TACAN Is an Ion Channel Involved in Sensing Mechanical Pain.

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying essential physiological functions such as touch and pain sensing, hearing, and proprioception. Although the mechanisms for some of these functions have been identified, the molecules essential to the sense of pain have remained elusive. Here we report identification of TACAN (Tmem120A), an ion channel involved in sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, a nociceptor-specific inducible knockout of TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to painful mechanical stimuli but not to thermal or touch stimuli. We propose that TACAN is an ion channel that contributes to sensing mechanical pain.

Scoliosis in osteogenesis imperfecta: results of posterior spinal fusion in 39 patients.

PURPOSE: To evaluate the outcomes of scoliosis corrective surgery in Osteogenesis Imperfecta (OI) patients with primarily pedicles screw fixation in terms of correcting and maintaining the correction of the spinal deformity, and to assess for several peri-operative parameters and complications associated with this surgical treatment. METHODS: Retrospective case series of 39 consecutive patients with OI treated surgically for scoliosis. The surgeries were performed between 2002 and 2020 by three different surgeons. All patients' medical peri-operative and post-operative charts were evaluated. Radiological assessment was performed by evaluation of the pre-operative, immediate post-operative and last follow-up plain radiographs. RESULTS: There were 20 females and 19 males included in this review with a mean age of 14 years (range, 6-20 years) at the time of surgery. The median follow-up time was 7.9 years. The mean pre-operative cobb angle (CA) of the major curve was 76.5 degrees (SD ± 18.9), decreasing to 42.6 (SD ± 17.4) in the long-term post-operative follow-up (P < 0.001). A total of 21 adverse events in 16 patients were noted. Only 4 patients required subsequent invasive surgical treatment or prolonged hospital stay. All other patients were treated conservatively with no lasting complication. CONCLUSION: Scoliosis surgical correction in OI patients seems to yield acceptable results, with maintained coronal plane surgical correction in the long-term follow-up. Even though a high peri-operative complications rate is observed in this series, there were no long-term sequelae or lasting complications. LEVEL OF EVIDENCE: Level IV, Case series.

Regional and age-related diversity of human mature oligodendrocytes.

Morphological and emerging molecular studies have provided evidence for heterogeneity within the oligodendrocyte population. To address the regional and age-related heterogeneity of human mature oligodendrocytes (MOLs) we applied single-cell RNA sequencing to cells isolated from cortical/subcortical, subventricular zone brain tissue samples, and thoracolumbar spinal cord samples. Unsupervised clustering of cells identified transcriptionally distinct MOL subpopulations across regions. Spinal cord MOLs, but not microglia, exhibited cell-type-specific upregulation of immune-related markers compared to the other adult regions. SVZ MOLs showed an upregulation of select number of development-linked transcription factors compared to other regions; however, pseudotime trajectory analyses did not identify a global developmental difference. Age-related analysis of cortical/subcortical samples indicated that pediatric MOLs, especially from under age 5, retain higher expression of genes linked to development and to immune activity with pseudotime analysis favoring a distinct developmental stage. Our regional and age-related studies indicate heterogeneity of MOL populations in the human CNS that may reflect developmental and environmental influences.

Prevention of postoperative pancreatic fistula after pancreatectomy: results of a Canadian RAND/UCLA appropriateness expert panel.

BACKGROUND: We aimed to define the appropriateness of interventions for the prevention of postoperative pancreatic fistulas (POPF) after pancreatectomy, given the lack of consistent data on this topic. METHODS: Using the RAND/UCLA appropriateness method, we assembled an expert panel to rate clinical scenarios for interventions to prevent POPF after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). RESULTS: The following interventions were rated appropriate: individualized risk prediction for all patients; perioperative pasireotide administration for patients undergoing PD who have a soft pancreatic gland and a pancreatic duct size of less 3 mm and for patients undergoing DP; pancreaticogastrostomy for patients undergoing PD who have a soft pancreatic gland and pancreaticojejunostomy for PD for patients with a pancreatic duct size of 6 mm or greater regardless of pancreatic gland texture; duct-to-mucosa anastomosis for all patients undergoing PD and dunking anastomosis for patients undergoing PD who have a pancreatic duct size of less than 3 mm with a firm pancreatic gland; simple stapled and reinforced stapled transection for all DP; surgical drains for PD and DP in patients with a soft pancreatic gland; and open and minimally invasive surgery for DP and open surgery for PD. The following were rated inappropriate: gastrointestinal anastomosis for stump closure in all DP and omission of surgical drain in PD for patients with a pancreatic duct diameter less than 3 mm and a soft pancreatic gland. CONCLUSION: The expert panel identified appropriate and inappropriate scenarios for POPF prevention following pancreatectomy, to provide guidance to clinicians. However, the appropriateness of the interventions in the majority of the clinical scenarios was rated as uncertain, demonstrating equipoise.

