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Cytomegalovirus (CMV) infection is asymptomatic in the majority of immunocompetent patients. However, it can cause severe presentations, particularly in patients who are immunocompromised. We are reporting a rare association between respiratory failure secondary to cavitary pneumonia and a large pericardial effusion due to CMV infection in a patient with human immunodeficiency virus. The patient presented with hypoxic respiratory failure and a large pericardial effusion at risk of tamponade. After extensive investigation, the sole pathogen identified in the patient’s bronchoalveolar lavage and pericardial fluid was CMV.

Background: The Lapidus procedure and scarf osteotomy are indicated for the operative treatment of hallux valgus; however, no prior studies have compared outcomes between the procedures. The aim of this study was to compare clinical and radiographic outcomes between patients with symptomatic hallux valgus treated with the modified Lapidus procedure versus scarf osteotomy. Methods: This retrospective cohort study included patients treated by 1 of 7 fellowship-trained foot and ankle surgeons. Inclusion criteria were age older than 18 years, primary modified Lapidus procedure or scarf osteotomy for hallux valgus, minimum 1-year postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores, and minimum 3-month postoperative radiographs. Revision cases were excluded. Clinical outcomes were assessed using 6 PROMIS domains. Pre- and postoperative radiographic parameters were measured on anteroposterior (AP) and lateral weightbearing radiographs. Statistical analysis utilized targeted minimum-loss estimation (TMLE) to control for confounders. Results: A total of 136 patients (73 Lapidus, 63 scarf) with an average of 17.8 months of follow-up were included in this study. There was significant improvement in PROMIS physical function scores in the modified Lapidus (mean change, 5.25; P < .01) and scarf osteotomy (mean change, 5.50; P < .01) cohorts, with no significant differences between the 2 groups ( P = .85). After controlling for bunion severity, the probability of having a normal postoperative intermetatarsal angle (IMA; Conclusion: Although the modified Lapidus procedure led to a higher probability of achieving a normal IMA, both procedures yielded similar improvements in 1-year patient-reported outcome measures. Level of Evidence: Level III, retrospective cohort.

Background: Previous studies have demonstrated that procedure-specific thresholds using preoperative patient-reported outcome scores may be used to predict postoperative outcomes. The primary purpose of this study was to determine if preoperative Patient-Reported Outcomes Measurement Information System (PROMIS) thresholds could be used to predict which patients would clinically improve at 2 years postoperatively following reconstruction of their flexible adult-acquired flatfoot deformity (AAFD). Methods: PROMIS physical function, pain interference, and depression scores were prospectively collected preoperatively and at a minimum of 2 years postoperatively for 75 feet with flexible AAFD. Minimal clinically important differences (MCIDs) were calculated to establish significant postoperative improvement. Receiver operating characteristic curves and area under the curve analyses were employed to determine whether preoperative PROMIS scores could be used to predict postoperative outcomes. Results: The PROMIS physical function receiver operating characteristic curve analysis (area under the curve = 0.913, P < .001) found that a preoperative PROMIS physical function score greater than 45.7 resulted in a 14.3% probability of achieving the MCID, whereas a preoperative score of less than 40.8 had a 97.7% probability of achieving the MCID. A preoperative PROMIS pain interference score (area under the curve = 0.799, P < .001) less than 54.1 had only a 23.1% probability of achieving the MCID at 2 years postoperatively. Conclusions: Preoperative PROMIS physical function and pain interference scores could be used to predict postoperative improvement in patients with flexible AAFD. These results may help surgeons counsel patients regarding the anticipated benefit of surgery. Level of Evidence: Level III, retrospective comparative series.

Tau pathology and vascular dysfunction are important contributors to Alzheimer's disease (AD), but vascular–tau associations and their effects on cognition are poorly understood. We investigated these associations in male and female humans by conducting voxelwise comparisons between cerebral blood flow (CBF) and tau positron emission tomography (PET) images in independent discovery [cognitively normal (CN), 19; mild cognitive impairment (MCI) risk, 43; MCI, 6] and replication (CN,73; MCI, 45; AD, 20) cohorts. In a subgroup, we assessed relationships between tau and soluble platelet-derived growth factor β (sPDGFRβ), a CSF marker of pericyte injury. We tested whether CBF/sPDGFRβ–tau relationships differed based on Montreal Cognitive Assessment (MoCA) global cognition performance, or based on amyloid burden. Mediation analyses assessed relationships among CBF/sPDGFRβ, tau, and cognition. Negative CBF–tau correlations were observed predominantly in temporal-parietal regions. In the replication cohort, early negative CBF–tau correlations increased in spatial extent and in strength of correlation with increased disease severity. Stronger CBF–tau and sPDGFRβ–tau correlations were observed in participants with greater amyloid burden and lower MoCA scores. Importantly, when stratifying by amyloid status, stronger CBF–tau relationships in individuals with lower MoCA scores were driven by amyloid+participants. Tau PET was a significant mediator CBF/sPDGFRβ–MoCA relationships in numerous regions. Our results demonstrate vascular–tau associations across the AD spectrum and suggest that early vascular–tau associations are exacerbated in the presence of amyloid, consistent with a two-hit model of AD on cognition. Combination treatments targeting vascular health, as well as amyloid-β and tau levels, may preserve cognitive function more effectively than single-target therapies.SIGNIFICANCE STATEMENTEmerging evidence demonstrates a role for vascular dysfunction as a significant contributor to Alzheimer's pathophysiology. However, associations between vascular dysfunction and tau pathology, and their effects on cognition remain poorly understood. Multimodal neuroimaging data from two independent cohorts were analyzed to provide novelin vivoevidence of associations between cerebral blood flow (CBF), an MRI measure of vascular health, and tau pathology using PET. CBF–tau associations were related to cognition and driven in part by amyloid burden. Soluble platelet-derived growth factor β, an independent CSF vascular biomarker, confirmed vascular–tau associations in a subgroup analysis. These results suggest that combination treatments targeting vascular health, amyloid-β, and tau levels may more effectively preserve cognitive function than single-target therapies.

Due to rising demands on productivity and flexibility, assembly processes are currently experiencing a substantial transformation. Workstations where humans and robots work closely together are becoming increasingly popular, as they provide major advantages compared to manual assembly and full automation. Yet, human-robot collaboration (HRC) can only be successful if the workforce is willing to accept it. How assembly workers perceive HRC still has to be properly investigated. An exploratory investigation using a Grounded Theory approach was conducted to identify factors that are likely to influence workers’ acceptance of introducing HRC at work. Seventeen workers with various levels of HRC experience from four different manufacturing companies were interviewed. Findings reveal that some workers perceive HRC as a threat, while others regard it as an opportunity. This perception seems to depend both on their thoughts and feelings about the technology, i.e., collaborative robots, and the organizational change associated with the introduction of this technology. Several factors related to the robot (object-related factors), the individual background of the workers (subject-related factors), and the organizational environment (context-related factors) are found to influence workers’ thoughts and feelings. Implications for researchers and manufacturing companies are outlined.

Vascular contributions to dementia and Alzheimer's disease are increasingly recognized1-6. Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction7, including the early clinical stages of Alzheimer's disease5,8-10. The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer's disease11-14, leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes15-19, which maintain BBB integrity20-22. It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the ε3/ε4 or ε4/ε4 alleles) are distinguished from those without APOE4 (ε3/ε3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-β or tau pathology measured in cerebrospinal fluid or by positron emission tomography23. High baseline levels of the BBB pericyte injury biomarker soluble PDGFRβ7,8 in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-β and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway19 in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer's disease pathology, and might be a therapeutic target in APOE4 carriers.

