An Update of a Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role and Timing of Decompressive Surgery.

STUDY DESIGN: Clinical practice guideline development. OBJECTIVES: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI). METHODS: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. RESULTS: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. CONCLUSIONS: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.

A Clinical Practice Guideline for Prevention, Diagnosis and Management of Intraoperative Spinal Cord Injury: Recommendations for Use of Intraoperative Neuromonitoring and for the Use of Preoperative and Intraoperative Protocols for Patients Undergoing Spine Surgery.

STUDY DESIGN: Development of a clinical practice guideline following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process. OBJECTIVE: The objectives of this study were to develop guidelines that outline the utility of intraoperative neuromonitoring (IONM) to detect intraoperative spinal cord injury (ISCI) among patients undergoing spine surgery, to define a subset of patients undergoing spine surgery at higher risk for ISCI and to develop protocols to prevent, diagnose, and manage ISCI. METHODS: All systematic reviews were performed according to PRISMA standards and registered on PROSPERO. A multidisciplinary, international Guidelines Development Group (GDG) reviewed and discussed the evidence using GRADE protocols. Consensus was defined by 80% agreement among GDG members. A systematic review and diagnostic test accuracy (DTA) meta-analysis was performed to synthesize pooled evidence on the diagnostic accuracy of IONM to detect ISCI among patients undergoing spinal surgery. The IONM modalities evaluated included somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), electromyography (EMG), and multimodal neuromonitoring. Utilizing this knowledge and their clinical experience, the multidisciplinary GDG created recommendations for the use of IONM to identify ISCI in patients undergoing spine surgery. The evidence related to existing care pathways to manage ISCI was summarized and based on this a novel AO Spine-PRAXIS care pathway was created. RESULTS: Our recommendations are as follows: (1) We recommend that intraoperative neurophysiological monitoring be employed for high risk patients undergoing spine surgery, and (2) We suggest that patients at "high risk" for ISCI during spine surgery be proactively identified, that after identification of such patients, multi-disciplinary team discussions be undertaken to manage patients, and that an intraoperative protocol including the use of IONM be implemented. A care pathway for the prevention, diagnosis, and management of ISCI has been developed by the GDG. CONCLUSION: We anticipate that these guidelines will promote the use of IONM to detect and manage ISCI, and promote the use of preoperative and intraoperative checklists by surgeons and other team members for high risk patients undergoing spine surgery. We welcome teams to implement and evaluate the care pathway created by our GDG.

Timing of Decompressive Surgery in Patients With Acute Spinal Cord Injury: Systematic Review Update.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Surgical decompression is a cornerstone in the management of patients with traumatic spinal cord injury (SCI); however, the influence of the timing of surgery on neurological recovery after acute SCI remains controversial. This systematic review aims to summarize current evidence on the effectiveness, safety, and cost-effectiveness of early (≤24 hours) or late (>24 hours) surgery in patients with acute traumatic SCI for all levels of the spine. Furthermore, this systematic review aims to evaluate the evidence with respect to the impact of ultra-early surgery (earlier than 24 hours from injury) on these outcomes. METHODS: A systematic search of the literature was performed using the MEDLINE database (PubMed), Cochrane database, and EMBASE. Two reviewers independently screened the citations from the search to determine whether an article satisfied predefined inclusion and exclusion criteria. For all key questions, we focused on primary studies with the least potential for bias and those that controlled for baseline neurological status and specified time from injury to surgery. Risk of bias of each article was assessed using standardized tools based on study design. Finally, the overall strength of evidence for the primary outcomes was assessed using the GRADE approach. Data were synthesized both qualitatively and quantitively using meta-analyses. RESULTS: Twenty-one studies met inclusion and exclusion criteria and formed the evidence base for this review update. Seventeen studies compared outcomes between patients treated with early (≤24 hours from injury) compared to late (>24 hours) surgical decompression. An additional 4 studies evaluated even earlier time frames: <4, <5, <8 or <12 hours. Based on moderate evidence, patients were 2 times more likely to recover by ≥ 2 grades on the ASIA Impairment Score (AIS) at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, moderate evidence suggested that patients receiving early decompression had an additional 4.50 (95% CI 1.70 to 7.29) point improvement on the ASIA motor score. With respect to administrative outcomes, there was low evidence that early decompression may decrease acute hospital length of stay. In terms of safety, there was moderate evidence that suggested the rate of major complications does not differ between patients undergoing early compared to late surgery. Furthermore, there was no difference in rates of mortality, surgical device-related complications, sepsis/systemic infection or neurological deterioration based on timing of surgery. Firm conclusions were not possible with respect to the impact of ultra-early surgery on neurological, functional or safety outcomes given the poor-quality studies, imprecision and the overlap in the time frames examined. CONCLUSIONS: This review provides an evidence base to support the update on clinical practice guidelines related to the timing of surgical decompression in acute SCI. Overall, the strength of evidence was moderate that early surgery (≤24 hours from injury) compared to late (>24 hours) results in clinically meaningful improvements in neurological recovery. Further studies are required to delineate the role of ultra-early surgery in patients with acute SCI.

