Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing.

Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.

Prevalence of Elevated ALT in Adolescents in the US 2011-2018.

OBJECTIVE: The objective of this study is to characterize suspected nonalcoholic fatty liver disease (NAFLD) using elevated alanine aminotransferase (ALT) in a diverse and nationally representative cohort of adolescents and to characterize higher ALT elevation in adolescents with obesity. METHODS: Data from the National Health and Nutrition Examination Survey 2011-2018 were analyzed for adolescents 12-19 years. Participants with causes for elevated ALT other than NAFLD were excluded. Race and ethnicity, sex, body mass index (BMI), and ALT were examined. Elevated ALT was defined as >22 U/L (females) and >26 U/L (males) using the biologic upper normal limit (ULN). Elevated ALT thresholds up to 2X-ULN were examined among adolescents with obesity. Multivariable logistic regression was used to determine the association of race/ethnicity and elevated ALT, adjusting for age, sex, and BMI. RESULTS: Prevalence of elevated ALT in adolescents was 16.5% overall and 39.5% among those with obesity. For White, Hispanic, and Asian adolescents, prevalence was 15.8%, 21.8%, and 16.5% overall, 12.8%, 17.7%, and 27.0% in those with overweight, and 43.0%, 43.5%, and 43.1% in those with obesity, respectively. Prevalence was much lower in Black adolescents (10.7% overall, 8.4% for overweight, 20.7% for obesity). Prevalence of ALT at 2X-ULN was 6.6% in adolescents with obesity. Hispanic ethnicity, age, male sex, and higher BMI were independent predictors of elevated ALT. CONCLUSIONS: Prevalence of elevated ALT in U.S. adolescents is high, affecting 1 in 6 adolescents during 2011-2018. The risk is highest in Hispanic adolescents. Asian adolescents with elevated BMI may comprise an emerging risk group for elevated ALT.

Performance of Biopsy Tools in Procurement of Lung Tissue in Robot-Assisted Peripheral Navigation: A Comparison.

INTRODUCTION: Robot-assisted navigation bronchoscopy (RANB) has been gaining traction as a new technology for minimally invasive biopsies of peripheral pulmonary lesions (PPLs). Cryobiopsy is an established method of procuring satisfactory lung tissues and can be safely paired with RANB. While some studies have evaluated the diagnostic accuracy and yield of this procedure, there is limited data on the utility of various biopsy tools, the sequence of use and differences in tissue characteristics based on the sampling techniques. Therefore, this study aims to examine the real-life performance of needle, forceps and cryoprobe when utilized in succession with RANB in the biopsy of PPLs, and to evaluate the specific types of tissue samples obtained from each instrument. METHODS: In a single-center retrospective study, 50 patients presenting 52 PPLs underwent biopsies sequentially using fine-needle aspiration (FNA), forceps, and cryoprobe. All procedures were performed via cone-beam CT-assisted RANB. Performance metrics, such as diagnostic yield, sensitivity, and specificity, were determined by classifying malignancy as true positives and explicit benign findings as true negatives. Tissue sizes and subtypes were based on pathology description and compared with Student's t test and χ2, respectively. RESULTS: Cryobiopsy, when performed sequentially after FNA then forceps, was able to retrieve more alveolar tissue (p = 0.0098) among diagnosed lesions and showed higher diagnostic yield (p = 0.001) in PPL biopsy with RANB platform. Cryobiopsy was also able to obtain larger sample size (p = 0.0087). No difference was observed in the diagnosis of malignancy between forceps and cryobiopsy (p = 0.8877). CONCLUSION: The integration of RANB and sequential biopsies, utilizing FNA, forceps, and cryoprobe, can efficiently diagnose PPLs and procure alveolar tissues. Further research based on histopathological subtypes is required to assess its prognostic significance.

The Prevalence of Elevated Alanine Aminotransferase Levels Meeting Clinical Action Thresholds in Children with Obesity in Primary Care Practice.

Using a clinically actionable threshold for alanine aminotransferase to define suspected nonalcoholic fatty liver disease in US children with obesity, the risk of suspected nonalcoholic fatty liver disease was highest for Asian and Hispanic race/ethnicity, male sex, and severe obesity.

