Factors predictive of survival and estimated years of life lost in the decade following nontraumatic and traumatic spinal cord injury.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: To identify factors predictive of survival after spinal cord injury (SCI). SETTING: Tertiary care institution. METHODS: Multiple-variable Cox proportional hazards regression analysis for 759 patients with SCI (535 nontraumatic and 221 traumatic) included age, sex, completeness of injury, level of injury, functional independence measure (FIM) scores, rehabilitation length of stay and SCI cause. Estimated years of life lost in the decade after injury was calculated for patients vs uninjured controls. RESULTS: Median follow-up was 11.4 years. Population characteristics included paraplegia, 58%; complete injury, 11%; male sex, 64%; and median rehabilitation length of stay, 16 days. Factors independently predictive of decreased survival were increased age (+10 years; hazard ratio (HR (95% CI)), 1.6 (1.4-1.7)), male sex (1.3 (1.0-1.6)), lower dismissal FIM score (-10 points; 1.3 (1.2-1.3)) and all nontraumatic causes. Metastatic cancer had the largest decrease in survival (HR (95% CI), 13.3 (8.7-20.2)). Primary tumors (HR (95% CI), 2.5 (1.7-3.8)), vascular (2.5 (1.6-3.8)), musculoskeletal/stenosis (1.7 (1.2-2.5)) and other nontraumatic SCI (2.3 (1.5-3.6)) were associated with decreased survival. Ten-year survival was decreased in nontraumatic SCI (mean (s.d.), 1.8 (0.3) years lost), with largest decreases in survival for metastatic cancer and spinal cord ischemia. CONCLUSIONS: Age, male sex and lower dismissal FIM score were associated with decreased survival, but neither injury severity nor level was associated with it. Survival after SCI varies depending on SCI cause, with survival better after traumatic SCI than after nontraumatic SCI. Metastatic cancer and vascular ischemia were associated with the greatest survival reduction.

Clinical features and inpatient rehabilitation outcomes of infection-related myelopathy.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVES: The objectives of this study were to determine clinical features of infection-related myelopathy (IRM) and functional outcomes compared with other nontraumatic and traumatic myelopathies. SETTING: US academic inpatient rehabilitation unit. METHODS: This was a 16-year retrospective review of patients with myelopathy discharged from inpatient rehabilitation between 1 January 1995 and 31 December 2010. Patients comprised three injury groups: IRM, nontraumatic myelopathy (NTM) and traumatic spinal cord injury (TSCI). Information collected includes demographic characteristics, functional data, length of stay, injury completeness and discharge destination. Primary outcome measures were change in Functional Independence Measure (FIM) and daily FIM change. For IRM, data were collected regarding injury characteristics, risk factors, presenting symptoms, neurologic impairment level and treatment. RESULTS: Of the 1601 patients, 40 (2.5%) had IRM, 1105 (69.0%) had NTM and 456 (28.5%) had TSCI. IRM mean (s.d.) age was 58.6 (15.7) years (male gender, 72.5%). The majority in each group had incomplete injuries. IRM had longer lengths of stay (P<0.001), lower admission (P=0.001) and discharge (P=0.005) FIM scores and lower FIM daily change (P=0.002) than NTM. Degree of functional improvement was similar in all groups, and most patients in each group were discharged home. Infectious pathogens were bacterial (80.0%, n=32), viral (7.5%, n=3), tuberculous (7.5%, n=3), parasitic (2.5%, n=1) and multiple types (2.5%, n=1). The most common bacterial cause (65.6%) was Staphylococcus aureus. CONCLUSIONS: Infectious etiologies comprise a small proportion of NTM but represent a unique entity with distinct recovery patterns and outcomes. These patients can achieve similar functional improvements as other NTM patients during inpatient rehabilitation, although over a longer period of time.

Development and validation of a computerized algorithm for International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI).

