Friction Burns: Defining the Rub of Road Rash After Motorcycle Trauma.

There is a paucity of literature on friction burn epidemiology, injury characteristics, and management after trauma. This study aims to characterize friction burns resulting from motorcycle accidents, evaluate the role of specialized burn surgery teams, and assess the need for operative intervention. The trauma registry of a Level 1 Trauma Center was queried for all admissions after motorcycle accidents between January 2018 and December 2022. Patients were included if there was an external cause of injury code for an abrasion. Chart review was conducted to confirm a road rash injury, identify burn consultation, wound care recommendations, need for operating room (OR) procedure and skin grafting, and outcomes. Among the 810 patients meeting inclusion criteria, the cohort was 92% male, 46% Hispanic, with median age of 33 (IQR 26-44), and median ISS 8 (IQR 5-14). The extremities were most affected by friction burn followed by the abdomen, thorax, and face. Burn surgery was consulted in 7% (n=57) of cases which had a median TBSA of 4% (IQR 2-6%); 23% (n=13) of these patients underwent excision in the OR, 16% (n=9) required autografting, and 61% (n=35) were referred for burn follow-up on discharge. On multivariable regression, consults to burn were more likely in female patients (OR 3.40, p=0.002) and those with involvement of the upper extremity, abdomen, or thorax. Friction burns are common after motorcycle-related trauma. Local wound care is sufficient for a vast majority of these injuries and the need for specialized burn care and operative intervention is rare.

Obesity-associated microbiomes instigate visceral adipose tissue inflammation by recruitment of distinct neutrophils.

Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.

Lateral line system diversification during the early stages of ecological speciation in cichlid fish.

BACKGROUND: The mechanosensory lateral line system is an important sensory modality in fishes, informing multiple behaviours related to survival including finding food and navigating in dark environments. Given its ecological importance, we may expect lateral line morphology to be under disruptive selection early in the ecological speciation process. Here we quantify the lateral line system morphology of two ecomorphs of the cichlid fish Astatotilapia calliptera in crater Lake Masoko that have diverged from common ancestry within the past 1,000 years. RESULTS: Based on geometric morphometric analyses of CT scans, we show that the zooplanktivorous benthic ecomorph that dominates the deeper waters of the lake has large cranial lateral line canal pores, relative to those of the nearshore invertebrate-feeding littoral ecomorph found in the shallower waters. In contrast, fluorescence imaging revealed no evidence for divergence between ecomorphs in the number of either superficial or canal neuromasts. We illustrate the magnitude of the variation we observe in Lake Masoko A. calliptera in the context of the neighbouring Lake Malawi mega-radiation that comprises over 700 species. CONCLUSIONS: These results provide the first evidence of divergence in this often-overlooked sensory modality in the early stages of ecological speciation, suggesting that it may have a role in the broader adaptive radiation process.

Predictors of direct oral anticoagulant concentrations in the trauma population.

Introduction: Direct oral anticoagulant (DOAC) use is becoming more prevalent in patients presenting after trauma. We sought to identify the prevalence and predictors of subtherapeutic and therapeutic DOAC concentrations and hypothesized that increased anti-Xa levels would correlate with increased risk of bleeding and other poor outcomes. Methods: A retrospective cohort study of all trauma patients on apixaban or rivaroxaban admitted to a level 1 trauma center between January 2015 and July 2021 was performed. Patients were excluded if they did not have a DOAC-specific anti-Xa level at presentation. Therapeutic levels were defined as an anti-Xa of 50 ng/mL to 250 ng/mL for rivaroxaban and 75 ng/mL to 250 ng/mL for apixaban. Linear regression was used to identify correlations between study variables and anti-Xa level, and binomial logistic regression was used to test the association of anti-Xa level with outcomes. Results: There were 364 trauma patients admitted during the study period who were documented to be on apixaban or rivaroxaban. Of these, 245 patients had anti-Xa levels measured at admission. The population was 53% woman, with median age of 78 years, and median Injury Severity Score of 5. In total, 39% of patients had therapeutic and 20% had supratherapeutic anti-Xa levels. Female sex, increased age, decreased height and weight, and lower estimated creatinine clearance were associated with higher anti-Xa levels at admission. There was no correlation between anti-Xa level and the need for transfusion or reversal agent administration, admission diagnosis of intracranial hemorrhage (ICH), progression of ICH, hospital length of stay, or mortality. Conclusions: Anti-Xa levels in trauma patients on DOACs vary widely; female patients who are older, smaller, and have decreased kidney function present with higher DOAC-specific anti-Xa levels after trauma. We were unable to detect an association between anti-Xa levels and clinical outcomes. Level of evidence: III-Prognostic and Epidemiological.

