Automated Identification of Germline de novo Mutations in Family Trios: A Consensus-Based Informatic Approach.

Accurate identification of germline de novo variants (DNVs) remains a challenging problem despite rapid advances in sequencing technologies as well as methods for the analysis of the data they generate, with putative solutions often involving ad hoc filters and visual inspection of identified variants. Here, we present a purely informatic method for the identification of DNVs by analyzing short-read genome sequencing data from proband-parent trios. Our method evaluates variant calls generated by three genome sequence analysis pipelines utilizing different algorithms-GATK HaplotypeCaller, DeepTrio and Velsera GRAF-exploring the assumption that a requirement of consensus can serve as an effective filter for high-quality DNVs. We assessed the efficacy of our method by testing DNVs identified using a previously established, highly accurate classification procedure that partially relied on manual inspection and used Sanger sequencing to validate a DNV subset comprising less confident calls. The results show that our method is highly precise and that applying a force-calling procedure to putative variants further removes false-positive calls, increasing precision of the workflow to 99.6%. Our method also identified novel DNVs, 87% of which were validated, indicating it offers a higher recall rate without compromising accuracy. We have implemented this method as an automated bioinformatics workflow suitable for large-scale analyses without need for manual intervention.

Valorization of waste engine oil to mono- and di-rhamnolipid in a sustainable approach to circular bioeconomy.

This study aims to valorize waste engine oil (WEO) for synthesizing economically viable biosurfactants (rhamnolipids) to strengthen the circular bioeconomy concept. It specifically focuses on investigating the influence of key bioprocess parameters, viz. agitation and aeration rates, on enhancing rhamnolipid yield in a fed-batch fermentation mode. The methodology involves conducting experiments in a stirred tank bioreactor (3 L) using Pseudomonas aeruginosa gi |KP 163922| as the test organism. Central composite design and response surface methodology (CCD-RSM) are employed to design the experiments and analyze the effects of agitation and aeration rates on various parameters, including dry cell biomass (DCBM), surface tension, tensoactivity, and rhamnolipid yield. It is also essential to determine the mechanistic pathway of biosurfactant production followed by the strain using complex hydrophobic substrates such as WEO. The study reveals that optimal agitation and aeration rates of 200 rpm and 1 Lpm result in the highest biosurfactant yield of 29.76 g/L with minimal surface tension (28 mN/m). Biosurfactant characterization using FTIR, 1H NMR, and UPLC-MS/MS confirm the presence of dominant molecular ion peaks m/z 543.9 and 675.1. This suggests that the biosurfactant is a mixture of mono- and di-rhamnolipids (RhaC10C10, RhaRhaC10C12:1, RhaRhaC12:1C10). The findings present a sustainable approach for biosurfactant production in a fed-batch bioreactor. This research opens the possibility of exploring the use of pilot or large-scale bioreactors for biosurfactant production in future investigations.

Oncogene-driven non-small cell lung cancers in patients with a history of smoking lack smoking-induced mutations.

Non-small cell lung cancers (NSCLCs) in non-smokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in non-smokers, alterations in these "non-smoking-related oncogenes" (NSROs) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared to typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and non-smokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC datasets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to regulation of the cell cycle. These findings suggest that, while the genomic landscape is similar between NSRO-driven NSCLC in smokers and non-smokers, smoking still affects the tumor phenotype independently of genomic alterations.

Development of a Novel Risk Stratification Score to Predict 30-Day Mortality in Cervical Trauma Patients: CLAAD Score.

