed epidural and subdural collections of CSF with associated meningeal enhancement. Repeated computed tomography myelograms localized the leak to multiple levels of the lower cervical and upper thoracic spine. A conservative management approach of bedrest and increased caffeine intake had no effect on the dural tear. The headache, hearing loss, and arm symptoms resolved completely after 2 epidural blood patches were performed. Practitioners performing manual therapy should be aware of this rare, yet potential complication of spinal mobilizations and manipulations.

Some prognostic models for traumatic brain injury were not valid.

OBJECTIVE: Various prognostic models have been developed to predict outcome after traumatic brain injury (TBI). We aimed to determine the validity of six models that used baseline clinical and computed tomographic characteristics to predict mortality or unfavorable outcome at 6 months or later after severe or moderate TBI. STUDY DESIGN AND SETTING: The validity was studied in two selected series of TBI patients enrolled in clinical trials (Tirilazad trials; n = 2,269; International Selfotel Trial; n = 409) and in two unselected series of patients consecutively admitted to participating centers (European Brain Injury Consortium [EBIC] survey; n = 796; Traumatic Coma Data Bank; n = 746). Validity was indicated by discriminative ability (AUC) and calibration (Hosmer-Lemeshow goodness-of-fit test). RESULTS: The models varied in number of predictors (four to seven) and in development technique (two prediction trees and four logistic regression models). Discriminative ability varied widely (AUC: .61-.89), but calibration was poor for most models. Better discrimination was observed for logistic regression models compared with trees, and for models including more predictors. Further, discrimination was better when tested on unselected series that contained more heterogeneous populations. CONCLUSION: Our findings emphasize the need for external validation of prognostic models. The satisfactory discrimination indicates that logistic regression models, developed on large samples, can be used for classifying TBI patients according to prognostic risk.

Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors.

BACKGROUND AND OBJECTIVE: The Marshall computed tomographic (CT) classification identifies six groups of patients with traumatic brain injury (TBI), based on morphological abnormalities on the CT scan. This classification is increasingly used as a predictor of outcome. We aimed to examine the predictive value of the Marshall CT classification in comparison with alternative CT models. METHODS: The predictive value was investigated in the Tirilazad trials (n = 2269). Alternative models were developed with logistic regression analysis and recursive partitioning. Six month mortality was used as outcome measure. Internal validity was assessed with bootstrapping techniques and expressed as the area under the receiver operating curve (AUC). RESULTS: The Marshall CT classification indicated reasonable discrimination (AUC = 0.67), which could be improved by rearranging the underlying individual CT characteristics (AUC = 0.71). Performance could be further increased by adding intraventricular and traumatic subarachnoid hemorrhage and by a more detailed differentiation of mass lesions and basal cisterns (AUC = 0.77). Models developed with logistic regression analysis and recursive partitioning showed similar performance. For clinical application we propose a simple CT score, which permits a more clear differentiation of prognostic risk, particularly in patients with mass lesions. CONCLUSION: It is preferable to use combinations of individual CT predictors rather than the Marshall CT classification for prognostic purposes in TBI. Such models should include at least the following parameters: status of basal cisterns, shift, traumatic subarachnoid or intraventricular hemorrhage, and presence of different types of mass lesions.

The effect of the selective NMDA receptor antagonist traxoprodil in the treatment of traumatic brain injury.

Traumatic brain injury (TBI) remains a major public health problem, and there is a great medical need for a pharmacological treatment that could improve long-term outcome. The excitatory neurotransmitter, glutamate, has been implicated in processes leading to neurodegeneration. Traxoprodil (CP-101,606) is a novel and potent glutamate receptor antagonist that is highly selective for the NR2B subunit of the NMDA receptor; it has been shown to be neuroprotective in animal models of brain injury and ischemia. A randomized, double-blind, placebo-controlled study was therefore conducted to assess the efficacy and safety of a 72-h infusion of traxoprodil compared to placebo in subjects with computed tomography scan evidence of severe TBI (GCS 4-8). A total of 404 males and non-pregnant females, aged 16-70, were treated within 8 h of injury. At baseline, subjects were stratified by motor score severity. The results showed that a greater proportion of the traxoprodil-treated subjects had a favorable outcome on the dichotomized Glasgow Outcome Scale (dGOS) at 6 months (delta 5.5%, OR 1.3, p = 0.21, 95% CI:[0.85, 2.06]) and at last visit (delta 7.5%, OR 1.47, p = 0.07, 95% CI:[0.97, 2.25]). The mortality rate with traxoprodil treatment was 7% less than with placebo treatment (OR 1.45, p = 0.08, 95% CI:[0.96, 2.18]). Differences between treatment groups were more pronounced in the severest subset (delta 11.8% for the dGOS at last visit and delta 16.6% for mortality). Traxoprodil was well tolerated. Although these results are intriguing, no definitive claim of efficacy can be made for traxoprodil for the treatment of severe TBI.