Case report: repair of eventration of the diaphragm in an octogenarian.

Eventration of the diaphragm is a cephalad displacement of the diaphragm because of congenital or acquired causes. The diaphragm maintains its anatomical continuity and normal attachments. It may be partial or complete and unilateral or bilateral. Most adult presentations are asymptomatic, but patients may present with respiratory, gastrointestinal, or cardiac symptoms. Surgical repair is indicated in the symptomatic patient with the most common being diaphragmatic plication. We present surgical repair of a symptomatic left diaphragmatic eventration in an octogenarian.

Communication profiles and sport experiences of collegiate track and field athletes.

OBJECTIVES: Athletes often communicate with one another and exchange information, attitudes, and feelings that can influence their sport experiences. In an effort to better understand the sport communication context, the purpose of the current study was to (a) describe communication profiles of athletes (b) examine potential predictors (i.e., team identity, sex) of profile membership, and (c) examine the salience of these profiles by assessing profile group differences on athletes' perceptions of burnout, engagement, satisfaction, and enjoyment. DESIGN: Cross-sectional survey-based study. METHOD: Collegiate track and field athletes (N = 219) completed measures of demographic information, team communication, team identity, burnout, engagement, enjoyment, and satisfaction. Communication profiles were examined using latent profile analysis. Using the three-step method in Mplus, possible prediction of profile membership and profile differences in perceptions of sport experiences were examined. RESULTS: Three profiles emerged: the Less Effective Communicators, the Supportive Communicators, and the Functional Communicators. Athletes with greater team identity were more likely to be in the Supportive Communicators profile (p < 0.001), male participants were more likely to be in the Functional Communicators profile (p < 0.05) than the other profiles, and female participants were less likely to be in the Less Effective Communicators profile than the Supportive Communicators profile (p < 0.05). The Less Effective Communicators had greater perceptions of burnout (ps < 0.01) and lower perceptions of engagement (p < 0.01 and p < 0.05), satisfaction (p < 0.001 and p = 0.001), and enjoyment (p < 0.001 and p < 0.05) than the Supportive and Functional Communicators. Supportive Communicators had greater satisfaction (p < 0.001) and enjoyment (p < 0.001) than the Functional Communicators. CONCLUSIONS: Different profiles of communication in track and field athletes may have implications for athletes' sport experiences and warrant continued study.

A scoping review of programme specific mammographic breast density related guidelines and practices within breast screening programmes.

Introduction: High mammographic breast density (MBD) is an independent breast cancer risk factor. In organised breast screening settings, discussions are ongoing regarding the optimal clinical role of MBD to help guide screening decisions. The aim of this scoping review was to provide an overview of current practices incorporating MBD within population-based breast screening programmes and from professional organisations internationally. Methods: This scoping review was conducted in accordance with the framework proposed by the Joanna Briggs Institute. The electronic databases, MEDLINE (PubMed), EMBASE, CINAHL Plus, Scopus, and Web of Science were systematically searched. Grey literature sources, websites of international breast screening programmes, and relevant government organisations were searched to identify further relevant literature. Data from identified materials were extracted and presented as a narrative summary. Results: The search identified 78 relevant documents. Documents were identified for breast screening programmes in 18 countries relating to screening intervals for women with dense breasts, MBD measurement, reporting, notification, and guiding supplemental screening. Documents were identified from 18 international professional organisations with the majority of material relating to supplemental screening guidance for women with dense breasts. Key factors collated during the data extraction process as relevant considerations for MBD practices included the evidence base needed to inform decision-making processes and resources (healthcare system costs, radiology equipment, and workforce planning). Conclusions: This scoping review summarises current practices and guidelines incorporating MBD in international population-based breast screening settings and highlights the absence of consensus between organised breast screening programmes incorporating MBD in current breast screening protocols.

Inhalation Injury: Which Providers Can Assess the Need for Intubation?