Background: The posteromedial ankle structures are at risk during total ankle replacement (TAR). The purpose of our study was to investigate the distance of these structures from the posterior cortex of the tibia and talus in order to determine their anatomy at different levels of bone resection during a TAR and whether plantarflexion of the ankle reliably moved these structures posteriorly. Methods: Ten feet in 10 patients with end-stage tibiotalar arthritis indicated for a TAR were included. Preoperative magnetic resonance images were obtained with the foot in a neutral position as well as in maximum plantarflexion to measure the distance of posteromedial ankle structures to the closest part of the posterior cortex of the tibia or talus. Wilcoxon signed-rank rests were used to investigate differences in these distances. Results: The mean distance from the posterior tibial cortex to the tibial nerve at 14 and 7 mm above the tibial plafond was 8.7 mm (range 5.0-11.8 mm) and 6.7 mm (range 2.7-10.6 mm), respectively, which represented a statistically significant movement anteriorly ( P = .021). The posterior tibial artery was, on average, 8.0 mm (range 3.6-13.9 mm) and 7.2 mm (range 3.1-9.4 mm) from the posterior tibial cortex at 14 and 7 mm above the tibial plafond, respectively. Distal to the tibial plafond, the posterior tibial artery and flexor digitorum longus tendons moved posteriorly by less than 1 mm in plantarflexion (all P < .05); otherwise, plantarflexion of the ankle did not affect the position of the tibial nerve, posterior tibial tendon, or flexor hallucis longus. Conclusion: In patients with end-stage ankle arthritis, the tibial nerve and posterior tibial artery lie, on average, between 6.5 and 10 mm from the posterior tibial and talar cortices. Plantarflexion of the ankle did not reliably move the posteromedial ankle structures posteriorly. Level of Evidence: Level IV, case series, therapeutic

Objective In patients with a history of lymphoma who demonstrate palatine tonsil uptake on posttreatment PET/CT (positron emission tomography/computed tomography), tonsillectomy is often performed to evaluate for lymphoma recurrence. However, predictive clinical and imaging factors for true tonsil recurrence in this setting are not well established; this will be explored herein. Study design Retrospective case series. Setting Patients treated at a tertiary medical center from January 2008 to May 2020. Methods Chart review was performed on all patients with a history of treated lymphoma in clinical remission who presented for evaluation of abnormal PET/CT imaging findings and subsequently underwent tonsillectomy. Results Among 15 patients who met inclusion criteria, 14 had benign findings on surgical pathology, yielding a false-positive rate of 93%. The patient with malignancy was identified on biopsy after inconclusive surgical pathology and is the only documented case of recurrence in this specific patient population throughout the literature. The patient presented with B symptoms, irregularly shaped tonsils, increased lymph node activity on PET/CT, and uptrending bilateral tonsil activity but with one of the lowest maximum standardized uptake values of the cohort. The singular distinguishing feature for the patient with recurrent disease was a prior tonsil biopsy suspicious for recurrence, which prompted the otolaryngology referral. Conclusion PET/CT lacks specificity in identifying lymphoma recurrence in the oropharynx. Clinical and radiographic features that were previously considered concerning for recurrence are most likely not indicative of malignancy in this patient population. Our findings call into question whether tonsillectomy should be routinely performed in this patient population.

Diet-induced obesity is a major risk factor for metabolic syndrome, diabetes and cardiovascular disease. Here, we show that a 5-d fasting-mimicking diet (FMD), administered every 4 weeks for a period of 2 years, ameliorates the detrimental changes caused by consumption of a high-fat, high-calorie diet (HFCD) in female mice. We demonstrate that monthly FMD cycles inhibit HFCD-mediated obesity by reducing the accumulation of visceral and subcutaneous fat without causing loss of lean body mass. FMD cycles increase cardiac vascularity and function and resistance to cardiotoxins, prevent HFCD-dependent hyperglycaemia, hypercholesterolaemia and hyperleptinaemia and ameliorate impaired glucose and insulin tolerance. The effect of monthly FMD cycles on gene expression associated with mitochondrial metabolism and biogenesis in adipocytes and the sustained ketogenesis in HFCD-fed mice indicate a role for fat cell reprogramming in obesity prevention. These effects of an FMD on adiposity and cardiac ageing could explain the protection from HFCD-dependent early mortality. While on a high-fat, high-calorie diet, a monthly cycle of 5 days of a fasting-mimicking diet can prevent obesity and related detrimental effects on cardiometabolic health and lifespan in mice.

Background Effective and rapid immunologic response to vaccines is a crucial strategy for the control SARS-CoV-2 pandemic. Here, we present the results of an ongoing longitudinal observational study conducted among the healthcare workers (HCWs) of the Pineta Grande Hospital (Castel Volturno, Italy), who were administered the two-dose prime-boost mRNA vaccine BNT162b2. Methods Volunteer HCWs underwent either (i) six RT-PCR assay for qualitative detection of SARS-CoV-2 nucleic acid in nasopharyngeal/oropharyngeal swabs; (ii) or six quantitative serology testing for the research of virus-specific immunoglobulins (Ig) through chemiluminescent immunoassay with a reactivity cut-off of an Index of ≥ 1.0. The first tests were taken before the administration of the vaccine and then according to a predefined timeline. An active surveillance follow-up of SARS-CoV-2 infections was set amongst the vaccinees after the end of the study. Results Overall, among the 435 HCWs who accepted to participated in the study, 9.3% reported a previous laboratory-confirmed infection with SARS-CoV-2, though all subjects tested negative at the time of first vaccine dose. In the swab cohort, seven subjects tested positive in the first 15 days after the first vaccine dose and one about a week from the second dose. At 45- and 60-day follow-ups all vaccinees tested negative, but two positive tests were registered at the third month. In the second cohort, two weeks after the first vaccine dose anti-SARS-CoV-2 antibodies exceeded the reactivity cut-off in 82.5% the participants. At one-month follow-up, almost all (98.4%) the vaccinees had reached the maximum Index value of 10. No statistically significant associations were found between antibody response and HCWs' characteristics. Conclusions Our results showed that surveillance is a critical component of providing safe healthcare during COVID-19 pandemic, also after extended vaccination campaigns, thus enhancing the protection of patients and HCWs. Key messages All healthcare facilities should implement continuous post-vaccination surveillance programs in order to ensure patients and healthcare workers safety, and limit in-hospital transmission of SARS-CoV-2. Longer field follow-ups are indispensable to investigate immunogenicity trends and effectiveness of COVID-19 vaccines over time, and to consider booster doses, especially in high-risk population.

Surgical management of progressive collapsing foot deformity continues to evolve. Previous studies have demonstrated that fusion of the talonavicular joint results in limited hindfoot motion and, therefore, may accelerate adjacent-joint arthrosis. Recent literature has supported using alternative arthrodesis constructs that spare the talonavicular joint, such as naviculocuneiform or isolated subtalar fusions, which may maintain some hindfoot motion through the talonavicular joint yet adequately address a patient's deformity. Concomitant reconstructive procedures may be used in addition to subtalar fusion to address severe deformities. Isolated subtalar fusions may be considered in cases of sinus tarsi or subfibular impingement deformities.

Reconstruction of the flexible adult-acquired flatfoot deformity (AAFD) is controversial, and numerous procedures are frequently used in combination, including flexor digitorum longus transfer, medializing calcaneal osteotomy (MCO), heel cord lengthening/gastrocnemius recession, lateral column lengthening (LCL), Cotton osteotomy or first tarsometatarsal fusion, and spring ligament reconstruction. This article summarizes recent studies demonstrating that patients have significant improvements after operative treatment of flexible AAFD. It reviews current literature on clinical and radiographic outcomes of the MCO, LCL, and Cotton osteotomies. The authors describe how this information can be used in surgical decision making in order to tailor operative treatment to an individual patient's deformity.