Single-Cell RNA-Seq Analysis of Cells from Degenerating and Non-Degenerating Intervertebral Discs from the Same Individual Reveals New Biomarkers for Intervertebral Disc Degeneration.

In this study, we used single-cell transcriptomic analysis to identify new specific biomarkers for nucleus pulposus (NP) and inner annulus fibrosis (iAF) cells, and to define cell populations within non-degenerating (nD) and degenerating (D) human intervertebral discs (IVD) of the same individual. Cluster analysis based on differential gene expression delineated 14 cell clusters. Gene expression profiles at single-cell resolution revealed the potential functional differences linked to degeneration, and among NP and iAF subpopulations. GO and KEGG analyses discovered molecular functions, biological processes, and transcription factors linked to cell type and degeneration state. We propose two lists of biomarkers, one as specific cell type, including C2orf40, MGP, MSMP, CD44, EIF1, LGALS1, RGCC, EPYC, HILPDA, ACAN, MT1F, CHI3L1, ID1, ID3 and TMED2. The second list proposes predictive IVD degeneration genes, including MT1G, SPP1, HMGA1, FN1, FBXO2, SPARC, VIM, CTGF, MGST1, TAF1D, CAPS, SPTSSB, S100A1, CHI3L2, PLA2G2A, TNRSF11B, FGFBP2, MGP, SLPI, DCN, MT-ND2, MTCYB, ADIRF, FRZB, CLEC3A, UPP1, S100A2, PRG4, COL2A1, SOD2 and MT2A. Protein and mRNA expression of MGST1, vimentin, SOD2 and SYF2 (p29) genes validated our scRNA-seq findings. Our data provide new insights into disc cells phenotypes and biomarkers of IVD degeneration that could improve diagnostic and therapeutic options.

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry.

BACKGROUND: The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. METHODS: Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. RESULTS: Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003). CONCLUSION: In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

A roadmap to surgery in osteogenesis imperfecta: results of an international collaboration of patient organizations and interdisciplinary care teams.

Background and purpose - Involvement of patient organizations is steadily increasing in guidelines for treatment of various diseases and conditions for better care from the patient's viewpoint and better comparability of outcomes. For this reason, the Osteogenesis Imperfecta Federation Europe and the Care4BrittleBones Foundation convened an interdisciplinary task force of 3 members from patient organizations and 12 healthcare professionals from recognized centers for interdisciplinary care for children and adults with osteogenesis imperfecta (OI) to develop guidelines for a basic roadmap to surgery in OI.Methods - All information from 9 telephone conferences, expert consultations, and face-to-face meetings during the International Conference for Quality of Life for Osteogenesis Imperfecta 2019 was used by the task force to define themes and associated recommendations.Results - Consensus on recommendations was reached within 4 themes: the interdisciplinary approach, the surgical decision-making conversation, surgical technique guidelines for OI, and the feedback loop after surgery.Interpretation - The basic guidelines of this roadmap for the interdisciplinary approach to surgical care in children and adults with OI is expected to improve standardization of clinical practice and comparability of outcomes across treatment centers.

Toll-like receptor involvement in adolescent scoliotic facet joint degeneration.