STUDY DESIGN: Validation study. OBJECTIVES: To describe the development and validation of a computerized application of the international standards for neurological classification of spinal cord injury (ISNCSCI). SETTING: Data from acute and rehabilitation care. METHODS: The Rick Hansen Institute-ISNCSCI Algorithm (RHI-ISNCSCI Algorithm) was developed based on the 2011 version of the ISNCSCI and the 2013 version of the worksheet. International experts developed the design and logic with a focus on usability and features to standardize the correct classification of challenging cases. A five-phased process was used to develop and validate the algorithm. Discrepancies between the clinician-derived and algorithm-calculated results were reconciled. RESULTS: Phase one of the validation used 48 cases to develop the logic. Phase three used these and 15 additional cases for further logic development to classify cases with 'Not testable' values. For logic testing in phases two and four, 351 and 1998 cases from the Rick Hansen SCI Registry (RHSCIR), respectively, were used. Of 23 and 286 discrepant cases identified in phases two and four, 2 and 6 cases resulted in changes to the algorithm. Cross-validation of the algorithm in phase five using 108 new RHSCIR cases did not identify the need for any further changes, as all discrepancies were due to clinician errors. The web-based application and the algorithm code are freely available at www.isncscialgorithm.com. CONCLUSION: The RHI-ISNCSCI Algorithm provides a standardized method to accurately derive the level and severity of SCI from the raw data of the ISNCSCI examination. The web interface assists in maximizing usability while minimizing the impact of human error in classifying SCI. SPONSORSHIP: This study is sponsored by the Rick Hansen Institute and supported by funding from Health Canada and Western Economic Diversification Canada.

Targeting the gastrointestinal tract to develop novel therapies for HIV.

Despite the use of antiretroviral therapy (ART), which delays and/or prevents AIDS pathogenesis, human immunodeficiency virus (HIV)-infected individuals continue to face increased morbidities and mortality rates compared with uninfected individuals. Gastrointestinal (GI) mucosal dysfunction is a key feature of HIV infection, and is associated with mortality. In this study, we review current knowledge about mucosal dysfunction in HIV infection, and describe potential avenues for therapeutic targets to enhance mucosal function and decrease morbidities and mortalities in HIV-infected individuals.

International survey of perceived barriers to admission and discharge from spinal cord injury rehabilitation units.

STUDY DESIGN: Survey. OBJECTIVES: To describe and compare perceived barriers with patient flow in spinal rehabilitation units (SRUs). SETTING: International. Ten SRUs (Australia, Canada, India, Ireland, Italy, Netherlands, Pakistan, Switzerland, UK and USA) that admit both traumatic and non-traumatic spinal cord injury patients. METHODS: Survey completed between December 2010 and February 2013 on perception of barriers for admission into and discharge from SRUs. Opinion was sought from the participants regarding the utility of collecting data on the timeliness of access to SRUs and occurrence of discharge barriers for benchmarking and quality improvement purposes. RESULTS: The perceived barriers in accessing SRUs ranged from no access problem to a severe access problem (no access problems n=3; minor access problems n=3; moderate access problems n=2; severe access problem n=1 and extreme n=1). Most units (n=9/10) agreed that collecting data on timeliness of access to SRUs for acute hospital patients may help improve patient outcomes and health system processes by providing information for benchmarking and quality improvement purposes. All units reported perceived barriers to discharge from SRUs. Compared with admission barriers, a greater perception of barriers to discharge was reported (minor problem n=3; moderate problem n=3; severe problem n=3; and extreme n=1). All units agreed that collecting data on barriers to discharge from SRU may help improve patient outcomes and system processes. CONCLUSIONS: Perceived barriers to patient flow in SRUs are reported in many countries. Projects to identify and minimise the occurrence and impact of admission and discharge barriers could increase access to rehabilitation and improve the rehabilitation outcomes for patients.

International comparison of the organisation of rehabilitation services and systems of care for patients with spinal cord injury.

STUDY DESIGN: Survey. OBJECTIVES: Describe and compare the organisation and delivery of rehabilitation services and systems of care for patients with spinal cord injury (SCI). SETTING: International. Nine spinal rehabilitation units that manage traumatic SCI and non-traumatic SCI (NTSCI) patients. METHODS: Survey based on clinical expertise and literature review. Completed between November 2010 and April 2011. RESULTS: All units reported public/government funding. Additional funding sources included compensation schemes, private insurance and self funding. Six units had formal attachment to an acute SCI unit. Five units (Italy, Ireland, India, Pakistan and Switzerland) provided a national service; two units (the Netherlands and USA) provided regional and two units (Australia and Canada) provided state/provincial services. The median number of SCI rehabilitation beds was 23 (interquartile range=16-30). All units admitted both traumatic SCI and NTSCI patients. The median proportion of patients admitted who had traumatic SCI was 45% (IQR 20-48%) and 40% (IQR 30-42%) had NTSCI. The rehabilitation team in all centres determined patient readiness for discharge. There was great variability between units in the availability of SCI speciality services, ancillary services and staff/patient ratios. CONCLUSION: There was a wide range of differences in the organisation, systems of care and services available for patients with SCI in rehabilitation units in different countries. Understanding these differences is important when comparing patient outcomes from different settings. A standardised collection of these system variables should be considered as part of future studies and could be included in the ISCoS data set project.

United States (US) multi-center study to assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III).