Alzheimer's disease (AD) clinical trials, focused on disease modifying drugs and conducted in patients with mild to moderate AD, as well as prodromal (early) AD, have failed to reach efficacy endpoints in improving cognitive function in most cases to date or have been terminated due to adverse events. Drugs that have reached clinical stage were reviewed using web resources (such as clinicaltrials.gov, alzforum.org, company press releases, and peer reviewed literature) to identify late stage (Phase II and Phase III) efficacy clinical trials and summarize reasons for their failure. For each drug, only the latest clinical trials and ongoing trials that aimed at improving cognitive function were included in the analysis. Here we highlight the potential reasons that have hindered clinical success, including clinical trial design and choice of outcome measures, heterogeneity of patient populations, difficulties in diagnosing and staging the disease, drug design, mechanism of action, and toxicity related to the long-term use. We review and suggest approaches for AD clinical trial design aimed at improving our ability to identify novel therapies for this devastating disease.

Adenosine receptors (ARs) are a class of purinergic G-protein-coupled receptors (GPCRs). Extracellular adenosine is a pivotal regulation molecule that adjusts physiological function through the interaction with four ARs: A1R, A2AR, A2BR, and A3R. Alterations of ARs function and expression have been studied in neurological diseases (epilepsy, Alzheimer’s disease, and Parkinson’s disease), cardiovascular diseases, cancer, and inflammation and autoimmune diseases. A series of Positron Emission Tomography (PET) probes for imaging ARs have been developed. The PET imaging probes have provided valuable information for diagnosis and therapy of diseases related to alterations of ARs expression. This review presents a concise overview of various ARs-targeted radioligands for PET imaging in diseases. The most recent advances in PET imaging studies by using ARs-targeted probes are briefly summarized.

The use of bedside ultrasound over the past few decades has created a new wave of options for visualizing pathological processes allowing for faster and better detection of disease. We aimed to evaluate the reliability of focused cardiac ultrasound (FCU) performed by first-year internal medicine residents at a community hospital after a short period of training. They received a two-hour lecture and initially performed a supervised FCU followed by ten unsupervised/independent FCUs each. The four parameters that were assessed were left systolic ventricular function, right systolic ventricular function, presence of pericardial effusion, and presence of IVC dilation. Interpretation and analysis of ultrasound images were then carried out by both the residents and an attending physician with expertise in FCU analysis and interpretation. Cohen’s Kappa values were obtained comparing the results found by the interns versus the attending. Our findings indicate that more training is required for reliable analysis of FCU by first-year medical residents. Our results also emphasize the need to carefully evaluate the medical residents’ FCU skills after the training.

Background: There is no consensus in the foot and ankle literature regarding how to measure pronation of the first metatarsal in patients with hallux valgus. The primary purpose of this study was to compare 2 previously published methods for measuring pronation of the first metatarsal and a novel 3-dimensional measurement of pronation to determine if different measurements of pronation are associated with each other. Methods: Thirty patients who underwent a modified Lapidus procedure for their hallux valgus deformity were included in this study. Pronation of the first metatarsal was measured on weightbearing computed tomography (WBCT) scans using the α angle with reference to the floor, a 3-dimensional computer-aided design (3D CAD) calculation with reference to the second metatarsal, and a novel method, called the triplanar angle of pronation (TAP), that included references to both the floor (floor TAP) and base of the second metatarsal (second TAP). Pearson’s correlation coefficients were used to determine if the 3 calculated angles of pronation correlated to each other. Results: Preoperative and postoperative α angle and 3D CAD had no correlation with each other ( r = 0.094, P = .626 and r = 0.076, P = .694, respectively). Preoperative and postoperative second TAP and 3D CAD also had no correlation ( r = 0.095, P = .624 and r = 0.320, P = .09, respectively). However, preoperative and postoperative floor TAP and α angle were found to have moderate correlations ( r = 0.595, P = .001 and r = 0.501, P = .005, respectively). Conclusion: The calculation of first metatarsal pronation is affected by the reference and technique used, and further work is needed to establish a consistent measurement for the foot and ankle community. Level of Evidence: Level III, retrospective cohort study.

Introduction In hallux valgus (HV), first metatarsal pronation is increasingly recognized as an important aspect of the deformity. The purpose of this study was to compare pronation in HV patients determined from the shape of the lateral head of the first metatarsal on AP weightbearing radiographs with pronation calculated from weightbearing CT (WBCT) scans. Methods Patients were included in this study if they had preoperative and 5-month postoperative WBCT scans and corresponding weightbearing AP radiographs of the affected foot. Pronation of the first metatarsal on WBCT scans was measured using a 3D CAD model and the alpha angle and categorized into four groups on radiographs. Association between pronation groups on radiographs and WBCT scans was determined using Spearman correlation coefficients (rs) and by comparing mean WBCT pronation of the first metatarsal between plain radiograph pronation groups. Results Agreement between the two observers’ pronation on radiographs was good (k = 0.634) and moderate (k = 0.501), respectively. There was no correlation between radiographic pronation and the 3D CAD model (rs Conclusion Pronation of the first metatarsal measured on weightbearing AP radiographs had moderate interobserver agreement and was only weakly associated with pronation measured from WBCT scans. These results suggest that first metatarsal pronation measured on weightbearing radiographs is not a substitute for pronation measured on WBCT scans. Level of evidence III, retrospective cohort study.

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Background: Previous studies have found an increased rate of deformity recurrence in hallux valgus (HV) patients with concomitant metatarsus adductus (MA) undergoing metatarsal osteotomies. The purpose of this paper was to determine if there were radiographic or clinical outcome differences between HV patients with and without MA undergoing a modified Lapidus procedure. Methods: One hundred forty-seven feet that underwent a modified Lapidus procedure for HV were divided into 2 groups based on their preoperative modified Sgarlato’s angle: (1) the MA group had an angle ≥20 degrees and (2) the HV-only group had an angle Results: Patients in the MA group had a significantly higher mean postoperative HVA (10.8 vs 7.5 degrees; P = .038). There was a trend toward higher PROMIS PI scores in the MA group at 1 year postoperatively (51.9 vs 47.6; P = .088). Patients in the MA group were more likely to have a revision surgery (7.3% vs 0%; P = .021), and there was a trend toward those patients having a higher recurrence rate (17.1% vs 6.6%; P = .064). Conclusion: Despite potentially worse postoperative outcomes in patients with HV and MA who undergo a modified Lapidus procedure, the recurrence rates reported here are lower than those reported in the literature for patients with MA undergoing metatarsal osteotomies, indicating that a modified Lapidus procedure may be an acceptable choice in these patients. Level of Evidence: Level III, retrospective comparative series.

Background:Severe adult-acquired flatfoot deformity (AAFD) is often associated with painful medial column collapse at the naviculocuneiform (NC) joint. However, many surgeons surgically correct the deformity without directly addressing this joint. The purpose of this study was to examine the role of first-tarsometatarsal (TMT) fusion combined with subtalar fusion in correcting deformity at the NC joint.Methods:We retrospectively analyzed 40 patients (41 feet) who underwent first-TMT and subtalar (ST) fusion as part of a flatfoot reconstructive procedure. We assessed 6 radiographic parameters both preoperatively and at a minimum of 6 months postoperatively, including talonavicular (TN) coverage angle, lateral talo–first metatarsal angle, lateral talocalcaneal angle, calcaneal pitch, hindfoot moment arm, and a newly defined navicular-cuneiform incongruency angle (NCIA). Patient-Reported Outcomes Measurement Information System (PROMIS) clinical outcomes were assessed preoperatively and at a minimum 1-year follow-up.Results:The NCIA demonstrated excellent interobserver reliability, with no significant change between pre- and postoperative measurements. All other radiographic parameters, except calcaneal pitch, demonstrated statistically significant improvement postoperatively ( P < .01). Overall, patients had statistically significant improvement in all PROMIS domains ( P < .01), except for depression. Worsening NC deformity was not associated with worse patient-reported outcomes.Conclusions:Our data suggest that when addressing painful collapse of the medial arch in patients with AAFD, fusion of the first-TMT joint in combination with other procedures leads to acceptable radiographic and clinical outcomes. There was no change in deformity at the NC joint in our patient cohort at short-term follow-up, and patients achieved significant improvement in multiple PROMIS domains. Although TMT fusion had no effect on NC deformity, residual or worsening NC deformity did not significantly affect clinical outcomes. In addition, the NCIA was found to be a reliable radiographic parameter to assess NC deformity in the presence of talonavicular and/or first-TMT fusion.Level of Evidence:Level III, retrospective comparative study.

