The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study.

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.

The Berlin Bimanual Test for Tetraplegia (BeBiTT): development, psychometric properties, and sensitivity to change in assistive hand exoskeleton application.

BACKGROUND: Assistive hand exoskeletons are promising tools to restore hand function after cervical spinal cord injury (SCI) but assessing their specific impact on bimanual hand and arm function is limited due to lack of reliable and valid clinical tests. Here, we introduce the Berlin Bimanual Test for Tetraplegia (BeBiTT) and demonstrate its psychometric properties and sensitivity to assistive hand exoskeleton-related improvements in bimanual task performance. METHODS: Fourteen study participants with subacute cervical SCI performed the BeBiTT unassisted (baseline). Thereafter, participants repeated the BeBiTT while wearing a brain/neural hand exoskeleton (B/NHE) (intervention). Online control of the B/NHE was established via a hybrid sensorimotor rhythm-based brain-computer interface (BCI) translating electroencephalographic (EEG) and electrooculographic (EOG) signals into open/close commands. For reliability assessment, BeBiTT scores were obtained by four independent observers. Besides internal consistency analysis, construct validity was assessed by correlating baseline BeBiTT scores with the Spinal Cord Independence Measure III (SCIM III) and Quadriplegia Index of Function (QIF). Sensitivity to differences in bimanual task performance was assessed with a bootstrapped paired t-test. RESULTS: The BeBiTT showed excellent interrater reliability (intraclass correlation coefficients > 0.9) and internal consistency (α = 0.91). Validity of the BeBiTT was evidenced by strong correlations between BeBiTT scores and SCIM III as well as QIF. Wearing a B/NHE (intervention) improved the BeBiTT score significantly (p < 0.05) with high effect size (d = 1.063), documenting high sensitivity to intervention-related differences in bimanual task performance. CONCLUSION: The BeBiTT is a reliable and valid test for evaluating bimanual task performance in persons with tetraplegia, suitable to assess the impact of assistive hand exoskeletons on bimanual function.

Association of age with the timing of acute spine surgery-effects on neurological outcome after traumatic spinal cord injury.

PURPOSE: To investigate the association of age with delay in spine surgery and the effects on neurological outcome after traumatic spinal cord injury (SCI). METHODS: Ambispective cohort study (2011-2017) in n = 213 patients consecutively enrolled in a Level I trauma center with SCI care in a metropolitan region in Germany. Age-related differences in the injury to surgery interval and conditions associated with its delay (> 12 h after SCI) were explored using age categories or continuous variables and natural cubic splines. Effects of delayed surgery or age with outcome were analyzed using multiple logistic regression. RESULTS: The median age of the study population was 58.8 years (42.0-74.6 IQR). Older age (≥ 75y) was associated with a prolonged injury to surgery interval of 22.8 h (7.2-121.3) compared to 6.6 h (4.4-47.9) in younger patients (≤ 44y). Main reasons for delayed surgery in older individuals were secondary referrals and multimorbidity. Shorter time span to surgery (≤ 12 h) was associated with higher rates of ASIA impairment scale (AIS) conversion (OR 4.22, 95%CI 1.85-9.65), as mirrored by adjusted spline curves (< 20 h 20-25%, 20-60 h 10-20%, > 60 h < 10% probability of AIS conversion). In incomplete SCI, the probability of AIS conversion was lower in older patients [e.g., OR 0.09 (0.02-0.44) for'45-59y' vs.' ≤ 44y'], as confirmed by spline curves (< 40y 20-80%, ≥ 40y 5-20% probability). CONCLUSION: Older patient age complexifies surgical SCI care and research. Tackling secondary referral to Level I trauma centers and delayed spine surgery imposes as tangible opportunity to improve the outcome of older SCI patients.

Supporting front crawl swimming in paraplegics using electrical stimulation: a feasibility study.

