mRNA-Decapping Associated DcpS Enzyme Controls Critical Steps of Neuronal Development.

Homozygous mutations in the gene encoding the scavenger mRNA-decapping enzyme, DcpS, have been shown to underlie developmental delay and intellectual disability. Intellectual disability is associated with both abnormal neocortical development and mRNA metabolism. However, the role of DcpS and its scavenger decapping activity in neuronal development is unknown. Here, we show that human neurons derived from patients with a DcpS mutation have compromised differentiation and neurite outgrowth. Moreover, in the developing mouse neocortex, DcpS is required for the radial migration, polarity, neurite outgrowth, and identity of developing glutamatergic neurons. Collectively, these findings demonstrate that the scavenger mRNA decapping activity contributes to multiple pivotal roles in neural development and further corroborate that mRNA metabolism and neocortical pathologies are associated with intellectual disability.

Utility of preoperative comorbidity burden on PROMIS outcomes after lumbar decompression: Cohort matched analysis.

The influence of Charlson Comorbidity Index (CCI) burden on Patient-Reported Outcomes Measurement Information System (PROMIS) outcomes following lumbar decompression (LD) is limited. The objective of this study is to evaluate CCI burden impact on PROMIS outcomes. Retrospective review of elective LD excluding revision or surgeries for infectious, malignant, or traumatic reasons. Demographics and PROMIS scores collected preoperatively and postoperatively up to 2 years included: PROMIS-Physical Function (PF)/Sleep Disturbance (SD)/Pain Interference (PI)/Anxiety (A), VR-12 Physical/Mental Health Composite scores (VR-12 PCS/MCS)/Oswestry Disability Index (ODI). Patients were divided into two groups based on their preoperative CCI score <3 (mild) or ≥4 (moderate to severe). Descriptive statistical analysis and MCID achievement rate calculations were conducted. A total of 182 patients were included: 93 CCI < 3 and 88 CCI ≥ 4. No significant differences were reported across preoperative PROMIS/legacy PROMs or final follow-up (p > 0.05, all). At 6-weeks, VR-12 PCS and ΔPROM scores indicated improved physician function in the CCI < 3 group (p = 0.020 and p = 0.040, respectively). Significant PROMIS-A ΔPROM score at final post-op was noted for CCI < 3 group (p = 0.026). MCID achievement demonstrated no significant differences for PROMIS outcomes and legacy PROMs. Results demonstrated that PROMIS outcomes were not impacted by a greater baseline comorbidity burden. At 6-weeks, the physical function scores were improved for the lower CCI group, and at final reported less anxiety. Our data suggests that comorbidity burden has a limited effect on PROMIS and legacy outcomes in patients undergoing LD.

Do Six-Week Postoperative Patient-Reported Outcomes Predict Long-Term Clinical Outcomes Following Lumbar Decompression?

BACKGROUND: Little research has been done to evaluate the prognostic value of short-term postoperative patient-reported outcomes (PROs) on long-term PROs following lumbar decompression (LD). We evaluated the prognostic value of short-term PROs on long-term PROs through 2 years after LD. METHODS: A single spine surgeon database was retrospectively queried for patients undergoing primary LD with 6-week postoperative PROs reported. The demographics, perioperative traits, and preoperative, 6-month, 1-year, and 2-year PROs were recorded. The PROs included the visual analog scale (VAS) for back pain, VAS for leg pain, PRO measure information system for physical function (PROMIS-PF), and Oswestry disability index. Two-step multivariate linear regression was performed to determine the predictive value of 6-week PROs for the 6-month, 1-year, and 2-year PROs. RESULTS: A total of 277 patients were included. The 6-week Oswestry disability index, VAS for leg pain, and 9-item patient health questionnaire (PHQ-9) are all positive predictors for their respective outcomes at 6 months. Additionally, the 6-week PROMIS-PF was a negative predictor of the 6-month PHQ-9. The 6-week PROMIS-PF positively predicted the PROMIS-PF through 1 year, and the PHQ-9 was a positive predictor of the PHQ-9 at 1 and 2 years postoperatively. CONCLUSIONS: The 6-week postoperative PROs are predictive of the same outcomes at 6 months, the PROMIS-PF is predictive through 1 year, and the PHQ-9 is predictive through 2 years. Determining the predictive value of early postoperative PROs can be helpful in understanding the likely postoperative trajectory following LD and informing patient expectations.

Preoperative motor weakness and the impact on patient reported outcomes in lateral lumbar interbody fusion.

