Improving Accuracy of Administrative Data for Perforated Appendicitis Classification.

INTRODUCTION: Reliance on International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes may misclassify perforated appendicitis with resultant research, fiscal, and public health implications. We aimed to improve the accuracy of administrative data for perforated appendicitis classification relying on ICD-10-CM codes from 2015 to 2018. METHODS: We conducted a retrospective study of randomly sampled patients aged ≤18 years diagnosed with acute appendicitis from eight children's hospitals. Patients were identified using the Pediatric Health Information System, and true perforation status was determined by medical record review. We developed two algorithms by leveraging Pediatric Health Information System data elements and data mining (DM) approaches. The two developed algorithm performance was compared against algorithms that exclusively relied on ICD-10-CM codes using area under the curve and other measures. RESULTS: Of 1051 clinically validated encounters that were included, 383 (36.4%) patients were identified to have perforated appendicitis. The two algorithms developed using DM approaches primarily leveraged ICD-10-CM codes and length of stay. DM-developed algorithms had a significantly higher accuracy than algorithms relying exclusively on ICD-10-CM (P value < 0.01): sensitivity and specificity for DM-developed algorithms were 0.86-0.88 and 0.95-0.97, respectively, which were overall higher than algorithms that relied on only ICD-10-CM. CONCLUSIONS: This study provides an algorithm that can improve the accuracy of perforated appendicitis classification using commonly available elements in administrative data. We recommend that this algorithm is used in future appendicitis classification to ensure valid reporting, hospital-level benchmarking, and fiscal or public health assessments.

Muscle-Specific Ablation of Glucose Transporter 1 (GLUT1) Does Not Impair Basal or Overload-Stimulated Skeletal Muscle Glucose Uptake.

Glucose transporter 1 (GLUT1) is believed to solely mediate basal (insulin-independent) glucose uptake in skeletal muscle; yet recent work has demonstrated that mechanical overload, a model of resistance exercise training, increases muscle GLUT1 levels. The primary objective of this study was to determine if GLUT1 is necessary for basal or overload-stimulated muscle glucose uptake. Muscle-specific GLUT1 knockout (mGLUT1KO) mice were generated and examined for changes in body weight, body composition, metabolism, systemic glucose regulation, muscle glucose transporters, and muscle [3H]-2-deoxyglucose uptake ± the GLUT1 inhibitor BAY-876. [3H]-hexose uptake ± BAY-876 was also examined in HEK293 cells-expressing GLUT1-6 or GLUT10. mGLUT1KO mice exhibited no impairments in body weight, lean mass, whole body metabolism, glucose tolerance, basal or overload-stimulated muscle glucose uptake. There was no compensation by the insulin-responsive GLUT4. In mGLUT1KO mouse muscles, overload stimulated higher expression of mechanosensitive GLUT6, but not GLUT3 or GLUT10. In control and mGLUT1KO mouse muscles, 0.05 µM BAY-876 impaired overload-stimulated, but not basal glucose uptake. In the GLUT-HEK293 cells, BAY-876 inhibited glucose uptake via GLUT1, GLUT3, GLUT4, GLUT6, and GLUT10. Collectively, these findings demonstrate that GLUT1 does not mediate basal muscle glucose uptake and suggest that a novel glucose transport mechanism mediates overload-stimulated glucose uptake.

Programmable chemical actuator control of soluble and membrane-bound enzymatic catalysis.

