Publications by authors named "Nathan Lee"

148 Publications

Expanding control of the tumor cell cycle with a CDK2/4/6 inhibitor.

Cancer Cell 2021 Sep 11. Epub 2021 Sep 11.

Pfizer Global Research and Development La Jolla, 10770 Science Center Drive, San Diego, CA 92121, USA.

The CDK4/6 inhibitor, palbociclib (PAL), significantly improves progression-free survival in HR/HER2 breast cancer when combined with anti-hormonals. We sought to discover PAL resistance mechanisms in preclinical models and through analysis of clinical transcriptome specimens, which coalesced on induction of MYC oncogene and Cyclin E/CDK2 activity. We propose that targeting the G kinases CDK2, CDK4, and CDK6 with a small-molecule overcomes resistance to CDK4/6 inhibition. We describe the pharmacodynamics and efficacy of PF-06873600 (PF3600), a pyridopyrimidine with potent inhibition of CDK2/4/6 activity and efficacy in multiple in vivo tumor models. Together with the clinical analysis, MYC activity predicts (PF3600) efficacy across multiple cell lineages. Finally, we find that CDK2/4/6 inhibition does not compromise tumor-specific immune checkpoint blockade responses in syngeneic models. We anticipate that (PF3600), currently in phase 1 clinical trials, offers a therapeutic option to cancer patients in whom CDK4/6 inhibition is insufficient to alter disease progression.
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http://dx.doi.org/10.1016/j.ccell.2021.08.009DOI Listing
September 2021

Femoral head to lower lumbar neural foramen distance as a novel radiographic parameter to predict postoperative stretch neuropraxia.

J Neurosurg Spine 2021 Sep 3:1-9. Epub 2021 Sep 3.

Objective: Lumbosacral fractional curves in adult spinal deformity (ASD) patients often have sharp coronal curves resulting in significant pain and imbalance. Postoperative stretch neuropraxia after fractional curve correction can lead to discomfort and unsatisfactory outcomes. The goal of this study was to use radiographic measures to increase understanding of the relationship between postoperative stretch neuropraxia and fractional curve correction.

Methods: In 62 ASD patients treated from 2015 to 2018, radiographic review was performed, including measurement of the distance between the lower lumbar neural foramen (L4 and L5) in the concavity and convexity of the lumbosacral fractional curve and the ipsilateral femoral heads (FHs; L4-FH and L5-FH) in pre- and postoperative anteroposterior spine radiographs. The largest absolute preoperative to postoperative change in distance between the lower lumbar neural foramen and the ipsilateral FH (ΔL4/L5-FH) was used for analysis. Chi-square analyses, independent and paired t-tests, and logistic regression were performed to study the relationship between L4/L5-FH and stretch neuropraxia for categorical and continuous variables, respectively.

Results: Of the 62 patients, 13 (21.0%) had postoperative stretch neuropraxia. Patients without postoperative stretch neuropraxia had an average ΔL4-FH distance of 16.2 mm compared to patients with stretch neuropraxia, who had an average ΔL4-FH distance of 31.5 mm (p < 0.01). Patients without postoperative neuropraxia had an average ΔL5-FH distance of 11.1 mm compared to those with stretch neuropraxia, who had an average ΔL5-FH distance of 23.0 mm (p < 0.01). Chi-square analysis showed that patients had a 4.78-fold risk of developing stretch neuropraxia with ΔL4-FH > 20 mm (95% CI 1.3-17.3) and a 5.17-fold risk of developing stretch neuropraxia with ΔL5-FH > 15 mm (95% CI 1.4-18.7). Logistic regression analysis indicated that the odds of developing stretch neuropraxia were 15:1 with a ΔL4-FH > 20 mm (95% CI 3-78) and 21:1 with a ΔL5-FH > 15 mm (95% CI 4-113).

Conclusions: The novel ΔL4/L5-FH distances are strongly associated with postoperative stretch neuropraxia in ASD patients. A ΔL4-FH > 20 mm and ΔL5-FH > 15 mm significantly increase the odds for patients to develop postoperative stretch neuropraxia.
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http://dx.doi.org/10.3171/2021.1.SPINE201989DOI Listing
September 2021

Brain-Derived Neurotrophic Factor Polymorphism and Aphasia after Stroke.

Behav Neurol 2021 28;2021:8887012. Epub 2021 Jul 28.

Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia.

Stroke is one of the most deliberating causes of mortality and disability worldwide. Studies have implicated 66 polymorphism of the brain-derived neurotrophic factor (BDNF) gene as a genetic factor influencing stroke recovery. Still, the role of BDNF polymorphism in poststroke aphasia is relatively unclear. This review assesses the recent evidence on the association between the BDNF polymorphism and aphasia recovery in poststroke patients. The article highlights BNDF polymorphism characteristics, speech and language interventions delivered, and the influence of BNDF polymorphism on poststroke aphasia recovery. We conducted a literature search through PubMed and Google Scholar with the following terms: "brain derived-neurotrophic factor" and "aphasia" for original articles from January 2000 until June 2020. Out of 69 search results, a detailed selection process produced a total of 3 articles that met the eligibility criteria. All three studies included 66 polymorphism as the studied human BDNF gene. One of the studies demonstrated insufficient evidence to conclude that BDNF polymorphism plays a role in poststroke aphasia recovery. The remaining two studies have shown that allele genotype (either single or double nucleotides) was associated with poor aphasia recovery, in either acute or chronic stroke. Carriers of the 66 polymorphism of BDNF gave a poorer response to aphasia intervention and presented with more severe aphasia.
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http://dx.doi.org/10.1155/2021/8887012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337153PMC
August 2021

Is There a Difference in Screw Accuracy, Robot Time Per Screw, Robot Abandonment, and Radiation Exposure Between the Mazor X and the Renaissance? A Propensity-Matched Analysis of 1179 Robot-Assisted Screws.

Global Spine J 2021 Jul 8:21925682211029867. Epub 2021 Jul 8.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY, USA.

Study Design: Prospective single-cohort analysis.

Objectives: To compare the outcomes/complications of 2 robotic systems for spine surgery.

Methods: Adult patients (≥18-years-old) who underwent robot-assisted spine surgery from 2016-2019 were assessed. A propensity score matching (PSM) algorithm was used to match Mazor X to Renaissance cases. Preoperative CT scan for planning and an intraoperative O-arm for screw evaluation were preformed. Outcomes included screw accuracy, robot time/screw, robot abandonment, and radiation. Screw accuracy was measured using Vitrea Core software by 2 orthopedic surgeons. Screw breach was measured according to the Gertzbein/Robbins classification.

Results: After PSA, a total of 65 patients (Renaissance: 22 vs. X: 43) were included. Patient/operative factors were similar between robot systems ( > .05). The pedicle screw accuracy was similar between robots (Renaissance: 1.1%% vs. X: 1.3%, = .786); however, the S2AI screw breach rate was significantly lower for the X (Renaissance: 9.5% vs. X: 1.2%, = .025). Robot time per screw was not statistically different (Renaissance: 4.6 minutes vs. X: 3.9 minutes, = .246). The X was more reliable with an abandonment rate of 2.3% vs. Renaissance:22.7%, = .007. Radiation exposure were not different between robot systems. Non-robot related complications including dural tear, loss of motor/sensory function, and blood transfusion were similar between robot systems.

Conclusion: This is the first comparative analyses of screw accuracy, robot time/screw, robot abandonment, and radiation exposure between the Mazor X and Renaissance systems. There are substantial improvements in the X robot, particularly in the perioperative planning processes, which likely contribute to the X's superiority in S2AI screw accuracy by nearly 8-fold and robot reliability by nearly 10-fold.
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http://dx.doi.org/10.1177/21925682211029867DOI Listing
July 2021

Maternal cold exposure induces distinct transcriptome changes in the placenta and fetal brown adipose tissue in mice.