BACKGROUND: Participation in physical and therapeutic activities is usually severely restricted after a spinal cord injury (SCI). Reasons for this are the associated loss of voluntary motor function, inefficient temperature regulation of the affected extremities, and early muscle fatigue. Hydrotherapy or swim training offer an inherent weight relief, reduce spasticity and improve coordination, muscle strength and fitness. METHODS: We present a new hybrid exercise modality that combines functional electrical stimulation (FES) of the knee extensors and transcutaneous spinal cord stimulation (tSCS) with paraplegic front crawl swimming. tSCS is used to stimulate the afferent fibers of the L2-S2 posterior roots for spasticity reduction. By activating the tSCS, the trunk musculature is recruited at a motor level. This shall improve trunk stability and straighten the upper body. Within this feasibility study, two complete SCI subjects (both ASIA scale A, lesion level Th5/6), who have been proficient front crawl swimmers, conducted a 10-week swim training with stimulation support. In an additional assessment swim session nine months after the training, the knee extension, hip extension, and trunk roll angles where measured using waterproof inertial measurement units (IMUs) and compared for different swimming conditions (no stimulation, tSCS, FES, FES plus tSCS). RESULTS: For both subjects, a training effect over the 10-week swim training was observed in terms of measured lap times (16 m pool) for all swimming conditions. Swimming supported by FES reduced lap times by 15.4% and 8.7% on average for Subject A and Subject B, respectively. Adding tSCS support yielded even greater mean decreases of 19.3% and 20.9% for Subjects A and B, respectively. Additionally, both subjects individually reported that swimming with tSCS for 30-45 minutes eliminated spasticity in the lower extremities for up to 4 hours beyond the duration of the session. Comparing the median as well as the interquartile range of all different settings, the IMU-based motion analysis revealed that FES as well as FES+tSCS improve knee extension in both subjects, while hip extension was only increased in one subject. Trunk roll angles were similar for all swimming conditions. tSCS had no influence on the knee and hip joint angles. Both subjects reported that stimulation-assisted swimming is comfortable, enjoyable, and they would like to use such a device for recreational training and rehabilitation in the future. CONCLUSIONS: Stimulation-assisted swimming seems to be a promising new form of hybrid exercise for SCI people. It is safe to use with reusable silicone electrodes and can be performed independently by experienced paraplegic swimmers except for transfer to water. The study results indicate that swimming speed can be increased by the proposed methods and spasticity can be reduced by prolonged swim sessions with tSCS and FES. The combination of stimulation with hydrotherapy might be a promising therapy for neurologic rehabilitation in incomplete SCI, stroke or multiples sclerosis patients. Therefore, further studies shall incorporate other neurologic disorders and investigate the potential benefits of FES and tSCS therapy in the water for gait and balance.

Clinical decision-making on spinal cord injury-associated pneumonia: a nationwide survey in Germany.

STUDY DESIGN: Survey study. OBJECTIVES: Spinal cord injury (SCI)-associated pneumonia (SCI-AP) is associated with poor functional recovery and a major cause of death after SCI. Better tackling SCI-AP requires a common understanding on how SCI-AP is defined. This survey examines clinical algorithms relevant for diagnosis and treatment of SCI-AP. SETTING: All departments for SCI-care in Germany. METHODS: The clinical decision-making on SCI-AP and the utility of the Centers for Disease Control and Prevention (CDC) criteria for diagnosis of 'clinically defined pneumonia' were assessed by means of a standardized questionnaire including eight case vignettes of suspected SCI-AP. The diagnostic decisions based on the case information were analysed using classification and regression trees (CART). RESULTS: The majority of responding departments were aware of the CDC-criteria (88%). In the clinical vignettes, 38-81% of the departments diagnosed SCI-AP in accordance with the CDC-criteria and 7-41% diagnosed SCI-AP in deviation from the CDC-criteria. The diagnostic agreement was not associated with the availability of standard operating procedures for SCI-AP management in the departments. CART analysis identified radiological findings, fever, and worsened gas exchange as most important for the decision on SCI-AP. Frequently requested supplementary diagnostics were microbiological analyses, C-reactive protein, and procalcitonin. For empirical antibiotic therapy, the departments used (acyl-)aminopenicillins/ß-lactamase inhibitors, cephalosporins, or combinations of (acyl-)aminopenicillins/ß-lactamase inhibitors with fluoroquinolones or carbapenems. CONCLUSIONS: This survey reveals a diagnostic ambiguity regarding SCI-AP despite the awareness of CDC-criteria and established SOPs. Heterogeneous clinical practice is encouraging the development of disease-specific guidelines for diagnosis and management of SCI-AP.

Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex.