Enzyme catalyzed reactions can be started, stopped, and throttled by regulating ion concentration in solution. The flow of charge through solution is related to the flow of electrons through an electric circuit using electrochemistry. However, current electrochemical methods to vary ionic concentration are largely limited to the electrode surface, making it impractical to exploit ionic concentration as a control variable in traditional enzyme assays. This chapter presents an electrochemical cell, termed a programmable chemical actuator (PCA), that uses selective electrochemical REDOX reactions to regulate the concentration of ions that control enzyme catalyzed reaction kinetics. The PCA is a polypyrrole polymerized and equilibrated to impart Mg2+, Mn2+, or OH- ion selectivity to working electrodes. Duplex pulse amperometry demonstrated reversible control over the pH-dependent kinetics of alkaline phosphatase, a soluble homodimeric enzyme, during a spectrophotometric assay. PCAs were also used to extend electrochemical control to the membrane-bound enzyme complex rubber transferase by modulating Mg2+ and Mn2+ concentrations during a radiometric enzyme assay. PCAs demonstrated tunable control over rubber transferase activity and rubber molecular weight without dislodging either the elongating rubber molecule or irreversibly inhibiting the rubber transferase complex. This chapter presents methods to fabricate and operate PCAs to facilitate insights into the roles of ions in biochemical pathways and environmental responses in plants.

Larvicidal Activity of Carbon Black against the Yellow Fever Mosquito Aedes aegypti.

The yellow fever mosquito Aedes aegypti is one of the deadliest animals on the planet because it transmits several medically important arboviruses, including Zika, chikungunya, dengue, and yellow fever. Carbon-based nanoparticles (CNPs) derived from natural sources have previously been shown to have toxic effects on mosquito larvae and offer a potential alternative to chemical insecticides such as pyrethroids, for which mosquitoes have evolved resistance. However, CNPs derived from industrial sources, such as carbon black, have not previously been evaluated as larvicides. Here, we evaluate the effects of a commercially-available carbon black, EMPEROR® 1800 (E1800), on mortality and development of pyrethroid-susceptible (PS) and pyrethroid-resistant (PR) strains of Ae. aegypti. We found that E1800 exhibited concentration-dependent mortality against 1st instar larvae of both strains within the first 120 h after exposure, but after this period, surviving larvae did not show delays in their development to adults. Physical characterization of E1800 suspensions suggests that they form primary particles of ~30 nm in diameter that fuse into fundamental aggregates of ~170 nm in diameter. Notably, larvae treated with E1800 showed internal accumulation of E1800 in the gut and external accumulation on the respiratory siphon, anal papillae, and setae, suggesting a physical mode of toxic action. Taken together, our results suggest that E1800 has potential use as a larvicide with a novel mode of action for controlling PS and PR mosquitoes.

Oncologic Fidelity of Minimally Invasive Surgery to Resect Neoadjuvant-Treated Wilms Tumors.

BACKGROUND: The Children's Oncology Group recommends upfront resection of Wilms tumor (WT), however, unique scenarios warrant neoadjuvant chemotherapy and delayed resection. We hypothesized that in the context of neoadjuvant chemotherapy, minimally invasive surgery (MIS) to resect WT achieves equivalent oncologic fidelity and better maintains therapy schedules. METHODS: A retrospective analysis of WT treated between 2010-2021 at a free-standing children's hospital was performed. Patient and disease specific characteristics were collected, and pre-resection tumor volumes (TV) were calculated. Impact of MIS or open resection on oncologic fidelity and time to resume chemotherapy was analyzed. RESULTS: For the study period, 62 patients were treated for 65 WT, and 14 patients (22.6%) received neoadjuvant chemotherapy to treat 17 WT (26.2%): 7 Stage I (all predisposition syndromes), 2 stage III, 7 stage IV, and 1 stage V (bilateral). MIS was utilized to resect 6 WT from 5 patients. For partial nephrectomy, pre-resection TV was 0.38 ml if MIS and 10.38 ml if open (P = .025). For radical nephrectomy, pre-resection TV was 31.58 ml if MIS and 175.00 ml if open (P = .101). No significant differences between surgical approach were detected regarding pathologic variables or survival. Epidural use was significantly greater with open procedures (P = .001). Length of stay was 2.00 days after MIS compared to 6.00 for open resection (P = .004). Time to resume chemotherapy was 7.00 days after MIS versus 27.00 for open (P = .004). CONCLUSION: After neoadjuvant chemotherapy for WT, MIS partial and radical nephrectomies achieved equivalent oncologic fidelity, reduced epidural use and post-operative stays, and better maintained adjuvant therapy timelines when compared to open resections.

