The Learning Curve for Robotic Lateral Pelvic Lymph Node Dissection for Rectal Cancer: A View from the West.

BACKGROUND: Lateral pelvic lymph-node dissection is performed for selected patients with rectal cancer with persistent lateral nodal disease after neoadjuvant therapy. This technique has been slow to be adopted in the West due to concerns regarding technical difficulty. This is the first report on the learning curve for lateral pelvic lymph node dissection in the US or Europe. OBJECTIVE: The aim of this study was to analyze the learning curve associated with robotic lateral pelvic lymph node dissection. DESIGN: Retrospective observational cohort. SETTING: Tertiary academic cancer center. PATIENTS: Consecutive patients from 2012 to 2021. INTERVENTION: All patients underwent robotic lateral pelvic lymph node dissection. MAIN OUTCOME MEASURES: The primary endpoints were the learning curves for maximum number of nodes retrieved and urinary retention which was evaluated with simple cumulative-sum and two-sided Bernoulli cumulative-sum charts. RESULTS: Fifty-four procedures were included. A single-surgeon (n = 35) and an institutional learning curve are presented in the analysis. In the single-surgeon learning curve, a turning point marking the end of a learning phase was detected at the 12th procedure for the number of retrieved nodes and at the 20th for urinary retention. In the institutional learning curve analysis, two turning points were identified at the 13th and 26th procedures indicating progressive improvements for the number of retrieved nodes and at the 27th for urinary retention. No sustained alarm signals were detected at any time point. LIMITATIONS: The retrospective nature, small sample size and the referral center nature of the reporting institution that may limit generalizability. CONCLUSIONS: In a setting of institutional experience with robotic colorectal surgery including beyond TME resections, the learning curve for robotic lateral pelvic lymph node dissection is acceptably short. Our results demonstrate feasibility of acquisition of this technique in a controlled setting, with sufficient case volume and proctoring can optimize the learning curve. See Video Abstract.

Early Postoperative Prediction of Complications and Readmission After Colorectal Cancer Surgery Using an Artificial Neural Network.

BACKGROUND: Early predictors of postoperative complications can risk-stratify patients undergoing colorectal cancer surgery. However, conventional regression models have limited power to identify complex nonlinear relationships among a large set of variables. We developed artificial neural network models to optimize the prediction of major postoperative complications and risk of readmission in patients undergoing colorectal cancer surgery. OBJECTIVE: The aim of this study was to develop an artificial neural network model to predict postoperative complications using postoperative laboratory values, and compare these models' accuracy to standard regression methods. DESIGN: This retrospective study included patients who underwent elective colorectal cancer resection between January 1, 2016, and July 31, 2021. Clinical data, cancer stage, and laboratory data from postoperative day 1 to 3 were collected. Models of complications and readmission risk were created using multivariable logistic regression and single-layer neural networks. SETTING: National Cancer Institute-Designated Comprehensive Cancer Center. PATIENTS: Adult colorectal cancer patients. MAIN OUTCOME MEASURES: Accuracy of predicting postoperative major complication, readmission and anastomotic leak using the area under the receiver-operating characteristic curve. RESULTS: Neural networks had larger areas under the curve for predicting major complications compared to regression models (neural network 0.811; regression model 0.724, p < 0.001). Neural networks also showed an advantage in predicting anastomotic leak (p = 0.036) and readmission using postoperative day 1-2 values (p = 0.014). LIMITATIONS: Single-center, retrospective design limited to cancer operations. CONCLUSIONS: In this study, we generated a set of models for early prediction of complications after colorectal surgery. The neural network models provided greater discrimination than the models based on traditional logistic regression. These models may allow for early detection of postoperative complications as soon as postoperative day 2. See Video Abstract.

A machine learning decision criterion for reducing scan time for hyperspectral neutron computed tomography systems.

We present the first machine learning-based autonomous hyperspectral neutron computed tomography experiment performed at the Spallation Neutron Source. Hyperspectral neutron computed tomography allows the characterization of samples by enabling the reconstruction of crystallographic information and elemental/isotopic composition of objects relevant to materials science. High quality reconstructions using traditional algorithms such as the filtered back projection require a high signal-to-noise ratio across a wide wavelength range combined with a large number of projections. This results in scan times of several days to acquire hundreds of hyperspectral projections, during which end users have minimal feedback. To address these challenges, a golden ratio scanning protocol combined with model-based image reconstruction algorithms have been proposed. This novel approach enables high quality real-time reconstructions from streaming experimental data, thus providing feedback to users, while requiring fewer yet a fixed number of projections compared to the filtered back projection method. In this paper, we propose a novel machine learning criterion that can terminate a streaming neutron tomography scan once sufficient information is obtained based on the current set of measurements. Our decision criterion uses a quality score which combines a reference-free image quality metric computed using a pre-trained deep neural network with a metric that measures differences between consecutive reconstructions. The results show that our method can reduce the measurement time by approximately a factor of five compared to a baseline method based on filtered back projection for the samples we studied while automatically terminating the scans.