Facet joint osteoarthritis is prevalent in young patients with adolescent idiopathic scoliosis (AIS) and might contribute to back pain. Toll-like receptors (TLR) have been linked to cartilaginous tissue degeneration but their involvement in facet joint osteoarthritis in AIS patients is still unknown. We compared baseline gene expression levels of TLRs -1, -2, -4, and -6 in scoliotic and non-scoliotic chondrocytes and found higher expression levels in scoliotic chondrocytes with significantly higher TLR2 levels. Furthermore, TLR expression correlated strongly and significantly with inflammatory and catabolic markers in scoliotic but not in non-scoliotic chondrocytes. TLR activation with a synthetic TLR2/6 agonist resulted in a robust induction and release of pro-inflammatory and catabolic factors which exacerbated proteoglycan loss in scoliotic but not in non-scoliotic cartilage. We also detected a higher abundance of alarmins including S100A8/9 and biglycan in scoliotic cartilage. Finally, the small-molecule antagonists Sparstolonin B and o-Vanillin reduced catabolism following induction with naturally occurring alarmins and the synthetic TLR2/6 agonist. The high baseline expression, robust responsiveness and strong and significant correlation with proteases and pro-inflammatory cytokines suggest that TLRs are key regulators of facet joint degeneration in AIS. Blocking their activity could therefore potentially modify disease progression.

Back pain in adolescents with idiopathic scoliosis: the contribution of morphological and psychological factors.

PURPOSE: To define the relationship between 3D radiological features, psychological factors, and back pain prevalence and intensity in patients with adolescent idiopathic scoliosis (AIS). METHODS: Consecutive AIS patients answered self-reported questionnaires and underwent simultaneous posterior-anterior and lateral scans of the spine (EOS Imaging, Paris, France). 3D reconstructions of the spine and pelvis reported 18 parameters in the coronal, sagittal, and axial plane. RESULTS: Hundred and twenty-four patients with AIS were included in the study. Overall, 90% of AIS patients reported having some back pain over the last 6 months and 85.8% over the last 30 days. Pain intensity in the last month was reported to be mild in 37.5%, moderate in 31.8%, moderate to severe in 24.3%, and severe in 6.54% of cases. Location of back pain was associated with location of main curve (P = 0.036). Low back pain was associated with higher lumbar apical AVR and lower lumbar lordosis (P < 0.05). Independent risk factors for back pain in AIS were pain catastrophizing (B = 0.061, P = 0.035), poorer self-reported state of mental health (B = - 0.872, P = 0.023), decreased thoracic kyphosis (B = - 0.033, P = 0.044) and greater pelvic asymmetry (B = 0.146, P = 0.047). There was a significant association between self-reported pain intensity in the last 24 h and levels of catastrophizing. Pain catastrophizing level influenced the relationship between deformity severity and pain intensity. In low catastrophizers, there was a significant association between greater deformity severity and higher pain levels. CONCLUSIONS: Back pain in AIS is multifactorial and associated with psychological and morphological parameters. Pain catastrophizing is an important construct in AIS-related pain and should be taken into consideration when evaluating these patients.

Improving delivery of care in rural emergency departments: a qualitative pilot study mobilizing health professionals, decision-makers and citizens in Baie-Saint-Paul and the Magdalen Islands, Québec, Canada.

BACKGROUND: Emergency departments (EDs) in rural and remote areas face challenges in delivering accessible, high quality and efficient services. The objective of this pilot study was to test the feasibility and relevance of the selected approach and to explore challenges and solutions to improve delivery of care in selected EDs. METHODS: We conducted an exploratory multiple case study in two rural EDs in Québec, Canada. A survey filled out by the head nurse for each ED provided a descriptive statistical portrait. Semi-structured interviews were conducted with ED health professionals, decision-makers and citizens (n = 68) and analyzed inductively and thematically. RESULTS: The two EDs differed with regards to number of annual visits, inter-facility transfers and wait time. Stakeholders stressed the influence of context on ED challenges and solutions, related to: 1) governance and management (e.g. lack of representation, poor efficiency, ill-adapted standards); 2) health services organization (e.g. limited access to primary healthcare and long-term care, challenges with transfers); 3) resources (e.g. lack of infrastructure, limited access to specialists, difficult staff recruitment/retention); 4) and professional practice (e.g. isolation, large scope, maintaining competencies with low case volumes, need for continuing education, teamwork and protocols). There was a general agreement between stakeholder groups. CONCLUSIONS: Our findings show the feasibility and relevance of mobilizing stakeholders to identify context-specific challenges and solutions. It confirms the importance of undertaking a larger study to improve the delivery of care in rural EDs.

