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The security of cyber-physical systems, such as vehicle platoons, is critical to ensuring their proper operation and acceptance to society. In platooning, vehicles follow one another according to an agreed-upon control law that determines vehicle separation. We show that a vehicle within a platoon and under the control of a malicious actor could cause collisions or decrease the efficiency of surrounding vehicles. This paper focuses on detecting, identifying, and mitigating so-called destabilizing attacks that could cause vehicle collisions. Our approach is decentralized and requires only local sensor information for each vehicle to identify the vehicle responsible for the attack and then deploy an appropriate mitigating controller that prevents collisions. We use a Deep Learning approach (Convolutional Neural Network) with various data preprocessing techniques to detect and identify the malicious vehicle. Results indicate that even with decent noise levels in range and relative speed data, we achieve accuracy up to 96.3\%. Also, once the adversarial vehicle is localized, we derive conditions for controller gains using the Routh Hurwitz criterion to mitigate the attack and ensure the stability of the platoon. Realistic simulator CARLA and MATLAB simulation results validate the effectiveness of our proposed approaches.

Introduction: Among adolescents and young adults, cannabis use is prevalent. Prior studies characterizing withdrawal effects in this age range have primarily included treatment seeking or comorbid ...

Keen observational skills are essential for veterinarians; however, the development of these skills is not usually an explicit part of the veterinary curriculum. Fine arts–based (FAB) observation training has been shown to improve medical students’ observational skills and might also improve veterinary students’ observational skills. We compared FAB and pathology-based (PB) observation training in a veterinary cytology course. Students initially wrote a pre-test in which they described two cytology images and one art image, followed by participation in either FAB or PB observation training. Both groups completed a similar post-test immediately after training and a delayed post-test 4 weeks later following instruction in cytology. Differences between groups were noted only in the immediate post-test cytology descriptions. The PB group used significantly more specific vocabulary terms and significantly more accurate observations than the FAB group, suggesting an immediate benefit to the discipline-specific information gained in the PB observation training. In the delayed post-test, results for both groups were similar. The FAB group significantly increased their use of specific vocabulary terms and maintained but did not increase accurate observations following cytology instruction, while accurate observations decreased significantly for the PB group. The FAB group might have been able to generalize their observation skills to the discipline of cytology and to better retain these skills. Neither type of training resulted in both achievement and maintenance of the highest recorded scores for accurate observations. Both FAB and PB training led to improved observational skills, and explicit observation training may be useful for veterinary students.

Innovative swallowable capsule technologies such as drug-loaded, dissolvable microneedles, mucoadhesive patches, and various microdevices present unique drug-carrying capabilities to overcome challenges regarding oral delivery of biologics. Here, we report a swallowable capsule for intestinal drug delivery (SCIDD) with the potential of directly injecting biological therapeutics into the insensate small intestine wall. The design, optimization, and validation of the SCIDD's primary subsystems were performed both ex-vivo and in-vivo. The assembled capsule was further tested in vivo to validate the actuation sequence and showed a 70% (n = 17) success rate in an animal model. Additionally, a drug delivery study indicated systemic uptake of adalimumab via SCIDD compared with luminal delivery in the small intestine. The pilot study presented here establishes that the novel platform could be used to orally deliver systemic biologics.

GOAL: To develop a low-cost magnetic resonance imaging (MRI)-free transcranial focused ultrasound (FUS) system for microbubble-mediated therapy. METHODS: A 128-element 11 MHz array for skull localization was integrated within a 256-module multi-frequency (306/612/1224 kHz) dual-mode phased array. The system’s transcranial transmit and receive performance was evaluated with ex-vivo human skullcaps using phase aberration corrections calculated from computed tomography (CT)-based simulations via ultrasound-based (USCT) and landmark-based (LMCT) registrations, and a gold-standard fixed source emitter (FSE)-based method. RESULTS: Displacement and rotation registration errors of 1.4 ± 0.4 mm and 2.1 ± 0.2° were obtained using USCT, resulting in sub-millimeter transmit targeting errors driven at 306 kHz (0.9 ± 0.2 mm) and 612 kHz (0.9 ± 0.3 mm), and source localization errors of 1.0 ± 0.3 mm and 0.6 ± 0.2 mm at receive frequencies of 306 kHz and 612 kHz, respectively (mean ± SD). Similar errors were obtained using LMCT and no significant differences between these two approaches were found on either transmit (p = 0.64/0.99) or receive (p = 0.45/0.36) at 306 kHz/612kHz. During volumetric multi-point exposures, approximately 70% and 60% of the transmit frames in which microbubble activity was detected via FSE were recovered using USCT when imaging at the second-harmonic and half-harmonic, respectively, compared to 60% and 69% using LMCT. CONCLUSION: This low-cost ultrasound-guided transcranial FUS system affords USCT skull registration with accuracy comparable to LMCT methods. SIGNIFICANCE: Such systems have great potential to advance the adoption of microbubble-mediated FUS brain therapy by improving access to the technology.

Objective The reconstruction of large scalp defects poses both functional and cosmetic challenges. While free tissue transfer remains the standard for defects larger than 30 cm2, prolonged anesthesia and postoperative complications remain significant limitations. The purpose of this study is to evaluate the use of O-Z flaps for the reconstruction of large scalp defects and to describe the techniques employed. Methods This is a retrospective analysis of ten patients who underwent reconstructive surgery using an O-Z flap approach for large scalp defects between July 2017 and June 2019. The parameters included in this study were patient demographics, tumor characteristics, and postoperative management, collected for at least a year after surgery. Results In this cohort, the mean age was 76.1 years and 90% were male. All patients were treated for neoplastic skin lesions, with 70% located on the vertex and 30% located on the temporoparietal region. The mean size of defect was 52.0 cm2 (range: 38.6–63.8 cm2). The maximum hospital stay was two days, and no patients were readmitted within 30 days of surgery. There were no cases of wound infection or flap necrosis. All patients reported pain control with acetaminophen and ibuprofen. Four patients received adjuvant radiation, and there was no delay to receiving treatment following surgery. Conclusions The O-Z flap is a reliable alternative for the reconstruction of non-irradiated scalp defects in the vertex and temporoparietal regions up to 63 cm2. This technique provides advantages for patients, including hairline preservation, shorter hospital stays, and decreased postoperative complications.

Background The number of primary and revision shoulder arthroplasties performed each year continues to increase. Relative value units (RVUs) are currently used by the Centers for Medicare and Medicaid Services (CMS) to determine physician reimbursement based on time, effort, and complexity of services rendered. Compared to primary shoulder arthroplasty, revision shoulder arthroplasties are often more technically challenging, have longer operative times, and pose a greater risk of intraoperative and postoperative complications. This study aims to compare surgeon reimbursement between primary and revision shoulder arthroplasty. Methods Utilizing a single institution shoulder arthroplasty database, we identified patients who underwent primary or revision shoulder arthroplasty between February 2011 and December 2013 by a single shoulder and elbow fellowship trained surgeon with over 20 years of experience at the time of data collection. The RVUs for primary and revision shoulder arthroplasty were obtained from the CMS Physician Fee schedule. Physician reimbursement for primary and revision shoulder arthroplasty was calculated using the CMS RVU to dollar conversion factor of $34.8921 per RVU. The RVU was divided by operative time to calculate an RVU/min for primary and revision shoulder arthroplasty. Monetary reimbursement per minute, case, day, and year was subsequently calculated. Results A total of 190 primary and 100 revision shoulder arthroplasties were performed during the study period. Mean RVU for primary shoulder arthroplasty was 22.13 ± 0.00 vs. 26.24 ± 1.10 for revision shoulder arthroplasty (P Conclusion While the RVU/case is higher for revision shoulder arthroplasty, the difference does not account for the additional operative time and complexity compared to primary shoulder arthroplasty. In light of this data, the current RVU reimbursement model should be reevaluated to account for these differences between primary and revision shoulder arthroplasty. Level of Evidence Level III; Retrospective Comparative Study