STUDY DESIGN: Case control. OBJECTIVE: Traumatic cervical spine injuries are associated with a substantial risk of mortality. The aim of this study is to develop a novel mortality prediction model for patients with cervical trauma who require operative treatment. SUMMARY OF BACKGROUND DATA: Patients with cervical spine trauma have a high risk of postoperative complications and mortality. There are few reliable systems that can accurately predict mortality after surgery for cervical spine trauma, and those that do exist are typically not specific to cervical trauma. MATERIALS AND METHODS: The National Surgical Quality Improvement Program (NSQIP) database was used to identify patients undergoing surgery for cervical spine trauma. Univariate analyses were performed to identify variables associated with mortality. Variables that were found to be significant in the univariate models were compiled into a multivariable model. The final model was compared with the American Society of Anesthesiologists (ASA), a modified Charlson comorbidity index (mCCI), and the 5-factor modified frailty index (mFI-5) in respect to predicting 30-day mortality after cervical trauma. The score was then externally validated using the Nationwide Inpatient Sample (NIS) database. RESULTS: Fifty-five (6.7%) of 822 patients did not survive 30 days after surgery. The final multivariable logistic regression model consisted of the following variables: circumferential fusion "C." long "L" fusion (more than 4 levels), anemia "A," age over 60 "A," and dialysis "D." The risk of mortality increased with increasing CLAAD score, with mortality rates of 0.9%, 3.1%, 7.4%, 22.7%, and 14.3% for scores of 0, 1, 2, 3, and 4, respectively. The CLAAD model had an AUC of 0.73 for predicting mortality after cervical trauma. CONCLUSIONS: The CLAAD score is a simple and effective system that can help identify patients at risk of increased mortality within 30 days of cervical trauma. LEVEL OF EVIDENCE: Level III.

The cost-utility of intraoperative tranexamic acid in adult spinal deformity patients undergoing long posterior spinal fusion.

PURPOSE: This study aims to evaluate the cost-utility of intraoperative tranexamic acid (TXA) in adult spinal deformity (ASD) patients undergoing long posterior (≥ 5 vertebral levels) spinal fusion. METHODS: A decision-analysis model was built for a hypothetical 60-year-old adult patient with spinal deformity undergoing long posterior spinal fusion. A comprehensive review of the literature was performed to obtain event probabilities, costs and health utilities at each node. Health utilities were utilized to calculate Quality-Adjusted Life Years (QALYs). A base-case analysis was carried out to obtain the incremental cost and effectiveness of intraoperative TXA. Probabilistic sensitivity analysis was performed to evaluate uncertainty in our model and obtain mean incremental costs, effectiveness, and net monetary benefits. One-way sensitivity analyses were also performed to identify the variables with the most impact on our model. RESULTS: Use of intraoperative TXA was the favored strategy in 88% of the iterations. The mean incremental utility ratio for using intraoperative TXA demonstrated higher benefit and lower cost while being lower than the willingness-to-pay threshold set at $50,000 per quality adjusted life years. Use of intraoperative TXA was associated with a mean incremental net monetary benefit (INMB) of $3743 (95% CI 3492-3995). One-way sensitivity analysis reported cost of blood transfusions due to post-operative anemia to be a major driver of cost-utility analysis. CONCLUSION: Use of intraoperative TXAs is a cost-effective strategy to reduce overall perioperative costs related to post-operative blood transfusions. Administration of intraoperative TXA should be considered for long fusions in ASD population when not explicitly contra-indicated due to patient factors.

Postoperative Herpes Viral Infections in Neurosurgery - An Experience and Arguments for and against the Plausible Hypotheses.

BACKGROUND: The literature contains several reports of herpes recrudescence after neurosurgery. We analyze our experience by vindicating or refuting the existing plausible hypotheses. MATERIAL AND METHODS: This is a retrospective review of all neurosurgical cases that developed postoperative herpes infection between January 2016 and June 2020. RESULTS: Six patients developed herpes infection after vestibular schwannoma (VS) surgery. Other neurosurgical cases did not develop herpes infection. There were five females and one male, with a mean age of 44.1 years. Four out of six patients developed delayed facial palsy (DFP) and did not improve after antiviral treatment. Postoperative herpes infections were 0.2% among all operated patients, 3.07% among all cerebellopontine (CP) angle surgeries, and 5.6% among VS surgeries. CONCLUSIONS: To date, none of the plausible hypotheses satisfactorily addresses all aspects of viral recrudescence. The etiology may be multi-factorial, and in all cases of unexplained clinical deterioration, herpes infection needs consideration in the differential diagnosis.

A case of metastatic lymphoepithelial carcinoma of parotid gland identified on 68gallium DOTA-[Tyr3] octreotate PET CT.

