Summary Of Data Research Articles

Pregnancy Among Reported Lyme Disease Cases-United States, 1992-2019.

Lyme disease (LD), the most common vector-borne disease in the United States, typically presents with a localised erythema migrans rash (EM). Left untreated, infection can disseminate to cause severe heart, joint or nervous system manifestations. Summaries of LD surveillance data have been published previously but did not include the frequency, demographic or clinical characteristics of LD cases during pregnancy. We summarised confirmed and probable LD cases by pregnancy status as reported to the U.S. Centers for Disease Control and Prevention during 1992-2019. We defined an LD case during pregnancy as one with (1) female sex, (2) age 14-49 years and (3) positive pregnancy indication. We evaluated the frequency, seasonality, age distribution, race and ethnicity, geographic distribution and clinical manifestations of LD cases during pregnancy and cases among non-pregnant females. We compared proportions using chi-squared tests. Among 698,876 reported LD cases, 112,002 (16%) were confirmed or probable cases among females aged 14-49 years; 32,301 (29%) were specifically reported as non-pregnant and 643 (0.6%) (568 confirmed and 75 probable cases) reported as pregnant. Illness onset peaked in June among LD cases during pregnancy, but in July for cases among non-pregnant females. A higher proportion of confirmed LD cases during pregnancy had only EM rash than did cases among non-pregnant females (66% vs. 60%, p = 0.019). LD cases during pregnancy are rare. Compared to non-pregnant females, cases among pregnant females more commonly involve early clinical manifestations. These patterns could suggest earlier detection or more complete reporting of LD cases during pregnancy than their non-pregnant counterparts. Earlier detection could be due to frequent contact with healthcare or increased self-advocacy during pregnancy. Prompt antimicrobial treatment is critical for preventing severe disease and reducing risk of adverse pregnancy or birth outcomes.

Static Versus Expandable Cages in Minimally Invasive Lateral Lumbar Interbody Fusion

Study Design: A meta-analysis approach to a systematic review. Objective: Perform a systematic review to identify all reports directly comparing outcomes of lateral lumbar interbody fusion (LLIF) using static versus expandable interbody cages. Specifically focusing on periprocedural complications, intraoperative morbidity, and fusion outcomes. Summary of Background Data: Minimally invasive surgical techniques, particularly LLIF, have gained popularity for their potential to reduce muscle and soft tissue dissection, leading to faster postoperative recovery. LLIF has been associated with fewer complications compared with open posterior approaches. The introduction of expandable lumbar interbody devices aims to further reduce surgical difficulty and potential complications. However, concerns include a small graft window due to the expansion mechanism and higher costs. Methods: The Web of Science, Scopus, and PubMed databases were systematically queried in accordance with PRISMA guidelines to identify articles comparing outcomes following LLIF using static and expandable interbodies. The Newcastle-Ottawa Scale (NOS) was employed to assess the risk of bias (ROB) in the selected studies. Extracted data underwent effect-size meta-analysis with the PyMARE library, using P<0.05 to define statistical significance. Results: Of the 77 identified articles, 4 studies comprising 283 patients (mean age: 67.1 y, 55.8% female) met the inclusion and exclusion criteria. A total of 150 patients (53%) were treated with static interbodies compared with 133 (47%) receiving expandable interbodies. The groups did not differ significantly with respect to operative time (P=0.59), blood loss (P=0.89), length of stay (P=0.78), subsidence (P=0.49), 24-month mean disc height (P=0.11), 24-month mean ODI (P=0.58), or 24-month mean visual analog scale (VAS) back pain (P=0.81). The expandable group saw a trend toward improved fusion rates (97% vs. 92%, P=0.06). Conclusions: The present meta-analysis suggests the use of expandable (vs. static) interbodies in LLIF surgery may result in similar surgical morbidity, subsidence, and decompression. Further prospective comparative studies are merited to validate these results.

The Benefits of Awake Spinal Surgery on Minimizing Positioning-related Complications

Study Design. Literature review and institutional analysis. Objective. This review examines the potential advantages of awake spinal surgery under neuroaxial anesthesia in minimizing positioning-related complications compared to traditional general anesthesia. Summary of Background Data. Spinal surgeries performed in the prone position under general anesthesia are associated with perioperative complications, such as ocular injury and vision loss, nerve damage, and pressure ulcers. Methods. A comprehensive literature search was conducted for articles published from 1986 to 2023 focusing on awake spinal surgery and positioning-related complications. Additionally, insights from the Mayo Clinic team were incorporated to assess the potential benefits of awake spine surgery. Results. The review identified several positioning-related complications associated with prone positioning during spine surgery, including perioperative visual loss, neuropathies, pressure ulcers, and intraabdominal hypertension leading to systemic cardiovascular effects and potential organ dysfunction. Advances at the Mayo Clinic have enabled the use of awake spinal surgery under neuroaxial anesthesia for complex procedures such as robotic transforaminal lumbar interbody fusion. The use of awake lumbar spine surgery has demonstrated advantages, including reduced positioning-related complications, immediate patient feedback to avoid harmful maneuvers, shorter operating room times, and improved hemodynamic stability. Conclusions. Awake lumbar spine surgery offers notable advantages in reducing positioning-related complications and presents a promising alternative to general anesthesia.

