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.

The Effect of Muscle Quality on Outcomes after Microdiscectomy.

OBJECTIVES: To investigate the relationship between muscle quality and 1) patient-reported outcomes and 2) surgical outcomes after lumbar microdiscectomy surgery. METHODS: Adult patients (≥18 years) who underwent lumbar microdiscectomy from 2014 to 2021 at a single academic institution were identified. Outcomes were collected during the preoperative, 3-month, 6-month, and 1-year postoperative periods. Those included were the Oswestry Disability Index (ODI), Visual Analog Scale Back and Leg (VAS-Back and VAS-Leg, respectively), and the mental and physical component of the short-form 12 survey (MCS and PCS). Muscle quality was determined by 2 systems: the normalized total psoas area (NTPA) and a paralumbar-based grading system. Surgical outcomes including 90-day surgical readmissions and 1-year reoperations were also collected. RESULTS: Of the 218 patients identified, 150 had good paralumbar muscle quality and 165 had good psoas muscle quality. Bivariant analysis demonstrated no difference between groups regarding surgical outcomes (P > 0.05). Multivariable analysis demonstrated that better paralumbar muscle quality was not associated with any consistent changes in patient reported outcomes. Higher NTPA was associated with improved PCS at 6 months (est. = 6.703, [95% CI: 0.759-12.646], P = 0.030) and 12 months (est. = 6.625, [95% CI: 0.845-12.405], P = 0.027). There was no association between muscle quality and surgical readmissions or reoperations. CONCLUSIONS: Our analysis demonstrated that higher psoas muscle quality was associated with greater physical improvement postoperatively. Muscle quality did not affect surgical readmissions or reoperations. Additional studies are needed for further assessment of the implications of muscle quality on postoperative outcomes.

Modified Frailty Index Does Not Provide Additional Value in Predicting Outcomes in Patients Undergoing Elective Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: To determine the predictive value of the modified Frailty Index (mFI) in evaluating sarcopenia and clinical outcomes in patients undergoing 1-level or 2-level transforaminal lumbar interbody fusion (TLIF). METHODS: Patients who underwent a 1-level or 2-level TLIF between 2012 and 2020 were retrospectively identified. Frailty was compared among groups using mFI, and sarcopenia was classified by the psoas muscle cross-sectional area. Bivariate statistics compared demographics, comorbidities, and clinical outcomes. A linear regression model was developed using the Charlson Comorbidity Index (CCI) or mFI as independent variables to determine potential predictors for improvement in 1-year patient-reported outcomes. RESULTS: Of 488 included patients, 60 were severely frail and 60 patients had sarcopenia, but sarcopenia was not associated with patient frailty (P = 0.469). Severely frail patients had worse baseline Oswestry Disability Index (ODI) (P < 0.001), Mental Component Score-12 (P = 0.001), and Physical Component Score-12 (P < 0.001), and worse improvement in ODI (P = 0.037), Physical Component Score-12 (P < 0.001), and visual analog scale (VAS) back (P = 0.007). mFI was an independent predictor of poorer improvement in VAS back and ODI, whereas age + CCI in addition predicted poorer improvement in VAS leg. Patients with higher mFI experienced longer length of stay, less frequent home discharge, and higher rates of complications, but similar readmission and reoperation rates. CONCLUSIONS: Frailer patients experience poorer improvement in back pain, physical functioning, and disability after TLIF. mFI and the combination of age and CCI comparably predict patient-reported outcomes but do not correlate to baseline sarcopenia. Frailty increased the risk of complications, length of hospital stay, and risk of nonhome discharge.

Tumor-Targeted Delivery of 6-Diazo-5-oxo-l-norleucine (DON) Using Substituted Acetylated Lysine Prodrugs.

6-Diazo-5-oxo-l-norleucine (DON) is a glutamine antagonist with robust anticancer efficacy; however, its therapeutic potential was hampered by its biodistribution and toxicity to normal tissues, specifically gastrointestinal (GI) tissues. To circumvent DON's toxicity, we synthesized a series of tumor-targeted DON prodrugs designed to circulate inert in plasma and preferentially activate over DON in tumor. Our best prodrug 6 (isopropyl 2-(6-acetamido-2-(adamantane-1-carboxamido)hexanamido)-6-diazo-5-oxohexanoate) showed stability in plasma, liver, and intestinal homogenates yet was readily cleaved to DON in P493B lymphoma cells, exhibiting a 55-fold enhanced tumor cell-to-plasma ratio versus that of DON and resulting in a dose-dependent inhibition of cell proliferation. Using carboxylesterase 1 knockout mice that were shown to mimic human prodrug metabolism, systemic administration of 6 delivered 11-fold higher DON exposure to tumor (target tissue; AUC0- t = 5.1 nmol h/g) versus GI tissues (toxicity tissue; AUC0- t = 0.45 nmol h/g). In summary, these studies describe the discovery of a glutamine antagonist prodrug that provides selective tumor exposure.