CohortFinder: an open-source tool for data-driven partitioning of digital pathology and imaging cohorts to yield robust machine-learning models.

Batch effects (BEs) refer to systematic technical differences in data collection unrelated to biological variations whose noise is shown to negatively impact machine learning (ML) model generalizability. Here we release CohortFinder (http://cohortfinder.com), an open-source tool aimed at mitigating BEs via data-driven cohort partitioning. We demonstrate CohortFinder improves ML model performance in downstream digital pathology and medical image processing tasks. CohortFinder is freely available for download at cohortfinder.com.

An Appraisal of the Quality of Development and Reporting of Predictive Models in Neurosurgery: A Systematic Review.

BACKGROUND AND OBJECTIVES: Significant evidence has indicated that the reporting quality of novel predictive models is poor because of confounding by small data sets, inappropriate statistical analyses, and a lack of validation and reproducibility. The Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) statement was developed to increase the generalizability of predictive models. This study evaluated the quality of predictive models reported in neurosurgical literature through their compliance with the TRIPOD guidelines. METHODS: Articles reporting prediction models published in the top 5 neurosurgery journals by SCImago Journal Rank-2 (Neurosurgery, Journal of Neurosurgery, Journal of Neurosurgery: Spine, Journal of NeuroInterventional Surgery, and Journal of Neurology, Neurosurgery, and Psychiatry) between January 1st, 2018, and January 1st, 2023, were identified through a PubMed search strategy that combined terms related to machine learning and prediction modeling. These original research articles were analyzed against the TRIPOD criteria. RESULTS: A total of 110 articles were assessed with the TRIPOD checklist. The median compliance was 57.4% (IQR: 50.0%-66.7%). Models using machine learning-based models exhibited lower compliance on average compared with conventional learning-based models (57.1%, 50.0%-66.7% vs 68.1%, 50.2%-68.1%, P = .472). Among the TRIPOD criteria, the lowest compliance was observed in blinding the assessment of predictors and outcomes (n = 7, 12.7% and n = 10, 16.9%, respectively), including an informative title (n = 17, 15.6%) and reporting model performance measures such as confidence intervals (n = 27, 24.8%). Few studies provided sufficient information to allow for the external validation of results (n = 26, 25.7%). CONCLUSION: Published predictive models in neurosurgery commonly fall short of meeting the established guidelines laid out by TRIPOD for optimal development, validation, and reporting. This lack of compliance may represent the minor extent to which these models have been subjected to external validation or adopted into routine clinical practice in neurosurgery.

Unraveling molecular advancements in chordoma tumorigenesis and treatment response: a review of scientific discoveries and clinical implications.

Chordomas are tumors thought to originate from notochordal remnants that occur in midline structures from the cloves of the skull base to the sacrum. In adults, the most common location is the sacrum, followed by the clivus and then mobile spine, while in children a clival origin is most common. Most chordomas are slow growing. Clinical presentation of chordomas tend to occur late, with local invasion and large size often complicating surgical intervention. Radiation therapy with protons has been proven to be an effective adjuvant therapy. Unfortunately, few adjuvant systemic treatments have demonstrated significant effectiveness, and chordomas tend to recur despite intensive multimodal care. However, insight into the molecular underpinnings of chordomas may guide novel therapeutic approaches including selection for immune and molecular therapies, individualized prognostication of outcomes, and real-time noninvasive assessment of disease burden and evolution. At the genomic level, elevated levels of brachyury stemming from duplications and mutations resulting in altered transcriptional regulation may introduce druggable targets for new surgical adjuncts. Transcriptome and epigenome profiling have revealed promoter- and enhancer-dependent mechanisms of protein regulation, which may influence therapeutic response and long-term disease history. Continued scientific and clinical advancements may offer further opportunities for treatment of chordomas. Single-cell transcriptome profiling has further provided insight into the heterogeneous molecular pathways contributing to chordoma propagation. New technologies such as spatial transcriptomics and emerging biochemical analytes such as cell-free DNA have further augmented the surgeon-clinician's armamentarium by facilitating detailed characterization of intra- and intertumoral biology while also demonstrating promise for point-of-care tumor quantitation and assessment. Recent and ongoing clinical trials highlight accelerating interest to translate laboratory breakthroughs in chordoma biology and immunology into clinical care. In this review, the authors dissect the landmark studies exploring the molecular pathogenesis of chordoma. Incorporating this into an outline of ongoing clinical trials and discussion of emerging technologies, the authors aimed to summarize recent advancements in understanding chordoma pathogenesis and how neurosurgical care of chordomas may be augmented by improvements in adjunctive treatments.

