Mastoid Fascia Tissue Graft as a Tip Camouflage Technique in Rhinoplasty: A Reliable Alternative to Soft Cartilage Grafts.

BACKGROUND: Traditional rhinoplasty tip grafts often lead to visibility issues, prompting patients to seek revision surgery. The mastoid fascia tissue graft (MFTG) provides a natural-looking alternative with an acceptable risk of complication. MFTG remains less visible through the skin and helps camouflage and conceal tip irregularities. This study of 193 patients examines MFTG's effectiveness in nasal tip refinement, evaluating revision and infection rates. METHODS: A retrospective analysis of MFTG use for nasal tip aesthetics during open rhinoplasty in the senior author's practice was conducted from January 2019 to June 2022. Inclusion criteria encompassed open rhinoplasty cases using mastoid tissue for tip aesthetics with at least 12 months of follow-up. Among 2003 cases, 193 met these criteria and were evaluated for subsequent revision and infection rates. RESULTS: The average patient age was 34.2 years (175 females, 18 males). Primary rhinoplasties were done on 113 patients, with 80 receiving revision surgeries. Average follow-up was 14.8 months. 6 (3.1%) patients overall needed extended antibiotics, including 1 (0.9%) primary rhinoplasty and 5 (6.3%) secondary rhinoplasty patients. Overall, 6 (3.1%) patients required revision rhinoplasty, comprising of 1 (0.9%) primary and 5 (6.3%) secondary rhinoplasty patients. CONCLUSIONS: MFTG use for nasal tip aesthetics is a safe, convenient, and effective technique in camouflaging and concealing nasal tip contour irregularities in both primary and revision rhinoplasty. Use of MTFG is associated with minimal morbidity.

Adverse Childhood Experiences and Chronic Low Back Pain in Adulthood: The Role of Emotion Regulation.

Chronic low back pain (cLBP) is characterized by biopsychosocial determinants that collectively result in a substantial burden at the individual, community, and health care system levels. A growing body of literature suggests that childhood adversity is longitudinally associated with the development and maintenance of various chronic pain conditions in adulthood. Little research has investigated the psychological processes that might underlie the association between adverse childhood experiences (ACEs) and cLBP. Emotion regulation comprises a substantive part of the subjective experience of pain and may be a potential mechanism through which ACEs contribute to cLBP etiology and maintenance. Thus, the current study examined the extent to which emotion dysregulation mediated the relationship between ACEs and pain severity (pain at rest and movement-evoked pain) in adults with cLBP. Participants included 183 adults (53.0% female, 62.5% non-Hispanic Black) between the ages of 18 and 85 with cLBP. Participants self-reported on ACEs, pain, difficulties in emotion regulation (DER), depression, and completed brief physical function tasks. In data analytic models, sociodemographic variables were included as covariates. Analyses revealed that emotion regulation mediated the relationship between ACEs and cLBP severity at rest (indirect effect = .15 [95% CI {.06-.25}]) and with movement (indirect effect = 1.50 [95% CI {.69-2.57}]). Findings suggest ACEs are linked to cLBP severity in adulthood through DER. This aligns with research demonstrating that childhood maltreatment can lead to DER, which perpetuate over the lifespan to impact adult health outcomes. PERSPECTIVE: This study presents emotion dysregulation as a psychological pathway through which childhood adversity may contribute to cLBP in adulthood. This work may bolster our understanding of social experiences as risk factors for chronic pain, while identifying targets for clinical intervention. TRIAL REGISTRATION: This study utilized baseline data collected as part of a parent trial titled "Examining Racial and SocioEconomic Disparities in Chronic Low Back Pain" (ClinicalTrials.gov ID: NCT03338192).

A Comprehensive Review of the Historical Description of Spine Surgery and Its Evolution.

