Correction: The arginine deaminase system plays distinct roles in Borrelia burgdorferi and Borrelia hermsii.

[This corrects the article DOI: 10.1371/journal.ppat.1010370.].

The arginine deaminase system plays distinct roles in Borrelia burgdorferi and Borrelia hermsii.

Borrelia species are amino acid auxotrophs that utilize di- and tri- peptides obtained through their oligopeptide transport system to supply amino acids for replicative growth during their enzootic cycles. However, Borrelia species from both the Lyme disease (LD) and relapsing fever (RF) groups harbor an amino acid transport and catabolism system, the Arginine Deiminase System (ADI), that could potentially augment intracellular L-arginine required for growth. RF spirochetes contain a "complete", four gene ADI (arcA, B, D, and C) while LD spirochetes harbor arcA, B, and sometimes D but lack arcC (encoding carbamate kinase). In this study, we evaluated the role of the ADI system in bacterial survival and virulence and discovered important differences in RF and LD ADIs. Both in vitro and in a murine model of infection, B. hermsii cells significantly reduced extracellular L-arginine levels and that reduction was dependent on arginine deiminase expression. Conversely, B. burgdorferi did not reduce the concentration of L-arginine during in vitro growth experiments nor during infection of the mammalian host, suggesting a fundamental difference in the ability to directly utilize L-arginine compared to B. hermsii. Further experiments using a panel of mutants generated in both B. burgdorferi and B. hermsii, identified important differences in growth characteristics and ADI transcription and protein expression. We also found that the ADI system plays a key role in blood and spleen colonization in RF spirochetes. In this study we have identified divergent metabolic strategies in two closely related human pathogens, that ultimately impacts the host-pathogen interface during infection.

The impact of hospital experience in bariatric surgery on short-term outcomes after minimally invasive esophagectomy: a nationwide analysis.

BACKGROUND: Minimally invasive esophagectomy (MIE) is a technically challenging procedure with a substantial learning curve. Composite volume of upper gastrointestinal (upper GI) procedures for cancer has been previously linked to postoperative outcomes. This study aimed to investigate an association between hospital experience in bariatric surgery and short-term outcomes in MIE. METHOD: Data on esophagectomy patients between 2016 and 2020 were collected from the Dutch Upper Gastrointestinal Cancer Audit, a mandatory nationwide registry. Hospitals were categorized as bariatric or non-bariatric. Multivariable logistic regression investigated short-term postoperative outcomes, adjusting for case mix. RESULTS: Of 3371 patients undergoing esophagectomy in sixteen hospitals, 2450 (72.7%) underwent MIE. Bariatric hospitals (N = 6) accounted for 1057 (43.1%) MIE. Annual volume of bariatric procedures was median 523 and esophagectomies 42. In non-bariatric hospitals, volume of esophagectomies was median 52 (P = 0.145). Overall postoperative complication rate was lower in bariatric hospitals (59.2% vs. 65.9%, P < 0.001). Bariatric hospitals were associated with a reduced risk of overall complications (aOR 0.76 [95% CI 0.62-0.92]), length of hospital (aOR 0.79 [95% CI 0.65-0.95]), and ICU stay (aOR 0.81 [95% CI 0.67-0.98]) after MIE. Surgical radicality (R0) did not differ. Lymph node yield (≥ 15) was lower in bariatric hospitals (90.0% vs. 94.7%, P < 0.001). Over the years, several short-term outcomes improved in bariatric hospitals compared to non-bariatric hospitals. CONCLUSION: In this nationwide analysis, there was an association between bariatric hospitals and improved short-term outcomes after MIE. Characteristics of bariatric hospitals that could explain this phenomenon and whether this translates to other upper GI procedures may be warranted to identify.

Integration of palliative care consultation into the management of patients with chronic limb-threatening ischemia.