Objectives Although adjuvant radiotherapy may be indicated in patients with sinonasal squamous cell carcinoma (SNSCC) following primary surgery, some patients choose to forgo recommended postoperative radiation therapy (PORT). This study aimed to elucidate factors associated with patient refusal of recommended PORT in SNSCC and examine overall survival. Methods Retrospective analysis of patients with SNSCC treated with primary surgery from the National Cancer Database diagnosed between 2004 and 2016. A multivariable logistic regression model was created to determine the association between clinical or demographic covariates and likelihood of PORT refusal. Unadjusted Kaplan–Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival. Results A total of 2,231 patients were included in the final analysis, of which 1,456 (65.3%) were males and 73 (3.3%) refused recommended PORT. Patients older than 74 years old were more likely to refuse PORT than those younger than 54 (odds ratio [OR] 3.43, 95% confidence interval [CI]: 1.84–6.62). Median survival among the entire cohort, those who received recommended PORT, and those who refused PORT was 83.0 months (95% CI: 74.6–97.1), 83.0 months (95% CI: 74.9–98.2), and 63.6 months (95% CI: 37.3–101.4), respectively. Refusal of PORT was not associated with overall survival (hazard ratio: 0.99, 95% CI: 0.69–1.42). Conclusions PORT refusal in patients with SNSCC is rare and was found to be associated with several patient factors. The decision to forgo PORT is not independently associated with overall survival in this cohort. Further study is required to determine the clinical implications of these findings as the treatment decisions are complex.

Objective Damage associated molecular patterns (DAMPs) are pathological mediators linking local tissue damage to systemic inflammation in various diseases. Some DAMPs, such as mitochondrial DNA (mtDNA), can be recognized by the cytoplasmic cGAS protein to trigger the activation of the stimulator of interferon genes (STING)-dependent innate immune pathway responsible for infection or sterile inflammation. The objective of our study was to evaluate the association between circulating mtDNA and cGAS-STING pathway activation in mediating inflammation following burn injury. Methods 48 adult Sprague-Dawley male rats were divided into eight groups (Sham, 2, 4, 8, 12, 24, 48, 72 h after burn injury). The animals underwent 40% total body surface area scald injury to produce a full-thickness burn. Plasma samples were collected via cardiac puncture under deep anesthesia. Tissues were harvested and placed in formalin, followed by paraffin embedment. Total plasma DNA was isolated followed by measurement of mtDNA using quantitative polymerase chain reaction. Haemotoxylin-Eosin stain and Western blot was used for lung histology and protein assays, respectively. Statistical analyses were performed using ANOVA and student’s t-test and represented as mean ± s.d. Results Plasma mtDNA trended upward at early time-points following burn injury with peak levels at 8 h after burn when compared to the control group (345 ± 83.4 copies/μl vs. 239 ± 43.1 copies/μl, p = 0.07) and followed a bell-shaped distribution. Lung slices from burned rats showed acute injury marked by increased inflammatory infiltrate, with the maximum changes seen at 24 h, accompanied with significant upregulation of neutrophil elastase (p = 0.04). Compared with sham animals, cGAS and STING protein levels in lung tissue were up-regulated at 4 and 8 h after burn (p = 0.03 and p Conclusion Activation of the cGAS-STING pathway by increased plasma mtDNA is an important pathway driving neutrophil infiltration in burn-induced acute lung injury in rats. A further understanding of the STING-mediated immunopathology in lung and other susceptible organs may be important for the development of novel therapies for burn injury.

Background: Hypoglossal and masseteric nerve transfer are currently the most popular cranial nerve transfer techniques for patients with facial paralysis. The authors performed a systematic review and meta-analysis to compare functional outcomes and adverse effects of these procedures. Methods: A review of online databases was performed to include studies with four or more patients undergoing hypoglossal or masseter nerve transfer without muscle transfer or other cranial nerve transposition. Facial nerve outcomes, time to reinnervation, and adverse events were pooled and studied. Results: A total of 71 studies were included: 15 studies included 220 masseteric-facial transfers, and 60 studies included 1312 hypoglossal-facial transfers. Oral commissure symmetry at rest was better for hypoglossal transfer (2.22 ± 1.6 mm vs. 3.62 ± 2.7 mm, p = 0.047). The composite Sunnybrook Facial Nerve Grading Scale was better for masseteric transfer (47.7 ± 7.4 vs. 33.0 ± 6.4, p < 0.001). Time to first movement (in months) was significantly faster in masseteric transfer (4.6 ± 2.6 vs. 6.3 ± 1.3, p < 0.001). Adverse effects were rare (

Objective Delays in care for patients with acute cardiac complaints are associated with increased morbidity and mortality. The objective of this study was to quantify rural and urban differences in prehospital time intervals for patients with cardiac complaints. Methods The ESO Data Collaborative dataset consisting of records from 1332 EMS agencies was queried for 9–1-1 encounters with acute cardiac problems among adults (age ≥ 18) from 1/1/2013–6/1/2018. Location was classified as rural or urban using the 2010 United States Census. The primary outcome was total prehospital time. Generalized estimating equations evaluated differences in the average times between rural and urban encounters while controlling for age, sex, race, transport mode, loaded mileage, and patient stability. Results Among 428,054 encounters, the median age was 62 (IQR 50–75) years with 50.7% female, 75.3% white, and 10.3% rural. The median total prehospital, response, scene, and transport times were 37.0 (IQR 29.0–48.0), 6.0 (IQR 4.0–9.0), 16.0 (IQR 12.0–21.0), and 13.0 (IQR 8.0–21.0) minutes. Rural patients had an average total prehospital time that was 16.76 min (95%CI 15.15–18.38) longer than urban patients. After adjusting for covariates, average total time was 5.08 (95%CI 4.37–5.78) minutes longer for rural patients. Average response and transport time were 4.36 (95%CI 3.83–4.89) and 0.62 (95%CI 0.33–0.90) minutes longer for rural patients. Scene time was similar in rural and urban patients (0.09 min, 95%CI -0.15-0.33). Conclusion Rural patients with acute cardiac complaints experienced longer prehospital time than urban patients, even after accounting for other key variables, such as loaded mileage.

Objective We aim to evaluate the impact gynecologic oncologists have on ovarian cancer adjuvant chemotherapy care from their role as surgeons recommending adjuvant chemotherapy care and their role as adjuvant chemotherapy providers while considering rural-urban differences. Methods Multivariable adjusted logistic regressions and Cox proportional hazards models were developed using a population-based, retrospective cohort of stage II-IV and unknown stage ovarian cancer patients diagnosed in Iowa, Kansas, and Missouri in 2010–2012 whose medical records were abstracted in 2017–2018. Results Gynecologic oncologist surgeons (versus other type of surgeon) were associated with increased odds of adjuvant chemotherapy initiation (adjusted odds ratio (OR) 2.18; 95% confidence interval (CI) 1.10–4.33) and having a gynecologic oncologist adjuvant chemotherapy provider (OR 10.0; 95% CI 4.58–21.8). Independent of type of surgeon, rural patients were less likely to have a gynecologic oncologist chemotherapy provider (OR 0.52; 95% CI 0.30–0.91). Gynecologic oncologist adjuvant chemotherapy providers (versus other providers) were associated with decreased surgery-to-chemotherapy time (rural: 6 days; urban: 8 days) and increased distance to chemotherapy (rural: 22 miles; urban: 11 miles). Rural women (versus urban) traveled 38 miles farther when their chemotherapy provider was a gynecologic oncologist and 27 miles farther when it was not. Conclusion Gynecologic oncologist surgeons may impact adjuvant chemotherapy initiation. Gynecologic oncologists serving as adjuvant chemotherapy providers were associated with some care benefits, such as reduced time from surgery-to-chemotherapy, and some care barriers, such as travel distance. The barriers and benefits of having a gynecologic oncologist involved in adjuvant chemotherapy care, including rural-urban differences, warrant further research in other populations.

