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Background: The recently validated Hand Questionnaire (HAND-Q) is a multifaceted patient-reported outcome measure (PROM) for hand/upper extremity (UE) pathology and treatment. Here, we conduct a pilot study utilising data collected as a participating site for the Phase II HAND-Q Pilot Multicenter International Validation Study. We hypothesised that self-reported hand functionality, symptom/disease severity, hand appearance, emotional dissatisfaction and treatment satisfaction would be worse in patients who perceived their disease severity to be more severe but would not differ between patients based on prior surgical history. Methods: Patients were prospectively enrolled for HAND-Q participation from September 2018 to August 2019. Patients were included in this analysis if they responded to the following scales of HAND-Q: Hand Functionality Satisfaction, Symptom Severity, Hand Appearance Satisfaction, Emotional Dissatisfaction and Treatment Satisfaction. Composite scores (CS) were created for each section. Surgical versus non-surgical CS and mild versus moderate/severe CS were compared with t-tests. Bi-variate comparisons of responses were performed between surgical and non-surgical groups, and between mild and moderate/severe groups. Results: HAND-Q individual question analysis revealed significant differences in functionality and symptom severity for patients with prior surgery (p < 0.047). CS analysis confirmed greater overall impairment in surgical patients, but no overall impact on symptom severity. Regarding disease severity HAND-Q individual question analysis, moderate/severe patients reported worse outcomes for specific aesthetic qualities and symptoms for almost all items (p < 0.05). CS analysis revealed significantly worse overall hand appearance satisfaction, hand functionality, emotional satisfaction and symptom severity for patients with moderate/severe hand conditions. Conclusions: HAND-Q revealed worsened outcomes for UE patients with self-reported moderate/severe conditions or previous surgical history. Understanding how previous surgery and disease severity may impact clinical outcomes is important for crafting appropriate treatment. Level of Evidence: Level II (Prognostic Study)

Background Currently, opioids are the standard of care for postoperative pain management. Avoiding unnecessary opioid exposure in patients is of current interest because of widespread abuse. Methods This is a prospective cohort study in which wide-awake, local anesthesia, no-tourniquet (WALANT) technique was used for 94 hand/upper extremity surgical patients and compared to patient cohorts undergoing similar procedures under monitored anesthesia care. Patients were not prescribed opioids postoperatively but were instead directed to use over-the-counter pain relievers. Pain scores on a visual analogue scale were collected from patients preoperatively, and on postoperative days 1 and 14. WALANT visual analogue scale scores were compared to those of the two patient cohorts who either did or did not receive postoperative opioids after undergoing similar procedures under monitored anesthesia care. Electronic medical records and New York State's prescription monitoring program, Internet System for Tracking Over-Prescribing, were used to assess prescription opioid-seeking. Information on sex, age, comorbidity burden, previous opioid exposure, and insurance coverage was also collected. Results Decreased pain was reported by WALANT patients 14 days postoperatively compared to preoperatively and 1 day postoperatively, with a total group mean pain score of 0.37. This is lower than mean scores of monitored anesthesia care patients with and without postoperative opioids. Only two WALANT patients (2.1 percent) sought opioid prescriptions from outside providers. There was little evidence suggesting factors including sex, age, comorbidity burden, previous opioid exposure, or insurance status alter these results. Conclusion WALANT may be a beneficial technique hand surgeons may adopt to mitigate use of postoperative opioids and reduce risk of abuse in patients. Clinical question/level of evidence Therapeutic, II.

Osteoporosis affects nearly 200 million individuals worldwide. Given this notable disease burden, there have been increased efforts to investigate complications in patients with osteoporosis undergoing cervical fusion (CF). However, there are limited data regarding long-term outcomes in osteoporotic patients in the setting of ≥4-level cervical fusion.The New York State Statewide Planning and Research Cooperative System database was used to identify patients who underwent posterior or combined anterior-posterior ≥4-level CF for cervical radiculopathy or myelopathy from 2009 to 2011, with a minimum follow-up surveillance of 2 years. The following were compared between patients with and without osteoporosis: demographics, hospital-related parameters, medical/surgical complications, readmissions, and revisions. Binary multivariate stepwise logistic regression was used to identify independent predictors of outcomes.A total of 2,604 patients were included (osteoporosis: n = 136 (5.2%); nonosteoporosis: n = 2,468). Patients with osteoporosis were older (66.9 ± 11.2 vs. 60.0 ± 11.4 years, P0.001), more often female (75.7% vs. 36.2%, P0.001), and White (80.0% vs. 65.3%, P = 0.007). Both cohorts had comparable comorbidity burdens (Charlson/Deyo: 1.1 ± 1.2 vs. 1.0 ± 1.3, P = 0.262), total hospital charges ($100,953 ± 94,933 vs. $91,618 ± 78,327, P = 0.181), and length of stay (9.7 ± 10.4 vs. 8.4 ± 9.6 days, P = 0.109). Patients with osteoporosis incurred higher rates of overall medical complication rates (41.9% vs. 29.4%, P = 0.002) and individual surgical complications, such as nonunion (2.9% vs. 0.7%, P = 0.006). Osteoporosis was associated with medical complications (OR = 1.57, P = 0.021), surgical complications (OR = 1.52, P = 0.030), and readmissions (OR = 1.86, P = 0.003) at 2 years.Among patients who underwent multilevel cervical fusion, those with osteoporosis had higher risk of adverse postoperative outcomes at two years. These data indicate that preoperative screening and management of osteoporosis may be important for optimizing long-term outcomes in patients who require multilevel CF.The data used in this study are available for public use at https://www.health.ny.gov/statistics/sparcs/.