OBJECTIVE: We assessed the feasibility of integrating palliative care consultation into the routine management of patients with chronic limb-threatening ischemia (CLTI). Additionally, we sought to describe patient-reported outcomes from the palliative care and vascular literature in patients with CLTI receiving a palliative care consultation at our institution. METHODS: This was a single-institution, prospective, observational study that aimed to assess feasibility of incorporating palliative care consultation into the management of patients admitted to our tertiary academic medical center with CLTI by looking at utilization of palliative care before and after implementation of a protocol-based palliative care referral system. A survey comprised of patient-reported outcomes from the palliative care literature was administered to patients before and after palliative consultation. Length of stay and mortality were compared between our study cohort and a historic cohort of patients admitted with CLTI. RESULTS: Over a 14-month enrollment period, 44% of patients (n = 39) with CLTI (rest pain, 36%; tissue loss, 64%) admitted to the vascular service received palliative care consultation, compared with 5% of patients (n = 4) who would have met criteria over the preceding 14 months before our protocol was instituted. The mean age was 69 years, 23% were female, 92% were white, and 49% were able to ambulate independently. Revascularization included bypass (46%), peripheral vascular intervention (23%), and femoral endarterectomy (21%). Additional procedures included minor amputation or wound debridement (26%) and major amputation (15%). No patients received medical management alone. After receiving palliative care consultation, patients reported experiencing less emotional distress than before consultation (P = .03). They also reported being less bothered by uncertainty regarding what to expect from the course of their illness (P = .002). Fewer patients reported being unsure of the purpose of their medical care after palliative care consultation (8%) vs before (18%), although this was not statistically significant (P = .10). Median length of stay was longer in the study group compared with the historic cohort (8 vs 7 days; P = .02). There was no difference in 30-day mortality (3% vs 8%; P = .42) between the study group and the historic cohort (n = 77). CONCLUSIONS: Integrating inpatient palliative care consultation into the routine management of patients with CLTI is feasible and may improve emotional domains of health-related quality of life. This study laid the foundation for future studies on longer term outcomes of patients with CLTI undergoing palliative care consultation as well as the benefit of outpatient palliative care consultation in patients with CLTI.

Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays.

In next generation risk assessment (NGRA), the Dietary Comparator Ratio (DCR) can be used to assess the safety of chemical exposures to humans in a 3R compliant approach. The DCR compares the Exposure Activity Ratio (EAR) for exposure to a compound of interest (EARtest) to the EAR for an established safe exposure level to a comparator compound (EARcomparator), acting by the same mode of action. It can be concluded that the exposure to a test compound is safe at a corresponding DCR ≤ 1. In this study, genistein (GEN) was selected as a comparator compound by comparison of reported safe internal exposures to GEN to its BMCL05, as no effect level, the latter determined in the in vitro estrogenic MCF7/Bos proliferation, T47D ER-CALUX, and U2OS ERα-CALUX assay. The EARcomparator was defined using the BMCL05 and EC50 values from the 3 in vitro assays and subsequently used to calculate the DCRs for exposures to 14 test compounds, predicting the (absence of) estrogenicity. The predictions were evaluated by comparison to reported in vivo estrogenicity in humans for these exposures. The results obtained support in the DCR approach as an important animal-free new approach methodology (NAM) in NGRA and show how in vitro assays can be used to define DCR values.

Bringing Trauma Education to the Frontier: Overcoming Distance Barriers Utilizing a Virtual Platform.

BACKGROUND: The American College of Surgeons and state regulations mandate that trauma facilities offer trauma-specific continuing education throughout the region they serve. These requirements come with unique challenges when serving a rural and sparsely populated state. A novel approach to providing education was necessitated by the coronavirus disease 2019 pandemic, travel distance, and limited local specialists. OBJECTIVE: The purpose of this article is to describe the development of a virtual educational program used to improve access to quality trauma education and decrease barriers to obtaining continuing education hours inherent in the region. METHODS: This article describes the development and implementation of the Virtual Trauma Education program, which provided one free continuing education hour per month from October 2020 to October 2021. The program reached more than 2,000 viewers and established a method to provide continuous monthly educational offerings throughout the region. RESULTS: After the Virtual Trauma Education program implementation, monthly educational attendance increased from an average of 55 to 190. Viewership data indicate that trauma education across our region is far more robust, available, and accessible using a virtual platform. With more than 2,000 views from October 2020 to October 2021, Virtual Trauma Education offerings have spread far beyond regional borders, reaching 25 states and 169 communities. CONCLUSION: Virtual Trauma Education delivers easily accessible trauma education and is a program that has proven its sustainability.

Diagnostic Criteria for Breast Cancer-Related Lymphedema of the Upper Extremity: The Need for Universal Agreement.

