Kinesiophobia in Injured Athletes: A Systematic Review.

Athletes have a high risk of injury. Kinesiophobia is a condition in which an individual experiences a fear of physical movement and activity after an injury occurs. Our purpose was to systematically review the literature about Kinesiophobia in athletes. A systematic review was conducted in February 2023 using PubMed, CINAHL, SPORTDiscus, Web of Science, Cochrane Library, and Medline. Studies were included if they were peer-reviewed, in English, within the last 20 years and included athletes who had been injured and tracked Kinesiophobia. Articles were checked for quality via the modified Downs and Black checklist. Fourteen studies were included in the review and had an average "fair" quality score. Authors examined Kinesiophobia in injured athletes with mostly lower-extremity injuries. Kinesiophobia was associated with lower physical and mental outcomes. Kinesiophobia exists in athletes and can affect both physical and mental factors. The Tampa Scale of Kinesiophobia (TSK) was the most common tool used to examine Kinesiophobia. Common mental factors associated with Kinesiophobia include anxiety, low confidence, and fear avoidance.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update.

PURPOSE: To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to update the 2020 guideline on systemic therapy for HCC. The panel updated the systematic review to include randomized controlled trials (RCTs) published through October 2023 and updated recommendations. RESULTS: Ten new RCTs met the inclusion criteria and were added to the evidence base. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) or durvalumab + tremelimumab (durva + treme) may be offered first-line for patients with advanced HCC, Child-Pugh class A liver disease, and Eastern Cooperative Oncology Group performance status 0-1. Where there are contraindications to these therapies, sorafenib, lenvatinib, or durvalumab may be offered first-line. Following first-line treatment with atezo + bev, second-line therapy with a tyrosine kinase inhibitor (TKI), ramucirumab (for patients with alpha-fetoprotein [AFP] ≥400 ng/mL), durva + treme, or nivolumab + ipilimumab (nivo + ipi) may be recommended for appropriate candidates. Following first-line therapy with durva + treme, second-line therapy with a TKI is recommended. Following first-line treatment with sorafenib or lenvatinib, second-line therapy options include cabozantinib, regorafenib for patients who previously tolerated sorafenib, ramucirumab (AFP ≥400 ng/mL), nivo + ipi, or durvalumab; atezo + bev or durva + treme may be considered for patients who did not have access to these therapies in the first-line setting, and do not have contraindications. Pembrolizumab or nivolumab are also options for appropriate patients following sorafenib or lenvatinib. Third-line therapy may be considered in Child-Pugh class A patients with good PS, using one of the agents listed previously that has a nonidentical mechanism of action with previously received therapy. A cautious approach to systemic therapy is recommended for patients with Child-Pugh class B advanced HCC. Further guidance on choosing between options is included within the guideline.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Correction: Jiménez-Ortigosa et al. Cryo-Electron Tomography of Candida glabrata Plasma Membrane Proteins. J. Fungi 2021, 7, 120.

The authors wish to update the article title to "Cryo-Electron Tomography of Candida glabrata Plasma Membrane Proteins" [...].

Pharmacologic targeting of coagulation factors XII and XI by monoclonal antibodies reduces thrombosis in nitinol stents under flow.

BACKGROUND: Cardiovascular implantable devices, such as vascular stents, are critical for the treatment of cardiovascular diseases. However, their success is dependent on robust and often long-term antithrombotic therapies. Yet, the current standard-of-care therapies often pose significant bleeding risks to patients. Coagulation factor (F)XI and FXII have emerged as potentially safe and efficacious targets to safely reduce pathologic thrombin generation in medical devices. OBJECTIVES: To study the efficacy of monoclonal antibody-targeting FXII and FXI of the contact pathway in preventing vascular device-related thrombosis. METHODS: The effects of inhibition of FXII and FXI using function-blocking monoclonal antibodies were examined in a nonhuman primate model of nitinol stent-related thrombosis under arterial and venous flow conditions. RESULTS: We found that function-blocking antibodies of FXII and FXI reduced markers of stent-induced thrombosis in vitro and ex vivo. However, FXI inhibition resulted in more effective mitigation of thrombosis markers under varied flow conditions. CONCLUSION: This work provides further support for the translation of contact pathway of coagulation inhibitors for their adjunctive clinical use with cardiovascular devices.

Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

BACKGROUND: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA. PATIENTS AND METHODS: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization). RESULTS: For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified. CONCLUSIONS: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.

Activation of coagulation FXI promotes endothelial inflammation and amplifies platelet activation in a nonhuman primate model of hyperlipidemia.

Background: Hyperlipidemia is associated with chronic inflammation and thromboinflammation. This is an underlying cause of several cardiovascular diseases, including atherosclerosis. In diseased blood vessels, rampant thrombin generation results in the initiation of the coagulation cascade, activation of platelets, and endothelial cell dysfunction. Coagulation factor (F) XI represents a promising therapeutic target to reduce thromboinflammation, as it is uniquely positioned at an intersection between inflammation and thrombin generation. Objectives: This study aimed to investigate the role of FXI in promoting platelet and endothelial cell activation in a model of hyperlipidemia. Methods: Nonhuman primates (NHPs) were fed a standard chow diet (lean, n = 6) or a high-fat diet (obese, n = 8) to establish a model of hyperlipidemia. Obese NHPs were intravenously administered a FXI blocking antibody (2 mg/kg) and studied at baseline and at 1, 7, 14, 21, and 28 days after drug administration. Platelet activation and inflammatory markers were measured using fluorescence-activated cell sorting or enzyme-linked immunosorbent assay. Molecular imaging was used to quantify vascular cell adhesion molecule 1 (VCAM-1) expression at the carotid bifurcation. Results: Obese NHPs demonstrated increased sensitivity for platelet P-selectin expression and phosphatidylserine exposure in response to platelet GPVI or PAR agonists compared with lean NHPs. Obese NHPs exhibited elevated levels of C-reactive protein, cathepsin D, and myeloperoxidase compared with lean NHPs. Following pharmacological inhibition of FIX activation by FXIa, platelet priming for activation by GPVI or PAR agonists, C-reactive protein levels, and endothelial VCAM-1 levels were reduced in obese NHPs. Conclusion: FXI activation promotes the proinflammatory phenotype of hyperlipidemia by priming platelet activation and inciting endothelial cell dysfunction.

Impact of a Pediatric Emergency Medicine Pharmacist, Institutional Guideline, and Electronic Order Set on Empiric Antimicrobial Use for Febrile Neutropenia.

OBJECTIVES: This study evaluated the difference in appropriateness of antimicrobial selection in pediatric patients with febrile neutropenia (FN) after implementation of an institutional guideline, a dedicated pediatric emergency medicine (EM) pharmacist, and an electronic order set. METHODS: This was a retrospective cohort study that included febrile patients aged younger than 18 years who were at risk of neutropenia, as defined by our institutional algorithm. Charts were evaluated for inclusion by searching for patients who presented to the emergency department (ED) between February 2018 and January 2022 who had International Classification of Diseases, Tenth Revision (ICD-10) codes for patients at risk of FN. Three independent groups were compared before, during, and after interventions. A historical control group (group 1), postdedicated EM pharmacist and institutional guideline cohort (group 2), and postdedicated EM pharmacist, institutional guideline, and electronic order set cohort (group 3) were compared. Secondary outcomes included time from registration in the ED to administration of the first dose of empiric antimicrobials, days to defervescence, pediatric intensive care unit length of stay, and hospital length of stay. RESULTS: Seventy-eight charts were reviewed for inclusion. Among those included (n = 38), there was an increase in appropriate use of antimicrobials from 71% to 92% to 100% ( P = 0.1534) between group 1, group 2, and group 3, respectively. In addition, the interventions in this study lead to an overall decrease in the median time from registration to first dose of antibiotics from 142 minutes to 72 minutes ( P = 0.1370). CONCLUSIONS: This study demonstrated the positive impact a pediatric EM pharmacist along with an institutional guideline and an electronic order set have on appropriate antimicrobial selection in pediatric FN patients. Institutions should consider multipronged approaches to improve the selection and time to administration of appropriate empiric antimicrobials in the ED.

Factor XI Inhibition for the Prevention of Catheter-Associated Thrombosis in Patients With Cancer Undergoing Central Line Placement: A Phase 2 Clinical Trial.