Better management of head and neck squamous cell carcinomas (HNSCCs) requires a clearer understanding of tumor biology and disease risk. Bitter taste receptors (T2Rs) have been studied in several cancers, including thyroid, salivary, and GI, but their role in HNSCC has not been explored. We found that HNSCC patient samples and cell lines expressed functional T2Rs on both the cell and nuclear membranes. Bitter compounds, including bacterial metabolites, activated T2R-mediated nuclear Ca2+ responses leading to mitochondrial depolarization, caspase activation and ultimately apoptosis. Buffering nuclear Ca2+ elevation blocked caspase activation. Furthermore, increased expression of T2Rs in HNSCCs from The Cancer Genome Atlas is associated with improved overall survival. This work suggests that T2Rs are potential biomarkers to predict outcomes and guide treatment selection, may be leveraged as therapeutic targets to stimulate tumor apoptosis, and may mediate tumor-microbiome crosstalk in HNSCC.

Elimination of dog-transmitted human rabies worldwide will require large-scale dog vaccination campaigns. However, this places participating vaccinators at increased risk. Data from the 2016–2017 Haitian mass rabies vaccination campaign was analyzed to determine dog bite incidence among vaccinators. A survey was then developed for completion by all identifiable bitten vaccinators covering demographics; experience and training; bite episode details; attitudes toward dogs and rabies; and medical care. A parallel group of unbitten vaccinators was also surveyed. Dog bite incidence was 0.03% (43/127,000) of all dogs vaccinated. The capture, vaccinate, and release method of vaccination carried a significantly higher risk of dog bite (0.35%, 6/1,739 vaccinations) than other methods (P < 0.001). Twenty-seven bitten vaccinators, and 54 control vaccinators were included in the survey analysis. No differences were found between groups in demographics, experience, or training. However, bitten vaccinators were significantly more likely than the control group to have experienced a dog bite before the study period (P < 0.001). This may be associated with a lesser appreciation of dogs, and/or a poorer ability to interpret dog behavioral signals within this group. Although 98% of the control group indicated they would seek medical care for a dog bite, only 35% of bitten vaccinators sought such care. On a yearly basis, for the Haitian campaign, a full series of postexposure rabies vaccinations for all bite victims would prove more cost-effective than preexposure vaccination of all vaccinators. These findings may prove useful for the planning and safety of future mass dog vaccination campaigns.

Purpose Three continuous dosing strategies of cisatracurium (CIS) for acute respiratory distress syndrome (ARDS) have been described in the literature. After implementation of a ventilator synchrony protocol (VSP), we sought to determine which continuous CIS dosing strategy utilized the least amount of drug without compromising efficacy. Methods We retrospectively reviewed patients with ARDS receiving continuous CIS from January 1, 2013 to December 31, 2018. We categorized patients into one of three dosing strategies: fixed dose (FD), titration based solely on train-of-four (TOF), or the VSP. We documented drug consumption and determined efficacy by comparing the change in PaO2/FiO2 ratio (P/F) and oxygenation index (OI) from baseline up to 48 h. Results A total of 1047 patients were screened, and 189 met inclusion criteria (VSP = 69, TOF = 99, FD = 21). Drug consumption (mg) was significantly lower in the VSP arm: 415 [IQR 318–528] compared to both the TOF: 665 [IQR 472–927] and the FD arms: 1730 [IQR 1695–1800], p < 0.001 for each. The change in P/F and OI from baseline were statistically equivalent at all time points. Conclusion Without impacting efficacy of gas exchange, a protocol using ventilator synchrony for CIS titration required significantly less drug compared to TOF-based titration and a fixed dosing regimen.

This review summarizes high-quality evidence supporting delayed umbilical cord clamping to promote placental transfusion to preterm and term neonates. In preterm neonates, delayed cord clamping may decrease mortality and the need for blood transfusions. Although robust data are lacking to guide cord management strategies in many clinical scenarios, emerging literature is reviewed on numerous topics including delivery mode, twin gestations, maternal comorbidities (eg, gestational diabetes, red blood cell alloimmunization, human immunodeficiency virus [HIV] infection, and severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and neonatal complications (eg, fetal growth restriction, congenital heart disease, and the depressed neonate). Umbilical cord milking is an alternate method of rapid placental transfusion, but has been associated with severe intraventricular hemorrhage in extremely preterm neonates. Data on long-term outcomes are discussed, as well as potential contraindications to delayed cord clamping. Overall, delayed cord clamping offers potential benefits to the estimated 140 million neonates born globally every year, emphasizing the importance of this simple and no-cost strategy.

Background: AAV-based gene therapy is an attractive approach to treat Duchenne muscular dystrophy (DMD) patients. Although the long-term consequences of a gene therapy approach for DMD are unknown, there is evidence in both DMD patients and animal models that dystrophin replacement by gene therapy leads to an anti-dystrophin immune response that is likely to limit the long-term use of these therapeutic strategies. Objective: Our objective is to test whether the anti-dystrophin immune response is affected by immunomodulatory drugs in mdx mice after rAAV gene therapy. Methods: mdx mice were treated with rAAV microdystrophin alone or in combination with immunomodulatory drugs. Dystrophin expression in skeletal muscle was assessed by mass spectrometry. Immune responses were assessed by immunophenotyping, western blot for anti-dystrophin antibodies and flow cytometry assays for antigen-specific T-cell cytokine expression. The impact on muscle was measured by grip strength assessment, in vivo torque, optical imaging for inflammation and H&E staining of sections to assess muscle damage. Results: We found that AAV-9-microdystrophin gene therapy induced expression of microdystrophin, anti-dystrophin antibodies, and T-cell cytokine responses. Immunomodulatory treatments, rituximab and VBP6 completely abrogated the anti-dystrophin antibody response. Prednisolone, CTLA4-Ig, and eplerenone showed variable efficacy in blocking the anti-dystrophin immune response. In contrast, none of the drugs completely abrogated the antigen specific IFN-γ response. AAV-microdystrophin treatment significantly reduced inflammation in both forelimbs and hindlimbs, and the addition of prednisolone and VBP6 further reduced muscle inflammation. Treatment with immunomodulatory drugs, except eplerenone, enhanced the beneficial effects of AAV-microdystrophin therapy in terms of force generation. Conclusions: Our data suggest that AAV-microdystrophin treatment results in anti-dystrophin antibody and T-cell responses, and immunomodulatory treatments have variable efficacy on these responses.

Since 2013, the U.S. Food and Drug administration (FDA) has required that intravenous immune globulin (IGIV) products carry a boxed warning concerning the risk of thromboembolic events (TEEs). This study assessed the incidence of TEEs attributable to IGIV in a large population-based cohort. A self-controlled risk interval design was used to quantify the transient increase in TEE risk during the risk interval (days 0-2 and 0-13 following IGIV for arterial and venous TEEs, respectively) relative to a later control interval (days 14-27 following IGIV). Potential IGIV-exposed TEE cases from 2006 to 2012 were identified from the FDA-sponsored Sentinel Distributed Database and confirmed through medical record review. Inpatient IGIV exposures were not included in the venous TEE analysis due to concerns about time-varying confounding. 19,069 new users of IGIV who received 93,555 treatment episodes were included. Charts were retrieved for 62% and 70% of potential venous and arterial cases, respectively. There was a transient increase in the risk of arterial TEEs during days 0-2 following IGIV treatment (RR = 4.69; 95% CI 1.87, 11.90; absolute increase in risk = 8.86 events per 10,000 patients, 95% CI 3.25, 14.6), but no significant increase in venous TEE risk during days 0-13 following outpatient IGIV treatments (RR = 1.07, 95% CI 0.34, 3.48). Our results suggest there is a small increase in the absolute risk of arterial TEEs following IGIV. However, lower-than-expected chart retrieval rates and the possibility of time-varying confounding mean that our results should be interpreted cautiously. Continued pharmacovigilance efforts are warranted.