A role for synapsin tetramerization in synaptic vesicle clustering.

Although synapsins have long been proposed to be key regulators of synaptic vesicle (SV) clustering, their mechanism of action has remained mysterious and somewhat controversial. Here, we review synapsins and their associations with each other and with SVs. We highlight the recent hypothesis that synapsin tetramerization is a mechanism for SV clustering. This hypothesis, which aligns with numerous experimental results, suggests that the larger size of synapsin tetramers, in comparison to dimers, allows tetramers to form optimal bridges between SVs that overcome the repulsive force associated with the negatively charged membrane of SVs and allow synapsins to form a reserve pool of SVs within presynaptic terminals.

CD39 Is Expressed on Functional Effector and Tissue-resident Memory CD8+ T Cells.

The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on Ag-specific CD8+ short-lived effector cells, while it's co-ectoenzyme, CD73, is found on memory precursor effector cells (MPECs) in vivo. Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory T cell (TRM cell) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine TRM cells across several nonlymphoid tissues and melanoma, whereas CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ TRM cells are fully functional when stimulated ex vivo with cognate Ag, further expanding the identity of CD39 beyond a T cell exhaustion marker.

Adolescents With a High Burden of New-Onset Mood Symptoms After Sport-Related Concussion Benefit From Prescribed Aerobic Exercise, a Secondary Analysis of 2 Randomized Controlled Trials.

OBJECTIVE: Approximately 20% of students with sport-related concussion (SRC) report new symptoms of anxiety and depression which may be associated with delayed recovery and increased risk for developing a mood disorder. Early prescribed aerobic exercise facilitates recovery in athletes with concussion-related exercise intolerance. We studied the effect of aerobic exercise treatment on new mood symptoms early after SRC. DESIGN: Exploratory secondary analysis of 2 randomized controlled trials (RCT). SETTING: Sports medicine clinics associated with UB (Buffalo, NY), CHOP (Philadelphia, PA), and Boston Children's Hospital (Boston, MA). PARTICIPANTS: Male and female adolescents (aged 13-18 years) diagnosed with SRC (2-10 days since injury). INTERVENTIONS: Participants were randomized to individualized targeted heart rate aerobic exercise (n = 102) or to a placebo intervention designed to mimic relative rest (n = 96). MAIN OUTCOME MEASURES: Incidence of Persisting Post-Concussive Symptoms (PPCS, symptoms ≥28 days). RESULTS: First RCT recruited from 2016 to 2018 and the second from 2018 to 2020. Of 198 adolescents, 156 (79%) reported a low burden (mean 1.2 ± 1.65/24) while 42 (21%) reported a high burden (mean 9.74 ± 3.70/24) of emotional symptoms before randomization. Intervention hazard ratio for developing PPCS for low burden was 0.767 (95% CI, 0.546-1.079; P = 0.128; ß = 0.085) and for high burden was 0.290 (95% CI, 0.123-0.683; P = 0.005; ß = 0.732). CONCLUSIONS: High burden of mood symptoms early after injury increases risk for PPCS, but the sports medicine model of providing early targeted aerobic exercise treatment reduces it. Nonsports medicine clinicians who treat patients with a high burden of new mood symptoms after concussion should consider prescribing aerobic exercise treatment to reduce the risk of PPCS and a mood disorder.

A specialized population of monocyte-derived tracheal macrophages promote airway epithelial regeneration through a CCR2-dependent mechanism.

Macrophages are critical for maintenance and repair of mucosal tissues. While functionally distinct subtypes of macrophage are known to have important roles in injury response and repair in the lungs, little is known about macrophages in the proximal conducting airways. Single-cell RNA sequencing and flow cytometry demonstrated murine tracheal macrophages are largely monocyte-derived and are phenotypically distinct from lung macrophages at homeostasis. Following sterile airway injury, monocyte-derived macrophages are recruited to the trachea and activate a pro-regenerative phenotype associated with wound healing. Animals lacking the chemokine receptor CCR2 have reduced numbers of circulating monocytes and tracheal macrophages, deficient pro-regenerative macrophage activation and defective epithelial repair. Together, these studies indicate that recruitment and activation of monocyte-derived tracheal macrophages is CCR2-dependent and is required for normal airway epithelial regeneration.

