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Serine rich splicing factor 3 (SRSF3) plays a critical role in liver function and its loss promotes chronic liver damage and regeneration. As a consequence, genetic deletion of SRSF3 in hepatocytes caused progressive liver disease and ultimately led to hepatocellular carcinoma. Here we show that SRSF3 is decreased in human liver samples with non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or cirrhosis that was associated with alterations in RNA splicing of known SRSF3 target genes. Hepatic SRSF3 expression was similarly decreased and RNA splicing dysregulated in mouse models of NAFLD and NASH. We showed that palmitic acid-induced oxidative stress caused conjugation of the ubiquitin like NEDD8 protein to SRSF3 and proteasome mediated degradation. SRSF3 was selectively neddylated at lysine11 and mutation of this residue (SRSF3-K11R) was sufficient to prevent both SRSF3 degradation and alterations in RNA splicing. Finally prevention of SRSF3 degradation in vivo partially protected mice from hepatic steatosis, fibrosis and inflammation. These results highlight a neddylation-dependent mechanism regulating gene expression in the liver that is disrupted in early metabolic liver disease and may contribute to the progression to NASH, cirrhosis and ultimately hepatocellular carcinoma.

Purpose Major peri-operative complications for adult spinal deformity (ASD) surgery remain common. However, risk factors have not been clearly defined. Our objective was to identify patient and surgical parameters that correlate with the development of major peri-operative complications with ASD surgery. Methods This is a multi-center, retrospective, consecutive, case–control series of surgically treated ASD patients. All patients undergoing surgical treatment for ASD at eight centers were retrospectively reviewed. Each center identified 10 patients with major peri-operative complications. Randomization tables were used to select a comparably sized control group of patients operated during the same time period that they did not suffer major complications. The two groups were analyzed for differences in clinical and surgical factors. Analysis was restricted to non-instrumentation related complications. Results At least one major complication occurred in 80 of 953 patients (8.4 %), including 72 patients with non-instrumentation related complications. There were no significant differences between the complications and control groups based on the demographics, ASA grade, co-morbidities, body mass index, prior surgeries, pre-operative anemia, smoking, operative time or ICU stay ( p  > 0.05). Hospital stay was significantly longer for the complications group (14.4 vs. 7.9 days, p  = 0.001). The complications group had higher percentages of staged procedures (46 vs. 37 %, p  = 0.011) and combined anterior–posterior approaches (56 vs. 32 %, p  = 0.011) compared with the control group. Conclusion The major peri-operative complication rate was 8.4 % for 953 surgically treated ASD patients. Significantly higher rates of complications were associated with staged and combined anterior–posterior surgeries. None of the patient factors assessed were significantly associated with the occurrence of major peri-operative complications. Improved understanding of risk profiles and procedure-related parameters may be useful for patient counseling and efforts to reduce complication rates.

Abstract BACKGROUND A surgical invasiveness index (SII) has been validated in general spine procedures but not adult spinal deformity (ASD). OBJECTIVE To assess the ability of the SII to determine the invasiveness of ASD surgery and to create and validate a novel ASD index incorporating deformity-specific factors, which could serve as a standardized metric to compare outcomes and risk stratification of different ASD procedures for a given deformity. METHODS Four hundred sixty-four patients who underwent ASD surgery between 2009 and 2012 were identified in 2 multicenter prospective registries. Multivariable models of estimated blood loss (EBL) and operative time were created using deformity-specific factors. Beta coefficients derived from these models were used to attribute points to each component. Scoring was iteratively refined to determine the R2 value of multivariate models of EBL and operative time using adult spinal deformity-surgical (ASD-S) as an independent variable. Similarly, we determined weighting of postoperative changes in radiographical parameters, which were incorporated into another index (adult spinal deformity-surgical and radiographical [ASD-SR]). The ability of these models to predict surgical invasiveness was assessed in a validation cohort. RESULTS Each index was a significant, independent predictor of EBL and operative time (P < .001). On multivariate analysis, ASD-S and ASD-SR explained more variability in EBL and operative time than did the SII (P < .001). The ASD-SR explained 21% of the variation in EBL and 10% of the variation in operative time, whereas the SII explained 17% and 3.2%, respectively. CONCLUSION The ASD-SR, which incorporates deformity-specific components, more accurately predicts the magnitude of ASD surgery than does the SII.

