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BACKGROUND AND OBJECTIVES: Anterior lumbar interbody fusion (ALIF) is a powerful procedure for sagittal correction and indirect decompression in the lumbar spine, though aggressive correction can cause stretch neuropraxia and implant subsidence. The aim of this study was to identify radiographic and clinical predictors of segmental correction, as well as to evaluate the degree to which segmental correction on supine intraoperative radiographs translates to postoperative upright alignment changes. METHODS: We identified patients treated with 1- or 2-level ALIF at a tertiary care center and extracted data on demographics, spinopelvic parameters, and surgical details. Patients treated with isolated ALIF and ALIF with supplementary posterior instrumentation were compared on pre- and postoperative intradiscal lordosis (IDL) and change in IDL. Multivariable linear regression was performed to identify independent predictors of postoperative IDL. RESULTS: We included 204 patients (median age 57 years, 55.4% male) treated at 258 levels, of whom 114 (55.9%) underwent supplementary posterior fixation and 150 (73.5%) underwent single-level implantation. Across all patients, postoperative IDL was significantly greater than preoperative segmental lordosis (25.4° vs 15.3°; P < .001). Standalone ALIF achieved less ΔIDL than circumferential fusion for L5/S1 procedures (7.4° vs 11.6°; P < .001), though ΔIDL for L3/4 and L4/5 was similar between the standalone and circumferential groups. Multivariable analysis showed postoperative IDL to be predicted by greater preoperative IDL (β = 0.26° per degree; [0.15, 0.36]; P < .001), L5/S1 [vs L4/5] implantation (β = 3.97°; [2.72, 5.21]; P < .001), use of supplementary posterior fixation (β = 1.80°; [0.70, 2.89]; P < .001), and greater implant lordosis (β = 0.62° per degree; [0.44, 0.79]; P < .001). CONCLUSION: Postoperative IDL after 1- or 2-level ALIF is best predicted by placement of larger interbody sizes, L5/S1 implantation, greater baseline IDL, and use of adjunct posterior fixation. Patients with higher preoperative lordosis experienced smaller postoperative increases in IDL, though this was likely influenced by a treatment bias.

Abstract Background Alzheimer's disease (AD) exhibits significant genetic heterogeneity, with no single model fully explaining its inheritance pattern. Structural variants (SVs) may contribute to the missing heritability of AD, particularly in disease pathology and familial AD, which remain largely unexplored. Method Structural variants (SVs) were analyzed in unrelated 1,162 individuals from the ROSMAP study (687 cognitively normal (CN), 475 AD patients), as well as 197 Non‐Hispanic White (NHW) families (926 individuals, 58.5% with AD) and 214 Caribbean Hispanic (CH) families (1,340 individuals, 59.17% with AD). Large insertions and deletions were identified using Manta, Absinthe, and MELT from whole‐genome sequencing, supplemented by Sniffles2 and external SV call sets. This approach generated a unified VCF file containing 45,251 insertions and 76,566 deletions. After filtering for missingness rate and allele counts, a total of 9,290 insertions and 9,529 deletions were retained for analysis. Genome‐wide SV analyses were performed with AD‐related metrics in ROSMAP, adjusting for age, sex, and principal components, and validated in an independent ADSP replication cohort comprising 29,055 unrelated individuals (17,110 CN and 11,945 AD patients). Result We identified nine SVs (one insertion and eight deletions) segregating in AD families. An insertion near PDCD10 in NHW families reached genome‐wide significance ( p <5×10 ‐8 ) for AD risk in the replication cohort. Two deletions in KIF26B and SPHKAP were found in both CH and NHW families, while five appeared only in NHW and one in CH. All eight deletions showed genome‐wide significance for AD risk. SV GWAS on AD pathologies in ROSMAP revealed an insertion in INPP4B with the strongest association to global brain pathology (β=0.19; p = 2.32×10 ‐5 ), also linked to pathological AD, diffuse plaques, and Braak staging. A deletion near ADGRB1 (β=1.53; p = 5.05×10 ‐6 ) was associated with neuritic plaques, and another near ARMC2 (β=1.66; p = 2.17×10 ‐6 ) was linked to diffuse plaques. All three SVs associated with AD ( p <5×10 ‐6 ) in replication. Conclusion Our findings reveal numerous SVs segregating in familial AD across both CH and NHW families, as well as additional SVs linked to sporadic AD. Prioritizing these SVs based on their potential effects on gene function and expression will provide deeper insight into their contributions to both familial and sporadic AD.

