Branko Skovrlj

Outcomes and complications of diabetes mellitus on patients undergoing degenerative lumbar spine surgery.

Study Design. Retrospective database analysis. Objective. To assess the effect glycemic control has on perioperative morbidity and mortality in patients undergoing elective degenerative lumbar spine surgery. Summary of Background Data. Diabetes mellitus (DM) is a prevalent disease of glucose dysregulation that has been demonstrated to increase morbidity and mortality after spine surgery. However, there is limited understanding of whether glycemic control influences surgical outcomes in patients with DM undergoing lumbar spine procedures for degenerative conditions. Methods. The Nationwide Inpatient Sample was analyzed from 2002 to 2011. Hospitalizations were isolated on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification, procedural codes for lumbar spine surgery and diagnoses codes for degenerative conditions of the lumbar spine. Patients were then classified into 3 cohorts: controlled diabetic, uncontrolled diabetic, and nondiabetic. Patient demographic data, acute complications, and hospitalization outcomes were determined for each cohort. Results. A total of 403,629 (15.7%) controlled diabetic patients and 19,421 (0.75%) uncontrolled diabetic patients underwent degenerative lumbar spine surgery from 2002 to 2011. Relative to nondiabetic patients, uncontrolled diabetic patients had significantly increased odds of cardiac complications, deep venous thrombosis, and postoperative shock; in addition, uncontrolled diabetic patients also had an increased mean length of stay (approximately, 2.5 d), greater costs (1.3-fold), and a greater risk of inpatient mortality (odds ratio = 2.6, 95% confidence interval = 1.5–4.8, P < 0.0009). Controlled diabetic patients also had increased risk of acute complications and inpatient mortality when compared with nondiabetic patients, but not nearly to the same magnitude as uncontrolled diabetic patients. Conclusion. Suboptimal glycemic control in diabetic patients undergoing degenerative lumbar spine surgery leads to increased risk of acute complications and poor outcomes. Patients with uncontrolled DM, or poor glucose control, may benefit from improving glycemic control prior to surgery. Level of Evidence: 3

Complications, outcomes, and need for fusion after minimally invasive posterior cervical foraminotomy and microdiscectomy

BACKGROUND CONTEXT Posterior cervical foraminotomy (PCF) with or without microdiscectomy (posterior cervical discectomy [PCD]) is a frequently used surgical technique for cervical radiculopathy secondary to foraminal stenosis or a laterally located herniated disc. Currently, these procedures are being performed with increasing frequency using advanced minimally invasive techniques. Although the safety and efficacy of minimally invasive PCF/PCD (MI-PCF/PCD) have been established, reports on long-term outcome and need for secondary surgical intervention at the index or adjacent level are lacking. PURPOSE To determine the rates of complications, long-term outcomes, and need for secondary surgical intervention at the index or adjacent level after MI-PCF and microdiscectomy. STUDY DESIGN Retrospective analysis of a prospective cohort. PATIENT SAMPLE Seventy patients treated with MI-PCF and/or MI-PCD for cervical radiculopathy. OUTCOME MEASURES Visual Analog Scale for neck/arm (VASN/A) pain and Neck Disability Index (NDI). METHODS Ninety-seven patients underwent MI-PCF with or without MI-PCD between 2002 and 2011. Adequate prospective follow-up was available for 70 patients (95 cervical levels). The primary outcome assessed was need for secondary surgical intervention at the index or adjacent level. The secondary outcomes assessed included complications and improvements in NDI and VASN/A scores. All complications were reviewed. Mixed-model analyses of variance with random subject effects and autoregressive first-order correlation structures were used to test for differences among NDI, VASA, and VASN measurements made over time while accounting for the correlation among repeated observations within a patient. All statistical hypothesis tests were conducted at the 5% level of significance. RESULTS Patients were followed for a mean of 32.1 months. Of 70 patients operated, there were 3 (4.3%) complications (1 cerebrospinal fluid leak, 1 postoperative wound hematoma, and 1 radiculitis), none of which required a secondary operative intervention. Five patients required an anterior cervical discectomy and fusion (eight total levels fused) on average 44.4 months after the index surgery. Of those, five (5.3%) were at the index level and three (2.1%) were at adjacent levels. Neck Disability Index scores improved significantly (p<.0001) immediately postoperatively and continued to decrease gradually with time. Visual Analog Scale for neck/arm scores improved significantly (p<.0001) from baseline immediately postoperatively but tended to plateau with time. CONCLUSIONS Minimally invasive PCF with or without MI-PCD is an excellent alternative for cervical radiculopathy secondary to foraminal stenosis or a laterally located herniated disc. There is a low rate (1.1% per index level per year) of future index site fusion and a very low rate (0.9% per adjacent level per year) of adjacent-level disease requiring surgery.