Acute spinal cord injury (SCI) causes systemic immunosuppression and life-threatening infections, thought to result from noradrenergic overactivation and excess glucocorticoid release via hypothalamus-pituitary-adrenal axis stimulation. Instead of consecutive hypothalamus-pituitary-adrenal axis activation, we report that acute SCI in mice induced suppression of serum norepinephrine and concomitant increase in cortisol, despite suppressed adrenocorticotropic hormone, indicating primary (adrenal) hypercortisolism. This neurogenic effect was more pronounced after high-thoracic level (Th1) SCI disconnecting adrenal gland innervation, compared with low-thoracic level (Th9) SCI. Prophylactic adrenalectomy completely prevented SCI-induced glucocorticoid excess and lymphocyte depletion but did not prevent pneumonia. When adrenalectomized mice were transplanted with denervated adrenal glands to restore physiologic glucocorticoid levels, the animals were completely protected from pneumonia. These findings identify a maladaptive sympathetic-neuroendocrine adrenal reflex mediating immunosuppression after SCI, implying that therapeutic normalization of the glucocorticoid and catecholamine imbalance in SCI patients could be a strategy to prevent detrimental infections.

Performance of the Labcor Dokimos Plus pericardial aortic prosthesis: a single-centre experience.

Objectives: In patients with a small aortic annulus, aortic valve replacement (AVR) is frequently associated with high residual pressure gradients. Supra-annular pericardial aortic prostheses are gaining popularity due to the increased effective orifice areas (EOA) and resulting lower gradients. This study reports the clinical and echocardiographic results following implantation of the new supra-annular pericardial aortic prosthesis Dokimos Plus (Labcor, Belo Horizonte, Brazil). Methods: Between October 2013 and July 2015, 137 patients (41% women, mean age: 74 years) underwent supra-annular AVR with or without concomitant procedures using the Dokimos Plus prosthesis in our department. Transthoracic echocardiography was performed pre- and postoperatively on all patients to assess haemodynamic parameters (gradients, acceleration time [AT], Doppler velocity indices [DVIs] and indexed EOA [EOAI]) and to detect paravalvular leakage (PVL). Data were collected retrospectively from our hospital databases. Methods: Patients were grouped by prosthesis size: Most patients received 23-mm (57.6%), followed by 21-mm (19%), 25-mm (15.4%) and 27-mm (8%) prostheses. The mean EOAI in all groups was 1.1 ± 0.26 cm 2 /m 2 . Pressure gradients were low in all groups (mean: 8.9 ± 4.4 mmHg; peak: 18.8 ± 6.8 mmHg); AT and DVI were in the normal range according to American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations (mean AT 73.3 ± 29 ms; mean DVI 0.5 ± 0.2). One patient had severe PVL and one presented with central regurgitation, both requiring re-intervention. The mortality rate was 5.1% ( n = 7); none of the cases was associated with valve insufficiency. Conclusions: The Dokimos prosthesis showed a satisfactory overall performance, presenting low gradients and DVIs as well as high EOAI. Further investigations are needed to analyse the cases of regurgitation and monitor long-term performance.

Natural Killer (NK) Cell Functionality after human Spinal Cord Injury (SCI): protocol of a prospective, longitudinal study.

BACKGROUND: Natural killer (NK) cells comprise the main components of lymphocyte-mediated nonspecific immunity. Through their effector function they play a crucial role combating bacterial and viral challenges. They are also thought to be key contributors to the systemic spinal cord injury-induced immune-deficiency syndrome (SCI-IDS). SCI-IDS increases susceptibility to infection and extends to the post-acute and chronic phases after SCI. METHODS AND DESIGN: The prospective study of NK cell function after traumatic SCI was carried out in two centers in Berlin, Germany. SCI patients and control patients with neurologically silent vertebral fracture also undergoing surgical stabilization were enrolled. Furthermore healthy controls were included to provide reference data. The NK cell function was assessed at 7 (5-9) days, 14 days (11-28) days, and 10 (8-12) weeks post-trauma. Clinical documentation included the American Spinal Injury Association (ASIA) impairment scale (AIS), neurological level of injury, infection status, concomitant injury, and medications. The primary endpoint of the study is CD107a expression by NK cells (cytotoxicity marker) 8-12 weeks following SCI. Secondary endpoints are the NK cell's TNF-α and IFN-γ production by the NK cells 8-12 weeks following SCI. DISCUSSION: The protocol of this study was developed to investigate the hypotheses whether i) SCI impairs NK cell function throughout the post-acute and sub-acute phases after SCI and ii) the degree of impairment relates to lesion height and severity. A deeper understanding of the SCI-IDS is crucial to enable strategies for prevention of infections, which are associated with poor neurological outcome and elevated mortality. TRIAL REGISTRATION: DRKS00009855 .