BMC Genomics 2021 Jul 3;22(1):500. Epub 2021 Jul 3.

Gene Regulation and Metabolism, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, Louisiana, 70808, USA.

Background: Brown adipose tissue (BAT) is specialized to dissipate energy in the form of heat. BAT-mediated heat production in rodents and humans is critical for effective temperature adaptation of newborns to the extrauterine environment immediately after birth. However, very little is known about whether and how fetal BAT development is modulated in-utero in response to changes in maternal thermal environment during pregnancy. Using BL6 mice, we evaluated the impact of different maternal environmental temperatures (28 °C and 18 °C) on the transcriptome of the placenta and fetal BAT to test if maternal cold exposure influences fetal BAT development via placental remodeling.

Results: Maternal weight gain during pregnancy, the average number of fetuses per pregnancy, and placental weight did not differ between the groups at 28 °C and 18 °C. However, the average fetal weight at E18.5 was 6% lower in the 18 °C-group compared to the 28 °C-group. In fetal BATs, cold exposure during pregnancy induced increased expression of genes involved in de novo lipogenesis and lipid metabolism while decreasing the expression of genes associated with muscle cell differentiation, thus suggesting that maternal cold exposure may promote fetal brown adipogenesis by suppressing the myogenic lineage in bidirectional progenitors. In placental tissues, maternal cold exposure was associated with upregulation of genes involved in complement activation and downregulation of genes related to muscle contraction and actin-myosin filament sliding. These changes may coordinate placental adaptation to maternal cold exposure, potentially by protecting against cold stress-induced inflammatory damage and modulating the vascular and extravascular contractile system in the placenta.

Conclusions: These findings provide evidence that environmental cold temperature sensed by the mother can modulate the transcriptome of placental and fetal BAT tissues. The ramifications of the observed gene expression changes warrant future investigation.
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http://dx.doi.org/10.1186/s12864-021-07825-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254942PMC
July 2021

What is the Comparison in Robot Time per Screw, Radiation Exposure, Robot Abandonment, Screw Accuracy, and Clinical Outcomes Between Percutaneous and Open Robot-Assisted Short Lumbar Fusion? A Multicenter, Propensity-Matched Analysis of 310 Patients.

Spine (Phila Pa 1976) 2021 Jun 4. Epub 2021 Jun 4.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY, USA New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA Department of Neurosurgery, University of Virginia Health System, Charlottesville, VA, USA Department of Neurosurgery, State University of New York, Buffalo, NY, USA Department of Orthopaedics, Virginia Spine Institute, Reston, VA, USA.

Study Design: Multicenter cohort.

Objective: To compare the robot time/screw, radiation exposure, robot abandonment, screw accuracy, and 90-day outcomes between robot-assisted percutaneous and robot-assisted open approach for short lumbar fusion (1-and 2-level).

Summary Of Background Data: There is conflicting literature on the superiority of robot-assisted minimally invasive spine surgery to open techniques. A large, multicenter study is needed to further elucidate the outcomes and complications between these two approaches.

Methods: We included adult patients (≥18 years old) who underwent robot-assisted short lumbar fusion surgery from 2015-2019 at four independent institutions. A propensity score matching (PSM) algorithm was employed to control for the potential selection bias between percutaneous and open surgery. The minimum follow-up was 90 days after the index surgery.

Results: After PSM, 310 patients remained. The mean (standard deviation) charlson comorbidity index was 1.6 (1.5) and 53% of patients were female. The most common diagnoses included high grade spondylolisthesis (grade >2)(48%), degenerative disc disease (22%), and spinal stenosis (25%), and the mean number of instrumented levels was 1.5(0.5). The operative time was longer in the open (198 minutes) vs. the percutaneous group (167 minutes, P-value=0.007). However, the robot time/screw was similar between cohorts (P-value>0.05). The fluoroscopy time/screw for percutaneous (14.4 seconds) was longer than the open group (10.1 seconds, P-value=0.021). The rates for screw exchange and robot abandonment, were similar between groups (P-value>0.05). The estimated blood loss (open:146 mL vs. percutaneous:61.3 mL, P-value < 0.001) and transfusion rate (open:3.9% vs. percutaneous:0%, P-value=0.013) were greater for the open group. The 90-day complication rate and mean length of stay were not different between cohorts(P-value>0.05).

Conclusion: Percutaneous robot-assisted spine surgery may increase radiation exposure, but can achieve a shorter operative time and lower risk for intraoperative blood loss for short-lumbar fusion. Percutaneous approaches do not appear to have an advantage for other short-term postoperative outcomes. Future multicenter studies on longer fusion surgeries and the inclusion of patient-reported outcomes are needed.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000004132DOI Listing
June 2021

Phosphorylation and Stabilization of PIN1 by JNK Promote Intrahepatic Cholangiocarcinoma Growth.

Hepatology 2021 May 28. Epub 2021 May 28.

Leeds Institute of Medical Research at St. James', Faculty of Medicine and Health, University of Leeds, St. James' University Hospital, Leeds, United Kingdom.

Background And Aims: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive type of liver cancer in urgent need of treatment options. Aberrant activation of the c-Jun N-terminal kinase (JNK) pathway is a key feature in ICC and an attractive candidate target for its treatment. However, the mechanisms by which constitutive JNK activation promotes ICC growth, and therefore the key downstream effectors of this pathway, remain unknown for their applicability as therapeutic targets. Our aim was to obtain a better mechanistic understanding of the role of JNK signaling in ICC that could open up therapeutic opportunities.

Approach And Results: Using loss-of-function and gain-of-function studies in vitro and in vivo, we show that activation of the JNK pathway promotes ICC cell proliferation by affecting the protein stability of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), a key driver of tumorigenesis. PIN1 is highly expressed in ICC primary tumors, and its expression positively correlates with active JNK. Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation. Moreover, pharmacological inhibition of PIN1 through all-trans retinoic acid, a Food and Drug Administration-approved drug, impairs the growth of both cultured and xenografted ICC cells.

Conclusions: Our findings implicate the JNK-PIN1 regulatory axis as a functionally important determinant for ICC growth, and provide a rationale for therapeutic targeting of JNK activation through PIN1 inhibition.
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http://dx.doi.org/10.1002/hep.31983DOI Listing
May 2021

Do Adult Spinal Deformity Patients Undergoing Surgery Continue to Improve From 1-Year to 2-Years Postoperative?

Global Spine J 2021 May 26:21925682211019352. Epub 2021 May 26.

Department of Orthopaedic Surgery, 21611Columbia University Medical Center, The Och Spine Hospital at New York Presbyterian, New York, NY, USA.

Objective: Evaluate clinical improvement as measured by patient-reported outcomes (PROs) during the 1 to 2-year interval.

Study Design: Retrospective Cohort.

Methods: A single-institution registry of ASD patients undergoing surgery was queried for patients with ≥6 level fusions. Demographics and radiographic variables were collected. PROs collected were the ODI and SRS-22r scores at: preoperative, 1-year and 2-years. Outcome measures of clinical improvement during the 1-2 year time interval were: 1) group medians, 2) percent minimum clinically important difference (MCID), and 3) percent minimal symptom scale (MSS)(ODI < 20 or SRS-pain + function >8). Wilcoxon rank-sum tests, chi-squared tests, Kruskal-Wallis tests, and logistic regression were performed.