Frailty Index Is a Significant Predictor of Complications and Mortality After Surgery for Adult Spinal Deformity

Study Design. Retrospective study of prospectively collected data. Objective. To determine if the modified Frailty Index (mFI) could be used to predict postoperative complications in patients undergoing surgery for adult spinal deformity (ASD). Summary of Background Data. Surgery for patients with ASD is associated with high complication rates and significant concerns present during risk stratification with older patients. The mFI is an evaluation tool to describe the frailness of an individual and how their preoperative status may impact postoperative survival and outcomes. Using a large nationwide database, we assessed the utility of this instrument in patients undergoing surgery for ASD. Methods. The American College of Surgeons National Surgical Quality Improvement Program is a large multicenter clinical registry that prospectively collects preoperative variables, patient demographics, operative factors, and 30-day postoperative morbidity and mortality outcomes from about 400 hospitals nationwide. Current Procedural Terminology codes were used to query the database for adults who underwent fusion for spinal deformity. The previously described mFI was calculated based on the number of positive factors and univariate and multivariate logistic regression analysis were used to analyze the risk factors associated with mortality. Results. Overall, 1001 patients were identified and the mean mFI score was 0.09 (range: 0–0.545). Increasing mFI score was associated with higher complication, reoperation, and mortality rates (P < 0.05). mFI of 0.09 and 0.18 was an independent predictor of any complication, mortality, requiring a blood transfusion, pulmonary embolism/deep vein thrombosis, and reoperation (all P < 0.05). In comparison with age >60 years obesity class III, mFI was a superior predictor of several postoperative complications and reoperation. Conclusion. Frailty was an independent predictor of postoperative complications, mortality, and reoperation in patients undergoing surgery for ASD. Preoperative assessment of the mFI in this patient population can be utilized to improve current risk models. Level of Evidence: 3

The impact of diabetes mellitus on patients undergoing degenerative cervical spine surgery.

Study Design. Retrospective administrative database analysis. Objective. To determine the impact of glycemic control on perioperative complications and outcomes in patients undergoing degenerative cervical spine surgery. Summary of Background Data. Diabetes mellitus (DM) is a highly prevalent systemic disease that has been shown to increase morbidity and mortality after spine surgery. Few studies have demonstrated negative effects on patients with DM who undergo cervical spine procedures; however, whether glycemic control influences surgical outcome is still unknown. Methods. The Nationwide Inpatient Sample was queried from 2002 to 2011. Patients who underwent cervical spine surgery for degenerative conditions were identified using the International Classification of Diseases Ninth Revision, Clinical Modification, codes. Three surgical cohorts were chosen: controlled diabetic, uncontrolled diabetic, and patients without diabetes. Patient demographics, surgical procedures, perioperative complications and postoperative outcomes were assessed. Results. The prevalence of controlled and uncontrolled diabetic patients undergoing degenerative cervical spine surgery had been increasing significantly from 2002 to 2011. Compared with patients without diabetes, uncontrolled diabetic patients had significantly increased odds of respiratory, cardiac, and genitourinary complications. Uncontrolled diabetic patients also had significantly increased risk of pulmonary embolism and postoperative infection. Uncontrolled diabetic patients had increased risk of inpatient mortality (odds ratio = 6.39, 95% confidence interval = 4.09–10.00, P < 0.0001) and increased mean length of stay (almost 5 d) compared with nondiabetic patients. Similarly, controlled diabetic patients increased the odds of perioperative complications; however not nearly to the same degree. Controlled diabetic patients extended the mean length of stay by almost a day (P < 0.0001) and significantly increased costs compared with nondiabetic patients. Conclusion. Poor glycemic control increases the odds of inpatient mortality and perioperative complications in patients undergoing degenerative cervical spine surgery. Controlling DM before degenerative cervical spine surgery may lead to better outcomes and decreased costs. Level of Evidence: Therapeutic Level 3