Predicting outcome after traumatic brain injury: development and validation of a prognostic score based on admission characteristics.

The early prediction of outcome after traumatic brain injury (TBI) is important for several purposes, but no prognostic models have yet been developed with proven generalizability across different settings. The objective of this study was to develop and validate prognostic models that use information available at admission to estimate 6-month outcome after severe or moderate TBI. To this end, this study evaluated mortality and unfavorable outcome, that is, death, and vegetative or severe disability on the Glasgow Outcome Scale (GOS), at 6 months post-injury. Prospectively collected data on 2269 patients from two multi-center clinical trials were used to develop prognostic models for each outcome with logistic regression analysis. We included seven predictive characteristics-age, motor score, pupillary reactivity, hypoxia, hypotension, computed tomography classification, and traumatic subarachnoid hemorrhage. The models were validated internally with bootstrapping techniques. External validity was determined in prospectively collected data from two relatively unselected surveys in Europe (n = 796) and in North America (n = 746). We evaluated the discriminative ability, that is, the ability to distinguish patients with different outcomes, with the area under the receiver operating characteristic curve (AUC). Further, we determined calibration, that is, agreement between predicted and observed outcome, with the Hosmer-Lemeshow goodness-of-fit test. The models discriminated well in the development population (AUC 0.78-0.80). External validity was even better (AUC 0.83-0.89). Calibration was less satisfactory, with poor external validity in the North American survey (p < 0.001). Especially, observed risks were higher than predicted for poor prognosis patients. A score chart was derived from the regression models to facilitate clinical application. Relatively simple prognostic models using baseline characteristics can accurately predict 6-month outcome in patients with severe or moderate TBI. The high discriminative ability indicates the potential of this model for classifying patients according to prognostic risk.

The science of shrinking human heads: tribal warfare and revenge among the South American Jivaro-Shuar.

THE PRACTICE OF "head-shrinking" has been the proper domain not of Africa but rather of the denizens of South America. Specifically, in the post-Columbian period, it has been most famously the practice of a tribe of indigenous people commonly called the Jivaro or Jivaro-Shuar. The evidence suggests that the Jivaro-Shuar are merely the last group to retain a custom widespread in northwestern South America. In both ceramic and textile art of the pre-Columbian residents of Peru, the motif of trophy heads smaller than normal life-size heads commonly recurs; the motif is seen even in surviving carvings in stone and shell. Moreover, although not true shrunken heads, trophy heads found in late pre-Columbian and even post-Columbian graves of the region demonstrate techniques of display very similar to those used by the Jivaro-Shuar, at least some of which are best understood in the context of head-shrinking. Regardless, the Jivaro-Shuar and their practices provide an illustrative counterexample to popular myth regarding the culture and science of the shrinking of human heads.

Syringocephaly.

Syringomyelia is associated with Arnold-Chiari Type I malformations. Syringobulbia describes the phenomenon of syrinx extension into the brain stem. Syringocephaly is the further dissection of the fluid-filled cavity into the cerebral peduncles and cerebrum. In this case report, we describe a patient who presented with bulbar, sensory, motor, and coordination deficits both ipsilateral and contralateral to the lesion. This is most likely attributable to the wandering course the syrinx takes as it dissects through the spinal cord and into the internal capsule. This ill-defined syrinx disrupts various nuclei and fasciculi, both pre- and post-decussation, thus explaining the multiple deficits on each side. We initially treated this patient with a suboccipital craniectomy, C1 laminectomy, and duraplasty, which mildly improved his deficits. During follow-up, the patient was then found to have an exacerbation of his symptoms, at which time we performed a VP shunt revision (the patient had a history of hydrocephalus treated by a functioning VP shunt). Approximately 2 weeks after revision of the VP shunt, the patient had worsening of his symptoms, which we treated with a syringopleural shunt. This proved to be the most effective treatment with the greatest clinical improvement. Several months later, however, the patient died secondary to pulmonary disease exacerbated by VP shunt infection. In this paper, we also review the literature regarding the formation and treatment of syringocephaly, a rare and poorly understood entity.