The authors present the case of a 59-year-old lady diagnosed with lymphoepithelial carcinoma (LEC) of the left parotid gland. The primary tumour was identified using contrast-enhanced CT, and diagnosis was confirmed via fine needle aspiration cytology and immunohistochemistry. Staging using fluorine-18 fluorodeoxyglucose PET CT revealed regional nodal metastases, while no distant metastasis was evident. Following radical radiotherapy, a favourable locoregional response was observed on MRI, yet the patient's plasma Epstein-Barr virus load continued to rise. Given her primary tumour's somatostatin receptor type 2 (SSTR2) positivity, gallium-68 DOTA-[Tyr3] octreotate PET CT (68Ga-DOTATATE PET CT) was performed, revealing multiple distant metastases with DOTATATE avidity. Despite attempts at palliative chemotherapy and immunotherapy, disease progression led to the decision for the best supportive care. The unique presentation of metastatic LEC on 68Ga-DOTATATE PET CT suggests a potential role for SSTR2-targeted imaging in diagnosis and management.

Development of an International AO Spine Guideline for the Use of Osteobiologics in Anterior Cervical Fusion and Decompression (AO-GO).

STUDY DESIGN: Methodological study for guideline development. OBJECTIVE: AO Spine Guideline for Using Osteobiologics (AO-GO) project for spine degenerative pathologies was an international, multidisciplinary collaborative initiative to identify and evaluate evidence on existing use of osteobiologics in Anterior Cervical Fusion and Decompression (ACDF). The aim was to formulate precisely defined, clinically relevant and internationally applicable guidelines ensuring evidence-based, safe and effective use of osteobiologics, considering regional preferences and cost-effectiveness. METHODS: Guideline was completed in two phases: Phase 1- evidence synthesis; Phase 2- recommendation development based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. In Phase 1, key questions identified by a panel of experts were addressed in a series of systematic reviews of randomized and non-randomized studies. In Phase 2, the GRADE approach was used to formulate a series of recommendations, including expert panel discussions via web calls and face-to-face meetings. DISCUSSION: AO-GO aims to bridge an important gap between evidence and use of osteobiologics in spine fusion surgeries. Owing to differences in osteobiologics preparation and functional characteristics, regulatory requirements for approval may vary, therefore it is highly likely that these products enter market without quality clinical trials. With a holistic approach the guideline aims to facilitate evidence-based, patient-oriented decision-making processes in clinical practice, thus stimulating further evidence-based studies regarding osteobiologics usage in spine surgeries. In Phase 3, the guideline will be disseminated and validated using prospectively collected clinical data in a separate effort of the AO Spine Knowledge Forum Degenerative in a global multicenter clinical study.

The Evidence for the Use of Osteobiologics in Hybrid Constructs (Anterior Cervical Discectomy and Fusion and Total Disc Replacement) in Multilevel Cervical Degenerative Disc Disease: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVE: Examine the clinical evidence for the use of osteobiologics in hybrid surgery (combined anterior cervical discectomy and fusion (ACDF) and total disc replacement (TDR)) in patients with multilevel cervical degenerative disc disease (DDD). METHODS: PubMed and Embase were searched between January 2000 and August 2020. Clinical studies investigating 18-80 year old patients with multilevel cervical DDD who underwent hybrid surgery with or without the use of osteobiologics were considered eligible. Two reviewers independently screened and assessed the identified articles. The methodological index for non-randomized studies (MINORS) tool and the risk of bias (RoB 2.0) assessment tool were used to assess risk of bias. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to evaluate quality of evidence across studies per outcome. RESULTS: Eleven studies were included. A decrease in cervical range of motion was observed in most studies for both the hybrid surgery and the control groups consisting of stand-alone ACDF or TDR. Fusion rates of 70-100% were reported in both the hybrid surgery and control groups consisting of stand-alone ACDF. The hybrid surgery group performed better or comparable to the control group in terms of adjacent segment degeneration. Studies reported an improvement in visual analogue scale for pain and neck disability index values after surgery compared to preoperative scores for both treatment groups. The included studies had moderate methodological quality. CONCLUSIONS: There is insufficient evidence for assessing the use of osteobiologics in multilevel hybrid surgery and additional high quality and controlled research is deemed essential.

AO Spine Guideline for the Use of Osteobiologics (AOGO) in Anterior Cervical Discectomy and Fusion for Spinal Degenerative Cases.