Pedicled omental flaps for complex wound reconstruction following surgery for primary spine tumors of the mobile spine and sacrum.

OBJECTIVE: Surgery for primary tumors of the mobile spine and sacrum often requires complex reconstruction techniques to cover soft-tissue defects and to treat wound and CSF-related complications. The anatomical, vascular, and immunoregulatory characteristics of the omentum make it an excellent local substrate for the management of radiation soft-tissue injury, infection, and extensive wound defects. This study describes the authors' experience in complex wound reconstruction using pedicled omental flaps to cover defects in surgery for mobile spine and sacral primary tumors. METHODS: A retrospective cohort analysis was conducted on 34 patients who underwent pedicled omental flap reconstruction after en bloc resection of primary sacral and mobile spine tumors between 2010 and 2020. The study focused on assessing the indications for omental flap usage, including soft-tissue coverage, protection against postoperative radiation therapy, infection management, vascular supply for bone grafts, and dural defect and CSF leak repair. Patient demographic characteristics, tumor characteristics, surgical outcomes, and follow-up data were analyzed to determine the procedure's efficacy and complication rates. RESULTS: From 2010 to 2020, 34 patients underwent pedicled omental flap reconstruction after en bloc resection of sacral (24 of 34 [71%]) and mobile spine (10 of 34 [29%]) primary tumors, mostly chordomas. The patient cohort included 21 men and 13 women with a median (range) age of 60 (32-89) years. The most common indication for omental flap was soft-tissue coverage (20 of 34 [59%]). Other indications included protecting abdominopelvic organs for postoperative radiation therapy (6 of 34 [18%]), treating infections (5 of 34 [15%]), providing vascular supply for free fibular bone graft (1 of 34 [3%]), and repairing large dural defects and CSF leak (2 of 34 [6%]). The median (range) follow-up was 24 (0-132) months, during which 71% (24 of 34) of patients did not require additional surgery for wound-related complications. At last follow-up, 59% (20 of 34) had stable disease and 32% (11 of 34) had recurrence, had progression of disease, or had been discharged to hospice after treatment. CONCLUSIONS: The pedicled omentum is an effective local tissue graft that can be used for complex wound reconstruction and management of high-risk closures in primary spine tumors. This technique may have a lower rate of complications than other approaches and may influence surgical planning and flap selection in challenging cases.

The Impact of Peri-operative Enhanced Recovery After Surgery Protocols on Outcomes Following Adult Cervical Deformity Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To assess the impact of Enhanced recovery after surgery (ERAS) protocols on peri-operative course in adult cervical deformity (ACD) corrective surgery. METHODS: Patients ≥18 yrs with complete pre-(BL) and up to 2-year (2Y) radiographic and clinical outcome data were stratified by enrollment in an ERAS protocol that commenced in 2020. Differences in demographics, clinical outcomes, radiographic alignment targets, peri-operative factors and complication rates were assessed via means comparison analysis. Logistic regression analysed differences while controlling for baseline disability and deformity. RESULTS: We included 220 patients (average age 58.1 ± 11.9 years, 48% female). 20% were treated using the ERAS protocol (ERAS+). Disability was similar between both groups at baseline. When controlling for baseline disability and myelopathy, ERAS- patients were more likely to utilize opioids than ERAS+ (OR 1.79, 95% CI: 1.45-2.50, P = .016). Peri-operatively, ERAS+ had significantly lower operative time (P < .021), lower EBL (583.48 vs 246.51, P < .001), and required significantly lower doses of propofol intra-operatively than ERAS- patients (P = .020). ERAS+ patients also reported lower mean LOS overall (4.33 vs 5.84, P = .393), and were more likely to be discharged directly to home (χ2(1) = 4.974, P = .028). ERAS+ patients were less likely to require steroids after surgery (P = .045), were less likely to develop neuromuscular complications overall (P = .025), and less likely experience venous complications or be diagnosed with venous disease post-operatively (P = .025). CONCLUSIONS: Enhanced recovery after surgery programs in ACD surgery demonstrate significant benefit in terms of peri-operative outcomes for patients.

