The Relationship Between Disc Herniation Morphology and Patient-Reported Outcomes after Microdiscectomy.

OBJECTIVE: Determine if herniation morphology based on the Michigan State University Classification is associated with differences in (1) patient-reported outcome measures (or (2) surgical outcomes after a microdiscectomy. METHODS: Adult patients undergoing single-level microdiscectomy between 2014 and 2021 were identified. Demographics and surgical characteristics were collected through a query search and manual chart review. The Michigan State University classification, which assesses disc herniation laterality (zone A was central, zone B/C was lateral) and degree of extrusion into the central canal (grade 1 was up to 50% of the distance to the intra-facet line, grade >1 was beyond this line), was identified on preoperative MRIs. patient-reported outcome measures were collected at preoperative, 3-month, and 1-year postoperative time points. RESULTS: Of 233 patients, 84 had zone A versus 149 zone B/C herniations while 76 had grade 1 disc extrusion and 157 had >1 grade. There was no difference in surgical outcomes between groups (P > 0.05). Patients with extrusion grade >1 were found to have lower Physical Component Score at baseline. On bivariate and multivariable logistic regression analysis, extrusion grade >1 was a significant independent predictor of greater improvement in Physical Component Score at three months (estimate = 7.957; CI: 4.443-11.471, P < 0.001), but not at 1 year. CONCLUSIONS: Although all patients were found to improve after microdiscectomy, patients with disc herniations extending further posteriorly reported lower preoperative physical function but experienced significantly greater improvement three months after surgery. However, improvement in Visual Analog Scale Leg and back, ODI, and MCS at three and twelve months was unrelated to laterality or depth of disc herniation.

Multilevel ossification of the posterior longitudinal ligament causing cervical myelopathy: An observational series of North American patients.

Background: Few studies regarding ossification of the posterior longitudinal ligament (OPLL) outside of Asia currently exist in the literature. A set of patients with multilevel cervical OPLL causing symptomatic myelopathy or radiculopathy from a North American sample is analyzed. Objective: The objective of this study was to describe the demographics, radiographic findings, and surgical outcomes of a cohort of North American patients with degenerative spondylosis presenting for operative management of multilevel (>3 segments) cervical OPLL. Materials and Methods: Forty-three patients diagnosed with multilevel cervical OPLL and degenerative spondylosis presenting with symptomatic cervical myelopathy or radiculopathy were surgically treated over a 9-year period at a single tertiary care academic medical center. Radiographic measurements were performed on preoperative computed tomography and magnetic resonance imaging images of the cervical spine. Clinical outcomes included pre- and postoperative Nurick scores, 90-day readmission, complication, and revision surgery rates. Results: The mean age was 66.1 ± 10.9 years with a mean latest follow-up time of 32.7 ± 16.4 months. Most patients had previous diagnoses of obesity (70.7%) and hypertension (55.8%). At least one-quarter of patients were diagnosed with type 2 diabetes (34.9%), hyperlipidemia (41.9%), cardiovascular disease (25.6%), or chronic kidney disease (25.3%). The most common OPLL subtype was segmental (39.5%) and spanned a mean of 3.54 ± 1.48 segments. Myelopathic symptoms were present in 88.4% of patients. All patients experienced significant neurologic improvement at 3-week and latest follow-up (P < 0.001 for both). Conclusions: Obesity, diabetes, and other metabolic derangements in patients with existing cervical spondylosis may be risk factors for a particularly aggressive form of multilevel OPLL. Various operative approaches may be employed to achieve adequate neurologic recovery. Further workup for OPLL in patients with these risk factors may prove beneficial to ensure appropriate operative management.