The PlexiQoL, a patient-reported outcome measure on quality of life in neurofibromatosis type 1-associated plexiform neurofibroma: translation, cultural adaptation and validation into the Dutch language for the Netherlands.

BACKGROUND: Half of the patients with Neurofibromatosis type 1 (NF1) develop one or more tumours called plexiform neurofibromas, which can have a significant impact on Quality of Life (QoL). The PlexiQoL questionnaire is a disease-specific QoL measure for adults with NF1-associated plexiform neurofibromas. The aim of this study was to adapt and validate a Dutch version of the PlexiQoL for the Netherlands. METHODS: The PlexiQoL was translated using the dual-panel methodology, followed by cognitive debriefing interviews to assess face and content validity. The psychometric properties were evaluated by administering the questionnaire on two separate occasions to a sample of adults with NF1 and plexiform neurofibromas. Feasibility was evaluated by the presence of floor/ceiling effects. Reliability was assessed by evaluating Cronbach's alpha coefficient and test-retest reliability, using Spearman's rank correlation coefficients. Mann-Whitney U tests were used to check for known group validity. The Nottingham Health Profile (NHP) questionnaire was used as comparator questionnaire to evaluate convergent validity. RESULTS: The translation and cognitive debriefing interviews resulted in a Dutch version of the PlexiQoL that reflected the original concept and underlying semantic meanings of the UK English version. Forty participants completed the validation survey. The Dutch PlexiQoL demonstrated excellent internal consistency (Cronbach's α 0.825) and test-retest reliability (Spearman correlation coefficient 0.928). The questionnaire detected differences in PlexiQoL scores between participants based on self-reported general health and disease severity. Convergent validity was confirmed for relevant NHP subsections. CONCLUSIONS: The Dutch PlexiQoL demonstrated excellent psychometric properties and can be reliably used to measure plexiform neurofibroma-related QoL in adults with NF1 in the Netherlands.

Surgical Ulcer Debridement in a Patient With Spina Bifida Complicated by Osteomyelitis, Obesity, and Diabetes.

