Overweight and smoking promote recurrent lumbar disk herniation after discectomy.

PURPOSE: Recurrent lumbar disk herniation (rLDH) following lumbar microdiscectomy is common. While several risk factors for primary LDH have been described, risk factors for rLDH have only sparsely been investigated. We evaluate the effect of Body mass index (BMI) and smoking on the incidence and timing of rLDH. METHODS: From a prospective registry, we identified all patients undergoing primary tubular microdiscectomy (tMD), with complete BMI and smoking data, and a minimum 12-month follow-up. We defined rLDH as reherniation at the same level and side requiring surgery. Overweight was defined as BMI > 25, and obesity as BMI > 30. Intergroup comparisons and age- and gender-adjusted multivariable regression were carried out. We conducted a survival analysis to assess the influence of BMI and smoking on time to reoperation. RESULTS: Of 3012 patients, 166 (5.5%) underwent re-microdiscectomy for rLDH. Smokers were reoperated more frequently (6.4% vs. 4.0%, p = 0.007). Similarly, rLDH was more frequent in obese (7.5%) and overweight (5.9%) than in normal-weight patients (3.3%, p = 0.017). Overweight smokers had the highest rLDH rate (7.6%). This effect of smoking (Odds ratio: 1.63, 96% CI: 1.12-2.36, p = 0.010) and BMI (Odds ratio: 1.09, 95% CI: 1.02-1.17, p = 0.010) persisted after controlling for age and gender. Survival analysis demonstrated that rLDH did not occur earlier in overweight patients and/or smokers. CONCLUSIONS: BMI and smoking may directly contribute to a higher risk of rLDH, but do not accelerate rLDH development. Smoking cessation and weight loss in overweight or obese patients ought to be recommended with discectomy to reduce the risk for rLDH.

Association of age with incidence and timing of recurrence after microdiscectomy for lumbar disc herniation.

OBJECTIVE: Recurrent lumbar disc herniation (LDH) is the most frequent reason for reoperation after lumbar microdiscectomy. While several risk factors for recurrent LDH have been well-described, the effect of age on recurrence remains unclear, especially concerning the timing of recurrent LDH. METHODS: From a prospective registry, we identified all patients who underwent tubular microdiscectomy for LDH. Recurrent LDH was defined as reoperation for LDH at the same index level and side. The associations among age and incidence of recurrent LDH as well as on time to recurrent LDH were statistically evaluated using multivariable analysis of covariance, linear regression, and Cox proportional hazards modelling. RESULTS: Of the 3013 patients who underwent surgery for LDH, 166 (5.5%) had to undergo reoperation due to LDH recurrence. Uni- and multivariable analysis revealed no influence of age on the incidence of recurrent LDH (both p > 0.05). Linear regression indicated earlier reoperation in older patients, both with (ß = -0.248) and without (ß = -0.374) correction for confounders (both p < 0.05). An additional survival analysis found that patients aged over 35 years had recurrent LDH significantly earlier (hazard ratio 0.617, p = 0.013). CONCLUSION: In an analysis of a large prospective database of patients undergoing microdiscectomy for lumbar disc herniation, we found that younger patients do not have a higher reoperation probability than their older counterparts, even after correcting for multiple confounders. However, older patients tend to experience recurrent LDH significantly earlier after the index surgery compared to younger patients.

Influence of dynamic preoperative body mass index changes on patient-reported outcomes after surgery for degenerative lumbar spine disease.

Psychological factors demonstrably and often massively influence outcomes of degenerative spine surgery, and one could hypothesize that preoperative weight loss may correlate with motivation and lifestyle adjustment, thus leading to potentially enhanced outcomes. We aimed to evaluate the effect of preoperative weight loss or gain, respectively, on patient-reported outcomes after lumbar spine surgery. Weight loss was defined as a BMI decrease of ≤ - 0.5 kg/m2 over a period of at least 1 month, and weight gain as a BMI increase of ≥ 0.5 kg/m2 in the same time period, respectively. The primary endpoint was set as the achievement of the minimum clinically important difference (MCID) in the ODI at 1 or 2 years postoperatively. A total of 154 patients were included. Weight loss (odds ratio (OR): 1.18, 95% confidence interval (CI): 0.52 to 2.80) and weight gain (OR: 1.03, 95% CI: 0.43 to 2.55) showed no significant influence on MCID achievement for ODI compared to a stable BMI. The same results were observed when analysing long-term NRS-BP and NRS-LP. Regression analysis showed no correlation between BMI change and PROM change scores for any of the three PROMs. Adjustment for age and gender did not alter results. Our findings suggest that both preoperative weight loss and weight gain may have no measurable effect on long-term postoperative outcome compared to a stable BMI. Weight loss preoperatively-as a potential surrogate sign of patient motivation and lifestyle change-may thus not influence postoperative outcomes.