Practice patterns and outcomes of maintenance dialysis in children < 2 years of age: a report of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS).

BACKGROUND: Peritoneal dialysis (PD) is the preferred mode of kidney replacement therapy (KRT) in infants and young children with kidney failure. Hemodialysis (HD) is used less often due to the technical challenges and risk of complications in smaller patients. There are limited data on chronic HD in this patient population. METHODS: This was a retrospective study of children younger than 24 months on HD and PD in the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry between January 1992 and December 2018. We compared demographic, clinical, and laboratory data and outcomes, including patient survival and kidney transplantation. RESULTS: We identified 1125 infants and toddlers younger than 2 years of age who initiated KRT from January 1992 to December 2018. Of those, 1011 (89.8%) initiated peritoneal dialysis and 114 (10.2%) initiated hemodialysis. Median (IQR) age at HD onset was 12 (5.6-18.7) months compared to 4.6 (0.8-11.7) months at PD onset (p < 0.001). The primary cause of kidney failure with replacement therapy was congenital anomalies of the kidney and urinary tract (56.2% of PD versus 39.5% of HD group). Patients on HD had superior growth and nutrition markers than those on PD. Patient survival was similar between the two groups. CONCLUSIONS: While HD may not be the modality of choice for chronic KRT in younger children, 10% of children younger than 24 months of age receive maintenance HD and the numbers have increased over time. Patient survival on dialysis is similar irrespective of dialysis modality. A higher resolution version of the Graphical abstract is available as Supplementary information.

Positive beliefs about worry: An evaluation of the Why Worry-II questionnaire in patients with anxiety and mood disorders: Implications for theory and treatment.

Positive beliefs about worry are an important factor that has been shown to be associated with the reduction of worry severity with cognitive behavioural therapy. The present study evaluated the psychometric properties of a measure of positive beliefs about worry, the Why Worry Questionnaire II (WW-II; Hebert et al., 2014, 0.1016/j.paid.2013.08.009) with a clinical sample. The present study also compared mean scores on the WW-II in the present clinical sample with scores found in non-clinical samples. Finally, the study compared mean scores on the WW-II between groups with primary diagnoses of generalized anxiety disorder (GAD), major depressive disorder (MDD) and anxiety disorder not otherwise specified (NOS). The confirmatory factor analysis found the five-factor model an adequate to good fit to the data, and the WW-II demonstrated excellent internal consistency within this clinical sample. Additionally, scores on the WW-II in the present sample were significantly higher than scores found by in their non-clinical sample. Finally, no significant mean differences were found between primary diagnoses of GAD, anxiety disorder NOS or MDD. Important theoretical and clinical implications and suggestions for future research are discussed.

Hepatic Steatosis is Negatively Associated with Bone Mineral Density in Children.

OBJECTIVE: To evaluate the relationship between hepatic steatosis and bone mineral density (BMD) in children. In addition, to assess 25-hydroxyvitamin D levels in the relationship between hepatic steatosis and BMD. STUDY DESIGN: A community-based sample of 235 children was assessed for hepatic steatosis, BMD, and serum 25-hydroxyvitamin D. Hepatic steatosis was measured by liver magnetic resonance imaging proton density fat fraction (MRI-PDFF). BMD was measured by whole-body dual-energy x-ray absorptiometry. RESULTS: The mean age of the study population was 12.5 years (SD 2.5 years). Liver MRI-PDFF ranged from 1.1% to 40.1% with a mean of 9.3% (SD 8.5%). Across this broad spectrum of hepatic fat content, there was a significant negative relationship between liver MRI-PDFF and BMD z score (R = -0.421, P < .001). Across the states of sufficiency, insufficiency, and deficiency, there was a significant negative association between 25-hydroxyvitamin D and liver MRI-PDFF (P < .05); however, there was no significant association between vitamin D status and BMD z score (P = .94). Finally, children with clinically low BMD z scores were found to have higher alanine aminotransferase (P < .05) and gamma-glutamyl transferase (P < .05) levels compared with children with normal BMD z scores. CONCLUSIONS: Across the full range of liver MRI-PDFF, there was a strong negative relationship between hepatic steatosis and BMD z score. Given the prevalence of nonalcoholic fatty liver disease and the critical importance of childhood bone mineralization in protecting against osteoporosis, clinicians should prioritize supporting bone development in children with nonalcoholic fatty liver disease.

