A methodological approach for collecting simultaneous measures of muscle, aponeurosis, and tendon behaviour during dynamic contractions.

Skeletal muscles and the tendons that attach them to bone are structurally complex and deform non-uniformly during contraction. While these tissue deformations dictate force production during movement, our understanding of this behaviour is limited due to challenges in obtaining complete measures of the constituent structures. To address these challenges, we present an approach for simultaneously measuring muscle, fascicle, aponeurosis, and tendon behaviour using sonomicrometry. To evaluate this methodology, we conducted isometric and dynamic contractions in in situ rabbit medial gastrocnemius. We found comparable patterns of strain in the muscle belly, fascicle, aponeurosis, and tendon during the isometric trials to those published in the literature. For the dynamic contractions, we found that our measures using this method were consistent across all animals and aligned well with our theoretical understanding of muscle-tendon unit behaviour. Thus, this method provides a means to fully capture the complex behaviour of muscle-tendon units across contraction types.

A systematic literature review of clinical evidence and treatment burden in newly diagnosed high-risk pediatric patients with classical Hodgkin lymphoma.

This systematic literature review evaluated frontline treatment burden in pediatric and adolescent/young adult (AYA) patients with high-risk classical Hodgkin lymphoma (cHL) among studies originating from the United States. Data were extracted from 32 publications (screened: total, n = 3115; full-text, n = 98) representing 12 studies (randomized controlled trials [RCTs], n = 2; non-comparative, non-randomized, n = 7; observational, n = 3). High-risk disease definitions varied across studies. Five-year event-free survival (EFS)/progression-free survival (PFS) was 86%-100% and 79%-94%, and complete response rates were 35%-100% and 5%-64% for brentuximab vedotin (BV)-containing and chemotherapy-alone regimens, respectively. In identified RCTs, BV-containing compared with chemotherapy-alone regimens demonstrated significantly longer 3-year EFS/5-year PFS. Hematological and peripheral neuropathy were the most commonly reported adverse events of interest, although safety data were inconsistently reported. Few studies evaluated humanistic and no studies evaluated economic burden. Results from studies with the highest quality of evidence indicate an EFS/PFS benefit for frontline BV-containing versus chemotherapy-alone regimens for pediatric/AYA patients with high-risk cHL.

Prevalence and characteristics of hepatitis delta virus infection in patients with hepatitis B in the United States: An analysis of the All-Payer Claims Database.

BACKGROUND AND AIMS: HDV leads to the most severe form of viral hepatitis; however, the prevalence of HDV is not well understood. Using real-world data from the All-Payer Claims Database, this study estimates the prevalence of HBV/HDV infection among the chronic HBV population and describes patient/clinical characteristics for adults with HBV/HDV infection in the United States. APPROACH AND RESULTS: Adults (≥18 years) with ≥1 inpatient claim or ≥2 outpatient claims for HDV infection or HBV in the All-Payer Claims Database from January 1, 2014, to December 31, 2020, were identified. HDV prevalence was calculated as the proportion of patients with HBV/HDV infection among total patients with HBV infection. Patient characteristics, socioeconomic status, advanced liver complications (eg, cirrhosis, HCC), and comorbidities were assessed. A total of 6719 patients were diagnosed with HBV/HDV among 144,975 with HBV and 12 months of continuous data, for a prevalence of 4.6%. At diagnosis, 31.7% of patients with HBV/HDV had advanced liver complications, including compensated cirrhosis (16.3%) and decompensated cirrhosis (10.4%). Diabetes (50.5%), hypertension (49.8%), and HIV infection (30.9%) were the top 3 comorbidities. CONCLUSIONS: In a large database capturing approximately 80% of the US-insured population, HBV/HDV infection prevalence was 4.6% among adults infected with HBV. Patients infected with HDV had high rates of baseline liver complications and other comorbidities at the time of diagnosis, suggesting potentially delayed diagnosis and/or treatment. Earlier identification of HBV/HDV infection among the population with HBV may provide opportunities to improve linkage to care and treatment, thereby reducing the risk of liver-related morbidity and mortality.