Results: 157 patients undergoing ASD surgery with minimum of 1-year follow-up were included. Mean age was 53.2 and mean instrumented levels was 13.1. Preoperative alignment was: Neutral Alignment (NA) 49%, Coronal Malalignment (CM) 17%, Sagittal Malalignment (SM 17%), and Combined Coronal/Sagittal Malalignment (CCSM) 18%. Preoperative to 1-year, and preoperative to 2-years, all ODI/SRS-22r significantly improved ( < .001). the only significant improvement in PROs between 1-and 2-year postoperative were those reaching ODI MCID (69% 1-year vs. 84% 2-years; < .001). ≥55 years had an improved median ODI (18 vs. 8; = .047) and an improved percent achieving ODI MCID (73% vs. 84%, = .048). CCSM patients experienced significant improvement in SRS-appearance score (75% vs. 100%; = .050), along with those with severe preoperative SM >7.5 cm (73% vs. 100%; = .032).

Conclusions: Most ASD patients experience the majority of PRO improvement by 1-year postoperative. However, subsets of patients that may continue to improve up to 2-years postoperative include patients ≥55 years, combined coronal/sagittal malalignment, and those with severe sagittal malalignment ≥7.5 cm.
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http://dx.doi.org/10.1177/21925682211019352DOI Listing
May 2021

Orphan nuclear receptor COUP-TFII enhances myofibroblast glycolysis leading to kidney fibrosis.

EMBO Rep 2021 06 25;22(6):e51169. Epub 2021 May 25.

Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Recent studies demonstrate that metabolic disturbance, such as augmented glycolysis, contributes to fibrosis. The molecular regulation of this metabolic perturbation in fibrosis, however, has been elusive. COUP-TFII (also known as NR2F2) is an important regulator of glucose and lipid metabolism. Its contribution to organ fibrosis is undefined. Here, we found increased COUP-TFII expression in myofibroblasts in human fibrotic kidneys, lungs, kidney organoids, and mouse kidneys after injury. Genetic ablation of COUP-TFII in mice resulted in attenuation of injury-induced kidney fibrosis. A non-biased proteomic study revealed the suppression of fatty acid oxidation and the enhancement of glycolysis pathways in COUP-TFII overexpressing fibroblasts. Overexpression of COUP-TFII in fibroblasts also induced production of alpha-smooth muscle actin (αSMA) and collagen 1. Knockout of COUP-TFII decreased glycolysis and collagen 1 levels in fibroblasts. Chip-qPCR revealed the binding of COUP-TFII on the promoter of PGC1α. Overexpression of COUP-TFII reduced the cellular level of PGC1α. Targeting COUP-TFII serves as a novel treatment approach for mitigating fibrosis in chronic kidney disease and potentially fibrosis in other organs.
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http://dx.doi.org/10.15252/embr.202051169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183413PMC
June 2021

Is there a difference between navigated and non-navigated robot cohorts in robot-assisted spine surgery? A multicenter, propensity-matched analysis of 2,800 screws and 372 patients.

Spine J 2021 Sep 19;21(9):1504-1512. Epub 2021 May 19.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY, USA.

Background Context: Robot-assisted spine surgery continues to rapidly develop as evidenced by the growing literature in recent years. In addition to demonstrating excellent pedicle screw accuracy, early studies have explored the impact of robot-assisted spine surgery on reducing radiation time, length of hospital stay, operative time, and perioperative complications in comparison to conventional freehand technique. Recently, the Mazor X Stealth Edition was introduced in 2018. This robotic system integrates Medtronic's Stealth navigation technology into the Mazor X platform, which was introduced in 2016. It is unclear what the impact of these advancements have made on clinical outcomes.

Purpose: To compare the outcomes and complications between the most recent iterations of the Mazor Robot systems: Mazor X and Mazor X Stealth Edition.

Study Design: Multicenter cohort PATIENT SAMPLE: Among four different institutions, we included adult (≥18 years old) patients who underwent robot-assisted spine surgery with either the Mazor X (non-navigated robot) or Stealth (navigated robot) platforms.

Outcome Measures: Primary outcomes included robot time per screw, fluoroscopic radiation time, screw accuracy, robot abandonment, and clinical outcomes with a minimum 90 day follow up.

Methods: A one-to-one propensity-score matching algorithm based on perioperative factors (e.g. demographics, comorbidities, primary diagnosis, open vs. percutaneous instrumentation, prior spine surgery, instrumented levels, pelvic fixation, interbody fusion, number of planned robot screws) was employed to control for the potential selection bias between the two robotic systems. Chi-square/fisher exact test and t-test/ANOVA were used for categorical and continuous variables, respectively.

Results: From a total of 646 patients, a total of 372 adult patients were included in this study (X: 186, Stealth: 186) after propensity score matching. The mean number of instrumented levels was 4.3. The mean number of planned robot screws was 7.8. Similar total operative time and robot time per screw occurred between cohorts (p>0.05). However, Stealth achieved significantly shorter fluoroscopic radiation time per screw (Stealth: 7.2 seconds vs. X: 10.4 seconds, p<.001) than X. The screw accuracy for both robots was excellent (Stealth: 99.6% vs. X: 99.1%, p=0.120). In addition, Stealth achieved a significantly lower robot abandonment rate (Stealth: 0% vs. X: 2.2%, p=0.044). Furthermore, a lower blood transfusion rate was observed for Stealth than X (Stealth: 4.3% vs. X: 10.8%, p=0.018). Non-robot related complications such as dura tear, motor/sensory deficits, return to the operating room during same admission, and length of stay was similar between robots (p>0.05). The 90-day complication rates were low and similar between robot cohorts (Stealth: 5.4% vs. X: 3.8%, p=0.456).

Conclusion: In this multicenter study, both robot systems achieved excellent screw accuracy and low robot time per screw. However, using Stealth led to significantly less fluoroscopic radiation time, lower robot abandonment rates, and reduced blood transfusion rates than Mazor X. Other factors including length of stay, and 90-day complications were similar.
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http://dx.doi.org/10.1016/j.spinee.2021.05.015DOI Listing
September 2021

Do robot-related complications influence 1 year reoperations and other clinical outcomes after robot-assisted lumbar arthrodesis? A multicenter assessment of 320 patients.

J Orthop Surg Res 2021 May 12;16(1):308. Epub 2021 May 12.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, 161 Fort Washington Avenue, New York, NY, 10032, USA.

Background: Robot-assisted platforms in spine surgery have rapidly developed into an attractive technology for both the surgeon and patient. Although current literature is promising, more clinical data is needed. The purpose of this paper is to determine the effect of robot-related complications on clinical outcomes METHODS: This multicenter study included adult (≥18 years old) patients who underwent robot-assisted lumbar fusion surgery from 2012-2019. The minimum follow-up was 1 year after surgery. Both bivariate and multivariate analyses were performed to determine if robot-related factors were associated with reoperation within 1 year after primary surgery.

Results: A total of 320 patients were included in this study. The mean (standard deviation) Charlson Comorbidity Index was 1.2 (1.2) and 52.5% of patients were female. Intraoperative robot complications occurred in 3.4% of patients and included intraoperative exchange of screw (0.9%), robot abandonment (2.5%), and return to the operating room for screw exchange (1.3%). The 1-year reoperation rate was 4.4%. Robot factors, including robot time per screw, open vs. percutaneous, and robot system, were not statistically different between those who required revision surgery and those who did not (P>0.05). Patients with robot complications were more likely to have prolonged length of hospital stay and blood transfusion, but were not at higher risk for 1-year reoperations. The most common reasons for reoperation were wound complications (2.2%) and persistent symptoms due to inadequate decompression (1.5%). In the multivariate analysis, robot related factors and complications were not independent risk factors for 1-year reoperations.

Conclusion: This is the largest multicenter study to focus on robot-assisted lumbar fusion outcomes. Our findings demonstrate that 1-year reoperation rates are low and do not appear to be influenced by robot-related factors and complications; however, robot-related complications may increase the risk for greater blood loss requiring a blood transfusion and longer length of stay.
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http://dx.doi.org/10.1186/s13018-021-02452-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114480PMC
May 2021

Do readmissions and reoperations adversely affect patient-reported outcomes following complex adult spinal deformity surgery at a minimum 2 years postoperative?