BACKGROUND: Despite the ubiquitous utilization of central venous catheters in clinical practice, their use commonly provokes thromboembolism. No prophylactic strategy has shown sufficient efficacy to justify routine use. Coagulation factors FXI (factor XI) and FXII (factor XII) represent novel targets for device-associated thrombosis, which may mitigate bleeding risk. Our objective was to evaluate the safety and efficacy of an anti-FXI mAb (monoclonal antibody), gruticibart (AB023), in a prospective, single-arm study of patients with cancer receiving central line placement. METHODS: We enrolled ambulatory cancer patients undergoing central line placement to receive a single dose of gruticibart (2 mg/kg) administered through the venous catheter within 24 hours of placement and a follow-up surveillance ultrasound at day 14 for evaluation of catheter thrombosis. A parallel, noninterventional study was used as a comparator. RESULTS: In total, 22 subjects (n=11 per study) were enrolled. The overall incidence of catheter-associated thrombosis was 12.5% in the interventional study and 40.0% in the control study. The anti-FXI mAb, gruticibart, significantly prolonged the activated partial thromboplastin time in all subjects on day 14 compared with baseline (P<0.001). Gruticibart was well tolerated and without infusion reactions, drug-related adverse events, or clinically relevant bleeding. Platelet flow cytometry demonstrated no difference in platelet activation following administration of gruticibart. T (thrombin)-AT (antithrombin) and activated FXI-AT complexes increased following central line placement in the control study, which was not demonstrated in our intervention study. CRP (C-reactive protein) did not significantly increase on day 14 in those who received gruticibart, but it did significantly increase in the noninterventional study. CONCLUSIONS: FXI inhibition with gruticibart was well tolerated without any significant adverse or bleeding-related events and resulted in a lower incidence of catheter-associated thrombosis on surveillance ultrasound compared with the published literature and our internal control study. These findings suggest that targeting FXI could represent a safe intervention to prevent catheter thrombosis. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465760.

Impact of Attentional Focus on Dance Performance: A Critically Appraised Topic.

CLINICAL SCENARIO: Dancing is a demanding esthetic activity with dancers having an 85% annual injury incident rate when performing complex dance motor skills. Teachers and clinicians use a combination of external and internal attentional cues when teaching dancers motor skills and when working on rehabilitation programs with injured dancers, respectively. External attentional focus (ie, focusing on movement outcome) reportedly results in superior performance than internal attentional focus (ie, focus on body movements). Interestingly, dancers reportedly often adopt an internal focus when dancing. Still, limited literature exists examining the effects of attentional focus on dancers' performance. CLINICAL QUESTION: How does attentional focus (external or internal) impact performance in dancers? SUMMARY OF KEY FINDINGS: Four original quasi-experimental studies met inclusion criteria. In the current examination, we found mixed results about the impact of attentional focus in dancers. Specifically, using an external attentional focus resulted in better performance in 2 studies, but these findings were limited to lesser experienced dancers. Experienced dancers did not have any physical performance differences when using external or internal focus. Internal focus also did not negatively affect dancers' performance in 2 studies. Some authors noted positive motivational effects (eg, increased perceived competence) when dancers used external focus. CLINICAL BOTTOM LINE: Low-quality evidence exists supporting the notion that in less experienced dance students, external focus improves performance. In experienced dancers, the type of attentional focus did not impact performance. External focus provides positive mental effects. Thus, clinicians working with dancers can integrate individualized feedback according to dancer level, with a preference toward external focus due to positive mental effects, to design optimal training and rehabilitation programs. STRENGTH OF RECOMMENDATION: Grade B evidence exists supporting the notion that an external attentional focus improves performance in less experienced dance students and also has positive mental effects. Internal attentional focus does not impede experienced dancers' performance.

Cardiovascular and renal outcomes with varying degrees of kidney disease in high-risk people with type 2 diabetes: An epidemiological analysis of data from the AMPLITUDE-O trial.