Distinct changes in all major components of the neurovascular unit across different neuropathological stages of Alzheimer's disease.

In the brain capillaries, endothelial cells, pericytes, astrocytes and microglia form a structural and functional complex called neurovascular unit (NVU) which is critically involved in maintaining neuronal homeostasis. In the present study, we applied a comprehensive immunohistochemical approach to investigate the structural alterations in the NVU across different Alzheimer's disease (AD) neuropathological stages. Post-mortem human cortical and hippocampal samples derived from AD patients and non-demented elderly control individuals were immunostained using a panel of markers representing specific components of the NVU including Collagen IV (basement membrane), PDGFR-ß (pericytes), GFAP (astrocytes), Iba1 (microglia), MRC1 (perivascular macrophages) and lectin as an endothelial cell label. Astrocytes (GFAP) and microglia (Iba1) were quantified both in the whole visual-field and specifically within the NVU, and the sample set was additionally analyzed using anti-tau (AT8) and three different anti-Aß (clones G2-10, G2-11, 4G8) antibodies. Analyses of lectin labeled sections showed an altered vascular distribution in AD patients as revealed by a reduced nearest distance between capillaries. Within the NVU, a Braak-stage dependent reduction in pericyte coverage was identified as the earliest structural alteration during AD progression. In comparison to non-demented elderly controls, AD patients showed a significantly higher astrocyte coverage within the NVU, which was paralleled by a reduced microglial coverage around capillaries. Assessment of perivascular macrophages moreover demonstrated a relocation of these cells from leptomeningeal arteries to penetrating parenchymal vessels in AD patients. Collectively, the results of our study represent a comprehensive first in-depth analysis of AD-related structural changes in the NVU and suggest distinct alterations in all components of the NVU during AD progression.

Timing of Surgery in Tubular Microdiscectomy for Lumbar Disc Herniation and Its Effect on Functional Impairment Outcomes.

OBJECTIVE: While it has been established that surgery for lumbar disc herniation, excluding emergent indications, should only be performed after weeks of conservative treatment, it has also been established that late surgery is associated with poorer outscomes in terms of leg pain. However, nothing is known concerning the timinig and functional outcome. We quantify the association of time to surgery (TTS) with functional impairment outcome and identify a maximum TTS cutoff. METHODS: A consecutive series of patients who underwent tubular microdiscectomy for lumbar disc herniation was included. A reduction of ≥ 30% in the Oswestry Disability Index from baseline to 12 months was defined as the minimum clinically important difference (MCID). TTS was defined as time of symptom onset to surgery in weeks. The maximum TTS cutoffs were derived both quantitatively by an area under the curve (AUC) analysis, as well as qualitatively based on cutoff-specific MCID rates. RESULTS: Inclusion was met by 372 patients, among which 327 (87.9%) achieved MCID. MCID achievement was associated with lower TTS (hazard ratio, 0.725; 95% confidence interval, 0.557-0.944; p = 0.014). The optimum maximum TTS based on AUC was 21.5 weeks. The qualitative analysis showed a continuous drop of MCID rates with increasing TTS, with values > 80% until week 14. CONCLUSION: Our findings suggest that longer TTS is associated with a poorer patient-reported outcome in terms of functional impairment, and that-depending on the calculation method and according to the literature-a maximum TTS of between 14 to 22 weeks should likely be aimed for.

The amyloid-ß degradation intermediate Aß34 is pericyte-associated and reduced in brain capillaries of patients with Alzheimer's disease.

An impairment of amyloid ß-peptide (Aß) clearance is suggested to play a key role in the pathogenesis of sporadic Alzheimer's disease (AD). Amyloid degradation is mediated by various mechanisms including fragmentation by enzymes like neprilysin, matrix metalloproteinases (MMPs) and a recently identified amyloidolytic activity of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1). BACE1 cleavage of Aß40 and Aß42 results in the formation of a common Aß34 intermediate which was found elevated in cerebrospinal fluid levels of patients at the earliest disease stages. To further investigate the role of Aß34 as a marker for amyloid clearance in AD, we performed a systematic and comprehensive analysis of Aß34 immunoreactivity in hippocampal and cortical post-mortem brain tissue from AD patients and non-demented elderly individuals. In early Braak stages, Aß34 was predominantly detectable in a subset of brain capillaries associated with pericytes, while in later disease stages, in clinically diagnosed AD, this pericyte-associated Aß34 immunoreactivity was largely lost. Aß34 was also detected in isolated human cortical microvessels associated with brain pericytes and its levels correlated with Aß40, but not with Aß42 levels. Moreover, a significantly decreased Aß34/Aß40 ratio was observed in microvessels from AD patients in comparison to non-demented controls suggesting a reduced proteolytic degradation of Aß40 to Aß34 in AD. In line with the hypothesis that pericytes at the neurovascular unit are major producers of Aß34, biochemical studies in cultured human primary pericytes revealed a time and dose dependent increase of Aß34 levels upon treatment with recombinant Aß40 peptides while Aß34 production was impaired when Aß40 uptake was reduced or BACE1 activity was inhibited. Collectively, our findings indicate that Aß34 is generated by a novel BACE1-mediated Aß clearance pathway in pericytes of brain capillaries. As amyloid clearance is significantly reduced in AD, impairment of this pathway might be a major driver of the pathogenesis in sporadic AD.