Double lumen endobronchial tube intubation: lessons learned from anatomy.

BACKGROUND: Double lumen endobronchial tubes (DLTs) are frequently used to employ single lung ventilation strategies during thoracic surgical procedures. Placement of these tubes can be challenging even for experienced clinicians. We hypothesized that airway anatomy, particularly of the glottis and proximal trachea, significantly impacts the ease or difficulty in placement of these tubes. METHODS: Images from 24 randomly selected Positron Emission Tomography - Computed Tomography (PET-CT) scans were evaluated for several anatomic aspects of the upper airway, including size and angulation of the glottis and proximal tracheal using calibrated CT measurements and an online digital protractor. The anatomic issues identified were confirmed in cadaveric anatomic models. RESULTS: Proximal tracheal diameter measurements in PET-CT scans demonstrated a mean ± standard deviation of 20.4 ± 2.5 mm in 12 males and 15.5 ± 0.98 mm in 12 females (p < 0.001), and both were large enough to accommodate 39 French and 37 French DLTs in males and females, respectively. Subsequent measurements of the posterior angulation of the proximal trachea revealed a mean angle of 40.8 ± 5.7 degrees with no sex differences. By combining the 24 individual posterior tracheal angles with the 16 angled distal tip measurements DLTs (mean angle 24.9 ± 2.1 degrees), we created a series of 384 patient intubation angle scenarios. This data clearly showed that DLT rotation to a full 180 degrees decreased the mean intubation angle between the DLT and the proximal trachea from a mean of 66.6 ± 5.9 to only 15.8 ± 5.9 degrees. CONCLUSIONS: Rotation of DLTs a full 180 instead of the recommended 90 degrees facilitates DLT intubations.

Assessing the Accessibility, Engagement, and Value of the Virtual Global Spine Conference as an Educational Platform for Spine: A Three-Year Review.

INTRODUCTION: The Coronavirus disease 2019 pandemic ushered a paradigm shift in medical education, accelerating the transition to virtual learning in select cases. The Virtual Global Spine Conference (VGSC), launched at the height of the pandemic, is a testament to this evolution, providing an independent educational series for spine care professionals worldwide. This study assesses VGSC's 3-year performance, focusing on accessibility, engagement, and educational value. METHODOLOGY: Through retrospective data analysis from April 2020 to August 2023, we examined our social media metrics to measure VGSC's reach and impact. RESULTS: Over the study period, VGSC's webinars successfully attracted 2337 unique participants, maintaining an average attendance of 47 individuals per session. The YouTube channel demonstrated significant growth, amassing over 2693 subscribers and releasing 168 videos. These videos collectively garnered 112,208 views and 15,823.3 hours of watch time. Viewer demographics reveal a predominant age group of 35-44 years, representing 56.81% of the audience, closely followed by the 25-34 age group at 40.2%. Male participants constituted 78.95% of the subscriber base. Geographically, the viewership primarily originates from the United States, with India, Canada, South Korea, and the United Kingdom also contributing substantial audience numbers. The VGSC's presence on the "X account" has grown to 2882 followers, significantly enlarging the digital community and fostering increased engagement. CONCLUSIONS: The VGSC has demonstrated significant value as a virtual educational tool in spine education. Its diverse content and ease of access will likely enable it to drive value well into the post-pandemic years. Maintaining and expanding engagement, beyond North America in particular, remains a priority.

Imaging of Adult Malignant Soft Tissue Tumors of the Spinal Canal: A Guide for Spine Surgeons.