Previous studies have suggested that many burn patients undergo unnecessary intubation due to concern for inhalation injury. We hypothesized that burn surgeons would intubate burn patients at a lower rate than non-burn acute care surgeons (ACSs). We performed a retrospective cohort study of all patients admitted to an American Burn Association-verified burn center who presented emergently following burn injury from June 2015 to December 2021. Patients excluded include polytrauma patients, isolated friction burns, and patients intubated prior to hospital arrival. Our primary outcome was intubation rates between burn and non-burn ACSs. 388 patients met inclusion criteria. 240 (62%) patients were evaluated by a burn provider and 148 (38%) were evaluated by a non-burn provider; the groups were well-matched. In total, 73 (19%) of patients underwent intubation. There was no difference in the rate of emergent intubation, diagnosis of inhalation injury on bronchoscopy, time to extubation, or incidence of extubation within 48 hours between burn and non-burn ACSs. We found no difference between burn and non-burn ACSs in the airway evaluation and management of burn patients. Surgical providers with acute care surgery backgrounds and Advanced Trauma Life Support training are well-equipped for initial airway management in burn patients. Further studies should seek to compare other types of provider groups to identify opportunities for intervention and education in preventing unnecessary intubations.

Cross-Border Antibiotic Resistance Patterns in Burn Patients.

Background: Antimicrobial resistance (AMR) is a growing problem worldwide, with differences in regional resistance patterns partially driven by local variance in antibiotic stewardship. Trauma patients transferring from Mexico have more AMR than those injured in the United States; we hypothesized a similar pattern would be present for burn patients. Patients and Methods: The registry of an American Burn Association (ABA)-verified burn center was queried for all admissions for burn injury January 2015 through December 2019 with hospital length-of-stay (LOS) longer than seven days. Patients were divided into two groups based upon burn location: United States (USA) or Mexico (MEX). All bacterial infections were analyzed. Results: A total of 73 MEX and 826 USA patients were included. Patients had a similar mean age (40.4 years MEX vs. 42.2 USA) and gender distribution (69.6% male vs. 64.4%). The MEX patients had larger median percent total body surface area burned (%TBSA; 11.1% vs. 4.3%; p ≤ 0.001) and longer hospital LOS (18.0 vs. 13.0 days; p = 0.028). The MEX patients more often had respiratory infections (16.4% vs. 7.4%; p = 0.046), whereas rates of other infections were similar. The MEX patients had higher rates of any resistant organism (47.2% of organisms MEX vs. 28.1% USA; p = 0.013), and were more likely to have resistant infections on univariable analysis; however, on multivariable analysis country of burn was no longer significant. Conclusions: Antimicrobial resistance is more common in burn patients initially burned in Mexico than those burned in the United States, but location was not a predictor of resistance compared to other traditional burn-related factors. Continuing to monitor for AMR regardless of country of burn remains critical.

Lateral line morphology, sensory perception and collective behaviour in African cichlid fish.

The lateral line system of fishes provides cues for collective behaviour, such as shoaling, but it remains unclear how anatomical lateral line variation leads to behavioural differences among species. Here we studied associations between lateral line morphology and collective behaviour using two morphologically divergent species and their second-generation hybrids. We identify collective behaviours associated with variation in canal and superficial lateral line morphology, with closer proximities to neighbouring fish associated with larger canal pore sizes and fewer superficial neuromasts. A mechanistic understanding of the observed associations was provided by hydrodynamic modelling of an artificial lateral line sensor, which showed that simulated canal-based neuromasts were less susceptible to saturation during unidirectional movement than simulated superficial neuromasts, while increasing the canal pore size of the simulated lateral line sensor elevated sensitivity to vortices shed by neighbouring fish. Our results propose a mechanism behind lateral line flow sensing during collective behaviour in fishes.

One size does not fit all: Sex bias in pharmacologic venous thromboembolism prophylaxis.