Weight-bearing CT (WBCT) scans of the foot and ankle have improved the understanding of deformities that are not easily identified on radiographs and are increasingly being used by orthopaedic surgeons for diagnostic and preoperative planning purposes. In contrast to standard CT scans, WBCT scans better demonstrate the true orientation of the bones and joints during loading. They have been especially useful in investigating the alignment of complex pathologies such as adult-acquired flatfoot deformity in which patients have been found to have a more valgus subtalar joint alignment than in a normal cohort and high rates of subfibular impingement. Studies using WBCT scans have also provided new insight into more common lower extremity conditions such as hallux valgus, ankle fractures, and lateral ankle instability. WBCT scans have allowed researchers to investigate pronation of the first metatarsal in patients with hallux valgus compared with normal feet, and patients with lateral ankle instability have been found to have more heel varus than healthy control subjects. Understanding the application of WBCT scans to clinical practice is becoming more important as surgeons strive for improved outcomes in the treatment of complicated foot and ankle disorders.

Publication of 2 (negative) randomized clinical trials (RCTs) in 2002 and 2008 demonstrating inefficacy of arthroscopic debridement of the knee (ADK) for osteoarthritis, and a 2004 national non-coverage Medicare determination, have decreased overall ADK utilization. However, because of potentially favorable outcomes associated with high volume, surgeons performing high arthroscopy volume may be slower to abandon performing ADK than would low volume surgeons. We examined the trends in ADKs performed by high and low volume surgeons before and after these 2 trials and the Medicare determination. New York state residents 40 years and older undergoing outpatient ADK from 1997 to 2010 were identified from a statewide database, and monthly population-based age and sex-adjusted ADK rates were calculated. We estimated the change in utilization trends over time, stratified by surgeon annual arthroscopy volume, for Medicare and non-Medicare patients. 1386 surgeons performed 29,658 ADKs during the study period, with the proportion performed by high volume surgeons increasing from 22% in 1997 to 66% in 2010. Overall monthly ADK rates declined from 2.4 to 1.3 per 100,000 population (45%) over the study period. Rates of ADK performed by high volume surgeons increased after the first RCT in the non-Medicare population and after the CMS decision in the Medicare population, and decreased after the second RCT. With more definitive evidence from the second negative trial, high volume surgeons performed less ADKs, suggesting that multiple RCTs with consistently negative results are needed to change practice of high volume surgeons.

National rates of lateral epicondylitis and surgical treatment are poorly defined. Disease burden of lateral epicondylitis (LE) continues to increase annually. Further study is necessary to optimize treatment algorithms to reduce associated health-care expenditures.The purpose of this study is to review the annual incidence of LE, surgical rates, and associated health-care costs in a population setting.A national database was queried for LE from 2007 to 2014. Surgical cases were identified and annual rates were recorded. Demographic and epidemiologic data were reported with descriptive statistics, while trends over time were analyzed using linear regression.Eighty-five thousand three hundred eighteen cases of LE were identified. The annual incidence per 10,000 patients remained constant (The annual incidence of LE and rate of surgical intervention have remained constant from 2007 to 2014. The proportion of patients over65 years diagnosed with, and receiving surgical treatment for, LE has significantly increased in recent years. Total reimbursement and average per-patient reimbursement have steadily risen, demonstrating the increasing burden of cost on the health-care system.

Aim We assessed the association between the presence and absence of androgen on the normal biodistribution of the positron emission tomography (PET) cellular proliferation imaging biomarker, [18F]-2'-Fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (18F-FMAU), in mice. Materials and methods Non-castrated (n=4) and castrated (n=4) athymic non-tumor-bearing male mice served as models for presence and absence, respectively, of androgen. MicroPET-CT scans were performed 1 h following tail vein administration of 200 uCi of 18F-FMAU. Imaging was performed at baseline and then at 7-day intervals longitudinally for 35 days only in castrated mice following subcutaneous introduction of a 12.5 mg, 21-day release, dihydrotestosterone pellet. Mean standardized uptake values (SUVmean) were obtained for liver, heart, and muscle. Several two-group comparisons of average of SUVmean were performed. Results Pre-pellet baseline average SUVmean (±s.d.) values in castrated mice were significantly lower than baseline non-castrated values, increased on day 15 and reached peak values on day 28, at which time they were significantly higher than corresponding baseline levels in both non-castrated and pre-pellet castrated mice. The peak values decreased significantly following dihydrotestosterone withdrawal. Conclusion There is a significant modulatory effect of androgen on normal 18F-FMAU uptake levels in mice liver, heart and muscle tissues.

Background: Despite the importance of shoe wear to patients with hallux valgus (HV), few studies have investigated changes in foot width following surgery in this population. The purpose of our study was to determine if the modified Lapidus procedure would effectively decrease foot width in patients with HV. Methods: Thirty-one feet (19 left, 12 right) in 30 patients (29 females, 1 male) who underwent a modified Lapidus procedure in combination with a modified McBride and Akin osteotomy for treatment of HV were included in the study. All patients had preoperative and at least 5-month postoperative imaging, consisting of both weightbearing radiographs and computed tomography (WBCT) scans, which were used to measure bony and soft tissue foot widths pre- and postoperatively by 2 independent observers. Results: Intraclass correlation coefficients (ICCs) demonstrated high interobserver reliability (all ICCs >0.90). Bony foot width decreased significantly, by a mean of 8.9 mm (9.1%) on radiographs and 7.9 mm (8.4%) on WBCT scans ( P < .001). The soft tissue foot width also decreased significantly, by a mean of 6.9 mm (6.3%) on radiographs and 6.7 mm (6.4%) on WBCT scans ( P < .001). Changes in the hallux valgus angle and intermetatarsal angle correlated with changes in bony foot width on WBCTs (both r > 0.4, P < .02). Conclusions: The modified Lapidus procedure in combination with a modified McBride and Akin osteotomy resulted in statistically significant changes in both bony and soft tissue foot width. Patients should be counseled that foot width decreases, on average, by 0.5 to 1 cm. Level of Evidence: Level III, comparative series.