Impact of Low-Density Lipoprotein Levels on Rates of Pseudarthrosis After Anterior Cervical Discectomy and Fusion

Study Design. Retrospective cohort study. Objective. To understand how pre-operative LDL levels, statin intake, and fish oil intake affect rates of pseudarthrosis after single-level and multi-level ACDF. Summary of Background Data. Anterior cervical discectomy and fusion (ACDF) is commonly performed to treat cervical degenerative diseases or injuries causing neck pain, myelopathy, and radiculopathy. Pseudarthrosis following ACDF can lead to persistent symptoms and may require revision surgery. No studies have explored the link between low-density lipoprotein (LDL) levels and statin or fish oil intake on pseudarthrosis in ACDF. Methods. Patients undergoing ACDF were identified using TriNetX, a healthcare database with over 100 million patients. Pseudarthrosis rates following single-level and multi-level ACDF were compared between patients with high versus low LDL within one year before surgery. Pseudarthrosis rates were also compared between patients taking or not taking a statin as well as patients taking or not taking fish oil within six months before surgery. For all analyses, patients underwent propensity score matching in a 1:1 ratio based on relevant demographic factors and co-morbidities. Results. Patients with an LDL above 142 mg/dL, compared to below 66 mg/dL, had significantly higher rates of pseudarthrosis at 6-months, 1-year, and 2-years after single-level and multi-level ACDF. Patients not taking a statin or fish oil, compared to those taking a statin or fish oil respectively, also had significantly higher rates of pseudarthrosis at all time points after multi-level ACDF, but not single-level ACDF. Conclusion. Low LDL levels are associated with reduced rates of pseudarthrosis after single-level and multi-level ACDF. Statin and fish oil intake prior to surgery are also associated with reduced rates of pseudarthrosis after multi-level, but not single-level, ACDF. These associations may be used for pre-operative planning, patient optimization, and risk stratification.

Prior Antidepressant Prescription is Associated with Greater Opioid Prescriptions and Complications in Cervical Spine Surgery

Study Design: Retrospective cohort study of national database. Objective: This study evaluates the impact of antidepressant prescriptions on postoperative outcomes and complications in cervical spine surgery. Summary of Background Data: Patients who underwent cervical spine surgery often receive antidepressant prescriptions (ADP) to address concurrent mental health issues such as depression and anxiety. However, the use of antidepressants can affect bone metabolism. Yet, there is an opacity in the literature regarding the effects of ADP on outcomes of cervical spine surgery. Methods: Utilizing the TriNetX database, ACDF and Cervical Arthroplasty patients were matched on a 1:1 basis according to ADP status. Outcome variables such as emergency department visits, hospital readmissions, opioid prescription, and misuse, pseudoarthrosis, adjacent segment disease, and hardware failure were evaluated over follow-up periods ranging from 2 to 24 months. Results: In a matched sample of 12,838 patients, those with ADP exhibited significantly higher rates of opioid prescriptions at 2 weeks (OR 1.34, P<0.0001), 6 months (OR 1.36, P<0.0001), 12 months (OR 1.36, P<0.0001), and 24 months (OR 1.33, P<0.0001). Emergency Department visits were significantly higher at 6 months (OR 1.11, P=0.0082) and 24 months (OR 1.083, P=0.014). Opioid abuse is notably higher by 24 months (OR 1.37, P=0.0033). Hospitalization rates were significantly increased at 12 months (OR 1.16, P=0.0013) and 24 months (OR 1.18, P<0.0001). Adjacent segment disease (OR 1.54, P<0.0001 at 24 mo), hardware failure (OR 1.42, P=0.013 at 24 mo), and pseudarthrosis (OR 1.48, P<0.0001 at 24 mo) were also significantly higher in the ADP group. Conclusions: Patients with ADP undergoing cervical spine surgery experience higher risks of opioid use and abuse, increased hospital readmissions, emergency department visits, and a higher rate of mechanical complications. Level of Evidence: III