STUDY DESIGN: Multi-center, prospective, cohort study. OBJECTIVES: To assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III) in measuring functional ability in persons with spinal cord injury (SCI). SETTING: Inpatient rehabilitation hospitals in the United States (US). METHODS: Functional ability was measured with the SCIM III during the first week of admittance into inpatient acute rehabilitation and within one week of discharge from the same rehabilitation program. Motor and sensory neurologic impairment was measured with the American Spinal Injury Association Impairment Scale. The Functional Independence Measure (FIM), the default functional measure currently used in most US hospitals, was used as a comparison standard for the SCIM III. Statistical analyses were used to test the validity and reliability of the SCIM III. RESULTS: Total agreement between raters was above 70% on most SCIM III tasks and all κ-coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.81 and intraclass correlation coefficients were above 0.81. Cronbach's-α was above 0.7, with the exception of the respiration task. The coefficient of Pearson correlation between the FIM and SCIM III was 0.8 (P<0.001). For the respiration and sphincter management subscale, the SCIM III was more responsive to change, than the FIM (P<0.0001). CONCLUSION: Overall, the SCIM III is a reliable and valid measure of functional change in SCI. However, improved scoring instructions and a few modifications to the scoring categories may reduce variability between raters and enhance clinical utility.

Production of bacteriocins by Streptococcus bovis strains from Australian ruminants.

AIMS: To examine the prevalence of bacteriocin production in Streptococcus bovis isolates from Australian ruminants and the feasibility of industrial production of bacteriocin. METHODS AND RESULTS: Streptococcus bovis strains were tested for production of bacteriocin-like inhibitory substances (BLIS) by antagonism assay against Lactococcus lactis. BLIS production was associated with source animal location (i.e. proximity of other bacteriocin-positive source animals) rather than ruminant species/breed or diet. One bacteriocin showing strong inhibitory activity (Sb15) was isolated and examined. Protein sequence, stability and activity spectrum of this bovicin were very similar to bovicin HC5. Production could be increased through serial culturing, and increased productivity could be partially maintained during cold storage of cultures. CONCLUSIONS: BLIS production is geographically widely distributed in Eastern Australia, and it appears that the bacteriocin(+) trait is maintained in animals at the same location. The HC5-like bacteriocin, originally identified in North America, is also found in Australia. Production of bacteriocin can be increased through serial culturing. SIGNIFICANCE AND IMPACT OF THE STUDY: The HC5-like bacteriocins appear to have a broad global distribution. Serial culturing may provide a route towards commercial manufacturing for use in industrial applications, and purified bacteriocin from S. bovis Sb15 could potentially be used to prevent food spoilage or as a feed additive to promote growth in ruminant species.

Vaccination with SIVmac239Deltanef activates CD4+ T cells in the absence of CD4 T-cell loss.

BACKGROUND: Pathogenic HIV and SIV infections characteristically deplete central memory CD4(+) T cells and induce chronic immune activation, but it is controversial whether this also occurs after vaccination with attenuated SIVs and whether depletion or activation of CD4(+) T-cell play roles in protection against wild-type virus challenge. METHODS: Rhesus macaques were vaccinated with SIVmac239Deltanef and quantitative and phenotypic polychromatic flow cytometry analyses were performed on mononuclear cells from blood, lymph nodes and rectal biopsies. RESULTS: Animals vaccinated with SIVmac239Deltanef demonstrated no loss of CD4(+) T cells in any tissue, and in fact CCR5(+) and CD28(+)CD95(+) central memory CD4(+) T cells were significantly increased. In contrast, CD4(+) T-cell numbers and CCR5 expression significantly declined in unvaccinated controls challenged with SIVmac239. Also, intracellular Ki67 increased acutely as much as 3-fold over baseline in all tissues after SIVmac239Deltanef vaccination then declined following primary infection. CONCLUSION: We demonstrated in this study that SIVmac239Deltanef vaccination did not deplete CD4(+) T cells but transiently activated and expanded the memory cell population. However, increases in numbers and activation of memory CD4(+) T cells did not appear to influence protective immunity.

Dynamic role of kallikrein 6 in traumatic spinal cord injury.