ABSTRACT BACKGROUND Distal junctional kyphosis (DJK) development after cervical deformity (CD)-corrective surgery is a growing concern for surgeons and patients. Few studies have investigated risk factors that predict the occurrence of DJK. OBJECTIVE To predict DJK development after CD surgery using predictive modeling. METHODS CD criteria was at least one of the following: C2-C7 Coronal/Cobb > 10°, C2-7 sagittal vertical axis (cSVA) > 4 cm, chin-brow vertical angle > 25°. DJK was defined as the development of an angle <−10° from the end of fusion construct to the second distal vertebra, and change in this angle by <−10° from baseline to postoperative. Baseline demographic, clinical, and surgical information were used to predict the occurrence of DJK using generalized linear modeling both as one overall model and as submodels using baseline demographic and clinical predictors or surgical predictors. RESULTS One hundred seventeen CD patients were included. At any postoperative visit up to 1 yr, 23.1% of CD patients developed DJK. DJK was predicted with high accuracy using a combination of baseline demographic, clinical, and surgical factors by the following factors: preoperative neurological deficit, use of transition rod, C2-C7 lordosis (CL)<−12°, T1 slope minus CL > 31°, and cSVA > 54 mm. In the model using only baseline demographic/clinical predictors of DJK, presence of comorbidities, presence of baseline neurological deficit, and high preoperative C2-T3 angle were included in the final model (area under the curve = 87%). The final model using only surgical predictors for DJK included combined approach, posterior upper instrumented vertebrae below C4, use of transition rod, lack of anterior corpectomy, more than 3 posterior osteotomies, and performance of a 3-column osteotomy. CONCLUSION Preoperative assessment and consideration should be given to these factors that are predictive of DJK to mitigate poor outcomes.

PurposeHealth-related quality of life (HRQL) instruments are essential in value-driven health care, but patients often have more specific, personal priorities when seeking surgical care. The Scoliosis Research Society-22R (SRS-22R), an HRQL instrument for spinal deformity, provides summary scores spanning several health domains, but these may be difficult for patients to utilize in planning their specific care goals. Our objective was to create preoperative predictive models for responses to individual SRS-22R questions at 1 and 2 years after adult spinal deformity (ASD) surgery to facilitate precision surgical care.MethodsTwo prospective observational cohorts were queried for ASD patients with SRS-22R data at baseline and 1 and 2 years after surgery. In total, 150 covariates were used in training machine learning models, including demographics, surgical data and perioperative complications. Validation was accomplished via an 80%/20% data split for training and testing, respectively. Goodness of fit was measured using area under receiver operating characteristic (AUROC) curves.ResultsIn total, 561 patients met inclusion criteria. The AUROC ranged from 56.5 to 86.9%, reflecting successful fits for most questions. SRS-22R questions regarding pain, disability and social and labor function were the most accurately predicted. Models were less sensitive to questions regarding general satisfaction, depression/anxiety and appearance.ConclusionsTo the best of our knowledge, this is the first study to explicitly model the prediction of individual answers to the SRS-22R questionnaire at 1 and 2 years after deformity surgery. The ability to predict individual question responses may prove useful in preoperative counseling in the age of individualized medicine.Graphic abstractThese slides can be retrieved under Electronic Supplementary Material.