This study measures the impact of preoperative motor weakness (MW) on Patient-Reported Outcome Measures (PROMs) in lateral lumbar interbody fusion (LLIF) patients. Retrospectively-sourced data from a prospectively-maintained, single-surgeon database created two cohorts of LLIF patients: patients with/without documented MW. Demographics/perioperative characteristics/PROMs were collected preoperatively and at six-weeks/final follow-up (FF). Studied outcomes were Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), 12-Item Short Form (SF-12) Physical/Mental Component Score (PCS/MCS), Patient Health Questionnaire (PHQ-9), Visual Analog Scale Back/Leg Pain (VAS-BP/LP), and Oswestry Disability Index (ODI). Multivariable linear/logistic regression calculated/compared intercohort minimum clinically important difference (MCID). Mean postoperative follow-up time was 11.5 ± 7.52 months. In total, 214 LLIF patients from December 2010 to May 2023 were included, with 149 having documented MW. In Table 1, self-reported gender was significant between cohorts (p < 0.025). Other significant demographic characteristics were smoker status (p < 0.002), diabetes (p < 0.016), and CCI score (p < 0.011). Table 2 shows notably significant perioperative characteristics: spinal pathology (degenerative spondylolisthesis/foraminal stenosis/herniated nucleus pulposus) (p < 0.005, all), estimated blood loss/length of stay/postoperative day (POD)-zero narcotic consumption (p < 0.001, all). Table 3 outcomes/MCID achievement percentages demonstrated insignificant intercohort differences besides a weakly significant FF ODI score (p < 0.036). MW, a frequently reported symptom in spine surgery, is poorly studied in LLIF patients. Thus, this study evaluates MW impact on PROMs and notes no significant differences. However, one exception regarding FF disability scores was recorded. MW did not affect MCID achievement for our patient population. Therefore, the preliminary findings suggest preoperative MW imparts minimal influence on PROMs/MCID in LLIF patients.

Prognostic Value in Preoperative Veterans RAND-12 Mental Component Score on Clinical Outcomes for Patients Undergoing Minimally Invasive Lateral Lumbar Interbody Fusion.

OBJECTIVE: To evaluate the effect of Veterans RAND 12-item health survey mental composite score (VR-12 MCS) on postoperative patient-reported outcome measures (PROMs) after undergoing lateral lumbar interbody fusion. METHODS: Retrospective data from a single-surgeon database created 2 cohorts: patients with VR-12 MCS ≥ 50 or VR-12 MCS < 50. Preoperative, 6-week, and final follow-up (FF)- PROMs including VR-12 MCS/physical composite score (PCS), 12-item Short Form health survey (SF-12) MCS/PCS, Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), Patient Health Questionnaire-9 (PHQ-9), visual analogue scale (VAS)-back/leg pain (VAS-BP/LP), and Oswestry Disability Index (ODI) were collected. ∆6-week and ∆FF-PROMs were calculated. Minimal clinically important difference (MCID) achievement rates were determined from established cutoffs from the literature. For intercohort comparison, chi-square analysis was used for categorical variables, and Student t-test for continuous variables. RESULTS: Seventy-nine patients were included; 25 were in VR-12 MCS < 50. Mean postoperative follow-up time was 17.12 ± 8.43 months. The VR-12 MCS < 50 cohort had worse VR-12 PCS, SF-12 MCS, PROMIS-PF, PHQ-9, VAS-BP, and ODI scores preoperatively (p ≤ 0.014, all), worse VR-12 MCS/PCS, SF-12 MCS, PROMIS-PF, PHQ-9, and ODI scores at 6-week postoperatively (p ≤ 0.039, all), and worse VR-12 MCS, SF-12 MCS, PROMIS-PF, PHQ-9, VAS-BP, VAS-LP, and ODI scores at FF (p ≤ 0.046, all). The VR-12 MCS < 50 cohort showed greater improvement in VR-12 MCS and SF-12 MCS scores at 6 weeks and FF (p ≤ 0.005, all). The VR-12 MCS < 50 cohort experienced greater MCID achievement for VR-12 MCS, SF-12 MCS, and PHQ-9 (p ≤ 0.006, all). CONCLUSION: VR-12 MCS < 50 yielded worse mental health, physical function, pain and disability postoperatively, yet reported greater improvements in magnitude and MCID achievement for mental health.

Severe Preoperative Disability Is Associated With Greater Mental Health Improvements Following Surgery for Degenerative Spondylolisthesis: A Cohort Matched Analysis.