Early Experience With Uniplanar Versus Biplanar Expandable Interbody Fusion Devices in Single-Level Minimally Invasive Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: To compare the early radiographic and clinical outcomes of expandable uniplanar versus biplanar interbody cages used for single-level minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: A retrospective review of 1-level MIS-TLIFs performed with uniplanar and biplanar polyetheretherketone cages was performed. Radiographic measurements were performed on radiographs taken preoperatively, at 6-week follow-up, and 1-year follow-up. Oswestry Disability Index (ODI) and visual analogue scale (VAS) for back and leg at 3-month and 1-year follow-up. RESULTS: A total of 93 patients (41 uniplanar, 52 biplanar) were included. Both cage types provided significant postoperative improvements in anterior disc height, posterior disc height, and segmental lordosis at 1 year. No significant differences in cage subsidence rates were found between uniplanar (21.9%) and biplanar devices (32.7%) at 6 weeks (odds ratio, 2.015; 95% confidence interval, 0.651-6.235; p = 0.249) with no additional instances of subsidence at 1 year. No significant differences in the magnitude of improvements based on ODI, VAS back, or VAS leg at 3-month or 1-year follow-up between groups and the proportion of patients achieving the minimal clinically important difference in ODI, VAS back, or VAS leg at 1 year were not statistically significantly different (p > 0.05). Finally, there were no significant differences in complication rates (p = 0.283), 90-day readmission rates (p = 1.00), revision surgical procedures (p = 0.423), or fusion rates at 1 year (p = 0.457) between groups. CONCLUSION: Biplanar and uniplanar expandable cages offer a safe and effective means of improving anterior disc height, posterior disc height, segmental lordosis, and patient-reported outcome measures at 1 year postoperatively. No significant differences in radiographic outcomes, subsidence rates, mean subsidence distance, 1-year patient-reported outcomes, and postoperative complications were noted between groups.

Evaluating Outcomes of Spinopelvic Fixation for Patients Undergoing Long Segment Thoracolumbar Fusion with a Prior Total Hip Arthroplasty.

INTRODUCTION: Understanding the relationship between spinal fusion and its effects on relative spinopelvic alignment in patients with prior total hip arthroplasty (THA) is critical. However, limited data exist on the effects of long spinal fusions on hip alignment in patients with a prior THA. Our objective was to compare clinical outcomes and changes in hip alignment between patients undergoing long fusion to the sacrum versus to the pelvis in the setting of prior THA. METHODS: Patients with a prior THA who underwent elective thoracolumbar spinal fusion starting at L2 or above were retrospectively identified. Patients were placed into one of two groups: fusion to the sacrum or pelvis. Preoperative, six-month postoperative, one-year postoperative, and delta spinopelvic and acetabular measurements were measured from standing lumbar radiographs. RESULTS: A total of 112 patients (55 sacral fusions, 57 pelvic fusions) were included. Patients who underwent fusion to the pelvis experienced longer length of stay (LOS) (8.31 vs. 4.21, P < 0.001) and less frequent home discharges (30.8% vs. 61.9%, P = 0.010), but fewer spinal revisions (12.3% vs. 30.9%, P = 0.030). No difference was observed in hip dislocation rates (3.51% vs. 1.82%, P = 1.000) or hip revisions (5.26% vs. 3.64%, P = 1.000) based on fusion construct. Fusion to the sacrum alone was an independent predictor of an increased spine revision rate (odds ratio: 3.56, P = 0.023). Patients in the pelvic fusion group had lower baseline lumbar lordosis (LL) (29.2 vs. 42.9, P < 0.001), six-month postoperative LL (38.7 vs. 47.3, P = 0.038), and greater 1-year ∆ pelvic incidence-lumbar lordosis (-7.98 vs. 0.21, P = 0.032). CONCLUSION: Patients with prior THA undergoing long fusion to the pelvis experienced longer LOS, more surgical complications, and lower rate of spinal revisions. Patients with instrumentation to the pelvis had lower LL preoperatively with greater changes in LL and pelvic incidence-lumbar lordosis postoperatively. No differences were observed in acetabular positioning, hip dislocations, or THA revision rates between groups.

Short-Segment versus Long-Segment Spinal Fusion Constructs for the Treatment of Adult Degenerative Scoliosis: A Comparison of Clinical Outcomes.

OBJECTIVE: To compare clinical outcomes of patients diagnosed with degenerative scoliosis undergoing short-segment versus long-segment spinal fusion. METHODS: A retrospective cohort study was conducted of patients with degenerative thoracolumbar scoliosis undergoing elective spinal fusion at a single academic medical center. Cohorts were divided into short-segment (<3) or long-segment (≥3) groups. RESULTS: A total of 197 patients (122 short, 75 long) were included. Patients undergoing short-segment fusion more frequently presented with radiculopathy (P < 0.001) and had greater baseline visual analog scale (VAS) leg scores (P < 0.001). Patients with long-segment fusions had longer hospital length of stay (short, 3.82 ± 2.98 vs. long, 7.40 ± 6.85 days; P < 0.001), lower home discharge rates (short, 80.3% vs. long, 51.8; P = 0.003), higher revision surgery rates (short, 10.77% vs. long, 25.3%; P = 0.012), and greater percentage curve correction (short, 37.3% ± 25.9% vs. long, 45.1% ± 23.9%; P = 0.048). No significant differences were noted in postoperative complication rates (short, 1.64% vs. long, 5.33%; P = 0.143). At 1 year, patients with long fusions had worse ΔOswestry Disability Index (ODI) (P = 0.024), ΔVAS leg score (P = 0.002), and VAS leg minimum clinically important difference % (P = 0.003). Multivariate regression found that short-segment fusions were associated with greater improvements in ODI (P = 0.029), Physical Component Summary-12 (P = 0.024), and VAS leg score at 1 year (P = 0.002). CONCLUSIONS: Patients undergoing short-segment fusions more frequently presented with radiculopathy and had higher preoperative VAS leg scores compared with those receiving long constructs. Short-construct fusions in appropriately selected patients may provide satisfactory improvements in patient-reported outcome measures, particularly ΔODI and ΔVAS leg score, and mitigate hospital length of stay, revision surgery rates, and nonhome discharge.