STUDY DESIGN: Guideline. OBJECTIVES: To develop an international guideline (AOGO) about the use of osteobiologics in anterior cervical discectomy and fusion (ACDF) for treating degenerative spine conditions. METHODS: The guideline development process was guided by AO Spine Knowledge Forum Degenerative (KF Degen) and followed the Guideline International Network McMaster Guideline Development Checklist. The process involved 73 participants with expertise in degenerative spine diseases and surgery from 22 countries. Fifteen systematic reviews were conducted addressing respective key topics and evidence was collected. The methodologist compiled the evidence into GRADE Evidence-to-Decision frameworks. Guideline panel members judged the outcomes and other criteria and made the final recommendations through consensus. RESULTS: Five conditional recommendations were created. A conditional recommendation is about the use of allograft, autograft or a cage with an osteobiologic in primary ACDF surgery. Other conditional recommendations are about the use of osteobiologic for single- or multi-level ACDF, and for hybrid construct surgery. It is suggested that surgeons use other osteobiologics rather than human bone morphogenetic protein-2 (BMP-2) in common clinical situations. Surgeons are recommended to choose 1 graft over another or 1 osteobiologic over another primarily based on clinical situation, and the costs and availability of the materials. CONCLUSION: This AOGO guideline is the first to provide recommendations for the use of osteobiologics in ACDF. Despite the comprehensive searches for evidence, there were few studies completed with small sample sizes and primarily as case series with inherent risks of bias. Therefore, high-quality clinical evidence is demanded to improve the guideline.

Structural Allograft Versus Mechanical Interbody Devices Augmented With Osteobiologics in Anterior Cervical Discectomy and Fusion: A Systematic Review.

STUDY DESIGN: Systematic Literature Review. OBJECTIVE: Perform a systematic review evaluating postoperative fusion rates for anterior cervical discectomy and fusion (ACDF) using structural allograft vs various interbody devices augmented with different osteobiologic materials. METHODS: Comprehensive literature search using PubMed, Embase, The Cochrane Library, and Web of Science was performed. Included studies were those that reported results of 1-4 levels ACDF using pure structural allograft compared with a mechanical interbody device augmented with an osteobiologic. Excluded studies were those that reported on ACDF with cervical corpectomy; anterior and posterior cervical fusions; circumferential (360° or 540°) fusion or revision ACDF for nonunion or other conditions. Risk of bias was determined using the Cochrane review guidelines. RESULTS: 8 articles reporting fusion rates of structural allograft and an interbody device/osteobiologic pair were included. All included studies compared fusion rates following ACDF among structural allograft vs non-allograft interbody device/osteobiologic pairs. Fusion rates were reported between 84% and 100% for structural allograft, while fusion rates for various interbody device/osteobiologic combinations ranged from 26% to 100%. Among non-allograft cage groups fusion rates varied from 73-100%. One study found PEEK cages filled with combinations of autograft, allograft, and demineralized bone matrix (DBM) to have an overall fusion rate of 26%. In one study comparing plate and zero-profile constructs, there was no difference in fusion rates for two-level fusions. CONCLUSION: There was limited data comparing fusion outcomes of patients undergoing ACDF using structural allograft vs interbody devices augmented with osteobiologic materials to support superiority of one method.

Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer.

BACKGROUND: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay. METHODS: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples. RESULTS: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001). CONCLUSIONS: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting.

Medicare Advantage Is Associated with Lower Utilization of Total Joint Arthroplasty.

BACKGROUND: Medicare Advantage (MA) insurers use managed care techniques to review the utilization of medical services and control costs. It is unclear if MA enrollees have a lower utilization of elective surgical procedures such as inpatient hip and knee total joint arthroplasty (TJA), which have traditionally been covered by traditional Medicare (TM) without restrictions. METHODS: We conducted a cross-sectional study using a 20% sample of 2018 TM claims and MA encounter records for 5,300,188 TM enrollees and 1,970,032 MA enrollees who were 65 to 85 years of age. We calculated unadjusted and adjusted differences (controlling for beneficiary and market characteristics) in the incidence of TJA for MA compared with TM, and by MA plan type. Finally, we calculated differences in the time to contact with an orthopaedic surgeon and time to the surgical procedure among enrollees with an osteoarthritis diagnosis. RESULTS: After controlling for observable characteristics, there was a 15.6% lower incidence of TJA in MA enrollees compared with TM enrollees (p < 0.001). Compared with TM enrollees, health maintenance organization (HMO) enrollees were 28.1% less likely to undergo TJA, controlling for observable characteristics (p < 0.001). From the initial diagnosis, the time to contact with an orthopaedic surgeon and the time to the surgical procedure were also lower among TM enrollees compared with MA enrollees. At 2 years after an osteoarthritis diagnosis, 10.4% of TM enrollees, 7.9% of preferred provider organization (PPO) enrollees, and 5.7% of HMO enrollees had undergone inpatient TJA. CONCLUSIONS: MA coverage was associated with a lower utilization of elective, inpatient hip and knee TJA. MA was also associated with a longer time to orthopaedic surgeon evaluation and surgical procedure. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Measuring Value in Spine Care Using the PROMIS-Preference Scoring System.