High-fat high-sucrose diet leads to dynamic structural and inflammatory alterations in the rat vastus lateralis muscle.

The influence of obesity on muscle integrity is not well understood. The purpose of this study was to quantify structural and molecular changes in the rat vastus lateralis (VL) muscle as a function of a 12-week obesity induction period and a subsequent adaptation period (additional 16-weeks). Male Sprague-Dawley rats consumed a high-fat, high-sucrose (DIO, n = 40) diet, or a chow control-diet (n = 14). At 12-weeks, DIO rats were grouped as prone (DIO-P, top 33% of weight change) or resistant (DIO-R, bottom 33%). Animals were euthanized at 12- or 28-weeks on the diet. At sacrifice, body composition was determined and VL muscles were collected. Intramuscular fat, fibrosis, and CD68+ cells were quantified histologically and relevant molecular markers were evaluated using RT-qPCR. At 12- and 28-weeks post-obesity induction, DIO-P rats had more mass and body fat than DIO-R and chow rats (p < 0.05). DIO-P and DIO-R rats had similar losses in muscle mass, which were greater than those in chow rats (p < 0.05). mRNA levels for MAFbx/atrogin-1 were reduced in DIO-P and DIO-R rats at 12- and 28-weeks compared to chow rats (p < 0.05), while expression of MuRF1 was similar to chow values. DIO-P rats demonstrated increased mRNA levels for pro-inflammatory mediators, inflammatory cells, and fibrosis compared to DIO-R and chow animals, despite having similar levels of intramuscular fat. The down-regulation of MAFbx/atrogin-1 may suggest onset of degenerative changes in VL muscle integrity of obese rats. DIO-R animals exhibited fewer inflammatory changes compared to DIO-P animals, suggesting a protective effect of obesity resistance on local inflammation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2069-2078, 2016.

Investigating the mechanisms of massage efficacy: the role of mechanical immunomodulation.

Massage has the potential to attenuate the inflammatory process, facilitate early recovery, and provide pain relief from muscular injuries. In this hypothesis-driven paper, we integrate the concept of mechanotransduction with the application of massage to explore beneficial mechanisms. By altering signaling pathways involved with the inflammatory process, massage may decrease secondary injury, nerve sensitization, and collateral sprouting, resulting in increased recovery from damage and reduction or prevention of pain. Our goal is to provide a framework that describes our current understanding of the mechanisms whereby massage therapy activates potentially beneficial immunomodulatory pathways.

Immunomodulatory effects of massage on nonperturbed skeletal muscle in rats.

Massage is an ancient manual therapy widely utilized by individuals seeking relief from various musculoskeletal maladies. Despite its popularity, the majority of evidence associated with massage benefits is anecdotal. Recent investigations have uncovered physiological evidence supporting its beneficial use following muscle injury; however, the effects of massage on healthy, unperturbed skeletal muscle are unknown. Utilizing a custom-fabricated massage mimetic device, the purpose of this investigation was to elucidate the effects of various loading magnitudes on healthy skeletal muscle with particular interest in the gene expression profile and modulation of key immune cells involved in the inflammatory response. Twenty-four male Wistar rats (200 g) were subjected to cyclic compressive loading (CCL) over the right tibialis anterior muscle for 30 min, once a day, for 4 consecutive days using four loading conditions: control (0N), low load (1.4N), moderate load (4.5N), and high load (11N). Microarray analysis showed that genes involved with the immune response were the most significantly affected by application of CCL. Load-dependent changes in cellular abundance were seen in the CCL limb for CD68(+) cells, CD163(+) cells, and CD43(+)cells. Surprisingly, load-independent changes were also discovered in the non-CCL contralateral limb, suggesting a systemic response. These results show that massage in the form of CCL exerts an immunomodulatory response to uninjured skeletal muscle, which is dependent upon the applied load.