Osteoporosis affects nearly 200 million individuals worldwide. There are little available data regarding outcomes in patients with osteoporosis who undergo short-segment lumbar fusion for degenerative disk disease (DDD). We sought to identify a relationship between osteoporosis and risk of adverse outcomes in patients with DDD undergoing short-segment lumbar fusion.Using the New York State Statewide Planning and Research Cooperative System, all patients with DDD who underwent 2- to 3-level lumbar fusion from 2009 through 2011 were identified. Patients with bone mineralization disorders and other systemic and endocrine disorders and surgical indications of trauma, systemic disease(s), and infection were excluded. Patients were stratified by the presence or absence of osteoporosis and compared for demographics, hospital-related parameters, and 2-year complications and revision surgeries. Multivariate binary logistic regression models were used to identify notable predictors of complications.A total of 29,028 patients (osteoporosis = 1,353 [4.7%], nonosteoporosis = 27,675 [95.3%]) were included. Patients with osteoporosis were older (66.9 vs 52.6 years), more often female (85.1% vs 48.4%), and White (82.8% vs 73.5%) (all P0.001). The Charlson/Deyo comorbidity index did not significantly differ between groups. Hospital lengths of stay and total charges were higher for patients with osteoporosis (4.9 vs 4.1 days; $74,484 vs $73,724; both P0.001). Medical complication rates were higher in patients with osteoporosis, including acute renal failure and deep-vein thrombosis (both P0.01). This cohort also had higher rates of implant-related (3.4% vs 1.9%) and wound (9.8% vs 5.9%) complications (both P0.01). Preoperative osteoporosis was strongly associated with 2-year medical and surgical complications (odds ratios, 1.6 and 1.7) as well as greater odds of revision surgeries (odds ratio, 1.3) (all P0.001).Patients with osteoporosis undergoing 2- to 3-level lumbar fusion for DDD were at higher risk of 2-year medical and surgical complications, especially implant-related and wound complications. These findings highlight the importance of rigorous preoperative metabolic workup and patients' optimization before spinal surgery.