BACKGROUND: Malignant soft tissue spinal canal tumors compromise 20% of all spinal neoplasms. They may be primary or metastatic lesions, originating from a diverse range of tissues within and surrounding the spinal canal. These masses can present as diverse emergencies such as secondary cauda equina syndrome, vascular compromise, or syringomyelia. Interpretation of malignant soft tissue spinal canal tumors imaging is an essential for non-radiologists in the setting of emergencies. This task is intricate due to a great radiologic pattern overlap among entities. METHODS: We present a step-by-step strategy that can guide nonradiologists identify a likely malignant soft tissue lesion in the spinal canal based on imaging features, as well as a review of the radiologic features of malignant soft tissue spinal canal tumors. RESULTS: Diagnosis of soft tissue spinal canal malignancies starts with the identification of the lesion's spinal level and its relationship to the dura and medulla. The second step consists of characterizing it as likely-malignant based on radiological signs like a larger size, ill-defined margins, central necrosis, and/or increased vascularity. The third step is to identify additional imaging features such as intratumoral hemorrhage or cyst formation that can suggest specific malignancies. The physician can then formulate a differential diagnosis. The most encountered malignant soft tissue tumors of the spinal canal are anaplastic ependymomas, anaplastic astrocytomas, metastatic tumors, lymphoma, peripheral nerve sheath tumors, and central nervous system melanomas. A review of the imaging features of every type/subtype of lesion is presented in this work. Although magnetic resonance imaging remains the modality of choice for spinal tumor assessment, other techniques such as dynamic contrast agent-enhanced perfusion magnetic resonance imaging or diffusion-weighted imaging could guide diagnosis in specific situations. CONCLUSIONS: In this review, diagnostic strategies for several spinal cord tumors were presented, including anaplastic ependymoma, metastatic spinal cord tumors, anaplastic and malignant astrocytoma, lymphoma, malignant peripheral nerve sheath tumors , and primary central nervous system melanoma. Although the characterization of spinal cord tumors can be challenging, comprehensive knowledge of imaging features can help overcome these challenges and ensure optimal management of spinal canal lesions.

Bridging the literacy gap for surgical consents: an AI-human expert collaborative approach.

Despite the importance of informed consent in healthcare, the readability and specificity of consent forms often impede patients' comprehension. This study investigates the use of GPT-4 to simplify surgical consent forms and introduces an AI-human expert collaborative approach to validate content appropriateness. Consent forms from multiple institutions were assessed for readability and simplified using GPT-4, with pre- and post-simplification readability metrics compared using nonparametric tests. Independent reviews by medical authors and a malpractice defense attorney were conducted. Finally, GPT-4's potential for generating de novo procedure-specific consent forms was assessed, with forms evaluated using a validated 8-item rubric and expert subspecialty surgeon review. Analysis of 15 academic medical centers' consent forms revealed significant reductions in average reading time, word rarity, and passive sentence frequency (all P < 0.05) following GPT-4-faciliated simplification. Readability improved from an average college freshman to an 8th-grade level (P = 0.004), matching the average American's reading level. Medical and legal sufficiency consistency was confirmed. GPT-4 generated procedure-specific consent forms for five varied surgical procedures at an average 6th-grade reading level. These forms received perfect scores on a standardized consent form rubric and withstood scrutiny upon expert subspeciality surgeon review. This study demonstrates the first AI-human expert collaboration to enhance surgical consent forms, significantly improving readability without sacrificing clinical detail. Our framework could be extended to other patient communication materials, emphasizing clear communication and mitigating disparities related to health literacy barriers.

Association of Malnutrition with Surgical and Hospital Outcomes after Spine Surgery for Spinal Metastases: A National Surgical Quality Improvement Program Study of 1613 Patients.

