Showing papers by "Christopher L. Mendias published in 2020"
TL;DR: The purpose of this article was to summarize the known musculoskeletal pathologies in patients with SARS or COVID-19 and to combine this with computational modeling and biochemical signaling studies to predict musculOSkeletal cellular targets and long-term consequences of the SARS-CoV-2 infection.
Abstract: Coronavirus disease 2019 (COVID-19) is an emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients who become infected with SARS-CoV-2 are asymptomatic or have mild symptoms, some patients develop severe symptoms that can permanently detract from their quality of life. SARS-CoV-2 is closely related to SARS-CoV-1, which causes severe acute respiratory syndrome (SARS). Both viruses infect the respiratory system, and there are direct and indirect effects of this infection on multiple organ systems, including the musculoskeletal system. Epidemiological data from the SARS pandemic of 2002 to 2004 identified myalgias, muscle dysfunction, osteoporosis, and osteonecrosis as common sequelae in patients with moderate and severe forms of this disease. Early studies have indicated that there is also considerable musculoskeletal dysfunction in some patients with COVID-19, although long-term follow-up studies have not yet been conducted. The purpose of this article was to summarize the known musculoskeletal pathologies in patients with SARS or COVID-19 and to combine this with computational modeling and biochemical signaling studies to predict musculoskeletal cellular targets and long-term consequences of the SARS-CoV-2 infection.
244 citations
TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus as a source of infection in animals and its role in the immune system is investigated.
Abstract: OBJECTIVE: To evaluate inpatient outcomes among patients with hip fracture treated during the COVID-19 pandemic in New York City. DESIGN: Multicenter retrospective cohort study. SETTING: One Level 1 trauma center and one orthopaedic specialty hospital in New York City. PATIENTS/PARTICIPANTS: Fifty-nine consecutive patients (average age 85 years, range: 65-100 years) treated for a hip fracture (OTA/AO 31, 32.1) over a 5-week period, March 20, 2020, to April 24, 2020, during the height of the COVID-19 crisis. MAIN OUTCOME MEASUREMENTS: COVID-19 infection status was used to stratify patients. The primary outcome was inpatient mortality. Secondary outcomes were admission to the intensive care unit, unexpected intubation, pneumonia, deep vein thrombosis, pulmonary embolus, myocardial infarction, cerebrovascular accident, urinary tract infection, and transfusion. Baseline demographics, comorbidities, treatment characteristics, and COVID-related symptomatology were also evaluated. RESULTS: Ten patients (15%) tested positive for COVID-19 (COVID+) (n = 9; 7 preoperatively and 2 postoperatively) or were presumed positive (n = 1), 40 (68%) patients tested negative, and 9 (15%) patients were not tested in the primary hospitalization. American Society of Anesthesiologists' scores were higher in the COVID+ group (d = -0.83; P = 0.04); however, the Charlson Comorbidity Index was similar between the study groups (d = -0.17; P = 0.63). Inpatient mortality was significantly increased in the COVID+ cohort (56% vs. 4%; odds ratio 30.0, 95% confidence interval 4.3-207; P = 0.001). Including the one presumed positive case in the COVID+ cohort increased this difference (60% vs. 2%; odds ratio 72.0, 95% confidence interval 7.9-754; P < 0.001). CONCLUSIONS: Hip fracture patients with concomitant COVID-19 infection had worse American Society of Anesthesiologists' scores but similar baseline comorbidities with significantly higher rates of inpatient mortality compared with those without concomitant COVID-19 infection. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
97 citations
TL;DR: A novel and interactive tendon atlas highlights previously underappreciated heterogeneity between and within tendon cell populations, and modeled cell-cell interactions and identified previously undescribed ligand-receptor signaling interactions involved in tendon homeostasis.
Abstract: Tendon is a dense connective tissue that stores and transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of t...