OBJECTIVE Glucagon-like peptide-1 (GLP-1) agonists are established therapeutics for weight loss that are increasingly used for BMI optimization prior to spine surgery. However, emerging evidence has suggested that GLP-1 agonists might reduce bone mineral density (BMD), increasing the risk of postoperative biomechanical complications. CT-based Hounsfield units (HUs) have gained popularity as a method for measuring spinal BMD. The aim of this study was to evaluate the effects of GLP-1 agonist–induced weight loss on spinal BMD as measured by opportunistic CT-based HUs. METHODS Patients who were treated with any GLP-1 agonist (2017–2022) for > 3 months were retrospectively identified. Patient body weight (BW), BMI, and HU measurements in the L1 vertebral body were measured before and after GLP-1 therapy. Patients were grouped according to the percentage of weight loss during GLP-1 therapy. One-way ANOVA was used to compare the mean changes in spinal HUs across the groups. RESULTS Among the 102 included patients, the mean ± standard error of the mean BW reduction was 14.5 ± 2.5 kg over 15.9 ± 1.2 months of GLP-1 agonist therapy. Of these, 7 patients (6.9%) lost > 20% BW (mean decrease of 31.9 ± 7.0 HU, p = 0.011), 14 (13.7%) lost 15%–20% BW (mean decrease of 19.1 ± 8.3 HU, p = 0.038), 14 (13.7%) lost 10%–15% BW (mean decrease of 12.2 ± 5.1 HU, p = 0.036), 24 (23.5%) lost 5%–10% BW (mean decrease of 15.7 ± 3.3 HU, p < 0.0001), 26 (25.5%) lost < 5% BW (mean decrease of 14.7 ± 6.0 HU, p = 0.022), and 17 (16.7%) gained BW during GLP-1 therapy (mean decrease of 6.3 ± 5.0 HU, p = 0.229). One-way ANOVA testing did not show a significant difference in HU reduction across the weight loss groups (F = 1.12, p = 0.355). In addition, there was a significant correlation between the decrease in L1 HUs and the duration of GLP-1 therapy (r = −0.38, p = 0.0001) but not the amount of weight loss (r = −0.18, p = 0.070). In the multivariate analysis, the duration of GLP-1 therapy (p = 0.032) was a significant independent predictor of vertebral HU reduction, but the amount of weight loss (p = 0.664) was not. CONCLUSIONS Despite similar pretreatment BW and HU measurements, all weight loss groups had significant decreases in vertebral HUs following GLP-1 agonist therapy, with a significant correlation observed between HU reduction and treatment duration. This suggests that long-term GLP-1 agonist therapy can significantly diminish spinal BMD regardless of the amount of weight loss achieved.

OBJECTIVE Surgical site infection (SSI) is a leading cause of morbidity following posterior spine surgery. The optimal choice of skin closure technique depending on patient- and procedure-specific characteristics remains to be elucidated. METHODS The Neurosurgery Enterprise Registry (NER) at Mayo Clinic was queried for patients who underwent posterior spine surgery from 2017 to 2023. Propensity matching was performed to match patients on the basis of the development of SSI and baseline characteristics, including age, sex, race, and comorbidities. Perioperative outcomes were analyzed using data from the NER and medical records. RESULTS A total of 18,842 cases of posterior spine surgery were identified in the NER, and SSI was observed in 154 cases (0.8%). Of these patients, 308 patients were included in the 1:1 propensity score–matched cohort analysis, with 154 patients included in each group. Sutures were used in 224 patients (72.7%) and staples in 84 patients (27.3%) (p < 0.01). Female patients comprised 45.1% of the sutures group and 46.4% of the staples group (p = 0.8). The mean ± SD age was 59.8 ± 15.4 years in the sutures group and 60.8 ± 11.9 years in the staples group (p = 0.6). Fusion was performed in 27.2% of patients in the sutures group and 44% in the staples group (p < 0.01). Multilevel fusion comprised 68.9% of fusion cases in the sutures group and 67.6% in the staples group (p = 0.8). Comorbidities, such as diabetes (p = 0.6), hypertension (p = 0.1), and the use of disease-modifying antirheumatic drugs (DMARDs) (p = 0.5) and immunosuppressants (p = 0.2), did not differ between groups. Univariate analysis performed in the propensity score–matched cohort showed that SSI was observed in 53.6% of patients in the sutures group and 40.5% in the staples group (p = 0.04). No significant differences were noted regarding 30-day (p = 0.3), 90-day (p = 0.2), and 1-year (p = 0.3) readmissions and 30-day (p = 0.7), 90-day (p = 0.8), and 1-year (p = 0.8) reoperations. On multivariable logistic regression, SSI was not significantly associated with the choice of skin closure technique (p = 0.3). CONCLUSIONS After adjustment for spinal fusion, number of fused levels, the use of immunosuppressants, and other risk factors, SSI development was not significantly associated with the use of sutures versus staples following posterior spine surgery in our institution. Additionally, no significant differences were observed regarding baseline characteristics and other perioperative outcomes. The authors’ analysis shows that skin closure technique did not significantly affect SSI rates and other outcomes in these patients.