Background: Malnutrition is a common condition that may exacerbate many medical and surgical pathologies. However, few have studied the impact of malnutrition on surgical outcomes for patients undergoing surgery for metastatic disease of the spine. This study aims to evaluate the impact of malnutrition on perioperative complications and healthcare resource utilization following surgical treatment of spinal metastases. Methods: We conducted a retrospective cohort study using the 2011-2019 American College of Surgeons National Surgical Quality Improvement Program database. Adult patients with spinal metastases who underwent laminectomy, corpectomy, or posterior fusion for extradural spinal metastases were identified using the CPT, ICD-9-CM, and ICD-10-CM codes. The study population was divided into two cohorts: Nourished (preoperative serum albumin values ≥ 3.5 g/dL) and Malnourished (preoperative serum albumin values < 3.5 g/dL). We assessed patient demographics, comorbidities, intraoperative variables, postoperative adverse events (AEs), hospital LOS, discharge disposition, readmission, and reoperation. Multivariate logistic regression analyses were performed to identify the factors associated with a prolonged length of stay (LOS), AEs, non-routine discharge (NRD), and unplanned readmission. Results: Of the 1613 patients identified, 26.0% were Malnourished. Compared to Nourished patients, Malnourished patients were significantly more likely to be African American and have a lower BMI, but the age and sex were similar between the cohorts. The baseline comorbidity burden was significantly higher in the Malnourished cohort compared to the Nourished cohort. Compared to Nourished patients, Malnourished patients experienced significantly higher rates of one or more AEs (Nourished: 19.8% vs. Malnourished: 27.6%, p = 0.004) and serious AEs (Nourished: 15.2% vs. Malnourished: 22.6%, p < 0.001). Upon multivariate regression analysis, malnutrition was found to be an independent and associated with an extended LOS [aRR: 3.49, CI (1.97, 5.02), p < 0.001], NRD [saturated aOR: 1.76, CI (1.34, 2.32), p < 0.001], and unplanned readmission [saturated aOR: 1.42, CI (1.04, 1.95), p = 0.028]. Conclusions: Our study suggests that malnutrition increases the risk of postoperative complication, prolonged hospitalizations, non-routine discharges, and unplanned hospital readmissions. Further studies are necessary to identify the protocols that pre- and postoperatively optimize malnourished patients undergoing spinal surgery for metastatic spinal disease.

Advances in Automated Insulin Delivery with the Medtronic 780G: The Australian Experience.

Aim: To assess the real-world performance of MiniMed™ 780G for Australians with type 1 diabetes (T1D) following advanced hybrid closed loop (AHCL) activation and to evaluate the effect of changing from MiniMed 670/770G to 780G. Methods: We analyzed deidentified Carelink™ continuous glucose monitoring (CGM) data from Australian users from January 2020 to December 2022, including the proportion attaining three major consensus targets: Glucose management indicator (GMI <7.0%), time in range (TIR 70-180 mg/dL >70%), and time below range (TBR 70 mg/dL <4%). Results: Comparing 670/770G users (n = 5676) for mean ± standard deviation 364 ± 244 days with 780G users (n = 3566) for 146 ± 145 days, the latter achieved a higher TIR (72.6% ± 10.6% vs. 67.3% ± 11.4%; P < 0.001), lower time above range (TAR) (25.5% ± 10.9% vs. 30.6% ± 11.7%; P < 0.001), and lower GMI (6.9% ± 0.4% vs. 7.2% ± 0.4%; P < 0.001) without compromising TBR (1.9% ± 1.8% vs. 2.0% ± 1.8%; P = 0.0015). Of 1051 670/770G users transitioning to 780G, TIR increased (70.0% ± 10.7% to 74.0% ± 10.2%; P < 0.001), TAR decreased (28.1% ± 10.9% to 24.0% ± 10.7%; P < 0.001), and TBR was unchanged. The percentage of users attaining all three CGM targets was higher in 780G users (50.1% vs. 29.5%; P < 0.001). CGM metrics were stable at 12 months post-transition. Conclusion: Real-world data from Australia shows that a higher proportion of MiniMed 780G users meet clinical targets for CGM consensus metrics compared to MiniMed 670/770G users and glucose control was sustained over 12 months.

The Impact of Preoperative Spinal Injection Timing on Postoperative Complications of Lumbar Decompression Surgery.