The combination of obesity, diabetes mellitus (DM), and reduced mobility due to spina bifida can contribute to an increased risk of osteomyelitis. Spina bifida, a congenital defect of the spinal cord, causes vertebral column deformities and neurological impairment. Obesity can lead to increased pressure and stress on the bones and joints, as well as poor circulation and immune dysfunction, including neutrophil migration disorders. Similarly, DM can also contribute to poor circulation and inadequate immune function. These changes can increase the risk of neuropathic ulcerations and osteomyelitis. We report a case of a 59-year-old man who presented for surgical consultation at the inpatient care unit. He had a nonhealing sacral ulcer on the left buttock that persisted for a year. He had a history of spina bifida, type 2 DM, and anemia, and his body mass index was 57.6 kg/m2. Physical examination revealed an unstageable left buttock pressure ulcer. The patient was afebrile, and his laboratory findings and imaging results indicated osteomyelitis. Despite intravenous antibiotic treatment, healing of the sacral ulcer remained poor, and the patient experienced chronic pain. Subsequent surgical intervention in the operating room involved debridement of the skin and soft tissue using high-powered water via the VERSAJET™ Hydrosurgery System (Smith & Nephew, London, UK). Ulcerated and necrotic skin and subcutaneous tissue extending deeper than the muscles and bones were observed. Loop colostomy was performed after determining that the wound would not heal owing to its proximity to the rectum and the inevitable contamination with stool. Postoperatively, sacral bone biopsy confirmed osteomyelitis. Alternative treatment options remained limited, as several other treatment methods failed prior to surgical debridement and colostomy placement. Although repeated debridement improved tissue viability, loop colostomy was performed to divert stool and prevent contamination of the ulcer.

Ten-year safety of pluripotent stem cell transplantation in acute thoracic spinal cord injury.

OBJECTIVE: The purpose of this study was to evaluate the safety of oligodendrocyte progenitor cells (LCTOPC1) derived from human pluripotent stem cells administered between 7 and 14 days postinjury to patients with T3 to T11 neurologically complete spinal cord injury (SCI). The rationale for this first-in-human trial was based on evidence that administration of LCTOPC1 supports survival and potential repair of key cellular components and architecture at the SCI site. METHODS: This study was a multisite, open-label, single-arm interventional clinical trial. Participants (n = 5) received a single intraparenchymal injection of 2 × 106 LCTOPC1 caudal to the epicenter of injury using a syringe positioning device. Immunosuppression with tacrolimus was administered for a total of 60 days. Participants were followed with annual in-person examinations and MRI for 5 years at the time of this report and will be followed with annual telephone questionnaires for 6 to 15 years postinjection. The primary endpoint was safety, as measured by the frequency and severity of adverse events related to the LCTOPC1 injection, the injection procedure, and/or the concomitant immunosuppression administered. The secondary endpoint was neurological function as measured by sensory scores and lower-extremity motor scores as measured by the International Standards for Neurological Classification of Spinal Cord Injury examinations. RESULTS: No unanticipated serious adverse events related to LCTOPC1 have been reported with 98% follow-up of participants (49 of 50 annual visits) through the first 10 years of the clinical trial. There was no evidence of neurological decline, enlarging masses, further spinal cord damage, or syrinx formation. MRI results during the long-term follow-up period in patients administered LCTOPC1 cells showed that 80% of patients demonstrated T2 signal changes consistent with the formation of a tissue matrix at the injury site. CONCLUSIONS: This study provides crucial first-in-human safety data supporting the pursuit of future human embryonic stem cell-derived therapies. While we cannot exclude the possibility of future adverse events, the experience in this trial provides evidence that this cell type can be well tolerated by patients, with an event-free period of up to 10 years. Based on the safety profile of LCTOPC1 obtained in this study, a cervical dose escalation trial was initiated (NCT02302157).

Anterior cervical pseudomeningocele causing syncope after spinal surgery: A case report.