SCISSOR-Spinal Cord Injury Study on Small molecule-derived Rho inhibition: a clinical study protocol.

INTRODUCTION: The approved analgesic and anti-inflammatory drugs ibuprofen and indometacin block the small GTPase RhoA, a key enzyme that impedes axonal sprouting after axonal damage. Inhibition of the Rho pathway in a central nervous system-effective manner requires higher dosages compared with orthodox cyclooxygenase-blocking effects. Preclinical studies on spinal cord injury (SCI) imply improved motor recovery after ibuprofen/indometacin-mediated Rho inhibition. This has been reassessed by a meta-analysis of the underlying experimental evidence, which indicates an overall effect size of 20.2% regarding motor outcome achieved after ibuprofen/indometacin treatment compared with vehicle controls. In addition, ibuprofen/indometacin may also limit sickness behaviour, non-neurogenic systemic inflammatory response syndrome (SIRS), neuropathic pain and heterotopic ossifications after SCI. Consequently, 'small molecule'-mediated Rho inhibition after acute SCI warrants clinical investigation. METHODS AND ANALYSIS: Protocol of an investigator-initiated clinical open-label pilot trial on high-dose ibuprofen treatment after acute traumatic, motor-complete SCI. A sample of n=12 patients will be enrolled in two cohorts treated with 2400 mg/day ibuprofen for 4 or 12 weeks, respectively. The primary safety end point is an occurrence of serious adverse events, primarily gastroduodenal bleedings. Secondary end points are pharmacokinetics, feasibility and preliminary effects on neurological recovery, neuropathic pain and heterotopic ossifications. The primary safety analysis is based on the incidence of severe gastrointestinal bleedings. Additional analyses will be mainly descriptive and casuistic. ETHICS AND DISSEMINATION: The clinical trial protocol was approved by the responsible German state Ethics Board, and the Federal Institute for Drugs and Medical Devices. The study complies with the Declaration of Helsinki, the principles of Good Clinical Practice and all further applicable regulations. This safety and pharmacokinetics trial informs the planning of a subsequent randomised controlled trial. Regardless of the result of the primary and secondary outcome assessments, the clinical trial will be reported as a publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02096913; Pre-results.

Breathing-synchronised electrical stimulation of the abdominal muscles in patients with acute tetraplegia: A prospective proof-of-concept study.

OBJECTIVE: To examine whether, by enhancing breathing depth and expectoration, early use of breathing-synchronised electrical stimulation of the abdominal muscles (abdominal functional electrical stimulation, AFES) is able to reduce pulmonary complications during the acute phase of tetraplegia. DESIGN: Prospective proof-of-concept study. SETTING: Spinal cord unit at a level 1 trauma center. METHOD: Following cardiovascular stabilisation, in addition to standard treatments, patients with acute traumatic tetraplegia (ASIA Impairment Scale A or B) underwent breathing-synchronised electrical stimulation of the abdominal muscles to aid expiration and expectoration. The treatment was delivered in 30-minute sessions, twice a day for 90 days. The target was for nine of 15 patients to remain free of pneumonia meeting Centers for Disease Control and Prevention (CDC) diagnostic criteria. RESULTS: Eleven patients were recruited to the study between October 2011 and November 2012. Two patients left the study before completion. None of the patients contracted pneumonia during the study period. No complications from electrical stimulation were observed. AFES led to a statistically significant increase in peak inspiratory and expiratory flows and a non-statistically significant increase in tidal volume and inspiratory and expiratory flow. When surveyed, 6 out of 9 patients (67%) reported that the stimulation procedure led to a significant improvement in breathing and coughing. CONCLUSION: AFES appears to be able to improve breathing and expectoration and prevent pneumonia in the acute phase of tetraplegia (up to 90 days post-trauma). This result is being validated in a prospective multicentre comparative study.

Airway complications in traumatic lower cervical spinal cord injury: A retrospective study.