Pediatric kidney transplant in undocumented immigrants: An American perspectives.

Kidney transplant in undocumented immigrants remains controversial. While in the United States the National Organ Transplant Act does not prohibit inclusion of these patients as transplant candidates, legislative and financial barriers and ethical concerns remain. The purpose of this article was to review the legal and financial barriers to kidney transplant for children with ESKD who are undocumented immigrants and consider arguments for and against inclusion of these children as kidney transplant candidates. While this discussion is largely restricted to the experience in the United States and its unique healthcare system, the themes and ideas may be more generalizable to the experience in many high-income countries. We conclude that access to kidney transplant is legal, ethically justifiable, and clearly in the best interest of these children. Transplant professionals should continue to advocate for changes in policy and greater resources to support these patients.

Dairy Fat Intake, Plasma Pentadecanoic Acid, and Plasma Iso-heptadecanoic Acid Are Inversely Associated With Liver Fat in Children.

OBJECTIVES: We sought to evaluate the relevance of pediatric dairy fat recommendations for children at risk for nonalcoholic fatty liver disease (NAFLD) by studying the association between dairy fat intake and the amount of liver fat. The effects of dairy fat may be mediated by odd chain fatty acids (OCFA), such as pentadecanoic acid (C15:0), and monomethyl branched chain fatty acids (BCFA), such as iso-heptadecanoic acid (iso-C17:0). Therefore, we also evaluated the association between plasma levels of OCFA and BCFA with the amount of liver fat. METHODS: Observational, cross-sectional, community-based sample of 237 children ages 8 to 17. Dairy fat intake was assessed by 3 24-hour dietary recalls. Plasma fatty acids were measured by gas chromatography-mass spectrometry. Main outcome was hepatic steatosis measured by whole liver magnetic resonance imaging proton density fat fraction (MRI-PDFF). RESULTS: Median dairy fat intake was 10.6 grams/day (range 0.0--44.5 g/day). Median liver MRI-PDFF was 4.5% (range 0.9%-45.1%). Dairy fat intake was inversely correlated with liver MRI-PDFF (r = -0.162; P = .012). In multivariable log linear regression, plasma C15:0 and iso-C17:0 were inverse predictors of liver MRI-PDFF (B = -0.247, P = 0.048; and B = -0.234, P = 0.009). CONCLUSIONS: Dairy fat intake, plasma C15:0, and plasma iso-C17:0 were inversely correlated with hepatic steatosis in children. These hypothesis-generating findings should be tested through clinical trials to better inform dietary guidelines.

Dilated cardiomyopathy myosin mutants have reduced force-generating capacity.

Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) can cause arrhythmias, heart failure, and cardiac death. Here, we functionally characterized the motor domains of five DCM-causing mutations in human ß-cardiac myosin. Kinetic analyses of the individual events in the ATPase cycle revealed that each mutation alters different steps in this cycle. For example, different mutations gave enhanced or reduced rate constants of ATP binding, ATP hydrolysis, or ADP release or exhibited altered ATP, ADP, or actin affinity. Local effects dominated, no common pattern accounted for the similar mutant phenotype, and there was no distinct set of changes that distinguished DCM mutations from previously analyzed HCM myosin mutations. That said, using our data to model the complete ATPase contraction cycle revealed additional critical insights. Four of the DCM mutations lowered the duty ratio (the ATPase cycle portion when myosin strongly binds actin) because of reduced occupancy of the force-holding A·M·D complex in the steady state. Under load, the A·M·D state is predicted to increase owing to a reduced rate constant for ADP release, and this effect was blunted for all five DCM mutations. We observed the opposite effects for two HCM mutations, namely R403Q and R453C. Moreover, the analysis predicted more economical use of ATP by the DCM mutants than by WT and the HCM mutants. Our findings indicate that DCM mutants have a deficit in force generation and force-holding capacity due to the reduced occupancy of the force-holding state.