AIMS: To estimate the incidence of a major adverse cardiovascular event (MACE) and a composite kidney outcome across estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) levels, and to determine whether efpeglenatide's effect varies with these indices. MATERIALS AND METHODS: AMPLITUDE-O trial data were used to estimate the relationship of eGFR, UACR, and Kidney Disease Improving Global Outcomes (KDIGO) category to the hazard of MACE and the kidney composite. Interactions on these outcomes between eGFR and the UACR, and between each of these variables and efpeglenatide were also assessed. RESULTS: Baseline eGFR and UACR were available for 3983 participants (mean age 64.5 years). During a median follow-up of 1.8 years, the hazards of MACE and the kidney composite for the lowest versus highest eGFR third were 1.6 (95% confidence interval [CI] 1.2, 2.2) and 2.3 (95% CI 1.9, 2.8), respectively. The hazards for the highest versus the lowest UACR third were 2.3 (95% CI 1.8, 3.1) and 18.0 (95% CI 12.7, 25.5), respectively, and for the high- versus low-risk KDIGO categories the hazards were 2.4 (95% CI 1.8, 3.1) and 16.0 (95% CI 11.6, 22.0), respectively. eGFR and UACR were independent determinants of both outcomes, but negatively interacted with each other for the kidney outcome. Efpeglenatide's effect on both outcomes did not vary with any kidney disease measure (all interaction p values ≥0.26). CONCLUSIONS: In high-risk people with diabetes, eGFR, UACR, and KDIGO category have different relationships to incident cardiovascular and kidney outcomes. The beneficial effect of efpeglenatide on these outcomes is independent of kidney-related risk category.

The Cost-Effectiveness of Rivaroxaban Plus Aspirin Compared with Aspirin Alone in the COMPASS Trial: A US Perspective.

BACKGROUND: Rivaroxaban 2.5 mg twice daily with aspirin 100 mg daily was shown to be better than aspirin 100 mg daily for preventing cardiovascular (CV) death, stroke or myocardial infarction in patients with either stable coronary artery disease (CAD) or peripheral artery disease (PAD). The cost-effectiveness of this regimen in this population is essential for decision-makers to know. METHODS: US direct healthcare system costs (in USD) were applied to hospitalized events, procedures and study drugs utilized by all patients. We determined the mean cost per participant for the full duration of the trial (mean follow-up of 23 months) plus quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) over a lifetime using a two-state Markov model with 1-year cycle length. Sensitivity analyses were performed on the price of rivaroxaban and the annual discontinuation rate. RESULTS: The costs of events and procedures were reduced for Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) patients who received rivaroxaban 2.5 mg orally (BID) plus acetylsalicylic acid (ASA) compared with ASA alone. Total costs were higher for the combination group ($7426 versus $4173) after considering acquisition costs of the study drug. Over a lifetime, patients receiving rivaroxaban plus ASA incurred $27,255 more and gained 1.17 QALYs compared with those receiving ASA alone resulting in an ICER of $23,295/QALY. ICERs for PAD only and polyvascular disease subgroups were lower. CONCLUSION: Rivaroxaban 2.5 mg BID plus ASA compared with ASA alone was cost-effective (high value) in the USA. COMPASS ClinicalTrials.gov identifier: NCT01776424.

Cytoprotective E-WE thrombin reduces disease severity in a murine model of relapsing-remitting multiple sclerosis.

The blood-brain barrier is composed of microvascular endothelial cells, immune cells, and astrocytes that work in concert with the coagulation cascade to control inflammation and immune cell infiltration into the central nervous system. Endothelial cell dysfunction leading to increased permeability and compromised barrier function are hallmarks of neuroinflammatory and autoimmune disorders, including multiple sclerosis (MS). Therapeutic strategies that improve or protect endothelial barrier function may be beneficial in the treatment or prevention of neuroinflammatory diseases. We therefore tested the hypothesis that biasing thrombin toward anticoagulant and cytoprotective activities would provide equivalent or even additive benefit compared with standard-of-care therapeutic strategies, including corticosteroids. In a mouse model of relapsing-remitting MS, treatment with the thrombin mutant, E-WE thrombin, an engineered thrombin mutant with cytoprotective activities that is biased toward anticoagulant and cytoprotective activity, reduced neuroinflammation and extracellular fibrin formation in SJL mice inoculated with proteolipid protein (PLP) peptide. When administered at the onset of detectable disease, E-WE thrombin significantly improved the disease severity of the initial attack as well as the relapse and delayed the onset of relapse to a similar extent as observed with methylprednisolone. Both methylprednisolone and E-WE thrombin reduced demyelination and immune cell recruitment. These results provide rationale for considering engineered forms of thrombin biased toward anticoagulant and cytoprotective activity as a therapeutic strategy and perhaps an effective alternative to high-dose methylprednisolone for the management of acute relapsing MS attacks.NEW & NOTEWORTHY There are limited treatment options for mitigating acute relapsing attacks for patients with multiple sclerosis. We tested the hypothesis that harnessing the cytoprotective activity of the blood coagulation enzyme, thrombin, would provide benefit and protection against relapsing disease in a mouse model of MS. Our results provide rationale for considering engineered forms of thrombin biased toward cytoprotective activity as a therapeutic strategy and perhaps an alternative to steroids for the management of relapsing MS attacks.