INTRODUCTION AND IMPORTANCE: Pseudomeningocele formation from incidental durotomy is a known risk in spine surgery. We present a case of incidental durotomy leading to anterior neck pseudomeningocele, compressing the carotid body (CB) resulting in syncopal episodes. To our knowledge, this is the first case report implicating syncopal episodes to CB compression via a pseudomeningocele. CASE PRESENTATION: A mid sixty-year-old patient with history of obesity, hypertension, and diabetes presented with gait impairment and hand weakness. Ossification of posterior longitudinal ligament (OPLL) was diagnosed with computed tomography imaging (CT) and magnetic resonance imaging (MRI). Elective surgery was completed with an anterior and posterior approach for decompression and fusion. Hospital course (San Jose, CA, USA) was complicated by respiratory depression and incomplete tetraplegia. On post-operative day (POD) six, CT revealed anterolateral soft tissue neck swelling; subsequent CT and MRI showed fluid collection expansion, with associated syncopal episodes on POD thirty-nine. Despite interventional radiology drainage, the fluid collection and symptoms returned five days later. The patient ultimately underwent durotomy revision and repair with muscle patch. CLINICAL DISCUSSION: This case highlights the challenges in managing anterior cervical dural tears resulting in pseudomeningocele. Risk factors include anterior cervical corpectomy and decompression, as well as an underlying diagnosis of OPLL. Untreated dural tears may develop into pseudomeningoceles which can contribute to life-threatening outcomes. CONCLUSION: This case report presents the serious consequences of incidental durotomy, the unique post-surgical complication of syncope due to compression of the CB from a pseudomeningocele, and the challenges of managing a persistent pseudomeningocele.

Topological network analysis of patient similarity for precision management of acute blood pressure in spinal cord injury.

Background: Predicting neurological recovery after spinal cord injury (SCI) is challenging. Using topological data analysis, we have previously shown that mean arterial pressure (MAP) during SCI surgery predicts long-term functional recovery in rodent models, motivating the present multicenter study in patients. Methods: Intra-operative monitoring records and neurological outcome data were extracted (n = 118 patients). We built a similarity network of patients from a low-dimensional space embedded using a non-linear algorithm, Isomap, and ensured topological extraction using persistent homology metrics. Confirmatory analysis was conducted through regression methods. Results: Network analysis suggested that time outside of an optimum MAP range (hypotension or hypertension) during surgery was associated with lower likelihood of neurological recovery at hospital discharge. Logistic and LASSO (least absolute shrinkage and selection operator) regression confirmed these findings, revealing an optimal MAP range of 76-[104-117] mmHg associated with neurological recovery. Conclusions: We show that deviation from this optimal MAP range during SCI surgery predicts lower probability of neurological recovery and suggest new targets for therapeutic intervention. Funding: NIH/NINDS: R01NS088475 (ARF); R01NS122888 (ARF); UH3NS106899 (ARF); Department of Veterans Affairs: 1I01RX002245 (ARF), I01RX002787 (ARF); Wings for Life Foundation (ATE, ARF); Craig H. Neilsen Foundation (ARF); and DOD: SC150198 (MSB); SC190233 (MSB).

Spinal cord injury is a devastating condition that involves damage to the nerve fibers connecting the brain with the spinal cord, often leading to permanent changes in strength, sensation and body functions, and in severe cases paralysis. Scientists around the world work hard to find ways to treat or even repair spinal cord injuries but few patients with complete immediate paralysis recover fully. Immediate paralysis is caused by direct damage to neurons and their extension in the spinal cord. Previous research has shown that blood pressure regulation may be key in saving these damaged neurons, as spinal cord injuries can break the communication between nerves that is involved in controlling blood pressure. This can lead to a vicious cycle of dysregulation of blood pressure and limit the supply of blood and oxygen to the damaged spinal cord tissue, exacerbating the death of spinal neurons. Management of blood pressure is therefore a key target for spinal cord injury care, but so far, the precise thresholds to enable neurons to recover are poorly understood. To find out more, Torres-Espin, Haefeli et al. used machine learning software to analyze previously recorded blood pressure and heart rate data obtained from 118 patients that underwent spinal cord surgery after acute spinal cord injury. The analyses revealed that patients who suffered from either low or high blood pressure during surgery had poorer prospects of recovery. Statistical models confirming these findings showed that the optimal blood pressure range to ensure recovery lies between 76 to 104-117 mmHg. Any deviation from this narrow window would dramatically worsen the ability to recover. These findings suggests that dysregulated blood pressure during surgery affects to odds of recovery in patients with a spinal cord injury. Torres-Espin, Haefeli et al. provide specific information that could improve current clinical practice in trauma centers. In the future, such machine learning tools and models could help develop real-time models that could predict the likelihood of a patient's recovery following spinal cord injury and related neurological conditions.

