Low-Avidity Autoantibodies against Bactericidal/Permeability-Increasing Protein Occur in Gram-Negative and Gram-Positive Bacteremia.

Antibody autoreactivity against bactericidal/permeability-increasing protein (BPI) is strongly associated with Pseudomonas aeruginosa infection in cystic fibrosis (CF), non-CF bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD). We examined the pathogen-specific nature of this autoreactivity by examining antibodies to BPI in bacteremia patients. Antibodies to BPI and bacterial antigens were measured in sera by ELISA from five patient cohorts (n = 214). Antibody avidity was investigated. Bacteremic patient sera (n = 32) exhibited IgG antibody autoreactivity against BPI in 64.7% and 46.7% of patients with positive blood cultures for P. aeruginosa and Escherichia coli, respectively. Autoantibody titers correlated with IgG responses to bacterial extracts and lipopolysaccharide (LPS). A prospective cohort of bacteremic patient sera exhibited anti-BPI IgG responses in 23/154 (14.9%) patients with autoreactivity present at the time of positive blood cultures in patients with Gram-negative and Gram-positive bacteria, including 8/60 (13.3%) patients with Staphylococcus aureus Chronic tissue infection with S. aureus was associated with BPI antibody autoreactivity in 2/15 patients (13.3%). Previously, we demonstrated that BPI autoreactivity in CF patient sera exhibits high avidity. Here, a similar pattern was seen in BE patient sera. In contrast, sera from patients with bacteremia exhibited low avidity. These data indicate that low-avidity IgG responses to BPI can arise acutely in response to bacteremia and that this association is not limited to P. aeruginosa This is to be contrasted with chronic respiratory infection with P. aeruginosa, suggesting that either the chronicity or the site of infection selects for the generation of high-avidity responses, with biologic consequences for airway immunity.

Reoperative robotic pyeloplasty in children.

INTRODUCTION: Reoperative pyeloplasty for recurrent ureteropelvic junction obstruction (UPJO) can be technically challenging and is associated with greater morbidity and lower success rates than an initial repair. Robotic-assisted laparoscopic pyeloplasty (RALP) previously has been demonstrated to be a safe and effective approach for management of recurrent UPJO; however, the length of follow-up has been limited. The objective of this study was to confirm the safety and efficacy of RALP for UPJO in children following failed previous pyeloplasty and provide clinical benchmarks for intermediate length follow-up in this patient population. METHODS: An IRB approved retrospective chart review was performed for all patients undergoing reoperative RALP from June 2006 to December 2014. All cases were performed by surgeons from two institutions for persistent UPJO following failed initial pyeloplasty. Information including demographic information, radiographic studies, and operative interventions performed between the initial repair and reoperative surgery, reoperative RALP intraoperative data, postoperative clinical course and imaging studies, and subsequent interventions following reoperative RALP were extracted. RESULTS: Twenty-three children underwent reoperative RALP. Eleven patients had right- and 12 left-sided repairs. Median age at reoperative RALP was 4.0 years and median interval between surgeries was 1.3 years. Indications for repeat repair included pain, infection, and/or radiographic evidence of worsening obstruction and/or deteriorating renal function. Mean operative time was 198 min from incision to port closure. Mean length of stay was 2.3 days. Six complications occurred in five patients within 30 days postoperatively, including ileus, pneumonia, and urinary tract infection. Median length of follow-up was 26 months (range 4-45 months) for all patients and 31 months (range 16-45 months) in 18 patients with >12 months of follow-up. More than 80% of patients presenting with flank pain prior to reoperative RALP had resolution of this symptom. To date, 78% of patients with >12 months of follow-up have not required further operative intervention. Excellent results have been achieved in 14 of 18 patients (78%) with sufficient postoperative follow-up in terms of length of follow-up (>12 months), symptom resolution, and/or improved imaging results. CONCLUSIONS: RALP following previous pyeloplasty is technically feasible with acceptable operative times, lengths of stay, and complication rates. Reoperative RALP is our preferred modality for repair of recurrent UPJO with the vast majority of patients having successful outcomes based on imaging, resolution of symptoms, and the rare need for further intervention across an intermediate length follow-up period.

Spinal cord essentials: The development of an individualized, handout-based patient and family education initiative for people with spinal cord injury.