OBJECTIVE: To investigate risk factors for pneumonia in patients with traumatic lower cervical spinal cord injury. DESIGN: Observational study, retrospective study. SETTING: Spinal cord unit in a maximum care hospital. METHODS: Thirty-seven patients with acute isolated traumatic spinal cord injury at levels C4-C8 and complete motor function injury (AIS A, B) treated from 2004 to 2010 met the criteria for inclusion in our retrospective analysis. The following parameters were considered: ventilation-specific parameters, re-intubation, creation of a tracheostomy, pneumonia, antibiotic treatment, and length of intensive care unit (ICU) stay and total hospitalization. RESULTS: Among the patients, 81% had primary invasive ventilation. In 78% of cases a tracheostomy was created; 3% of these cases were discharged with invasive ventilation and 28% with a tracheostomy without ventilation. Pneumonia according to Centers for Disease Control criteria occurred in 51% of cases within 21±32 days of injury, and in 3% at a later date. The number of pre-existing conditions was significantly associated with pneumonia. Length of ICU stay was 25±34 days, and average total hospital duration was 230±144 days. Significant factors affecting the duration of ventilation were the number of pre-existing conditions and tetraplegia-specific complications. CONCLUSIONS: Our results confirm that patients with traumatic lower cervical spinal cord injuries defined by lesion level and AIS constitute a homogeneous group. This group is characterized by a high rate of pneumonia during the first 4 weeks after injury. The number of pre-existing general conditions and spinal injury-specific comorbidities are the only risk factors identified for the development of pneumonia and/or duration of ventilation.

The SCIentinel study--prospective multicenter study to define the spinal cord injury-induced immune depression syndrome (SCI-IDS)--study protocol and interim feasibility data.

BACKGROUND: Infections are the leading cause of death in the acute phase following spinal cord injury and qualify as independent risk factor for poor neurological outcome ("disease modifying factor"). The enhanced susceptibility for infections is not stringently explained by the increased risk of aspiration in tetraplegic patients, neurogenic bladder dysfunction, or by high-dose methylprednisolone treatment. Experimental and clinical pilot data suggest that spinal cord injury disrupts the balanced interplay between the central nervous system and the immune system. The primary hypothesis is that the Spinal Cord Injury-induced Immune Depression Syndrome (SCI-IDS) is 'neurogenic' including deactivation of adaptive and innate immunity with decreased HLA-DR expression on monocytes as a key surrogate parameter. Secondary hypotheses are that the Immune Depression Syndrome is i) injury level- and ii) severity-dependent, iii) triggers transient lymphopenia, and iv) causes qualitative functional leukocyte deficits, which may endure the post-acute phase after spinal cord injury. METHODS/DESIGN: SCIentinel is a prospective, international, multicenter study aiming to recruit about 118 patients with acute spinal cord injury or control patients with acute vertebral fracture without neurological deficits scheduled for spinal surgery. The assessment points are: i) <31 hours, ii) 31-55 hours, iii) 7 days, iv) 14 days, and v) 10 weeks post-trauma. Assessment includes infections, concomitant injury, medication and neurological classification using American Spinal Injury Association impairment scale (AIS) and neurological level. Laboratory analyses comprise haematological profiling, immunophenotyping, including HLA-DR expression on monocytes, cytokines and gene expression of immune modulators. We provide an administrative interim analysis of the recruitment schedule of the trial. DISCUSSION: The objectives are to characterize the dysfunction of the innate and adaptive immune system after spinal cord injury and to explore its proposed 'neurogenic' origin by analyzing its correlation with lesion height and severity. The trial protocol considers difficulties of enrolment in an acute setting, and loss to follow up. The administrative interim analysis confirmed the feasibility of the protocol. Better understanding of the SCI-IDS is crucial to reduce co-morbidities and thereby to attenuate the impact of disease modifying factors to protect neurological "outcome at risk". This putatively results in improved spinal cord injury medical care. TRIAL REGISTRATION DRKS-ID: DRKS00000122 (German Clinical Trials Registry).

Assessment of gadolinium leakage into traumatic spinal cord lesion using magnet resonance imaging.

