A Multicenter, Single-Arm, Prospective Trial Assessing the Diagnostic Yield of Electromagnetic Bronchoscopic and Transthoracic Navigation for Peripheral Pulmonary Nodules.

Rationale: Strict adherence to procedural protocols and diagnostic definitions is critical to understand the efficacy of new technologies. Electromagnetic navigational bronchoscopy (ENB) for lung nodule biopsy has been used for decades without a solid understanding of its efficacy, but offers the opportunity for simultaneous tissue acquisition via electromagnetic navigational transthoracic biopsy (EMN-TTNA) and staging via endobronchial ultrasound (EBUS). Objective: To evaluate the diagnostic yield of EBUS, ENB, and EMN-TTNA during a single procedure using a strict a priori definition of diagnostic yield with central pathology adjudication. Methods: A prospective, single-arm trial was conducted at eight centers enrolling participants with pulmonary nodules (<3 cm; without computed tomography [CT]- and/or positron emission tomography-positive mediastinal lymph nodes) who underwent a staged procedure with same-day CT, EBUS, ENB, and EMN-TTNA. The procedure was staged such that, when a diagnosis had been achieved via rapid on-site pathologic evaluation, the procedure was ended and subsequent biopsy modalities were not attempted. A study finding was diagnostic if an independent pathology core laboratory confirmed malignancy or a definitive benign finding. The primary endpoint was the diagnostic yield of the combination of CT, EBUS, ENB, and EMN-TTNA. Measurements and Main Results: A total of 160 participants at 8 centers with a mean nodule size of 18 ± 6 mm were enrolled. The diagnostic yield of the combined procedure was 59% (94 of 160; 95% confidence interval [CI], 51-66%). Nodule regression was found on same-day CT in 2.5% of cases (4 of 160; 95% CI, 0.69-6.3%), and EBUS confirmed malignancy in 7.1% of cases (11 of 156; 95% CI, 3.6-12%). The yield of ENB alone was 49% (74 of 150; 95% CI, 41-58%), that of EMN-TTNA alone was 27% (8 of 30; 95% CI, 12-46%), and that of ENB plus EMN-TTNA was 53% (79 of 150; 95% CI, 44-61%). Complications included a pneumothorax rate of 10% and a 2% bleeding rate. When EMN-TTNA was performed, the pneumothorax rate was 30%. Conclusions: The diagnostic yield for ENB is 49%, which increases to 59% with the addition of same-day CT, EBUS, and EMN-TTNA, lower than in prior reports in the literature. The high complication rate and low diagnostic yield of EMN-TTNA does not support its routine use. Clinical trial registered with www.clinicaltrials.gov (NCT03338049).

Use of Dual-Task Timed-Up-and-Go Tests for Predicting Falls in Physically Active, Community-Dwelling Older Adults-A Prospective Study.

This prospective study aimed to determine which specific mobility tests were the most accurate for predicting falls in physically active older adults living in the community. Seventy-nine physically active older adults who met the American College of Sports Medicine physical activity guidelines volunteered. Participants were assessed and followed up for 12 months. Mobility assessments included the 30-s sit-to-stand test, five times sit-to-stand test, single-task timed-up-and-go test (TUG), motor dual-task TUG (Mot-TUG), and cognitive dual-task TUG (Cog-TUG). Mot-TUG and Cog-TUG performances were moderately correlated with number of falls (r = .359, p < .01 and r = .372, p < .01, respectively). When Mot-TUG, Cog-TUG, or Age were included as fall predictors, discrimination scores represented by the area under the receiver operating characteristic curve (AUC) were AUC (Mot-TUG) = 0.843 (p < .01), AUC (Cog-TUG) = 0.856 (p < .01), and AUC (Age) = 0.734 (p < .05). The cutoff point for Cog-TUG was 10.98 s, with test sensitivity of 1.00 and specificity of 0.66. Fall predictors for different populations may be based on different test methods. Here, the dual-task TUG test more accurately predicted falls in older adults who met American College of Sports Medicine's physical activity guidelines.

Intermittent fasting and continuous energy restriction result in similar changes in body composition and muscle strength when combined with a 12 week resistance training program.