Cecostomy tubes improve bowel continence for pediatric patients with spina bifida: A retrospective analysis of outcomes from a single clinic.

PURPOSE: Pediatric patients with spina bifida often experience neurogenic bowel dysfunction. Although cecostomy tubes could improve bowel continence, their effectiveness is not well established in this population. The aims of this study were to better understand the effectiveness of cecostomy tubes relative to other management strategies (between-subject) and to explore their effectiveness among patients who received these placements (within-subject). METHODS: Retrospective analysis of data from pediatric patients enrolled in a national spina bifida patient registry (n = 297) at a single multidisciplinary clinic was performed, covering visits between January 2014 -December 2021. Linear and ordinal mixed effect models (fixed and random effects) tested the influence of cecostomy status (no placement vs placement) and time (visits) on bowel continence while controlling for demographic and condition-specific covariates. RESULTS: Patients with cecostomy tubes had higher bowel continence compared to patients without placements (B = 0.695, 95% CI [0.333, 1.050]; AOR = 2.043, p = .007). Patients with cecostomy tubes had higher bowel continence after their placements compared to before (B = 0.834, 95% CI [0.142, 1.540]; AOR = 3.259, p = 0.011). CONCLUSION: Results indicate cecostomy tubes are effective for improving bowel continence in this pediatric population. Future research is needed to conduct risk analyses and determine the clinical significance of these effects.

The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma.

PURPOSE: Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA. METHODS: A multi-institutional cohort of patients with CCA diagnosed with intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC) was used for analysis. Retrospective chart review was conducted on patients who were 50 years old and younger (young; n = 124) and older than 50 years (older; n = 723). RESULTS: Among 1,039 patients screened, 847 patients met eligibility (72% ICC, 28% ECC). Young patients had a larger median tumor size at resection compared with older patients (4.2 v 3.6 cm; P = .048), more commonly had N1 disease (65% v 43%; P = .040), and were more likely to receive adjuvant therapy (odds ratio, 4.0; 95% CI, 1.64 to 9.74). Tumors of young patients were more likely to harbor an FGFR2 fusion, BRAF mutation, or ATM mutation (P < .05 for each). Young patients were more likely to receive palliative systemic therapy (96% v 69%; P < .001), targeted therapy (23% v 8%; P < .001), and treatment on a clinical trial (31% v 19%; P = .004). Among patients who presented with advanced disease, young patients had a higher median overall survival compared with their older counterparts (17.7 v 13.5 months; 95% CI, 12.6 to 22.6 v 11.4 to 14.8; P = .049). CONCLUSION: Young patients with CCA had more advanced disease at resection, more commonly received both adjuvant and palliative therapies, and demonstrated improved survival compared with older patients. Given the low clinical trial enrollment and poor outcomes among some AYA cancer populations, data to the contrary in CCA are highly encouraging.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Female Collegiate Dancers' Physical Fitness across Their Four-Year Programs: A Prospective Analysis.

Dance is physically demanding, requiring physical fitness (PF) that includes upper body, lower body, core fitness, and balance for successful performance. Whether PF changes as dancers advance from when they enter (freshmen) to when they graduate from their collegiate program (seniors) is unclear. We prospectively compared collegiate dancers' freshman-to-senior PF. We recorded PF in regard to upper body strength endurance (push-ups), core strength endurance (front, left-side, right-side, and extensor plank hold times), lower body power (single leg hop-SLH-distances % height; Leg Symmetry Index: LSI = higher/lower × 100, %), and balance (anterior reach balance, % leg length, LL; LSI balance = higher/lower × 100, %) in 23 female collegiate dancers (freshman age = 18.2 ± 0.6 years). Repeated measures ANOVAs (p ≤ 0.05) were used to compare measures from freshman to senior years. Across their collegiate programs, dancers' PF remained unchanged. Specifically, their upper body strength endurance push-up numbers (p = 0.93), their core strength endurance plank times (left: p = 0.44, right: p = 0.67, front: p = 0.60, p = 0.22), their SLH distances (left: p = 0.44, right: p = 0.85), and their symmetry (p = 0.16) stayed similar. Also, dancers' right leg (p = 0.08) and left leg balance (p = 0.06) remained similar, with better balance symmetry (p < 0.001) in seniors. Overall, dancers' PF did not change across their collegiate programs. Thus, female dancers' freshman PF may be an adequate baseline reference measure when devising rehabilitation programs and determining readiness-to-return-to-activity post injury.