Surgical outcomes and complications of bedside tracheostomy in the ICU for patients on ECMO.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is increasingly employed in the management of patients with severe cardiac and pulmonary dysfunction. Patients commonly require tracheostomy for ventilator liberation. Though bedside percutaneous tracheostomy is commonly performed, it has the potential for increased complications, both surgical and with the ECMO circuit. We examined surgical outcomes of bedside percutaneous tracheostomy in the ECMO population. METHODS: Patients were identified from an institutional database for bedside procedures. Demographics and data on complications were recorded. Descriptive statistics were calculated. RESULTS: 37 patients on ECMO at the time of tracheostomy were identified. Median age and BMI were 43.2 and 28.0, respectively. 33 patients (89%) were on VV ECMO, and 4 (11%) were on VA ECMO. All were on anticoagulation prior to tracheostomy, which was held for 4 h before and after the procedure in all cases. There were no procedure-related deaths or airway losses. No patients experienced periprocedural clotting events of their ECMO circuit or oxygenator within 24 h. 3 patients (8%) required reintervention (re-exploration or bronchoscopy) for bleeding. Four other patients (10%) had minor bleeding controlled with packing. One patient had pneumomediastinum which resolved without intervention, and one had an occlusion of their tracheostomy which was treated with tracheostomy exchange. CONCLUSIONS: Bedside percutaneous tracheostomy is feasible for patients on ECMO. Further study is needed to determine specific risk factors for complications and means to mitigate these. Bedside percutaneous tracheostomy may be considered as part of the management of patients on ECMO to help facilitate liberation from mechanical support.

Implementation of General Surgery Care into a Student-Run Free Clinic.

BACKGROUND: Student-run free clinics (SRFCs) provide medical care to uninsured, and surgical issues are often outside the normal scope of care of these clinics. The Shade Tree Clinic (STC) is an SRFC serving 300 patients with complex medical conditions. This study describes the implementation and efficacy of a General Surgery Specialty Clinic in this setting. METHODS: This descriptive study examines the demographics and referral patterns of patients seen in two pilot Specialty Clinics and other patients evaluated for general surgical issues from December 2017 to January 2020. Providers were surveyed regarding their experience in clinic. RESULTS: Twenty patients were evaluated by six general surgeons during 22 separate encounters (n = 20). Nine patients were seen in two pilot Specialty Clinics for biliary colic, hernia, hemorrhoids, anal mass, toenail lesion, surgical weight loss, and venous insufficiency. Referrals from these clinics to affiliated Vanderbilt University Medical Center included six ultrasounds; referrals to vascular surgery and podiatry clinics; and referrals for laparoscopic cholecystectomy and anal mass excision. STC also directly referred eight patients for colonoscopies and five patients for major operations through primary care clinic. Hundred percent of care was cost-free to patients. Providers reported a median satisfaction score of five with the Specialty Clinics (Very Satisfied; [4, 5]). Hundred percent of providers felt that the concerns of patients were addressed. CONCLUSIONS: A surgery specialty clinic in the setting of an SRFC is an effective way to provide surgical care to underserved populations with the potential to reduce unplanned hospital utilization.

Therapeutic laparoscopy for pediatric abdominal trauma.