BACKGROUND: The optimal enoxaparin dosing strategy to achieve venous thromboembolism (VTE) prophylaxis in trauma patients remains unclear. Current dosing guidelines often include weight, age, and renal function but still fail to achieve appropriate prophylactic anti-Xa levels in many patients. We hypothesized that additional patient factors influence anti-Xa response to enoxaparin in trauma patients. METHODS: This is a retrospective review of patients admitted to a Level 1 trauma center for ≥4 days from July 2015 to September 2020, who received enoxaparin VTE prophylaxis per protocol (50-59 kg, 30 mg/dose; 60-99 kg, 40 mg/dose; ≥100 kg, 50 mg/dose; all doses every 12 hours) and had an appropriately timed peak anti-Xa level. Multivariate regression was performed to identify independent predictors of prophylactic anti-Xa levels (0.2-0.4 IU/mL) upon first measurement. RESULTS: The cohort (N = 1,435) was 76.4% male, with a mean ± SD age of 49.9 ± 20.0 years and a mean ± SD weight of 82.5 ± 20.2 kg (males, 85.2 kg; females, 73.7 kg; p <0.001). Overall, 68.6% of patients (n = 984) had a prophylactic anti-Xa level on first assessment (69.6% of males, 65.1% of females). Males were more likely to have a subprophylactic level than females (22.1% vs. 8.0%, p <0.001), whereas females were more likely to have supraprophylactic levels than males (26.9% vs. 8.3%, p < 0.001). When controlling for creatinine clearance, anti-Xa level was independently associated with dose-to-weight ratio (odds ratio, 0.191 for 0.5 mg/kg; p < 0.001; confidence interval, 0.151-0.230) and female sex (odds ratio, 0.060; p < 0.001; confidence interval, 0.047-0.072). Weight and age were not significant when controlling for the other factors. CONCLUSION: Male patients have a decreased anti-Xa response to enoxaparin when compared with female patients, leading to a greater incidence of subprophylactic anti-Xa levels in male patients at all dose-to-weight ratios. To improve the accuracy of VTE chemoprophylaxis, sex should be considered as a variable in enoxaparin dosing models. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Small bowel obstruction in older patients: challenges in surgical management.

BACKGROUND: Small bowel obstruction (SBO) is a common disease affecting all segments of the population, including the frail elderly. Recent retrospective data suggest that earlier operative intervention may decrease morbidity. However, management decisions are influenced by surgical outcomes. Our goal was to determine the current surgical management of SBO in older patients with particular attention to frailty and the timing of surgery. STUDY DESIGN: A retrospective review of patients over the age of 65 with a diagnosis of bowel obstruction (ICD-10 K56*) using the 2016 National Inpatient Sample (NIS). Demographics included age, race, insurance status, medical comorbidities, and median household income by zip code. Elixhauser comorbidities were used to derive a previously published frailty score using the NIS dataset. Outcomes included time to operation, mortality, discharge disposition, and hospital length of stay. Associations between demographics, frailty, timing of surgery, and outcomes were determined. RESULTS: 264,670 patients were included. Nine percent of the cohort was frail; overall mortality was 5.7%. Frail had 1.82 increased odds of mortality (95% CI 1.64-2.03). Hospital LOS was 1.6 times as long for frail patients; a quarter of the frail were discharged home. Frail patients waited longer for surgery (3.58 days vs 2.44 days; p < 0.001). Patients transferred from another facility had increased mortality (aOR 1.58; 95% CI 1.36-1.83). There was an increasing mortality associated with a delay in surgery. CONCLUSION: Patients with frailty and SBO have higher mortality, more frequent discharge to dependent living, longer hospital length of stay, and longer wait to operative intervention. Mortality is also associated with male gender, black race, transfer status from another facility, self-pay status, and low household income. Every day in delay in surgical intervention for those who underwent operations led to higher mortality. If meeting operative indications, older patients with bowel obstruction have a higher chance of survival if they undergo surgery earlier.

Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination.