STUDY DESIGN: Mixed (environmental scan, qualitative and semiquantitative). OBJECTIVES: To develop a customizable patient and family education resource for people with spinal cord injury (SCI). SETTING: SCI rehabilitation center (Canada). METHODS: An environmental scan was conducted and stakeholder input sought to generate a list of potential handouts and inform content development. Staff members were recruited to draft handouts, which were later edited and finalized by the project team. Hardcopies of handouts were placed in cabinets throughout the rehabilitation center. Staff members were also trained/coached to facilitate and promote usage; which was then tracked for 2 years. RESULTS: One hundred and fifty-six potential handouts were identified; 83 deemed high priority. Seventy-two handouts addressing patient organization, self-management and community integration were finalized for phase 1. At inpatient admission, patients receive a binder containing base materials. The binder is then customized and populated with pertinent handouts throughout the rehabilitation admission, and taken home at discharge for future reference. Handouts with the highest usage covered medical management (for example, bladder, bowel and pressure ulcers), mobility and activities of daily living. Handouts were also helpful for staff training and orientation, as well as increasing the confidence of staff providing education outside their immediate area of expertise. CONCLUSION: Spinal Cord Essentials is a novel patient and family education initiative comprised of practical handouts that address many important aspects of SCI management. Handouts can be downloaded for free in four languages (English, French, Chinese and Farsi) at www.spinalcordessentials.ca. Additional handouts are planned for subsequent phases of the project.

The Walking Index for Spinal Cord Injury (WISCI/WISCI II): nature, metric properties, use and misuse.

STUDY DESIGN: Literature review. OBJECTIVE: To critically review all publications/internet sites that have described/used the Walking Index for Spinal Cord Injury (WISCI II), as a measure of impairment of walking function after spinal cord injury (SCI), in order to identify its psychometric properties, clarify its nature, specify misuse and incorporate the findings in an updated guide. METHOD: A systematic literature search was done of Ovid MEDLINE, CINAHL, PsychINFO, Cochrane Central Register of Controlled Trials, Scopus and electronic sites using key words: WISCI or WISCI II, SCI, paraplegia/ tetraplegia/ quadriplegia and ambulation/gait/walking. Among 1235 citations retrieved, 154 relevant articles/sites were identified, classified and examined by the authors; recommendations were made based on findings. RESULTS AND DISCUSSION: The validity (face/concurrent/content/construct/convergent/criterion) and reliability of the WISCI II has been documented in clinical trials and clinical series, and considered adequate by systematic reviewers. In chronic SCI subjects, reliable determination of the maximum (as opposed to self-selected) WISCI II level requires more time and experience by the assessor. The correct use of WISCI II is clarified for testing acute/chronic phases of recovery after SCI, age of subjects, devices and settings. The WISCI II and walking speed measures may be performed simultaneously. CONCLUSION: The increased use of the WISCI II is attributed to its unique characteristics as a capacity measure of walking function and its strong metric properties. Appropriate use of the WISCI II was clarified and incorporated into a new guide for its use. Combining it with a walking speed measure needs further study.

Impact of benchmarking and clinical decision making tools on rehabilitation length of stay following spinal cord injury.

STUDY DESIGN: Performance improvement initiative. OBJECTIVES: To improve efficiency of spinal cord rehabilitation by reducing length of stay (LOS) while maintaining or improving patient outcomes. SETTING: Academic hospital in Canada. METHODS: LOS benchmarking was completed using national comparator data from the Canadian Institute for Health Information (CIHI). Clinical decision-making tools were developed to support implementation and sustainability. A standardized 'tentative discharge date' calculator was created to establish objective LOS targets. Defined discharge criteria and an accompanying clinical decision tree were developed to support team decision making and improve transparency. A revised patient census tool was also implemented to improve team communication and facilitate data collection. The initiative was implemented in March 2010 and the following metrics were evaluated: LOS, Functional Independence Measure (FIM) change and FIM efficiency. RESULTS: Outcomes are reported for the 2010/11 fiscal year, and compared with the two prior fiscal years. Mean LOS for individuals undergoing initial inpatient rehabilitation was 71.5 days for 2010/11, a 14 and 17% reduction compared with the 2008/09 and 2009/10 fiscal years, respectively. While LOS decreased, FIM change increased 9 and 16% compared with 2008/09 and 2009/10, respectively. Similarly, FIM efficiency increased 54 and 32% compared with 2008/09 and 2009/10. CONCLUSION: The use of benchmarking and decision support tools improved rehabilitation efficiency while increasing standardization in practice and transparency in LOS determination.