With advances in breast cancer treatments and resultant increased survival rates, emphasis has been placed on post-treatment complications such as breast cancer-related lymphedema (BCRL), a chronic, negative sequela of breast cancer treatment. Accurate BCRL diagnosis necessitates longitudinal screening beginning at preoperative baseline. Prospective screening programs incorporating symptoms, objective measurements and clinical examination allow for early detection, early intervention, and improved BCRL prognosis. Currently, varied diagnostic criteria for BCRL exist, and this lack of consensus leads to variation in diagnostic and screening practices across institutions. This review outlines current diagnostic tools, including subjective and objective measurement methods and clinical examination. The merits of different criteria are evaluated and recommendations are made regarding measurement tools and diagnostic criteria for BCRL. Ultimately, the BCRL diagnostic process should be universalized and combine objective measurements, clinical evaluation, and symptoms assessment, and adhere to the best practices of the measurement tools used.

The transcription factor ETS1 is an important regulator of human NK cell development and terminal differentiation.

Natural killer (NK) cells are important in the immune defense against tumor cells and pathogens, and they regulate other immune cells by cytokine secretion. Although murine NK cell biology has been extensively studied, knowledge about transcriptional circuitries controlling human NK cell development and maturation is limited. By generating ETS1-deficient human embryonic stem cells and by expressing the dominant-negative ETS1 p27 isoform in cord blood hematopoietic progenitor cells, we show that the transcription factor ETS1 is critically required for human NK cell differentiation. Genome-wide transcriptome analysis determined by RNA-sequencing combined with chromatin immunoprecipitation-sequencing analysis reveals that human ETS1 directly induces expression of key transcription factors that control NK cell differentiation (ie, E4BP4, TXNIP, TBET, GATA3, HOBIT, BLIMP1). In addition, ETS1 regulates expression of genes involved in apoptosis and NK cell activation. Our study provides important molecular insights into the role of ETS1 as an important regulator of human NK cell development and terminal differentiation.

The potential for floral evolution in response to competing selection pressures following the loss of hawkmoth pollination in Ruellia humilis.

PREMISE: In the absence of hawkmoth pollinators, chasmogamous (CH) flowers of Ruellia humilis self-pollinate by two secondary mechanisms. Other floral visitors might exert selection on CH floral traits to restore outcrossing, but at the same time preferential predation of CH seeds generates selection to increase the allocation of resources to cleistogamous (CL) flowers. METHODS: To assess the potential for an evolutionary response to these competing selection pressures, we estimated additive genetic variances ( σ A 2 ${\sigma }_{{\rm{A}}}^{2}$ ) and covariances for 14 reproductive traits and three fitness components in a Missouri population lacking hawkmoth pollinators. RESULTS: We found significant σ A 2 ${\sigma }_{{\rm{A}}}^{2}$ for all 11 floral traits and two measures of resource allocation to CL flowers, indicating the potential for a short-term response to selection on most reproductive traits. Selection generated by seed predators is predicted to increase the percentage of CL flowers by 0.24% per generation, and mean stigma-anther separation is predicted to decrease as a correlated response, increasing the fraction of plants that engage in prior selfing. However, the initial response to this selection is opposed by strong directional dominance. CONCLUSIONS: The predicted evolutionary decrease in the number of CH flowers available for potential outcrossing, combined with the apparent preclusion of potential diurnal pollinators by the pollen-harvesting activities of sweat bees, suggest that 100% cleistogamy is the likely outcome of evolution in the absence of hawkmoths. However, rare mutations with large effects, such as delaying budbreak until after sunrise, could provide pathways for the restoration of outcrossing that are not reachable by gradual quantitative-genetic evolution.

Military sexual trauma in context: Ethnoracial differences in ecological resources among treatment-seeking veterans.