Head-to-pelvis CT imaging after sudden cardiac arrest: Current status and future directions.

Causes for sudden circulatory arrest (SCA) can vary widely making early treatment and triage decisions challenging. Additionally, cardiopulmonary resuscitation (CPR), while a life-saving link in the chain of survival, can be associated with traumatic injuries. Computed tomography (CT) can identify many causes of SCA as well as its sequelae. However, the diagnostic and therapeutic impact of CT in survivors of SCA has not been reviewed to date. This general review outlines the rationale and potential applications of focused head, chest, and abdomen/pelvis CT as well as comprehensive head-to-pelvis CT imaging after SCA. CT has a diagnostic yield approaching 30% to identify causes of SCA while the addition of ECG-gated chest CT provides further information about coronary anatomy and cardiac function. Risks of CT include radiation exposure, contrast-induced kidney injury, and incidental findings. This review's findings suggest that routine head-to-pelvis CT can yield clinically actional findings with the potential to improve clinical outcome after SCA that merits further investigation.

Forest inventory tree core archive reveals changes in boreal wood traits over seven decades.

Boreal forests play an important role in the global carbon (C) cycle, and there is great interest in understanding how they respond to environmental change, including nitrogen (N) and water limitation, which could impact future forest growth and C storage. Utilizing tree cores archived by the Swedish National Forest Inventory, we measured stemwood traits, including stable N and C isotope composition which provides valuable information related to N availability and water stress, respectively, as well as N and C content, and C/N ratio over 1950-2017 in two central Swedish counties covering an area of ca. 55,000 sq. km (n = 1038). We tested the hypothesis that wood traits are changing over time, and that temporal patterns would differ depending on alternative dendrochronological reconstruction methods, i.e. the commonly applied "single tree method" (STM) or a conceptually stronger "multiple tree method" (MTM). Averaged across all MTMs, our data showed that all five wood traits for Picea abies and Pinus sylvestris changed over time. Wood δ15N strongly declined, indicating progressive nitrogen limitation. The decline in δ13C tracked the known atmospheric δ13CO2 signal, suggesting no change in water stress occurred. Additionally, wood N significantly increased, while C and C/N ratios declined over time. Furthermore, wood trait patterns sometimes differed between dendrochronological methods. The most notable difference was for δ15N, where the slope was much shallower for the STM compared to MTMs for both species, indicating that mobility of contemporary N is problematic when using the STM, resulting in substantially less sensitivity to detect historical signals. Our study indicates strong temporal changes in boreal wood traits and also indicates that the field of dendroecology should adopt new methods and archiving practices for studying highly mobile element cycles, such as nitrogen, which are critical for understanding environmental change in high latitude ecosystems.

New Opportunities to Individualize Frontline Therapy in Advanced Stages of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally and is rising in incidence. Until recently, treatment options for patients with advanced stages of HCC have been limited to antiangiogenic therapies with modest improvements in overall survival. The emerging role of immunotherapy with immune checkpoint inhibitors (ICI) in oncology has led to a rapid expansion in treatment options and improvements in outcomes for patients with advanced stages of HCC. Recent clinical trials have shown meaningful survival improvement in patients treated with the combination of bevacizumab and atezolizumab, as well as with the combination of tremelimumab with durvalumab, resulting in regulatory approvals of these regimens as frontline therapy. Beyond improvements in overall survival, ICI-based combination regimens achieve higher rates of durable treatment response than multikinase inhibitors and have favorable side effect profiles. With the emergence of doublet anti-angiogenic and immune checkpoint inhibitor (ICI) and dual ICI combinations, individualized therapy is now possible for patients based on co-morbidity profiles and other factors. These more potent systemic therapies are also being tested in earlier stages of disease and in combination with loco-regional therapies such as trans-arterial chemoembolization and stereotactic body radiotherapy. We summarize these advances and emerging therapeutic combinations currently in clinical trials.