International spinal cord injury musculoskeletal basic data set.

OBJECTIVES: To develop an International Spinal Cord Injury (SCI) Musculoskeletal Basic Data Set as part of the International SCI Data Sets to facilitate consistent collection and reporting of basic musculoskeletal findings in the SCI population. SETTING: International. METHODS: A first draft of an SCI Musculoskeletal Basic Data Set was developed by an international working group. This was reviewed by many different organizations, societies and individuals over 9 months. Revised versions were created successively. RESULTS: The final version of the International SCI Musculoskeletal Basic Data Set contains questions on neuro-musculoskeletal history before spinal cord lesion; presence of spasticity/spasms; treatment for spasticity within the last 4 weeks; fracture(s) since the spinal cord lesion; heterotopic ossification; contracture; the location of degenerative neuromuscular and skeletal changes due to overuse after SCI; SCI-related neuromuscular scoliosis; the method(s) used to determine the presence of neuromuscular scoliosis; surgical treatment of the scoliosis; other musculoskeletal problems; if any of the musculoskeletal challenges above interfere with activities of daily living. Instructions for data collection and the data collection form are freely available on the International Spinal Cord Society (ISCoS) website (www.iscos.org.uk). CONCLUSION: The International SCI Musculoskeletal Basic Data Set will facilitate consistent collection and reporting of basic musculoskeletal findings in the SCI population.

Relationship of endothelial function and atherosclerosis to treatment response in late-life depression.

OBJECTIVE: Treatment response in late-life depression has been linked to cerebrovascular disease notably via the vascular depression hypothesis. This study investigated the relationship between endothelial function and atherosclerosis and treatment response to antidepressant monotherapy. METHODS: Twenty five patients with late-life depression were compared with 21 non-depressed control subjects in a case control study. Nine of the depressed subjects were responders to antidepressant monotherapy and 16 were not. Vascular measures included assessment of carotid intima media thickness (IMT) representing atherosclerosis and biopsied small artery dilatation to acetylcholine to assess endothelial function in a subset of subjects. RESULTS: There were no group differences in vascular risks or sociodemographic variables. There was a significant group difference (responders versus non-responders versus controls) on both IMT and endothelial function (p < 0.01 and p < 0.05, respectively) with a significant difference between controls and non-responders (p < 0.001) on IMT and between controls and responders (p < 0.05) and control versus non-responders (p < 0.05) on endothelial function but no significant difference between responders and non-responders. On both IMT and endothelial function, there was a gradient across groups, with control subjects having best vascular structure or function, non-responders worse and responders in-between. CONCLUSIONS: The results are consistent with a hypothesis that poorer antidepressant response in later life depressive disorder may be linked to an underlying vascular dysfunction and pathology. The study is small, and the results require replication but if confirmed, trials with vasoprotective medication aimed at improving vascular function in order to alter the prognosis of late-life depression would be a rational development.

The early evolution of spinal cord lesions on MR imaging following traumatic spinal cord injury.

BACKGROUND AND PURPOSE: How early spinal cord injury (SCI) lesions evolve in patients after injury is unknown. The purpose of this study was to characterize the early evolution of spinal cord edema and hemorrhage on MR imaging after acute traumatic SCI. MATERIALS AND METHODS: We performed a retrospective analysis of 48 patients with clinically complete cervical spine injury. Inclusion criteria were the clear documentation of the time of injury and MR imaging before surgical intervention within 72 hours of injury. The length of intramedullary spinal cord edema and hemorrhage was assessed. The correlation between time to imaging and lesion size was determined by multiple regression analysis. Short-interval follow-up MR imaging was also available for a few patients (n = 5), which allowed the direct visualization of changes in spinal cord edema. RESULTS: MR imaging demonstrated cord edema in 100% of patients and cord hemorrhage in 67% of patients. The mean longitudinal length of cord edema was 10.3 +/- 4.0 U, and the mean length of cord hemorrhage was 2.6 +/- 2.0 U. Increased time to MR imaging correlated to increased spinal cord edema length (P = .002), even after accounting for the influence of other variables. A difference in time to MR imaging of 1.2 days corresponded to an average increase in cord edema by 1 full vertebral level. Hemorrhage length was not affected by time to imaging (P = .825). A temporal increase in the length of spinal cord edema was confirmed in patients with short-interval follow-up MR imaging (P = .003). CONCLUSION: Spinal cord edema increases significantly during the early time period after injury, whereas intramedullary hemorrhage is comparatively static.