OBJECTIVE: To evaluate preoperative disability's influence on patient-reported outcomes (PROs) following surgery for degenerative spondylolisthesis (DS). METHODS: DS patients who underwent surgical intervention were retrospectively identified from a single-surgeon spine registry. Cohorts based on Oswestry Disability Index (ODI) < 41 (milder disability) and ≥ 41 (severe disability) were created. Demographic differences were accounted for with 1:1 propensity score matching. For the matched sample, perioperative and PRO data were additionally collected. PROs assessed included mental health, physical function, pain, and disability. Pre- and up to 2-year postoperative PROs were utilized. Average time to final follow-up was 15.7 ± 8.8 months. Improvements in PROs and minimal clinically important difference (MCID) rates were calculated. Continuous variables were compared through Student t-test and categorical variables were compared through chi-square tests. RESULTS: Altogether, 214 patients were included with 77 in the milder disability group. The severe disability group had worse postoperative day (POD) 1 pain scores and longer hospital stays (p ≤ 0.038, both). The severe disability group reported worse outcomes pre- and postoperatively (p < 0.011, all), but had greater average improvement in 12-item Short Form health survey mental composite score (SF-12 MCS), 9-Item Patient Health Questionnaire (PHQ-9), visual analogue scale (VAS)-back, and ODI by 6 weeks (p ≤ 0.037, all) and PHQ-9, VAS-back and ODI by final follow-up (p ≤ 0.015, all). The severe disability cohort was more likely to achieve MCID for SF-12 MCS, PHQ-9, and ODI (p ≤ 0.003, all). CONCLUSION: Patients with greater baseline disability report higher POD 1 pain and discharge later than patients with milder disability. While these patients report inferior physical/mental health before and after surgery, they report greater improvements in mental health and disability postoperatively.

Cervical Disk Replacement Versus Anterior Cervical Diskectomy and Fusion: Effect of Procedural Variant on Patients With a Prolonged Preoperative Duration of Symptoms From Disk Herniation.

INTRODUCTION: Patients with a prolonged preoperative symptom duration (PSD) in the setting of cervical disk herniation (DH) may suffer inferior outcomes after surgical intervention. Comparison between anterior cervical diskectomy and fusion (ACDF) versus cervical disk arthroplasty (CDA) in this at-risk population has not yet been conducted. METHODS: Patients undergoing ACDF or CDA for DH with a PSD > 180 days were selected. Six-week (6W) and final follow-up (FF) patient-reported outcome measures (PROMs) as well as magnitude of postoperative improvements (∆PROM) were compared between cohorts using multivariable linear regression. Intercohort achievement rates of minimal clinically important difference (MCID) in each PROM were compared. RESULTS: Seventy-seven of 190 patients were in the CDA cohort. 6W Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) was superior in the CDA cohort. The ACDF cohort demonstrated notable improvements in the 6W Neck Disability Index (NDI), visual analog scale-neck pain (VAS-N), visual analog scale-arm pain (VAS-A), and 9-item Patient Health Questionnaire (PHQ-9). The CDA cohort demonstrated notable improvements in 6W PROMIS-PF, NDI, VAS-N, and VAS-A. FF VAS-A was better in the CDA cohort. The ACDF cohort demonstrated notable improvements in FF PROMIS-PF, NDI, VAS-N, and VAS-A. The CDA cohort demonstrated notable improvements in all FF PROMs. ∆PROM-6W in PROMIS-PF was greater in the CDA cohort. CONCLUSION: Patients with prolonged PSD due to cervical DH demonstrated notable improvements in physical function, disability, pain, and mental health regardless of fusion versus arthroplasty techniques. Accounting for demographic variations, patients undergoing CDA demonstrated a greater magnitude of improvement and superior scores in physical function at the first postoperative follow-up. Rates of clinically tangible improvements in PROMs did not markedly vary by surgical procedure. Patients undergoing CDA may perceive greater early improvements to physical function compared with patients undergoing ACDF for prolonged PSD due to DH.

Impact of Early Depressive Burden on Patient-Reported Outcomes Following Minimally Invasive Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective review. OBJECTIVE: To evaluate mental health influence on minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) patients. SUMMARY OF BACKGROUND DATA: Poor mental health has been postulated to indicate inferior patient perceptions of surgical outcomes in spine literature. Few studies have assessed mental health as a dynamic metric throughout the perioperative period. METHODS: A single-surgeon database was retrospectively searched for patients who underwent primary, elective MIS-TLIF for degenerative or isthmic spondylolisthesis. Summative depressive burden (SDB) was defined by the sum of preoperative and 6-week postoperative 9-item Patient Health Questionnaire (PHQ-9), with Lesser Burden (LB, SDB<10) and Greater Burden (GB, SDB≥10) cohorts. Patient-reported outcomes measures (PROMs) were compared preoperatively, at 6 weeks, and at final postoperative follow-up (11.4±10.9 mo), using Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), Oswestry disability index (ODI), visual analog scale-back (VAS-B), VAS-leg (VAS-L), and PHQ-9. Improvements at 6-week (∆PROM-6W), final follow-up (∆PROM-FF), and minimum clinically important difference (MCID) achievement were compared. RESULTS: The GB cohort consisted of 44 of 105 patients. Demographic variations included older age, higher Charlson comorbidity index, increased hypertension prevalence, and private insurance in the LB cohort (P≤0.018). The LB cohort demonstrated better baseline and 6-week PROMIS-PF/ODI/VAS-L (P≤0.032) and better final PROMIS-PF/ODI/VAS-L/PHQ-9 (P≤0.031). Both cohorts improved in all PROMs at 6 weeks and final follow-up (P≤0.029), except for PROMIS-PF at 6 weeks in the GB cohort. ∆PROM-6W, ∆PROM-FF, and MCID achievement rate for PHQ-9 were greater in the GB cohort (P≤0.001). CONCLUSION: On average, patients undergoing MIS-TLIF for degenerative or isthmic spondylolisthesis improved in all PROMs by final follow-up. Patients with GB suffered inferior perceptions of physical function, disability, and leg pain. MCID rates in mental health were higher for GB cohort. Surgeons are encouraged to adopt a compassionate understanding of depressive burden and educate the patient on possible consequential postoperative outcomes.