Major strides in the advancement of spine surgery came about in the 21st century. However, the extensive history of spine surgery can be traced back to long before this time. A clear description of the journey from a primitive yet accurate understanding of the human musculoskeletal system to today's modern aspects of spinal techniques is lacking. A narrative literature review was conducted to elucidate where spine surgery began and the techniques used that evolved over time. This review was conducted using PubMed and Google Scholar. Search terms used included "history of spine surgery," "evolution of spine surgery," "origins of spine surgery," "history of laminectomy," "history of spinal fusion," "history of lumbar interbody fusion," "minimally invasive spine surgery," and "navigation in spine surgery." We highlight the evolution of the basic understanding of anatomy and non-surgical and surgical techniques, including bracing, laminectomy, discectomy, and spinal fusion. The current evolution and integration of minimally invasive techniques, lumbar interbody fusion techniques, robotics, navigation, and motion preservation are discussed, as these are the major areas of focus for technological advancement. This review presents an overarching synopsis of the events that chronicle the progress made in spine surgery since its conception. The review uniquely contributes to the growing body of literature on the expansion of spine surgery and highlights major events in its history.

Biobehavioral Predictors of Pain Intensity, Pain Interference, and Chronic Pain Episodes: A Prospective Cohort Study of African-American Adults.

Racial disparities in pain experiences are well-established, with African-American (AA) adults reporting higher rates of daily pain, increased pain severity, and greater pain-related interference compared to non-Hispanic Whites. However, the biobehavioral factors that predict the transition to chronic pain among AA adults are not well understood. This prospective cohort study provided a unique opportunity to evaluate predictors of chronic pain onset among 130 AA adults (81 women), ages 18 to 44, who did not report chronic pain at their baseline assessment and subsequently completed follow-up assessments at 6- and 12-months. Outcome measures included pain intensity, pain-related interference, and chronic pain status. Comprehensive assessments of sociodemographic and biobehavioral factors were used to evaluate demographics, socioeconomic status, stress exposure, psychosocial factors, prolonged hypothalamic-pituitary-adrenal secretion, and quantitative sensory testing responses. At baseline, 30 adults (23.1%) reported a history of prior chronic pain. Over the 12-month follow-up period, 13 adults (10.0%) developed a new chronic pain episode, and 18 adults (13.8%) developed a recurrent chronic pain episode. Whereas socioeconomic status measures (ie, annual income, education) predicted changes in pain intensity over the follow-up period, quantitative sensory testing measures (ie, pain threshold, temporal summation of pain) predicted changes in pain interference. A history of chronic pain and higher depressive symptoms at baseline independently predicted the onset of a new chronic pain episode. The present findings highlight distinct subsets of biobehavioral factors that are differentially associated with trajectories of pain intensity, pain-related interference, and onset of chronic pain episodes in AA adults. PERSPECTIVE: This prospective study sought to advance understanding of biobehavioral factors that predicted pain outcomes over a 12-month follow-up period among AA adults without chronic pain at their initial assessment. Findings revealed distinct subsets of factors that were differentially associated with pain intensity, pain-related interference, and onset of chronic pain episodes.

Diversity in emotion regulation strategy use: Resilience against posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is associated with impaired emotion regulation (ER). ER diversity, the variety, prevalence, and relative abundance of ER strategy use, may provide resilience against PTSD. This study examined the prospective relation between ER diversity and PTSD, while accounting for negative and positive life events, in interpersonal violence (IPV) survivors. IPV-exposed women with PTSD onset (PTSD; n = 22), without PTSD onset (IPV; n = 37), and non-traumatized control participants (NTC; n = 41) rated their ER strategy use and experience of negative and positive life events. The ER diversity index differentiated the participant groups. Importantly, group differences in ER diversity depended on the experience of life events. When experiencing fewer positive life events and more negative life events, the IPV and NTC groups, but not the PTSD group, demonstrated higher ER diversity. Thus, greater ER diversity during periods with more negative life events and fewer positive life events may play a protective role against PTSD onset for IPV survivors.

Physical activity, sitting time, and thermal quantitative sensory testing responses in African Americans.