Static versus Expandable Interbody Fusion Devices: A Comparison of 1-Year Clinical and Radiographic Outcomes in Minimally Invasive Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. PURPOSE: To compare the radiographic and clinical outcomes of static versus expandable interbody cages in transforaminal lumbar interbody fusion using minimally invasive surgery (MIS-TLIF). OVERVIEW OF LITERATURE: Expandable interbody cages may potentially improve radiographic and clinical outcomes following MIS-TLIF compared to static pages, but at a potentially higher cost and increased rates of subsidence. METHODS: A retrospective chart review of 1- and 2-level MIS-TLIFs performed from 2014 to 2020 was reviewed. Radiographic measurements were obtained preoperatively, 6 weeks postoperatively, and at final follow-up. Patient-reported outcome measures (PROMs) including the Oswestry Disability Index, Visual Analog Scale (VAS) back, and VAS leg were evaluated. Multivariate linear regression analysis determined the effect of cage type on the change in PROMs, controlling for demographic characteristics. Alpha was set at 0.05. RESULTS: A total of 221 patients underwent MIS-TLIF including 136 static and 85 expandable cages. Expandable cages had significantly greater anterior (static: 11.41 mm vs. expandable: 13.11 mm, p <0.001) and posterior disk heights (static: 7.22 mm vs. expandable: 8.11 mm, p <0.001) at 1-year follow-up. Expandable cages offered similar improvements in segmental lordosis at 6 weeks (static: 1.69° vs. expandable: 2.81°, p =0.243), but segmental lordosis was better maintained with expandable cages leading to significant differences at 1-year follow-up (static: 0.86° vs. expandable: 2.45°, p =0.001). No significant differences were noted in total complication (static: 12.5% vs. expandable: 16.5%, p =0.191) or cage subsidence rates (static: 19.7% vs. expandable: 22.4%, p =0.502) groups at 1-year follow-up. CONCLUSIONS: Expandable devices provide greater improvements in radiographic measurements including anterior disk height, posterior disk height, and segmental lordosis, but this did not lead to significant improvements in PROMs, complication rates, subsidence rates, or subsidence distance.

The Use of Cement and Tourniquet During Total Knee Arthroplasty Does Not Increase the Risk of Venous Thromboembolism Postoperatively.

Background: Venous thromboembolism (VTE) is a severe complication of total knee arthroplasty (TKA). Cementation and the use of tourniquet during TKA have both been hypothesized to be risk factors of VTE. The purpose of our study was to determine if either of these surgical factors increases the risk of VTE in patients undergoing TKA. Methods: A single-institution, retrospective study was conducted, consisting of 16,972 patients undergoing a primary or revision TKA from 2008 to 2020. Of the total, 1020 patients were excluded from the tourniquet analysis as tourniquet data were unavailable. Clinical records were consulted to identify demographics, surgical variables, and outcomes. Queries of clinical notes and phone-call logs were conducted to capture VTE events following discharge. Statistical analysis consisted of univariate analysis, regression analysis, and propensity score matching. Results: Compared to patients who did not receive tourniquet, the patients with tourniquet did not demonstrate a significantly higher rate of VTE in the univariate analysis (1.00 vs 1.31, P = .132). Propensity score analysis also showed no difference between the 2 cohorts (1.10 vs 0.85, P = .306). Cemented patients similarly did not demonstrate an increased risk of VTE in either the univariate (1.26 vs 1.22, P = .895) or propensity score analysis (1.42 vs 1.26, P = .710) compared to cementless patients. Regression analysis, looking at the interaction between cement and tourniquet with VTE risk as the dependent variable, revealed neither to be risk factors for VTE (odds ratio 1.38, 95% confidence interval 0.63-3.08, P = .426). Conclusions: In our cohort, neither tourniquet nor cement was a significant risk factor for VTE following TKA.