Spinal shock revisited: a four-phase model.

Spinal shock has been of interest to clinicians for over two centuries. Advances in our understanding of both the neurophysiology of the spinal cord and neuroplasticity following spinal cord injury have provided us with additional insight into the phenomena of spinal shock. In this review, we provide a historical background followed by a description of a novel four-phase model for understanding and describing spinal shock. Clinical implications of the model are discussed as well.

The molecular pathology of p53 in primitive neuroectodermal tumours of the central nervous system.

One hundred and one pre-treatment primary central primitive neuroectodermal tumours were analysed for the expression of p53 protein by immunohistochemistry using the monoclonal antibody DO-7. The staining intensity was classified into four groups: strong, medium, weak and negative and strong staining intensity was associated with the poorest survival. DNA sequencing of the p53 gene was performed in 28 cases representing all four staining groups. Mutations were found in only three of the strong staining tumours suggesting that DNA mutations were not common events and that in the majority of the tumours with over-expressed p53, the protein was likely to be wild-type. Results of immunohistochemistry showed a significantly positive relationship between the expression of p53 and Bax and Bcl-2 proteins, but not Waf-1. Multivariate analyses supported the prognostic value of p53 immunostaining in central primitive neuroectodermal tumours and also of age and gender of patients.

Intrathecal baclofen in tetraplegia of spinal origin: efficacy for upper extremity hypertonia.

STUDY DESIGN: Retrospective analysis. OBJECTIVES: To evaluate the efficacy of intrathecal baclofen (ITB) for upper extremity spastic hypertonia in tetraplegia of spinal origin. SETTING: University of Alabama at Birmingham hospital. METHODS: The medical records of 14 individuals with tetraplegia of spinal origin who underwent intrathecal baclofen pump placement were reviewed. The effects of intrathecal baclofen on spasm frequency, deep tendon reflexes, and tone (Ashworth scale) were assessed for the upper and lower extremities for a 1-year follow-up period. RESULTS: There were statistically significant declines in upper extremity spasm scores (1.8 points, P=0.012), reflex scores (1.4 points, P<0.0001) and Ashworth scores (0.6 points, P<0.0001) for the 1-year follow-up period. For the lower extremities, all decreases were significant (P<0.0001). There was also a statistically significant (P<0.0001) increase in intrathecal baclofen dosage requirements during the 1-year follow-up period to maintain the reductions in spasm frequency, reflexes and tone. CONCLUSIONS: Intrathecal baclofen is a safe and effective intervention for treating upper extremity hypertonia of spinal origin. In addition, the level of intrathecal catheter placement is felt to be of importance.

Deep water running: an effective non-weightbearing exercise for the maintenance of land-based running performance.

Deep water running (DWR) has become a well-recognized from of cardiovascular conditioning for injured athletes and has been used successfully to maintain running performance. DWR provides for decreased stress and weightbearing to injured tissue and joints, allows for maintenance of cardiovascular fitness and a training effect, and offers greater specificity of exercise in relation to running. During a 22-month period, 181 active duty Army soldiers, placed on temporary profiles for injuries that precluded them from their regular weightbearing physical fitness activities, participated in a DWR program. Injuries to the back, knee, and ankle were the most common reasons for referral to the program. This article reviews the physiological characteristics of DWR, specifics of DWR program design, DWR mechanics, and the advantages of DWR over other aerobic forms of exercise to maintain land running performance in military personnel on temporary non-weightbearing profiles.

The management of neurogenic bladder and sexual dysfunction after spinal cord injury.