Introduction: Prior research suggests that African Americans (AAs) have more frequent, intense, and debilitating pain and functional disability compared with non-Hispanic Whites (NHWs). Potential contributing factors to this disparity are physical activity and sedentary behavior, given that AAs are less physically active, and physical activity is associated with antinociception (whereas sedentary behavior is linked to pronociception). However, impact of these factors on pain processing has largely been unexplored in AAs, especially before chronic pain onset. Objective: This study examined relationships between physical activity, sedentary behavior (sitting time), and laboratory measures of pain and pain modulation in adult AAs. These included heat pain threshold and tolerance, temporal summation of pain (TSP, a marker of central sensitization), and conditioned pain modulation (CPM, a marker of descending pain inhibition). Methods: Multiple regressions were conducted to examine the effects of physical activity and sitting time on heat threshold and tolerance. Multilevel models were conducted to assess the relationship between physical activity, sitting time, and temporal summation of pain. Additional multilevel models were conducted to assess the relationship between physical activity, sitting time, and conditioned pain modulation. Results: Higher level of physical activity, but not sitting time, was associated with reduced TSP slopes. Neither physical activity nor sitting time was associated with CPM slopes. No significant relationships between physical activity or sitting time and heat pain threshold or tolerance were detected. Conclusions: These findings suggest that physical activity is associated with reduced TSP, an effect which may be driven by reduced spinal hyperexcitability in more active individuals. Thus, structural and individual interventions designed to increase physical activity in healthy, young AAs may be able to promote antinociceptive processes (ie, reduced TSP/reduced pain facilitation) potentially protective against chronic pain.

A regulatory pathway model of neuropsychological disruption in Havana syndrome.

Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio-behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature. Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both. Method: Automated text-mining of >9,000 publications produced a network consisting of 273 documented regulatory interactions linking 29 neuro-chemical markers with 9 neuropsychological constructs from the Brief Mood Survey, PTSD Checklist, and the Frontal Systems Behavior Scale. Analysis of information flow through this network produced a set of regulatory rules reconciling to within a 6% departure known mechanistic pathways with neuropsychological profiles in N = 6 subjects. Results: Predicted expression of neuro-chemical markers that jointly satisfy documented pathways and observed symptom profiles display characteristically elevated IL-1B, IL-10, NGF, and norepinephrine levels in the context of depressed BDNF, GDNF, IGF1, and glutamate expression (FDR < 5%). Elevations in CRH and IL-6 were also predicted unanimously across all subjects. Furthermore, simulations of neurological regulatory dynamics reveal subjects do not appear to be "locked in" persistent illness but rather appear to be engaged in a slow recovery trajectory. Discussion: This computational analysis of measured neuropsychological symptoms in Havana-based diplomats proposes that these AHI symptoms may be supported in part by disruption of known neuroimmune and neurotransmission regulatory mechanisms also associated with mTBI.

Predicting incident cardiovascular disease among African-American adults: A deep learning approach to evaluate social determinants of health in the Jackson heart study.

The present study sought to leverage machine learning approaches to determine whether social determinants of health improve prediction of incident cardiovascular disease (CVD). Participants in the Jackson Heart study with no history of CVD at baseline were followed over a 10-year period to determine first CVD events (i.e., coronary heart disease, stroke, heart failure). Three modeling algorithms (i.e., Deep Neural Network, Random Survival Forest, Penalized Cox Proportional Hazards) were used to evaluate three feature sets (i.e., demographics and standard/biobehavioral CVD risk factors [FS1], FS1 combined with psychosocial and socioeconomic CVD risk factors [FS2], and FS2 combined with environmental features [FS3]) as predictors of 10-year CVD risk. Contrary to hypothesis, overall predictive accuracy did not improve when adding social determinants of health. However, social determinants of health comprised eight of the top 15 predictors of first CVD events. The social determinates of health indicators included four socioeconomic factors (insurance status and types), one psychosocial factor (discrimination burden), and three environmental factors (density of outdoor physical activity resources, including instructional and water activities; modified retail food environment index excluding alcohol; and favorable food stores). Findings suggest that whereas understanding biological determinants may identify who is currently at risk for developing CVD and in need of secondary prevention, understanding upstream social determinants of CVD risk could guide primary prevention efforts by identifying where and how policy and community-level interventions could be targeted to facilitate changes in individual health behaviors.