Spine Deform 2021 May 16;9(3):789-801. Epub 2021 Apr 16.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, 161 Fort Washington Avenue, New York, NY, 10032, USA.

Background: Unplanned readmissions and reoperations are known to be associated with undesirable costs and potentially inferior outcomes in complex adult spinal deformity (ASD) surgery. A paucity of literature exists on the impact of readmissions/reoperations on patient-reported outcomes (PRO) in this population.

Methods: Consecutively treated adult patients who underwent complex ASD surgery at a single institution from 2015-2018 and minimum 2-year follow-up were studied. Demographics/comorbidities, operative factors, inpatient complications, and postoperative clinical and patient-reported outcomes (SRS-22r, ODI) were assessed for those with and without readmission/reoperation.

Results: 175 patients (72% female, mean age 52.6 ± 16.4) were included. Mean total instrumented/fused levels was 13.3 ± 4.1, range 6-25. The readmission and reoperation rates were 16.6% and 12%, respectively. The two most common causes of reoperation were pseudarthrosis (5.1%) and PJK (4.0%). Predictors for readmission within 2 years following surgery included pulmonary, cardiac, depression and gastrointestinal comorbidities, along with performance of a VCR, and TLIF. At 2 years postoperatively, those who required a readmission/reoperation had significant increases in SRS and reductions in ODI compared to 1-year and preoperative values. Inpatient complications did not negatively impact 2-year PRO's. The 2-year MCID in PROs was not significantly different between those with and without readmission/reoperation.

Conclusion: Complex ASD surgery carries risk, but the vast majority can achieve MCID (SRS-86.4%, ODI-68.2%) in PROs by 2 years. Importantly, even those with inpatient complications and those who required unplanned readmission/reoperation can improve PROs by 2-year follow-up compared to preoperative baseline and 1-year follow-up and achieve similar improvements compared to those who did not require a readmission.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s43390-020-00235-wDOI Listing
May 2021

The role of ketamine in opioid-free spinal deformity surgery: is it possible and beneficial?

J Spine Surg 2021 Mar;7(1):55-61

The Och Spine Hospital, NewYork-Presbyterian/Columbia University Medical Center, New York, NY, USA.

Background: As the opioid epidemic in the United States has continued to gain momentum in recent years, the current study aims to explore the efficacy of ketamine in a traditionally challenging setting regarding pain control, and contribute toward developing an opioid-free intraoperative pain protocol in spinal deformity surgery.

Methods: Fifty-four patients who underwent spinal deformity surgery between January 1, 2017 and December 31, 2017 by one senior surgeon were included. Demographic data and preoperative opioid use was collected. Surgical details including number of levels fused, estimated blood loss, and operative time was also collected. All patients received a hydromorphone patient-controlled anesthesia (PCA) device postoperatively. 36/54 patients received perioperative ketamine during their procedure, both intraoperatively and postoperatively. The consumption of postoperative hydromorphone and the ratio of doses given by doses attempted postoperatively were recorded. Patient charts were also reviewed for documented ileus during their inpatient stay.

Results: Mean age was 49 years, and 31% were male. Average BMI was 24.3 kg/m. The average number of levels fused was 11.6. Mean operative time was 10.7 hrs, and average EBL was 1,522 mL. The mean length of stay was 8 days. Average postoperative PCA use of hydromorphone in the no ketamine group (NK) (n=18) was 5.99 mg compared to 6.91 mg for those who received perioperative ketamine (K) (n=36); there was no significant difference between populations (P=0.57), although the variances was significant (P=0.044). There was no correlation between intraoperative ketamine and postoperative PCA use (r=-0.05; P=0.72). Additionally, there was no correlation between postoperative PCA use and dose of postoperative ketamine received (r=-0.15; P=0.27). The ratio of doses given: attempted was 0.61 in the NK group and 0.59 in those in the K group (P=0.79). Average postoperative hydromorphone use was 5.48 mg in patients that did not use opioids preoperatively (n=39) compared to 12.77 mg in those who used opioids preoperatively (n=9; P=0.0003). 9/54 patients had a documented ileus during their admission, while 4/9 (11%) had received ketamine (P=0.095).

Conclusions: Though our study showed no significant change in postoperative opioid requirement in our population, our results show that integration of ketamine in these extensive operations fare similarly to traditional opioid-based regimens. There was also no significant association seen between ketamine use and adverse side effects such as ileus. At our institution we are currently establishing opioid-free intraoperative pain protocols that use ketamine as an adjunct, and further study will explore the effect this may have on postoperative opioid consumption for spinal surgery patients as well as postoperative patients in general.
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http://dx.doi.org/10.21037/jss-19-475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024753PMC
March 2021

Flexion-extension standing radiographs underestimate instability in patients with single-level lumbar spondylolisthesis: comparing flexion-supine imaging may be more appropriate.

J Spine Surg 2021 Mar;7(1):48-54

Department of Orthopaedics, Columbia University Medical Center, The Spine Hospital at New York-Presbyterian, New York, NY, USA.

Background: Generally, most spine surgeons agree that increased segmental motion viewed on flexion-extension radiographs is a reliable predictor of instability; however, these views can be limited in several ways and may underestimate the instability at a given lumbar segment.

Methods: Consecutively collected adult (≥18 years old) patients with symptomatic single-level lumbar spondylolisthesis were reviewed from a two-surgeon database from 2015 to 2019. Routine standing lumbar X-rays (neutral, flexion, extension) and supine lumbar MRI (sagittal T2-weighted imaging sequence) were performed. Patients were excluded if they had prior lumbar surgery, missing radiographic data, or if the time between X-rays and MRI was >6 months.

Results: All 39 patients with symptomatic, single-level lumbar spondylolisthesis were identified. The mean age was 57.3±16.7 years and 66% were female. There was good intra- and inter-rater reliability agreement between measured values on the presence of instability. The slip percentage (SP) difference was significantly highest in the flexion-supine (FS) (5.7 mm, 12.3%) and neutral standing-supine (NS) (4.3 mm, 8.7%) groups, both of which were significantly higher compared with the flexion-extension (FE) group (1.8 mm, 4.5%, P<0.001). Ventral instability based on SP >8% was observed more frequently in FS (79.5%) and NS (52.6%) groups compared with FE group (16.7%, P<0.001). No statistically significant correlation was found between SP and disc angle for all radiographic views.

Conclusions: Comparing standing lateral and flexion X-rays with supine MRIs provides higher sensitivity to assess instability than standard flexion-extension radiographs. The FS and NS comparisons also show greater slip percentage differences at higher slip grades, but not at different lumbar levels. These changes are not dependent on age or gender.
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http://dx.doi.org/10.21037/jss-20-631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024755PMC
March 2021

Circumferential Operations of the Cervical Spine.

Neurospine 2021 Mar 31;18(1):55-66. Epub 2021 Mar 31.

Department of Orthopedics, Columbia University, New York, NY, USA.

Generally, a combined anterior and posterior cervical approach is associated with significant morbidity since it requires an extended operative time, greater intraoperative blood loss, and both anterior- and posterior-related surgical complications. However, there are some instances where a circumferential cervical fusion can be advantageous. Our objective is to discuss the indications for circumferential cervical spine procedures. A narrative review of the literature was performed. We include the indications for circumferential cervical approaches of the senior author (KDR). Indications for circumferential approaches include: (1) high-risk patients for pseudoarthrosis, (2) cervical deformity (e.g. , degenerative, posttraumatic, cervicothoracic kyphosis), (3) cervical spine metastases (especially those with multilevel involvement), (4) cervical spine infection, (5) unstable cervical trauma, (6) movement disorders and cerebral palsy, (7) Multiply operated patient (especially postlaminectomy kyphosis and patients with massive ossification of the posterior longitudinal ligament), and when (8) early fusion is desirable. Circumferential procedures may be useful in many different cervical spine conditions requiring surgery. Despite its advantages, particularly with reducing the risk for pseudarthrosis, the benefits of a combined approach must be weighed against the risks associated with a dual approach. With appropriate preoperative planning, intraoperative decision-making, and surgical techniques, excellent clinical outcomes can be achieved.
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http://dx.doi.org/10.14245/ns.2040528.264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021816PMC
March 2021

Revision Surgeries at the Index Level After Cervical Disc Arthroplasty - A Systematic Review.