Background: Hallux valgus (HV) is a triplanar deformity of the first ray including pronation of the first metatarsal with subluxation of the sesamoids. The purpose of this study was to investigate if a first tarsometatarsal fusion (modified Lapidus technique), without preoperative knowledge of pronation measured on weightbearing computed tomographic (CT) scans, changed pronation of the first metatarsal and determine if reduction of the sesamoids was correlated with changes in first metatarsal pronation. Methods: Thirty-one feet in 31 patients with HV who underwent a modified Lapidus procedure had preoperative and at least 5-month postoperative weightbearing CT scans and radiographs. Differences in preoperative and postoperative pronation of the first metatarsal using a 3-dimensional computer-aided design, HV angle, and intermetatarsal angle (IMA) were calculated using Wilcoxon signed-rank tests. After dividing patients into groups based on sesamoid station, Kruskal-Wallis H tests were used to compare first metatarsal pronation between the groups. Results: The mean preoperative and postoperative pronation of the first metatarsal was 29.0 degrees (range 15.8-51.1, SD 8.7) and 20.2 degrees (range 10.4-32.6, SD 5.4), respectively, which was a mean change in pronation of the first ray of −8.8 degrees ( P < .001). There was no difference in pronation of the first ray when stratified by postoperative sesamoid position ( P > .250). The average preoperative and postoperative IMA was 16.7 degrees (SD 3.2) and 8.8 degrees (SD 2.8), which demonstrated a significant change ( P < .001). Conclusions: The modified Lapidus procedure was an effective tool to change pronation of the first ray. Reduction of the sesamoids was not associated with postoperative first metatarsal pronation. Level of Evidence: Level IV, case series.

Category: Ankle Arthritis Introduction/Purpose: Peripheral vascular disease (PVD) is often cited as a contraindication for total ankle replacement (TAR); however, there are no studies looking at its impact on postoperative complications. The primary purpose of our study was to identify whether preoperative PVD increased the rate of infection, postoperative irrigation and debridement, or failure of the implant in patients undergoing total ankle arthroplasty using a large dataset. Methods: The PearlDiver Database was used to identify Medicare patients who underwent a TAR from 2005 to 2014 using ICD- 9 and CPT codes. The cohort was queried for postoperative infections within 90 days, subsequent irrigation and debridement, and failure of TAR. Failure of TAR was defined was a revision, conversion to tibiotalar arthrodesis, lower extremity amputation, or implant removal. A diagnosis of preoperative PVD only included those patients who had PVD as an ICD-9 diagnosis code and underwent a preoperative lower extremity angiogram prior to TAR. Preoperative co-morbidities including prior corticosteroid injections, diabetes mellitus, smoking, rheumatoid arthritis, congestive heart failure, hypertension, obesity, and end-stage renal disease requiring dialysis were taken into consideration. Three multivariable logistic regression models were then developed in order to identify risk factors associated with postoperative infections and failure after TAR. Results: 10,698 Medicare patients who underwent a primary TAR were identified. 334 patients had a postoperative infection within 90 days of their TAR and 95 of those patients required an irrigation and debridement. Patients with a preoperative diagnosis of PVD had the highest acute infection rate at 10.5% as well as the highest incidence of failure at 12.3%. Multivariable logistic regression modeling demonstrated that patients with PVD had the greatest risk of developing a postoperative infection within 90 days (OR 2.85, 95% CI 1.45-5.13, PConclusion: Our study suggests that a preoperative diagnosis of PVD has significant negative effects on outcomes following TAR. Preoperative PVD is an independent risk factor for an acute postoperative infection, postoperative irrigation and debridement, and failure of the implant.

Head and neck lymphedema (HNL) is a disfiguring disease affecting over 90% of patients treated for head and neck cancer. Animal models of lymphedema are used to test pharmacologic and microsurgical therapies; however, no animal model for HNL is described in the literature to date. In this study we describe the first reproducible rat model for HNL. Animals were subjected to two surgical protocols: (1) lymphadenectomy plus irradiation; and (2) sham surgery and no irradiation. Head and neck expansion was measured on post-operative days 15, 30 and 60. Magnetic resonance imaging (MRI) was acquired at the same time points. Lymphatic drainage was measured at day 60 via indocyanine green (ICG) lymphography, after which animals were sacrificed for histological analysis. Postsurgical lymphedema was observed 100% of the time. Compared to sham-operated animals, lymphadenectomy animals experienced significantly more head and neck swelling at all timepoints (P + cell density (P = 0.04), 1.7-fold increase in TGFβ1 mRNA expression (P = 0.03), and 114% greater T-cell infiltration (P = 0.005) compared to sham-operated animals. In conclusion, animals subjected to complete lymph node dissection and irradiation developed changes consistent with human clinical postsurgical HNL. This was evidenced by significant increase in all head and neck measurements, slower lymphatic drainage, subcutaneous tissue expansion, increased fibrosis, and increased inflammation compared to sham-operated animals.

This review explores recent work directed toward the development of nanoparticles (NPs) for multimodality cancer imaging and targeted cancer therapy. In the growing era of precision medicine, theranostics, or the combined use of targeted molecular probes in diagnosing and treating diseases is playing a particularly powerful role. There is a growing interest, particularly over the past few decades, in the use of NPs as theranostic tools due to their excellent performance in receptor target specificity and reduction in off-target effects when used as therapeutic agents. This review discusses recent advances, as well as the advantages and challenges of the application of NPs in cancer imaging and therapy.

With further research into the molecular mechanisms and roles linking immune suppression and restraint of (pre)malignancies, immunotherapies have revolutionized clinical strategies in the treatment of cancer. However, nearly 70% of patients who received immune checkpoint therapeutics showed no response. Complementary and/or synergistic effects may occur when extracellular checkpoint antibody blockades combine with small molecules targeting intracellular signal pathways up/downstream of immune checkpoints or regulating the innate and adaptive immune response. After radiolabeling with radionuclides, small molecules can also be used for estimating treatment efficacy of immune checkpoint blockades. This review not only highlights some significant intracellular pathways and immune-related targets such as the kynurenine pathway, purinergic signaling, the kinase signaling axis, chemokines, etc., but also summarizes some attractive and potentially immunosuppression-related small molecule agents, which may be synergistic with extracellular immune checkpoint blockade. In addition, opportunities for small molecule-based theranostics in cancer immunology will be discussed.

Background: Despite limited evidence, peripheral vascular disease is often cited as a contraindication for total ankle arthroplasty. The purpose of our study was to identify whether peripheral vascular disease in patients undergoing total ankle arthroplasty increased the rate of infection, postoperative irrigation and debridement, or failure of the implant. Methods: The PearlDiver Database was used to identify Medicare patients who underwent a total ankle arthroplasty from 2005 to 2014. These data were then analyzed for postoperative infections within 90 days, subsequent irrigation and debridements, and failure of total ankle arthroplasties. A diagnosis of preoperative peripheral vascular disease only included those patients who had peripheral vascular disease as an ICD-9 diagnosis code and underwent a preoperative lower extremity angiogram prior to total ankle arthroplasty. Medical comorbidities were identified using ICD-9 diagnosis codes. Three multivariable logistic regression models were then developed in order to identify risk factors associated with postoperative infections and failure after total ankle arthroplasty. Results: A total of 10 698 Medicare patients who underwent a primary total ankle arthroplasty were identified. There were 334 patients who had a postoperative infection within 90 days of their total ankle arthroplasty, and 95 of those patients required an irrigation and debridement. Regression analysis demonstrated that patients with peripheral vascular disease had the greatest risk of developing a postoperative infection within 90 days (OR 2.85, P < .01), requiring an irrigation and debridement postoperatively (OR 4.87, P < .001), and having a total ankle arthroplasty failure at any time point postoperatively (OR 2.51, P < .001). Conclusions: Our study suggests that preoperative peripheral vascular disease is a significant risk factor for an acute postoperative infection, postoperative irrigation and debridement, and failure of the implant in Medicare patients undergoing a total ankle arthroplasty. Level of Evidence: Level III, therapeutic.