BACKGROUND AND OBJECTIVES: Epidural steroid injections (ESIs) are commonly used for lower back pain management. The effect of these injections on lumbar decompression surgery outcomes is hitherto underexplored. The study objective was to determine the impact of ESIs on postoperative rates of medical and surgical complications and to define the appropriate interval before lumbar decompression surgery. METHODS: This retrospective all-payer database analysis identified 587 651 adult patients undergoing one- to three-level laminectomies from January 2010 to October 2021. A 2:1 propensity score match accounting for comorbidities, levels of surgery, and demographics was performed to create two cohorts: (1) 43 674 patients who had received an ESI in the 90 days before laminectomy and (2) 87 348 patients who had not received an ESI. The primary outcome was the rates of medical and surgical complications between groups at 30 days postoperatively. Patients were divided into five cohorts based on injection time before surgery: 1 to 30 days, 31 to 45 days, 46 to 60 days, 61 to 75 days, and 76 to 90 days. Logistic regression was performed between groups to identify temporal associations of complication rates. Confidence intervals of 95% are provided when appropriate. P values < .01 were considered significant. RESULTS: Rates of medical complications within 30 days of surgery were significantly higher in those with ESI compared with control (4.83% vs 3.9%, P < .001). Cerebrospinal fluid (CSF) leak rates were increased in the ESI group at 0.28% vs 0.1% (P < .001), but surgical site infection rates were not significantly different between groups (1.31% vs 1.42% P = .11). ESI performed within 30 days was associated with increased odds of CSF leak (OR: 5.32, 95% CI: 3.96-7.15). CONCLUSION: Preoperative ESI increases the risk of CSF leak and medical complications after lumbar decompression. Because these complications were significantly associated with ESIs given 1 to 30 days before surgery, avoiding ESIs at least 30 days before surgery may be advisable.

Early Real-World Performance of the MiniMed™ 780G Advanced Hybrid Closed-Loop System and Recommended Settings Use in the United States.

Background: The MiniMed™ 780G system (MM780G) with Guardian™ 4 sensor includes a 100 mg/dL glucose target (GT) and automated insulin corrections up to every 5 min and was recently approved for use in the United States. In the present study, early real-world MM780G performance and the use of recommended system settings (100 mg/dL GT with an active insulin time of 2 h), by individuals with type 1 diabetes, were evaluated. Methods: CareLink™ personal data uploaded between the launch of the MM780G to August 22, 2023 were aggregated and underwent retrospective analysis (based on user consent) and if users had ≥10 days of continuous glucose monitoring (CGM) data. The 24-h day CGM metrics, including mean glucose, percentage of time spent in (%TIR), above (%TAR), and below (%TBR) target range (70-180 mg/dL), in addition to delivered insulin and closed-loop (CL) exits, were compared between an overall group (n = 7499) and individuals who used recommended settings (each, for >95% of the time). An analysis of the same metrics for MiniMed™ 770G system (MM770G) users (n = 3851) who upgraded to the MM780G was also conducted (paired t-test or Wilcoxon signed-rank test, P < 0.05 considered statistically significant). Results: For MM780G users, CGM use, and time in CL were >90% and all MM780G CGM metrics exceeded consensus-recommended goals. With recommended settings (22% of all users), mean %TIR and %TITR (70-140 mg/dL) were 81.4% and 56.4%, respectively. For individuals who upgraded from the MM770G, %TIR and %TITR increased from 73.2% to 78.3% and 45.8% to 52.6%, respectively, while %TAR reduced from 25.1% to 20.2% (P < 0.001, for all three). CL exits/week averaged <1, for all MM780G users. Conclusions: Early real-world MM780G use in the United States demonstrated a high percentage of time in range with low time above and below range. These outcomes are similar to those observed for real-world MM780G use in other countries.

Reducing Diabetes Burden in Medtronic's Automated Insulin Delivery Systems.