Kallikrein 6 (K6) is a member of the kallikrein gene family that comprises 15 structurally and functionally related serine proteases. In prior studies we showed that, while this trypsin-like enzyme is preferentially expressed in neurons and oligodendroglia of the adult central nervous system (CNS), it is up-regulated at sites of injury due to expression by infiltrating immune and resident CNS cells. Given this background we hypothesized that K6 is a key contributor to the pathophysiology of traumatic spinal cord injury (SCI), influencing neural repair and regeneration. Examination of K6 expression following contusion injury to the adult rat cord, and in cases of human traumatic SCI, indicated significant elevations at acute and chronic time points, not only at the injury site but also in cord segments above and below. Elevations in K6 were particularly prominent in macrophages, microglia and reactive astrocytes. To determine potential effects of elevated K6 on the regeneration environment, the ability of neurons to adhere to and extend processes on substrata which had been exposed to recombinant K6 was examined. Limited (1 h) or excess (24 h) K6-mediated proteolytic digestion of a growth-facilitatory substrate, laminin, significantly decreased neurite outgrowth. By contrast, similar hydrolysis of a growth-inhibitory substrate, aggrecan, significantly increased neurite extension and cell adherence. These data support the hypothesis that K6 enzymatic cascades mediate events secondary to spinal cord trauma, including dynamic modification of the capacity for axon outgrowth.

Placental immunopathology and pregnancy failure in the FIV-infected cat.

Placental HIV infections frequently result in infected babies or miscarriage. Aberrant placental cytokine expression during HIV infections may facilitate transplacental viral transmission or pregnancy perturbation. The feline immunodeficiency virus (FIV)-infected cat is a model for HIV infections due to similarities in biology and clinical disease. The purpose of this study was to evaluate placental immunomodulator expression and reproductive outcome using the FIV-infected cat model. Kittens were cesarean delivered from FIV-B-2542-infected and control queens near term; placental and fetal tissues were collected. Real-time RT-PCR was used to measure expression of representative placental Th1 cytokines, interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma), a Th2 cytokine, IL-10, and chemokine receptor CXCR4. On average, control queens delivered 3.8 kittens/litter; 1 of 31 kittens (3.2%) was non-viable. FIV-infected queens produced 2.7 kittens/litter; 15 of 25 concepti (60%) were non-viable. FIV was detected in 14 of 15 placentas (93%) and 21 of 22 fetuses (95%) using PCR. Placental immunomodulator expression did not differ significantly when placentas from infected cats were compared to those of control cats. However, elevated expression of Th1 cytokines and increased Th1/Th2 ratios (IL-1beta/IL-10) occurred in placentas from resorptions. Therefore, increased placental Th1 cytokine expression was associated with pregnancy failure in the FIV-infected cat.

Hyperthermia, rhabdomyolysis, and disseminated intravascular coagulation associated with baclofen pump catheter failure.

A 29-year-old man with C6 tetraplegia (ASIA A) using an implanted baclofen pump and intrathecal catheter infusion system for spasticity control developed severe spasticity, hyperthermia, hypotension, rhabdomyolysis, and disseminated intravascular coagulation after catheter disconnection. Tracheal intubation and mechanical ventilation were necessary. Extensive workup for a concurrent infection was negative except for urine cultures. The patient remained febrile for 10 days despite empirical antibiotic trials. Administration of high-dose benzodiazepines was inadequate for spasticity control. Spasticity control and his clinical condition, including body temperature, did not improve until his catheter was surgically replaced and intrathecal baclofen administration was resumed. The pharmacopathology of abrupt baclofen withdrawal and the similarities between this presentation, sepsis, neuroleptic malignant syndrome, and malignant hyperthermia are discussed. High-dose dantrolene was not used; however, based on similarities between this patient's presentation and neuroleptic malignant syndrome, it may have been the drug of choice.

Weight training injuries: part 1: diagnosing and managing acute conditions.

When patients present with acute weight training injuries, familiarity with the demands of the activity can help physicians get the most out of the patient history. Probable risk factors for injury include errors in technique (described in a sidebar), skeletal immaturity, and anabolic steroid abuse. Common acute injuries in weight training include sprains, strains, tendon avulsions, and compartment syndrome. Possible nonmusculoskeletal problems include retinal hemorrhage, radiculopathy, and various cardiovascular complications. Treatment of acute musculoskeletal injuries varies, but usually includes sports medicine mainstays such as prompt RICE. Chronic weight training injuries will be described in part 2 of this series.

Weight training injuries: part 2: diagnosing and managing chronic conditions.

The repetitive nature of weight training and the often heavy loads involved provide fertile ground for chronic injuries. Common chronic injuries include rotator cuff tendinopathy and stress injuries to the vertebrae, clavicles, and upper extremities. In addition, muscle hypertrophy, poor technique, or overuse can contribute to nerve injuries such as thoracic outlet syndrome or suprascapular neuropathy. Chronic medical conditions that are known to occur in weight trainers include vascular stenosis and weight lifter's cephalgia. Management of chronic problems will vary by condition, but relative rest and correction of poor technique are important for many.