BACKGROUND: A transition to value-based care requires a thorough understanding of the costs and impacts of various interventions on patients' overall health utility. The Patient-Reported Outcomes Measurement Information System (PROMIS) has gained popularity and is frequently used to assess physical, mental, and social health domains in clinical and research settings. To assess health utility, the PROMIS-Preference (PROPr) score, a societal preference-based measure, has been proposed to produce a single estimate of health utility. We determined the psychometric properties (validity and responsiveness) of the PROPr score as a health state utility measure in patients undergoing spine surgery. We hypothesized that PROPr score would be lower in the presence of comorbid conditions and lower socioeconomic status and in those with more severe pain-related disability and would be responsive to changes in health status following spine surgery. METHODS: In this prospective cohort study, 904 adults presented for cervical (n = 359) and/or lumbar (n = 622) conditions, and 624 underwent surgery, from August 2019 through January 2022. To assess concurrent validity, we correlated the PROPr score with Neck Disability Index (NDI)/Oswestry Disability Index (ODI) values. To assess known-groups validity, we regressed the PROPr score on participant age, sex, pain-related disability, and social determinants of health. To assess responsiveness, we used an anchor-based approach, evaluating change from preoperatively to 6 and 12 months postoperatively anchored by the Patient Global Impression of Change. A p level of <0.05 was considered significant. RESULTS: The median overall preoperative PROPr score was 0.20 (interquartile range [IQR], 0.10 to 0.32; range, -0.02 to 0.95). The PROPr score was associated with higher educational attainment (p = 0.01), higher household income (p < 0.001), and a greater number of comorbid conditions (p = 0.04). The median PROPr score decreased (worse health utility) with greater disability (NDI, 0.44 [none] to 0.09 [severe/complete], p < 0.001; ODI, 0.57 [none] to 0.08 [severe/complete], p < 0.001). The change in the median PROPr score differed in participants who rated their postoperative health as improved (0.17) compared with little or no change (0.04; p < 0.001) or worse (-0.06; p = 0.025) at 6 months and in those who rated their health as improved (0.15) compared with little or no change (0.02; p < 0.001) or worse (-0.05; p = 0.043) at 12 months. CONCLUSIONS: The PROPr score is a valid and responsive preference-based assessment of health utility for patients undergoing spine surgery. It can be calculated from PROMIS outcome data. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Inflation-adjusted medicare physician reimbursement for adult spinal deformity surgery substantially declined from 2002 to 2020.

PURPOSE: Physician fees for orthopaedic surgeons by the Centers for Medicare and Medicaid Services (CMS) are increasingly scrutinized. The present retrospective review aims to assess whether adult spinal deformity (ASD) surgeries are properly valued for Medicare reimbursement. METHODS: Current Procedural Terminology (CPT) codes related to posterior fusion of spinal deformity of ≤ 6, 7-12, and ≥ 13 vertebral levels, as well as additional arthrodesis and osteotomy levels, were assessed for (1) Compound annual growth rate (CAGR) from 2002 to 2020, calculated using physician fee data from the CMS Physician Fee Schedule Look-Up Tool; and (2) work relative value units (RVUs) per operative minute, using data from the National Surgical Quality Improvement Program. RESULTS: From 2002 to 2020, all CPT codes for ASD surgery had negative inflation-adjusted CAGRs (range, - 18.49% to - 27.66%). Mean physician fees for spinal fusion declined by 26.02% (CAGR, - 1.66%) in ≤ 6-level fusion, 27.91% (CAGR, - 1.80%) in 7- to 12-level fusion, and 28.25% (CAGR, - 1.83%) ≥ 13-level fusion. Fees for both 7-12 (P < 0.00001) and ≥ 13 levels (P < 0.00001) declined more than those for fusion of ≤ 6 vertebral levels. RVU per minute was lower for 7- to 12-level and ≥ 13-level (P < 0.00001 for both) ASD surgeries than for ≤ 6-level. CONCLUSIONS: Reimbursement for ASD surgery declined overall. CAGR for fusions of ≥ 7 levels were lower than those for fusions of ≤ 6 levels. For 2012-2018, ≥ 7-level fusions had lower RVU per minute than ≤ 6-level fusions. Revaluation of Medicare reimbursement for longer-level ASD surgeries may be warranted. LEVEL OF EVIDENCE: III.