Antibiotic use in spine surgery: A narrative review based in principles of antibiotic stewardship.

Background: A growing emphasis on antibiotic stewardship has led to extensive literature regarding antibiotic use in spine surgery for surgical prophylaxis and the treatment of spinal infections. Purpose: This article aims to review principles of antibiotic stewardship, evidence-based guidelines for surgical prophylaxis and ways to optimize antibiotics use in the treatment of spinal infections. Methods: A narrative review of several society guidelines and spine surgery literature was conducted. Results: Antibiotic stewardship in spine surgery requires multidisciplinary investment and consistent evaluation of antibiotic use for drug selection, dose, duration, drug-route, and de-escalation. Developing effective surgical prophylaxis regimens is a key strategy in reducing the burden of antibiotic resistance. For treatment of primary spinal infection, the diagnostic work-up is vital in tailoring effective antibiotic therapy. The future of antibiotics in spine surgery will be highly influenced by improving surgical technique and evidence regarding the role of bacteria in the pathogenesis of degenerative spinal pathology. Conclusions: Incorporating evidence-based guidelines into regular practice will serve to limit the development of resistance while preventing morbidity from spinal infection. Further research should be conducted to provide more evidence for surgical site infection prevention and treatment of spinal infections.

The Veterans Rand-12 Physical Composite Score Prognosticates Postoperative Clinical Outcomes in Patients Undergoing Anterior Cervical Discectomy and Fusion.

OBJECTIVE: To determine prognostic value of preoperative Veterans RAND 12-Item Health Survey (VR-12) physical composite score (PCS) on outcomes in patients undergoing anterior cervical discectomy and fusion (ACDF). METHODS: ACDF patients with preoperative VR-12 PCS formed 2 cohorts: VR-12 PCS <35 and VR-12 PCS ≥35. The following patient-reported outcome measures (PROMs) were gathered preoperatively and postoperatively up to 2 years: VR-12 mental composite score (MCS)/PCS, Neck Disability Index (NDI), Patient-Reported Outcomes Measurement Information System (PROMIS) PF, 9-Item Patient Health Questionnaire (PHQ-9), visual analog scale (VAS) neck/arm pain, and 12-Item Short Form Health Survey (SF-12) PCS/MCS. Comparing PROMs change with established thresholds determined achievement of minimum clinically important difference (MCID). Univariate analysis compared demographics, perioperative characteristics, and preoperative PROMs. Multivariable regression analysis compared postoperative PROMs and MCID achievement. RESULTS: Of 174 patients, 83 had VR-12 PCS <35. Preoperatively, patients with reduced PF displayed lower patient-reported outcome scores in NDI, PHQ-9, and SF-12 MCS (P ≤ 0.008), but not in VAS arm. At 6 weeks postoperatively, these patients continued to score lower in NDI (P ≤ 0.014) and SF-12 PCS (P ≤ 0.001), among others. By the final check, most scores remained lower (P ≤ 0.002) except for PHQ-9 and VAS arm (P > 0.05). Greater improvements at 6 weeks postoperatively were especially noted in patients with lower initial VR-12 PCS for NDI, PROMIS PF, and SF-12 PCS (P < 0.05). However, by final follow-up, only PROMIS PF showed noteworthy improvement (P = 0.19). Regarding MCID achievement, significant differences were largely absent except in NDI, where patients with reduced PF exhibited more MCID achievement (P = 0.016). CONCLUSIONS: ACDF patients with VR-12 PCS <35 experienced inferior PF, mental health, and disability postoperatively until final follow-up. There were no significant differences in postoperative improvement magnitude and MCID achievement. Results suggest that baseline VR-12 PCS in ACDF patients may indicate poorer PF, mental health, and disability postoperatively. However, VR-12 PCS does not limit extent of postoperative improvement.