BACKGROUND: For the surgical treatment of traumatic hollow viscus injuries, laparoscopy offers a potentially less morbid approach to open exploration among appropriately selected patients. This study aimed to evaluate utilization trends and efficacy of laparoscopy in the management of pediatric abdominal trauma. STUDY DESIGN: To gain both study granularity and power, our institutional trauma registry (2005-2017) and the National Trauma Data Bank (NTDB; 2010-2015) identified patients ≤18 years who required celiotomy for abdominal trauma. Injury mechanisms, patient characteristics, and hospital courses were compared between open and laparoscopic approaches. Unadjusted and adjusted statistical analyses were performed. RESULTS: Overall, data were similar among 393 institutional and 11,399 NTDB patients undergoing laparoscopic (n = 88, 22%; n = 1663, 16%) or open (n = 305, 78%; n = 9736, 85%) surgery for abdominal trauma. In both registries, laparoscopy was more commonly employed in younger (institutional p = 0.026; NTDB p < 0.001) female (p = 0.019; p < 0.001) patients having lower injury severity (p < 0.001) and blunt injuries (p = 0.031; p < 0.001). Laparoscopy was associated with fewer complications overall when adjusting for demographics and injury severity [institutional OR 0.25 (0.08-0.75), p = 0.013; NTDB OR 0.69 (0.55-0.88), p = 0.002]. An increase in utilization of MIS for pediatric abdominal trauma was detected over time (NTDB: r = 0.88, p = 0.02). CONCLUSION: For the management of pediatric abdominal trauma, laparoscopy was employed typically in younger, more stable, and female patients sustaining blunt injuries. Appropriately selected patients have similar or better outcomes to patients treated with laparotomy, with no increase in adverse events or missed injuries. Increased utilization of laparoscopy to manage abdominal trauma in children suggests greater acceptance of this approach. LEVEL OF EVIDENCE: Level III.

The financial burden of musculoskeletal firearm injuries in children with and without concomitant intra-cavitary injuries.

BACKGROUND: Musculoskeletal pediatric firearm injuries are a clinically significant and expensive public health problem in the United States. In this retrospective cohort analysis, we sought to characterize musculoskeletal firearm injuries in children and to describe the financial burden associated with these injuries. METHODS: This study is a single center, retrospective review. Patients were identified from January 2002 - December 2015 from an institutional database using ICD-9 codes pertaining to firearm injury. Inclusion criteria were: 1) age < 18 years at injury; 2) firearm injury to an extremity, spine, or pelvis; and 3) patient received orthopedic evaluation and/or treatment. 140 patients with 142 distinct orthopedic injuries meeting inclusion criteria were analyzed (N = 142). Primary measures were demographic and situational data including intent, length of stay, follow-up, and complications; and financial outcomes including charges, costs, and net revenues. RESULTS: Median age was 15.3 years [IQR: 13.3, 16.4], 84% were male, and 52% were African American. 59% of the firearm injuries were of violent intent. 32% of patients were privately insured, 61% were publicly insured, and 6% were uninsured. Median length of stay was 2 days [0, 4], with 73% of patients being admitted. 43% of patients required additional hospitalizations, emergency room visits, and/or outpatient surgeries, and 93% of patients had outpatient follow-up. 42% of patients experience an injury-related or long-term orthopedic complication. Total charges for the cohort were $11.4 million, with $3.7 million in costs and $45,042 in net revenues. In the multivariable analysis, more surgeries predicted higher charges, and more secondary encounters predicted higher costs and net revenues. Only privately-insured patients had a positive median net revenue. CONCLUSIONS: Children who sustain musculoskeletal injuries from firearms experience high rates of orthopedic complications. Institutional costs to manage these preventable injuries are excessive. Policy makers should continue to pursue measures to reduce gun violence and improve gun safety in the pediatric population. LEVEL OF EVIDENCE: Level III, economic/decision.

Regulation of Skeletal Muscle Glucose Transport and Glucose Metabolism by Exercise Training.

Aerobic exercise training and resistance exercise training are both well-known for their ability to improve human health; especially in individuals with type 2 diabetes. However, there are critical differences between these two main forms of exercise training and the adaptations that they induce in the body that may account for their beneficial effects. This article reviews the literature and highlights key gaps in our current understanding of the effects of aerobic and resistance exercise training on the regulation of systemic glucose homeostasis, skeletal muscle glucose transport and skeletal muscle glucose metabolism.

Peer-led Surgical Clerkship Programming Support Through the General Surgery Interest Group at the Vanderbilt University School of Medicine.