Elevated preoperative blood pressure and its relationship to intraoperative mean arterial pressure and blood loss in posterior spinal fusion for adolescent idiopathic scoliosis.

PURPOSE: The relationship between preoperative blood pressure (BP) and intraoperative mean arterial pressure (MAP) and estimated blood loss (EBL) in pediatric spine surgery is currently unknown. The objectives of this study were to determine if elevated preoperative BP is associated with elevated intraoperative MAP, EBL, and percentage estimated blood volume (EBV) lost, and to determine if intraoperative MAP is associated with percentage of EBV lost during posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). METHODS: This is a retrospective cohort analysis of 209 patients undergoing PSF for AIS between 2016 and 2019 by a single surgeon. Data extracted included demographic characteristics, preoperative systolic and diastolic BP, continuous intraoperative MAP measured by arterial line, EBL, radiographic, and surgical characteristics. Time points of interest for MAP included incision and exposure. Elevated BP was defined as > 1 standard deviation above the mean BP of patients included in the study, and elevated MAP was defined as > 65 mmHg. RESULTS: Elevated preoperative systolic BP was associated with elevated MAP at incision (p = 0.002). Patients with elevated preoperative diastolic BP had significantly higher MAP at exposure and throughout the procedure (p = 0.04). MAP > 65 at incision was associated with a 5% increase in EBV lost (p < 0.001). CONCLUSIONS: Patients with elevated preoperative BP parameters have increased MAPs at incision, exposure, and throughout surgery. Elevated MAP at incision is associated with an increased percentage of EBV lost in a small number of patients undergoing PSF for AIS.

Using a Modern Linked Research Database to Examine Gender Disparities in Orthopaedic Grant Funding from 2010 to 2022.

BACKGROUND: Gender disparities in research grant funding persist in many disciplines. With use of the Dimensions database, we sought to examine the extent of gender disparities in U.S. orthopaedic grant funding from 2010 onward. Our aim was to provide insights into the extent of gender disparities in the field of orthopaedic research and to highlight the potential need for future action to address these disparities. METHODS: Using orthopaedic-related search terms, we queried all U.S. grants awarded for orthopaedic research from 2010 to 2022. A total of 22,326 results were then manually screened to exclude those without a direct focus on orthopaedic research. The amounts received per principal investigator were reported in U.S. dollars and adjusted for inflation. Author gender was predicted with use of the Genderize.io algorithm application programming interface. The iCite Relative Citation Ratio (RCR) was utilized to assess the impact of the publications linked to each grant. RESULTS: A total of 1,723 grants were included. Men principal investigators received significantly higher median funding per grant in 2011, 2012, and 2013; however, this trend reversed with women receiving nonsignificantly higher funding in 2015, 2017, 2018, 2021, and 2022. In 2020, women received significantly higher median funding per grant than men ($166,234 versus $121,384; p = 0.04). Throughout the 13-year period, men principal investigators accounted for approximately 71% of grants, with a very weak increasing trend in the percent of grants attributed to women (R 2 = 0.16; p < 0.001). Grants with men principal investigators resulted in more publications than those with women principal investigators (mean publications, 11.1 versus 6.6; p = 0.001). Publications resulting from grants awarded to men had a significantly higher mean RCR than those resulting from grants awarded to women (2.42 versus 2.09; p = 0.04). CONCLUSIONS: There was no significant difference in the median amounts of funding per grant awarded to men and to women in 7 of the past 8 years, despite significantly greater funding per grant having been awarded to men from 2011 to 2013. Men principal investigators accounted for the majority of grants received during the study period, although this proportion was lower than the proportion of men among orthopaedic surgeons in 2022. This study could inform initiatives aimed at promoting equity in grant funding for orthopaedic research.