Adversity type and timing predict temporal summation of pain in African-American adults.

African Americans are disproportionately exposed to adversity across the lifespan, which includes both stressful and traumatic events. Adversity, in turn, is associated with alterations in pain responsiveness. Racial differences in pain responsiveness among healthy adults are well established. However, the extent to which adversity type and timing are associated with alterations in pain responsiveness among healthy African-American adults is not well understood. The present study included 160 healthy African-American adults (98 women), ages 18 to 45. Outcome measures included pain tolerance and temporal summation of pain to evoked thermal pain. Composite scores were created for early-life adversity (childhood trauma, family adversity) and recent adversity (perceived stress, chronic stress burden). A measure of lifetime racial discrimination was also included. Higher levels of recent adversity were associated with higher temporal summation of pain, controlling for gender, age, and education. Neither early-life adversity nor lifetime racial discrimination were associated with temporal summation of pain. The present findings suggest that heightened temporal summation of pain among healthy African-American adults is associated with exposure to recent adversity events. Improved understanding of how recent adversity contributes to heightened temporal summation of pain in African Americans could help to mitigate racial disparities in pain experiences by identifying at-risk individuals who could benefit from early interventions.

Dynamics of diurnal cortisol and alpha-amylase secretion and their associations with PTSD onset in recent interpersonal trauma survivors.

BACKGROUND: Dysfunction in major stress response systems during the acute aftermath of trauma may contribute to risk for developing posttraumatic stress disorder (PTSD). The current study investigated how PTSD diagnosis and symptom severity, depressive symptoms, and childhood trauma uniquely relate to diurnal neuroendocrine secretion (cortisol and alpha-amylase rhythms) in women who recently experienced interpersonal trauma compared to non-traumatized controls (NTCs). METHOD: Using a longitudinal design, we examined diurnal cortisol and alpha-amylase rhythms in 98 young women (n = 57 exposed to recent interpersonal trauma, n = 41 NTCs). Participants provided saliva samples and completed symptom measures at baseline and 1-, 3-, and 6-month follow-up. RESULTS: Multilevel models (MLMs) revealed lower waking cortisol predicted the development of PTSD in trauma survivors and distinguished at-risk women from NTCs. Women with greater childhood trauma exposure exhibited flatter diurnal cortisol slopes. Among trauma-exposed individuals, lower waking cortisol levels were associated with higher concurrent PTSD symptom severity. Regarding alpha-amylase, MLMs revealed women with greater childhood trauma exposure exhibited higher waking alpha-amylase and slower diurnal alpha-amylase increase. CONCLUSIONS: Results suggest lower waking cortisol in the acute aftermath of trauma may be implicated in PTSD onset and maintenance. Findings also suggest childhood trauma may predict a different pattern of dysfunction in stress response systems following subsequent trauma exposure than the stress system dynamics associated with PTSD risk; childhood trauma appears to be associated with flattened diurnal cortisol and alpha-amylase slopes, as well as higher waking alpha-amylase.

Survey of Palliative Care Use in Primary Malignant Bone Tumors: A National Cancer Database Review.

Background/Objectives: Palliative care (PC) has been associated with reduced patient symptom burden, improved physician satisfaction, and reduced cost of care. However, its use in primary bone tumors has not been well classified. Design/Setting and Subjects: Patients diagnosed with primary malignant bone tumors (osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma) between 2004 and 2018 were identified in the National Cancer Database. Cross tabulations with chi-square analysis were performed to evaluate frequencies of PC use by patient, facility, and tumor characteristics. Multivariate logistic binary regression was performed to evaluate relationships between patient, treatment facility, and tumor characteristics and the use of PC. Results: Around 24,401 patients were identified. Overall, 2.52% had any form of PC utilization. Of those receiving PC, 55.5-65.1% were treated with only noncurative surgery, radiation, chemotherapy, or any combination of these modalities. Odds of PC utilization were decreased for patients with chordomas, patients living >24 miles from the treatment facility, or patients with private insurance, Medicare, or unknown insurance status. Odds of PC utilization were increased in patients with greater tumor diameter or unknown tumor size, tumors in midline, increased tumor grade, stage IV tumors, or living in urban areas. Conclusion: PC use in patients with primary bone tumors increases with tumor stage, tumor grade, tumor size, and if the tumor is midline, and in patients living in urban areas. However, overall utilization remains markedly low. Future studies should be done to investigate these patterns of care and help expand the utilization of PC.