STUDY DESIGN: Review article. OBJECTIVES: To review the medical literature and comprehensively discuss the management of bladder and sexual dysfunction after spinal cord injury. SUMMARY OF BACKGROUND DATA: The physiologic alterations that accompany spinal cord injury can lead to significant bladder and sexual dysfunction. Fertility in men is also diminished. Without appropriate intervention, the above conditions can lead to significant morbidity and mortality. METHODS: Structured review of published reports obtained through a MED-LINE search and texts. RESULTS/CONCLUSION: With appropriate surveillance and management, morbidity and mortality from neurogenic bladder dysfunction can be successfully prevented. Current treatment interventions also facilitate the restoration of sexual function and fertility after spinal cord injury.

Establishing prognosis and maximizing functional outcomes after spinal cord injury: a review of current and future directions in rehabilitation management.

STUDY DESIGN: Review article. OBJECTIVES: To review the medical literature and provide a framework for predicting neurorecovery and functional outcomes after spinal cord injury based on injury severity. SUMMARY OF BACKGROUND DATA: The ability to accurately predict the magnitude of neurorecovery and expected functional outcomes after spinal cord injury is of great importance. This information is needed to justify medical and rehabilitation interventions to third party payers as well as to begin the process of planning for postdischarge care. Over the past several decades, significant progress has been made in accurately predicting neurorecovery and its impact on functional outcomes. METHODS: Structured review of published reports obtained through MED-LINE search and texts. RESULTS/CONCLUSION: Within 72 hours to 1 month after a spinal cord injury, it is possible to predict with reasonable accuracy the magnitude of expected recovery based on physical examination. The impact of motor level on long-term functional outcomes is also clear and has remained relatively unchanged for several decades. Functional outcomes are likely to improve in upcoming years as novel interventions, such as drugs and functional neuromuscular stimulation, are developed with the goals of limiting secondary injury and restoring neurologic function. New training methods, such as body weight support, that use activity-dependent neuroplasticity will also have a more prominent role.

Gynecologic and reproductive issues in women with spinal cord injury.

As the treatment of SCI and its secondary medical complications improves, women with SCI are becoming increasingly successful in re-integrating themselves into society. Part of this re-integration involves the resumption of active sexual lives and motherhood. Clinicians who care for patients with SCIs play an important role in facilitating the resumption of these roles. With appropriate follow-up and care, women with SCI should be expected to maintain good gynecologic health and deliver healthy children with minimal complications.

Importance of gadolinium enhancement when using MRI to evaluate spinal cord pathology.

Since its introduction, magnetic resonance imaging has become an indispensable diagnostic tool for the physiatrist evaluating potential spinal cord pathology. Despite ongoing advances in MRI technology and subsequent improved sensitivity, significant pathology can still be missed. In this article, we review the clinical role of contrast enhancement in visualizing many forms of spinal cord pathology.

Is subcortical disease associated with a poor response to antidepressants? Neurological, neuropsychological and neuroradiological findings in late-life depression.

BACKGROUND: Late-life depression is associated with increased subcortical white matter hyperintensities. There is some evidence that they are associated with a poorer response to acute treatment. Neurological signs and neuropsychological dysfunction are further evidence of abnormalities in the brain, but they have not been studied in relation to therapy resistance. METHODS: A prospective study of 24 normal controls and 75 consecutive elderly (aged 65 to 85) patients with DSM-III-R major depression entered a naturalistic study of treatment. Assessment of response to monotherapy and then lithium augmentation or ECT created three outcome groups. Investigations included magnetic resonance brain imaging, neuropsychological and neurological examination. RESULTS: Response to monotherapy within 12 weeks was shown by 42.7%, a further 37.3% responded to lithium augmentation or ECT within 24 weeks and 20% had responded poorly to all treatments at 24 weeks. Subcortical hyperintensities were significantly increased in the more resistant patients. These included confluent deep white matter, multiple (> 5) basal ganglia lesions and pontine reticular formation lesions. Most of the neuropsychological impairment was restricted to the resistant groups and was of a subcortico-frontal type. Extrapyramidal, frontal and pyramidal neurological signs characterized the resistant groups. The combination of extrapyramidal signs, pyramidal tract signs and impairment of motor hand sequencing strongly predicted resistance to 12 weeks of antidepressant monotherapy with 89% sensitivity and 95% specificity. CONCLUSION: In late-life depression a poor response to antidepressant monotherapy can be expected in those patients with a frontal lobe syndrome, extrapyramidal signs or if MRI T2-weighted lesions are present in both the basal ganglia and the pontine reticular formation.