Veterans who have experienced military sexual trauma (MST) are at increased risk for a host of negative outcomes, including posttraumatic stress disorder, depressive disorders, and substance use disorders. Previous studies have shown racial differences in MST exposure, namely that Black veterans experience MST more frequently than White veterans. One way to help clinicians and researchers understand the impact of these ethnoracial differences in MST exposure is through an applied theory of ecological resources, which has demonstrated ecological factors (e.g., aspects of identity, beliefs, and environmental stressors) contribute to veteran well-being in the aftermath of MST. The present study aimed to examine ethnoracial differences in ecological resources (i.e., available social support, spiritual coping, past-year interpersonal violence, financial sufficiency, and stable living environment). Participants (N = 505) were U.S. veterans who sought care at a Veterans Healthcare Administration clinic in the midwestern United States for mental health issues related to MST. Results demonstrated Black veterans were more likely than White veterans to report being financially insecure, U = 18,091.50, z = -2.04, p = .042, r = .10. Black veterans were also more likely to report spiritual beliefs that assisted with coping, Cramer's V = .19, but less likely to report having a social support system, Cramer's V = .16. These findings highlight the importance of assessing and addressing disparities illuminated by ethnoracial differences in ecological resources and barriers in veterans seeking care for MST.

The effect of physician training and patient education on the discussion of care decisions at the internal medicine outpatient clinic.

BACKGROUND: Care decision discussions are intended to align treatment with the patient's wishes, goals and values. To overcome the numerous barriers to such discussions, physicians as well as patients need tailored support. We evaluate the effect of a physicians' training and a conversation aid for patients about care decisions on patient and physician outcomes. METHODS: At the internal medicine outpatient clinic of the University Medical Centre Utrecht, a 1:1 randomized, parallel-group study (patient conversation aid) was combined with a pre-post intervention (physicians' training) design. Primary outcome was patient satisfaction, secondary outcomes were patient-doctor relationship, shared-decision-making, doctor preparedness and patient appreciation of the conversation aid. RESULTS: Between October 2018 and February 2020 11 physicians (36% residents, 73% female) and 185 patients (median age 58 years (interquartile range (IQR) 50-68), 60% male) participated. Only 28% of the patients reported a care decision discussion during the consultation. We found no effect of the interventions on patient satisfaction (effect sizes -0.14 (95% confidence interval (CI) -0.56-0.27) for conversation aid; 0.04 (95% CI -0.40-0.48) for physician's training), nor on the patient-doctor relationship or shared-decision-making. However, physicians felt more prepared to discuss care decisions after training (median 3 (IQR 1-4) vs 1 (IQR 0-3), p = 0.015). Patients assessed the conversation aid informative and gave an overall mark of median 7 (IQR 7-8). CONCLUSIONS: First steps towards fruitful discussions about care decisions were made: patients considered the conversation aid informative and physicians felt better prepared to discuss care decisions after training. The low number of care decision conversations patients reported shows exactly how important it is to focus on interventions that facilitate these discussions, for both the patient and physician. Further work needs to be done to establish the best way to empower patients and physicians. TRIAL REGISTRATION: Dutch trial register, trial 6998 (NTR 7188), registered 04/05/2018, https://www.trialregister.nl/trial/6998 .

Weight loss does not decrease risk of breast cancer-related arm lymphedema.

BACKGROUND: The goal of this study was to determine the relationship between postoperative weight change and breast cancer-related lymphedema (BCRL). METHODS: In this cohort study, 1161 women underwent unilateral breast surgery for breast cancer from 2005 to 2020 and were prospectively screened for BCRL. Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow-up setting every 6 to 12 months. Mean follow-up from preoperative baseline was 49.1 months. The main outcome was BCRL, defined as a relative volume change of the ipsilateral arm of ≥10% at least 3 months after surgery. RESULTS: A total of 92 patients (7.9%) developed BCRL. Net weight loss versus net weight gain from baseline to last follow-up was not protective against developing BCRL (hazard ratio, 1.38; 95% confidence interval, 0.89-2.13; P = .152). CONCLUSIONS: Although weight loss may be recommended as part of an individualized lifestyle management program for overall health, weight loss alone may not decrease the risk of developing BCRL.