Longitudinal Predictors of Pain in Pediatric Sickle Cell Disease.

OBJECTIVE: Despite the identified pathophysiology of vaso-occlusive pain in sickle cell disease (SCD), predictors of pain in youth with SCD remain elusive. In this study, we measured changes in pain frequency, intensity, and interference over 1 year and examined biopsychosocial risk factors (SCD disease severity, age, female, depression, and sleep quality) as possible longitudinal predictors. METHODS: Medical history was obtained from retrospective chart review for 79 children with SCD (ages 2-18 years; 48.1% female; 100% Black/African American; 83.5% SCD, SS genotype). As part of a clinical screening protocol, caregivers (n = 79) and youth 8-18 years (n = 43) completed psychosocial questionnaires approximately 1 year apart (M = 15.52 months, SD = 5.69). Zero-order correlations, paired t-tests, and hierarchical linear models examined longitudinal predictors of pain. The longitudinal bidirectional relationship between pain and sleep was also examined. RESULTS: The rate of severe SCD disease increased from 41.8% to 55.7% across the year, while most hematologic medical parameters remained stable. Increased depression and pain interference at survey 1 significantly predicted increased pain interference at survey 2. Poor sleep quality and increased pain frequency at survey 1 predicted increased pain frequency at survey 2. Finally, increased pain interference at survey 1 predicted poor sleep quality at survey 2. DISCUSSION: History of pain, depression, and sleep quality were longitudinal predictors of pain over 1 year in youth with SCD. Identifying longitudinal predictors of pain may lead to earlier identification of patients with a high-risk SCD pain phenotype and earlier medical, psychological, and behavioral interventions.

Odds of Stage IV Bone Cancer Diagnosis Based on Socioeconomic and Geographical Factors: A National Cancer Database (NCDB) Review.

BACKGROUND: There are significant differences in prognosis for osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordomas based on the stage at diagnosis. The five-year survival of these bone cancers varies from 75-87% at an early stage of diagnosis and falls to 27-55% at a late stage of diagnosis. PATIENTS AND METHODS: This study retrospectively evaluated the odds of stage I vs stage IV cancer at the time of diagnosis in patients with primary malignant bone tumors (osteosarcoma, chondrosarcoma, Ewing sarcoma and chordoma) diagnosed in the National Cancer Database (NCDB) between 2004 and 2018. Cross tabulations with Chi-square analysis were performed to evaluate frequencies of different socioeconomic and geographical characteristics between patients with stage I vs stage IV cancer. Multivariable binary logistic regression was performed to evaluate relationships between socioeconomic and geographical factors and the odds of stage IV cancer at the time of diagnosis. Statistical significance was set at α = 0.05. RESULTS: 8882 patients with stage I and 3063 with stage IV primary malignant bone tumors were identified. The odds of stage IV bone cancer at diagnosis are increased for patients on Medicaid (odds ratio [OR] = 1.298, 95% confidence interval [CI]: 1.043-1.616) or Medicare (OR = 1.795, 1.411-2.284). Odds of stage IV bone cancer at diagnosis were decreased with female sex (OR = 0.733, 0.671-0.800), private insurance (OR = 0.738, 0.601-0.905), and those treated at community cancer programs (OR = 0.542, 0.369-0.797), comprehensive cancer program (OR = 0.312, 0.215-0.452), or academic/research facilities (OR = 0.370, 0.249-0.550). No significant relationship was identified between the stage at diagnosis and race, ethnicity, Charlson-Deyo score, or education level. Stage IV cancer at diagnosis showed was proportionally lower in chondrosarcomas (17.1%) and chordomas (2.1%) than osteosarcomas (45.0%) and Ewing sarcomas (35.8%). CONCLUSION: Odds of stage IV bone cancer at diagnosis are greater with male sex, Medicaid or Medicare insurance status, or treatment at community cancer programs. Providers should have a low suspicion for additional evaluation when treating patients with symptoms of bone cancer and should be aware of these disparities when treating people in these groups. This is to the authors' knowledge the first such study conducted through the NCDB.