Background The morbidity and mortality rates associated with cholecystectomy for acute cholecystitis are higher in the critically ill elderly population. As an alternative to cholecystectomy, we report the results of treatment of acute cholecystitis in the elderly after open cholecystolithotomy with cholecystostomy tube placement under local anesthesia. Methods A case series was performed on 5 patients from August 2007 to April 2010 who presented with acute cholecystitis and underwent an open cholecystolithotomy and tube placement. Thirty-day mortality, intra- and immediate-postoperative complications, clinical improvement after drainage, additional biliary procedures needed, and outcome after cholecystostomy tube removal were recorded. Results Open cholecystolithotomy and tube placement were performed successfully in all patients and permitted resolution of the acute attack in all after a mean period of 3.75 days. Thirty-day mortality was 0%. Patients did not experience any intraoperative complications. We observed 100% rate of successful short-term outcomes in our patients including resolution pain, and objectively, normalization of leukocytosis, and defervescence. None of the patients required emergency cholecystectomy. All patients had their cholecystostomy tubes removed at a mean postoperative day 27. There were no cases of biliary leakage or tube dislodgement. There were no recurrences of acute cholecystitis within the mean follow-up of 20.75 months. Discussion Emergency open cholecystolithotomy and cholecystostomy tube placement represent an effective, safe, and definitive alternative treatment strategy for acute gallstone cholecystitis in selected elderly patients with a mortality rate of 0% in the authors’ experience.

Objective: To implement a skull-conformal phased array for ultrasound-guided transcranial focused ultrasound therapy with improved patient comfort. Methods: Using patient-specific computed tomography and MRI neuroimaging data, tightly-conforming helmet scaffolds were designed computationally. The helmet scaffolds were designed to hold reusable transducer modules at near-normal incidence in an optimal configuration for the treatment location(s) of interest. Numerical simulations of trans-skull ultrasound propagation were performed to evaluate different conformal array designs and to compare with hemispherical arrays similar to those employed clinically. A 4096-element phased array was constructed by 3D printing a helmet scaffold optimised for an ex vivo human skullcap, and its performance was evaluated via benchtop and in vivo experiments. Results: Acoustic field measurements confirmed the system's ability to focus through human skull bone using simulation-based transcranial aberration corrections. Preliminary in vivo testing demonstrated safe trans-human skull blood-brain barrier (BBB) opening in rodents. Conclusion: Patient-specific conformal ultrasound phased arrays appear to be a feasible and safe approach for conducting transcranial BBB opening procedures. Significance: Skull-conformal phased arrays stand to improve patient comfort and have the potential to accelerate the adoption of transcranial FUS therapy by improving access to the technology.

OBJECTIVE To establish a pathoepidemiological model to evaluate the role of SARS-CoV-2 infection in the first 10 companion animals that died while infected with SARS-CoV-2 in the US. ANIMALS 10 cats and dogs that tested positive for SARS-CoV-2 and died or were euthanized in the US between March 2020 and January 2021. PROCEDURES A standardized algorithm was developed to direct case investigations, determine the necessity of certain diagnostic procedures, and evaluate the role, if any, that SARS-CoV-2 infection played in the animals’ course of disease and death. Using clinical and diagnostic information collected by state animal health officials, state public health veterinarians, and other state and local partners, this algorithm was applied to each animal case. RESULTS SARS-CoV-2 was an incidental finding in 8 animals, was suspected to have contributed to the severity of clinical signs leading to euthanasia in 1 dog, and was the primary reason for death for 1 cat. CONCLUSIONS AND CLINICAL RELEVANCE This report provides the global community with a standardized process for directing case investigations, determining the necessity of certain diagnostic procedures, and determining the clinical significance of SARS-CoV-2 infections in animals with fatal outcomes and provides evidence that SARS-CoV-2 can, in rare circumstances, cause or contribute to death in pets.

Background During the COVID-19 pandemic, there have been an increasing number of emergency department visits for behavioral health reasons, even as overall emergency department volumes have decreased. The impact of the pandemic and related public health interventions on specialized psychiatric emergency services has not been described. These services provide high-intensity care for severely ill patients who are likely to be homeless and underserved. Objective We describe the change in total volume and psychiatric hospitalization rates among three psychiatric emergency services across the United States. Methods Changes in volumes and hospitalization were assessed for statistical significance using a seasonal autoregressive integrated moving average with exogenous factors model from January 2018 to December 2020. Results The pandemic's impact on volumes and hospitalization varied by site. In Denver (CO), there was a statistically significant 9% decrease in overall volumes, although an 18% increase in hospitalizations was not significant. In New York City (NY), there was a significant 7% decrease in volumes as well as a significant 6% decrease in hospitalizations. In Portland (OR), volumes decreased by 4% and hospitalizations increased by 6% although differences did not reach statistical significance. Conclusions There has been a decrease in volume at these services after the pandemic, but there are substantial variations in the magnitude of change and demand for hospitalization by region. These findings suggest a need to understand where patients in crisis are seeking care and how systems of care must adapt to changing utilization in the pandemic era.

Background Human immunodeficiency virus (HIV)-associated lipodystrophy is a known consequence of long-term highly active antiretroviral therapy (HAART). However, a significant number of patients on HAART therapy were left with the stigmata of complications, including fat redistribution. Few studies have described the successful removal of focal areas of lipohypertrophy with successful outcomes. This manuscript reviews the outcomes of excisional lipectomy versus liposuction for HIV-associated cervicodorsal lipodystrophy. Methods We performed a 15-year retrospective review of HIV-positive patients with lipodystrophy. Patients were identified by query of secure operative logs. Data collected included demographics, medications, comorbidities, duration of HIV, surgical intervention type, pertinent laboratory values, and the amount of tissue removed. Results Nine male patients with HIV-associated lipodystrophy underwent a total of 17 procedures. Of the patients who underwent liposuction initially (n=5), 60% (n=3) experienced a recurrence. There were a total of three cases of primary liposuction followed by excisional lipectomy. One hundred percent of these cases were noted to have a recurrence postoperatively, and there was one case of seroma formation. Of the subjects who underwent excisional lipectomy (n=4), there were no documented recurrences; however, one patient’s postoperative course was complicated by seroma formation. Conclusions HIV-associated lipodystrophy is a disfiguring complication of HAART therapy with significant morbidity. Given the limitations of liposuction alone as the primary intervention, excisional lipectomy is recommended as the primary treatment. Liposuction may be used for better contouring and for subsequent procedures. While there is a slightly higher risk for complications, adjunctive techniques such as quilting sutures and placement of drains may be used in conjunction with excisional lipectomy.

Aims Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA. Methods A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml. Results A total of 22 patients were included in final analysis. At one, four, and 24 hours postoperatively, mean (95% confidence interval (CI)) serum concentrations were 2.4 (0.7 to 4.1), 5.0 (3.1 to 6.9), and 4.8 (2.8 to 6.9) for vancomycin and 4.9 (3.4 to 6.3), 7.0 (5.8 to 8.2), and 1.3 (0.8 to 1.8) for tobramycin; intra-articular concentrations were 1,900.6 (1,492.5 to 2,308.8), 717.9 (485.5 to 950.3), and 162.2 (20.5 to 304.0) for vancomycin and 2,105.3 (1,389.9 to 2,820.6), 403.2 (266.6 to 539.7), and 98.8 (0 to 206.5) for tobramycin. Conclusion Intra-articular administration of 1 g of vancomycin and 600 mg of tobramycin as a solution after closure of the arthrotomy in primary cementless TKA achieves therapeutic intra-articular concentrations over the first 24 hours postoperatively and does not reach sustained toxic levels in peripheral blood. Cite this article: Bone Joint J 2021;103-B(11):1702–1708.