PURPOSE: Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136). METHODS: Eligible patients with unresectable stage III-IV melanoma with confirmed progressive disease (PD) within 12 weeks of the last dose of a PD-1/L1 inhibitor given alone or with other therapies, including cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4) inhibitors, received lenvatinib 20 mg orally once daily plus ≤ 35 doses of pembrolizumab 200 mg intravenously once every 3 weeks until PD or unacceptable toxicity. The primary end point was objective response rate (ORR) per RECIST, version 1.1, by independent central review. RESULTS: A total of 103 patients were enrolled and treated. The median study follow-up was 15.3 months. ORR in the total population was 21.4% (95% CI, 13.9 to 30.5), with three (2.9%) complete responses and 19 (18.4%) partial responses. The median duration of response was 8.3 months (range, 3.2-15.9+). ORR was 33.3% in the 30 patients with PD on prior anti-PD-1 plus anti-CTLA-4 therapy. The median progression-free survival and overall survival in the total population were 4.2 months (95% CI, 3.8 to 7.1) and 14.0 months (95% CI, 10.8 to not reached), respectively. Grade 3-5 treatment-related adverse events occurred in 47 (45.6%) patients, most commonly hypertension (21.4%); one patient died from a treatment-related event (decreased platelet count). CONCLUSION: Lenvatinib plus pembrolizumab provides clinically meaningful, durable responses in patients with advanced melanoma with confirmed PD on prior PD-1/L1 inhibitor-based therapy, including those with PD on anti-PD-1 plus anti-CTLA-4 therapy. The safety profile was as expected. These data support lenvatinib plus pembrolizumab as a potential regimen for this population of high unmet need.

Developing and testing the ExerciseGuide UK website for people with lung cancer: reflections on the added value of patient and public involvement within a doctoral degree.

BACKGROUND: Lung cancer has one of the highest incidence and mortality rates worldwide. Physical activity can provide those diagnosed with lung cancer with several physical and psychological benefits. However, the examination of digitally delivered physical activity to those with lung cancer is not as researched as other common cancers. Often, those diagnosed with lung cancer are older adults (65 years or older). Older adults are often wrongly assumed to lack digital skills, interest, and not engage with digital technology regularly. Although individuals are interested, would involving older people in designing of websites and apps result in better engagement? MAIN BODY: In this article, the authors discuss the process of adapting a digital platform with a patient and public involvement group to provide those who have received a lung cancer diagnosis with a tailored physical activity program and health educational modules. We discuss the influence of recurrent patient and public involvement on the study, the patient and public involvement members, and the doctoral researcher. CONCLUSION: Working with a patient and public involvement group over several months, especially potential users of a digital intervention, may enhance its relevance, accessibility, and usability. By engaging with patients, family, or caregivers for someone with lung cancer, the doctoral student gained insight into the needs of the study population and what to consider during development. All group members expressed their interest and enjoyment in their involvement, and several are now active members of a wider patient and public involvement network.

This commentary describes how patient public involvement has been used to adapt a website called ExerciseGuide UK. This website provides a personalised physical activity program and education to those diagnosed with lung cancer. The programme is altered to allow for each patient's capabilities. Reflections on how the study affected both the researcher and the PPI members are discussed. The commentary gives the patient and public involvement members a voice in their involvement experience. It highlights the difference that their sustained involvement made to the study, the doctoral researcher, and those who were involved. Globally, lung cancer is a leading cause of cancer-related death and remains one of the most common types of cancer. Digital technology, such as websites, mobile applications, and smart wearable devices (e.g., Apple Watch and Fitbits), have increasingly been used in health research over the last few decades. Since the beginning of the COVID-19 pandemic in 2020, research into digital technology has increased rapidly. Individuals diagnosed with lung cancer may experience a large number of physically and emotionally limiting symptoms, such as a higher risk of severe illness due to infections. With the large symptom burden they experience, digital technology may provide alternative and more accessible methods which can be altered to suit and help their specific needs. The patient and public involvement group members had all either been diagnosed with lung cancer, cared for someone with lung cancer, or experienced lung cancer in their family.

Management of choledocholithiasis in the elderly: Same-admission cholecystectomy remains the standard of care.