Predicting benzodiazepine prescriptions: A proof-of-concept machine learning approach.

Introduction: Benzodiazepines are the most commonly prescribed psychotropic medications, but they may place users at risk of serious adverse effects. Developing a method to predict benzodiazepine prescriptions could assist in prevention efforts. Methods: The present study applies machine learning methods to de-identified electronic health record data, in order to develop algorithms for predicting benzodiazepine prescription receipt (yes/no) and number of benzodiazepine prescriptions (0, 1, 2+) at a given encounter. Support-vector machine (SVM) and random forest (RF) approaches were applied to outpatient psychiatry, family medicine, and geriatric medicine data from a large academic medical center. The training sample comprised encounters taking place between January 2020 and December 2021 (N = 204,723 encounters); the testing sample comprised data from encounters taking place between January and March 2022 (N = 28,631 encounters). The following empirically-supported features were evaluated: anxiety and sleep disorders (primary anxiety diagnosis, any anxiety diagnosis, primary sleep diagnosis, any sleep diagnosis), demographic characteristics (age, gender, race), medications (opioid prescription, number of opioid prescriptions, antidepressant prescription, antipsychotic prescription), other clinical variables (mood disorder, psychotic disorder, neurocognitive disorder, prescriber specialty), and insurance status (any insurance, type of insurance). We took a step-wise approach to developing a prediction model, wherein Model 1 included only anxiety and sleep diagnoses, and each subsequent model included an additional group of features. Results: For predicting benzodiazepine prescription receipt (yes/no), all models showed good to excellent overall accuracy and area under the receiver operating characteristic curve (AUC) for both SVM (Accuracy = 0.868-0.883; AUC = 0.864-0.924) and RF (Accuracy = 0.860-0.887; AUC = 0.877-0.953). Overall accuracy was also high for predicting number of benzodiazepine prescriptions (0, 1, 2+) for both SVM (Accuracy = 0.861-0.877) and RF (Accuracy = 0.846-0.878). Discussion: Results suggest SVM and RF algorithms can accurately classify individuals who receive a benzodiazepine prescription and can separate patients by the number of benzodiazepine prescriptions received at a given encounter. If replicated, these predictive models could inform system-level interventions to reduce the public health burden of benzodiazepines.

Racial, Gender, and Neighborhood-Level Disparities in Pediatric Trauma Care.

BACKGROUND: Disparities in trauma outcomes and care are well established for adults, but the extent to which similar disparities are observed in pediatric trauma patients requires further investigation. The objective of this study was to evaluate the unique contributions of social determinants (race, gender, insurance status, community distress, rurality/urbanicity) on trauma outcomes after controlling for specific injury-related risk factors. STUDY DESIGN: All pediatric (age < 18) trauma patients admitted to a single level 1 trauma center with a statewide, largely rural, catchment area from January 2010 to December 2020 were retrospectively reviewed (n = 14,398). Primary outcomes were receipt of opioids in the emergency department, post-discharge rehabilitation referrals, and mortality. Multivariate logistic regressions evaluated demographic, socioeconomic, and injury characteristics. Multilevel logistic regressions evaluated area-level indicators, which were derived from abstracted home addresses. RESULTS: Analyses adjusting for demographic and injury characteristics revealed that Black children (n = 6255) had significantly lower odds (OR = 0.87) of being prescribed opioid medications in the emergency department compared to White children (n = 5883). Children living in more distressed and rural communities had greater odds of receiving opioid medications. Girls had significantly lower odds (OR = 0.61) of being referred for rehabilitation services than boys. Post hoc analyses revealed that Black girls had the lowest odds of receiving rehabilitation referrals compared to Black boys and White children. CONCLUSION: Results highlight the need to examine both main and interactive effects of social determinants on trauma care and outcomes. Findings reinforce and expand into the pediatric population the growing notion that traumatic injury care is not immune to disparities.