Association of time to surgery with leg pain after lumbar discectomy: is delayed surgery detrimental?

OBJECTIVE: While it has been established that lumbar discectomy should only be performed after a certain waiting period unless neurological deficits are present, little is known about the association of late surgery with outcome. Using data from a prospective registry, the authors aimed to quantify the association of time to surgery (TTS) with leg pain outcome after lumbar discectomy and to identify a maximum TTS cutoff anchored to the minimum clinically important difference (MCID). METHODS: TTS was defined as the time from the onset of leg pain caused by radiculopathy to the time of surgery in weeks. MCID was defined as a minimum 30% reduction in the numeric rating scale score for leg pain from baseline to 12 months. A Cox proportional hazards model was utilized to quantify the association of TTS with MCID. Maximum TTS cutoffs were derived both quantitatively, anchored to the area under the curve (AUC), and qualitatively, based on cutoff-specific MCID rates. RESULTS: From a prospective registry, 372 patients who had undergone first-time tubular microdiscectomy were identified; 308 of these patients (83%) obtained an MCID. Attaining an MCID was associated with a shorter TTS (HR 0.718, 95% CI 0.546-0.945, p = 0.018). Effect size was preserved after adjustment for potential confounders. The optimal maximum TTS was estimated at 23.5 weeks based on the AUC, while the cutoff-specific method suggested 24 weeks. Discectomy after this cutoff starts to yield MCID rates under 80%. The 24-week cutoff also coincided with the time point after which the specificity for MCID first drops below 50% and after which the negative predictive value for nonattainment of MCID first surpasses ≥ 20%. CONCLUSIONS: The study findings suggest that late lumbar discectomy is linked with poorer patient-reported outcomes and that-in accordance with the literature-a maximum TTS of 6 months should be aimed for.

Machine learning-based preoperative predictive analytics for lumbar spinal stenosis.

OBJECTIVEPatient-reported outcome measures (PROMs) following decompression surgery for lumbar spinal stenosis (LSS) demonstrate considerable heterogeneity. Individualized prediction tools can provide valuable insights for shared decision-making. The authors aim to evaluate the feasibility of predicting short- and long-term PROMs, reoperations, and perioperative parameters by machine learning (ML) methods.METHODSData were derived from a prospective registry. All patients had undergone single- or multilevel mini-open facet-sparing decompression for LSS. The prediction models were trained using various ML-based algorithms to predict the endpoints of interest. Models were selected by area under the receiver operating characteristic curve (AUC). The endpoints were dichotomized by minimum clinically important difference (MCID) and included 6-week and 12-month numeric rating scales for back pain (NRS-BP) and leg pain (NRS-LP) severity and the Oswestry Disability Index (ODI), as well as prolonged surgery (> 45 minutes), extended length of hospital stay (> 28 hours), and reoperations.RESULTSA total of 635 patients were included. The average age was 62 ± 10 years, and 333 patients (52%) were male. At 6 weeks, MCID was seen in 63%, 76%, and 61% of patients for ODI, NRS-LP, and NRS-BP, respectively. At internal validation, the models predicted MCID in these variables with accuracies of 69%, 76%, and 85%, and with AUCs of 0.75, 0.79, and 0.92. At 12 months, 66%, 63%, and 51% of patients reported MCID; the observed accuracies were 62%, 74%, and 66%, with AUCs of 0.68, 0.72, and 0.79. Reoperations occurred in 60 patients (9.5%), of which 27 (4.3%) occurred at the index level. Overall and index-level reoperations were predicted with 69% and 63% accuracy, respectively, and with AUCs of 0.66 and 0.61. In 15%, a length of surgery greater than 45 minutes was observed and predicted with 78% accuracy and AUC of 0.54. Only 15% of patients were admitted to the hospital for longer than 28 hours. The developed ML-based model enabled prediction of extended hospital stay with an accuracy of 77% and AUC of 0.58.CONCLUSIONSPreoperative prediction of a range of clinically relevant endpoints in decompression surgery for LSS using ML is feasible, and may enable enhanced informed patient consent and personalized shared decision-making. Access to individualized preoperative predictive analytics for outcome and treatment risks may represent a further step in the evolution of surgical care for patients with LSS.