Predicting Mortality Following Odontoid Fracture Fixation in Elderly Patients: CAADS-16 Score.

STUDY DESIGN: Retrospective Review of a National Database. INTRODUCTION: By utilizing a national database, this study aims to quantify the predictors of 30-day mortality after odontoid fixation and guide appropriate management for patients in whom the choice between operative and non-operative management is unclear. METHODS: The American College of Surgeons National Surgical Quality Improvement Database was queried using Current Procedural Terminology (CPT) codes and International Classification of Disease (ICD) codes to identify patients 60 or older who underwent surgical fixation of an odontoid fracture from 2005 to 2020. Risk factors for mortality significant in univariate and subsequent multivariate analysis were used to develop a scoring system to predict post-operative mortality. RESULTS: 608 patients were identified. Patients were split into a non-mortality 30 days post-op group, and into a mortality 30 days post-op group. The following risk factors were included in the scoring system: functional dependency, disseminated cancer, albumin less than 3.5, WBC count greater than 16 k, anterior surgical approach, and pre-op SIRS. Using a cutoff value of 2, the CAAD-16 score had a sensitivity and specificity of 82% and 81%, respectively. The ASA score, cutoff at 4, showed a sensitivity and specificity of 64% and 75% respectively. CONCLUSIONS: This sample of 294 patients represents one of the largest samples of odontoid fracture fixation patients available in the literature and comes from a nationally representative database. We structure relevant risk factors into the CAADS-16 score, which has the potential to be a clinically relevant tool to prevent short-term postoperative mortality.

Gender diversity at spine surgery academic conferences: a 15-year investigation.

BACKGROUND CONTEXT: Enhancing gender diversity at academic conferences is critical for advancing women's representation and career trajectories in spine surgery. PURPOSE: To discover trends in women's representation at major spine conferences over a 15-year period. STUDY DESIGN/SETTING: Conference records from the 2007-2021 annual meetings of the Congress of Neurological Surgeons, North American Spine Society, and Scoliosis Research Society (SRS). PATIENT SAMPLE: Authors of spine-related presentations. OUTCOME MEASURES: Authorship by gender. METHODS: Retrospective bibliometric analysis with univariate and multivariate modeling to identify trends and predictors of gender diversity. RESULTS: Among 8,948 presentations, 750 (8.4%) had female first authors and 618 (6.9%) had female senior authors. There was no change in rates of female first authorship (p=.41) or senior authorship (p=.88) over time. The strongest predictors of female first authorship were having a female senior author (OR 7.32, p<.001), and delivering presentations at SRS (OR 1.95, p=.001). Factors negatively associated with female first authorship included poster format (OR 0.82, p=.039) and conference location in the United States/Canada (OR 0.76, p=.045). Similar trends were encountered for senior authorship. Productivity per senior author was similar between genders (p=.160); whereas a gender gap in productivity per first author during 2007 to 2011 (p=.020) equalized by 2017 to 2021 (p=.300). Among the 10 most productive authors of each gender, male authors delivered more presentations, but all authors shared similar format, content, and location. CONCLUSIONS: Women's representation in spine-related presentations did not increase at three major conferences over a 15-year period. Our findings regarding the positive effects of female mentorship, and international or virtual venues merit further investigation to address the gender gap. The upstream pipeline of recruiting women into academic spine surgery also needs to be addressed.

Impact of basic psychological support on stigma and mental well-being of people with disabilities due to leprosy and lymphatic filariasis: a proof-of-concept study.