Comparative Analysis of 30-Day Readmission, Reoperation, and Morbidity between Posterior Cervical Decompression and Fusion Performed in Inpatient and Outpatient Settings.

STUDY DESIGN: A retrospective cohort study. PURPOSE: To compare 30-day readmission, reoperation, and morbidity for patients undergoing posterior cervical decompression and fusion (PCDF) in inpatient vs. outpatient settings. OVERVIEW OF LITERATURE: PCDF has recently been increasingly performed in outpatient settings, often utilizing minimally invasive techniques. However, literature evaluating short-term outcomes for PCDF is scarce. Moreover, no currently large-scale database studies have compared short-term outcomes between PCDF performed in the inpatient and outpatient settings. METHODS: Patients who underwent PCDF from 2005 to 2018 were identified using the National Surgical Quality Improvement Program database. Regression analysis was utilized to compare primary outcomes between surgical settings and evaluate for predictors thereof. RESULTS: We identified 8,912 patients. Unadjusted analysis revealed that outpatients had lower readmission (4.7% vs. 8.8%, p =0.020), reoperation (1.7% vs. 3.8%, p =0.038), and morbidity (4.5% vs. 11.2%, p <0.001) rates. After adjusting for baseline differences, readmission, reoperation, and morbidity no longer statistically differed between surgical settings. Outpatients had lower operative time (126 minutes vs. 179 minutes) and levels fused (1.8 vs. 2.2) (p <0.001). Multivariate analysis revealed that age (p =0.008; odds ratio [OR], 1.012), weight loss (p =0.045; OR, 2.444), and increased creatinine (p <0.001; OR, 2.233) independently predicted readmission. The American Society of Anesthesiologists (ASA) classification of ≥3 predicted reoperation (p =0.028; OR, 1.406). Rehabilitation discharge (p <0.001; OR, 1.412), ASA-class of ≥3 (p =0.008; OR, 1.296), decreased hematocrit (p <0.001; OR, 1.700), and operative time (p <0.001; OR, 1.005) predicted morbidity. CONCLUSIONS: The 30-day outcomes were statistically similar between surgical settings, indicating that PCDF can be safely performed as an outpatient procedure. Surrogates for poor health predicted negative outcomes. These results are particularly important as we continue to shift spinal surgery to outpatient centers. This importance has been highlighted by the need to unburden inpatient sites, particularly during public health emergencies, such as the coronavirus disease 2019 pandemic.

Cognitive-Affective-Behavioral Pathways Linking Adversity and Discrimination to Daily Pain in African-American Adults.

The tendency to ruminate, magnify, and experience helplessness in the face of pain - known as pain catastrophizing - is a strong predictor of pain outcomes and is associated with adversity. The ability to maintain functioning despite adversity - referred to as resilience - also influences pain outcomes. Understanding the extent to which pain catastrophizing and resilience influence relations between adversity and daily pain in healthy African-American adults could improve pain risk assessment and mitigate racial disparities in the transition from acute to chronic pain. This study included 160 African-American adults (98 women). Outcome measures included daily pain intensity (sensory, affective) and pain impact on daily function (pain interference). Adversity measures included childhood trauma exposure, family adversity, chronic burden from recent stressors, and ongoing perceived stress. A measure of lifetime racial discrimination was also included. Composite scores were created to capture early-life adversity (childhood trauma, family adversity) versus recent-life adversity (perceived stress, chronic burden). Increased pain catastrophizing was correlated with increased adversity (early and recent), racial discrimination, pain intensity, and pain interference. Decreased pain resilience was correlated with increased recent-life adversity (not early-life adversity or racial discrimination) and correlated with increased pain intensity (not pain-related interference). Bootstrapped multiple mediation models revealed that relationships between all adversity/discrimination and pain outcomes were mediated by pain catastrophizing. Pain resilience, however, was not a significant mediator in these models. These findings highlight opportunities for early interventions to reduce cognitive-affective-behavioral risk factors for persisting daily pain among African-American adults with greater adversity exposure by targeting pain catastrophizing.