Association Between BMP-2 and Carcinogenicity.

Study Design. Literature review. Objective. To evaluate the association between recombinant human bone morphogenetic protein-2 (rhBMP-2) and malignancy. Summary of Background Data. The use of rhBMP-2 in spine surgery has been the topic of much debate as studies assessing the association between rhBMP-2 and malignancy have come to conflicting conclusions. Methods. A systematic review of the literature was performed using the PubMed-National Library of Medicine/National Institute of Health databases. Only non-clinical studies directly addressing BMP-2 and cancer were included. Articles were categorized by study type (animal, in vitro cell line/human/animal), primary malignancy, cancer attributes, and whether BMP-2 was pro-malignancy or not. Results. A total of 4,131 articles were reviewed. Of those, 515 articles made reference to both BMP-2 and cancer, 99 of which were found to directly examine the role of BMP-2 in cancer. Seventy-five studies were in vitro and 24 were animal studies. Forty-three studies concluded that BMP-2 enhanced cancer function, whereas 18 studies found that BMP-2 suppressed malignancy. Thirty-six studies did not examine whether BMP-2 enhanced or suppressed cancer function. Fifteen studies demonstrated BMP-2 dose dependence (9 enhancement, 6 suppression) and one study demonstrated no dose dependence. Nine studies demonstrated BMP-2 time dependence (6 enhancement, 3 suppression). However, no study demonstrated that BMP-2 caused cancer de novo. Conclusion. Currently, conflicting data exist with regard to the effect of exogenous BMP-2 on cancer. The majority of studies addressed the role of BMP-2 in prostate (17%), breast (17%), and lung (15%) cancers. Most were in vitro studies (75%) and examined cancer invasiveness and metastatic potential (37%). Of 99 studies, there was no demonstration of BMP-2 causing cancer de novo. However, 43% of studies suggested that BMP-2 enhances tumor function, motivating more definitive research on the topic that also includes clinically meaningful dose- and time-dependence. Level of Evidence: 2

The Top 100 Classic Papers in Lumbar Spine Surgery

Study Design. Bibliometric review of the literature. Objective. To analyze and quantify the most frequently cited papers in lumbar spine surgery and to measure their impact on the entire lumbar spine literature. Summary of Background Data. Lumbar spine surgery is a dynamic and complex field. Basic science and clinical research remain paramount in understanding and advancing the field. While new literature is published at increasing rates, few studies make long-lasting impacts. Methods. The Thomson Reuters Web of Knowledge was searched for citations of all papers relevant to lumbar spine surgery. The number of citations, authorship, year of publication, journal of publication, country of publication, and institution were recorded for each paper. Results. The most cited paper was found to be the classic paper from 1990 by Boden et al that described magnetic resonance imaging findings in individuals without back pain, sciatica, and neurogenic claudication showing that spinal stenosis and herniated discs can be incidentally found when scanning patients. The second most cited study similarly showed that asymptomatic patients who underwent lumbar spine magnetic resonance imaging frequently had lumbar pathology. The third most cited paper was the 2000 publication of Fairbank and Pynsent reviewing the Oswestry Disability Index, the outcome-measure questionnaire most commonly used to evaluate low back pain. The majority of the papers originate in the United States (n = 58), and most were published in Spine (n = 63). Most papers were published in the 1990s (n = 49), and the 3 most common topics were low back pain, biomechanics, and disc degeneration. Conclusion. This report identifies the top 100 papers in lumbar spine surgery and acknowledges those individuals who have contributed the most to the advancement of the study of the lumbar spine and the body of knowledge used to guide evidence-based clinical decision making in lumbar spine surgery today. Level of Evidence: 3

Patient-Reported Outcome Instruments in Spine Surgery.

