Preoperative HbA1c and Postoperative Outcomes in Spine Surgery: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To perform a systematic review and meta-analysis of previous studies on HbA1c in preoperative risk stratification in patients undergoing spinal procedures and provide an overview of the consensus recommendations. SUMMARY OF BACKGROUND DATA: Diabetes mellitus (DM) and hyperglycemia have been shown to be independent risk factors for increased surgical complications. Glycated Hemoglobin A1C (HbA1c), a surrogate for long term glycemic control, is an important preoperative parameter that may be optimized to reduce surgical complications and improve patient-reported outcomes. However, comprehensive systematic reviews on preoperative HbA1c and postoperative outcomes in spine surgery have been limited. METHODS: We systematically searched PubMed, EMBASE, Scopus, and Web-of-Science for English-language studies from inception through April 5 th , 2022, including references of eligible articles. The search was conducted according to PRISMA guidelines. Only studies in patients undergoing spine surgery with preoperative HbA1c values and postoperative outcomes available were included. RESULTS: A total of 22 articles (18 retrospective cohort studies, 4 prospective observational studies) were identified with level of evidence III or greater. The majority of studies (n=17) found that elevated preoperative HbA1c was associated with inferior outcomes or increased risk of complications. Random-effect meta-analysis demonstrated that patients with preoperative HbA1c >8.0% had increased risk(s) of postoperative complications (RR: 1.85, 95% CI: [1.48, 2.31], P <0.01) and that patients with surgical site infection (SSI) had higher preoperative HbA1c (Mean Difference: 1.49%, 95% CI: [0.11, 2.88], P =0.03). CONCLUSION: The findings of this study suggest that HbA1c >8.0% is associated with an increased risk of complications. HbA1c was higher by 1.49% on average among patients with SSI when compared to patients who did not experience SSI. These results suggest that elevated HbA1c is associated with less favorable outcomes following spine surgery. LEVEL OF EVIDENCE: IV.

Bariatric Surgery Before Spine Surgery is Associated With Fewer Postsurgical Complications: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To perform a systematic review and meta-analysis investigating the rate of adverse events after spine surgery in patients who underwent bariatric surgery (BS). SUMMARY OF BACKGROUND DATA: Obesity is an established risk factor for postoperative complications after spine surgery. BS has been associated with improvements in health in patients with severe obesity. However, it is not known whether undergoing BS before spine surgery is associated with reduced adverse outcomes. MATERIALS AND METHODS: PubMed, EMBASE, Scopus, and Web-of-Science were systematically searched according to "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" guidelines. The search included indexed terms and text words from database inception to the date of the search (May 27, 2022). Data and estimates were pooled using the Mantel-Haenszel method for random-effects meta-analysis. Risk of bias was assessed using the Joanna Briggs Institute risk of bias tool. The primary outcome was an all-cause complication rate after surgery. Relative risks for surgical and medical complications were assessed. RESULTS: A total of 4 studies comprising 177,273 patients were included. The pooled analysis demonstrated that the all-cause medical complication rate after spine surgery was lower in patients undergoing BS (relative risk: 0.54, 95% CI: 0.39, 0.74, P < 0.01). There was no difference in rates of surgical complications and 30-day hospital readmission rates between the cohort undergoing BS before spine surgery and the cohort that did not. CONCLUSION: These analyses suggest that obese patients undergoing BS before spine surgery have significantly lower adverse event rates. Future prospective studies are needed to corroborate these findings. LEVEL OF EVIDENCE: 4.

Do Obese Patients Lose Weight After Lumbar Spine Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: Obesity is a major health care concern in the United States and is associated with high rates of postoperative complications after spine surgery. Obese patients assert that weight reduction is not possible unless spine surgery first relieves their pain and concomitant immobility. We describe the post-spine surgery effects on patient weight, with an emphasis on obesity. METHODS: PubMed, EMBASE, Scopus, Web of Science, and Cochrane databases were systematically searched according to the PRISMA guidelines. The search included indexed terms and text words from database inception to the date of the search (15 April 2022). Studies chosen for inclusion had to have data reporting on pre- and postoperative patient weight after spine surgery. Data and estimates were pooled using the Mantel-Haenszel method for random-effects meta-analysis. RESULTS: Eight articles encompassing 7 retrospective and 1 prospective cohort were identified. A random effects model analysis demonstrated that overweight and obese patients (body mass index [BMI], >25 kg/m2) had increased odds of clinically significant weight loss after lumbar spine surgery compared with non-obese patients (odds ratio, 1.63; 95% confidence interval, 1.43-1.86, P < 0.0001). There was no significant difference in the raw weight change between BMI categories (mean difference, -0.67 kg, 95% confidence interval, -4.71 to 3.37 kg, P = 0.7463). CONCLUSIONS: Compared with non-obese patients (BMI, <25 kg/m2), overweight and obese patients have higher odds of clinically significant weight loss after lumbar spine surgery. No difference in pre-operative and post-operative weight was found, although statistical power was lacking in this analysis. Randomized controlled trials and additional prospective cohorts are needed to further validate these findings.