Aspirin May Be a Suitable Prophylaxis for Patients with a History of Venous Thromboembolism Undergoing Total Joint Arthroplasty.

BACKGROUND: In recent years, aspirin has become a popular agent for venous thromboembolism (VTE) prophylaxis following total joint arthroplasty (TJA). Yet patients with a history of VTE are often given more aggressive prophylactic agents because of their increased baseline risk. The purpose of this study was to assess whether aspirin is an effective prophylactic agent in patients with a history of VTE. METHODS: This was a single-institution, retrospective cohort study. The electronic clinical records of 36,333 patients undergoing TJA between 2008 and 2020 were reviewed. Data on demographic characteristics, comorbidities, intraoperative factors, and postoperative complications were collected. A propensity score-matched analysis was performed, as well as a multivariate regression analysis to account for confounders. RESULTS: Of the 36,333 patients undergoing TJA, 1,087 patients (3.0%) had a history of VTE and were not receiving chronic non-aspirin. The risk for subsequent VTE was significantly higher (p = 0.03) in patients with a history of VTE (1.4%) compared with patients without prior VTE (0.9%). However, the incidence of VTE was not significantly lower (p = 0.208) in patients with a history of VTE who received aspirin (0.4%) compared with patients who received other VTE prophylaxis (1.5%). Propensity score matching showed no difference in VTE rates between the 2 groups (2.2% compared with 0.55%; p = 0.372). In a regression analysis accounting for VTE risk, the administration of aspirin was not associated with an increased risk for subsequent VTE (adjusted odds ratio, 0.32 [95% confidence interval, 0.02 to 1.66]; p = 0.274). CONCLUSIONS: Our findings suggest that, although patients with a history of VTE have an increased baseline risk for subsequent VTE, aspirin may be a suitable VTE prophylaxis in this group of patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Thirty Days of Aspirin for Venous Thromboembolism Prophylaxis Is Adequate Following Total Knee Arthroplasty, Regardless of the Dose Used.

BACKGROUND: The optimal length of aspirin prophylaxis to minimize venous thromboembolism (VTE) following total knee arthroplasty (TKA) remains unknown. This study aimed to determine the timing of VTE after TKA in patients who received low and high dose aspirin, and determine if 30 days of prophylaxis remains adequate. METHODS: We retrospectively reviewed records of 9208 patients undergoing primary TKA between 2010 and 2020 who received either low (81 mg twice daily, n = 4413) or high (325 mg twice daily, n = 4795) dose aspirin for VTE prophylaxis. Symptomatic VTEs occurring within 90 days of surgery were identified from medical records and phone call logs. Major bleeding events (MBE) within the first 30 days were also documented. Time to event was recorded. RESULTS: Overall, 88 patients (1.0%) developed symptomatic VTE, with no significant differences in incidence between the low (n = 40, 0.9%) and high (n = 48, 1.0%) dose groups (P = .669). The median time to VTE was 8 days (interquartile range [IQR] 2-15.5), median time to deep vein thrombosis was 12 days (IQR 5-18), and median time to pulmonary embolism was 5 days (IQR 1.5-15). There was a similar distribution in time to VTE in both the low and high dose groups. Aside from a single DVT occurring at day 44, all VTE occurred within 30 days of surgery. During the prophylactic time period, 41 patients (0.4%) developed MBE, which tended to occur more frequently (0.6% vs 0.3%, P = .018) and earlier in the high dose group. CONCLUSION: Based on the findings, a 30-day low or high dose aspirin regimen remains optimal for prevention of VTE without increasing MBE in TKA patients.

Protective role of DJ-1 in endotoxin-induced acute kidney injury.

Acute kidney injury (AKI) is a frequent complication of sepsis and an important cause of morbidity and mortality worldwide. A cornerstone of sepsis-associated AKI is dysregulated inflammation, leading to increased tissue oxidative stress and free radical formation, which leads to multiple forms of cell death. DJ-1 is a peroxiredoxin protein with multiple functions, including its ability to control cellular oxidative stress. Although DJ-1 is expressed prominently by renal tubules, its role in AKI has not been investigated. In the present study, we examined the effect of DJ-1 deficiency in a murine model of endotoxin-induced AKI. Endotoxemia induced greater kidney injury in DJ-1-deficient mice. Furthermore, DJ-1 deficiency increased renal oxidative stress associated with increased renal tubular apoptosis and with expression of death domain-associated protein (DAXX). Similar to the in vivo model, in vitro experiments using a medullary collecting duct cell line (mIMCD3) and cytotoxic serum showed that serum obtained from wild-type mice resulted in increased expression of s100A8/s100A9, DAXX, and apoptosis in DJ-1-deficient mIMCD3 cells. Our findings demonstrate a novel renal protective role for renal tubular DJ-1 during endotoxemia through control of oxidative stress, renal inflammation, and DAXX-dependent apoptosis.