Patient age and outcome following severe traumatic brain injury: an analysis of 5600 patients.

OBJECT: Increasing age is associated with poorer outcome in patients with closed traumatic brain injury (TBI). It is uncertain whether critical age thresholds exist, however, and the strength of the association has yet to be investigated across large series. The authors studied the shape and strength of the relationship between age and outcome, that is, the 6-month mortality rate and unfavorable outcome based on the Glasgow Outcome Scale. METHODS: The shape of the association was examined in four prospective series with individual patient data (2664 cases). All patients had a closed TBI and were of adult age (96% < 65 years of age). The strength of the association was investigated in a metaanalysis of the aforementioned individual patient data (2664 cases) and aggregate data (2948 cases) from TBI studies published between 1980 and 2001 (total 5612 cases). Analyses were performed with univariable and multivariable logistic regression. Proportions of mortality and unfavorable outcome increased with age: 21 and 39%, respectively, for patients younger than 35 years and 52 and 74%, respectively, for patients older than 55 years. The association between age and both mortality and unfavorable outcome was continuous and could be adequately described by a linear term and expressed even better statistically by a linear and a quadratic term. The use of age thresholds (best fitting threshold 39 years) in the analysis resulted in a considerable loss of information. The strength of the association, expressed as an odds ratio per 10 years of age, was 1.47 (95% confidence interval [CI] 1.34-1.63) for death and 1.49 (95% CI 1.43-1.56) for unfavorable outcome in univariable analyses, and 1.39 (95% CI 1.3-1.5) and 1.46 (95% CI 1.36-1.56), respectively, in multivariable analyses. Thus, the odds for a poor outcome increased by 40 to 50% per 10 years of age. CONCLUSIONS: An older age is continuously associated with a worsening outcome after TBI; hence, it is disadvantageous to define the effect of age on outcome in a discrete manner when we aim to estimate prognosis or adjust for confounding variables.

Paramedic-administered neuromuscular blockade improves prehospital intubation success in severely head-injured patients.

BACKGROUND: The purpose of this study was to evaluate the effect of paramedic-administered neuromuscular blocking agents as part of a rapid-sequence intubation (RSI) protocol on successful intubation of severely head-injured patients in a large, urban prehospital system. METHODS: Adult head-injured patients were prospectively enrolled over 1 year using these inclusion criteria: Glasgow Coma Scale (GCS) score of 3 to 8, transport time > 10 minutes, and inability to intubate without RSI. Midazolam and succinylcholine were administered before laryngoscopy; rocuronium was given after tube placement was confirmed using capnometry, syringe aspiration, and pulse oximetry. The Combitube was used as a salvage airway device. All adult trauma victims with a GCS score of 3 to 8 were identified during the first 12 months of the study as the trial cohort and from the preceding 12 months as the control cohort. The trial and control cohorts were compared with regard to demographic data, mechanism of injury, initial vital signs, and GCS scores. The primary outcome measure was intubation success, defined as insertion of either an endotracheal tube or a Combitube, with patients stratified by GCS score. RESULTS: The trial cohort (n = 249) and control cohort (n = 189) were similar with regard to demographic data, mechanism of injury, and initial vital signs and GCS scores. Intubation success rates increased significantly during the trial period for all patients and when stratified into GCS score of 3 and GCS score of 4 to 8. The percentage of patients intubated without neuromuscular blocking agents actually increased during the trial period. Although the number of intubations by helicopter flight crews decreased during the trial, the overall use of aeromedical resources did not change. CONCLUSION: Paramedic-administered neuromuscular blockade as part of an RSI protocol improves intubation success in a large, urban prehospital system.