Neurospine 2021 Mar 31;18(1):34-44. Epub 2021 Mar 31.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY, USA.

Objective: To perform a systematic literature review on revision surgeries at the index level after cervical disc arthroplasty (CDA) failure.

Methods: A systematic literature review was performed according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Prospective studies on patients who required a secondary surgery after CDA failure were included for analysis. The minimum follow-up for these studies was 5 years.

Results: Out of 864 studies in the original search group, a total of 20 studies were included. From a total of 4,087 patients, 161 patients required a reoperation at the index level. A total of 170 surgeries were performed, as some patients required multiple surgeries. The most common secondary procedures were anterior cervical discectomy and fusion (ACDF) (68%, N = 61) and posterior cervical fusion (15.5%, N = 14), followed by other reoperation (13.3%, N = 12). The associated outcomes for those who required a revision surgery were rarely mentioned in the included literature.

Conclusion: The long-term revision rate at the index level of failed CDA surgery was 3.9%, with a minimum 5-year follow-up. ACDF was the most commonly performed procedure to salvage a failed CDA. Some patients who required a new surgery after CDA failure may require a more extensive salvage procedure and even subsequent surgeries.
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http://dx.doi.org/10.14245/ns.2040454.227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021828PMC
March 2021

Intraoperative versus postoperative radiographic coronal balance for adult spinal deformity surgery.

Spine Deform 2021 Jul 24;9(4):1077-1084. Epub 2021 Feb 24.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine, Hospital At New York-Presbyterian, 5141 Broadway, New York, NY, 10034, USA.

Background: Coronal malalignment in adult spinal deformity (ASD) has a close relationship with patient clinical outcomes. The purpose of this study is to evaluate the relationship between intra- and postoperative coronal radiographic parameters. A novel parameter, the central sacral pelvic line (CSPL), and its relation to the central sacral vertical line (CSVL) is explored. CSPL is a measure of spinal alignment referenced to the patient's pelvis as an intraoperative proxy for CSVL. CSVL is difficult to measure intraoperatively, because a C7-plumb line (referenced to gravity) cannot be drawn in the supine position.

Methods: 47 subjects ≥ 18 years old undergoing a spinal fusion of ≥ 6 levels from 2015 to 2017 were enrolled. The CSPL is defined as the perpendicular line bisecting the midpoint of the line that connects the superior aspects of the acetabuli. Two metrics describing coronal alignment were derived from each radiograph: (1) horizontal distance between the C7-plumb line and the CSPL at C7 (C7-CSPL) and (2) horizontal distance between the C7-plumb line and CSVL (C7-CSVL). Pearson's correlation and linear regression analysis was used to study the relationship between the intraoperative C7-CSPL and the postoperative C7-CSVL.

Results: On average, the intraoperative C7-CSPL distance was 32.1 mm, postoperative C7-CSPL 20.8 mm, and postoperative C7-CSVL 18.9 mm. 15/47 (32%) had intraoperative C7-CSPL measurements > 4 cm, requiring intraoperative correction. Of those 15, 10 patients (67%) still had a postoperative C7-CSVL < 4 cm. Linear regression modeling indicates that when intraoperative CSPL is < 7.7 cm on average, the postoperative C7-CSVL will < 4 cm-our threshold for adequate coronal alignment. Patients with intraoperative C7-CSPL > 5 cm had a 50% chance of having a postoperative C7-CSVL > 4 cm; patients with intraoperative C7-CSPL < 5 cm had a 3% chance of having coronal malalignment. There is a strong positive relationship between postoperative C7-CSPL and C7-CSVL (r = 0.80 and 0.85, respectively).

Conclusion: In adult spinal surgery, the intraoperative coronal alignment measured using the novel C7-CSPL distance correlates well with postoperative C7-CSVL distance. This gives the surgeon an objective measurement of the correction they need after assessing initial intraoperative imaging. Our findings suggest an intraoperative C7-CSPL distance < 5 cm as a threshold value to predict postoperative C7-CSVL < 4 cm in 97% of patients tested.
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http://dx.doi.org/10.1007/s43390-021-00297-4DOI Listing
July 2021

What Is the Impact of Surgical Approach in the Treatment of Degenerative Cervical Myelopathy in Patients With OPLL? A Propensity-Score Matched, Multi-Center Analysis on Inpatient and Post-Discharge 90-Day Outcomes.

Global Spine J 2021 Feb 19:2192568221994797. Epub 2021 Feb 19.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY, USA.

Study Design: Retrospective cohort.

Objective: Provide a comparison of surgical approach in the treatment of degenerative cervical myelopathy in patients with OPLL.

Methods: A national database was queried to identify adult (≥18 years) patients with OPLL, who underwent at least a 2-level cervical decompression and fusion for cervical myelopathy from 2012-2014. A propensity-score-matching algorithm was employed to compare outcomes by surgical approach.

Results: After propensity-score matching, 627 patients remained. An anterior approach was found to be an independent predictor for higher inpatient surgical complications(OR 5.9), which included dysphagia:14%[anterior]vs.1.1%[posterior] -value < 0.001, wound hematoma:1.7%[anterior]vs.0%[posterior] -value = 0.02, and dural tear:9.4%[anterior]vs.3.2%[posterior] -value = 0.001. A posterior approach was an predictor for longer hospital length of stay by nearly 3 days(OR 3.4; 6.8 days[posterior]vs.4.0 days[anterior] -value < 0.001). The reasons for readmission/reoperation did not vary by approach for 2-3-level fusions; however, for >3-level fusions, patients with an anterior approach more often had respiratory complications requiring mechanical ventilation(-value = 0.038) and required revision fusion surgery(-value = 0.015).

Conclusions: The national estimates for inpatient complications(25%), readmissions(9.9%), and reoperations(3.5%) are substantial after the surgical treatment of multi-level OPLL. An anterior approach resulted in significantly higher inpatient surgical complications, but this did not result in a longer hospital length of stay and the overall 90-day complication rates requiring readmission or reoperation was similar to those seen after a posterior approach. For patients requiring >3-level fusion, an anterior approach is associated with significantly higher risk for respiratory complications requiring mechanical ventilation and revision fusion surgery. Precise neurological complications and functional outcomes were not included in this database, and should be further assessed in future studies.
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http://dx.doi.org/10.1177/2192568221994797DOI Listing
February 2021

TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation.

Nat Cell Biol 2021 03 11;23(3):243-256. Epub 2021 Feb 11.

Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Cell proliferation and differentiation require signalling pathways that enforce appropriate and timely gene expression. We find that Tor2, the catalytic subunit of the TORC1 complex in fission yeast, targets a conserved nuclear RNA elimination network, particularly the serine and proline-rich protein Pir1, to control gene expression through RNA decay and facultative heterochromatin assembly. Phosphorylation by Tor2 protects Pir1 from degradation by the ubiquitin-proteasome system involving the polyubiquitin Ubi4 stress-response protein and the Cul4-Ddb1 E3 ligase. This pathway suppresses widespread and untimely gene expression and is critical for sustaining cell proliferation. Moreover, we find that the dynamic nature of Tor2-mediated control of RNA elimination machinery defines gene expression patterns that coordinate fundamental chromosomal events during gametogenesis, such as meiotic double-strand-break formation and chromosome segregation. These findings have important implications for understanding how the TOR signalling pathway reprogrammes gene expression patterns and contributes to diseases such as cancer.
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http://dx.doi.org/10.1038/s41556-021-00631-yDOI Listing
March 2021

Comorbid Dysphagia and Malnutrition in Elderly Hospitalized Patients.

