Citations

Abstract Muscle plasticity is defined as the ability of a given muscle to alter its structural and functional properties in accordance with the environmental conditions imposed on it. As such, respiratory muscle is in a constant state of remodeling, and the basis of muscle's plasticity is its ability to change protein expression and resultant protein balance in response to varying environmental conditions. Here, we will describe the changes of respiratory muscle imposed by extrinsic changes in mechanical load, activity, and innervation. Although there is a large body of literature on the structural and functional plasticity of respiratory muscles, we are only beginning to understand the molecular‐scale protein changes that contribute to protein balance. We will give an overview of key mechanisms regulating protein synthesis and protein degradation, as well as the complex interactions between them. We suggest future application of a systems biology approach that would develop a mathematical model of protein balance and greatly improve treatments in a variety of clinical settings related to maintaining both muscle mass and optimal contractile function of respiratory muscles. © 2012 American Physiological Society. Compr Physiol 2:1441‐1462, 2012.

Abstract Pulmonary vascular disease is a frequent complication of chronic liver disease and portal hypertension, affecting up to 30% of patients. There are two distinct pulmonary vascular complications of liver disease: hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). HPS affects 25% of patients with chronic liver disease and is characterized by intrapulmonary vasodilatation and abnormal arterial oxygenation. HPS negatively impacts quality of life and is associated with a 2‐fold increased risk of death compared to controls with liver disease without HPS. Angiogenesis, endothelin‐1 mediated endothelial dysfunction, monocyte influx, and alveolar type 2 cell dysfunction seem to play important roles in disease pathogenesis but there are currently no effective medical therapies. Fortunately, HPS resolves following liver transplant (LT) with improvements in hypoxemia. POPH is a subtype of pulmonary arterial hypertension (PAH) characterized by an elevated mean pulmonary arterial pressure and pulmonary vascular resistance in the setting of normal left‐sided filling pressures. POPH affects 5% to 6% of patients with chronic liver disease. Although the pathogenesis has not been fully elucidated, endothelial dysfunction, inflammation, and estrogen signaling have been identified as key pathways involved in disease pathogenesis. POPH is typically treated with PAH targeted therapy and may also improve with liver transplantation in selected patients. This article highlights what is currently known regarding the diagnosis, management, pathobiology, and outcomes of HPS and POPH. Ongoing research is needed to improve understanding of the pathophysiology and outcomes of these distinct and often misunderstood pulmonary vascular complications of liver disease. © 2021 American Physiological Society. Compr Physiol 12:3281‐3302, 2022.

To address the limitations of existing instruments, the authors developed the Vestibular Schwannoma Quality of Life (VSQOL) Index. The Index captures the multifaceted impacts of vestibular schwannoma (VS) on daily life across eight categories: hearing problems; dizziness and imbalance; pain, discomfort, and tinnitus; problems with face or eyes; impact on physical, emotional, and social well-being; difficulty with thinking and memory; satisfaction or regret; and impact on employment. Initially developed in English, this digital supplement of the Journal of Neurosurgery presents translations of the VSQOL Index to Simplified Chinese, Spanish, Japanese, Arabic, French, and Norwegian. These translations aim to improve access to VS quality of life (QOL) research globally with enhanced racial, ethnic, and geographic representation. The goal is to comprehensively evaluate the impact of VS diagnosis and management on well-being and QOL by offering the VSQOL Index in patients’ native, or first-learned, languages. The English version and these translations may be used for noncommercial research, clinical, or educational purposes without written permission from the authors. Investigators interested in translating the VSQOL Index to other languages should contact the corresponding author for translation methodology instructions.

OBJECTIVE Triceps motor branch transfer to the anterior division of the axillary nerve (AXN) was originally described for patients with a loss of deltoid function secondary to upper trunk (UT) brachial plexus injuries but has evolved to restore deltoid function in isolated peripheral AXN injuries. The purpose of this study was to compare functional outcomes in patients who had undergone this procedure in the setting of UT brachial plexus injury versus peripheral AXN injury. METHODS The records of patients who had undergone triceps branch to anterior division of the AXN transfer at a single academic institution between 2001 and 2023 were retrospectively reviewed. Patients were included in the study if they had either a UT or an AXN injury and were excluded if their follow-up was less than 2 years. Pre- and postoperative outcomes, including modified British Medical Research Council grade and range of motion, were compared between the two groups. RESULTS Forty-two patients met the criteria for inclusion. Thirty cases were classified as UT injury and 12 cases as AXN injury. The mean postoperative abduction strength was significantly higher in the AXN injury group (3.2 ± 1.5 vs 1.9 ± 1.2, p = 0.007), as was the postoperative change in abduction strength (2.8 ± 1.7 vs 1.6 ± 1.4, p = 0.01). The mean postoperative forward flexion (136° ± 57° vs 79° ± 54°, p = 0.005) and abduction (129° ± 64° vs 59° ± 47°, p = 0.004) were significantly better in the AXN group, although postoperative changes in flexion and abduction were not different between the groups. Triceps strength preoperatively was similar to that postoperatively in both groups. CONCLUSIONS Patients with an AXN injury, compared to those with a UT injury, had better postoperative abduction strength and shoulder range of motion after triceps branch transfer to the anterior division of the AXN. Triceps strength was not significantly changed after the procedure in the two groups. The study findings suggest that the outcomes of triceps branch transfer to the anterior division of the AXN are different based on the location and type of injury, providing insight into prognosis while counseling patients.