Safety of direct injection of oligodendrocyte progenitor cells into the spinal cord of uninjured Göttingen minipigs.

OBJECTIVE: This study was conducted as a final proof-of-safety direct injection of oligodendrocyte progenitor cells into the uninjured spinal cord prior to translation to the human clinical trials. METHODS: In this study, 107 oligodendrocyte progenitor cells (LCTOPC1, also known as AST-OPC1 and GRNOPC1) in 50-µL suspension were injected directly into the uninjured spinal cords of 8 immunosuppressed Göttingen minipigs using a specially designed stereotactic delivery device. Four additional Göttingen minipigs were given Hanks' Balanced Salt Solution and acted as the control group. RESULTS: Cell survival and no evidence of histological damage, abnormal inflammation, microbiological or immunological abnormalities, tumor formation, or unexpected morbidity or mortality were demonstrated. CONCLUSIONS: These data strongly support the safety of intraparenchymal injection of LCTOPC1 into the spinal cord using a model anatomically similar to that of the human spinal cord. Furthermore, this research provides guidance for future clinical interventions, including mechanisms for precise positioning and anticipated volumes of biological payloads that can be safely delivered directly into uninjured portions of the spinal cord.

Psoriatic Arthritis Quality of Life Questionnaire: translation, cultural adaptation and validation into Brazilian Portuguese language.

INTRODUCTION: Psoriatic arthritis (PsA) is a multifaceted inflammatory disease that can cause joint destruction and impair quality of life. The Psoriatic Arthritis Quality of Life Questionnaire (PsAQoL) was the first disease-specific tool for determining the impact of the disease on the quality of life of people with PsA. OBJECTIVES: The primary objective was to develop and validate a Brazilian Portuguese version of the PsAQoL. METHODS: The UK PsAQoL was translated into Brazilian Portuguese using two translation panels. This translation then checked for face validity and construct validity with new samples of patients. Finally, a test-retest validation study was conducted with 52 patients with PsA. The survey included the Nottingham Health Profile (NHP) as a comparator instrument. RESULTS: Internal consistency and reproducibility were both excellent for the new adaptation (0.91 and 0.90 respectively Scores on the PsAQoL were found to correlate as expected with the comparator measure and the instrument was able to detect differences in score related to perceived severity of PsA, general health status and presence of a flare. CONCLUSION: The Brazilian PsAQoL was found easy to understand and complete and has excellent reliability and construct validity. The new measure will be a valuable new tool for use in routine PsA practice and clinical trials.

Psoriatic Arthritis Quality of Life Questionnaire: translation, cultural adaptation and validation into Brazilian Portuguese language

Abstract Introduction: Psoriatic arthritis (PsA) is a multifaceted inflammatory disease that can cause joint destruction and impair quality of life. The Psoriatic Arthritis Quality of Life Questionnaire (PsAQoL) was the first disease-specific tool for determining the impact of the disease on the quality of life of people with PsA. Objectives: The primary objective was to develop and validate a Brazilian Portuguese version of the PsAQoL. Methods: The UK PsAQoL was translated into Brazilian Portuguese using two translation panels. This translation then checked for face validity and construct validity with new samples of patients. Finally, a test-retest validation study was conducted with 52 patients with PsA. The survey included the Nottingham Health Profile (NHP) as a comparator instrument. Results: Internal consistency and reproducibility were both excellent for the new adaptation (0.91 and 0.90 respectively Scores on the PsAQoL were found to correlate as expected with the comparator measure and the instrument was able to detect differences in score related to perceived severity of PsA, general health status and presence of a flare. Conclusions: The Brazilian PsAQoL was found easy to understand and complete and has excellent reliability and construct validity. The new measure will be a valuable new tool for use in routine PsA practice and clinical trials.