Subclinical Lymphedema After Treatment for Breast Cancer: Risk of Progression and Considerations for Early Intervention.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a devastating complication of breast cancer (BC) treatment. The authors hypothesized that identifying subclinical lymphedema (SCL) presents an opportunity to prevent BCRL development. They aimed to assess rates of SCL progression (relative volume change [RVC], 5-10%) to BCRL (RVC, ≥10%) in women undergoing axillary surgery for BC via axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB). METHODS: Patients treated for BC were prospectively screened at preoperative baseline and throughout the follow-up period using the perometer. The cohort was stratified according to nodal surgery (ALND or SLNB) to analyze rates of progression to BCRL. RESULTS: The study cohort included 1790 patients. Of the 1359 patients who underwent SLNB, 331 (24.4%) experienced SCL, with 38 (11.5%) of these patients progressing to BCRL. Of the 431 patients who underwent ALND, 171 (39.7%) experienced SCL, with 67 (39.2%) of these patients progressing to BCRL. Relative to the patients without SCL, those more likely to experience BCRL were the ALND patients with early SCL (< 3 months postoperatively; hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.58-4.27; p = 0.0002) or late SCL (≥3 months postoperatively; HR, 3.14; 95% CI, 1.95-5.05; p < 0.0001) and the SLNB patients with early SCL (HR, 6.75; 95% CI, 3.8-11.98; p < 0.0001 or late SCL (HR, 3.02; 95% CI, 1.65-5.50; p = 0.0003). CONCLUSION: The study suggests that patients with SCL after axillary nodal surgery for BC are more likely to progress to BCRL than those who do not experience SCL. This presents a tremendous opportunity for early intervention to prevent BCRL and improve the quality of life for women treated for BC.

Unintentional guideline deviations in hospitalized patients with two or more antithrombotic agents: an intervention study.

PURPOSE: Treatment schedules for antithrombotic therapy are complex, and there is a risk of inappropriate prescribing or continuation of antithrombotic therapy beyond the intended period of time. The primary aim of this study was to determine the frequency of unintentional guideline deviations in hospitalized patients. Secondary aims were to determine whether the frequency of unintentional guideline deviations decreased after intervention by a pharmacist, to determine the acceptance rate of the interventions and to determine the type of interventions. METHODS: We performed a non-controlled prospective intervention study in three teaching hospitals in the Netherlands. We examined whether hospitalized patients who used the combination of an anticoagulant plus at least one other antithrombotic agent had an unintentional guideline deviation. In these cases, the hospital pharmacist contacted the physician to assess whether this deviation was intentional. If the deviation was unintentional, a recommendation was provided how to adjust the antithrombotic regimen according to guideline recommendations. RESULTS: Of the 988 included patients, 407 patients had an unintentional guideline deviation (41.2%). After intervention, this was reduced to 22 patients (2.2%) (p < 0.001). The acceptance rate of the interventions was 96.6%. The most frequently performed interventions were discontinuation of an low molecular weight heparin in combination with a direct oral anticoagulant and discontinuation of an antiplatelet agent when there was no indication for the combination of an antiplatelet agent and an anticoagulant. CONCLUSION: A significant number of hospitalized patients who used an anticoagulant plus one other antithrombotic agent had an unintentional guideline deviation. Intervention by a pharmacist decreased unintentional guideline deviations.

Bidirectional learning opportunities: How GP-supervisors and trainees exchange knowledge.

INTRODUCTION: Workplace-based learning conversations can be a good opportunity for supervisors and trainees to learn from each other. When both professionals discuss their specific knowledge openly with each other, learning conversations may be a useful educational tool, for instance for learning how to apply evidence-based medicine (EBM) in the workplace. We do, however, need a better understanding of how the exchange of knowledge provides opportunities for such bidirectional learning. The aim of this study was therefore to analyse how trainees and supervisors currently handle bidirectional learning opportunities by describing in detail how supervisors respond to knowledge expressed by trainees during a learning conversation. METHOD: We video-recorded learning conversations between supervisors and trainees in general practice (GP). Within these learning conversations, EBM discussions on medical topics were selected and transcribed. We then identified, analysed using Conversation Analysis (CA) and categorised each expression of knowledge by the trainee and the supervisor's subsequent response. RESULTS: We found that when a trainee expresses knowledge during the learning conversation, supervisors either (a) refute the expressed knowledge, (b) immediately suggest an alternative or (c) pose (additional) questions. These responses have consequences for the learning opportunities of both trainee and supervisor: it is only when supervisors pose further questions that trainees are encouraged to elaborate on their knowledge, leading to a bidirectional learning opportunity. DISCUSSION: Improving EBM learning opportunities for both supervisors and trainees requires more than simply instructing trainees to express knowledge-based-for instance-on recent evidence more often. Inflexible institutional roles related to historical claims of supervisors' epistemic authority hamper bidirectional learning. Posing open questions during learning conversations enhances the flexibility of institutional roles while also creating bidirectional learning opportunities.

Artificial Intelligence System Approaching Neuroradiologist-level Differential Diagnosis Accuracy at Brain MRI.