Study Design. A critical review of the current literature. Objective. The purpose of this study was to determine frequency, trends, and methods of utilization of spine-related PROIs over the last 10 years. Summary of Background Data. . Patient-reported outcome instruments (PROIs) have become the gold standard to assess the efficacy of various medical and surgical treatments. Currently, however, there is an expansive range of PROIs without a clear consensus or guideline addressing which PROIs should be used for a particular diagnosis or surgical intervention. Methods. A PubMed search was conducted from 2004 to 2013 of 5 orthopedic journals (The Journal of Bone and Joint Surgery, The Bone and Joint Journal, The Spine Journal, The European Spine Journal, and Spine) that publish spine articles, chosen on the basis of readership and impact factor. Journal abstracts were inspected for spine surgery and inclusion of at least 1 PROI. All articles containing PROIs and investigating a surgical intervention with a level of evidence (LOE) 1 to 4 were included for analysis. Article title, LOE, journal, and chosen PROI were recorded for selected articles. Results. Out of 19,736 articles published in our selected time frame, 1,079 utilized PROIs. Most studies were LOE 4 (32.7%). Nearly half (48.9%) of all articles addressed degenerative thoracolumbar conditions. In total, there were 206 unique PROIs in the studies chosen for inclusion. The top 6 instruments utilized were the (1) visual analog scale, (2) Oswestry disability index, (3) Short Form-36, (4) Japanese Orthopaedic Association Outcome Questionnaire, (5) Neck Disability Index, and (6) Scoliosis Research Society-22. Conclusion. The breadth of PROIs in spine surgery is extensive. Although there are preferred patient-reported outcome measures, a consensus or guideline addressing which instruments should be used for a particular diagnosis or procedure may be warranted. Level of Evidence: 4

Impact of Gender on 30-Day Complications After Adult Spinal Deformity Surgery.

Study Design. Retrospective study of prospectively collected data. Objective. To determine if postoperative morbidity for patients undergoing spinal deformity surgery varies by sex. Summary of Background Data. Influence of sex has been investigated in other surgical procedures but has not yet been studied in adult spinal deformity surgery. Methods. The American College of Surgeons National Surgical Quality Improvement Program is a large multicenter clinical registry that prospectively collects preoperative risk factors, intraoperative variables, and 30-day postoperative morbidity and mortality outcomes from about 400 hospitals nationwide. Current Procedural Terminology codes were used to query the database for adults who underwent fusion for spinal deformity. Patients were separated into groups of male and female sex. Univariate analysis and multivariate logistic regression were used to analyze the effect of sex on the incidence of postoperative morbidity and mortality. Results. Female sex was found to be a predictor of any complication[odds ratio (OR): 1.4, 95% confidence interval (CI) 1.2–1.7, P < 0.0001], intra- or postoperative RBC transfusion (OR: 1.6, 95% CI 1.4–1.9, P < .0001), urinary tract infection (OR: 2.0, 95% CI 1.2–3.3, P = 0.0046), and length of stay >5 days (OR: 1.3, 95% CI 1.1–1.5, P = 0.0015). Male sex was associated with higher rate of pulmonary (2.9% vs. 2.0%, P = 0.0344) and cardiac complications (0.9% vs. 0.5%, P = 0.0497). However, male sex as an independent risk factor for pulmonary (OR: 1.4, 95% CI 1.0–2.1, P = 0.0715) and cardiac complications (OR: 1.9, 95% CI 0.9–4.0, P = 0.1076) did not reach significance. Conclusion. Female sex was found to increase overall morbidity, particularly for urinary tract infection, transfusion, and length of stay >5 days. Male sex was associated with greater incidence of pulmonary and cardiac complications. Thus, sex and other patient characteristics highlighted must be considered as part of surgical risk planning and patient counseling. Level of Evidence: 3