BACKGROUND: Current guidelines recommend that patients with choledocholithiasis undergo same-admission cholecystectomy. The compliance with this guideline is poor in elderly patients. We hypothesized that elderly patients treated with endoscopic retrograde cholangiopancreatography (ERCP) alone would have higher complication and readmission rates than the patients treated with cholecystectomy. METHODS: The Nationwide Readmissions Database was queried for all patients aged ≥65 years with admission for choledocholithiasis January to June 2016. The patients were divided based on index treatment received: (1) no intervention; (2) ERCP alone; or (3) cholecystectomy. Multivariate analyses identified predictors of cholecystectomy during index admission and of readmissions. RESULTS: A total of 16,121 patients with choledocholithiasis were admitted; 38.4% underwent cholecystectomy, 37.6% endoscopic retrograde cholangiopancreatography alone, and 24.0% no intervention. The patients not receiving a cholecystectomy were more likely to be older, female, have a higher Elixhauser score, do-not-resuscitate status, and at a teaching hospital (all P < .001). Emergency readmissions for recurrent biliary disease were lowest in patients undoing a cholecystectomy (2.2% vs 9.2% endoscopic retrograde cholangiopancreatography and 12.4% no intervention, P < .001), as were readmissions for complications (3.6% vs 5.5% and 7.8%, P < .001). Cholecystectomy reduced rates of readmissions for recurrent disease (odds ratio 0.168, P < .001), for complications (odds ratio 0.540, P < .001), and death during readmission (odds ratio 0.503, P = .007); endoscopic retrograde cholangiopancreatography alone reduced only rates of readmissions. Age was not a predictor of readmission or death. CONCLUSION: Index admission cholecystectomy is associated with a lower risk of readmission for biliary disease or complications, as well as death during readmission, in elderly patients. Age alone is not predictive of outcomes; surgical intervention should be guided by clinical condition, comorbidities, and patient preference.

Intravascular lobular capillary hemangioma of the temporal artery.

Lobular capillary hemangiomas (LCHs) are a common form of benign vascular tumors originating from the skin and subcutaneous tissues. We have described the case of a 47-year-old man who had presented with a 1-month history of a tender swelling to the right temporal region. Biopsy was performed to rule out temporal arteritis and demonstrated a subset of LCH, now formally known as intravascular LCH. We have described the occurrence of a rare subtype of LCH arising from the intravascular wall of the temporal artery. To the best of our knowledge, this is the only reported case of an intravascular LCH in the Caribbean.

The proximity of the N- and C- termini of bovine knob domains enable engineering of target specificity into polypeptide chains.

Cysteine-rich knob domains can be isolated from the ultralong heavy-chain complementarity-determining region (CDR) 3, which are unique to a subset of bovine antibodies, to create antibody fragments of ~4 kDa. Advantageously, the N- and C- termini of these small binding domains are in close proximity, and we propose that this may offer a practical route to engineer extrinsic binding specificity into proteins. To test this, we transplanted knob domains into various loops of rat serum albumin, targeting sites that were distal to the interface with the neonatal Fc receptor. Using knob domains raised against the clinically validated drug target complement component C5, we produced potent inhibitors, which exhibit an extended plasma half-life in vivo via attenuated renal clearance and neonatal Fc receptor-mediated avoidance of lysosomal catabolism. The same approach was also used to modify a Camelid VHH, targeting a framework loop situated at the opposing end of the domain to the CDRs, to produce a small, single-chain bispecific antibody and a dual inhibitor of Complement C3 and C5. This study presents new protein inhibitors of the complement cascade and demonstrates a broadly applicable method to engineer target specificity within polypeptide chains, using bovine knob domains.

Youth violence prevention can be enhanced by geospatial analysis of trauma registry data.

BACKGROUND: Geographic information systems (GIS) have been used to understand relationships between trauma mechanisms, locations, and social determinants for injury prevention. We hypothesized that GIS analysis of trauma center registry data for assault patients aged 14 years to 29 years with census tract data would identify geospatial and structural determinants of youth violence. METHODS: Admissions to a Level I trauma center from 2010 to 2019 were retrospectively reviewed to identify assaults in those 14 years to 29 years. Prisoners were excluded. Home and injury scene addresses were geocoded. Cluster analysis was performed with the Moran I test for spatial autocorrelation. Census tract comparisons were done using American Communities Survey (ACS) data by t-test and linear regression. RESULTS: There were 1,608 admissions, 1,517 (92.4%) had complete addresses and were included in the analysis. Mean age was 23 ± 3.8 years, mean ISS was 7.5 ± 6.2, there were 11 (0.7%) in-hospital deaths. Clusters in six areas of the trauma catchment were identified with a Moran I value of 0.24 ( Z score = 17.4, p < 0.001). Linear regression of American Communities Survey demographics showed predictors of assault were unemployment (odds ratio, 4.5; 95% confidence interval, 2.7-6.4; p < 0.001), Spanish spoken at home (odds ratio, 6.6; 95% confidence interval, 3.4-9.8; p < 0.001) and poverty level (odds ratio, 1.9; 95% confidence interval, 1.1-2.7; p < 0.001). Education level of less than high school diploma, single parent households and race were not significant predictors. CONCLUSION: GIS analysis of registry data can identify high-risk areas for youth violence and correlated social and structural determinants. Violence prevention efforts can be better targeted geographically and socioeconomically with better understanding of these risk factors. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level III.

Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies.

INTRODUCTION: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor that has shown efficacy and manageable safety across multiple cancer types. The recommended starting doses for lenvatinib differ across cancer types and indications based on whether it is used as monotherapy or as combination therapy. AREAS COVERED: This review covers clinical trials that established the dosing paradigm and efficacy of lenvatinib and defined its adverse-event profile as a monotherapy; or in combination with the mTOR inhibitor, everolimus; or the anti-PD-1 antibody, pembrolizumab; and/or chemotherapy. EXPERT OPINION: Lenvatinib has been established as standard-of-care either as a monotherapy or in combination with other anticancer agents for the treatment of radioiodine-refractory differentiated thyroid carcinoma, hepatocellular carcinoma, renal cell carcinoma, and endometrial carcinoma, and is being investigated further across several other tumor types. The dosing and adverse-event management strategies for lenvatinib have been developed through extensive clinical trial experience. Collectively, the data provide the rationale to start lenvatinib at the recommended doses and then interrupt or dose reduce as necessary to achieve required dose intensity for maximized patient benefit. The adverse-event profile of lenvatinib is consistent with that of other tyrosine kinase inhibitors, and clinicians are encouraged to review and adopt relevant symptom-management strategies.

Assessing the Safety and Efficacy of Two Starting Doses of Lenvatinib Plus Everolimus in Patients with Renal Cell Carcinoma: A Randomized Phase 2 Trial.

BACKGROUND: Lenvatinib (18 mg) plus everolimus (5 mg) is approved for patients with advanced renal cell carcinoma (RCC) after one or more prior antiangiogenic therapies. OBJECTIVE: To assess whether a lower starting dose of lenvatinib has comparable efficacy with improved tolerability for patients with advanced RCC treated with lenvatinib plus everolimus. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 2 global trial was conducted in patients with advanced clear cell RCC and disease progression after one prior vascular endothelial growth factor-targeted therapy (prior anti-programmed death-1/programmed death ligand-1 therapy permitted). INTERVENTION: Patients were randomly assigned 1:1 to the 14- or 18-mg lenvatinib starting dose, both in combination with everolimus 5 mg/d. Patients in the 14-mg arm were to be uptitrated to lenvatinib 18 mg at cycle 2, day 1, barring intolerable grade 2 or any grade ≥3 treatment-emergent adverse events (TEAEs) requiring dose reduction occurring in the first 28-d cycle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary efficacy endpoint was investigator-assessed objective response rate (ORR) as of week 24 (ORRwk24); the noninferiority threshold of the 14- versus 18-mg arm was p ≤ 0.045. The primary safety endpoint was the proportion of patients with intolerable grade 2 or any grade ≥3 TEAEs within 24 wk of randomization. RESULTS AND LIMITATIONS: The ORRwk24 for the 14-mg arm (32% [95% confidence interval {CI} 25-39]) was not noninferior to the ORRwk24 in the 18-mg arm (35% [95% CI 27-42]; odds ratio: 0.88; 90% CI 0.59-1.32; p = 0.3). The proportion of intolerable grade 2 or any grade ≥3 TEAEs was similar between the two arms (14 mg, 83% vs 18 mg, 80%; p = 0.5). The secondary endpoints of overall ORR, progression-free survival, and overall survival numerically favored the 18-mg arm. A limitation of this study was that the study design did not allow for a full comparison of progression-free survival between treatment arms. CONCLUSIONS: The study findings support the approved dosing regimen of lenvatinib 18 mg plus everolimus 5 mg daily for patients with advanced RCC. PATIENT SUMMARY: In this report, we examined two doses of lenvatinib (the approved 18-mg dose and a lower dose of 14 mg) in people with advanced renal cell carcinoma to determine whether the lower dose (which was increased to the approved 18-mg dose after the first treatment cycle) could improve safety without affecting efficacy. The results showed that the efficacy of the lower lenvatinib dose (14 mg) was not the same as that of the approved (18 mg) dose, although safety results were similar, so the approved lenvatinib 18-mg dose should still be used.