STUDY DESIGN: Exploratory study in patients with acute spinal cord trauma using magnetic resonance imaging (MRI). OBJECTIVE: The aim of this study was to assess the leakage of Gd-DTPA into traumatic lesions of the human spinal cord using MRI. SUMMARY OF BACKGROUND DATA: While MRI of acute spinal cord trauma is a routine type of clinical investigation, the time course of Gd-DTPA enhancement in traumatic spinal cord injury is not known. METHODS: In early stage after spinal cord injury (<24 hours) and at follow-up on day 4, 7, 14, 21, 28, and 84, the accumulation of Gd-DTPA within 30 minutes after bolus injection was investigated in sagittal and axial T2-weighted images and T1-weighted images. RESULTS: In 4 men aged between 23 and 55 years with severe paraparesis, the traumatic spinal cord lesion had a maximum of spatial extent after 7 days. Gd-enhancement was first detected on day 4 in T1-weighted images, was most pronounced between day 7 and 28 but absent on day 84. The Gd-enhancement progressively increased in intensity after intravenous injection between 5 and 10 minutes when a maximum was reached, which remained stable for up to 30 minutes. CONCLUSION: We used MRI to study the dynamics of post-traumatic Gd-DTPA leakage into the injured spinal cord. This appears as a promising approach for monitoring the local secondary lesion changes.

Airway management in acute tetraplegics: a retrospective study.

The objective of this study was to develop an evidence-based airway management protocol for patients with acute tetraplegia. The method consisted of an analysis of the medical records of patients (September 1997-December 2002) with a spinal cord injury and a neurological deficit less than 8 weeks old. Of the 175 patients, 72 (41, 14%) were tracheotomised. This was influenced by the origin of the paralysis, Frankel score, and number of cervical spine operations, accompanying injuries and accompanying illnesses. Tracheotomy did not affect the duration of treatment, duration of ventilation or length of stay in the intensive care unit. The need for a tracheotomy was able to be predicted in 73.31% with neurological level, Frankel score and severity of accompanying injuries. In patients with acute tetraplegia, primary tracheotomy is indicated in sub C1-C3 with Frankel stage A/B, sub C4-C6 with Frankel stage A/B with trauma and accompanying injuries/accompanying illnesses, and in patients with complex cervical spine trauma that requires a combined surgical approach. In other patients, an attempt at extubation should be made.

Propiverine vs oxybutynin for treating neurogenic detrusor overactivity in children and adolescents: results of a multicentre observational cohort study.

OBJECTIVE: To compare, in a retrospective observational cohort study, the efficacy, tolerability, safety and clinical effectiveness of propiverine and oxybutynin in children and adolescents with neurogenic detrusor overactivity (NDO). PATIENTS AND METHODS: In all, 255 children and adolescents (aged 1-18 years) with NDO (199 myelomeningocele, 46 spinal cord injury, 10 other diagnoses) were enrolled at 14 study centres. To evaluate the efficacy of propiverine and oxybutynin, urodynamic and clinical variables were assessed before and after at least 12 month of the antimuscarinic agents administered at variable doses. RESULTS: In all, 127 patients given propiverine and 128 given oxybutynin were enrolled. The primary efficacy outcome, i.e. reductions in urodynamically assessed individual maximum detrusor pressure (P(detmax)), was assumed to indicate success in 74.2% of those on propiverine vs 49.6% on oxybutynin. The mean P(detmax) was significantly reduced during treatment, from 59.8 to 36.7 cmH(2)O in the propiverine and from 65.2 to 54.9 cmH(2)O in the oxybutynin groups. The mean maximum cystometric bladder capacity increased from 146 to 242 mL in the propiverine and from 222 to 310 mL in the oxybutynin group. Propiverine was better tolerated than oxybutynin, having fewer adverse drug reactions (9.4% vs 17.2%, odds ratio 2.04), and for its severity grades and premature treatment termination (none vs 11 cases). CONCLUSION: In this non-interventional study, reflecting 'real-life' clinical practice, comparing the efficacy, tolerability and safety of propiverine and oxybutynin in children and adolescents with NDO, propiverine was at least as effective as oxybutynin, but better tolerated, resulting in superior clinical effectiveness than for oxybutynin.

Treatment of intracardiac thrombi with argatroban.