Laryngoscope 2021 Jan 25. Epub 2021 Jan 25.

Department of Otolaryngology - Head and Neck Surgery, Loma Linda University Health, Loma Linda, California, U.S.A.

Objective/hypothesis: Elderly individuals account for one-third of all hospitalizations. The goal of this study was to evaluate the prevalence of dysphagia in elderly patients admitted to a tertiary care center. It also sought to investigate how dysphagia is identified, how it covaries with malnutrition and other conditions, and how it impacts hospital stay.

Study Design: Case Series.

Methods: A retrospective chart review was performed. All patients >65 years admitted to a tertiary care center in January and February 2016 were included. Patients with primary psychiatric diagnoses and patients with upper aerodigestive tract malignancy or surgery were excluded.

Results: A total of 655 patients were identified. Mean age was 76.6 years. Twenty-four percent (155 patients) had dysphagia while 43% (282 patients) had malnutrition. Thirteen percent (84 patients) had both dysphagia and malnutrition. Fifty percent of patients who had malnutrition were seen by speech language pathology (SLP). One hundred percent of malnourished patients that saw SLP were identified as having dysphagia. Three hundred and eighty-two patients (58%) were seen by the dietician but not by SLP. Multiple logistic regression indicated that the presence of dysphagia was positively associated with age, presence of malnutrition, admission to either cardiology or neurology service as compared to medicine service, and history of stroke.

Conclusions: One-quarter of elderly patients admitted to our tertiary care center had dysphagia. Dysphagia, especially when linked with malnutrition, has poorer outcomes and increased healthcare costs. Our data suggests a possible disconnect between malnutrition diagnosis and dysphagia identification. This is an important area of intervention that has the potential to improve the treatment and outcomes of these patients.

Level Of Evidence: 4 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29329DOI Listing
January 2021

Revision Anterior Cervical Disc Arthroplasty: A National Analysis of the Associated Indications, Procedures, and Postoperative Outcomes.

Global Spine J 2021 Jan 19:2192568220979140. Epub 2021 Jan 19.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY, USA.

Study Design: Retrospective study.

Objective: To examine the associated indications, procedures, and postoperative outcomes after revision ACDA.

Methods: We utilized a national database to identify adult(≥18 years) patients who underwent either a primary ACDA or removal of ACDA over a 10-year period(2008-2017). An in-depth assessment of the reasons for revision surgery and the subsequent procedures performed after the removal of ACDA was done by using both Current Procedural Terminology(CPT) and International Statistical Classification of Diseases (ICD-9,10) coding.

Results: From 2008 to 2017, a total of 3,350 elective, primary ACDA cases were performed. During this time, 69 patients had a revision surgery requiring the removal of ACDA. The most common reasons for revision surgery included cervical spondylosis(59.4%) and mechanical complications(27.5%). After removal of ACDA, common procedures performed included anterior cervical fusion with or without decompression(69.6%), combined anterior/posterior fusion/decompression (11.6%), and replacement of ACDA (7.2%). The indications for surgery did not vary significantly among the different procedures performed (p = 0.318). Patients requiring revision surgery for mechanical complications or those who underwent a combined surgical approach were at significantly higher risk for subsequent short-term complications (p<0.05).

Conclusion: Over a 10-year period, the rate of revision surgery for ACDA was low (2.1%). Nearly 90% of revision cases were due to either cervical spondylosis or mechanical complications. These indications for surgery did not vary significantly among the different procedures performed. These findings will be important during the shared-decision making process for patients undergoing primary or revision ACDA.
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http://dx.doi.org/10.1177/2192568220979140DOI Listing
January 2021

Respiratory Compromise After Anterior Cervical Spine Surgery: Incidence, Subsequent Complications, and Independent Predictors.

Global Spine J 2021 Jan 7:2192568220984469. Epub 2021 Jan 7.

The Spine Hospital, New York-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.

Study Design: Retrospective cohort study.

Objective: Respiratory compromise (RC) is a rare but catastrophic complication of anterior cervical spine surgery (ACSS) commonly due to compressive fluid collections or generalized soft tissue swelling in the cervical spine. Established risk factors include operative duration, size of surgical exposure, myelopathy, among others. The purpose of this current study is to identify the incidence and clinical course of patients who develop RC, and identify independent predictors of RC in patients undergoing ACSS for cervical spondylosis.

Methods: A large, prospectively-collected registry was used to identify patients undergoing ACSS for spondylosis. Patients with posterior cervical procedures were excluded. Baseline patient characteristics were compared using bivariate analysis, and multivariate analysis was employed to compare postoperative complications and identify independent predictors of RC.

Results: 298 of 52,270 patients developed RC (incidence 0.57%). Patients who developed RC had high rates of 30-day mortality (11.7%) and morbidity (75.8%), with unplanned reoperation and pneumonia the most common. The most common reason for reoperations were hematoma evacuation and tracheostomy. Independent patient-specific factors predictive of RC included increasing patient age, male gender, comorbidities such as chronic cardiac and respiratory disease, preoperative myelopathy, prolonged operative duration, and 2-level ACCFs.

Conclusion: This is among the largest cohorts of patients to develop RC after ACSS identified to-date and validates a range of independent predictors, many previously only described in case reports. These results are useful for taking preventive measures, identifying high risk patients for preoperative risk stratification, and for surgical co-management discussions with the anesthesiology team.
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http://dx.doi.org/10.1177/2192568220984469DOI Listing
January 2021

A Comparison of Various Surgical Treatments for Degenerative Cervical Myelopathy: A Propensity Score Matched Analysis.

Global Spine J 2020 Dec 30:2192568220976092. Epub 2020 Dec 30.

Department of Orthopaedics, Columbia University Medical Center, The Spine Hospital at New York-Presbyterian, New York, NY, USA.

Study Design: Retrospective Cohort.

Objective: To compare the short-term outcomes for Laminoplasty, Laminectomy/fusion, and ACDF.

Methods: We utilized a prospectively-collected, multi-center national database with a propensity score matching algorithm to compare the short-term outcomes for laminoplasty, laminectomy/fusion, and multi-level (3) ACDF (with and without corpectomy). Bivariate analyses involved both chi-square/fisher exact test and t-test/ANOVA on perioperative factors. Multivariate analyses were performed to determined independent risk factors for short term outcomes.

Results: 546 patients remained after propensity score matching, with 182 patients in each cohort. ACDF required the longest operative time 188 ± 79 versus laminectomy/fusion (169 ± 75, p = 0.017), and laminoplasty (167 ± 66, p = 0.004). ACDF required the shortest hospital stay (LOS ≥ 2: ACDF 56.6%, laminoplasty 89.6%, laminectomy/fusion 93.4%, p < 0.05). ACDF had lower overall complications (ACDF 3.9%, laminoplasty 7.7%, laminectomy/fusion 11.5%, p < 0.05), mortality (ACDF 0%, laminoplasty 0.55%, laminectomy/fusion 2.2%, p < 0.05), and unplanned readmissions (ACDF 4.4%, laminoplasty 4.4%, laminectomy/fusion 9.9%, p < 0.05). No significant differences were seen in the other outcomes including DVT/PT, acute renal failure, UTI, stroke, cardiac complications, or sepsis. In the multivariate analysis, laminectomy/fusion (OR 17, reference: ACDF) and laminoplasty (OR10, reference: ACDF) were strong independent risk factors for LOS ≥ 2 days. Laminectomy/fusion (OR 3.2, reference: ACDF) was an independent predictor for any adverse events 30-days after surgery.

Conclusions: Laminectomy/fusion carries the highest risk for morbidity, mortality, and unplanned readmissions in the short-term postoperative period. Laminoplasty and ACDF cases carry similar short-term complications risks. ACDF is significantly associated with the longest operative duration and shortest LOS without an increase in individual or overall complications, readmissions, or reoperations.
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http://dx.doi.org/10.1177/2192568220976092DOI Listing
December 2020

Determining the concentration and enantiomeric composition of histidine using one fluorescent probe.

Chem Commun (Camb) 2021 Jan;57(5):587-590

Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, USA.

A chemoselective as well as enantioselective fluorescent probe has been developed to determine both the concentration and enantiomeric composition of the biologically important amino acid histidine by measuring the fluorescence responses when excited at two different wavelengths.
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http://dx.doi.org/10.1039/d0cc07498eDOI Listing
January 2021

The risks, reasons, and costs for 30- and 90-day readmissions after fusion surgery for adolescent idiopathic scoliosis.

J Neurosurg Spine 2020 Nov 6:1-9. Epub 2020 Nov 6.

Objective: With the continued evolution of bundled payment plans, there has been a greater focus within orthopedic surgery on quality metrics up to 90 days of care. Although the Centers for Medicare and Medicaid Services does not currently penalize hospitals based on their pediatric readmission rates, it is important to understand the drivers for unplanned readmission to improve the quality of care and reduce costs.

Methods: The National Readmission Database provides a nationally representative sample of all discharges from US hospitals and allows follow-up across hospitals up to 1 calendar year. Adolescents (age 10-18 years) who underwent idiopathic scoliosis surgery from 2012 to 2015 were included. Patients were separated into those with and those without readmission within 30 days or between 31 and 90 days. Demographics, operative conditions, hospital factors, and surgical outcomes were compared using the chi-square test and t-test. Independent predictors for readmissions were identified using stepwise multivariate logistic regression.

Results: A total of 30,677 patients underwent adolescent idiopathic scoliosis surgery from 2012 to 2015. The rates of 30- and 90-day readmissions were 2.9% and 1.4%, respectively. The mean costs associated with the index admission and 30- and 90-day readmissions were $60,680, $23,567, and $16,916, respectively. Common risk factors for readmissions included length of stay > 5 days, obesity, neurological disorders, and chronic use of antiplatelets or anticoagulants. The index admission complications associated with readmissions were unintended durotomy, syndrome of inappropriate antidiuretic hormone, and superior mesenteric artery syndrome. Hospital factors, discharge disposition, and operative conditions appeared to be less important for readmission risk. The top reasons for 30-day and 90-day readmissions were wound infection (34.7%) and implant complications (17.3%), respectively. Readmissions requiring a reoperation were significantly higher for those that occurred between 31 and 90 days after the index readmission.

Conclusions: Readmission rates were low for both 30- and 90-day readmissions for adolescent idiopathic scoliosis surgery patients. Nevertheless, readmissions are costly and appear to be associated with potentially modifiable risk factors, although some risk factors remain potentially unavoidable.
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http://dx.doi.org/10.3171/2020.6.SPINE20197DOI Listing
November 2020

Can spinal deformity patients maintain proper arm positions while undergoing full-body X-ray?

Spine Deform 2021 Mar 2;9(2):387-394. Epub 2020 Nov 2.

Department of Orthopaedic Surgery, Columbia University Medical Center, The Och Spine Hospital, New York Presbyterian/Allen, 5141 Broadway, New York, NY, 10034, USA.

Obtaining proper lateral full-body X-rays is paramount in accurately and consistently evaluating sagittal spinal alignment. This study explored the patient compliance rate of maintaining standardized arm position (fingers on the clavicles with shoulders in 45° of forward elevation while the patient is in a free-standing posture) during full-body X-rays at a single institution.

Hypothesis: The compliance rate of arm positioning during full-body X-rays varies depending on operative status (preoperative vs postoperative), age, and diagnosis.

Design: Retrospective cohort.

Introduction: Despite the importance of patients maintaining arms in the same position in preoperative and postoperative standing films, patients are known to have their arms in varying positions, confounding radiographic interpretation and making global sagittal and coronal spinal balance assessment variable and potentially less reliable. This study seeks to examine arm position compliance among adult and pediatric surgical spinal deformity patients undergoing total body X-rays over the course of 4 years (2015-2018).

Methods: A retrospective radiographic review was performed on 382 spinal deformity patients from July 2015 to July 2018. The study's dependent variable of interest was standardized arm position (fingers on the clavicles with shoulders in 45° of forward elevation while the patient is in a free-standing posture) observed during full-body X-rays obtained for spinal deformity evaluation. Deviations and compliance to the standard protocol for full-body X-ray arm positioning was recorded and analyzed across various independent factors, including year of surgery, pre- and postoperative periods, type of spine surgery, and patient age. Chi-square and Cochran-Armitage analyses were performed to study categorical and trends, respectively.

Results: The overall compliance rate for maintaining standardized arm position was 90% for all 370 patients (277 adult and 93 pediatric), in preoperative and postoperative setting. Adults were more likely to follow protocol than pediatric patients (92.9% vs. 82.4%, P value = 0.003). The postoperative setting observed a significantly lower overall compliance rate when compared to the preoperative period (67.8% vs. 87.0%, P value < 0.0001). Patients undergoing neuromuscular scoliosis (73.3%), vertebral column resection (VCR) (70%), and growing rod lengthening (GRL) (57.1%) had the lowest overall compliance rate in the preoperative setting. In the postoperative setting, patients with GRL, VCR, revision congenital scoliosis, congenital scoliosis, neuromuscular scoliosis, and pedicle subtraction osteotomy (PSO) surgeries were compliant less than or equal to 50% of the time. From 2015 to 2018, there was an overall statistically significant increase in compliance rate (61.1% to 90.6%). Over the study period, adult patients became significantly more compliant to protocol. This was not observed in the pediatric population.

Conclusion: This study documented the patient compliance rate of maintaining standardized arm position during full-body X-rays of spinal deformity patients. The overall compliance rate was 90.0% for all patients in the preoperative and postoperative setting. Risk factors for lower compliance rates included patients that were pediatric, postoperative, neuromuscular, and those who underwent a complex vertebral osteotomy or GRL. There was a trend showing improved compliance rate throughout the 4-year study period, which highlights the importance of having an ancillary staff who is comfortable with a consistent standard of care protocol. These results should help other centers optimize arm positioning in their patients undergoing full-body X-rays in the future.
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March 2021

Spinal fusion in pediatric patients with marfan syndrome: a nationwide assessment on short-term outcomes and readmission risk.

Eur Spine J 2021 03 19;30(3):775-787. Epub 2020 Oct 19.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, 161 Fort Washington Avenue, New York, NY, USA.

Purpose: The purpose of this study was to utilize the National Readmission Database (NRD) to determine estimates for complication rates, 90-day readmission rates, and hospital costs associated with spinal fusion in pediatric patients with Marfan syndrome.

Methods: The 2012-2015 NRD databases were queried for all pediatric (< 19 years old) patients diagnosed with Marfan syndrome undergoing spinal fusion surgery. The primary outcome variables in this study were index admission complications and 90-day readmissions.

Results: A total of 249 patients with Marfan syndrome underwent spinal fusion surgery between 2012 and 2015 (mean age ± standard deviation at the time of surgery: 14 ± 2.0, 132 (53%) female). 25 (10.1%) were readmitted within 90 days of the index hospital discharge date. Overall, 59.7% of patients experienced at least one complication during the index admission. Unplanned 90-day readmission could be predicted by older age (odds ratio 2.3, 95% confidence interval 1.3-4.2, p = 0.006), Medicaid insurance status (56.0, 3.8-820.0, p = 0.003), and experiencing an inpatient medical complication (42.9, 4.6-398.7, p = 0.001). Patients were readmitted for wound dehiscence (8 patients, 3.2%), nervous system related complications (3 patients, 1.2%), and postoperative infectious related complications (4 patients, 1.6%).