A Systematic Review and Meta-Analysis of Perioperative Parameters in Robot-Guided, Navigated, and Freehand Thoracolumbar Pedicle Screw Instrumentation.

BACKGROUND: Robotic guidance (RG) and navigation (NV) have been shown to reduce radiologic and clinically relevant pedicle screw malpositions. It remains unknown if there are any additional benefits to these techniques in intraoperative and perioperative end points. METHODS: We conducted a systematic review in MEDLINE, Embase, Scopus, and the Cochrane Library and identified controlled studies comparing RG, NV, and freehand (FH) thoracolumbar pedicle screw insertion and carried out random-effects meta-analyses. RESULTS: Thirty-two studies (24,008 patients) were included. Only 8 studies (26%) were randomized, and study quality was rated as very low or low in 24 cases (77%). Compared with NV, FH procedures showed longer length of hospital stay (Δ, 0.7 days; 95% confidence interval, 0.2-1.2; P = 0.006) and more overall complications (odds ratio, 1.6; 95% confidence interval, 1.3-1.9; P < 0.001). No statistically significant differences among RG and FH were identified, likely because of lack in statistical power (all P > 0.05). In particular, both RG and NV did not show increased intraoperative radiation use, as determined by seconds of fluoroscopy, compared with FH (both P > 0.05). CONCLUSIONS: It seems that navigation may offer potential benefits in perioperative outcomes such as length of hospital stay and overall complications, without significant increase in intraoperative radiation, which cannot yet be said for robotic guidance. The findings must be interpreted with caution, because the evidence is severely limited in both quantity and quality. Further evaluation will establish any demonstrable intraoperative or perioperative benefits to computer assistance, which may warrant the high costs often associated with these devices.

Tandem Disc Herniation of the Lumbar and Cervical Spine: Case Series and Review of the Epidemiological, Pathophysiological and Genetic Literature.

Introduction Lumbar disc herniation (LDH) and cervical disc herniation (CDH) represent a relevant public health problem. Patients with symptomatic tandem herniations of the cervical and lumbar spine are rare and not described in the literature. In these patients, certain variables may predispose the development of disc herniation which could increase the understanding of the development of disc herniations. Our aim is to present the first case series of tandem disc herniation, and to elucidate whether tandem herniation is attributable to a certain propensity for disc herniation or not. Methods  From a prospective registry, patients with symptomatic tandem disc herniations were included, and the literature was reviewed on the comparative pathophysiology, genetics, and epidemiology of disc herniation and disc degeneration. Results Out of 3,156 patients with disc herniations in our registry, 16 presented with symptomatic tandem LDH and CDH that required discectomy. Therefore, we estimate the incidence of tandem disc herniation at 0.51% (95% confidence interval (CI): 0.26% - 0.75%) in the surgical population. The mean number of degenerated lumbar discs was 2.1 ± 1.1. Compared to the 1,241 patients with isolated LDH, no investigated factors were significantly associated with tandem herniations. Conclusion From a genetic, pathophysiological, and epidemiological position, disc herniation is not commonly a consequence of disc degeneration. Rather, degeneration and herniation seem to exist as two separate and distinctly different processes. Based on the literature, it is tenable that tandem disc herniation does not deviate from the normal pathophysiology, but rather occurs in the rare case that two individual herniated discs coincide.

Is elective degenerative lumbar spine surgery in older adults safe in a short-stay clinic? Data from an institutional registry.