Heparin anticoagulation therapy is an indispensable feature of clinical care yet has a narrow therapeutic window and is the second most common intensive care unit (ICU) medication error. The active partial thromboplastin time (aPTT) monitors heparin but suffers from long turnaround times, a variable reference range, limited utility with low molecular weight heparin, and poor correlation to dose. Here, we describe a photoacoustic imaging technique to monitor heparin concentration using methylene blue as a simple and Federal Drug Administration-approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) and blood. Clinically relevant heparin concentrations were detected in blood in 32 s with a detection limit of 0.28 U/mL. We validated this imaging approach by correlation to the aPTT (Pearson's r = 0.86; p0.05) as well as with protamine sulfate treatment. This technique also has good utility with low molecular weight heparin (enoxaparin) including a blood detection limit of 72 μg/mL. We then used these findings to create a nanoparticle-based hybrid material that can immobilize methylene blue for potential applications as a wearable/implantable heparin sensor to maintain drug levels in the therapeutic window. To the best of our knowledge, this is the first use of photoacoustics to image anticoagulation therapy with significant potential implications to the cardiovascular and surgical community.

Category: Bunion; Other Introduction/Purpose: In hallux valgus (HV), first metatarsal pronation is increasingly recognized as an important aspect of the deformity. Weightbearing CT (WBCT) scans have allowed investigators to quantify pronation of the first metatarsal. Yamaguchi et al. (J Orthop Sci 2015) proposed that pronation of the first metatarsal can be estimated by looking at the shape of the lateral aspect of the first metatarsal head on weightbearing AP radiographs of the foot, which would provide surgeons with a simple and readily available guide for evaluation of pronation. The purpose of this study was to compare pronation determined from the shape of the lateral head of the first metatarsal on AP weightbearing radiographs in HV patients with pronation calculated from WBCT scans. Methods: Patients were included in this study if they had preoperative (n=22 patients) or 5-month postoperative (n=22 patients) WBCT scans and corresponding weightbearing AP radiographs of the affected foot. Pronation on weightbearing AP radiographs was grouped into four groups 0–9°, 10–19°, 20–30°, and >30° as described by Wagner and Wagner (Foot Ankle Clin 2018) by two independent observers. Pronation of the first metatarsal on WBCT scans was measured using a technique developed by Campbell et al. (Foot Ankle Int 2018), which calculates pronation of the first metatarsal in reference to the second metatarsal using a 3D CAD model, and using the alpha angle as described by Kim et al. (Foot Ankle Int 2015) and was categorized into the same four groups described for the radiographs. Weighted kappa coefficients (k) were used to determine interobserver reliability and agreement between pronation groups on radiographs and WBCT scans. Intraclass correlation coefficients were used to determine reliability of the alpha angle measurements on WBCT scans. After dividing patients into plain radiograph pronation groups, differences in mean WBCT pronation of the first metatarsal was compared using Kruskal-Wallis tests. Results: Agreement between the two observers for preoperative and postoperative pronation on radiographs was moderate (k=.529,P 0.80, P30° (n=2), mean pronation calculated from WBCT scans using a 3D CAD method was 21.1°, 25.2°,and 20.9°, respectively (P=.752), and mean pronation calculated using the alpha angle was 13.2°, 15.8°, and 22.3°, respectively (P=.308). Postoperatively, in the plain radiograph pronation groups of 0-9° (n=9), 10-19° (n=6), and 20-29° (n=7), mean pronation calculated from WBCT scans using a 3D CAD method was 22.3°, 22.5°, and 21.0°, respectively (P=.976), and mean pronation calculated using the alpha angle was 3.1°, 5.7°, and 6.4°, respectively (P=.252). Conclusion:: Pronation of the first metatarsal measured on weightbearing AP radiographs using the lateral first metatarsal head had only fair to moderate interobserver agreement and did not statistically significantly agree with pronation measured on WBCT scans using either a 3D CAD model or the alpha angle. Additionally, mean pronation on WBCT scans did not significantly differ by any magnitude between the plain radiograph pronation groups, which indicates that there was no association between pronation measured on WBCT scans and plain radiographs. These results suggest that surgeons should use caution when trying to derive first metatarsal pronation from AP weightbearing radiographs for surgical planning purposes.

Category: Bunion Introduction/Purpose: The progression of hallux valgus (HV) deformities results in dislocation of the sesamoids from their position (station) under the plantar surface of the distal first metatarsal. With this dislocation, the crista separating the two sesamoids erodes as the contact of the medial sesamoid with the crista applies pressure with weightbearing. Recently, three dimensional (3D) reconstructions of the metatarsals and first phalanx have demonstrated a means to find a consistently quantify first metatarsal pronation. These same reconstructions can also produce a reliable technique to compute the volumes of the bones involved. The purpose of the current investigation is to examine the relationship of the volume of the crista to pronation and to sesamoid station. Methods: Eleven HV patients and five normal subjects with weightbearing or weightbearing equivalent CT (WBCT) imaging were randomly selected from the senior author’s patients. Pronation was quantified on WBCT scans using 3D reconstructions as described by Campbell et al. (FAI 2018). Crista volume was determined using a line drawn to connect the nadir of each sulcus on either side of the intersesamoidal crista in each slice of the WBCT image (Figure 1). Sesamoid station was also quantified on WBCT scans using the established four point categorization. A linear regression was performed to determine if the volume of the crista was associated with the pronation angle. The sesamoid station was simplified into two categories - mild medial sesamoid subluxation (less than 50% of the medial sesamoid was lateral to the nadir of the crista) and severe medial sesamoid subluxation - and crista volume between these two groups was compared using a t-test. Results: The regression of crista volume against first metatarsal pronation angle did not show statistical significance (P=0.94, r2=0.03). The mean crista volume in the mild medial sesamoid subluxation group was 156(+-47, range 72 - 231)mm3. The mean crista volume in severe medial sesamoid subluxation was 95 (SD 39, range 35 - 160) mm3. The t-test using simplified sesamoid station to compare crista volumes found that the mean crista volume in the mild medial sesamoid subluxation group was statistically significantly greater the than the mean crista volume in the severe sesamoid subluxation group (P=0.01). Conclusion: In HV, it has been hypothesized that the medial sesamoid erodes the crista resulting in arthritis. This is often overlooked as a source of pain in these patients. Our study found that pronation of the first metatarsal was not correlated with crista volume suggesting that pronation does not affect erosion of the crista. Instead, our results are the first to demonstrate that medial sesamoid subluxation as determined from sesamoid station results in erosion of the crista. This supports the hypothesis that sesamoid subluxation, arthritis, and crista erosion are important components of the HV deformity.

Category: Hindfoot; Midfoot/Forefoot Introduction/Purpose: Surgical correction of the collapsing flatfoot deformity has been well studied in the literature, with the average patient being a female in her 50s. While reconstruction of the flexible, symptomatic flatfoot in children and adolescents has been described, assessment of outcomes across age groups is limited. Therefore, the purpose of our study is to compare the clinical and radiographic outcomes in younger patients 30 years or less undergoing flatfoot reconstruction with that of older patients. In addition, the procedures performed for reconstruction and the incidence of subsequent reoperations were compared between the two groups. Methods: Ninety-four feet (51 left, 43 right) in 87 patients who underwent reconstruction for flexible collapsing flatfoot deformity were divided into 2 groups based on age: 30 years (n=72). Exclusion criteria included tarsal coalition or neuromuscular disease. Average age and BMI was 20.8 years (range, 13 to 30) and 26.8 (range, 18 to 38) in the younger cohort, and 57.5 years (range, 35 to 81) and 29.8 (range, 18 to 46) in the older cohort. Preoperative and minimum 2-year postoperative PROMIS scores were compared. Average follow-up was 30.6 and 27 months in the younger and older cohorts, respectively. We assessed five radiographic parameters both preoperatively and postoperatively, including talonavicular (TN) coverage angle, lateral talo-first metatarsal angle (Meary’s), lateral talocalcaneal angle, calcaneal pitch, and hindfoot moment arm (HMA). Operative reports and hospital records were reviewed to compare procedures performed for reconstruction as well as subsequent reoperations. Results: Younger patients demonstrated significant preoperative to postoperative improvements in Physical Function (p=0.01), Pain Interference (pConclusion: While the approach to surgical correction of younger patients with symptomatic, collapsing flatfoot deformity is similar to that of older adult patients, our data suggest that age may play a role in clinical outcomes, procedures indicated, and subsequent corrective reoperations. These findings point towards the efficacy of surgical correction in addressing this symptomatic pathology at a younger age. [Table: see text][Table: see text]