Location of Vascular Structures at Risk in Relation to Sacroiliac Joint Fusion

Study Design: Retrospective Cohort Objective: This study seeks to establish the normal distribution of the vasculature surrounding the SI joint while also demonstrating associations between distribution and laterality, sex, and ethnicity. Summary of Background Data: Sacroiliac (SI) joint fusion surgery has emerged as a viable treatment option for patients suffering from low back pain due to chronic SI joint dysfunction. Due to potential complications from iatrogenic injury to vasculature, it becomes critical to understand normal anatomy and locations with a high vasculature concentration surrounding the SI joint. Methods: The authors retrieved medical and radiographic records of patients who underwent computed tomography angiography (CTA) of the pelvis. Anterior and posterior compartments of the SI joint were established on the transverse view by creating an even coronal division of the SI joint. The superior, middle, and inferior compartments were established on the coronal view as three equal transverse compartments. The compartments in which vasculature was visualized were recorded. Results: Distribution of vasculature around the right and left hemipelvis concentrated in the inferior compartments and decreased in concentration while moving superiorly. Anterior compartments contain a higher vascularity than posterior compartments. Vasculature was present in less than 3% of the posterior middle, and posterior superior compartments while present in more than 83% of the inferior compartments. There were no significant differences with respect to vascular distribution when comparing the laterality of the right versus left hemipelvis. There were statistically significant relationships between vascular distribution and sex (P<0.05), as well as across self-reported ethnicity (P<0.05). Conclusion: SI screw placement in the posterior superior has the lowest risk of iatrogenic vascular injury. Careful consideration should be taken during SI joint fusion surgery in the inferior compartments due to its high vasculature density.

Revisiting the Consistency of Financial Disclosure Reporting by Authors at Annual Spine Conferences Show Inconsistent Improvements After 14 Years

Study Design: Cross-sectional study of presenter disclosures from the 2022 North American Spine Society (NASS), Scoliosis Research Society (SRS), and Cervical Spine Research Society (CSRS) annual research conferences. Objective: The current study aimed to evaluate the consistency of financial disclosures for authors presenting at multiple 2022 spine conferences and compared results to those previously reported in 2008. Summary of Background Data: Transparent reporting of financial relationships between physicians and industry is seen as an important way to limit/address potential bias. Thus, many research conferences require authors to disclose such relationships. Despite these requirements, variability in the financial disclosure reporting for matched speakers at 2008 major spine conferences was previously reported. Since then, the Sunshine Act mandated public financial relationships, potentially furthering attention and leading to improvements in financial disclosures. Methods: Disclosures of authors presenting at >1 of the three 2022 spine conferences were compiled from conference websites, and discrepancies were determined based on conference disclosure policies. For comparisons where both conferences required disclosure of all relationships, the discrepancy was identified if there was not a match. For comparisons where 1 conference required paper-specific relationships, and the other required all relationships, discrepancy was identified if the first was not a subset of the other. Results were compared with those reported from 2008. Results: NASS and SRS both required disclosure of all relationships, had 208 overlapping authors, and had 36.5% discrepancies. SRS and CSRS required all and paper-specific disclosures, had 37 overlapping authors, and had 29.7% discrepancies. NASS and CSRS required all and paper-specific disclosures, had 81 overlapping authors, and had 29.6% discrepancies. Overall, the average discrepancy for pairs of conferences in 2008 was 26%, and for 2022 was 32%, indicating a lack of improvement. Compared with 2008, discrepancies decreased more when disclosure requirements were the same for both conferences being considered. Conclusions: These findings demonstrate that significant variability remains in the reporting of financial conflicts of interest by authors presenting at 3 major spine conferences last year, despite previous scrutiny and the evolution of the Sunshine Act. These discrepancies may reflect the ambiguity caused by different disclosure policies and further attention is needed for this topic.

Multidimensional Plasma Lipids Affect Preeclampsia/Eclampsia: A Mendelian Randomization Study.

Circulating lipids play a crucial role during pregnancy and may impact various pregnancy-related diseases. This study employed a two-sample Mendelian randomization (MR) framework to investigate the causal relationship between alterations in multidimensional plasma lipid levels and the risk of preeclampsia or eclampsia, offering deeper insight into this association. The inverse variance weighted (IVW) method was utilized as the main analysis. Summary statistics from plasma lipidomics of 7174 Finnish individuals and summary data on preeclampsia/eclampsia from the FinnGen consortium involving 219 817 European participants were employed. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. The study identified 17 lipid species from a total of 179 lipid species associated with susceptibility to preeclampsia/eclampsia. Notably, ten species, including six triacylglycerols (TAGs) (50:1, 48:1, 56:4, 49:2, 48:2, 54:3), a diacylglycerol (DAG) (16:1_18:1), and three sphingomyelins (SMs) (d36:1, d34:1, d38:1), were found to increase the risk of preeclampsia/eclampsia. Conversely, seven species, including five phosphatidylcholines (PCs) (16:1_20:4, O-18:1_20:4, 18:1_20:4, 16:0_20:4, 17:0_20:4) and two phosphatidylethanolamines (PEAs) (18:0_20:4, 16:0_20:4), all containing arachidonic acid (ARA) in the sn-2 position, were associated with a reduced risk of preeclampsia/eclampsia (all p < 0.05). The results of thestratified analysis were consistent with these findings. Furthermore, reverse MR analysis indicated that preeclampsia/eclampsia does not causally affect plasma levels of these lipids. Our findings established a causal relationship between specific plasma lipid species and modulation of preeclampsia/eclampsia risk, providing improved resolution for risk assessment and potential therapeutic targets in the disease.