The development of the PlexiQoL: A patient-reported outcome measure for adults with neurofibromatosis type 1-associated plexiform neurofibromas.

BACKGROUND: To develop and validate a patient-reported outcome (PRO) measure of quality of life (QoL), specific to patients with Neurofibromatosis Type 1 (NF1)-associated plexiform neurofibromas (pNFs), suitable for use in clinical efficacy trials. The study was conducted in parallel in the UK and US. METHODS: Qualitative interviews were conducted with patients to generate questionnaire content. Face and content validity of the draft scale was assessed by cognitive debriefing interviews (CDIs). A postal validation survey was conducted to identify the final version of the questionnaire (the PlexiQoL), establish its unidimensionality, and assess its psychometric properties. RESULTS: Thematic analysis was performed on 42 interview transcripts. Thirty-one CDIs revealed that patients found the draft scale to be comprehensible, relevant, and easy to complete. The postal validation survey was completed by 273 patients. Rasch analysis identified an 18-item unidimensional scale that showed excellent internal consistency, reproducibility, and sensitivity to differences in patient-perceived pNF severity, general health, and the use of pain medication. CONCLUSIONS: The PlexiQoL is the first disease-specific PRO assessing the ability of adults with NF-1 associated pNFs to meet their basic human needs. Clinical trials are planned to assess the sensitivity to change of the PlexiQoL in people undergoing treatment for pNFs.

Exploration of surgical blood pressure management and expected motor recovery in individuals with traumatic spinal cord injury.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: To assess the impact of mean arterial blood pressure (MAP) during surgical intervention for spinal cord injury (SCI) on motor recovery. SETTING: Level-one Trauma Hospital and Acute Rehabilitation Hospital in San Jose, CA, USA. METHODS: Twenty-five individuals with traumatic SCI who received surgical and acute rehabilitation care at a level-one trauma center were included in this study. The Surgical Information System captured intraoperative MAPs on a minute-by-minute basis and exposure was quantified at sequential thresholds from 50 to 104 mmHg. Change in International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor score was calculated based on physiatry evaluations at the earliest postoperative time and at discharge from acute rehabilitation. Linear regression models were used to estimate the rate of recovery across the entire MAP range. RESULTS: An exploratory analysis revealed that increased time within an intraoperative MAP range (70-94 mmHg) was associated with ISNCSCI motor score improvement. A significant regression equation was found for the MAP range 70-94 mmHg (F[1, 23] = 5.07, r2 = 0.181, p = 0.034). ISNCSCI motor scores increased 0.039 for each minute of exposure to the MAP range 70-94 mmHg during the operative procedure; this represents a significant correlation between intraoperative time with MAP 70-94 and subsequent motor recovery. Blood pressure exposures above or below this range did not display a positive association with motor recovery. CONCLUSIONS: Hypertension as well as hypotension during surgery may impact the trajectory of recovery in individuals with SCI, and there may be a direct relationship between intraoperative MAP and motor recovery.

Needs-based quality of life in adults dependent on home parenteral nutrition.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) provides life sustaining treatment for people with chronic intestinal failure. Individuals may require HPN for months or years and are dependent on regular intravenous infusions, usually 12-14 h overnight between 1 and 7 days each week. This regime can have adverse impact on the life of people dependent on the treatment. The aim of this study was to establish mean values for the Parenteral Nutrition Impact Questionnaire (PNIQ) and to determine the effect of disease, frequency of infusions per week and patient characteristics on quality of life of patients fed HPN. METHOD: The PNIQ was distributed to patients across nine UK HPN clinics. Data were analysed using linear regression, with PNIQ score as the dependent variable and potential confounders as independent variables. Unadjusted and adjusted models are presented. Higher PNIQ scores reflect poorer quality of life. RESULTS: Completed questionnaires were received from 466 people dependent on HPN. Mean PNIQ score was 11.04 (SD 5.79). A higher PNIQ score (effect size 0.52, CI 0.184 to 0.853) was recorded in those dependent on a higher frequency of HPN infusions per week. Respondents with cancer had a similar mean PNIQ score to those with inflammatory bowel disease (mean 10.82, SD 6.00 versus 11.04, SD 5.91). Those with surgical complications reported a poorer QoL (effect size 3.03, CI 0.642 to 5.418) and those with severe gastro-intestinal dysmotility reported a better QoL (effect size -3.03, CI -5.593 to -0.468), compared to other disease states. CONCLUSIONS: This large cohort study of quality of life in chronic intestinal failure demonstrates that HPN impacts individuals differently depending on their underlying disease. Furthermore, since the number of HPN infusions required per week is inversely related to an individual's needs-based quality of life, therapies that reduce PN burden should lead to an improvement in QoL.