Assessment of Functional and Behavioral Changes Sensitive to Painful Disc Degeneration

The development of an in vivo rodent discogenic pain model can provide insight into mechanisms for painful disc degeneration. Painful disc degeneration in rodents can be inferred by examining responses to external stimuli, observing pain‐related behaviors, and measuring functional performance. This study compared the sensitivity of multiple pain and functional assessment methods to disc disruption for identifying the parameters sensitive to painful disc degeneration in rats. Disc degeneration was induced in rats by annular injury with saline injection. The severity of disc degeneration, pain sensitivity, and functional performance were compared to sham and naïve control rats. Saline injection induced disc degeneration with decreased disc height and MRI signal intensity as well as more fibrous nucleus pulposus, disorganized annular lamellae and decreased proteoglycan. Rats also demonstrated increased painful behaviors including decreased hindpaw mechanical and thermal sensitivities, increased grooming, and altered gait patterns with hindpaw mechanical hyperalgesia and duration of grooming tests being most sensitive. This is the first study to compare sensitivities of different pain assessment methods in an in vivo rat model of disc degeneration. Hindpaw mechanical sensitivity and duration of grooming were the most sensitive parameters to surgically induced degenerative changes and overall results were suggestive of disc degeneration associated pain.

Annular puncture with tumor necrosis factor-alpha injection enhances painful behavior with disc degeneration in vivo

BACKGROUND CONTEXT Painfulintervertebral disc degeneration is extremely common and costly. Effective treatments are lacking because the nature of discogenic pain is complex with limited capacity to distinguish painful conditions from age-related changes in the spine. Hypothesized sources of discogenic pain include chronic inflammation, neurovascular ingrowth, and structural disruption. PURPOSE This study aimed to investigate inflammation, pro-neurovascular growth factors, and structural disruption as sources of painful disc degeneration STUDY DESIGN/SETTING This study used an in vivo study to address these hypothesized mechanisms with anterior intradiscal injections of tumor necrosis factor-alpha (TNFα), pro-neurovascular growth factors: nerve growth factor and vascular endothelial growth factor (NGF and VEGF), and saline with additional sham surgery and naïve controls. Depth of annular puncture was also evaluated for its effects on structural and painful degeneration. METHODS Rat lumbar discs were punctured (shallow or deeper puncture) and intradiscally injected with saline, TNFα, or NGF and VEGF. Structural disc degeneration was assessed using X-ray, magnetic resonance imaging (MRI), and histology. The rat painful condition was evaluated using Von Frey hyperalgesia measurements, and substance P immunostaining in dorsal root ganglion (DRG) was performed to determine the source of pain. RESULTS Saline injection increased painful responses with degenerative changes in disc height, MRI intensity, and morphologies of disc structure and cell. TNFα and NGF/VEGF accelerated painful behavior, and TNFα-injected animals had increased substance P in DRGs. Deeper punctures led to more severe disc degeneration. Multiple regression analysis showed that the painful behavior was correlated with disc height loss. CONCLUSIONS We concluded that rate and severity of structural disc degeneration was associated with the amount of annular disruption and puncture depth. The painful behavior was associated with disc height loss and discal inflammatory state, whereas pro-inflammatory cytokines might play a more important role in the level of pain, which might have resulted from enhanced DRG sensitization. These in vivo painful disc degeneration models with different severities of structural changes may be useful for investigating discogenic pain mechanisms and for screening therapies, although interpretations must note the differences between all surgically induced animal models and the human condition.