Role of CD38 in mediating the effect of Bacillus on acute pancreatitis: a study of mediated Mendelian randomization

BackgroundSome studies suggest a potential link between intestinal flora and acute pancreatitis (AP). However, the causal relationships between specific intestinal flora and AP, and the possible mediating role of immune cell traits, remain unclear.MethodsA genome-wide association study (GWAS) involving 5,959 participants was conducted to identify genetic instrumental variables associated with 473 intestinal flora taxa. Summary statistics for AP were obtained from the UK Biobank. Immune cell traits were also identified using large-scale GWAS summary data. We employed a two-sample bidirectional Mendelian randomization (MR) approach to investigate the causal relationships between intestinal flora, immune cell traits, and AP, with inverse variance weighting (IVW) as the primary statistical method. Sensitivity analyses, including the MR-Egger intercept test, Cochran’s Q test, MR-PRESSO test, and leave-one-out test, were conducted to assess the robustness of our findings. Additionally, we explored whether immune cell traits mediate the pathway from intestinal flora to AP.Results11 positive and 11 negative causal relationships were identified between genetic susceptibility in intestinal flora and AP. Furthermore, 19 positive and 9 negative causal relationships were observed between immune cell traits and AP. Notably, CD38 mediated the causal relationship between Bacillus C and AP.ConclusionsThis study is the first to uncover novel causal relationships between various intestinal flora and acute pancreatitis, emphasizing the mediating role of immune cell traits in the pathway from intestinal flora to AP. It also provides new evidence supporting the conditional pathogenicity of the Bacillus genus.

Abstract PR004: Second generation RNA Polymerase I inhibitor PMR-116 targets ribsomal RNA synthesis to potently treat a broad spectrum of malignancies

Abstract Purpose and rational for the study: The purpose of the study was to develop novel 2nd generation ribosomal RNA synthesis inhibitors for cancer treatment. Ribosome biogenesis (RiBi) is essential for cell growth and proliferation. Transcription of ribosomal RNA genes by Pol I is a critical step in RiBi and is tightly regulated by tumor suppressors and oncoproteins. Indeed, the ability of the potent oncoprotein, MYC, to drive RiBi is necessary for its oncogenic activity (Bywater et al., Cancer Cell, 2011). These data suggested that targeting RiBi, might be a promising strategy to treat malignancies, especially those driven by MYC. To test this, we developed the 1st small molecule inhibitor of Pol I transcription, CX-5461 (Drgyin et al., Cancer Research 2011). While CX-5461 has shown promising activity in pre-clinical studies (Bywater et al., Cancer Cell, 2011; Rebello et al., Clin Cancer Res., 2016; Hein et al., Blood, 2017) and in early Phase trials (Khot et al., Cancer Discovery, 2019; Hilton et al., Nat Commun. 2022) its mechanism of action remains controversial with evidence of off-target activity inducing DNA damage through inhibition of TOPO2a (Cameron et al., Biomedicines, 2024; Koh et al., Nature Genetics, 2024). Thus, to determine if selective inhibition of Pol I transcription in the absence of DNA damage can be used to therapeutical treat cancer in vivo, we developed a series of more selective 2nd generation Pol I inhibitors with our lead compound being PMR-116. Methods and summary of data: We demonstrate that PMR-116 is selective for inhibition of Pol I over Poll II transcription and functions by stalling the Pol I complex at the rDNA promoter. PMR-116, exhibits improved drug-like properties and pharmacokinetics compared to 1st generation CX-5461. As a single agent PMR-116 efficiently treats a range of pre-clinical models of hematologic and solid tumors including lymphoma, AML, hepatocellular carcinoma and prostate cancer. MYC expression positively correlates with sensitivity to PMR-116 in human cancer cell lines and high MYC tumors in vivo are exceptionally sensitive to PMR-116. In contrast to CX-5461, the therapeutic response to PMR-116 occurs in the absence of DNA damage suggesting that DNA damage is not an obligatory response to Pol I transcription inhibition but rather an off-target effect of the 1st generation drug. Small molecule drug combination screens in AML cells demonstrate that PMR-116 works synergistically to reduce cell viability with a range of drugs including carfilzomib and quisinostat used for treatment of hematologic malignancies. Conclusions: Our data establishes inhibition of RNA polymerase I as a bone fide therapeutic target for cancer therapy and demonstrated that PMR-116 is a promising new broad- spectrum anti-cancer drug particularly for those tumors driven by MYC, which are highly refractory to standard therapies. Based on these data we have launched a Phase I clinical trial of PMR-116 in patients with advanced solid tumors (CTRN12620001146987). Citation Format: Rita Ferreira, Katherine M. Hannan, Konstantin Panov, Thejanni Udumanne, Amee J George, Zaka Yuen, Perlita Poh, Eric Kusnadi, Alisee Huglo, Mitchell Lawrence, Mustapha Haddach, Denis Drygin, Luc Furic, Ross D Hannan, Nadine Hein. Second generation RNA Polymerase I inhibitor PMR-116 targets ribsomal RNA synthesis to potently treat a broad spectrum of malignancies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR004.