Impact of an Integrated Human Performance Support Group: Evaluation of Air Force Special Warfare Candidate Training and Musculoskeletal Injury Outcomes Over Eight Fiscal Years.

INTRODUCTION: The Special Warfare Training Wing and Special Warfare Human Performance Support Group (HPSG; all-co-authors) were established in fiscal year (FY) 2019 to consolidate and oversee all Air Force Special Warfare (AFSPECWAR) training and provide embedded medical and human performance support to candidates with the goal of improving graduation rates and the longevity of the AFSPECWAR operator. The purpose of this manuscript is to assess the impact of the HPSG on AFSPECWAR graduation rates, musculoskeletal injury (MSKI) incidence, and cost. MATERIALS AND METHODS: Graduation rates, MSKI incidence (including incidence density and cumulative incidence probability), and MSKI-related health care costs were assessed across all AFSPECWAR training pipelines spanning 8 FYs 2015-22, including Indoctrination, Assessment, and Selection Courses (Selection); Tactical Air Control Party (TACP); Special Tactics (ST), and Guardian Angel (GA). RESULTS: A total of 5,728 distinct candidates were assessed over the time frame. There were significant decreases in attrition when comparing the HPSG era (FY 19-22) with the prior 4-year period for the ST (47% vs. 82% graduates) and TACP (34% vs. 41% graduates) training pipelines. The corresponding Selection (36% graduates) and GA (80% graduates) pipeline attrition rates remained stable. MSKI incidence rates (both incidence density and cumulative incidence probability) overall were not significantly different when comparing the pre-HPSG and HPSG time frames; however, they varied between the two time frames by course. GA candidates had a decrease in MSKI during the apprentice course in the HPSG era compared with the pre-HPSG era (2.4-1.0 cases per 100 trainee weeks; P < .001), which corresponds to a nearly 20% reduction in the cumulative incidence probability (i.e., proportion of trainees injured) after 10 weeks of course. For ST and TACP courses, however, significantly increased incidence of MSKI was observed when comparing the two time frames (P < .001), while for Selection courses, the rates remained stable. A significant reduction in the cost of MSKI-related management (62% total relative value units, 83% total costs) was observed. CONCLUSION: The impact of the HPSG on attrition, MSKI incidence, and cost-of-care was not consistent across all training pipelines; however, taken together, there were no increases in attrition, and the cost of MSKI management was significantly lower.

Estimated Financial Impact of 2021 Office-Visit Work Relative Unit Updates on Surgical Global Periods.

This cross-sectional study assesses the impact of changes to medical billing and coding work relative value units in 2021.

Clinical and Radiographic Results After Treatment of Traumatic Syndesmotic Instability Using a Novel Screw-Suture Syndesmotic Fixation Device.

OBJECTIVES: The objective of this study was to report early outcomes of a novel screw-suture syndesmotic device compared with suture button fixation devices when treating traumatic syndesmotic instability. DESIGN: Retrospective chart review. SETTING: Single academic Level 1 Trauma Center. PATIENT SELECTION CRITERIA: All adult patients who had syndesmotic fixation with the novel device [novel syndesmotic repair implant (NSRI) group] compared with a suture button device (SB group) between January 2018 and December 2022. OUTCOME MEASURES AND COMPARISONS: Medial clear space and tibiofibular overlap measurements were compared immediately postoperatively and at the final follow-up. Patients were followed for a minimum of 1 year or skeletal healing. RESULTS: Fifty-nine patients (25 female) with an average age of 47 years (range 19-78 years) were in the NSRI group compared with 52 patients (20 female) with an average age of 41 years (range 18-73 years) in the SB group. There were no significant differences when comparing body mass index, diabetes, or smoking status between groups (P > 0.05). There was no difference when comparing the postoperative and final medial clear space measurements in the NSRI group compared with the SB group (P = 0.86; 95% confidence interval, -0.32 to 0.27). There was no difference when comparing the postoperative and final tibiofibular overlap measurements in the NSRI group compared with the SB group (P = 0.79; 95% confidence interval, -0.072 to 0.09). There were 3 cases of implant removal in the NSRI group compared with 2 in the SB group (P = 0.77). There was 1 failure in the NSRI group and none in the SB group. The remaining patients were all fully ambulatory at the final follow-up (P = 0.35). CONCLUSIONS: A novel screw-suture syndesmotic implant provides the fixation of a screw, and the flexibility of a suture had similar radiographic outcomes compared with suture button fixation devices in treating ankle syndesmotic instability. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Effect of Different Isolation Methods on Bioaerosol Distribution: An In Vitro Study.