PURPOSE: The objective of this study was to compare the effects of 12 weeks of resistance training combined with either 5:2 intermittent fasting or continuous energy restriction on body composition, muscle size and quality, and upper and lower body strength. METHODS: Untrained individuals undertook 12 weeks of resistance training plus either continuous energy restriction [20% daily energy restriction (CERT)] or 5:2 intermittent fasting [~ 70% energy restriction 2 days/week, euenergetic consumption 5 days/week (IFT)], with both groups prescribed a mean of ≥ 1.4 g of protein per kilogram of body weight per day. Participants completed 2 supervised resistance and 1 unsupervised aerobic/resistance training combination session per week. Changes in lean body mass (LBM), thigh muscle size and quality, strength and dietary intake were assessed. RESULTS: Thirty-four participants completed the study (CERT = 17, IFT = 17). LBM was significantly increased (+ 3.7%, p < 0.001) and body weight (- 4.6%, p < 0.001) and fat (- 24.1%, p < 0.001) were significantly reduced with no significant difference between groups, though results differed by sex. Both groups showed improvements in thigh muscle size and quality, and reduced intramuscular and subcutaneous fat assessed by ultrasonography and peripheral quantitative computed tomography (pQCT), respectively. The CERT group demonstrated a significant increase in muscle surface area assessed by pQCT compared to the IFT group. Similar gains in upper and lower body strength and muscular endurance were observed between groups. CONCLUSION: When combined with resistance training and moderate protein intake, continuous energy restriction and 5:2 intermittent fasting resulted in similar improvements in body composition, muscle quality, and strength. ACTRN: ACTRN12620000920998, September 2020, retrospectively registered.

Effects of Pre-exercise Acute Vibration Training on Symptoms of Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis.

ABSTRACT: Tan, J, Shi, X, Witchalls, J, Waddington, G, Lun Fu, AC, Wu, S, Tirosh, O, Wu, X, and Han, J. Effects of pre-exercise acute vibration training on symptoms of exercise-induced muscle damage: a systematic review and meta-analysis. J Strength Cond Res 36(8): 2339-2348, 2022-Exercise-induced muscle damage (EIMD) normally occurs after unaccustomed high-intensity eccentric exercises. Symptoms of EIMD include delayed-onset muscle soreness (DOMS), tenderness, stiffness, swelling, reduced strength, and increased creatine kinase (CK) levels in the blood. Vibration training (VT) may be useful as a pre-exercise intervention in attenuating EIMD on the basis of tonic vibration reflex (TVR) through a more efficient distribution of contractile stress over muscle fibers. The objective of this meta-analysis is to examine the effects of acute VT on symptoms of EIMD when performed as the pre-exercise intervention. Randomized controlled trials (RCTs) published in the 8 databases of Cochrane Library, PubMed, Embase, Web of Science, EBSCO, China National Knowledge Infrastructure, Airiti Library and WanFang Data from 1966 (the earliest available time) to January 2019 were searched. A total of 2,324 records were identified and 448 articles were screened with the title and abstract. Two investigators identified eligible studies, extracted data, and assessed the risk of bias independently. Review Manager 5.3 designed by Cochrane was used for the current meta-analysis. Six RCTs involving 180 subjects were included in the analysis. A low-to-moderate methodological quality of the included studies was revealed using the physiotherapy evidence database scale. The results showed that acute VT was superior to the control group for the reduction of DOMS on pain visual analogue scale at 24, 48 hours and pressure pain threshold at 24 hours. In addition, superior effects of acute VT were also found on the indirect markers of muscle damage including CK at 24, 72 hours, and lactate dehydrogenase at 24 hours. The current meta-analysis has collated the evidence to demonstrate that receiving acute VT before unaccustomed high-intensity eccentric exercises may be effective in attenuating markers of muscle damage and the development of DOMS when compared with a control group. The possible mechanisms of this effect could be attributed to an improved synchronization of muscle fiber caused by TVR, which could result in even distribution of exterior loads and eventually attenuate disruptions of muscle fibers. In addition, increased blood flow may also be helpful to prevent accumulation of metabolic substances and attenuate subsequent symptoms of EIMD. Vibration training may be used as a pre-exercise intervention to alleviate symptoms of EIMD caused by unaccustomed high-intensity eccentric exercise. Because of the limited quantity and quality of included studies, more high-quality studies are required to ascertain the effect of VT on symptoms of EIMD.

Compression Socks Reduce Running-Induced Intestinal Damage.