Background: The MiniMed™ 780G advanced hybrid closed-loop system (MM780G) builds on the basal automation and low-glucose protection features of the MiniMed™ 670G and 770G systems. While previous publications have focused on glycemic control improvements with MM780G, burden reduction has not been fully described. Methods: Data from two 3-month pivotal trials for the MM670G with Guardian™ Sensor 3 (GS3) (104 adults; 125 children) and MM780G with Guardian™ 4 Sensor (G4S) (67 adults;109 children) were compared. Real-world data (RWD) from United States users (N = 3851) transitioning from MM770G+GS3 to MM780G+G4S were also analyzed. Analyses included a new metric for diabetes management burden (i.e., pentagon composite metric), glycemic outcomes and system burden (e.g., closed-loop exits and fingersticks per day). Results: Diabetes burden metric (-22.8% and -28.5%), time in range (+3.1% [*P = 0.035] and +6.4% [P < 0.001]) and time below range (-1.8% [*P < 0.001] and -0.7% [*P < 0.001]) significantly improved, compared to MM670G for adult and pediatric participants, respectively. The pediatric mean sensor glucose (SG) reduced by -8.6 mg/dL (*P < 0.001), while the adults' saw no change. Closed-loop use significantly increased for both cohorts (+17.1% [*P < 0.001] and +20.5% [*P < 0.001]). Closed-loop exits were significantly reduced to about 1 per week (-0.5 [*P < 0.001] and -0.7 [*P < 0.001]); fingerstick tests were also reduced (-6.2 [*P < 0.001] and -6.9 [*P < 0.001]). Similar outcomes were observed from U.S. RWD. Conclusions: MiniMed™ 780G with G4S use was associated with significant reduction in diabetes management burden with fewer closed-loop exits, fingersticks and other interactions, and improvements in glycemic control when compared to the MiniMed™ 670G with GS3.

The Myth of MARD (Mean Absolute Relative Difference): Limitations of MARD in the Clinical Assessment of Continuous Glucose Monitoring Data.

The mean absolute relative difference (MARD) is a numerical metric that has been adopted by the diabetes technology community as the main indicator that describes the accuracy of a glucose sensor at a single point in time. The appropriateness of this adoption is questionable because there is limited evidence that MARD has meaningful clinical relevance in the current era of sensor technology. The calculation may be simple, but evaluation of MARD can be very complex because it is substantially impacted by the design of the data collection in an accuracy study. Factors that can influence the overall MARD include participant demographics such as type of diabetes and age, site of sensor wear, and the percentage of collected values in each glycemic range during the study that is, in turn, a function of the study design. MARD is only one of several important statistical metrics such as bias and precision that are relevant to assessing accuracy of a sensor. Furthermore, these analytic metrics convey little information about the safety and effectiveness of sensor use with an automated insulin delivery system or a standalone device. There are no clinical studies in people with diabetes (PWD) proving that MARD can accurately differentiate between a safe and unsafe sensor or between a more and less clinically effective sensor. Moreover, there are alternatives to MARD that can do this in a clinically meaningful way, which include error grid analyses and clinical studies in PWD. This review attempts to demythologize the status of MARD for the diabetes community in an effort to shift the focus from MARD to using clinically relevant assessments.

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.

The Biochemical Impact of Extracting an Embedded Adenylate Kinase Domain Using Circular Permutation.

Adenylate kinases (AKs) have evolved AMP-binding and lid domains that are encoded as continuous polypeptides embedded at different locations within the discontinuous polypeptide encoding the core domain. A prior study showed that AK homologues of different stabilities consistently retain cellular activity following circular permutation that splits a region with high energetic frustration within the AMP-binding domain into discontinuous fragments. Herein, we show that mesophilic and thermophilic AKs having this topological restructuring retain activity and substrate-binding characteristics of the parental AK. While permutation decreased the activity of both AK homologues at physiological temperatures, the catalytic activity of the thermophilic AK increased upon permutation when assayed >30 °C below the melting temperature of the native AK. The thermostabilities of the permuted AKs were uniformly lower than those of native AKs, and they exhibited multiphasic unfolding transitions, unlike the native AKs, which presented cooperative thermal unfolding. In addition, proteolytic digestion revealed that permutation destabilized each AK in differing manners, and mass spectrometry suggested that the new termini within the AMP-binding domain were responsible for the increased proteolysis sensitivity. These findings illustrate how changes in contact order can be used to tune enzyme activity and alter folding dynamics in multidomain enzymes.