Vertebral Fracture Prediction from MRI-based Vertebral Bone Quality Scores in Postmenopausal Women

Study Design. A longitudinal cohort study Objective. The study aims to assess the lumbar MRI-based vertebral bone quality (VBQ) score and dual energy x-ray absorptiometry (DXA) T score in a longitudinal cohort of postmenopausal women and to evaluate the performance of these scores in predicting VF over 5 years of follow-up. Summary of Background Data. VBQ scores can be used for osteoporosis screening and identification of vertebral fractures (VFs). However, due to limitations in prior cross-sectional studies, definitive conclusions about the causal associations between the VBQ score and incident VF have not been drawn. Methods. Postmenopausal women with baseline DXA and lumbar MRI data were enrolled. Follow-up assessments were conducted over 5 years after the baseline examination; both anteroposterior- and lateral-view thoracolumbar spine radiographs were captured to evaluate incident VF. At baseline, correlation analyses between the VBQ score and osteoporosis or preexisting VF were performed. A Cox regression model for multivariate logistic regression was used to analyze the risk factors for incident VF. The hazard ratio (HR) was calculated. Results. 137 postmenopausal women were included. The VBQ score was moderately correlated with lumbar bone mineral density at baseline (r=0.4, P&lt;0.001). Patients with incident VF had significantly lower T scores (-3.4 vs. -1.87, P&lt;0.001) and higher VBQ scores (4.62 vs. 4.03, P&lt;0.001) at baseline than those without incident VF. After adjusting for age, weight, creatinine clearance, and alkaline phosphatase levels, the HRs for the VBQ score and T score were 1.93 and 0.71, respectively. After adjusting for the T score, an increased VBQ score was independently associated with an increased risk of incident VF, with an HR of 1.87. Conclusion. The VBQ score was moderately correlated with DXA T score and was a predictor of incident VF risk independent of bone mineral density in postmenopausal women.

Impact of Enhanced Recovery After Surgery (ERAS) Protocols on Outcomes Up to Two Years After Adult Structural Spine Disorder Surgery

Study Design. Retrospective cohort study of prospectively enrolled database Objective. We analyze the recovery pattern of Adult Structural Spine Disorder (ASD) patients who underwent corrective surgery with Enhanced Recovery After Surgery protocol (ERAS+), including physical and psychological prehabilitation components, compared to non-ERAS protocol (ERAS-) up to 2-years after surgery. Summary of Background Data. Spine surgery for ASD is often highly invasive, which can contribute to prolonged recovery. The trajectory of recovery may be accelerated by the application of enhanced recovery principles. Methods. Inclusion criteria were operative patients with ASD&gt;18yrs with complete baseline, 90 days perioperative, and 2-year postoperative data. We assessed differences in baseline demographics, surgical details, baseline Health-Related Quality of Life (HRQL), and surgical outcomes between ERAS+ and ERAS- patients. Outcomes included adverse events, reoperations, and radiographic parameters such as sacral slope (SS), pelvic tilt (PT), pelvic incidence-lumbar lordosis (PI-LL) mismatch, sagittal vertical axis (SVA), lumbar lordosis (LL), T2–T12 kyphosis, and maximum Cobb angle. Additionally, HRQL measures included the PCS, ODI, NDI, EQ-5D, SRS-22r total and domain scores, NRS-Back, and NRS-Leg. We used multivariable logistic regression and ANCOVA to adjust for confounding. Results. 471 patients with ASD met inclusion criteria, with 59 designated ERAS+. Those individuals ERAS+ were older (64.1±13.0 vs. 58.0±16.0;P=0.005), had a higher CCI, (2.4±1.8 vs. 1.4±1.6;P&lt;0.001), and exhibited a higher modified ASD frailty index (8.2±5.4 vs. 6.3±4.9;P=0.019). Adjusted analysis demonstrated the ERAS+ cohort demonstrated lower likelihood of overall reoperations (OR:0.3; 95%CI:0.13-0.89), and a lower likelihood of overall adverse events (OR:0.4;CI95%:0.19-0.93). ERAS+ was more likely to achieve the MCID in the SRS-22r Total scores at 6 months(OR:3.1;CI95%:1.2-8.4), self-image domain at 6 months (OR:9.0;CI95%:1.6-50.0), in the pain domain at 6 months (OR:3.5;CI95%:1.01-11.9) and 1 year postoperatively (OR:2.6;CI95%:1.03-6.7), and in the SF-36’s physical component summary scores (PCS) at 1 year (OR:2.1;CI95%:1.05-4.2). No other statistically significant differences in HRQL were observed at the remaining time points (P&gt;0.05). Conclusion. Our work is the first to evaluate HRQL metrics and complication over two-years following ASD correction with ERAS. Despite presenting with more severe baseline frailty and higher comorbidity profiles, patients with ASD who underwent corrective surgery with an ERAS protocol experienced fewer short-term adverse events, and improved HRQL. We believe ERAS following ASD surgery leads to faster functional recovery, reduced postoperative deconditioning, and improved quality of life.