BACKGROUND: People with leprosy and lymphatic filariasis (LF)-related disabilities experience higher levels of poor mental well-being compared with the general community. Mental health services are often not available. This study was conducted to provide proof of concept that basic psychological support for people affected by neglected tropical diseases (BPS-N) can be given by peer supporters to reduce stigma, improve mental well-being and participation among clients. METHODS: The BPS-N approach was tested in a quasi-experimental design using mixed methods. To provide psychological support using the BPS-N, peer supporters were selected and trained. They supported people with leprosy- and LF-related disabilities. Preintervention and postintervention, stigma, mental well-being, depression and participation were measured through standard scales within 4 wk of the intervention; differences were tested using standard tests of significance. RESULTS: After 3 mo of intervention, the mean level of stigma had decreased (30.3 to 24, p<0.001); high mental well-being increased (0% to 13.3%, p<0.001); and moderate to severe depression decreased (88% to 47%, p<0.001). No significant change occurred in participation restrictions (87% to 92%, p=0.497). CONCLUSIONS: Psychological peer support using the BPS-N guideline appears effective in reducing stigma and improving mental well-being and can be operationalised. However, this should be confirmed through a randomised controlled trial. CONTEXTE: Les personnes atteintes de lèpre et de handicaps liés à la filariose lymphatique (FL) souffrent davantage d'un manque de bien-être mental que le reste de la population. Les services de santé mentale ne sont souvent pas disponibles hors des zones urbaines. Cette étude a été menée pour démontrer que le soutien psychologique de base pour les personnes atteintes de MTN (BPS-N) peut être dispensé par des pairs (dans une logique de transfert de tâches) afin de réduire la stigmatisation et d'améliorer le bien-être mental et la participation des clients. MÉTHODES: L'approche du BPS-N a été testée dans le cadre d'un modèle quasi-expérimental utilisant des méthodes mixtes. Pour fournir un soutien psychologique à l'aide du BPS-N, des pairs ont été sélectionnés et formés. Ils sont venus en aide aux personnes atteintes de lèpre et de déficiences liées à la FL. Avant et après l'intervention, les éléments suivants ont été mesurés à l'aide d'échelles standardisées: niveau de stigmatisation, bien-être mental, symptômes dépressifs, et enfin, la participation sociale. Les différences ont été testées à l'aide de tests de signification standardisés. RÉSULTATS: Après 3 mois d'intervention, le niveau moyen de stigmatisation a diminué (30,3 à 24, p<0 001) ; le niveau de bien-être mental a augmenté (0% à 13,3%, p<0 001) et la dépression modérée à sévère a diminué (88% à 47%, p<0 001). Aucun changement significatif n'a été observé en ce qui concerne les restrictions de participation (87% contre 92%, p=0 497). CONCLUSIONS: Le soutien psychologique par les pairs utilisant la ligne directrice BPS-N semble efficace pour réduire la stigmatisation et améliorer le bien-être mental. Toutefois, cette efficacité doit être confirmée par un essai contrôlé randomisé. ANTECEDENTES: Las personas con lepra y discapacidades relacionadas con la filariasis linfática (FL) sufren niveles más altos de malestar mental en comparación con la comunidad en general. Los servicios de salud mental no suelen estar disponibles a nivel periférico. Este estudio se llevó a cabo para proporcionar una prueba de concepto de que el Apoyo Psicológico Básico para personas afectadas por NTDs (BPS-N) puede ser dado por compañeros de apoyo (rotación de tareas) para reducir el estigma, mejorar el bienestar mental y la participación entre los clientes. MÉTODOS: El enfoque BPS-N se probó en un diseño cuasi-experimental utilizando métodos mixtos. Para proporcionar apoyo psicológico con el BPS-N, se seleccionaron y formaron compañeros de apoyo. Apoyaron a personas con lepra y discapacidades relacionadas con la FL. El estigma, el bienestar mental, la depresión y la participación se midieron antes y después de la intervención, mediante escalas estándar; las diferencias se comprobaron mediante pruebas estándar de significación. RESULTADOS: Después de 3 meses de intervención, el nivel medio de estigma disminuyó (30,3 a 24, p<0 001); el bienestar mental alto aumentó (0% a 13,3%, p<0 001) y la depresión moderada a grave disminuyó (88% a 47%, p<0 001). No se produjeron cambios significativos en las restricciones de participación (87% frente a 92%, p=0 497)). CONCLUSIONES: El apoyo psicológico entre iguales, utilizando la guía BPS-N, parece eficaz para reducir el estigma y mejorar el bienestar mental. Sin embargo, esto debe confirmarse mediante un ensayo controlado aleatorizado.