Prevalence of Nonalcoholic Fatty Liver Disease in Children with Obesity.

OBJECTIVES: To determine the prevalence of nonalcoholic fatty liver disease (NAFLD) in children with obesity because current estimates range from 1.7% to 85%. A second objective was to evaluate the diagnostic accuracy of alanine aminotransferase (ALT) for NAFLD in children with obesity. STUDY DESIGN: We evaluated children aged 9-17 years with obesity for the presence of NAFLD. Diseases other than NAFLD were excluded by history and laboratories. Hepatic steatosis was measured by liver magnetic resonance imaging proton density fat fraction. The diagnostic accuracy of ALT for detecting NAFLD was evaluated. RESULTS: The study included 408 children with obesity that had a mean age of 13.2 years and mean body mass index percentile of 98.0. The study population had a mean ALT of 32 U/L and median hepatic magnetic resonance imaging proton density fat fraction of 3.7%. The estimated prevalence of NAFLD was 26.0% (95% CI 24.2%-27.7%), 29.4% in male patients (CI 26.1%-32.7%) and 22.6% in female patients (CI 16.0%-29.1%). Optimal ALT cut-point was 42 U/L (47.8% sensitivity, 93.2% specificity) for male and 30 U/L (52.1% sensitivity, 88.8% specificity) for female patients. The classification and regression tree model with sex, ALT, and insulin had 80% diagnostic accuracy for NAFLD. CONCLUSIONS: NAFLD is common in children with obesity, but NAFLD and obesity are not concomitant. In children with obesity, NAFLD is present in nearly one-third of boys and one-fourth of girls.

Clinical Practice Approach to Nonalcoholic Fatty Liver Disease by Pediatric Gastroenterologists in the United States.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is common; however, no information is available on how pediatric gastroenterologists in the United States manage NAFLD. Therefore, study objectives were to understand how pediatric gastroenterologists in the US approach the management of NAFLD, and to identify barriers to care for children with NAFLD. METHODS: We performed structured one-on-one interviews to ascertain each individual pediatric gastroenterologist's approach to the management of NAFLD in children. Responses were recorded from open-ended questions regarding screening for comorbidities, recommendations regarding nutrition, physical activity, medications, and perceived barriers to care. RESULTS: Response rate was 72.0% (486/675). Mean number of patients examined per week was 3 (standard deviation [SD] 3.5). Dietary intervention was recommended by 98.4% of pediatric gastroenterologists. Notably, 18 different dietary recommendations were reported. A majority of physicians provided targets for exercise frequency (72.6%, mean 5.6 days/wk, SD 1.6) and duration (69.9%, mean 40.2 minutes/session, SD 16.4). Medications were prescribed by 50.6%. Almost one-half of physicians (47.5%) screened for type 2 diabetes, dyslipidemia, and hypertension. Providers who spent more than 25 minutes at the initial visit were more likely to screen for comorbidities (P = 0.003). Barriers to care were reported by 92.8% with 29.0% reporting ≥3 barriers. CONCLUSIONS: The majority of US pediatric gastroenterologists regularly encounter children with NAFLD. Varied recommendations regarding diet and exercise highlight the need for prospective clinical trials. NAFLD requires a multidimensional approach with adequate resources in the home, community, and clinical setting.

Sexual activity after spine surgery: a systematic review.

INTRODUCTION: Sexual function is an important determinant of quality of life, and factors such as surgical approach, performance of fusion, neurological function and residual pain can affect it after spine surgery. Our aim was to perform a systematic review to collate evidence regarding the impact of spine surgery on sexual function. METHODS: A systematic review of studies reporting measures of sexual function, and incidence of adverse sexual outcomes (retrograde ejaculation) after major spine surgery was done, regardless of spinal location. Pubmed (MEDLINE) and Google Scholar databases were queried using the following search words "Sex", "Sex life", "Sexual function", "Sexual activity", "retrograde ejaculation", "Spine", "Spine surgery", "Lumbar surgery", "Lumbar fusion", "cervical spine", "cervical fusion", "Spinal deformity", "scoliosis" and "Decompression". All articles published between 1997 and 2017 were retrieved from the database. A total of 81 studies were included in the final review. RESULTS: Majority of the studies were retrospective case series and were low quality (Level IV) in evidence. Anterior lumbar approaches were associated with a higher incidence of retrograde ejaculation, especially with the utilization of transperitoneal laparoscopic approach. There is inconclusive evidence on the preferred sexual position following fusion, and also on the impact of BMP-2 usage on retrograde ejaculation/sexual dysfunction. CONCLUSION: Despite limited evidence from high-quality articles, there is a general trend towards improvement of sexual activity and function after spine surgery. Future studies incorporating specific assessments of sexual activity will be required to address this important determinant of quality of life so that appropriate pre-operative counselling can be done by providers. These slides can be retrieved under Electronic Supplementary Material.