OBJECTIVE: We present a systematic, sustainable, student-led model for supporting the Surgical Clerkship experience. DESIGN: Our model includes student-led suturing and knot-tying classes, operating room tours, skills sessions, and shelf review sessions provided systematically for each of 5 Surgical Clerkship blocks in the 2017 to 2018 academic year. SETTING: Vanderbilt University School of Medicine. PARTICIPANTS: Vanderbilt University School of Medicine Surgical Clerkship students and senior medical student instructors. RESULTS: Successful implementation of a peer-led support program for the Surgical Clerkship with a majority of students rating the helpfulness of both the operating room tours and the skills sessions a 4 or 5 on a Likert scale. CONCLUSION: Our student-led model for a Surgical Clerkship support program can be successfully implemented and demonstrates positive initial indicators of effectiveness.

Is There a Preoperative Morphine Equianalgesic Dose that Predicts Ability to Achieve a Clinically Meaningful Improvement Following Spine Surgery?

BACKGROUND: Preoperative opioid use is widespread and associated with worse patient-reported outcomes following spine surgery. OBJECTIVE: To calculate a threshold preoperative morphine equianalgesic (MEA) dose beyond which patients are less likely to achieve the minimum clinically important difference (MCID) following elective surgery for degenerative spine disease. METHODS: The study included 543 cervical and 1293 lumbar patients. Neck Disability Index and Oswestry Disability Index scores were collected at baseline and 12 mo postoperatively. Preoperative MEA doses were calculated retrospectively. Multivariate logistic regression was then performed to determine the relationship between MEA dose and the odds of achieving MCID. As a part of this regression, Bayesian inference and Markov Chain Monte Carlo methods were used to estimate the values of inflection points (or "thresholds") in MEA. RESULTS: Overall, 1020 (55.5%) patients used preoperative opioids. A total of 50.3% of cervical and 61.9% of lumbar patients achieved MCID. The final logistic regression model demonstrated that MCID achievement decreased significantly when mean preoperative MEA dose exceeded 47.8 mg/d, with a 95% credible interval of 29.0 to 60.0 mg/d. CONCLUSION: Minimum and maximum MEA doses exist, between which increasing opioid dose is associated with decreased ability to achieve clinically meaningful improvement following spine surgery. Patients with preoperative MEA dose exceeding 29 mg/d, the lower limit of the 95% credible interval for the mean MEA dose above which patients exhibit significantly decreased achievement of MCID, may be considered for preoperative opioid weaning.

Hirano bodies differentially modulate cell death induced by tau and the amyloid precursor protein intracellular domain.

BACKGROUND: Hirano bodies are actin-rich paracrystalline inclusions found in brains of patients with Alzheimer's disease (AD), frontotemporal dementia (FTD), and in normal aged individuals. Although studies of post-mortem brain tissue provide clues of etiology, the physiological function of Hirano bodies remains unknown. A cell culture model was utilized to study the interactions of mutant tau proteins, model Hirano bodies, and GSK3ß in human astrocytoma cells. RESULTS: Most tau variants showed co-localization with model Hirano bodies. Cosedimentation assays revealed this interaction may be direct, as recombinant purified forms of tau are all capable of binding F-actin. Model Hirano bodies had no effect or enhanced cell death induced by tau in the absence of amyloid precursor protein intracellular domain (AICD). In the presence of AICD and tau, synergistic cell death was observed in most cases, and model Hirano bodies decreased this synergistic cell death, except for forms of tau that caused significant cell death in the presence of Hirano bodies only. A role for the kinase GSK3ß is suggested by the finding that a dominant negative form of GSK3ß reduces this synergistic cell death. A subset of Hirano bodies in brain tissue of both Alzheimer's disease and normal aged individuals was found to contain tau, with some Hirano bodies in Alzheimer's disease brains containing hyperphosphorylated tau. CONCLUSION: The results demonstrate a complex interaction between tau and AICD involving activation of GSK3ß in promoting cell death, and the ability of Hirano bodies to modulate this process.