Cervical Disc Arthroplasty for the Treatment of Adjacent Segment Disease after Anterior Cervical Discectomy and Fusion

Study Design. A retrospective chart review was conducted at a single institution. Objective. The purpose of this study was to investigate clinical outcomes of cervical disc arthroplasty (CDA) used for the treatment of symptomatic adjacent segment disease (ASD) developed after anterior cervical discectomy and fusion (ACDF). Summary of Background Data. A major clinical concern following ACDF is the development of ASD. ASD after ACDF is often treated with an additional fusion, but risks include pseudoarthrosis and further ASD. CDA is a motion preserving alternative that addresses these concerns, and therefore, has been proposed as an alternative treatment for ASD after ACDF. Methods. CDA patients with prior adjacent-level ACDF (n=120) were identified from a consecutive series of CDA patients at one institution. Pre- to post- CDA patient-reported outcome measures were compared using the paired Wilcoxon signed-rank test. Results. A total of 142 devices were implanted – 98 patients underwent a one-level CDA, and 22 patients underwent two-level CDA. The mean follow-up duration after CDA was 32.11 months. Neck pain, arm pain, and Neck Disability Index (NDI) scores significantly improved from the preoperative to postoperative timepoint (respectively: 6.14 to 3.02, 4.42 to 1.61, 44.28 to 28.62, all P&lt;0.001). In total, 7 patients underwent reoperation (5.83%). One of these patients underwent reoperation for pseudarthrosis at the level of ACDF following a hybrid procedure. The indications for index level reoperations (n=3) were foraminal stenosis, osteolysis, and postoperative hematoma. All patients with an adjacent level reoperation (n=3) received surgery at levels adjacent to the prior fusion, not the more recent CDA. Conclusion. The results of this study found CDA was effective for the treatment of ASD following ACDF. CDA appears to be a viable treatment option for ASD after ACDF in appropriately selected patients.

Impact of Obstructive Sleep Apnea on Outcomes after Anterior Cervical Discectomy and Fusion

Study Design. Retrospective Cohort Objective. To evaluate the impact of having a history of Obstructive Sleep Apnea (OSA) in patients undergoing anterior cervical discectomy and fusion (ACDF) on postoperative outcomes. Summary of Background Data. With an aging population and rates of obesity increasing, comorbidities that influence patient safety are increasingly common. One frequently overlooked comorbidity is OSA which affects nearly 24% of the population. Despite its prevalence, the impact of OSA on outcomes following ACDF is poorly understood. Methods. A retrospective analysis of patients &gt;18 years who underwent 1-4 level ACDF at an academic medical center from 2014-2020 was performed. Patient’s age, sex, BMI, CCI, hypertension, diabetes, and levels fused were propensity matched in a 3:1 fashion. Outcomes assessed included inpatient complications, 30 and 90-day ED visits, 30 and 90-day readmissions, reoperations, and one-year PROMs. Results. A total of 344 ACDF patients (86 OSA, 258 No OSA) were included. 30-day ED visits were higher among the OSA compared to the non-OSA group (5.85% vs 0%, P=0.001). Among ED visits, there were 2 patients with pneumonia, 1 with dysphagia, and 1 with extremity weakness, none of which warranted readmission. ED visits equalized in the 30–90-day window. There were no significant differences in inpatient complications, LOS, discharge disposition, readmissions, reoperations, and one-year PROMs. Conclusion. Patients with a history of OSA underwent ACDF without an increased risk of postoperative complications, readmissions, or reoperations and experienced a complication rate much lower than previously suggested by current literature. OSA patients experienced similar improvements in PROMs at 1-year follow-up. Surgeons should counsel OSA patients regarding the increased risk of 30-day ED visits. But overall, patients can expect safe and equivalent outcomes compared to non-OSA patients which lends support for safe outpatient surgery in this population.