Background:Operative correction of flatfoot deformity has been well studied in the older population. There is a subset of younger patients without congenital foot deformity that also develop a collapsing flatfoot. However, assessment of outcomes across age groups is limited, especially in the young demographic. The purpose of our study was to compare operative outcomes of flatfoot reconstruction between these 2 age groups.Methods:Seventy-six feet (41 left, 35 right) in 71 patients who underwent flexible flatfoot reconstruction were divided into 2 groups based on age: ≤30 years (n = 22) and >30 years (n = 54). Exclusion criteria included congenital causes of flatfoot (tarsal coalition, vertical talus, overcorrected clubfoot). Average age was 20.8 years (range, 14-30) and 55.4 years (range, 35-74) in the younger and older cohorts, respectively. Preoperative and minimum 2-year postoperative Patient-Reported Outcomes Measurement Information Systems (PROMIS) scores were compared. Five radiographic parameters were assessed pre- and postoperatively: talonavicular coverage angle, lateral talo–first metatarsal angle, lateral talocalcaneal angle, calcaneal pitch, and hindfoot moment arm. Procedures performed and incidence of minor (removal of symptomatic hardware) and major (revision) reoperations were compared.Results:Younger patients were less likely to undergo flexor digitorum longus transfer, first tarsometatarsal fusion, spring ligament repair, and posterior tibial tendon repair (all P < .05). Both younger and older cohorts demonstrated significant improvement in multiple PROMIS domains at an average follow-up of 30.6 (range, 24-44) and 26.8 (range, 24-45) months, respectively ( P = .07). Younger patients demonstrated significantly higher pre- and postoperative Physical Function (mean difference postoperatively, 4.6; 95% confidence interval, 1.5-7.8; P = .03). There were no differences in radiographic parameters postoperatively. There were 8 (36.4%) reoperations (all minor) in the younger group, and 21 (38.9%) reoperations (6 major, 15 minor) in the older group ( P = .84).Conclusion:Our data suggest that age may play a role in clinical outcomes, procedures indicated, and subsequent corrective reoperations. Younger patients maintained greater physical function with comparable radiographic correction, with less frequent indication for tendon transfers, arthrodesis, and additional corrective surgeries.Level of Evidence:Level III, retrospective comparative study.

Background: Residual supination of the midfoot during reconstruction of the stage II adult-acquired flatfoot deformity (AAFD) is often addressed with a medial cuneiform (Cotton) osteotomy after adequate correction of the hindfoot valgus deformity. The purpose of this study was to determine if there was a correlation between postoperative alignment of the medial cuneiform and patient-reported outcomes. Methods: Sixty-three feet in 61 patients with stage II AAFD who underwent a Cotton osteotomy as part of a flatfoot reconstruction were included in the study. Radiographic angles were measured on weightbearing lateral radiographs at a minimum of 40 weeks postoperatively. Pearson’s correlation analysis was used to determine if there was an association between postoperative radiographic angles and Foot and Ankle Outcome Score (FAOS) at a minimum of 24 months postoperatively. Patients were also divided into mild plantarflexion (cuneiform articular angle [CAA] ≥–2 degrees) and moderate plantarflexion (CAA Results: Postoperative CAA was significantly positively correlated with the postoperative FAOS symptoms ( r = .27, P = .03), daily activities ( r = .29, P = .02), sports activities ( r = .26, P = .048), and quality of life ( r = .28, P = .02) subscales. Patients in the mild plantarflexion group had statistically and clinically better outcomes compared with the moderate plantarflexion group in the FAOS symptoms ( P = .04), daily activities ( P = .04), and sports activities ( P = .01) subscales. Conclusions: Our study suggests that the surgeon should avoid excessive plantarflexion of the medial cuneiform and use the Cotton osteotomy judiciously as part of a flatfoot reconstruction for stage II AAFD. Level of Evidence: Level III, comparative series.

32 Background: Ra-223 is a targeted alpha therapy that showed a survival advantage and favorable safety profile in the phase 3 ALSYMPCA trial in pts with mCRPC. REASSURE (NCT02141438) is evaluating the long-term safety of Ra-223 in routine clinical practice in pts with mCRPC over a 7-year follow-up period. Methods: In this global, prospective, single-arm, observational study, the second prespecified interim analysis (data cut-off March 2019) evaluated safety and clinical outcomes of Ra-223 in pts with mCRPC. Primary outcome measures were incidence of second primary malignancies (SPM), bone marrow suppression and short- and long-term safety in pts who had ≥1 Ra-223 dose. Secondary outcomes included overall survival (OS). Results: For 1465 pts in the safety analysis, median follow up was 11.5 months. Median PSA (n=1053), ALP (n=1048), and LDH (n=555) levels at baseline were 59 ng/mL, 135 U/L, and 269 U/L, respectively. 81% of pts had bone metastases only at baseline; 19% of pts had other metastatic sites, mostly in the lymph nodes. 19% of pts had 20 lesions but not a superscan, and 6% had a superscan. 45%, 38%, 37%, 9%, and 8% of pts received prior abiraterone, docetaxel, enzalutamide, cabazitaxel, or sipuleucel-T as prior therapies, respectively. Median number of Ra-223 doses received was 6; 67% of pts had ≥5 doses. SPM occurred in 1% of pts. The most common treatment-emergent drug-related adverse event (AE) of any grade was diarrhea (11%). 10% of pts had a bone-associated event, 5% had fractures, and 15% had a hematological AE. Median OS was 15.6 months (95% CI 14.6–16.5). Conclusions: In REASSURE, there was a low incidence of SPM, bone fractures, and bone marrow suppression after Ra-223 treatment, with no new AEs identified. This study confirms that in routine clinical practice, Ra-223 AE rates were low, and pts generally received ≥5 doses. Clinical trial information: NCT02141438. [Table: see text]

Background: Reconstruction of the stage II adult-acquired flatfoot deformity (AAFD) often requires the use of multiple osteotomies and soft tissue procedures that may not heal well in older patients. The purpose of our study was to determine whether patients older than 65 years with stage II AAFD had inferior clinical outcomes or an increased number of subsequent surgical procedures after flatfoot reconstruction when compared with younger patients. Methods: One-hundred forty consecutive feet (70 right, 70 left) with stage II AAFD in 137 patients were divided into 3 groups based on age: younger than 45 years (young; n = 21), 45 to 65 years (middle-aged; n = 87), and 65 years and older (older; n = 32). Preoperative and postoperative Foot and Ankle Outcome Scores (FAOSs) at a minimum of 2 years were compared. Hospital records were reviewed to determine if patients underwent a subsequent procedure postoperatively. Results: Patients in the older group did not demonstrate any differences in changes in FAOS subscales compared with patients in the young and middle-aged groups (all P > .15). The older group had significant preoperative to postoperative improvements in all the FAOS subgroups ( P < .01). In addition, patients in the older group were not more likely to undergo a subsequent surgery than were the younger patients (all P > .10). Conclusions: Our study found that patients older than 65 years with stage II AAFD have improvements in patient-reported outcomes and rates of revision surgery after surgical reconstruction that were not significantly different than those of younger patients. Level of Evidence: Therapeutic Level III, comparative series.