High-Throughput, Time-Resolved Mechanical Phenotyping of Prostate Cancer Cells.

Worldwide, prostate cancer sits only behind lung cancer as the most commonly diagnosed form of the disease in men. Even the best diagnostic standards lack precision, presenting issues with false positives and unneeded surgical intervention for patients. This lack of clear cut early diagnostic tools is a significant problem. We present a microfluidic platform, the Time-Resolved Hydrodynamic Stretcher (TR-HS), which allows the investigation of the dynamic mechanical response of thousands of cells per second to a non-destructive stress. The TR-HS integrates high-speed imaging and computer vision to automatically detect and track single cells suspended in a fluid and enables cell classification based on their mechanical properties. We demonstrate the discrimination of healthy and cancerous prostate cell lines based on the whole-cell, time-resolved mechanical response to a hydrodynamic load. Additionally, we implement a finite element method (FEM) model to characterise the forces responsible for the cell deformation in our device. Finally, we report the classification of the two different cell groups based on their time-resolved roundness using a decision tree classifier. This approach introduces a modality for high-throughput assessments of cellular suspensions and may represent a viable application for the development of innovative diagnostic devices.

A qualitative study of the impact of plexiform neurofibromas on need fulfilment in adults with neurofibromatosis type 1.

OBJECTIVE: To explore the impact of plexiform neurofibromas on the lives of adults with neurofibromatosis type 1. BACKGROUND: Neurofibromatosis type 1 is a complex neurogenetic syndrome that affects many aspects of health and functioning. A common manifestation of neurofibromatosis type 1 is plexiform neurofibromas, non-cancerous tumours that can cause disfigurement, pain and neurologic disability. Patient-reported outcome measures used in this condition have addressed symptoms and functional ability but not how the condition affects patients' lives, particularly, their ability to meet their human needs. METHODS: Unstructured qualitative interviews were conducted with adults with neurofibromatosis type 1-associated plexiform neurofibromas in the United Kingdom and United States. Interviewees were encouraged to describe how plexiform neurofibromas affected their ability to meet their needs. Interviews were audio-recorded and transcribed verbatim. The UK and US transcripts were combined and theoretical thematic analysis was conducted. RESULTS: In all, 42 interviews (United Kingdom = 20, United States = 22) were conducted. Transcripts revealed 696 statements on the impact of plexiform neurofibromas on need fulfilment. Five major themes emerged: appearance, relationships, independence, role fulfilment and pleasure. CONCLUSION: Neurofibromatosis type 1-associated plexiform neurofibromas have a major effect on individuals' ability to meet their needs. An understanding of need fulfilment will complement information generated from traditional patient-reported outcome measures, particularly in a multi-faceted syndrome such as neurofibromatosis type 1.

Structure Prediction for Gland Segmentation With Hand-Crafted and Deep Convolutional Features.