AbstractNeuroblastoma (NB) is an aggressive malignant tumor arising from a primitive neural crest origin. While the significance of tumor location in survival outcomes is recognized, it remains inadequately explored. This study provides a comprehensive analysis of the survival and characteristics of pediatric adrenal and nonadrenal NBs in the United States.A retrospective analysis of pediatric primary NB between 1975 and 2016 was conducted using the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate regression analyses were used to determine prognostic variables.A total of 4,554 patients were included, comprising 52% males (n = 2,385) and 79.2% Caucasians (n = 3,569). The median age of the patients was one year (range: 0–19 years). In all, 44.4% (n = 1,996) of the patients had adrenal NB and 55.6% (n = 2,496) patients had nonadrenal NB. Adrenal NB was significantly more prevalent among males and those presenting at a younger age (p < 0.001). Adrenal NB was more likely to have a higher grade and distant metastasis at diagnosis (p < 0.001). Nonadrenal NB, female sex, surgical resection, and later year of diagnosis were associated with improved survival (p < 0.001).This study highlights important factors that are helpful for prognostication of NB patients in the United States. Tailored approaches considering tumor site are crucial for effective management of NB.

Abstract Introduction Case reports and series are critical to guide initial decision-making in a pandemic, but may have lower rigor because of the need to publish them quickly. This meta-epidemiologic study compares the methodological quality of case series that described the acute coronavirus disease 2019 (COVID-19) pandemic in 2020 versus those that described long-haul cases. Methods We conducted a systematic review in multiple databases for long-haul case series and reports. We identified early cases of acute COVID-19 synthesized in published systematic reviews. We evaluated the methodological quality by pairs of independent reviewers using a tool dedicated for appraising case series. Results We included 239 original case series (81 published in the first year of the pandemic and 158 published later describing long-haul COVID). The methodological quality of both groups of case series was very good (80–100% of series satisfying quality items) except for two items, the selection approach of cases included in the series and ruling out other causes that can explain the main finding described in the series. The appraisal tool demonstrated high agreement and reliability between reviewers. Conclusion The methodological quality of modern case series is high, except for two quality items that represent an area for potential for improvement for authors of case series describing future pandemics.

Abstract Cholangiocytes are epithelial cells that line the intra‐ and extrahepatic ducts of the biliary tree. The main physiologic function of cholangiocytes is modification of hepatocyte‐derived bile, an intricate process regulated by hormones, peptides, nucleotides, neurotransmitters, and other molecules through intracellular signaling pathways and cascades. The mechanisms and regulation of bile modification are reviewed herein. © 2013 American Physiological Society. Compr Physiol 3:541‐565, 2013.

ABSTRACT This review concentrates on the determinants of gas exchange abnormalities in liver‐induced pulmonary vascular disorders, more specifically in the hepatopulmonary syndrome. Increased alveolar‐arterial O 2 difference, with or without different levels of arterial hypoxemia, and reduced diffusing capacity represent the most characteristic gas exchange disturbances in the absence of cardiac and pulmonary comorbidities. Pulmonary gas exchange abnormalities in the hepatopulmonary syndrome are unique encompassing all three pulmonary factors determining arterial PO 2 , that is, ventilation‐perfusion imbalance, increased intrapulmonary shunt and oxygen diffusion limitation that, combined, interplay with two relevant nonpulmonary determinants, that is, increased total ventilation and high cardiac output. Behind the complexity of this lung‐liver association there is an abnormal pulmonary vascular tone that combines inhibition of hypoxic pulmonary vasoconstriction with a reduced (or blunted) hypoxic vascular response. The pathology and pathobiology include the presence of intrapulmonary vascular dilatations with or without pulmonary vascular remodeling, i.e. angiogenesis. Liver transplantation, the only effective therapeutic approach to successfully improve and resolve the vast majority of complications induced by the hepatopulmonary syndrome, along with a large list of frustrating pharmacologic interventions, are also reviewed. Another liver‐induced pulmonary vascular disorder with less gas exchange involvement, such as portopulmonary hypertension, is also considered. © 2018 American Physiological Society. Compr Physiol 8:711‐729, 2018.

Abstract The lung is an inherently mechanosensitive organ, where cells of the airway and parenchyma experience a range of mechanical forces throughout life including shear, stretch, and compression, in both health and disease. In this regard, pediatric and adult lung diseases such as wheezing and asthma, bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF) all involve macroscopic and cellular changes to the mechanical properties of the bronchial airways and/or parenchyma to varying extents. Accordingly, understanding how mechanical forces are sensed in the lung, and the responses of cells and tissues in the context of normal development and health versus disease conditions becomes highly relevant. There is increasing recognition that transduction of mechanical forces into cellular responses involves a number of channels, some of which are inherently mechanosensitive. Such channels trigger mechanotransduction pathways that may further mediate cellular remodeling, inflammation, and other pathophysiologic mechanisms in response to stretch, stiffness, and inflammatory cascades. Two particularly important channel families have emerged in pulmonary pathophysiology: the transient receptor potential vanilloid family with focus on member TRPV4 and the recently identified Piezo (PZ) channels. Here, we explore current understanding of the contributions of TRPV4 and PZ channels in lung health and disease states, focusing on the interactions between these mechanosensitive channels and their local environment including immune cells, the extracellular matrix, and cellular cytoskeletal elements. We further discuss potential areas for future research to better understand the impact of mechanical channels on pulmonary health and disease. © 2023 American Physiological Society. Compr Physiol 13:5157‐5178, 2023.