Background: Few authors have directly compared multiple types of lateralizing calcaneal osteotomies (LCOs) in terms of their ability to achieve deformity correction. The aim of this research was to use a digital model of a varus hindfoot to compare 4 different LCOs in terms of deformity correction and amount of tuberosity lateralization required. The authors hypothesis was that osteotomies involving a wedge resection would achieve greater correction with less lateralization. Methods: A weightbearing computed tomographic scan of a patient with a varus hindfoot deformity was used to construct a 3-dimensional digital model of the hindfoot, preserving weightbearing alignment. Four different LCOs were modeled: a standard oblique osteotomy, a Dwyer osteotomy, a modified Dwyer osteotomy involving lateralization in addition to wedge resection, and a Malerba Z-type osteotomy with wedge resection and lateralization. Incremental corrections were performed with each osteotomy type, and amount of correction was assessed with a vertical hindfoot angle and measurement of the lateral translation of the most inferior aspect of the calcaneus. Calcaneal length and osteotomy contact surface area were also measured. Results: The modified Dwyer osteotomy led to the greatest improvements in the vertical hindfoot angle and lateral translation, followed by the Malerba osteotomy. The standard and Malerba osteotomies allowed the most preservation of calcaneal length; the Malerba and Dwyer osteotomies had the greatest contact surface area. Conclusion: LCOs that involve wedge resection as well as lateralization were able to achieve the greatest correction of hindfoot varus. Clinical Relevance: For the surgical treatment of cavovarus foot deformities, osteotomies with wedge resection in addition to lateralization enable more powerful correction.

Much information technology has been implemented into cars over the last years. The HMI for these new applications has to comply with several requirements for automotive HMI. The purpose of the current article is to show which standards, technical specifications and technical reports have been developed in the International Standard Organisation (ISO) in the field of design rules and methods for cognitive HMI. It is an updated version of (Heinrich, 2012).

Positron emission tomography (PET) is one of the most rapidly growing areas of medical imaging for cancer research. The principal goal of PET imaging is to visualize, characterize, and measure biological processes at the molecular and cellular levels in living subjects using non-invasive procedures. Taking advantage of the traditional diagnostic imaging techniques, PET imaging introduces positron-emitting probes to determine the expression of indicative molecular targets at different stages of cancer progression. As a key component of PET technique, an appropriate imaging probe must be able to specifically reach the target of interest in vivo while retaining in the target within reasonable time to be detected. Over the last decade, numerous target-specific PET probes have been developed and evaluated in preclinical and clinical studies. This review provides an overview of recent advances made in PET imaging of cancer biology with a focus on the best-studied biological targets. The trends in developing future PET imaging probes are also discussed.

Background: No studies investigating the effect of the midfoot (talonavicular joint) position on clinical outcomes following flatfoot reconstruction have been performed. The purpose of our study was to determine whether a postoperative abducted or adducted forefoot alignment, as determined from anteroposterior (AP) radiographs, was associated with a difference in outcomes using the Foot and Ankle Outcome Score (FAOS). Methods: Midfoot abduction was defined on postoperative AP radiographs, evaluated at a mean of 1.9 years in 55 patients from the authors’ institution who underwent flatfoot reconstruction for a stage II adult acquired flatfoot deformity (AAFD), as a lateral incongruency angle greater than 5 degrees, a talonavicular uncoverage angle greater than 8 degrees, and a talo–first metatarsal angle greater than 8 degrees based on previously reported measurements. Patients with 2 or more measurements in the abduction category were classified as the abduction group (n = 30); those with 1 or fewer measurements in the abduction category were placed in the adduction group (n = 25). The preoperative and postoperative FAOS values with a mean follow-up of 3.1 years were compared using Wilcoxon rank-sum tests. Results: Patients corrected to a position of adduction showed significantly lower improvement in the FAOS daily activities ( P = .012) and quality of life subscales ( P = .046). The mean improvement in subscale scores for the adducted group was lower for pain ( P = .052) and sports activities ( P = .085) but did not reach statistical significance. No significant difference in the FAOS symptoms subscale ( P = .372) between groups was found. Conclusion: Correction of the talonavicular joint to a position of adduction following a stage II AAFD was associated with decreased patient outcomes in daily activities and quality of life compared with an abducted position. These results suggest that overcorrection to a position of midfoot adduction leads to a lesser amount of individual patient improvement in reconstruction of a stage II AAFD. Level of Evidence: Level III, comparative series.

Expressed by Fitts in 1954, there is an inverse relationship between movement time and target size and/or the distance between the participant and a target; smaller and further away targets require longer movement times than larger, closer targets. Here, the applicability of Fitts’ law to an in-vehicle, dual-task setting is under investigation. In the current experiment, different target sizes and spaces between target and non-target elements (target-element space), were investigated in simulated driving and non-driving scenarios in two age groups (18 – 35 and 45 – 65 years old). The aim of this experiment was to investigate whether target size and target-element space (i.e., the space between targets and non-targets) would have an effect on the mean movement times of younger and older participants for driving and non-driving conditions. Participants pointed to and touched targets on a smartphone touch screen in a vehicle mock-up. Movement times were recorded while concurrently performing a simulated driving task (dual-task condition) and while performing just the pointing task (single task condition). Errors were defined and are presented. Mean movement times in the dual-task condition were significantly faster than in the single task condition. Additionally, in line with Fitts’ law, in-vehicle movement time decreased as a function of target size. Elements that had the most target-element space were moved to most quickly, however, the medium and small spaces did not differ. Differences between the two age groups were not found.

Introduction:64Cu-BaBaSar-RGD2 is a positron emission radiotracer taken up by integrin αvβ3, which is overexpressed in many malignancies. The aim of this study was to evaluate the biodistribution of 64Cu-BaBaSar-RGD2 in a non-human primate with positron emission tomography (PET) and to estimate the absorbed doses in major organs for human.Materials and Methods: Whole-body PET imaging was done on a Siemens Biograph scanner with a male macaque monkey. After an i.v. injection of 13.1–19.7 MBq/kg of 64Cu-BaBaSar-RGD2, whole body scan was collected for a total duration of 180 min. Attenuation and scatter corrections were applied to reconstructions of the whole-body emission scan. After image reconstruction, three-dimensional volumes of interest (VOI) were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves (TACs) for each VOI were obtained, and residence times of each organ were calculated by integration of the time-activity curves. Human absorbed doses were estimated using the standard human model in OLINDA/EXM software.Results: Injection of 64Cu-BaBaSar-RGD2 was well-tolerated in the macaque monkey, with no serious tracer-related adverse events observed. 64Cu-BaBaSar-RGD2 was cleared rapidly from the blood pool, with a 12.1-min biological half-life. Increased 64Cu-BaBaSar-RGD2 uptake was observed in the kidneys, and bladder, with mean percentage injected dose (ID%) values at 1 h after injection ~35.50 ± 6.47 and 36.89 ± 5.48, respectively. The calculated effective dose was 15.30 ± 2.21 μSv/MBq, and the kidneys had the highest absorbed dose at 108.43 ± 16.41 μGy/MBq using the non-voiding model. For an injected activity of 925 MBq 64Cu for human, the effective dose would be 14.2 ± 2.1 mSv.Discussion: Due to the limited availability of the primates, we evaluated 64Cu-BaBaSar-RGD2 in the same monkey using three imaging sessions. Measured absorbed doses and effective doses of 64Cu-BaBaSar-RGD2 are comparable to other reported RGD-derived radiopharmaceuticals labeled with 64Cu and 18F. Therefore, 64Cu-BaBaSar-RGD2 can be safely injected into humans for studying integrin αvβ3 expression non-invasively.