Effects of hypertrophic and dilated cardiomyopathy mutations on power output by human ß-cardiac myosin.

Hypertrophic cardiomyopathy is the most frequently occurring inherited cardiovascular disease, with a prevalence of more than one in 500 individuals worldwide. Genetically acquired dilated cardiomyopathy is a related disease that is less prevalent. Both are caused by mutations in the genes encoding the fundamental force-generating protein machinery of the cardiac muscle sarcomere, including human ß-cardiac myosin, the motor protein that powers ventricular contraction. Despite numerous studies, most performed with non-human or non-cardiac myosin, there is no clear consensus about the mechanism of action of these mutations on the function of human ß-cardiac myosin. We are using a recombinantly expressed human ß-cardiac myosin motor domain along with conventional and new methodologies to characterize the forces and velocities of the mutant myosins compared with wild type. Our studies are extending beyond myosin interactions with pure actin filaments to include the interaction of myosin with regulated actin filaments containing tropomyosin and troponin, the roles of regulatory light chain phosphorylation on the functions of the system, and the possible roles of myosin binding protein-C and titin, important regulatory components of both cardiac and skeletal muscles.

Optimism/pessimism and future orientation as predictors of suicidal ideation: Are there ethnic differences?

OBJECTIVE: The present study sought to test the generalizability of Chang et al.'s (2013) model, which suggests that optimism/pessimism and future orientation function as additive and interactive predictors of suicidal risk, to specific ethnic minority college student groups (i.e., Asian Americans, African Americans, and Latino Americans). METHOD: The present study used Chang et al.'s (2013) model to predict suicidal ideation among 81 (34 male and 47 female) Asian-American, 71 (22 male and 49 female) African-American adults, and 83 (34 male and 49 female) Latino-American college students. RESULTS: Our results indicated that this model did not predict suicidal ideation well for Asian-American college students; however, it did work well to predict suicidal ideation for African-American and Latino-American college students. CONCLUSIONS: Our findings indicate that optimism/pessimism and future orientation are important positive cognitions involved with suicidal ideation for African-American and Latino-American college students. Further research is needed to better understand the cultural underpinnings of how these positive cognitions work to predict suicide-related outcomes. (PsycINFO Database Record

Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist.

Peroxisome proliferator-activated receptor delta (PPARδ), a member of the nuclear receptor family, is emerging as a key metabolic regulator with pleiotropic actions on various tissues including fat, skeletal muscle, and liver. Here we show that the PPARδ agonist KD3010, but not the well-validated GW501516, dramatically ameliorates liver injury induced by carbon tetrachloride (CCl(4)) injections. Deposition of extracellular matrix proteins was lower in the KD3010-treated group than in the vehicle- or GW501516-treated group. Interestingly, profibrogenic connective tissue growth factor was induced significantly by GW501516, but not by KD3010, following CCl(4) treatment. The hepatoprotective and antifibrotic effect of KD3010 was confirmed in a model of cholestasis-induced liver injury and fibrosis using bile duct ligation for 3 wk. Primary hepatocytes treated with KD3010 but not GW501516 were protected from starvation or CCl(4)-induced cell death, in part because of reduced reactive oxygen species production. In conclusion, our data demonstrate that an orally active PPARδ agonist has hepatoprotective and antifibrotic effects in animal models of liver fibrosis, suggesting a possible mechanistic and therapeutic approach in treating patients with chronic liver diseases.

Does less invasive spine surgery result in increased radiation exposure? A systematic review.