Purpose: The purposes of this in vitro study were to evaluate the effect of three isolation methods to mitigate bioaerosols during stainless steel crown (SSC) preparations and assess the distribution of Streptococcus mutans by aerosolization in closed-room operatories. Methods: Melamine teeth coated in laboratory-grown S. mutans biofilm were prepared for SSCs using three different isolation methods. Agar plates were placed in five locations throughout the operatory and opened during each preparation as well as for 10 minutes immediately following to collect aerosolized S. mutans. Bacterial colonies were counted after incubating plates for 48 hours. Data were analyzed for differences between the isolation method and plate locations. Results: Bacterial colony counts for teeth prepared using high-volume evacuation suction (HVE) with dental dam (DD) isolation were statistically significantly higher than for those prepared using HVE with a DryShield®(DS) and HVE with no isolation at the assistant (A) (P<0.001), operator face shield (FS) (P<0.001), and patient (Pt) (P=0.002) locations. No significant differences were found among isolation methods for parent (Pa) or rear delivery (RD) locations. The location that produced the most bacterial colony counts using HVE with DD isolation was FS (P<0.001), followed by A (P=0.04), Pt (P<0.001), and RD and Pa (P<0.001). Counts produced from teeth prepared with DS isolation were significantly higher at the Pt location than the A (P<0.001), FS (P=0.002), RD (P<0.001), and Pa (P=0.008) locations. Conclusion: The use of dental dam with high-volume evacuation suction during stainless steel crown preparations increased bioaerosols near the procedure, while dental evacuation systems (DryShield®) may effectively limit their spread.

Longitudinal Follow-up Comparing Future Care of Primary Teeth Treated with Silver Diammine Fluoride: A Private Dental Claims Review.

Purpose: The purpose of this study was to longitudinally evaluate follow-up treatment on primary teeth initially treated with silver diammine fluoride (SDF). Methods: This retrospective cohort evaluated private insurance (not Medicaid) claims data from 2018 to 2019 for children no older than 12 years with at least one primary tooth initially treated with SDF. Additional treatment per tooth was recorded over a follow-up of at least 24 months. Results: The mean and standard deviation (±SD) age of 46,884 patients was 5.7±2.3 and for SDF-treated teeth per patient was 2.6±2.1. Forty percent (95 percent confidence interval [95% CI] equals 39 to 40.7 percent) of teeth initially treated with SDF received additional treatment. The odds of SDF-treated teeth receiving future treatment significantly decreased with patient age by 22 percent per year (odds ratio equals 0.78; 95% CI equals 0.077 to 0.79; P<0.001). Pediatric dentists had only slightly lower odds than general dentists for providing additional treatment (0.91, P<0.001). Posterior teeth and teeth expected to exfoliate in two or more years had significantly higher odds of receiving additional treatment (2.47 and 1.27, respectively, P<0.001). Conclusions: Beginning at age four, patient age at placement of silver diammine fluoride was inversely proportional to future treatment provided. Posterior teeth and teeth expected to exfoliate in two or more years were more likely to receive additional treatment.

Long-Term Efficacy of Teprotumumab in Thyroid Eye Disease: Follow-Up Outcomes in Three Clinical Trials.

Introduction: Thyroid eye disease (TED) is an autoimmune process characterized by extraocular muscle and orbital fat remodeling/expansion resulting in swelling, pain, redness, proptosis, and diplopia. Teprotumumab, an insulin-like growth factor-I receptor inhibitor, demonstrated improvements in TED signs and symptoms in three adequately powered clinical trials of 24 weeks duration. Here we analyze the long-term maintenance of responses with teprotumumab from these trials. Methods: A total of 112 patients who received 7 or 8 infusions of teprotumumab in the Phase 2, Phase 3 (OPTIC study), and OPTIC Extension (OPTIC-X) studies were included in this analysis. Responses, including clinical activity score (CAS ≥2-point improvement), the European Group of Graves' Orbitopathy ophthalmic composite outcome, diplopia (≥1 Gorman grade improvement), proptosis (≥2 mm improvement), Overall (improvement in proptosis + CAS), and disease inactivation (CAS ≤1), were assessed and pooled from study baseline to week 24 (formal study) and up to week 72 (formal follow-up). Graves' Ophthalmopathy quality-of-life (GO-QoL) scores were also assessed. Outcomes included the percentages of observed patient responses from the study baseline. Additional alternative treatments for TED were assessed as a surrogate of persistent benefit from week 24 through week 120 (extended follow-up). Studies differed in the timing of follow-up visits, and data from some visits were unavailable. Results: At week 72, 52/57 (91.2%), 51/57 (89.5%), 35/48 (72.9%), 38/56 (67.9%), and 37/56 (66.1%) of patients were responders for CAS, composite outcome, diplopia, proptosis, and Overall response, respectively. The mean reduction in proptosis was 2.68 mm (SD 1.92, n = 56), mean GO-QoL improvement was 15.22 (SE 2.82, n = 56), and disease inactivation (CAS ≤1) was detected in 40/57 (70.2%). Over 99 weeks following teprotumumab therapy, 19/106 (17.9%) patients reported additional TED therapy during formal and extended follow-up. Conclusion: The long-term response to teprotumumab as observed 51 weeks after therapy was similar to week 24 results in the controlled clinical trials. Inflammatory and ophthalmic composite outcome improvements were seen in 90% of patients with nearly 70% reporting improvement in diplopia and proptosis. Further, 82% of patients in this analysis did not report additional TED treatment (including surgery) over 99 weeks following the final teprotumumab dose.