Abstract BACKGROUND Acute kidney injury (AKI) is a serious postoperative complication. OBJECTIVE To determine whether AKI in patients after craniotomy is associated with heightened 30-day mortality. METHODS We performed a 2-center, retrospective cohort study of 1656 craniotomy patients who received critical care between 1998 and 2011. The exposure of interest was AKI defined as meeting RIFLE (Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease) class risk, injury, and failure criteria, and the primary outcome was 30-day mortality. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both AKI and mortality. Additionally, mortality in craniotomy patients with AKI was analyzed with a risk-adjusted Cox proportional hazards regression model and propensity score matching as a sensitivity analysis. RESULTS The incidences of RIFLE class risk, injury, and failure were 5.7%, 2.9%, and 1.3%, respectively. The odds of 30-day mortality in patients with RIFLE class risk, injury, or failure fully adjusted were 2.79 (95% confidence interval “CI”, 1.76-4.42), 7.65 (95% CI, 4.16-14.07), and 14.41 (95% CI, 5.51-37.64), respectively. Patients with AKI experienced a significantly higher risk of death during follow-up; hazard ratio, 1.82 (95% CI, 1.34-2.46), 3.37 (95% CI, 2.36-4.81), and 5.06 (95% CI, 2.99-8.58), respectively, fully adjusted. In a cohort of propensity score-matched patients, RIFLE class remained a significant predictor of 30-day mortality.

This study was a retrospective multi-center comparative cohort study. A retrospective institutional database of operative adult spinal deformity patients was utilized. All fusions > 5 vertebral levels and including the sacrum/pelvis were eligible for inclusion. Revisions, 3 column osteotomies, and patients with < 2-year clinical follow-up were excluded. Patients were separated into 3 groups based on surgical approach: 1) posterior spinal fusion without interbody (PSF), 2) PSF with interbody (PSF-IB), and 3) anteroposterior (AP) fusion (anterior lumbar interbody fusion or lateral lumbar interbody fusion with posterior screw fixation). Intraoperative, radiographic, and clinical outcomes, as well as complications, were compared between groups with ANOVA and χ tests. One-hundred and thirty-eight patients were included for study (PSF, n = 37; PSF-IB, n = 44; AP, n = 57). Intraoperatively, estimated blood loss was similar between groups (p = 0.171). However, the AP group had longer operative times (547.5 min) compared to PSF (385.1) and PSF-IB (370.7) (p < 0.001). Additionally, fusion length was shorter in PSF-IB (11.4) compared to AP (13.6) and PSF (12.9) (p = 0.004). There were no differences between the groups in terms of change in alignment from preoperative to 2 years postoperative. There were no differences in clinical outcomes. While postoperative complications were largely similar between groups, operative complications were higher in the AP group (31.6%) compared to the PSF (5.4%) and PSF-IB (9.1) groups (p < 0.001). While there were differences in intraoperative outcomes (operative time and fusion length), there were no differences in postoperative clinical or radiographic outcomes. AP fusion was associated with a higher rate of operative complications.

Purpose: The aim is to investigate the relationship between cervical parameters and the modified Japanese Orthopedic Association scale (mJOA). Materials and Methods: Surgical adult cervical deformity (CD) patients were included in this retrospective analysis. After determining data followed a parametric distribution through the Shapiro-Wilk Normality (P = 0.15, P > 0.05), Pearson correlations were run for radiographic parameters and mJOA. For significant correlations, logistic regressions were performed to determine a threshold of radiographic measures for which the correlation with mJOA scores was most significant. mJOA score of 14 and <12 reported cut-off values for moderate (M) and severe (S) disability. New modifiers were compared to an existing classification using Spearman's rho and logistic regression analyses to predict outcomes up to 2 years. Results: A total of 123 CD patients were included (60.5 years, 65%F, 29.1 kg/m2). For significant baseline factors from Pearson correlations, the following thresholds were predicted: MGS (M:-12 to-9° and 0°-19°, P = 0.020; S: >19° and <−12°, χ2 = 4.291, P = 0.036), TS-CL (M: 26°to 45°, P = 0.201; S: >45°, χ2 = 7.8, P = 0.005), CL (M:-21° to 3°, χ2 = 8.947, P = 0.004; S: <−21°, χ2 = 9.3, P = 0.009), C2-T3 (M: −35° to −25°, χ2 = 5.485, P = 0.046; S: <−35°, χ2 = 4.1, P = 0.041), C2 Slope (M: 33° to 49°, P = 0.122; S: >49°, χ2 = 5.7, P = 0.008), and Frailty (Mild: 0.18-0.27, P = 0.129; Severe: >0.27, P = 0.002). Compared to existing Ames- International Spine Study Group classification, the novel thresholds demonstrated significant predictive value for reoperation and mortality up to 2 years. Conclusions: Collectively, these radiographic values can be utilized in refining existing classifications and developing collective understanding of severity and surgical targets in corrective surgery for adult CD.