Intracardiac thrombi are well known complications associated with diverse cardiac diseases and venous thromboembolism. Therapeutic recommendations like thrombolysis, surgical thrombectomy, or treatment with low molecular heparin and intravenous unfractionated heparin based on small numbers of patients or retrospective case series have failed to reach a consensus. We report on the use of argatroban, a new direct thrombin inhibitor in 4 patients with intracardiac thrombi. Therapy was effective in all patients with complete resolution of thrombi. Treatment was complicated by recurrent strokes with complete neurological recovery in one patient. Therapy of intracardiac thrombi by argatroban is safe and effective. The drug requires no dosage adjustments for age, sex, or renal impairment, including in dialysis-dependent patients. Argatroban has been found to increase predictably activated partial thromboplastin time (aPTT) and activated clotting time (ACT) in a dose-dependent manner.

Infrahyoid muscle flap for pharyngeal fistulae after cervical spine surgery: a novel approach--report of six cases.

A report of our experiences involving the treatment six male patients with a new method of closing perforations in the pharynx and upper esophagus, following surgery of the cervical spine region. Perforation of the pharynx and upper esophagus are rare complications following cervical spine surgery. The grave consequences of these complications necessitate in most cases immediate surgical therapy. In most cases, the first step involves the removal of the cervical plate and screws. The defect was then closed using a vascular pedicled musculofascia flap derived from the infrahyoid musculature. In all cases, the flap healed into place without complications. The patients began taking oral nutrients after an average of seven postoperative (5-12) days. In none of the cases did functional disorders or complications arise during the follow-up period (1-5 years). The infrahyoid muscle flap is well suited for reconstruction of the posterior pharyngeal wall and the upper esophagus.

Comparison of the 6-minute walk test with established parameters for assessment of cardiopulmonary capacity in adults with complex congenital cardiac disease.

BACKGROUND: Objective assessment of the cardiopulmonary capacity in patients with complex congenital cardiac disease often remains difficult in clinical practice. The cardiopulmonary exercise test and determination of the levels of brain natriuretic peptide in the plasma are established tests, but expensive. The 6-minute walk test is also validated, but has not often been used in patients with heart failure due to congenital heart disease, nor compared with other tests. We sought to compare its value with the results of cardiopulmonary exercise testing and measuring the levels of brain natriuretic peptide in the plasma. METHODS: We carried out a standardized 6-minute walk test in 31 patients with complex congenital cardiac disease on the same day that they underwent cardiopulmonary exercise testing and determination of levels of brain natriuretic peptide in the plasma. Of the patients, 7 had functionally univentricular hearts, 9 had transposition, 9 had tetralogy of Fallot, 3 had common arterial trunk, and 3 had pulmonary atresia with intact interventricular septum. Uptakes of oxygen at peak exercise, and at the anaerobic threshold, were determined using cardiopulmonary exercise testing, and classified as suggested by Weber. The 6-minute walk test was performed according to a standard protocol. RESULTS: There was a significant correlation between brain natriuretic peptide, oxygen uptakes at peak exercise and 6-minute walk. The correlation between the 6-minute walk test and oxygen uptakes at the anaerobic threshold, however, was not significant. CONCLUSIONS: The 6-minute walk test can be performed easily, is inexpensive, widely available, and correlates well with measurements of brain natriuretic peptide and cardiopulmonary exercise testing, even in patients with corrected or palliated congenital cardiac malformations. A cut-off value of 450 metres in the 6-minute walk test allows a semi-quantitative classification in analogy to the classification suggested by Weber for cardiopulmonary exercise testing, and to a level of brain natriuretic peptide in the plasma of less or more than 100 picograms per millilitre.

Reconstitution of lost cervical spine function: management strategies.

The cervical spine (CS) is the most vulnerable part of the whole spine because it has least protection. This is due to its high mobility (few bone, but largely muscle and joint support) which is associated with a high injury risk. The anatomical characteristics are based on evolutionary biological reasons, i.e. humans had to be able to freely controlling the surrounding space with their eyes and to have permanent postural control by an upright position of the head. The cervical spine, its joint and the surrounding muscles are highly interconnected (e.g. direct neuronal projections into the brain stem, connections to the TMJ, Head's zones with projections to the skin surface). Moreover, the spinal pain memory store can lead to a variets of multi-facette clinical pictures. In addition to reversible disorders of the cervical spine, posttraumatic disorders play a major role. The therapy options available include physiotherapy, drug therapy and surgical measures. However, a multidisciplinary approach is most favourable.