BACKGROUND: Radiation exposure to patients and spine surgeons during spine surgery is expected. The risks of radiation exposure include thyroid cancer, cataracts, and lymphoma. Although imaging techniques facilitate less invasive approaches and improve intraoperative accuracy, they may increase radiation exposure. QUESTIONS/PURPOSES: We performed a systematic review to determine whether (1) radiation exposure differs in open spine procedures compared with less invasive spine procedures; (2) radiation exposure differs in where the surgeon is positioned in relation to the C-arm; and (3) if radiation exposure differs using standard C-arm fluoroscopy or fluoroscopy with computer-assisted navigation. METHODS: A PubMed search was performed from January 1980 to July 2013 for English language articles relating to radiation exposure in spine surgery. Twenty-two relevant articles met inclusion criteria. Level of evidence was assigned on clinical studies. Traditional study quality evaluation of nonclinical studies was not applicable. RESULTS: There are important risks of radiation exposure in spine surgery to both the surgeon and patient. There is increased radiation exposure in less invasive spine procedures, but the use of protective barriers decreases radiation exposure. Where the surgeon stands in relation to the image source is important. Increasing the distance between the location of the C-arm radiation source and the surgeon, and standing contralateral from the C-arm radiation source, decreases radiation exposure. The use of advanced imaging modalities such as CT or three-dimensional computer-assisted navigation can potentially decrease radiation exposure. CONCLUSIONS: There is increased radiation exposure during less invasive spine surgery, which affects the surgeon, patient, and operating room personnel. Being cognizant of radiation exposure risks, the spine surgeon can potentially minimize radiation risks by optimizing variables such as the use of barriers, knowledge of position, distance from the radiation source, and use of advanced image guidance navigation-assisted technology to minimize radiation exposure. Continued research is important to study the long-term risk of radiation exposure and its relationship to cancer, which remains a major concern and needs further study as the popularity of less invasive spine surgery increases.

Predictive factors of symptomatic lumbar pseudoarthrosis following multilevel primary lumbar fusion.

Background: Lumbar spinal fusion surgery is a well-established treatment for various spinal disorders. However, one of its complications, pseudoarthrosis, poses a significant concern. This study aims to explore the incidence, time and predictive factors contributing to pseudoarthrosis in patients who have undergone lumbar fusion surgery over a 10-year period. Methods: Data for this research was sourced from the PearlDiver database where insurance claims of patients who underwent multilevel lumbar spinal fusion between 01/01/2010 and 10/31/2022 were examined for claims of pseudoarthrosis within the 10 years of their index procedure. A variety of demographic, comorbid, and surgical factors were assessed, including age, gender, Elixhauser Comorbidity Index (ECI), surgical approach, substance use disorders and history of spinal disorders. Statistical analyses, including chi-squared tests, multivariate analysis, and cox survival analysis were employed to determine significant associations. Results: Among the 76,337 patients included in this retrospective study, 2.70% were diagnosed with symptomatic lumbar pseudoarthrosis at an average of 7.38 years in a 10-year follow-up. Multivariate and Cox hazard analyses revealed that significant predictors of symptomatic pseudoarthrosis development following multilevel primary lumbar fusion include vitamin D deficiency, osteoarthritis, opioid and NSAID use, tobacco use, and a prior history of congenital spine disorders. Conclusions: In summary, this study revealed a 2.70% incidence of symptomatic lumbar pseudoarthrosis within 10 years of the index procedure. It highlighted several potential predictive factors, including comorbidities, surgical approaches, and substance use disorders, associated with the development of symptomatic pseudoarthrosis. Future research should focus on refining our understanding of these factors to improve patient outcomes and optimize healthcare resource allocation.

Exploring the incidence and risk factors of reoperation for symptomatic adjacent segment disease following cervical decompression and fusion.