Membrane separation has enjoyed tremendous advances in relevant material and engineering sciences, making it the fastest growing technology in water treatment. Although membranes as a broad-spectrum physical barrier have great advantages over conventional treatment processes in a myriad of applications, the need for higher selectivity and specificity in membrane separation is rising as we move to target contaminants at trace concentrations and to recover valuable chemicals from wastewater with low energy consumption. In this review, we discuss the drivers, fundamental science, and potential enabling materials for high selectivity membranes, as well as their applications in different water treatment processes. Membrane materials and processes that show promise to achieve high selectivity for water, ions, and small molecules—as well as the mechanisms involved—are highlighted. We further identify practical needs, knowledge gaps, and technological barriers in both material development and process design for high selectivity membrane processes. Finally, we discuss research priorities in the context of existing and future water supply paradigms.

A new specimen ofBasilosaurus cetoideswas discovered on the banks of the Flint River in Albany, Georgia, USA, in 2010. This fossil, which was the most complete specimen of the species from Georgia to date, consisted of five nearly complete and two partial post-thoracic vertebrae, tentatively identified as S4 through Ca6. During excavation, however, the site was looted and most of the specimen was lost to science. Nonetheless, we use this discovery as an opportunity to update the current state of knowledge on the stratigraphic, biogeographic, and environmental distribution ofBasilosaurusin North America, as well as the position of the late Eocene shoreline in the southeastern United States. The results show thatBasilosauruswas most abundant across the southeastern coastal plain during the early to middle Priabonian, coincident with the late Eocene maximum marine transgression. The decline inBasilosauruslocalities is associated with the retreating shoreline of the terminal Eocene. The majority ofBasilosauruslocalities fall well south of the position of the late Eocene shoreline hypothesized in this study, suggesting the genus favored middle to outer neritic zones of the epicontinental sea. The comparatively low number of Priabonian specimens in the Atlantic Coastal Plain versus the Gulf Coastal Plain, then, suggests the presence of shallow zones in the Atlantic Coastal Plain that may have limited the distribution ofBasilosaurusacross the region. The hypothesized shoreline of this study ultimately differs from earlier reconstructions by extending the Mississippi embayment at the Bartonian/Priabonian boundary farther north than previously noted.

Pediatric tectal gliomas generally have a benign clinical course with the majority of these observed radiologically. However, patients often need treatment for obstructive hydrocephalus and occasionally require cytotoxic therapy. Given the lack of level I data, there is a need to further characterize management strategies for these rare tumors. We have therefore performed the first systematic review comparing various management strategies. The literature was systematically searched from January 1, 2000, to July 30, 2020, to identify studies reporting treatment strategies for pediatric tectal gliomas. The systematic review included 355 patients from 14 studies. Abnormal ocular findings-including gaze palsies, papilledema, diplopia, and visual field changes-were a common presentation with between 13.6 and 88.9% of patients experiencing such findings. CSF diversion was the most performed procedure, occurring in 317 patients (89.3%). In individual studies, use of CSF diversion ranged from 73.1 to 100.0%. For management options, 232 patients were radiologically monitored (65.4%), 69 received resection (19.4%), 30 received radiotherapy (8.4%), and 19 received chemotherapy (5.4%). When examining frequencies within individual studies, chemotherapy ranged from 2.5 to 29.6% and radiotherapy ranged from 2.5 to 28.6%. Resection was the most variable treatment option between individual studies, ranging from 2.3 to 100.0%. Most tectal gliomas in the pediatric population can be observed through radiographic surveillance and CSF diversion. Other forms of management (i.e., chemotherapy and radiotherapy) are warranted for more aggressive tumors demonstrating radiological progression. Surgical resection should be reserved for large tumors and/or those that are refractory to other treatment modalities.

A persistent challenge that has limited access and delivery of digit replantation surgery is timing, as ischemia time has traditionally been considered an important determinant of success. However, reports that the viability of amputated digits decreases after 6 hours of warm ischemia and 12 hours of cold ischemia are largely anecdotal. This review evaluates the quality and generalizability of available evidence regarding ischemia times after digit amputation and reported outcomes of “delayed” replantation. We identify substantial limitations in the literature supporting ischemia time cutoffs and recent evidence supporting the feasibility of delayed digit replantation. The current treatment approach for amputation injuries often necessitates transfers or overnight emergency procedures that increase costs and limit availability of digit replantation nationwide. Evidence-based changes to digit replantation protocols could lead to broader availability of this service, as well as improved care quality.

BACKGROUND: Major bleeding (MB) events are independent predictors of mortality after cardiac interventional procedures. The clinical relevance of MB following left atrial appendage occlusion (LAAO) remains unclear.AIMS: This study aimed to investigate the incidence and clinical impact of MB after LAAO in a real-world population at high risk for bleeding and contraindicated to anticoagulation.METHODS: The two-year results of the Amplatzer Amulet Observational Post-Market Study were analysed. An independent committee adjudicated MBs according to the Bleeding Academic Research Consortium scale. Cox proportional hazards regression identified variables associated with MB events and mortality.RESULTS: The MB rate was 7.2%/year, with a rate of 10.1%/year during year one, decreasing to 4.0%/year over year two. The most common bleeding location was gastrointestinal, accounting for 48% of MBs. Pre-LAAO MB was associated with an increased risk for post-LAAO MB (HR 2.34, 95% CI: 1.37-3.99). The occurrence of post-LAAO MB was associated with increased mortality (37.3% vs 12.7%; pCONCLUSIONS: In real-world patients at high bleeding risk, MB following LAAO was not uncommon and associated with a significant increase in mortality, without increasing the risk of stroke. ClinicalTrials.gov Identifier: NCT02447081. https://clinicaltrials.gov/ct2/show/NCT02447081.

Background Postoperative pain after complex revision spine surgery, especially for the treatment of persistent spinal pain syndrome (PSPS), is frequently severe and can be debilitating, requiring the use of intravenous and oral opioids. To the best of our knowledge, the present study is the first to evaluate the effectiveness and safety of a continuous infusion regional anesthesia pump placed after thoracopelvic fusion for the treatment of PSPS. Methods We performed a retrospective comparative study of consecutive patients who had undergone thoracopelvic fusion for PSPS. The patients included in the present study had either had a continuous infusion regional anesthesia pump placed during surgery or had not (control). Demographics, use of preoperative and postoperative opioids, postoperative adverse events, length of hospital stay, and 90-day readmission were recorded. Results The patients in the pump group (n = 14) had used fewer opioids during their hospital stay compared with the control group (n = 12; P = 0.6). This difference was greater for postoperative days 1 and 2 (P = 0.3 and P = 0.2, respectively). No significant difference was found in opioid usage during the first 14 days after surgery (P = 0.8) or at the 3-month postoperative follow-up evaluation (P = 0.8). Furthermore, no significant difference was found between the 2 groups in terms of postoperative complications. The pump group had a 1.4-day shorter hospital stay (P = 0.7). The control group had more 90-day readmissions than did the pump group (P = 0.2). Conclusions Despite showing a trend toward less usage of opioids during the first 2 days after surgery and a shorter hospital stay with no increased complications in the pump group, the study data failed to demonstrate a statistically significant difference between the two groups.