Adolescent idiopathic scoliosis: evaluating perioperative back pain through a simultaneous morphological and biomechanical approach.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) has been associated with diminished postural stability and a greater prevalence of back pain. Currently, the literature is lacking information on the effect of spinal fusion on both postural stability and its association with back pain. Our objectives were to evaluate the postsurgical effect of spinal morphological changes on static standing balance and assess the influence of these alterations on reported pain throughout the perioperative period. METHODS: Twenty consecutive AIS patients schedule to undergo spinal fusion surgery were recruited and followed prospectively at the Shriners Hospitals for Children-Canada. Data was collected at the preoperative, 6 weeks and 6 months postoperative visits. Spinal morphology data was collected through 3D reconstructed simultaneous standing biplanar radiographs using the SterEOS software. Postural balance was assessed through Moticon© sensor insoles and analyzed through their software. The data was simultaneously collected as part of the Global Biomechanical and morphological Assessment. Pain was evaluated through self-reported questionnaires. RESULTS: Morphological curve parameters were significantly reduced after surgery. Balance parameters did not change significantly throughout the perioperative period with the exception of the Center of Pressure of the left foot medial/lateral transient shift (P = 0.017) at 6 weeks. Of note, preoperative balance parameters were associated with the degree of right thoracic Cobb angles (P = 0.029 R = 0.528). Pain scores significantly improved 6 weeks and 6 months after the surgery. Pain intensity diminished in the thoracic and lumbar spine but worsen in the neck region at the 6 weeks and 6 months postoperative time points (P = 0.044). Greater residual Cobb angle difference between Mid thoracic and Thoracolumbar/Lumbar curves was associated with greater pain severity at 6 weeks postop (P < 0.005). In addition, greater residual thoracic deformity was associated with significant pain severity 6 months after surgery (P < 0.05). CONCLUSIONS: Improved spinal morphology of postsurgical AIS patients has no significant impact on their static standing balance. Suggesting that other factors apart from the spinal morphology may contribute to AIS patients' balance during stance. Although balance did not influence pain severity, spinal morphology and its correction appear to have influenced the intensity and location of back pain.

The Tampa Scale of Kinesiophobia: Structural Validation among Adolescents with Idiopathic Scoliosis Undergoing Spinal Fusion Surgery.

AIMS: Spinal fusion surgery is one of the most invasive orthopedic surgeries. Pain while moving or a fear of experiencing pain after surgery may delay return to function and cause prolonged disability. The purpose of the study was to examine the psychometric properties of the Tampa Scale of Kinesiophobia (TSK) in pediatric patients undergoing scoliosis surgery. METHODS: Fifty-five adolescents (10-18 years old) scheduled for spinal fusion surgery were enrolled. Participants completed the TSK questionnaire before surgery and six weeks after surgery. Reliability, exploratory and confirmatory factor analyses were performed on the two-factors TSK including activity avoidance (TSK-AA) and somatic focus (TSK-SF). RESULTS: Before and after surgery, all TSK-AA items conformed into the same factor component and revealed good internal reliability with Cronbach's alpha of .76 and .70 respectively. TSK-SF items were separated into different factor components and revealed poor reliability (.11 and .56). The TSK-AA also produced an adequate fit to the data, as reflected with several fit indices at both timepoints, respectively: χ2/df = 1.19 and 1.22; CFI=.96 and .94; and RMSEA=.06 and .06. CONCLUSIONS: The TSK-AA demonstrated good psychometric properties in patients undergoing scoliosis surgery, which provides empirical evidence for pediatrics. Its validation in distinct populations and settings is recommended prior to its use.

Additional value of gadoxetic acid-enhanced MRI to conventional extracellular gadolinium-enhanced MRI for the surgical management of colorectal and neuroendocrine liver metastases.