PURPOSE: Physicians are increasingly confronted with degenerative spinal pathologies and the possibility of elective surgical treatment in older adults. Little is known on safety and effectiveness of short-stay, elective lumbar spine surgery in this population. We aim to describe patient profiles of older adults undergoing surgery at a specialized short-stay clinic, and describe associated risk profiles and outcomes. METHODS: From a prospective registry, patients older than 65 were compared to younger controls. All patients underwent a strict anesthesiologic screening preoperatively, leading to a carefully selected cohort of relatively robust older adults suited for safe treatment at a short-stay clinic. A range of perioperative data and reoperations were available from all patients, and a subgroup of patients completed outcome assessments for disability, pain, and health-related quality of life (HRQOL). RESULTS: Of the 3279 included patients, 382 (12%) were older than 65. Older patients presented more often with spinal stenosis, and index levels were placed higher (p < 0.001). While there was no difference in complications, reoperations, and blood loss (p > 0.05), older people had longer surgical times and length of stay, although not by a clinically relevant margin (p < 0.001). Long-term patient-reported outcomes were equal (p > 0.05). However, older adults had worse 6-week outcomes for leg pain, functional disability, and HRQOL (all p < 0.05). CONCLUSIONS: Higher age should not be considered a contraindication for elective lumbar spine surgery at short-stay clinics. If the anesthesiologic risk can be controlled, conservative treatments have failed, and muscle-sparing techniques are applied, favorable outcomes can be achieved with an acceptable risk profile in a safe manner.

Patient-reported outcomes unbiased by length of follow-up after lumbar degenerative spine surgery: Do we need 2 years of follow-up?

BACKGROUND: In modern clinical research, the accepted minimum follow-up for patient-reported outcome measures (PROMs) after lumbar spine surgery is 24 months, particularly after fusion. Recently, this minimum requirement has been called into question. PURPOSE: We aim to quantify the concordance of 1- and 2-year PROMs to evaluate the importance of long-term follow-up after elective lumbar spine surgery. STUDY DESIGN: Retrospective analysis of data from a prospective registry. PATIENT SAMPLE: We identified all patients in our prospective institutional registry who underwent degenerative lumbar spine surgery with complete baseline, 12-month, and 24-month follow-up for ODI and numeric rating scales for back and leg pain (NRS-BP and NRS-LP). OUTCOME MEASURES: Oswestry Disability Index (ODI) and NRS-BP and NRS-LP at 1 year and at 2 years. METHODS: We evaluated concordance of 1- and 2-year change scores by means of Pearson's product-moment correlation and performed logistic regression to assess if achieving the minimum clinically important difference (MCID) at 12 months predicted 24-month MCID. Odds ratios (OR) and their 95% confidence intervals (CI), as well as model areas-under-the-curve were obtained. RESULTS: A total of 210 patients were included. We observed excellent correlation among 12- and 24-month ODI (r = 0.88), NRS-LP (r = 0.76) and NRS-BP (r = 0.72, all p <.001). Equal results were obtained when stratifying for discectomy, decompression, or fusion. Patients achieving 12-month MCID were likely to achieve 24-month MCID for ODI (OR: 3.3, 95% CI: 2.4-4.1), NRS-LP (OR: 2.99, 95% CI: 2.2-4.2) and NRS-BP (OR: 3.4, 95% CI: 2.7-4.2, all p <.001) with excellent areas-under-the-curve values of 0.81, 0.77, and 0.84, respectively. Concordance rates between MCID at both follow-ups were 87.2%, 83.8%, and 84.2%. A post-hoc power analysis demonstrated sufficient statistical power. CONCLUSIONS: Irrespective of the surgical procedure, 12-month PROMs for functional disability and pain severity accurately reflect those at 24 months. In support of previous literature, our results suggest that 12 months of follow-up may be sufficient for evaluating spinal patient care in clinical practice as well as in research.

Gender differences in degenerative spine surgery: Do female patients really fare worse?

PURPOSE: Prior data has set the precedent that female patients fare somewhat worse than men after spine surgery. We aimed to evaluate the effect of gender on patient-reported outcomes after lumbar spine surgery for degenerative pathologies. METHODS: We identified a consecutive cohort of patients from a prospective registry. Absolute values, as well as change scores for back and leg pain severity (numeric rating scale [NRS]), functional disability (Oswestry disability index [ODI]), and health-related quality of life (HRQOL) as assessed by EQ-5D were compared among male and female patients. RESULTS: Of the 3279 included patients, 1543 (47%) were female. At baseline, women reported higher NRS for back and leg pain, higher ODI, but equal HRQOL (all p < 0.05). Otherwise, both groups had comparable baseline data. The absolute differences in patient-reported outcomes persisted at the 6-week, 12- and 24-months follow-up, with women now additionally reporting worse HRQOL as assessed by EQ-5D (all p < 0.05). For all outcome measures, change scores were equal among male and female patients, as were the incidences of complications and reoperations (all p > 0.05). Clinical success was achieved in 82% of men and 79% of women (p = 0.34). CONCLUSIONS: Female patients are generally scheduled for surgery with a more advanced disease state. While women seem to report more severe symptoms at long-term follow-up, the degree of improvement is equal among men and women. Female patients may thus fare worse in terms of absolute scores, but enjoy the same benefit from surgery in relative terms. These slides can be retrieved under Electronic Supplementary Material.