Changes in Physical Function After Long Corrective Fusion to the Ilium for Adult Spinal Deformity

Study Design. Prospective cohort study. Objective. To investigate longitudinal changes in physical functional status after long corrective fusion in patients with adult spinal deformity (ASD) during 2 years of follow-up. Summary of Background Data. In ASD surgery, reports assessing physical functional status in long-term observations for more than a year are lacking. Assessing whether patients maintain significant improvements in their physical status with a longer follow-up duration is crucial. Methods. A total of 70 female patients with ASD who underwent long corrective fusion of ≥ 7 segments between June 2016 and June 2022 were included in this study. Preoperative and postoperative assessments (at 6 months, 1 year, and 2 years) included radiographic spinopelvic parameters, health-related quality of life (HRQOL) using the Scoliosis Research Society Outcome Instrument-22 (SRS-22) questionnaire, and physical function tests conducted by a physical therapist. Results. All domains of the SRS-22 improved the most in the first 6 months after surgery (P &lt;0.0001); however, the Pain and Function domains continued to improve gradually until 2 years postoperatively. Regarding trunk dynamic balance, the timed up-and-go test score improved gradually until 2 years postoperatively (P &lt;0.0001). Regarding gait performance, gait speed and the 6-minute walking test improved the most in the first 6 months after surgery (P &lt;0.01) and almost reached a plateau 1 year postoperatively. Conclusions. Long corrective fusion for ASD significantly enhanced physical function and HRQOL within 2 years, with the greatest improvement in the first 6 months after surgery. These findings underscore the importance of increasing activities of daily living through early exercise instruction, as well as preventive measures to avoid early surgery-related complications. Level of Evidence. 3

Meta-Analysis of Exposure-Adverse Event Relationships for Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) have become a vital class of therapeutics in oncology because of their ability to selectively deliver potent drug molecules to tumor cells. However, ADC-associated toxicities cause high failure rates in the clinic and hinder their full potential. Due to the complex structure and pharmacokinetics of ADCs, it is challenging to identify the drivers of their toxicities. Here, quantitative analysis was performed to correlate the incidence of clinical adverse events (AEs) with nine different commonly measured exposure parameters collected from study-level summary data. We considered ADC analytes for different classes of ADCs, to identify ADC analytes that are strongly associated with the AEs for ADCs. Published clinical exposure and safety data for any grade and grade ≥3 AEs from 40 publications across six ADCs and three payloads were collected and analyzed. Exposure-AE relationships were quantified using logit models, and the strength of the correlations and rank order were determined. The analysis suggests that deruxtecan ADC-related toxicities correlated most strongly with the exposure of the free payload; monomethyl auristatin E (MMAE) ADC-related toxicities correlated with the free MMAE area under the curve; and pyrrolobenzodiazepine ADC-related toxicities correlated with no specific analyte but the dose. These findings agree with the published literature and support the notion that AE profiles are often shared by ADCs that deliver the same cytotoxic payload. The exposure-AE relationships presented here, together with identification of the most informative ADC analytes, may facilitate more focused mechanistic studies on the drivers of clinical AEs and could support dosing decisions during clinical development of ADCs.

Gastroesophageal reflux disease and risk factors in schoolchildren

Aim. To study the association between family predisposition to gastrointestinal diseases with gastroesophageal reflux disease (GERD) in schoolchildren in ethnic populations of Tuva. Material and methods. A total of one thousand seventy nine children (761 Mongoloid-Tuvinian and 318 Caucasian) aged of 7–17 years in the Republic of Tyva were examined. Anamnestic data and information on gastrointestinal complaints in schoolchildren were obtained. The diagnostic criterion for GERD was complaints of weekly heartburn. Statistical analysis was performed using the Pearson chi-square test. Results. GERD children more often had anamnestic data on gastritis (p = 0.025), gastric ulcer (p = 0.039) and oncological diseases of the gastrointestinal tract (p = 0.052) in parents. At the same time, schoolchildren of the indigenous population with GERD manifestations had greater unfavourable conditions for a number of diseases in parents: gastritis (p = 0.01), gastric ulcer (p = 0.012). Whereas in Caucasians, a similar association was not established. The association between GERD in schoolchildren and gastrointestinal pathology in grandparents (2nd degree of kinship) also concerned only Tuvans in the presence of gastritis (p = 0.023). Summary data on family history of gastrointestinal diseases (1st and 2nd generation relatives) in GERD children, as expected, prevailed in Tuvans (gastritis (p = 0.004), peptic ulcer (p = 0.033) and specifically gastric ulcer (p = 0.02)). A more negative association between GERD in Tuvan children and a family predisposition to gastrointestinal diseases, in contrast to Caucasians, may be due to a higher prevalence of a number of gastrointestinal diseases in adults and is related with the functional features of the system, formed under the influence of the features of traditional life and nutrition. Conclusion. In the Republic of Tyva, GERD in native schoolchildren is associated with a wide range of gastrointestinal diseases in relatives.