Background Malingering is a common and challenging clinical presentation in emergency departments (EDs). Objective This study describes characteristics and outcomes among patients diagnosed as malingering in a psychiatric emergency service. Methods Index psychiatric ED encounters were identified for all adult patients seen during a 27-month period. Mortality data were obtained for patients from the state public health authority, and repeat ED visits for self-harm were obtained from the state hospital association. Patients with a diagnosis of malingering were compared with those without a malingering diagnosis using correlative statistics and multivariable analyses. Results Of 4710 encounters analyzed, 236 (5%) had a malingering diagnosis. No patients diagnosed as malingering died of suicide within 365 days of discharge, compared with 16 (0.4%) nonmalingering patients. Self-harm outcomes were available for 2689 encounters; 129 (5%) had a malingering diagnosis. Malingering was significantly associated with a repeat ED visit for self-harm within 365 days in multivariable analyses (adjusted odds ratio 2.52; 95% confidence interval 1.35–4.70); p Conclusions No psychiatric emergency service patients diagnosed as malingering died by suicide after discharge. New clinical approaches must balance malingering patients’ apparent low suicide risk with their other substantial comorbidities and risk for self-harm.

Suicide is a leading cause of death among children and adolescents, and research has shown a significant increase in the rates of emergency department (ED) visits because of suicide ideation and attempts for children younger than 18 years. OBJECTIVE This study examined the feasibility of screening all patients entering the ED using the Columbia-Suicide Severity Rating Scale as well as examining the rates of suicide ideation and attempts endorsed by adolescents who present at the ED. METHODS This study used a sample of 12,113 patients between the ages of 11 and 19 years. RESULTS Results revealed that 13.5% of the participants endorsed passive suicide ideation in the month leading up to their ED visit and 11.3% of the participants reported active ideation in the prior month. Results also revealed that patients whose chief complaints were coded as psychiatric or medical trauma were more likely to endorse either active or passive suicidal ideation than other presenting problems. Patients with a psychiatric or medical trauma chief complaint were also more likely to report lifetime suicidal behavior and suicidal behavior 3 months before the ED visit. CONCLUSIONS In addition to findings, implications, feasibility, and lessons learned are discussed for other institutions or departments considering implementation of a widespread screening.Highlights:• Suicide screenings were implemented in a large pediatric emergency department.• One in 5 endorsed suicidal ideation or behavior regardless of presenting problem.• Feasibility and lessons learned are discussed for others hoping to implement a widespread screening.

New findings What is the central question of this study? The passive leg movement (PLM) assessment of vascular function utilizes the blood flow response in the common femoral artery (CFA): what is the impact of baseline CFA blood flow on the PLM response? What is the main finding and its importance? Although an attenuated PLM response is not an obligatory consequence of increased baseline CFA blood flow, increased blood flow through the deep femoral artery will diminish the response. Care should be taken to ensure that a genuine baseline leg blood flow is obtained prior to performing a PLM vascular function assessment. Abstract The passive leg movement (PLM) assessment of vascular function utilizes the blood flow response in the common femoral artery (CFA). This response is primarily driven by vasodilation of the microvasculature downstream from the deep (DFA) and, to a lesser extent, the superficial (SFA) femoral artery, which facilitate blood flow to the upper and lower leg, respectively. However, the impact of baseline CFA blood flow on the PLM response is unknown. Therefore, to manipulate baseline CFA blood flow, PLM was performed with and without upper and lower leg cutaneous heating in 10 healthy subjects, with blood flow (ultrasound Doppler) and blood pressure (finometer) assessed. Baseline blood flow was significantly increased in the CFA (∼97%), DFA (∼109%) and SFA (∼78%) by upper leg heating. This increase in baseline CFA blood flow significantly attenuated the PLM-induced total blood flow in the DFA (∼62%), which was reflected by a significant fall in blood flow in the CFA (∼49%), but not in the SFA. Conversely, lower leg heating increased blood flow in the CFA (∼68%) and SFA (∼160%), but not in the DFA. Interestingly, this increase in baseline CFA blood flow only significantly attenuated the PLM-induced total blood flow in the SFA (∼60%), and not in the CFA or DFA. Thus, although an attenuated PLM response is not an obligatory consequence of an increase in baseline CFA blood flow, an increase in baseline blood flow through the DFA will diminish the PLM response. Therefore, care should be taken to ensure that a genuine baseline leg blood flow is obtained prior to performance of a PLM vascular function assessment.

Severe burns result in cardiovascular dysfunction, but responses in the peripheral vasculature are unclear. We hypothesize that severe burns disturb arterial contractility through acute changes in adrenergic and cholinergic receptor function. To address this, we investigated the changes in carotid artery contractility and relaxation following a severe burn. Thirty-four adult Sprague–Dawley male rats received a 40% total body surface area (TBSA) scald burn and fluid resuscitation using the Parkland formula. Control animals received sham burn procedure. Animals were serially euthanized between 6 h and 14 days after burn and endothelium-intact common carotid arteries were used for ex vivo force/relaxation measurements. At 6 h after burn, carotid arteries from burned animals demonstrated a > 50% decrease in cumulative dose-responses to norepinephrine (p −7 M angiotensin II (p p p

Pain is a complex syndrome that is difficult to treat. The increasing numbers of patients living with chronic diseases has led to increasing pain management needs and the rise of opioid use disorder (OUD) as a major and potentially lethal public health concern. Treatment of chronic pain with prescription opioids alone is not always successful, and a multidisciplinary approach is paramount to address the needs of patients at risk of developing or suffering from OUD. Interventional radiologists trained to perform minimally invasive procedures with negligible downtime and postprocedure pain can help stem the tide of opioid-related deaths and disability. This article reviews a wide range of minimally invasive procedures, including vertebral augmentation, sacroplasty, thermal ablation of osseous metastasis, nerve blocks, and gonadal vein embolization, that interventional radiologists are now using successfully to treat chronic pain. The evidence to support use of such procedures is highlighted. This article also briefly discusses emerging techniques such as arterial embolization and ablation for knee and shoulder osteoarthritis that have not yet been fully tested but exhibit strong potential in chronic pain management. By reducing opioid use in patients suffering from chronic pain, these minimally invasive procedures can potentially prevent escalation to OUD.

OBJECTIVES To identify the incidence of distal articular fractures in a series of distal third tibia shaft fractures and to report the utility of both computed tomography (CT) scans and Radiographic Investigation of the Distal Extension of Fractures into the Articular Surface of the Tibia (RIDEFAST) ratios for identification of articular involvement. DESIGN Retrospective cohort. SETTING Level 1 trauma center. PATIENTS Four hundred seventeen patients with distal third tibia shaft fractures were included in the study. INTERVENTION Intramedullary nail or plate fixation. MAIN OUTCOME MEASURES Type of articular fracture, time of diagnosis, and RIDEFAST ratios. RESULTS One hundred one of the 417 distal third fractures (24%) had a fracture of the distal tibia articular surface. Of these 101 fractures, 41 (41%) represented an extension of the primary fracture line and 60 (59%) were separate malleolar fractures. Of the 101 articular fractures, 95 (94%) were identified preoperatively and 6 (6%) were identified intraoperatively. Of the 95 fractures identified preoperatively, 87 (92%) were identified on plain radiographs and 8 (8%) by CT scan. Thirty-five preoperative CT scans were performed on distal third tibia shaft fractures in search of an intra-articular fracture. In 27 patients (77%), no articular fracture was present, representing an overall yield of 23% among CT scans performed to rule out an articular fracture in distal third tibia shaft fractures. RIDEFAST ratios for all 101 distal tibia shaft fractures with articular involvement and 100 fractures with no articular involvement were not significantly different (P > 0.05) using both coronal and sagittal plane measurements. CONCLUSIONS CT scans performed on distal third tibia shaft fractures in search of articular fractures had a low yield (23%). Widespread use of CT scan to diagnose fractures of the distal tibia articular surface in the setting of distal tibia shaft fractures does not seem warranted. No statistically significant differences in RIDEFAST ratios were found between fractures with and without articular involvement, indicating that more work is necessary before RIDEFAST can be used to reliably rule out articular involvement in this setting. LEVEL OF EVIDENCE Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background As the science of consultation-liaison psychiatry advances, the Academy of Consultation-Liaison Psychiatry's Guidelines and Evidence-Based Medicine Subcommittee reviews articles of interest to help academy members remain familiar with the latest in evidence-based practice. Objective We identify the 10 most important articles for clinical practice in consultation-liaison psychiatry from 2020 using the new Importance and Quality instrument for assessing scientific literature. Methods The subcommittee published annotated abstracts for 97 articles on the academy website in 2020. Reviewers then rated all articles on clinical importance to practice and quality of scholarship using the Importance and Quality instrument. We describe the 10 articles with the highest aggregate scores and analyze the reliability of Importance and Quality instrument. Results Twenty-four raters identified the top 10 scoring articles of 2020. These articles provide practical guidance on key areas of consultation-liaison psychiatry including management of COVID-19, lithium treatment for complex patients, medical risks among patients with severe mental illness, and substance use disorders in medical settings. The assessment instrument demonstrated good to excellent interrater reliability. Conclusion These articles offer valuable guidance for consultation-liaison psychiatrists regardless of their practice area. Collaborative literature reviews with standardized assessments help clinicians deliver evidence-based care and foster a high standard of practice across the specialty.