Purpose Previous work comparing ASD to a normative population demonstrated that a large proportion of lumbar lordosis is lost proximally (L1-L4). The current study expands on these findings by collectively investigating regional angles and spinal contours. Methods 119 asymptomatic volunteers with full-body free-standing radiographs were used to identify age-and-PI models of each Vertebra Pelvic Angle (VPA) from L5 to T10. These formulas were then applied to a cohort of primary surgical ASD patients without coronal malalignment. Loss of lumbar lordosis (LL) was defined as the offset between age-and-PI normative value and pre-operative alignment. Spine shapes defined by VPAs were compared and analyzed using paired t-tests. Results 362 ASD patients were identified (age = 64.4 ± 13, 57.1% females). Compared to their age-and-PI normative values, patients demonstrated a significant loss in LL of 17 ± 19° in the following distribution: 14.1% had “No loss” (mean = 0.1 ± 2.3), 22.9% with 10°-loss (mean = 9.9 ± 2.9), 22.1% with 20°-loss (mean = 20.0 ± 2.8), and 29.3% with 30°-loss (mean = 33.8 ± 6.0). “No loss” patients’ spine was slightly posterior to the normative shape from L4 to T10 (VPA difference of 2°), while superimposed on the normative one from S1 to L2 and became anterior at L1 in the “10°-loss” group. As LL loss increased, ASD and normative shapes offset extended caudally to L3 for the “20°-loss” group and L4 for the “30°-loss” group. Conclusion As LL loss increases, the difference between ASD and normative shapes first occurs proximally and then progresses incrementally caudally. Understanding spinal contour and LL loss location may be key to achieving sustainable correction by identifying optimal and personalized postoperative shapes.

Background The greater likelihood of morbidity, mortality, length of hospital stays and poorer long-term outcomes as a result of surgical site infections secondary to spinal surgery makes prophylactic measures an imperative focus. Therefore, the aim of this review was to evaluate the available research related to the efficacy of different intraoperative irrigation techniques used in spinal surgery for surgical site infection (SSI) prophylaxis. Methods We performed a comprehensive search using Ovid Medline, EMBASE, Web of Science and the Cochrane library pertaining to this topic. Our meta-analysis was conducted according to PRISMA guidelines. The inclusion criteria consist of spine surgeries with intraoperative use of any wound irrigation technique, comparison groups with a different intraoperative irrigation technique or no irrigation, SSI identified with bacterial cultures or clinically in the postoperative period, reported SSI rates. Data extracted from eligible studies included, but was not limited to, SSI rates, irrigation technique and control technique. Exclusion criteria consist of articles with no human subjects, reviews, meta-analyses and case control studies and no details about SSI identification or rates. Pooled risk ratios were calculated. A meta-analysis was performed with a forest plot to determine risk estimates’ heterogeneity with I 2 index, Q-statistic, and p value under a random-effects model. Funnel plot was used to assess publication bias. All databases were last checked on January, 2022. PROBAST tool was used to assess both risk of bias and applicability concerns. Results After reviewing 1494 titles and abstracts, 18 articles met inclusion criteria. They included three prospective randomized-controlled trials, 13 retrospective cohort studies, two prospective cohort studies. There were 54 (1.8%) cases of SSIs in the povidone-iodine irrigation group ( N  = 2944) compared to 159 (4.6%) in the control group ( N  = 3408). Using intraoperative povidone-iodine wound irrigation produced an absolute risk reduction of 2.8%. Overall risk ratio was 0.32 (95% CI 0.20–0.53, p  < 0.00001). In a global analysis, study heterogeneity and synthesizing mostly retrospective data were primary limitations. Conclusion The most evidence exists for povidone-iodine and has Level 2 evidence supporting SSI reduction during spinal surgery. Other antiseptic solutions such as dilute chlorhexidine lack published evidence in this patient population which limits the ability to draw conclusions related to its use in spinal surgery. Level of Evidence II – Systematic Review with Meta-Analysis.