OBJECTIVE Lordotic devices have garnered increased attention for improving the segmental lordosis (SL) achieved with transforaminal lumbar interbody fusion (TLIF). However, it is unclear the degree to which surgeons maximize the "ideal" or listed lordosis of the interbody device. METHODS Patients undergoing one- or two-level TLIF for degenerative pathologies were identified and data were extracted on demographics, baseline lumbopelvic radiographic parameters, and TLIF details. The primary outcome of interest was the degree to which postoperative SL approximated the listed cage lordosis (Δtarget). Change in SL was a secondary outcome. Linear mixed-effects modeling was used to identify significant predictors of the percentage of ideal lordosis achieved. RESULTS A total of 239 treated levels were included (median patient age 66.6 years; 56.9% female); 151 levels were part of single-level TLIF constructs. The median segmental corrections were a 2.8° increase in SL and 2.8 mm in disc height. The median difference between listed cage lordosis and postoperative SL (Δtarget) was 0.5°. However, only 56.1% of levels achieved at least the listed cage lordosis. Linear mixed-effects modeling found that independent predictors of Δtarget were lower implant lordosis (estimate −1.01° [95% CI −1.15° to −0.87°] per degree, p < 0.001), greater preoperative SL (estimate 0.38° [95% CI 0.28°–0.48°] per degree, p < 0.001), greater preoperative PI (estimate 0.06° [95% CI 0.02°–0.11°] per degree, p = 0.007), and closer approximation of the anterior apophyseal ring of the caudal vertebrae (estimate −0.27° [95% CI −0.39° to −0.15°] per mm, p < 0.001). Similarly, independent predictors of postoperative SL were larger implant lordosis (estimate 0.16° [95% CI 0.05°–0.27°] per degree, p = 0.004), lower preoperative SL (estimate −0.70° [95% CI −0.79° to −0.62°] per degree, p < 0.001), greater preoperative PI (estimate 0.08° [95% CI 0.04°–0.12°] per degree, p < 0.001), and closer approximation of the anterior apophyseal ring of the cranial vertebrae (estimate −0.15° [95% CI −0.28° to −0.03°] per mm, p = 0.014). CONCLUSIONS The present results suggest that while lordosing, only 56% TLIF operations obtain the listed interbody lordosis ("target" lordosis). Anterior placement within the disc space is the only modifiable intraoperative technical factor for maximizing lordosis for a given interbody, highlighting the importance of effective disc space exenteration.

BACKGROUND AND OBJECTIVES: The Patient-Generated Subjective Global Assessment (PG-SGA) is a standardized tool for assessing malnutrition in patients with cancer. The primary aim of this study was to assess the impact of preoperative nutritional status as measured by PG-SGA on survival in patients requiring surgical intervention and/or radiotherapy for spinal metastases. METHODS: Patients with spinal metastases who underwent surgery and/or radiation therapy for symptomatic spinal metastases were enrolled in the AO Spine Metastatic Tumor Research and Outcomes Network, a prospective international multicenter research registry, between September 2017 and August 2022. Using the PG-SGA, nutritional status was classified into 3 categories: A, well nourished; B, moderately malnourished; and C, severely malnourished. RESULTS: A total of 589 patients met the inclusion criteria; 362 were classified as well nourished (61%), 159 were moderately malnourished (27%), and 68 were severely malnourished (12%). The median survival was 491 days, 328 days, and 117 days for well-nourished, moderately malnourished, and severely malnourished patients, respectively. In the multivariate analyses, severe malnourishment (HR 2.5 95% CI 1.4-4.3, P < .01) and an ECOG performance status of 3 or 4 (HR 2.7 95% CI 1.2-6.0) remained associated with significantly worse survival. CONCLUSION: Malnutrition as measured by the PG-SGA demonstrated to be significantly and independently associated with postoperative survival. The PG-SGA is a simple and useful tool to identify spinal metastases patients at risk of early postoperative mortality, and inclusion in the preoperative evaluation of these patients should be considered.