ABSTRACT: Zadow, EK, Edwards, KH, Kitic, CM, Fell, JW, Adams, MJ, Singh, I, Kundur, A, Johnstone, ANB, Crilly, J, Bulmer, AC, Halson, SL, and, and Wu, SSX. Compression socks reduce running-induced intestinal damage. J Strength Cond Res 36(9): 2461-2464, 2022-Exercise is associated with a reduction in splanchnic blood flow that leads to the disruption of intestinal epithelium integrity, contributing to exercise-induced gastrointestinal syndrome. Strategies that promote intestinal blood flow during exercise may reduce intestinal damage, which may be advantageous for subsequent recovery and performance. This study aimed to explore if exercise-associated intestinal damage was influenced by wearing compression garments, which may improve central blood flow. Subjects were randomly allocated to wear compression socks ( n = 23) or no compression socks (control, n = 23) during a marathon race. Blood samples were collected 24 hours before and immediately after marathon and analyzed for intestinal fatty acid-binding protein (I-FABP) concentration as a marker of intestinal damage. The magnitude of increase in postmarathon plasma I-FABP concentration was significantly greater in control group (107%; 95% confidence interval [CI], 72-428%) when compared with runners wearing compression socks (38%; 95% CI, 20-120%; p = 0.046; d = 0.59). Wearing compression socks during a marathon run reduced exercise-associated intestinal damage. Compression socks may prove an effective strategy to minimize the intestinal damage component of exercise-induced gastrointestinal syndrome.

Vibration of calf muscles has reverse effects on right and left ankle proprioception in high and low proprioceptive performer groups.

PURPOSE: Previous research has found hemispheric asymmetries in the utilization of proprioceptive information. It is undetermined, however, if there is any change in asymmetry in proprioceptive function when external stimulation, such as vibration, is presented. The present study was to investigate the immediate effects of vibration stimulation (VS) on bilateral ankle proprioception. MATERIALS AND METHODS: Forty-six recreational male basketball players were included. Proprioception was assessed by using the active movement extent discrimination apparatus (AMEDA) in standing, and vibration was provided by using a vibrating form roller on the peroneal or gastrocnemius muscles. RESULTS: When participants were divided into high score and low score groups, according to the median of the baseline proprioceptive performance, VS (irrespective of whether vibrating the peroneal or gastrocnemius muscles) significantly improved left non-dominant ankle proprioception in the low proprioceptive performer group (p = 0.019), while significantly deteriorated right dominant ankle proprioception in the high proprioceptive performer group (p = 0.011). CONCLUSIONS: The results found that external stimuli reversely affect proprioception in better and worse performing groups. This suggests that there are differences in the processing of external stimulus signals on different bilateral hemispheres and in different groups (high score vs low score groups), which may be related to hemispheric asymmetry and stochastic resonance. Therefore, it is necessary to explore more specific interventions in the future.

Effects of wrist position on eccentric exercise-induced muscle damage of the elbow flexors.

We tested the hypothesis that the magnitude of changes in indirect muscle damage markers would be greater after maximal elbow flexor eccentric exercise in the supinated (shorter biceps brachii) than neutral wrist (longer) position, and the difference in the magnitude would be associated with greater elongation over contractions for the supinated than neutral position, rather than the initial muscle length. Ten untrained men (21-39 years) performed two bouts of 10 sets of 6 maximal isokinetic eccentric contractions of the elbow flexors in the supinated position for one arm and neutral position for the other arm separated by 2 weeks in a randomized order. Biceps brachii myotendinous junction (MTJ) movements during eccentric contractions were recorded by B-mode ultrasonography, and the displacement from the start to end of each contraction was quantified. Peak torque (supinated: 367.8 ± 112.5 Nm, neutral: 381.5 ± 120.4 Nm) and total work (1816 ± 539 J, 1865 ± 673 J) produced during eccentric contractions were similar between conditions. The average MTJ displacement increased (P < .05) from the 1st set (8.0 ± 2.0 mm) to 10th set (15.8 ± 1.9 mm) for the supinated condition, but no such increase was found in the neutral condition (1st set: 5.1 ± 1.0 mm, 10th set: 5.0 ± 0.8 mm). Changes in indirect muscle damage markers (maximal voluntary isometric contraction torque, range of motion, serum creatine kinase activity, and muscle soreness) after exercise were greater (P < .05) for the supinated than neutral condition. These results suggest that the greater muscle damage marker changes for the supinated than neutral wrist position was associated with the greater muscle lengthening (strain).