We present a novel method to segment instances of glandular structures from colon histopathology images. We use a structure learning approach which represents local spatial configurations of class labels, capturing structural information normally ignored by sliding-window methods. This allows us to reveal different spatial structures of pixel labels (e.g., locations between adjacent glands, or far from glands), and to identify correctly neighboring glandular structures as separate instances. Exemplars of label structures are obtained via clustering and used to train support vector machine classifiers. The label structures predicted are then combined and post-processed to obtain segmentation maps. We combine hand-crafted, multi-scale image features with features computed by a deep convolutional network trained to map images to segmentation maps. We evaluate the proposed method on the public domain GlaS data set, which allows extensive comparisons with recent, alternative methods. Using the GlaS contest protocol, our method achieves the overall best performance.

Psoriatic Arthritis Quality of Life questionnaire: translation, cultural adaptation and validation into Portuguese language.

Psoriatic arthritis (PsA) has a strong negative impact on the quality of life of patients. The Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire is a disease-specific instrument developed to measure the quality of life in patients with PsA. The aims of this study were to culturally adapt the questionnaire for Portugal and evaluate its reliability and validity in patients with PsA. The original UK English version of the PsAQoL was translated into Portuguese by a bilingual and lay panel. Structured cognitive debriefing interviews were conducted with ten PsA patients. The Portuguese PsAQoL was subsequently applied to PsA patients followed at the Rheumatology Department of Centro Hospitalar do Baixo Vouga, E.P.E. To assess reproducibility, 30 patients with PsA completed the Portuguese PsAQoL on two occasions, 2 weeks apart. A larger sample was recruited to determine internal consistency and construct validity. The Nottingham Health Profile (NHP) was used as a comparator instrument. Translation and adaptation were successful. Cronbach´s alpha for the Portuguese version of the PsAQoL was 0.91 and the test-retest reliability was 0.93. The PsAQoL could distinguish between groups of patients defined by self-reported general health status, self-reported severity of PsA and flare of arthritis. There was a positive correlation between the total score of the PsAQoL and each of the sections of the NHP. The Portuguese version of the PsAQoL was found to be relevant, understandable and easy to complete, reliable and valid.

Adaptation of Chinese and English versions of the Psoriatic Arthritis Quality of Life (PsAQoL) scale for use in Singapore.

BACKGROUND: To develop Singapore Chinese and English versions of the Psoriatic Arthritis Quality of Life (PsAQoL) scale that were equivalent to and met the same psychometric and acceptability standards as the original UK measure. METHODS: Translation of the original PsAQoL into contextualised English and Chinese versions for use in Singapore was performed by professional and lay translation panels. Ten Chinese speaking and ten English speaking local patients were interviewed to assess face and content validity. Psoriatic arthritis (PsA) patients (either Chinese or English speaking) fulfilling the Classification criteria of Psoriatic Arthritis were then invited to participate in a validation survey. Clinical variables, the Health Assessment Questionnaire (HAQ) and the Medical Outcome Short-form 36 (SF-36) were used as comparator instruments for convergent validity. A separate sample of PsA patients were invited to participate in a test-retest postal study, with two weeks between administrations. RESULTS: The validation sample included 98 patients (51 % men) with a mean (SD) age of 51.5 (13.8) years. The PsAQoL had excellent internal consistency (Cronbach's α = 0.92) and scores on the measure were moderately correlated with health status measures (pain, HAQ score, SF-36 scores) and patient and physician global assessments. The scale was able to distinguish between groups with active or inactive disease assessed by composite scores, HAQ and minimal disease activity. Test-retest reliability was excellent (r = 0.92). CONCLUSIONS: This study provides evidence that the adapted English and Chinese versions of the PsAQoL can be used in clinical studies with PsA patients in Singapore.

Comparing computer-generated and pathologist-generated tumour segmentations for immunohistochemical scoring of breast tissue microarrays.

BACKGROUND: Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review. METHODS: In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software. RESULTS: Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (κ=0.81) than between pathologists' masks (κ=0.91), this had little impact on computed IHC scores (Allred; =0.91, Quickscore; =0.92). CONCLUSIONS: The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials.