The Impact of Preoperative Symptom Duration on Patient Outcomes After Posterior Cervical Decompression and Fusion.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: To determine if decreased preoperative symptom duration is associated with greater clinical improvement in function and myelopathic symptoms after posterior cervical decompression and fusion (PCDF). METHODS: All patients over age 18 who underwent primary PCDF for cervical myelopathy or myeloradiculopathy at a single institution between 2014 and 2020 were retrospectively identified. Patient demographics, surgical characteristics, duration of symptoms, and preoperative and postoperative patient reported outcomes measures (PROMs) including modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), Visual Analogue Scale (VAS) Neck, VAS Arm, and SF-12 were collected. Univariate and multivariate analyses were performed to compare change in PROMs and minimum clinically important difference achievement (%MCID) between symptom duration groups (< 6 months, 6 months-2 years, > 2 years). RESULTS: Preoperative symptom duration groups differed significantly by sex and smoking status. Patients with < 6 months of preoperative symptoms improved significantly in all PROMs. Patients with 6 months-2 years of preoperative symptoms did not improve significantly in mJOA, Physical Component Scores (PCS), or NDI. Patients with > 2 years of symptoms failed to demonstrate significant improvement in mJOA, NDI, or Mental Component Scores (MCS). Univariate analysis demonstrated significantly decreased improvement in mJOA with longer symptom durations. Increased preoperative symptom duration trended toward decreased %MCID for mJOA and MCS. Regression analysis demonstrated that preoperative symptom duration of > 2 years relative to < 6 months predicted decreased improvement in mJOA and NDI and decreased MCID achievement for mJOA and MCS. CONCLUSION: Increased duration of preoperative symptoms (> 2 years) before undergoing PCDF was associated with decreased postoperative improvement in myelopathic symptoms.

Depression Increases Posterior Cervical Decompression and Fusion Revision Rates and Diminishes Neck Disability Index Improvement.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To determine if depression and/or anxiety significantly affect patient-reported outcome measures (PROMs) after posterior cervical decompression and fusion (PCDF). SUMMARY OF BACKGROUND DATA: Mental health diagnoses are receiving increased recognition for their influence of outcomes after spine surgery. The magnitude that mental health disorders contribute to patient-reported outcomes following PCDF requires increased awareness and understanding. MATERIALS AND METHODS: A review of electronic medical records identified patients who underwent a PCDF at a single institution during the years 2013-2020. Patients were placed into either depression/anxiety or nondepression/anxiety group based on their medical history. A delta score (∆) was calculated for all PROMs by subtracting postoperative from preoperative scores. χ 2 tests and t tests were utilized to analyze categorical and continuous data, respectively. Regression analysis determined independent predictors of change in PROMs. Alpha was set at 0.05. RESULTS: A total of 195 patients met inclusion criteria, with 60 (30.8%) having a prior diagnosis of depression/anxiety. The depression/anxiety group was younger (58.8 vs . 63.0, P =0.012), predominantly female (53.3% vs . 31.9%, P =0.007), and more frequently required revision surgery (11.7% vs . 0.74%, P =0.001). In addition, they had worse baseline mental component (MCS-12) (42.2 vs . 48.6, P <0.001), postoperative MCS-12 (46.5 vs . 52.9, P =0.002), postoperative neck disability index (NDI) (40.7 vs . 28.5, P =0.001), ∆NDI (-1.80 vs . -8.93, P =0.010), NDI minimum clinically important difference improvement (15.0% vs . 29.6%, P =0.046), and postoperative Visual Analog Scale (VAS) Neck scores (3.63 vs . 2.48, P =0.018). Only the nondepression/anxiety group improved in MCS-12 ( P =0.002) and NDI ( P <0.001) postoperatively. Depression and/or anxiety was an independent predictor of decreased magnitude of NDI improvement on regression analysis (ß=7.14, P =0.038). CONCLUSION: Patients with history of depression or anxiety demonstrate less improvement in patient-reported outcomes and a higher revision rate after posterior cervical fusion, highlighting the importance of mental health on clinical outcomes after spine surgery.

UCP2 modulates cardiomyocyte cell cycle activity, acetyl-CoA, and histone acetylation in response to moderate hypoxia.

Developmental cardiac tissue is regenerative while operating under low oxygen. After birth, ambient oxygen is associated with cardiomyocyte cell cycle exit and regeneration. Likewise, cardiac metabolism undergoes a shift with cardiac maturation. Whether there are common regulators of cardiomyocyte cell cycle linking metabolism to oxygen tension remains unknown. The objective of the study is to determine whether mitochondrial UCP2 is a metabolic oxygen sensor regulating cardiomyocyte cell cycle. Neonatal rat ventricular myocytes (NRVMs) under moderate hypoxia showed increased cell cycle activity and UCP2 expression. NRVMs exhibited a metabolic shift toward glycolysis, reducing citrate synthase, mtDNA, mitochondrial membrane potential (ΔΨm), and DNA damage/oxidative stress, while loss of UCP2 reversed this phenotype. Next, WT and mice from a global UCP2-KO mouse line (UCP2KO) kept under hypoxia for 4 weeks showed significant decline in cardiac function that was more pronounced in UCP2KO animals. Cardiomyocyte cell cycle activity was reduced, while fibrosis and DNA damage was significantly increased in UCP2KO animals compared with WT under hypoxia. Mechanistically, UCP2 increased acetyl-CoA levels and histone acetylation, and it altered chromatin modifiers linking metabolism to cardiomyocyte cell cycle under hypoxia. Here, we show a potentially novel role for mitochondrial UCP2 as an oxygen sensor regulating cardiomyocyte cell cycle activity, acetyl-CoA levels, and histone acetylation in response to moderate hypoxia.

Adult Isthmic Spondylolisthesis: A Radiographic and Outcomes Analysis Comparing Circumferential Fusions Versus TLIF Procedures.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: The objective of this study was to compare radiographic and patient-reported outcome measures (PROMs) between circumferential fusions and transforaminal lumbar interbody fusion (TLIF) for adult isthmic spondylolisthesis (IS). SUMMARY OF BACKGROUND DATA: Definitive management of adult IS typically requires decompression and fusion. Multiple fusion techniques have been described, but literature is sparse in identifying the optimal technique. METHODS: Patients with IS undergoing single-level or 2-level circumferential fusion or TLIF with a minimum 1-year follow-up were included. Patient demographics, surgical characteristics, and PROMs were extracted from patients' electronic medical records. Descriptive statistics and multivariate regression analysis compared outcomes with significance set at P -value <0.05. RESULTS: A total of 78 circumferential fusions (48 open decompression and fusions and 30 circumferential fusions utilizing posterior percutaneous instrumentation) and 50 TLIF procedures were included. Length of stay was significantly longer when comparing circumferential procedures (3.56±0.96 d) versus TLIFs (2.88±1.14 d) ( P =0.002). The circumferential fusion group resulted in greater postoperative improvement in segmental lordosis [anterior/posterior (A/P): 6.45, TLIF: -1.99, P <0.001], posterior disk height (A/P: 12.6 mm, TLIF: 8.9 mm, P <0.001), and ∆disk height (A/P: 7.7 mm, TLIF: 3.6 mm, P <0.001). Both groups significantly improved in all PROMs ( P <0.001). While the circumferential fusion group had a significantly higher rate of perioperative surgical complications (12.82% vs. 2.00%, P =0.049), there was no difference in the rate of 30-day readmissions ( P =0.520) or revision surgeries between techniques ( P =0.057). CONCLUSIONS: Circumferential fusions are associated with improvements in radiographic outcomes compared with TLIFs, but this is at the expense of longer hospital length of stay and increased risk for perioperative complications. The surgical technique did not result in superior postoperative PROMs or differences in readmissions or revisions.

Uncoupling protein 2-mediated metabolic adaptations define cardiac cell function in the heart during transition from young to old age.

Cellular replacement in the heart is restricted to postnatal stages with the adult heart largely postmitotic. Studies show that loss of regenerative properties in cardiac cells seems to coincide with alterations in metabolism during postnatal development and maturation. Nevertheless, whether changes in cellular metabolism are linked to functional alternations in cardiac cells is not well studied. We report here a novel role for uncoupling protein 2 (UCP2) in regulation of functional properties in cardiac tissue derived stem-like cells (CTSCs). CTSC were isolated from C57BL/6 mice aged 2 days (nCTSC), 2 month (CTSC), and 2 years old (aCTSC), subjected to bulk-RNA sequencing that identifies unique transcriptome significantly different between CTSC populations from young and old heart. Moreover, results show that UCP2 is highly expressed in CTSCs from the neonatal heart and is linked to maintenance of glycolysis, proliferation, and survival. With age, UCP2 is reduced shifting energy metabolism to oxidative phosphorylation inversely affecting cellular proliferation and survival in aged CTSCs. Loss of UCP2 in neonatal CTSCs reduces extracellular acidification rate and glycolysis together with reduced cellular proliferation and survival. Mechanistically, UCP2 silencing is linked to significant alteration of mitochondrial genes together with cell cycle and survival signaling pathways as identified by RNA-sequencing and STRING bioinformatic analysis. Hence, our study shows UCP2-mediated metabolic profile regulates functional properties of cardiac cells during transition from neonatal to aging cardiac states.