Extended Combined Neonatal Treatment With Erythropoietin Plus Melatonin Prevents Posthemorrhagic Hydrocephalus of Prematurity in Rats.

Posthemorrhagic hydrocephalus of prematurity (PHHP) remains a global challenge. Early preterm infants (<32 weeks gestation), particularly those exposed to chorioamnionitis (CAM), are prone to intraventricular hemorrhage (IVH) and PHHP. We established an age-appropriate, preclinical model of PHHP with progressive macrocephaly and ventriculomegaly to test whether non-surgical neonatal treatment could modulate PHHP. We combined prenatal CAM and postnatal day 1 (P1, equivalent to 30 weeks human gestation) IVH in rats, and administered systemic erythropoietin (EPO) plus melatonin (MLT), or vehicle, from P2 to P10. CAM-IVH rats developed progressive macrocephaly through P21. Macrocephaly was accompanied by ventriculomegaly at P5 (histology), and P21 (ex vivo MRI). CAM-IVH rats showed impaired performance of cliff aversion, a neonatal neurodevelopmental test. Neonatal EPO+MLT treatment prevented macrocephaly and cliff aversion impairment, and significantly reduced ventriculomegaly. EPO+MLT treatment prevented matted or missing ependymal motile cilia observed in vehicle-treated CAM-IVH rats. EPO+MLT treatment also normalized ependymal yes-associated protein (YAP) mRNA levels, and reduced ependymal GFAP-immunolabeling. Vehicle-treated CAM-IVH rats exhibited loss of microstructural integrity on diffusion tensor imaging, which was normalized in EPO+MLT-treated CAM-IVH rats. In summary, combined prenatal systemic inflammation plus early postnatal IVH caused progressive macrocephaly, ventriculomegaly and delayed development of cliff aversion reminiscent of PHHP. Neonatal systemic EPO+MLT treatment prevented multiple hallmarks of PHHP, consistent with a clinically viable, non-surgical treatment strategy.

Repetitive Neonatal Erythropoietin and Melatonin Combinatorial Treatment Provides Sustained Repair of Functional Deficits in a Rat Model of Cerebral Palsy.

Cerebral palsy (CP) is the leading cause of motor impairment for children worldwide and results from perinatal brain injury (PBI). To test novel therapeutics to mitigate deficits from PBI, we developed a rat model of extreme preterm birth (<28 weeks of gestation) that mimics dual intrauterine injury from placental underperfusion and chorioamnionitis. We hypothesized that a sustained postnatal treatment regimen that combines the endogenous neuroreparative agents erythropoietin (EPO) and melatonin (MLT) would mitigate molecular, sensorimotor, and cognitive abnormalities in adults rats following prenatal injury. On embryonic day 18 (E18), a laparotomy was performed in pregnant Sprague-Dawley rats. Uterine artery occlusion was performed for 60 min to induce placental insufficiency via transient systemic hypoxia-ischemia, followed by intra-amniotic injections of lipopolysaccharide, and laparotomy closure. On postnatal day 1 (P1), approximately equivalent to 30 weeks of gestation, injured rats were randomized to an extended EPO + MLT treatment regimen, or vehicle (sterile saline) from P1 to P10. Behavioral assays were performed along an extended developmental time course (n = 6-29). Open field testing shows injured rats exhibit hypermobility and disinhibition and that combined neonatal EPO + MLT treatment repairs disinhibition in injured rats, while EPO alone does not. Furthermore, EPO + MLT normalizes hindlimb deficits, including reduced paw area and paw pressure at peak stance, and elevated percent shared stance after prenatal injury. Injured rats had fewer social interactions than shams, and EPO + MLT normalized social drive. Touchscreen operant chamber testing of visual discrimination and reversal shows that EPO + MLT at least partially normalizes theses complex cognitive tasks. Together, these data indicate EPO + MLT can potentially repair multiple sensorimotor, cognitive, and behavioral realms following PBI, using highly translatable and sophisticated developmental testing platforms.