BACKGROUND: Liver resection being the only potentially curative treatment for patients with liver metastasis, it is critical to select the appropriate preoperative imaging modality. The aim of this study was to assess the impact of preoperative gadoxetic acid-enhanced MRI compared to a conventional extracellular gadolinium-enhanced MRI on the surgical management of colorectal and neuroendocrine liver metastasis. METHODS: We included 110 patients who underwent both a gadoxetic acid-enhanced MRI (hepatospecific contrast) and conventional extracellular gadolinium for the evaluation of colorectal or neuroendocrine liver metastases, from January 2012 to December 2015 at the CHU de Québec - Université Laval. When the number of lesions differed, a hepatobiliary surgeon evaluated if the gadoxetic acid-enhanced MRI modified the surgical management. RESULTS: Gadoxetic acid-enhanced MRI found new lesions in 25 patients (22.7%), excluded lesions in 18 patients (16.4%) and identified the same number in 67 patients (60.9%). The addition of the gadoxetic acid-enhanced MRI directly altered the surgical management in 19 patients overall (17.3% (95% CI [10.73-25.65])). CONCLUSION: Despite the additional cost associated with gadoxetic acid-enhanced MRI compared to conventional extracellular gadolinium-enhanced MRI, the use of this contrast agent has a significant impact on the surgical management of patients with liver metastases.

Patient blood management for liver resection: consensus statements using Delphi methodology.

BACKGROUND: Blood loss and transfusion remain a significant concern in liver resection (LR). Patient blood management (PBM) programs reduce use of transfusions and improve outcomes and costs, but are not standardized for LR. This study sought to create an expert consensus statement on PBM for LR using modified Delphi methodology. METHODS: An expert panel representing hepato-biliary surgery, anesthesiology, and transfusion medicine was invited to participate. 28 statements addressing the 3 pillars of PBM were created. Panelists were asked to rate statements on a 7-point Likert scale. Three-rounds of iterative rating and feedback were completed anonymously, followed by an in-person meeting. Consensus was reached with at least 70% agreement. RESULTS: The 35 experts panel recommended routine pre-operative transfusion risk assessment, and investigation and management of anemia with iron supplementation. Intra-operatively, restrictive fluid administration without routine central line insertion was recommended, along with intermittent hepatic pedicle occlusion and surgical techniques considerations. Specific criteria for restrictive intra-operative and post-operative transfusion strategy were recommended. CONCLUSIONS: PBM for LR included medical and technical interventions throughout the perioperative continuum, addressing specificities of LR. Diffusion and adoption of these recommendations can standardize PBM for LR to improve patient outcomes and resource utilization.

Recessive osteogenesis imperfecta caused by missense mutations in SPARC.

Secreted protein, acidic, cysteine-rich (SPARC) is a glycoprotein that binds to collagen type I and other proteins in the extracellular matrix. Using whole-exome sequencing to identify the molecular defect in two unrelated girls with severe bone fragility and a clinical diagnosis of osteogenesis imperfecta type IV, we identified two homozygous variants in SPARC (GenBank: NM_003118.3; c.497G>A [p.Arg166His] in individual 1; c.787G>A [p.Glu263Lys] in individual 2). Published modeling and site-directed mutagenesis studies had previously shown that the residues substituted by these mutations form an intramolecular salt bridge in SPARC and are essential for the binding of SPARC to collagen type I. The amount of SPARC secreted by skin fibroblasts was reduced in individual 1 but appeared normal in individual 2. The migration of collagen type I alpha chains produced by these fibroblasts was mildly delayed on SDS-PAGE gel, suggesting some overmodification of collagen during triple helical formation. Pulse-chase experiments showed that collagen type I secretion was mildly delayed in skin fibroblasts from both individuals. Analysis of an iliac bone sample from individual 2 showed that trabecular bone was hypermineralized on the material level. In conclusion, these observations show that homozygous mutations in SPARC can give rise to severe bone fragility in humans.

Assessing tools for management of noncolorectal nonneuroendocrine liver metastases: External validation of a prognostic model.