Background Postoperative prophylactic antibiotics are commonly used in pituitary surgery, but evidence supporting their use is lacking, which has implications for antibiotic stewardship. Objective To evaluate whether receipt of postoperative oral antibiotics results in superior sinonasal quality of life (QOL) compared with placebo among patients who undergo endoscopic endonasal transsphenoidal pituitary surgery. Methods Patients were randomized to receive either oral placebo or cefdinir (trimethoprim-sulfamethoxazole in patients intolerant to cefdinir) for 7 d after surgery. They were monitored for 12 wk. The primary outcome measure was sinonasal QOL at 2 wk on the Anterior Skull Base Nasal Inventory-12. Supplementary end points included sinonasal QOL reported on the Sinonasal Outcome Test-22 and objective endoscopy scores to assess nasal healing according to the Lund-Kennedy method. Results A total of 461 patients were screened, 131 were randomized, and 113 (placebo arm: 55; antibiotic arm: 58) were analyzed. There was no clinically meaningful or statistically significant difference in sinonasal QOL at any measured time point (P ≥ .24) using either instrument. Nasal cavity endoscopy scores were not significantly different at 1 to 2 wk after surgery (P = .25) or at 3 to 4 wk after surgery (P = .08). Conclusion Postoperative prophylactic oral antibiotics did not result in superior sinonasal QOL compared with placebo among patients who underwent standard endoscopic transsphenoidal surgery.

Background: Multiteam, multi-institution prospective studies of both women’s and men’s sports are essential for collectively investigating injury and primary to the generalization and individualization of injury prevention strategies. Hypothesis: Characteristics of workload, sleep, and contextual factors will be associated with injury risk in collegiate soccer athletes. Study Design: Cohort study; Level of evidence, 2. Methods: Injuries, workload, and sleep characteristics were recorded daily throughout a complete season for 256 athletes from 12 separate National Collegiate Athletic Association Division I men’s and women’s soccer teams. Workload and contextual factors were assessed via multilevel Poisson regression to capture differences in injury incidence rate ratio (IRR). Paired t test and multilevel logistic regressions were used to assess the relationship between sleep behavior and injury. Results: Collegiate soccer athletes had lower rates of noncontact injury in the in-season (IRR, 0.42) and postseason (IRR, 0.48) compared with preseason, lower rates of injury in training (IRR, 0.64) compared with matches, and higher injury rates with only 1 day of rest in the previous week (IRR, 1.58) compared with >1 day. Injury rates peaked when training occurred 4 days before a match (IRR, 2.24) compared with a match. Injury rate increased exponentially with increases in the number of noncontact injuries incurred throughout the season (IRR, 2.23). Lower chronic loading, higher training monotony, and acute spikes and lulls in workload were associated with higher noncontact injury rates. Alterations in previous week sleep quality were associated with injury, while chronic sleep behavior and acute alterations ( .05). Conclusion: Athlete and schedule-specific contextual factors, combined with characteristics of workload and weekly sleep behavior, are significantly associated with injury in collegiate soccer. Multiteam prospective cohort studies involving objective and subjective monitoring allow for the identification of multiple injury risk factors in sports, which can be used to guide injury prevention strategies. Maintaining higher chronic workloads, lowering training monotony, minimizing acute spikes or lulls in workloads, managing workloads during preseason and for athletes with previous injury, integrating more rest and recovery during congested periods, and optimizing sleep quality are all practical considerations for reducing injury risk in collegiate soccer.

Sepsis is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The skeletal muscle system is among the host organ systems compromised by sepsis. The resulting neuromuscular dysfunction and impaired regenerative capacity defines sepsis-induced myopathy and manifests as atrophy, loss of strength, and hindered regeneration after injury. These outcomes delay recovery from critical illness and confer increased vulnerability to morbidity and mortality. The mechanisms underlying sepsis-induced myopathy, including the potential contribution of peripheral organs, remain largely unexplored. The gut microbiome is an immunological and homeostatic entity that interacts with and controls end-organ function, including the skeletal muscle system. Sepsis induces alterations in the gut microbiota composition, which is globally termed a state of "dysbiosis" for the host compared to baseline microbiota composition. In this review, we critically evaluate existing evidence and potential mechanisms linking sepsis-induced myopathy with gut microbiota dysbiosis.

Background National Comprehensive Cancer Network guidelines recommend ovarian cancer patients receive cancer-directed surgery from a gynecologic oncologist surgeon. We aimed to determine if rurality impacts type of surgeon and estimate if the interaction between rurality and type of surgeon impacts cytoreductive surgery, chemotherapy initiation, and survival. Methods Our population-based cohort of Iowan (N=675) ovarian cancer patients included women diagnosed with histologically confirmed stages IB-IV cancer in 2010 to 2016 at the ages of 18 to 89 years old and who received cancer-directed surgery in Iowa. Multivariable logistic regression analysis and Cox proportional hazards models were used. Results Rural (vs. urban) patients were less likely to receive surgery from a gynecologic oncologist (adjusted odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.30-0.78). Rural patients with a gynecologic oncologist (vs. nongynecologic oncologist) surgeon were more likely to receive cytoreduction (OR: 2.84; 95% CI: 1.31-6.14) and chemotherapy (OR: 4.22; 95% CI: 1.82-9.78). Gynecologic oncologist-provided surgery conferred a 3-year cause-specific survival advantage among rural patients (adjusted hazard ratio: 0.57; 95% CI: 0.33-0.97) and disadvantage among urban patients (hazard ratio: 1.77; 95% CI: 1.02-3.06) in the model without treatment covariates. Significance dissipated in models with treatment variables. Discussion The variation in the gynecologic oncologist survival advantage may be because of treatment, referral, volume, or nongynecologic oncologist surgeons' specialty difference by rurality. This is the first study to investigate the ovarian cancer survival advantage of having a gynecologic oncologist surgeon by rurality.