Coronavirus (COVID-19), Coagulation, and Exercise: Interactions That May Influence Health Outcomes.

The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis. Coagulopathy has been reported as associated with mortality in people with COVID-19 and is partially reflected by enhanced D-dimer levels. Poor vascular health, which is associated with the cardiometabolic health conditions frequently reported in people with severer forms of COVID-19, might exacerbate the risk of coagulopathy and mortality. Sedentary lifestyles might also contribute to the development of coagulopathy, and physical activity participation has been inherently lowered due to at-home regulations established to slow the spread of this highly infectious disease. It is possible that COVID-19, coagulation, and reduced physical activity may contribute to generate a "perfect storm," where each fuels the other and potentially increases mortality risk. Several pharmaceutical agents are being explored to treat COVID-19, but potential negative consequences are associated with their use. Exercise is known to mitigate many of the identified side effects from the pharmaceutical agents being trialled but has not yet been considered as part of management for COVID-19. From the limited available evidence in people with cardiometabolic health conditions, low- to moderate-intensity exercise might have the potential to positively influence biochemical markers of coagulopathy, whereas high-intensity exercise is likely to increase thrombotic risk. Therefore, low- to moderate-intensity exercise could be an adjuvant therapy for people with mild-to-moderate COVID-19 and reduce the risk of developing severe symptoms of illness that are associated with enhanced mortality.

PD-L1 and LAG-3 expression in advanced cutaneous squamous cell carcinomas.

BACKGROUND: Expression of programmed death ligand 1 (PD-L1) by cutaneous squamous cell carcinomas has been shown to correlate with advanced disease and risk of metastasis. Lymphocyte activation gene 3 (LAG-3, or CD223) is an inhibitory receptor that interacts with the PD-L1 axis, which has been shown to be a marker of immune exhaustion and a potential immunotherapy target. However, the role of LAG-3 in cutaneous squamous cell carcinoma has not been established. METHODS: We reviewed 18 cases of locally advanced and/or metastatic cutaneous squamous cell carcinomas and assessed for PD-L1 expression, presence or absence of tumor-infiltrating lymphocytes (TILs), and expression of LAG-3 by TILs. RESULTS: PD-L1 expression was present in 11 of 13 locally advanced primary tumors and 5 of 5 metastases. TILs were present in all 18 tumors, of which 14 cases were positive for LAG-3 expression. In positive cases, LAG-3 was expressed on average by 32% of TILs. CONCLUSIONS: Advanced cutaneous squamous cell carcinomas frequently express PD-L1 and are associated with an inflammatory response. LAG-3 expression by TILs was identified in a majority of cases. Our findings suggest that LAG-3 positive tumor-associated inflammatory cells may play a role in the development of advanced disease and offer another potential target for drug therapy.

A case of bullous Sézary syndrome.

Sézary syndrome is a rare leukemic subtype of cutaneous T cell lymphoma that is characterized by erythroderma, lymphadenopathy, and malignant T cells in the peripheral blood. Poor prognostic factors of Sézary syndrome include advanced disease stage, older age at onset, and large cell transformation. Presentation with bullous lesions, though rare, has been reported in a few patients. We present an elderly woman with bullous Sézary syndrome who presented with a two-month history of progressive rash. Upon admission, the patient had pruritic, erythematous, edematous plaques with overlying flaccid bullae and erosions involving the scalp, neck, torso, and extremities. Despite treatment, the patient died two months after presentation. Although rare, bullous lesions associated with Sézary syndrome may indicate poor prognosis.

Deep vein thrombosis in a well-trained masters cyclist, is popliteal vein entrapment syndrome to blame?

Whilst athletes are the epitome of health, venous thromboembolisms (VTE) including deep vein thrombosis and pulmonary embolism have been demonstrated to occur in well-trained athletes. VTE is frequently misdiagnosed and poorly treated within this population, often resulting in career or life-threatening ramifications. Furthermore, VTE risk rises with increasing age (> 40 years), potentially affecting masters athletes. A 44-year-old well-trained male cyclist volunteered to participate in a research project investigating the influence of exercise on haemostasis in well-trained athletes. The cyclist presented with elevated D-Dimer levels both pre- (2251 ng/mL) and post-exercise (2653 ng/mL). The cyclist reported constant mild-pain in the left mid-calf region, with a cold tingling sensation in their left foot. Diagnosis of DVT was confirmed via a DVT squeeze test and Doppler ultrasound, with the clot located in the left popliteal vein. During the research project, the cyclist was exposed to numerous thrombogenic risk factors including travel, dehydration, prolonged sitting and exercise. The DVT in the popliteal vein may have resulted from repetitive movements associated with cycling. Additionally, hypertrophy of the gastrocnemius muscle may have impinged the vein. When diagnosing DVT within a cycling population, PVES should not be overlooked as a contributing factor.