INTRODUCTION: Selection criteria and benefits for resection of noncolorectal, nonneuroendocrine liver metastases (NCNNELM) remain debated. A prognostic score was developed by the Association Française de Chirurgie (AFC) for patient selection, but not validated. We performed a geographic external validation of this score. METHODS: Patients with resected NCNNELM from six institutions (2000-2014) were assigned risk groups based on the AFC score. Discrimination was evaluated by visually inspecting separation of overall survival (OS) curves among risk categories. The slope of the continuous score on OS and hazard ratios for risk categories were examined. RESULTS: Of 165 patients, 53 (32.1%) were low-risk, 85 (51.5%) intermediate-risk, and 27 (16.4%) high-risk. The OS curves did not separate among risk groups: 5-year OS were 60.1% (low), 57.1% (intermediate), and 55.6% (high). The parameter estimate (0.02) indicated lower discrimination than in the AFC cohort. Hazard ratios of 1.05 (0.63 to 1.70) for low vs intermediate, 0.87 (0.46 to 1.64) for low vs high, and 0.83 (0.46 to 1.49) for intermediate vs. high, demonstrated lack of discrimination in OS among risk groups. CONCLUSION: While long-term survival is achievable, discrimination of the AFC score is not maintained in a geographic external cohort of resected NCNNELM. It is not generalizable to this external population.

Nerve Growth Factor Is Regulated by Toll-Like Receptor 2 in Human Intervertebral Discs.

Nerve growth factor (NGF) contributes to the development of chronic pain associated with degenerative connective tissue pathologies, such as intervertebral disc degeneration and osteoarthritis. However, surprisingly little is known about the regulation of NGF in these conditions. Toll-like receptors (TLR) are pattern recognition receptors classically associated with innate immunity but more recently were found to be activated by endogenous alarmins such as fragmented extracellular matrix proteins found in degenerating discs or cartilage. In this study we investigated if TLR activation regulates NGF and which signaling mechanisms control this response in intervertebral discs. TLR2 agonists, TLR4 agonists, or IL-1ß (control) treatment increased NGF, brain-derived neurotrophic factor (BDNF), and IL-1ß gene expression in human disc cells isolated from healthy, pain-free organ donors. However, only TLR2 activation or IL-1ß treatment increased NGF protein secretion. TLR2 activation increased p38, ERK1/2, and p65 activity and increased p65 translocation to the cell nucleus. JNK activity was not affected by TLR2 activation. Inhibition of NF-κB, and to a lesser extent p38, but not ERK1/2 activity, blocked TLR2-driven NGF up-regulation at both the transcript and protein levels. These results provide a novel mechanism of NGF regulation in the intervertebral disc and potentially other pathogenic connective tissues. TLR2 and NF-κB signaling are known to increase cytokines and proteases, which accelerate matrix degradation. Therefore, TLR2 or NF-κB inhibition may both attenuate chronic pain and slow the degenerative progress in vivo.

Effect of N-acetylcysteine on liver recovery after resection: A randomized clinical trial.

BACKGROUND AND OBJECTIVES: Liver failure following hepatic resection is a multifactorial complication. In experimental studies, infusion of N-acetylcysteine (NAC) can minimize hepatic parenchymal injury. METHODS: Patients undergoing liver resection were randomized to postoperative care with or without NAC. No blinding was performed. Overall complication rate was the primary outcome; liver failure, length of stay, and mortality were secondary outcomes. Due to safety concerns, a premature multivariate analysis was performed and included within the model randomization to NAC, preoperative ASA, extent of resection, and intraoperative vascular occlusion as factors. RESULTS: Two hundred and six patients were randomized (110 to conventional therapy; 96 to NAC). No significant differences were noted in overall complications (32.7% and 45.7%, P = 0.06) or hepatic failure (3.6% and 5.4%, P = 0.537) between treatment groups. There was significantly more delirium within the NAC group (2.7% and 9.8%, P < 0.05) that caused early trial termination. In multivariate analysis, only randomization to NAC (OR = 2.21, 95%CI = 1.16-4.19) and extensive resections (OR = 2.28, 95%CI = 1.22-4.29) were predictive of postoperative complications. CONCLUSIONS: Patients randomized to postoperative NAC received no benefit. There was a trend toward a higher rate of overall complications and a significantly higher rate of delirium in the NAC group. J. Surg. Oncol. 2016;114:446-450. © 2016 Wiley Periodicals, Inc.