Background: Patients with long-term follow-up after cervical decompression and fusion have often been noted to have development of adjacent segment degeneration with a smaller subset of these patients progressing to adjacent segment disease (ASD), which results in the development of new symptomatic radiculopathy or myelopathy referable to a site either directly above or below a prior fused segment. The cause of ASD is multifactorial often involving natural age-related progression of spondylosis, accelerated progression following cervical decompression and fusion, operative technique, and patient-related factors. The effect of age at the time of index cervical decompression and fusion on the need for reoperation for ASD is not fully understood. This study aims to establish underlying risk factors for the development of symptomatic cervical ASD following cervical decompression and fusion requiring reoperation in patients of various age groups. Methods: A retrospective database review of patients aged 20 or greater with insurance claims of primary cervical decompression and fusion over the course of 11 years and 10 months (January 01, 2010-October 31, 2022) was conducted using an insurance claims database. The primary outcome was to evaluate the incidence of cervical ASD requiring reoperation amongst patients stratified by age at the time of their primary procedure. Secondary outcomes included an evaluation of various risk factors for ASD following cervical decompression and fusion including surgeon-controlled factors such as the number of levels fused and approach taken, patient cervical pathology including cervical disc disorder and cervical spondylosis, and underlying patient medical comorbidities including osteoporosis and vitamin D deficiency, and substance use. Results: A total of 60,292 patient records were analyzed, where the overall reoperation incidence for symptomatic ASD was 6.57%, peaking at 8.12% among those aged 30 to 39 and decreasing with age. Regression analysis revealed ages lower than 50 years as more predictive for the development of symptomatic ASD requiring reoperation. Multivariate regression analysis identified predictive factors for reoperation, including age, Elixhauser Comorbidity Index (ECI), multiple-level surgery, cervical spondylosis, cervical disc disorder, osteoporosis, and vitamin D deficiency. Notably, these factors had a variable impact across various age groups, as revealed by subgroup analysis. Conclusions: The incidence of reoperation secondary to symptomatic ASD is 6.57%, highest in those aged 30 to 39. The surgical approach had no significant impact on the need for reoperation, but multiple-level fusions posed a consistent risk in the development of symptomatic ASD requiring reoperation. Patient factors like degenerative disc disease, spondylosis, osteoporosis, and vitamin D deficiency were associated, urging further age-specific risk assessment and nonoperative intervention exploration.

Posterior Cervical Fusion for Fracture Is Not the Same as Fusion for Degenerative Cervical Spine Disease: Implications for a Bundled Payment Model.

STUDY DESIGN/SETTING: Retrospective. OBJECTIVE: To understand differences in 30-day outcomes between patients undergoing posterior cervical fusion (PCF) for fracture versus degenerative cervical spine disease. SUMMARY OF BACKGROUND DATA: Current bundled payment models for cervical fusions, such as the Bundled Payments for Care Improvement revolve around the use of diagnosis-related groups to categorize patients for reimbursement purposes. Though a PCF performed for a fracture may have a different postoperative course of care as compared with a fusion being done for degenerative cervical spine pathology, the current DRG system does not differentiate payments based on the indication/cause of surgery. METHODS: The 2012-2017 American College of Surgeons-National Surgical Quality Improvement Program was queried using Current Procedural Terminology code 22600 to identify patients receiving elective PCFs. Multivariate analyses were used to compare rates of 30-day severe adverse events, minor adverse events, readmissions, length of stay, and nonhome discharges between the 2 groups. RESULTS: A total 2546 (91.4%) PCFs were performed for degenerative cervical spine pathology and 240 (8.6%) for fracture. After adjustment for differences in baseline clinical characteristics, patients undergoing a PCF for a fracture versus degenerative pathology had higher odds of severe adverse events [18.8% vs. 10.6%, odds ratio (OR): 1.65 (95% CI, 1.10-2.46); P =0.015], prolonged length of stay >3 days [54.2% vs. 40.5%, OR: 1.93 (95% CI, 1.44-2.59); P <0.001], and nonhome discharges [34.2% vs. 27.6%, OR: 1.54 (95% CI, 1.10-2.17); P =0.012]. CONCLUSIONS: Patients undergoing PCFs for fracture have significant higher rates of postoperative adverse events and greater resource utilization as compared with individuals undergoing elective PCF for degenerative spine pathology. The study calls into question the need of risk adjustment of bundled prices based on indication/cause of the surgery to prevent the creation of a financial disincentive when taking care/performing surgery in spinal trauma patients.