Abstract 4136550: In-hospital cardiac arrest can be detected by Innovative smart healthcare syste

Background: Predicting in-hospital cardiac arrest (IHCA) is crucial for preventing patient fatalities. However, it remains challenging due to the irregularities in time series data across various features. Previous studies relied on traditional medical scoring systems, but their accuracy was limited as the models were overly simplistic. Recent research using machine learning methods has shown improved results. In our work, we employ deep learning and time series approaches, which are considered the most powerful models for addressing complex problems in recent years. Method/Research Design: The cohort study took place in a hospital in Taiwan from January 2016 to August 2022, involving 252,000 patients in general wards. Input data encompassed basic information, vital signs, Glasgow Coma Scale scores, medication, etc., to predict IHCA occurrences within 24 hours. Given the immediacy of IHCA events, we utilized left alignment to handle time series. Evaluation metrics included the area under the receiver operating characteristic curve (AUROC). Results: We compared three types of settings. The first was based on scoring systems, where the national early warning system (NEWS) achieved an AUROC of 0.756, and the modified early warning score (MEWS) reached 0.653. In the next setting, based on the data summary within a given time interval, the machine learning models XGBoost and deep learning model TabNet achieved AUROCs of 0.863 and 0.839, respectively. This indicates that machine learning outperforms traditional medical methods. The final setting involved time series analysis, where XGBoost and the Gate Recurrent Unit (GRU) network achieved 0.848 and 0.904, respectively, surpassing all previous settings. Conclusion: Our study demonstrates that learning-based methods outperform rule-based methods in predicting IHCA events. Machine learning algorithms offer more possibilities and have the potential to address complex problems effectively. Moreover, considering time series data rather than summarizing within fixed intervals preserves information and leads to better scores. Leveraging the time series deep learning method, GRU shows promising potential in significantly reducing the risk of IHCA events.

The protective effect of higher serum triacylglycerol (51:4) levels against Parkinson's disease.

Emerging evidence has shown a strong correlation between serum triacylglycerol (TAG) levels, the inflammatory response, and Parkinson's disease (PD) onset. However, the causal relationship between TAG levels and PD has not been well-established. We aimed to investigate the relationship between serum TAG levels and risk of PD and explore the potential mediating role of circulating immune cells and inflammatory proteins. We utilised genotype data from the GeneRISK cohort, and summary data from genome wide association studies investigating PD, circulating immune cells, inflammatory proteins, and plasma lipidomes. Using Mendelian randomization (MR) and multivariate MR (MVMR) analysis, we further adjusted for phosphatidylcholine (17:0_18:1) and triacylglycerol (58:7). Our results suggested a robust causal link between higher serum TAG (51:4) levels and a decreased risk of PD, with one standard deviation genetically instrumented higher serum TAG (51:4) level leading to a 21 percent [95% CI, 0.66 - 0.96] reduction in the risk of PD (p = 0.015). Additionally, the results of the mediation analysis suggested a possible role for mediation through circulating immune cells (including IgD-CD38-B cells and resting CD4 regulatory T cells), but not circulating inflammatory proteins, in the causal relationship between the plasma lipidomes and PD. Our study confirms a causal relationship between higher serum TAG (51:4) levels and a lower risk of PD and clarifies a possible role for mediation through circulating immune cells, but not inflammatory proteins. These findings indicate that serum triacylglycerol (51:4) regulates immunity to effectively lower the risk of PD.

Indoor and ambient influences on PM2.5 exposure and well-being for a rail impacted community and implications for personal protections

Abstract Background&amp;#xD;Higher air pollution concentrations can be observed near rail networks, local and highway automobile corridors, and shipyards. Communities adjacent to such sources are disproportionately exposed to air pollution from these stationary and mobile sources. One such community is West San Bernardino in California, where households are feet away from the Burlington Northern Santa Fe intermodal facility and are impacted by activities that are estimated to continuously emit air pollutants due to 24/7 operation.&amp;#xD;Objective&amp;#xD;This study aimed to (1) quantify the impact of personal mobility and housing characteristics on daily PM2.5 exposures and well-being for West San Bernardino community members, and (2) develop individualized resilience plans for community collaborators to support future PM2.5 exposure reduction. &amp;#xD;Methods&amp;#xD;Personal PM2.5 exposures were measured for community collaborators for seven consecutive days during three deployment periods: October 2021, January 2022, and March 2022. Indoor and ambient PM2.5 levels were also continuously measured for five households over six months using PurpleAir Classic monitors. Demographic and well-being data were collected upon recruitment and after each week of engagement, respectively. &amp;#xD;Results&amp;#xD;Personal exposures in home microenvironments were highest near the railyard and lower farthest away from the railyard. Home exposures were 40% higher on average compared to non-home microenvironments. Household PM2.5 had a higher-than-expected average infiltration factor of 0.55, and indoor 98th percentiles across the households far exceeded a healthy level at an average of 165 μg/m3. Resilience plans featured summaries of personal data and recommendations for mitigating exposures. &amp;#xD;Significance&amp;#xD;Results suggest that surrounding land use and residential building characteristics compound to worsen air pollution exposures beyond what is expected for exposures in non-industrialized areas. Findings prompt a call for stronger regulation, not only for emissions, but also for indoor air quality and zoning standards that specifically protect disproportionately impacted communities.