BACKGROUND CONTEXT Spinal fusion is increasingly considered for management of patients with osteoporosis (OP) and degenerative disc disease (DDD). Little data is available regarding long-term outcomes in OP patients undergoing short-segment, lumbar fusion for DDD. PURPOSE Analyze the impact of OP on long-term outcomes in patients who have had 2-3-level lumbar fusions for degenerative disc disease. STUDY DESIGN/SETTING Retrospective review of the New York State Statewide Planning and Research Cooperative System (NYS SPARCS) database. PATIENT SAMPLE Patients with DDD undergoing 2-3-level lumbar fusion. OUTCOME MEASURES Frequency of 2-year medical and surgical complications and reoperations. METHODS Utilizing SPARCS, all patients from 2009-2011 with ICD-9 codes for DDD who underwent 2-3-level lumbar fusion were identified. Patients with bone mineralization disorders, systemic and endocrine disorders affecting bone quality were excluded. Surgical indications of trauma, systemic disease(s), and infection were excluded. Patients with and without OP were compared for demographics, hospital-related parameters, and 2-year complications and reoperations. Logistic regression models were utilized to identify predictors of complications. RESULTS A total of 29,028 patients (OP=1,353 (4.7%), No-OP=27,675) were included. OP patients were older (66.9 vs 52.6 years) as well as more often female (85.1% vs 48.4%) and white (82.8% vs 73.5%), all p CONCLUSIONS Patients with OP undergoing 2-3-level lumbar fusion for DDD were at higher risk of 2-year medical and surgical complications, and 3.4% of OP patients experienced implant-related complication. These findings highlight the importance of rigorous preoperative metabolic workup prior to spinal surgery. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT Osteoporosis (OP) is a common condition affecting nearly 200 million individuals globally. Similarly, adult spinal deformity has a peak prevalence of 65% of the adult population. While bone health is instrumental in orthopaedic surgery, few studies have described the long-term outcomes of osteoporosis following surgery for ASD. PURPOSE We sought to evaluate the impact of OP on two-year postoperative complication rates when compared to patients without OP. STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE Utilizing the New York State Statewide Planning and Research Cooperative System (SPARCS), we identified all patients who underwent ≥4-level fusion with ICD-9 codes diagnostic for ASD (progressive idiopathic scoliosis and degenerative lumbar disease) from 2009-2011 with ≥2-year follow-up. Patients with osteoporosis (OP) and without OR were identified following exclusions. OUTCOME MEASURES Patient demographics, hospital-related parameters, postoperative complications and reoperations. METHODS Using SPARCS, we identified all patients who underwent ≥4-level fusion with ICD-9 codes diagnostic for ASD (progressive idiopathic scoliosis and degenerative lumbar disease) from 2009-2011 for ≥2-year minimum follow-up. Patients with osteoporosis (OP) and without OP were identified. Any patients with bone mineralization disorders (osteomalacia, rickets, hyperparathyroidism [primary, secondary, tertiary], vitamin D deficiency) and other systemic (fibrous dysplasia, sickle cell disease, renal osteodystrophy) and endocrine disorders (thyroid hypo- or hyperfunctioning disorders, adrenal insufficiency, adrenal hyperplastic syndromes) affecting bone quality or production were excluded, as were patients with surgical indications of trauma, systemic disease, infection, or cancer. The two cohorts were compared for demographics, hospital-related parameters, and 2-year postoperative complications and reoperations. Multivariate binary stepwise logistic regressions was utilized to identify significant predictors of these outcomes (covariates: OP, age, sex, race, and Charlson/Deyo). RESULTS A total of 6,132 patients were identified (OP, n=490 (7.99%); No-OP, n=5,642). OP patients were older (67.6 vs 56.7 years), more often female (83.7% vs 46.2%) and white (84.3% vs 79.1%), and had higher comorbidity scores (Charlson/Deyo: 0.72 vs 0.61), all p CONCLUSIONS Osteoporosis was associated with two-year postoperative complications in ASD patients. Aside from being an etiology of ASD due to vertebral fracture, osteoporosis should be considered as a comorbidity that needs to be optimized and managed perioperatively. Furthermore, this data is a call to every spine surgeon to consider metabolic bone disorders screening prior to any spinal deformity surgery. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Adult neurogenesis and Alzheimer's disease Alzheimer's disease (AD) pathology destroys neurons and synapses in the brain, leading to dementia. The brain generates new neurons throughout life in the hippocampus, a process called adult hippocampal neurogenesis (AHN). Choi et al. found that blocking AHN exacerbated cognitive impairment in an AD mouse model (see the Perspective by Spires-Jones and Ritchie). Inducing neurogenesis alone did not improve cognition in AD mice, whereas inducing neurogenesis while simultaneously ameliorating the neuronal environment via exercise did. The use of genetic or pharmacological treatments that simultaneously induced neurogenesis and increased levels of brain-derived neurotrophic factor (BDNF) mimicked the benefits of exercise on cognition. Thus, inducing both neurogenesis and providing BDNF may be useful as an AD therapeutic. Science , this issue p. eaan8821 ; see also p. 975

β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of β-amyloid (Aβ), one of the major pathogenic molecules of Alzheimer’s disease (AD), and is therefore being actively pursued as a drug target for AD. Adult hippocampal neurogenesis (AHN) is a lifelong process that is known to be important for learning and memory and may have the potential to regenerate damaged neural tissue. In this study, we examined whether BACE1 regulates AHN, which holds important implications for its suitability as a drug target in AD. Cohorts of 2-month-old wild-type (BACE1+/+), heterozygous, and homozygous BACE1 knockout mice (BACE1+/–and BACE1–/–, respectively) were injected with 5-bromo-2′-deoxyuridine (BrdU) and sacrificed 1 day later to examine the impact of loss of BACE1 on neural precursor cell (NPC) proliferation in the adult brain. Parallel cohorts of mice were sacrificed 4 weeks after BrdU injection to determine the effects of BACE1 on survival and differentiation of newborn NPCs. We found that NPC proliferation was increased in BACE1–/–mice compared to BACE1+/+mice, while no difference was observed in NPC survival across genotypes. Differentiation of NPCs to neuronal lineage was impaired in BACE1–/–mice. However, no differences were observed in astrogenesis, the proportion of immature neurons, or the production of oligodendrocytes across genotypes. Importantly, corresponding with a decrease in neuronal differentiation in the absence of a complementary increase in an alternate cell fate, BACE1–/–mice were found to have a pool of undifferentiated NPCs in the hippocampus compared to BACE1+/+and BACE1+/–mice.