Objectives The aim of this study was to determine the frequency and severity of adverse events (AEs) reported from use of an adjuvanted whole-cell autologous cancer vaccine in cats with solid tumors under field conditions. Methods The case accession database at Torigen Pharmaceuticals was searched to identify client-owned cats that underwent biopsy or surgical resection of their primary tumor, had histologic confirmation of neoplasia and received at least one subcutaneous dose of an adjuvanted whole-cell autologous cancer vaccine. Records were reviewed for any reported AEs. Results In total, 117 cats met the inclusion criteria and received 422 doses of autologous cancer vaccine. Six (5.1%) cats had seven reported AEs, with the majority of these (85.7%) being characterized as grade 1 or 2 (mild) and resolving without medical intervention. Conclusions and relevance AEs were infrequent in cats treated with an adjuvanted whole-cell autologous cancer vaccine under typical field use conditions. This form of active cancer immunotherapy appears to be well tolerated by cats and may represent a treatment option for owners who are concerned about AEs associated with chemotherapy or radiotherapy. Additional studies are warranted to determine the efficacy of this form of individualized immunotherapy in cats with solid tumors.

ObjectiveTo explore the use of health plan quality measures specified for electronic clinical data to monitor immunizations.Materials and MethodsWe analyzed 2018 data submitted by health plans reporting 2 new Healthcare Effectiveness Data and Information Set measures assessing receipt of clinically recommended vaccines among pregnant women and adults. We analyzed the number of plans reporting a valid performance rate and electronic data source used. We consulted expert panels and reviewed coverage rates from other sources to understand the results.ResultsWe received 136 data submissions across commercial, Medicaid and Medicare plans and 87 submissions across commercial and Medicaid plans for the adult and prenatal immunization measures, respectively. These submissions represent approximately 15% of possible submissions. Plans used claims, registries and electronic health records. Mean performance rates for adult immunizations were 21.2 (commercial), 14.0 (Medicaid) and 19.5% (Medicare). Mean rates for prenatal immunizations were 33.1 (commercial) and 16.7% (Medicaid).DiscussionResults from the first year of reporting 2 electronic clinical data measures suggest health plans can feasibly report these measures and are seeking electronic data to supplement claims. Comparison of rates to other national results showed lower than expected rates for the adult immunization measure. However, prenatal immunization rates were on par with those from a national survey, suggesting this measure is closer to use for quality improvement.ConclusionQuality measure reporting that encourages connection to electronic data sources is a step forward in performance monitoring and improvement. The use of electronic sources may advance health information exchange for patient care.

To assess the impact of sociodemographic factors on primary treatment choice (surgery vs radiotherapy) in patients with human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC).Retrospective analysis of the National Cancer Database.Data from1500 Commission on Cancer institutions (academic and community) via the National Cancer Database.Our sample consists of patients diagnosed with HPV+ OPSCC from 2010 to 2015. The primary outcome of interest was initial treatment modality: surgery vs radiation. We performed multivariable logistic models to assess the relationship between treatment choice and sociodemographic factors, including sex, race, treatment facility, and insurance status.Of the 16,043 patients identified, 5894 (36.7%) underwent primary surgery while 10,149 (63.3%) received primary radiotherapy. Black patients were less likely than White patients to receive primary surgery (odds ratio [OR], 0.80; 95% CI, 0.66-0.96). When compared with privately insured patients, those who were uninsured or on Medicaid or Medicare were also less likely to receive primary surgery (OR, 0.70 [95% CI, 0.56-0.86]; OR, 0.77 [95% CI, 0.65-0.91]; OR, 0.85 [95% CI, 0.75-0.96], respectively). Patients receiving treatment at an academic/research cancer program were more likely to undergo primary surgery than those treated at comprehensive community cancer programs (OR, 1.33; 95% CI, 1.14-1.56).In this large sample of patients with HPV+ OPSCC, race and insurance status affect primary treatment choice. Specifically, Black and nonprivately insured patients are less likely to receive primary surgery as compared with White or privately insured patients. Our findings illuminate potential disparities in HPV+ OPSCC treatment.

Oligometastatic disease was originally defined by Hellman and Weichselbaum as an intermediate-state existing between locally confined and widely disseminated malignancy, whose natural history could be positively impacted with systemic and importantly local therapies such as radiation. Currently oligometastatic prostate cancer (OPCa) is defined clinically by lesion enumeration and several subgroups exist: de novo (synchronous) oligometastatic disease present at initial diagnosis, oligorecurrent (metachronous) disease arising after definitive therapy to the prostate, and oligoprogressive disease where isolated lesions progress in a background of otherwise stable disease. In this review we highlight current knowledge and the potential future of local therapies, such as radiation to the primary prostate and metastasis-directed therapy (MDT), in the disease management of OPCa for all three subgroups. In addition, we examine more recent studies classifying the patterns of failure and natural history of OPCa following treatment with local therapies. Finally, while current clinical definitions of OPCa dominate, we introduce studies attempting to elucidate a more biological definition of OPCa to allow for improved selection of patients to treat with local therapies and to better inform precision combination approaches with systemic therapy.

Background The gut microbiome protects the host from infection by promoting epithelial integrity and providing basal immunologic stimulation. Disruption of this delicate ecosystem is linked to morbidity and mortality among critically ill patients, but the impact of traumatic injury on the gut microbiome is poorly understood. This study sought to identify alterations in gut microbiota following trauma and persistent stress in rodents without confounding antibiotics. Methods Male Sprague-Dawley rats aged 9 weeks to 11 weeks were randomized to naive, lung contusion with hemorrhagic shock (LCHS), and LCHS plus either 7 (LCHS/CS 7/7) or 14 days (LCHS/CS 14) of restraint cylinder stress for 2 hours daily. Stool was collected on Days 0, 3, 7, and 14 for bacterial whole genome DNA isolation. Alpha diversity, or the number and relative abundance of unique bacterial species within each cohort, was assessed using Chao1 indices. Beta diversity, or the measure of differences in biodiversity across cohorts, was assessed by principle coordinate analysis. False discovery rate correction was applied to all statistical analyses and corrected for cohousing effects. Results Rodent groups subject to restraint stress demonstrated a progressive increase in alpha diversity over time. These microbiota changes resolved after cessation of stress (LCHS/CS 7/7) but continued to increase among rats subjected to ongoing stress (LCHS/CS 14). The LCHS/CS 7/7 also demonstrated reductions in class Actinobacteria and increased abundance of the genus Bacteroides by Day 7, which resolved by Day 14. Increased abundance of Bacteroides was also noted in the LCHS/CS 14 cohort, suggesting the role of chronic stress in its destabilization. Conclusion This study points to persistent stress as a potential source of the destabilization of microbial diversity seen after trauma. This lack of microbiota stability could be associated with worse long-term outcomes in critically ill trauma patients. Further studies are warranted to elucidate mechanistic pathways and potential therapeutic modalities.

To report our experience using the scan-and-plan workflow and review current literature on surgical efficiency, safety, and accuracy of next-generation robot-assisted (RA) spine surgery.The records of patients who underwent RA pedicle screw fixation were reviewed. The accuracy of pedicle screw placement was determined based on the Ravi classification system. To evaluate workflow efficiency, 3 demographically matched cohorts were created to analyze differences in time per screw placement (defined as operating room [OR] time divided by number of screws placed). Group A had4 screws placed, Group B had 4 screws placed, and Group C had4 screws placed. Intraoperative errors and postoperative complications were collected to elucidate safety.Eighty-four RA cases (306 pedicle screws) were included for analysis. The mean number of screws placed was 2.1 ± 0.3 in Group A and 6.4 ± 1.2 in Group C; 4 screws were placed in Group B patients. The accuracy rate (Ravi grade I) was 98.4%. Screw placement time was significantly longer in Group A (101 ± 37.7 minutes) than Group B (50.5 ± 25.4 minutes) or C (43.6 ± 14.7 minutes). There were no intraoperative complications, robot failures, or in-hospital complications requiring a return to the OR.The scan-and-plan workflow allowed for a high degree of accuracy. It was a safe method that provided a smooth and efficient OR workflow without registration errors or robotic failures. After the placement of 4 pedicle screws, the per-screw time remained constant. Further studies regarding efficiency and utility in multilevel procedures are necessary.