Characteristics of Adolescents with and without a Family History of Substance Use Disorder from a Minority Cohort.

Family history (FH+) of substance use disorder (SUD) is an established risk factor for offspring SUD. The extent to which offspring psychological traits or the family environment, each of which may be relevant to familial transmission of SUD risk, vary by FH+ in socioeconomically disadvantaged populations is less clear. We compared the family/social environmental and psychological characteristics of 73 FH+ and 69 FH- youth ages 12-16, from a study of parental criminal justice system involvement in a primarily low-income, minority urban population. A latent profile analysis (LPA) empirically identified groups of subjects with similar psychological characteristics, which were then compared by FH+. FH+ youths were found to have greater mean household size, greater parental psychological aggression, and a higher mean number of adverse childhood experiences, even without considering parental SUD. FH+ individuals had lower report card grades according to parental report and were more likely to have a history of externalizing disorders than FH- individuals. However, FH+ was not significantly associated with many psychological characteristics or with the class membership from the LPA. In conclusion, among a population of low-income, minority urban youth, FH+ was associated with differences in the family environment and only subtle differences in individual psychological characteristics.

School-Based Intervention for Adolescents With ADHD: Predictors of Effects on Academic, Behavioral, and Social Functioning.

Adolescents with attention-deficit/hyperactivity disorder (ADHD) experience significant academic, behavioral, and social skill difficulties including underachievement, risk for school dropout, poor peer relations, and emotion dysregulation. Although stimulant medication reduces ADHD symptoms, psychosocial and educational interventions are necessary to address functional impairments. We examined the nature and predictors of academic, behavioral, and social skills trajectories in response to multicomponent organizational and interpersonal skills training in 92 high school students with ADHD. Latent trajectory class analyses revealed positive treatment response ranging from 61.5% (report card grades) to 100% (inattention symptoms, organizational skills, social skills). Organizational skill and academic grade treatment response trajectories were predicted by assigned sex, pretreatment anxiety, and treatment dosage, while improvement in behavioral and social functioning was associated with better emotion regulation and family relations prior to treatment along with stronger working alliance with treatment coach at midtreatment. Multicomponent organizational and interpersonal skills training appears effective for most high school students with ADHD and the degree treatment-induced change is associated with multiple malleable factors can be leveraged to enhance intervention response.

Testing Machine Learning Models to Predict Postoperative Ileus after Colorectal Surgery.

Background: Postoperative ileus (POI) is a common complication after colorectal surgery, leading to increased hospital stay and costs. This study aimed to explore patient comorbidities that contribute to the development of POI in the colorectal surgical population and compare machine learning (ML) model accuracy to existing risk instruments. Study Design: In a retrospective study, data were collected on 316 adult patients who underwent colorectal surgery from January 2020 to December 2021. The study excluded patients undergoing multi-visceral resections, re-operations, or combined primary and metastatic resections. Patients lacking follow-up within 90 days after surgery were also excluded. Eight different ML models were trained and cross-validated using 29 patient comorbidities and four comorbidity risk indices (ASA Status, NSQIP, CCI, and ECI). Results: The study found that 6.33% of patients experienced POI. Age, BMI, gender, kidney disease, anemia, arrhythmia, rheumatoid arthritis, and NSQIP score were identified as significant predictors of POI. The ML models with the greatest accuracy were AdaBoost tuned with grid search (94.2%) and XG Boost tuned with grid search (85.2%). Conclusions: This study suggests that ML models can predict the risk of POI with high accuracy and may offer a new frontier in early detection and intervention for postoperative outcome optimization. ML models can greatly improve the prediction and prevention of POI in colorectal surgery patients, which can lead to improved patient outcomes and reduced healthcare costs. Further research is required to validate and assess the replicability of these results.