The use of computer-assisted surgery as an educational tool for the training of orthopedic surgery residents in pedicle screw placement: a pilot study and survey among orthopedic residents.

BACKGROUND: The training of orthopedic residents in adequate pedicle screw placement is very important. We sought to investigate orthopedic residents' perspectives on the use of computer-assisted surgery (CAS) in a training trial. METHODS: Orthopedic residents were randomly assigned to independently place a screw using the free-hand technique and the CAS technique on 1 of 3 cadavers (Cobb angles 5º, 15º and 67º) at randomly selected thoracolumbar vertebral levels. All residents were blinded to their colleagues' pedicle screw placements and were asked to complete a short questionnaire at the end of the session to evaluate their experience with CAS. We obtained CT images for each cadaver to assess pedicle screw placement accuracy and classified placement as A) screw completely in pedicle, B) screw < 2 mm outside pedicle, C) screw 2-4 mm outside pedicle, or D) screw > 4 mm outside pedicle. RESULTS: Twenty-four orthopedic residents participated in this trial study. In total, 65% preferred using the free-hand technique in an educational setting even though most (60%) said that CAS is safer. The main reason for free-hand technique preference was the difficult technical aspects encountered with CAS. In addition, accuracy of pedicle screw placement in this trial showed that 5 screws were classified as A or B (safe zone) and 19 as grade C or D (unsafe zone) using the free-hand technique compared with 15 and 9, respectively, using CAS (p = 0.008). CONCLUSION: Orthopedic residents perceived CAS as safe and demonstrated improved accuracy in pedicle screw placement in a single setting. However, the residents preferred the free-hand technique in an educational stetting owing to the difficult technical aspects of CAS.

CONTEXTE: Il est très important d'apprendre aux médecins résidents en chirurgie orthopédique comment positionner adéquatement une vis pédiculaire. Notre objectif était d'obtenir l'opinion des médecins résidents sur le recours à la chirurgie assistée par ordinateur (CAO) dans un essai sur la formation. MÉTHODES: Des médecins résidents en chirurgie orthopédique répartis aléatoirement ont placé indépendamment une vis à l'aide d'une technique à main libre basée sur les repères topographiques et la palpation, et de la CAO dans 1 de 3 cadavres (angles de Cobb de 5°, 15° et 67°) dans une vertèbre dorsolombaire sélectionnée aléatoirement. Aucun des médecins résidents n'a pu observer le positionnement de la vis de ses collègues, et les participants ont rempli un court questionnaire à la fin de la séance pour évaluer leur expérience de la CAO. Nous avons obtenu un tomodensitogramme pour chaque cadavre afin d'évaluer la précision du positionnement de la vis pédiculaire, classée selon 4 catégories : A) vis entièrement dans le pédicule, B) vis < 2 mm hors du pédicule, C) vis de 2­4 mm hors du pédicule, ou D) vis > 4 mm hors du pédicule. RÉSULTATS: Vingt-quatre médecins résidents en chirurgie orthopédique ont participé à l'étude clinique. Au total, 65 % d'entre eux ont préféré utiliser la technique à main libre dans un contexte de formation, même si la plupart (60 %) considéraient que la CAO était plus sécuritaire. La principale raison justifiant cette préférence était le degré de difficulté technique associé à la CAO. De plus, une évaluation de la précision du positionnement a montré qu'avec la technique à main libre, 5 des vis posées se classaient dans les catégories A ou B (sécuritaire) et 19 dans les catégories C ou D (non sécuritaire), alors que la CAO a permis de positionner 15 vis dans les catégories A ou B et 9 dans les catégories C ou D (p = 0,008). CONCLUSION: Chez un sous-groupe de patients souffrant de traumatismes abdominaux pénétrants, le traitement conservateur est sécuritaire et se traduit par une durée de séjour inférieure de 1,9 jour. La présence de fluide détectée par tomodensitographie est un indicateur de l'échec du traitement.