Modulation of iron homeostasis with hepcidin ameliorates spontaneous murine lupus nephritis.

Lupus nephritis is the end organ manifestation of systemic lupus erythematosus. Iron metabolism and its master regulator, hepcidin, are known to regulate cell proliferation and inflammation, but their direct role in the pathophysiology of lupus nephritis remains under-investigated. Exogenous hepcidin reduced the severity of lupus nephritis in MRL/lpr mice, a preclinical model of spontaneous systemic lupus erythematosus without worsening anemia of inflammation. Hepcidin treatment reduced renal iron accumulation, systemic and intrarenal cytokines, and renal immune cell infiltration, independent of glomerular immune complex deposits and circulating autoantibodies. Hepcidin increased renal H-ferritin (a ferroxidase), reduced expression of free iron dependent DNA synthesis enzymes, Ribonucleotide Reductase 1 and 2, and intra-renal macrophage proliferation. These findings were recapitulated in vitro upon treatment of macrophages with hepcidin and murine colony stimulation factor-1. Furthermore, hepcidin-treated macrophages secreted less IL-1ß and IL-6 upon stimulation with the TLR3 agonist polyinosine-polycytidylic acid. Of clinical relevance, hepcidin reduced progression and severity of nephritis in old mice with established systemic autoimmunity and overt proteinuria, highlighting its therapeutic potential. Thus, our findings provide a proof-of-concept that targeting cellular iron metabolism with hepcidin represents a promising therapeutic strategy in lupus nephritis.

Protective Role of Hepcidin in Polymicrobial Sepsis and Acute Kidney Injury.

Background: Acute kidney injury (AKI) portends worse prognosis following sepsis, with limited available interventions. Host iron acquisition by pathogens and systemic inflammatory response are key events in the pathogenesis of sepsis. In sepsis, hepcidin induces iron sequestration to limit iron availability to pathogens. Hepcidin is also known to limit inflammation. Since its role in pathophysiology of sepsis-associated AKI is unknown, we investigated the effect of exogenous hepcidin in endotoxin- and peritonitis-induced pathology and AKI. Methods: C57BL/6 mice were treated with saline or 50-100 µg of hepcidin, pre- and post-LPS injection, or cecal ligation and puncture (CLP, model of peritonitis). Splenectomized mice were challenged with LPS, with and without hepcidin. Mice were euthanized at 24 h after LPS injection and at different time points after CLP. Systemic inflammation and renal injury markers were assessed. Direct effect of hepcidin on renal tubular and endothelial cells was evaluated using endotoxin-induced cytotoxic serum. Role of heavy chain ferritin (H-ferritin) in mediating hepcidin-induced anti-inflammatory effect on LPS stimulated macrophages was evaluated with siRNA studies. Results: Twenty-four hours pretreatment with hepcidin significantly reduced LPS-induced AKI. Hepcidin ameliorated LPS-induced increase in serum TNFα and renal Cox-2, and prevented loss in PGC1α and cytochrome c oxidase activity. This was associated with reduced glomerular injury and preserved mitochondrial structure. Hepcidin did not exert direct protection on the renal parenchymal cells but reduced endotoxin-induced serum cytotoxicity to mitigate renal injury. Splenectomy reduced LPS-induced early inflammation and AKI, independent of hepcidin, indicating the importance of systemic inflammation. Higher splenic H-ferritin in hepcidin-treated animals was associated with reduced splenocytes apoptosis and inflammation. Hepcidin reduced LPS-induced IL-6 secretion in macrophages in H-ferritin dependent manner. Hepcidin significantly reduced CLP-induced AKI, and mortality (20% hepcidin treated vs 80% PBS treated). Importantly hepcidin reduced bacteremia and AKI even when administered after onset of sepsis. Conclusion: We demonstrate a protective role of hepcidin in endotoxin- and peritonitis-induced pathologies and AKI, exerted primarily through its anti-inflammatory effects, and antibacterial property. Macrophage H-ferritin plays an important role in hepcidin-mediated protection against endotoxin-induced inflammation. We uncover a novel prophylactic and therapeutic role of hepcidin in sepsis-associated bacteremia, AKI, and mortality.