Old drugs, new tricks: leveraging known compounds to disrupt coronavirus-induced cytokine storm.

A major complication in COVID-19 infection consists in the onset of acute respiratory distress fueled by a dysregulation of the host immune network that leads to a run-away cytokine storm. Here, we present an in silico approach that captures the host immune system's complex regulatory dynamics, allowing us to identify and rank candidate drugs and drug pairs that engage with minimal subsets of immune mediators such that their downstream interactions effectively disrupt the signaling cascades driving cytokine storm. Drug-target regulatory interactions are extracted from peer-reviewed literature using automated text-mining for over 5000 compounds associated with COVID-induced cytokine storm and elements of the underlying biology. The targets and mode of action of each compound, as well as combinations of compounds, were scored against their functional alignment with sets of competing model-predicted optimal intervention strategies, as well as the availability of like-acting compounds and known off-target effects. Top-ranking individual compounds identified included a number of known immune suppressors such as calcineurin and mTOR inhibitors as well as compounds less frequently associated for their immune-modulatory effects, including antimicrobials, statins, and cholinergic agonists. Pairwise combinations of drugs targeting distinct biological pathways tended to perform significantly better than single drugs with dexamethasone emerging as a frequent high-ranking companion. While these predicted drug combinations aim to disrupt COVID-induced acute respiratory distress syndrome, the approach itself can be applied more broadly to other diseases and may provide a standard tool for drug discovery initiatives in evaluating alternative targets and repurposing approved drugs.

Proteomic Network Analysis of Bronchoalveolar Lavage Fluid in Ex-Smokers to Discover Implicated Protein Targets and Novel Drug Treatments for Chronic Obstructive Pulmonary Disease.

Bronchoalveolar lavage of the epithelial lining fluid (BALF) can sample the profound changes in the airway lumen milieu prevalent in chronic obstructive pulmonary disease (COPD). We compared the BALF proteome of ex-smokers with moderate COPD who are not in exacerbation status to non-smoking healthy control subjects and applied proteome-scale translational bioinformatics approaches to identify potential therapeutic protein targets and drugs that modulate these proteins for the treatment of COPD. Proteomic profiles of BALF were obtained from (1) never-smoker control subjects with normal lung function (n = 10) or (2) individuals with stable moderate (GOLD stage 2, FEV1 50−80% predicted, FEV1/FVC < 0.70) COPD who were ex-smokers for at least 1 year (n = 10). After identifying potential crucial hub proteins, drug−proteome interaction signatures were ranked by the computational analysis of novel drug opportunities (CANDO) platform for multiscale therapeutic discovery to identify potentially repurposable drugs. Subsequently, a literature-based knowledge graph was utilized to rank combinations of drugs that most likely ameliorate inflammatory processes. Proteomic network analysis demonstrated that 233 of the >1800 proteins identified in the BALF were significantly differentially expressed in COPD versus control. Functional annotation of the differentially expressed proteins was used to detail canonical pathways containing the differential expressed proteins. Topological network analysis demonstrated that four putative proteins act as central node proteins in COPD. The drugs with the most similar interaction signatures to approved COPD drugs were extracted with the CANDO platform. The drugs identified using CANDO were subsequently analyzed using a knowledge-based technique to determine an optimal two-drug combination that had the most appropriate effect on the central node proteins. Network analysis of the BALF proteome identified critical targets that have critical roles in modulating COPD pathogenesis, for which we identified several drugs that could be repurposed to treat COPD using a multiscale shotgun drug discovery approach.