Abstract The sections in this article are: Molecular Actions of Thyroid Hormone Thyroid Hormone Regulation of Growth and Development Extrahypothalamic Thyrotropin‐Releasing Hormone Metabolic Actions of Islet Cell Hormones Insulin Glucagon Amylin Calcitonin Gene‐Related Peptide Somatostatin Pancreatic Polypeptide Thyroid Hormone Regulation of Insulin Metabolic Actions Euthyroidism Hyperthyroidism Hypothyroidism Thyroid Hormone Regulation of Glucagon Metabolic Actions Hyperthyroidism Hypothyroidism Thyroid Hormone Regulation of Somatostatin Metabolic Actions Hyperthyroidism Hypothyroidism Thyroid Hormone Regulation of Pancreatic Polypeptide Metabolic Actions Summary and Conclusions

Abstract Disclosure: A.A. Khan: Alexion Pharmaceuticals, Inc., Amgen Inc, Amolyt Pharma, Ascendis Pharma. B.L. Clarke: Amolyt Pharma, Ascendis Pharma, EnteraBio, Extend Bio, Takeda. M.R. Rubin: Ascendis Pharma, MBX Biosciences. P.E. Schwarz: Aventis Pharmaceuticals, Genmab, Novo Nordisk. D.M. Shoback: Ascendis Pharma. C. Gagnon: Amgen Inc, Ascendis Pharma, Novo Nordisk, Shire, Takeda. A. Palermo: None. L.G. Abbott: Abbott Laboratories, Ascendis Pharma, Clarus, Shire, Takeda. L. Kohlmeier: Amgen Inc, Ascendis Pharma, Radius Health, Inc. E. Tsourdi: Alexion Pharmaceuticals, Inc., Ascendis Pharma, Kyowa Kirin, Takeda, UCB. F. Cetani: None. R. Jain: Amgen Inc, Ascendis Pharma. C. Zhao: Ascendis Pharma. B. Lai: Ascendis Pharma. M.A. Makara: Ascendis Pharma. J. Ukena: Ascendis Pharma. C.T. Sibley: Ascendis Pharma. A.D. Shu: Ascendis Pharma. L. Rejnmark: Amolyt Pharma, Ascendis Pharma, BridgeBio, Kyowa Kirin, Takeda. Background: Hypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH) and is associated with reduced quality of life and a high comorbidity burden. Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) aims to alleviate hypocalcemia but does not address insufficient PTH and may increase the risk of renal complications. Palopegteriparatide is a prodrug of PTH(1-34), administered subcutaneously once daily, designed to provide active PTH within the physiological range for 24 hours/day. It is approved by the Food and Drug Administration, European Commission, and Medicines and Healthcare products Regulatory Agency. This analysis evaluated the long-term efficacy and safety of palopegteriparatide in adults with chronic hypoparathyroidism through week 156 of the PaTHway trial. Methods: PaTHway is a phase 3 trial with a 26-week randomized, double-blind, placebo-controlled period followed by an ongoing open-label extension period. Serum biochemistries were assessed at baseline and regular intervals. Renal function was assessed by estimated glomerular filtration rate (eGFR). Safety assessments included 24-hour urine calcium and treatment-emergent adverse events (TEAEs). Results: At week 156, 89% (73/82) of participants remained in the trial; of those, 96% were independent from conventional therapy (no active vitamin D and ≤600 mg/day elemental calcium) and 88% had normal albumin-adjusted serum calcium levels (8.3-10.6 mg/dL) with a mean (SD) of 8.9 (0.6) mg/dL. Mean (SD) serum phosphate (3.4 [0.6] mg/dL) and calcium x phosphate product (30.6 [5.4] mg2/dL2) levels remained within normal ranges through week 156. Mean (SD) eGFR at week 156 was 78.0 (14.5) mL/min/1.73 m2, reflecting a mean (SD) increase of 8.8 (11.9) mL/min/1.73 m2 from baseline (P&lt;0.0001); 59% and 43% of participants had an increase in eGFR of ≥5 mL/min/1.73 m2 and ≥10 mL/min/1.73 m2, respectively. Among participants with baseline eGFR &lt;60 mL/min/1.73 m2 (n=23), the mean (SD) increase in eGFR was 14.0 (8.9) mL/min/1.73 m2 from baseline to week 156. Mean (SD) 24-hour urine calcium levels normalized with palopegteriparatide treatment, remaining below the upper limit of normal (≤250 mg/day) through week 156 (162.1 [117.8] mg/day). TEAEs were mostly grade 1 or 2, with no new safety signals identified. Conclusion: Through year 3 of the PaTHway trial, retention rate was high and palopegteriparatide demonstrated consistent longer-term safety and efficacy, which included the maintenance of serum and urine biochemistries within normal levels and sustained improvement in renal function. Presentation: Saturday, July 12, 2025