Background Although artificial intelligence (AI) shows promise across many aspects of radiology, the use of AI to create differential diagnoses for rare and common diseases at brain MRI has not been demonstrated. Purpose To evaluate an AI system for generation of differential diagnoses at brain MRI compared with radiologists. Materials and Methods This retrospective study tested performance of an AI system for probabilistic diagnosis in patients with 19 common and rare diagnoses at brain MRI acquired between January 2008 and January 2018. The AI system combines data-driven and domain-expertise methodologies, including deep learning and Bayesian networks. First, lesions were detected by using deep learning. Then, 18 quantitative imaging features were extracted by using atlas-based coregistration and segmentation. Third, these image features were combined with five clinical features by using Bayesian inference to develop probability-ranked differential diagnoses. Quantitative feature extraction algorithms and conditional probabilities were fine-tuned on a training set of 86 patients (mean age, 49 years ± 16 [standard deviation]; 53 women). Accuracy was compared with radiology residents, general radiologists, neuroradiology fellows, and academic neuroradiologists by using accuracy of top one, top two, and top three differential diagnoses in 92 independent test set patients (mean age, 47 years ± 18; 52 women). Results For accuracy of top three differential diagnoses, the AI system (91% correct) performed similarly to academic neuroradiologists (86% correct; P = .20), and better than radiology residents (56%; P < .001), general radiologists (57%; P < .001), and neuroradiology fellows (77%; P = .003). The performance of the AI system was not affected by disease prevalence (93% accuracy for common vs 85% for rare diseases; P = .26). Radiologists were more accurate at diagnosing common versus rare diagnoses (78% vs 47% across all radiologists; P < .001). Conclusion An artificial intelligence system for brain MRI approached overall top one, top two, and top three differential diagnoses accuracy of neuroradiologists and exceeded that of less-specialized radiologists. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Zaharchuk in this issue.

Patients who report cording after breast cancer surgery are at higher risk of lymphedema: Results from a large prospective screening cohort.

OBJECTIVES: To identify the association between cording and breast cancer-related lymphedema (BCRL); describe time course, location, symptoms and functional impairments. METHODS: A total of 1181 patients were prospectively screened for BCRL after breast cancer (BC) surgery, including patient-reported outcome measures (4193) and perometric arm volume measurements (BCRL defined as relative or weight-adjusted volume change [RVC or WAC] ≥10% ≥3 months postoperatively). RESULTS: A total of 374/1181 patients (31.7%) reported cording first a median of 4.5 months postoperatively, and were more likely to: have body mass index less than 30 kg/m2 ; be less than 55 years of age; have had mastectomy, axillary lymph node dissection, regional lymph node radiation, neoadjuvant chemotherapy (all P < .001), or RVC/WAC ≥10% (P = .002). Patients who reported cording had 2.4 times the odds of developing BCRL compared to those who did not (odds ratio = 2.40; 95% confidence interval = 1.40-4.11; P = .002), and most frequently reported these symptoms: tenderness (61.2%), aching (60.7%), and firmness/tightness (59.8%). On multivariable analysis, cording was significantly correlated with functional difficulty for 17 actions. CONCLUSIONS: Patients frequently present with cording, potentially months after BC surgery. Risk factors for and symptoms of cording are identified, and treatment is recommended. Patients reporting cording are at higher risk of BCRL, therefore, cording should be incorporated into BCRL risk stratification.

The relationship between pitch velocity and shoulder distraction force and elbow valgus torque in collegiate and high school pitchers.

