Possible Strategies to Optimize a Biomarker Discovery Approach to Correlate with Neurological Outcome in Patients with Spinal Cord Injury: A Pilot Study.

The lack of reliable diagnostic and prognostic markers for spinal cord injured (SCI) patients is a severe obstacle in development and testing of new therapies, and it also impairs appropriate rehabilitation care. The sparse available data on the biochemical composition of cerebrospinal fluid (CSF) during the acute and/or chronic phase of the lesion provide, up until now, inconsistent results. In this pilot study, we then explored the possibility of combining a multi-parametric and bioinformatic analysis of CSF for its biological properties tested on different cells types, suitable for investigating inflammation and re-myelination. The patient enrollment was based on stringent inclusion criteria; that is, cervical and thoracic SCI trauma, CSF collection within 24 h of trauma, type of surgical approach for spine stabilization, and absence of steroid therapy before CSF collection. Eleven SCI patients and four healthy controls were included, and in three patients, CSF was also collected at 3 months after lesion. We identified 19 proteins among the 60 investigated cytokines, chemokines, growth factors, and structural biomarkers, which are transiently regulated 24 h after SCI. A bioinformatic analysis indicated that interleukin (IL)-6 and IL-10 are in the core of the interconnected net of activated proteins. Cell-based experiments indicate that CSF from SCI patients stimulates astroglia derivation from neural precursor cells, and an inverse correlation between IL-8 CSF level and oligodendrocyte precursor cells generated from neural stem cells was also observed. Results from this pilot study suggest that using a combined bioanalytic and biological approach to analyze SCI CSF at different times after injury could be a useful approach for identifying reliable diagnostic and prognostic markers in SCI.

Validation of the Italian version of the Critical Pain Observation Tool in brain-injured critically ill adults.

BACKGROUND AND AIM: Pain in intensive care units (ICUs) is a frequent and often undermanaged problem. Brain-injured patients are often unable to reliably self-report their pain, calling forth the need to use behavioural scales such as the Critical-Care Pain Observation Tool (CPOT). This study aimed to test the reliability and validity of the Italian CPOT use with brain-injured ICU adults. METHOD: A sample of 50 adults critical care patients was included. Each patient was assessed by two independent observers at three predefined times - at rest; during mobilization for hygiene; 20 minutes later - using the CPOT, PAINAD, and NRS. RESULTS: A good correlation was found between independent observers scores during painful procedure, establishing interrater reliability of CPOT. Criterion validation was supported by a strong correlation between CPOT and PAINAD scores, and a moderate relation between CPOT and NRS scores. The CPOT was able to discriminate between patients undergoing painful versus non-painful procedures. However, PAINAD performed better in this sample, as revealed by the comparison between the two AUC of ROC curves. CONCLUSIONS: The Italian CPOT use was found reliable and valid in this patient group.

Pharyngo-oesophageal perforation following anterior cervical discectomy and fusion: management and results.

OBJECTIVES: Pharyngo-oesophageal perforation is a rare, life-threatening complication of anterior cervical discectomy and fusion surgery; its management remains poorly defined. We reviewed our experience to understand the treatment of this dreadful complication. METHODS: Data regarding the demographics, clinical course, diagnosis, management and outcomes of 15 cases of pharyngo-oesophageal perforations in 14 patients were collected during the period from 2003 to 2016. RESULTS: Pharyngo-oesophageal perforation occurred at a median of 32 days (range 1 day-102 months) after anterior cervical discectomy and fusion surgery. Clinical manifestations included neck abscesses and cutaneous fistulas (10 cases), cervical swelling (two cases), salivary leakage from cervicotomy (two cases), dysphagia, halitosis and regurgitation (one case). In all cases, conservative management was utilized. Two patients affected by minor external fistulas were successfully managed conservatively. In 13 cases, the following surgery was performed: (i) radical bone debridement, total or partial removal of spine fixation devices, autologous bone graft insertion or plate/cage replacement in one case each; (ii) anatomical suture of the fistula; or (iii) suture line reinforcement with myoplasty (in 11/13 cases). Perforation recurred in three cases. One patient underwent reoperation. The other two patients were treated conservatively At a median follow-up of 82 months (range 1-157 months), all patients exhibited permanent resolution of the perforation. CONCLUSIONS: Patients with minimal leaks in the absence of systemic infection can be managed conservatively. For cases of large fistulas with systemic infection, we recommend partial or total removal of the fixation devices, direct suture of the oesophageal defect and coverage with tissue flaps.

Pulmonary function and expiratory flow limitation in acute cervical spinal cord injury.

OBJECTIVE: To identify the nature of the changes of respiratory mechanics in patients with middle cervical spinal cord injury (SCI) and their correlation with posture. DESIGN: Clinical trial. SETTING: Acute SCI unit. PARTICIPANTS: Patients with SCI (N=34) at C4-5 level studied within 6 months of injury. INTERVENTIONS: Patients were assessed by the negative expiratory pressure test, maximal static respiratory pressure test, and standard spirometry. MAIN OUTCOME MEASURES: The following respiratory variables were recorded in both the semirecumbent and supine positions: (1) tidal expiratory flow limitation (TEFL); (2) airway resistances; (3) mouth occlusion pressure developed 0.1 seconds after occluded inspiration at functional residual capacity (P(0.1)); (4) maximal static inspiratory pressure (MIP) and maximal static expiratory pressure (MEP); and (5) spirometric data. RESULTS: TEFL was detected in 32% of the patients in the supine position and in 9% in the semirecumbent position. Airway resistances and P(0.1) were much higher compared with normative values, while MIP and MEP were markedly reduced. The ratio of forced expiratory volume in 1 second to forced vital capacity was less than 70%, while the other spirometric data were reduced up to 30% of predicted values. CONCLUSIONS: Patients with middle cervical SCI can develop TEFL. The presence of TEFL, associated with increased airway resistance, could increase the work of breathing in the presence of a reduced capacity of the respiratory muscles to respond to the increased load. The semirecumbent position and the use of continuous positive airway pressure can be helpful to (1) reduce the extent of TEFL and avoid the opening/closure of the small airways; (2) decrease airway resistance; and (3) maintain the expiratory flow as high as possible, which aids in the removal of secretions.