Cutaneous toxicity associated with enfortumab vedotin treatment of metastatic urothelial carcinoma.

Enfortumab vedotin is an antibody-drug conjugate targeting nectin-4 and is being studied in the treatment of various epithelial carcinomas including urothelial carcinoma; early data suggests efficacy and tolerability. Rash has been described as an adverse event associated with treatment with enfortumab vedotin, but has not been characterized to date. We report a patient with metastatic urothelial carcinoma treated with enfortumab vedotin who developed erythematous, scaly papules and plaques on his torso and extremities with corresponding histologic features of vacuolar interface dermatitis and maturation disarray of keratinocytes. He was successfully treated with topical corticosteroids. Cutaneous toxicity appears to be a common adverse reaction in this growing class of antibody-drug conjugates.

Acquired and Genetic Thrombotic Risk Factors in the Athlete.

While athletes are often considered the epitome of health due to their physique and lowered potential for metabolic and cardiovascular diseases, they may also be at risk for the onset and development of venous thromboembolism (VTE). In an attempt to achieve and remain competitive, athletes are frequently exposed to numerous athlete-specific risk factors, which may predispose them to VTE through the disruption of factors associated with Virchow's triad (i.e., hypercoagulability, venous stasis, and vessel wall injury). Indeed, hypercoagulability within an athletic population has been well documented to occur due to a combination of multiple factors including exercise, dehydration, and polycythemia. Furthermore, venous stasis within an athletic population may occur as a direct result of prolonged periods of immobilization experienced when undertaking long-distance travels for training and competition, recovery from injury, and overdevelopment of musculature. While all components of Virchow's triad are disrupted, injury to the vessel wall has emerged as the most important factor contributing to thrombosis formation within an athletic population, due to its ability to influence multiple hemostatic mechanisms. Vessel wall injury within an athletic population is often related to repetitive microtrauma to the venous and arterial walls as a direct result of sport-dependent trauma, in addition to high metabolic rates and repetitive blood monitoring. Although disturbances to Virchow's triad may not be detrimental to most individuals, approximately 1 in 1,000 athletes will experience a potentially fatal post-exercise thrombotic incidence. When acquired factors are considered in conjunction with genetic predispositions to hypercoagulability present in some athletes, an overall increased risk for VTE is present.

The Interface of Clinical Decision-Making With Study Protocols for Knowledge Translation From a Walking Recovery Trial.

BACKGROUND AND PURPOSE: Despite efforts to translate knowledge into clinical practice, barriers often arise in adapting the strict protocols of a randomized, controlled trial (RCT) to the individual patient. The Locomotor Experience Applied Post-Stroke (LEAPS) RCT demonstrated equal effectiveness of 2 intervention protocols for walking recovery poststroke; both protocols were more effective than usual care physical therapy. The purpose of this article was to provide knowledge-translation tools to facilitate implementation of the LEAPS RCT protocols into clinical practice. METHODS: Participants from 2 of the trial's intervention arms: (1) early Locomotor Training Program (LTP) and (2) Home Exercise Program (HEP) were chosen for case presentation. The two cases illustrate how the protocols are used in synergy with individual patient presentations and clinical expertise. Decision algorithms and guidelines for progression represent the interface between implementation of an RCT standardized intervention protocol and clinical decision-making. OUTCOMES: In each case, the participant presents with a distinct clinical challenge that the therapist addresses by integrating the participant's unique presentation with the therapist's expertise while maintaining fidelity to the LEAPS protocol. Both participants progressed through an increasingly challenging intervention despite their own unique presentation. SUMMARY: Decision algorithms and exercise progression for the LTP and HEP protocols facilitate translation of the RCT protocol to the real world of clinical practice. The two case examples to facilitate translation of the LEAPS RCT into clinical practice by enhancing understanding of the protocols, their progression, and their application to individual participants.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A147).