BACKGROUND: The relationship between pitch velocity, shoulder distraction force, and elbow valgus torque is not well understood. The purpose of this study was to (1) determine the association between baseball pitch velocity and shoulder distraction force and (2) determine the association between baseball pitch velocity and elbow valgus torque. A subpurpose was to determine these same associations within subgroups of college baseball and high school baseball pitchers. METHODS: Collegiate and high school baseball pitchers were biomechanically analyzed; variables extracted from the pitching reports included fastball pitch velocity, shoulder distraction force, and elbow valgus torque. Linear regression was performed to analyze the relationship between fastball velocity and shoulder and elbow kinetics. Subgroup analyses were then performed for college and high school pitches. Coefficients and 95% confidence intervals (95% CI) were calculated, with R squared (r2) used to assess model fit. RESULTS: A total of 70 pitchers (college: n = 23; high school: n = 47) were included in this study. There was a positive weak linear relationship between pitch velocity and shoulder distraction force (3.24 %body weight [BW] [95% CI: 2.07, 4.40], r2 = 0.32, P < .001) and elbow valgus torque (0.16 %body weight × height [BW × H] [95% CI: 0.11, 0.20], r2 = 0.44, P < .001). College pitchers did not exhibit a relationship between pitch velocity and shoulder distraction force (1.44 %BW [95% CI: -2.50, 5.38], r2 = 0.02, P < .001), whereas high school pitchers did exhibit a weak positive linear relationship between pitch velocity and shoulder distraction force (3.69 %BW [95% CI: 2.25, 5.14], r2 = 0.36, P < .001). Both college and high school pitchers exhibited a weak positive relationship between pitch velocity and elbow valgus torque (college: 0.15 %BW × H [95% CI: 0.05, 0.25], r2 = 0.29, P < .001; high school: 0.16 %BW × H [95% CI: 0.09, 0.22], r2 = 0.36, P < .001). DISCUSSION: Pitching velocity exhibited a weak positive linear relationship with both shoulder distraction force and elbow valgus torque. However, only high school pitchers were observed to have a weak positive linear relationship between pitch velocity and shoulder distraction force, whereas both college and high school pitchers exhibited a weak positive relationship between pitch velocity and elbow valgus torque. These findings suggest that older pitchers may attenuate shoulder forces with increased pitch velocity due to physical maturity or increased pitching mechanical skill in comparison with younger pitchers.

Incidence of peripheral edema in patients receiving PI3K/mTOR/CDK4/6 inhibitors for metastatic breast cancer.

PURPOSE: This study evaluated development of edema in patients receiving PI3K/mTOR/CDK4/6 targeted therapy for metastatic breast cancer (MBC). METHODS: We reviewed medical records of 160 patients receiving targeted therapy with PI3K/mTOR/CDK4/6 inhibitors to treat MBC (n = 160; 185 treatment occurrences). Clinicopathologic data, treatment details, and edema incidence were recorded. RESULTS: Edema incidence was 43.1% (69/160) overall and 25.6% (41/160) in the upper extremity ipsilateral to the treated breast. In 185 therapy regimens administered, 6.8% of patients on a PI3K inhibitor, 8.8% of patients on an mTOR inhibitor, and 9.2% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting upper extremity edema. Further, 9.1% of patients on a PI3K inhibitor, 18.8% of patients on an mTOR inhibitor, and 10.5% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting edema elsewhere in the body. Multivariate logistic regression showed that, beyond the established breast cancer-related lymphedema (BCRL) risk factors [axillary lymph node dissection (Odds Ratio (OR) 2.69, p = 0.020), regional lymph node irradiation (OR 6.47, p < 0.001), and body-mass index ≥ 30 kg/m2 (OR 3.46, p = 0.006)], a relative decrease in serum albumin after 3 months of treatment increased risk of developing edema (OR 2.07, p = 0.062). Neither duration nor type of therapy were significant risk factors for edema. CONCLUSION: PI3K/mTOR/CDK4/6 inhibitors may influence the development of edema, which may cause or exacerbate progression of BCRL in patients with MBC. The varied incidence of edema between therapeutic regimens warrants vigilant monitoring of patients treated with these therapies, especially those at high risk of developing BCRL.

Semantic memory for objects, actions, and events: A novel test of event-related conceptual semantic knowledge.

People possess significant knowledge about how real-world events typically unfold. Such event-related semantic memory connects action and object knowledge, is essential for multiple stages of language processing, and may be impaired in neurological conditions like aphasia. However, current assessments are not well designed for measuring this knowledge. This study presents and tests a novel measure of event-related semantic memory. Task-performance data were collected from unimpaired adults across the lifespan and a sample of stroke survivors with aphasia. Individuals with aphasia also completed measures of language processing and action-/object-related semantic memory, to establish the novel measure's convergent validity. Results demonstrate that performance on the event-knowledge measure correlated with action and object semantic-memory measures and was also associated with a broader range of language-processing performance than other semantic-memory measures. These findings suggest that the novel measure can be used to detect the presence and impact of event-knowledge impairments in neurological conditions.