Conclusion: This study is the first to demonstrate on a national level the complications and potential risk factors for 90-day hospital readmission for patients with Marfan syndrome undergoing spinal fusion. Patients with Marfan syndrome undergoing spinal fusion often present with multiple medical comorbidities that must be managed carefully perioperatively to reduce inpatient complications and early hospital readmissions.
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http://dx.doi.org/10.1007/s00586-020-06645-8DOI Listing
March 2021

Cervical Spinal Fusion in Adult Patients With Rheumatoid Arthritis: A National Analysis of Complications and 90-day Readmissions.

Spine (Phila Pa 1976) 2021 Jan;46(1):E23-E30

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY.

Study Design: Retrospective cohort study.

Objective: The purpose of this study was to utilize the National Readmission Database to determine the national estimates of complication and 90-day readmission rates associated with cervical spinal fusion in adult patients with rheumatoid arthritis (RA).

Summary Of Background: RA patients who undergo cervical spine surgery are known to be at high risk for readmissions, which are costly and may not be reimbursed by Medicare.

Methods: The National Readmission Database was queried for adults (>18 years) diagnosed with RA undergoing cervical spine fusion. Patient, operative, and hospital factors were assessed in bivariate analyses. Independent risk factors for readmissions were identified using stepwise multivariate logistic regression.

Results: From 2013 to 2014, a total of 5597 RA patients (average age: 61.5 ± 11.2 years, 70.9% female) underwent cervical spine fusion. A total of 691 (12.3%) patients were readmitted within 90 days (). Index inpatient complications included dysphagia (readmitted: 7.9% vs. non-readmitted: 5.1%; P = 0.003), urinary tract infection (UTI) (8.8% vs. 3.7%; P < 0.001), respiratory-related complications (7.6% vs. 3.4%; P < 0.001), and implant-related complications (5.4% vs. 2.7%; P < 0.001). Multivariate logistic regression demonstrated the following as the strongest independent predictors for 90-day readmission: intraoperative bleeding (odds ratio [OR]: 3.6, P = 0.001), inpatient Deep Vein Thrombosis (DVT) (OR 4.1, P = 0.004), and patient discharge against medical advice (OR 33.5, P = 0.001).

Conclusion: Readmission rates for RA patients undergoing cervical spine surgery are high and most often due to postoperative infection (septicemia, UTI, pneumonia, wound). Potential modifiable factors which may improve outcomes include minimizing intraoperative blood loses, postoperative DVT prophylaxis, and discharge disposition.

Level Of Evidence: 3.
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January 2021

Are outpatient three- and four-level anterior cervical discectomies and fusion safe?

Spine J 2021 02 10;21(2):231-238. Epub 2020 Oct 10.

The Spine Hospital, New York-Presbyterian/Columbia University Irving Medical Center, 622 W. 168th St. PH-11, New York, NY 10032, USA.

Background Context: The safety of outpatient one- and two-level anterior cervical discectomy and fusion (ACDF) has been validated in a number of recent studies. However, recent advancements in anesthetic and surgical technique have rendered procedures previously only performed in an inpatient setting, such as three- and four-level ACDF, potentially amenable to outpatient management.

Purpose: The present study aimed to investigate the safety of outpatient three- and four-level ACDF.

Study Design: Retrospective cohort study PATIENT SAMPLE: The National Surgical Quality Improvement Program - a large, prospectively-collected registry - was queried to identify patients undergoing three- and four-level ACDF in an inpatient and outpatient setting.

Outcome Measures: The rates of total complications, perioperative blood transfusion, and unplanned hospital readmission in three- and four-level ACDF by inpatient or outpatient surgery status.

Methods: Baseline patient characteristics and 30-day outcomes were tabulated and compared by inpatient or outpatient status using bivariate analysis. A multivariate analysis was also employed to adjust for differences in baseline patient characteristics when comparing outcomes, and was also used to identify independent predictors of complications and readmissions in patients undergoing three- and four-level ACDF.

Results: In total 3,441 patients underwent three- or four-level ACDF, with 2,718 (79.0%) procedures occurring inpatient and 723 (21.0%) outpatient. Of patients undergoing outpatient ACDF, 596 patients (82.4%) underwent a three-level and 127 patients (17.6%) underwent four-level procedures. There was an increase in the utilization of outpatient procedures, increasing from 7.0% to 32.9% between 2011 and 2018. Patients undergoing outpatient surgery were younger, white, more likely to have three-level fusions (vs four-level), had a lower American Society of Anesthesiologists (ASA) classification, and were less likely to have a history of diabetes mellitus or dependent functional status. Among the inpatient and outpatient cohorts, there was no significant difference in the rates of total complications (4.49% vs 2.49%) or unplanned readmissions (4.96% vs 3.72%). Increasing age, operative duration, and ASA classification were independent predictors of complications and readmissions, however, inpatient or outpatient surgery status and number of levels fused was not.

Conclusions: This present study represents one of the largest cohorts of patients undergoing outpatient three- and four-level ACDF. Outpatient multilevel ACDF is performed in younger and healthier patients, with three-level procedures more commonly the four-level. There was no observed increased rates of total complications or readmissions in patients undergoing outpatient relative to inpatient surgery, however, we did identify increased age, operative duration, and ASA classification as independent predictors of these complications. Patient selection for outpatient procedures is of the highest importance, and future studies developing reproducible selection criteria are warranted.
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February 2021

Can Machine Learning Accurately Predict Postoperative Compensation for the Uninstrumented Thoracic Spine and Pelvis After Fusion From the Lower Thoracic Spine to the Sacrum?

Global Spine J 2020 Oct 8:2192568220956978. Epub 2020 Oct 8.

Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY, USA.

Study Design: Consecutively collected cases.

Objective: To determine if a machine-learning (ML) program can accurately predict the postoperative thoracic kyphosis through the uninstrumented thoracic spine and pelvic compensation in patients who undergo fusion from the lower thoracic spine (T10 or T11) to the sacrum.

Methods: From 2015 to 2019, a consecutive series of adult (≥18 years old) patients with adult spinal deformity underwent corrective spinal fusion from the lower thoracic spine (T10 or T11) to the sacrum. Deidentified data was processed by a ML system-based platform to predict the postoperative thoracic kyphosis (TK) and pelvic tilt (PT) for each patient. To validate the ML model, the postoperative TK (T4-T12, instrumented thoracic, and uninstrumented thoracic) and the pelvic tilt were compared against the predicted values.

Results: A total of 20 adult patients with a minimum 6-month follow-up (mean: 22.4 ± 11.3 months) were included in this study. No significant differences were observed for TK (predicted 37.6° vs postoperative 38.3°, = .847), uninstrumented TK (predicted 33.9° vs postoperative 29.8°, = .188), and PT (predicted 23.4° vs postoperative 22.7°, = .754). The predicted PT and the TK of the uninstrumented thoracic spine correlated well with postoperative values (uninstrumented TK: = 0.764, < .001; PT: = 0.868, < .001). The mean error with which kyphosis through the uninstrumented thoracic spine can be measured was 4.8° ± 4.0°. The mean error for predicting PT was 2.5° ± 1.7°.

Conclusion: ML algorithms can accurately predict the spinopelvic compensation after spinal fusion from the lower thoracic spine to the sacrum. These findings suggest that surgeons may be able to leverage this technology to reduce the risk of proximal junctional kyphosis in this population.
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October 2020
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