59 citations
TL;DR: A protocol for universal testing of all orthopaedic surgery admissions at 1 hospital in New York City during a 3-week period revealed a high rate of COVID-19 infections, and the majority of these patients were asymptomatic.
Abstract: BACKGROUND: The long incubation period and asymptomatic spread of COVID-19 present considerable challenges for health-care institutions. The identification of infected individuals is vital to prevent the spread of illness to staff and other patients as well as to identify those who may be at risk for disease-related complications. This is particularly relevant with the resumption of elective orthopaedic surgery around the world. We report the results of a universal testing protocol for COVID-19 in patients undergoing orthopaedic surgery during the coronavirus pandemic and to describe the postoperative course of asymptomatic patients who were positive for COVID-19. METHODS: A retrospective review of adult operative cases between March 25, 2020, and April 24, 2020, at an orthopaedic specialty hospital in New York City was performed. Initially, a screening questionnaire consisting of relevant signs and symptoms (e.g., fever, cough, shortness of breath) or exposure dictated the need for nasopharyngeal swab real-time quantitative polymerase chain reaction (RT-PCR) testing for all admitted patients. An institutional policy change occurred on April 5, 2020, that indicated nasopharyngeal swab RT-PCR testing for all orthopaedic admissions. Screening and testing data for COVID-19 as well as relevant imaging, laboratory values, and postoperative complications were reviewed for all patients. RESULTS: From April 5, 2020, to April 24, 2020, 99 patients underwent routine nasopharyngeal swab testing for COVID-19 prior to their planned orthopaedic surgical procedure. Of the 12.1% of patients who tested positive for COVID-19, 58.3% were asymptomatic. Three asymptomatic patients developed postoperative hypoxia, with 2 requiring intubation. The negative predictive value of using the signs and symptoms of disease to predict a negative test result was 91.4% (95% confidence interval [CI], 81.0% to 97.1%). Including a positive chest radiographic finding as a screening criterion did not improve the negative predictive value of screening (92.5% [95% CI, 81.8% to 97.9%]). CONCLUSIONS: A protocol for universal testing of all orthopaedic surgery admissions at 1 hospital in New York City during a 3-week period revealed a high rate of COVID-19 infections. Importantly, the majority of these patients were asymptomatic. Using chest radiography did not significantly improve the negative predictive value of screening. These results have important implications as hospitals anticipate the resumption of elective surgical procedures. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
58 citations
TL;DR: On the basis of the findings, the use of BFRT in conjunction with high-intensity resistance exercise in patients undergoing ACLR to improve quadriceps muscle function may not be warranted.
Abstract: Background:A major goal of rehabilitation after anterior cruciate ligament reconstruction (ACLR) is restoring quadriceps muscle strength. Unfortunately, current rehabilitation paradigms fall short ...
32 citations
TL;DR: The results indicate that scleraxis is required for mechanically-stimulated adult tendon growth by causing the commitment of CD146+ pericytes into the tenogenic lineage, and by promoting the initial expansion of newly committed tenocytes and the production of extracellular matrix proteins.
Abstract: Scleraxis is a basic helix-loop-helix transcription factor that plays a central role in promoting tenocyte proliferation and matrix synthesis during embryonic tendon development. However, the role of scleraxis in the growth and adaptation of adult tendons is not known. We hypothesized that scleraxis is required for tendon growth in response to mechanical loading, and that scleraxis promotes the specification of progenitor cells into tenocytes. We conditionally deleted scleraxis in adult mice using a tamoxifen-inducible Cre-recombinase expressed from the Rosa26 locus (ScxΔ), and then induced tendon growth in Scx+ and ScxΔ adult mice via plantaris tendon mechanical overload. Compared to the wild type Scx+ group, ScxΔ mice demonstrated blunted tendon growth. Transcriptional and proteomic analyses revealed significant reductions in cell proliferation, protein synthesis, and extracellular matrix genes and proteins. Our results indicate that scleraxis is required for mechanically-stimulated adult tendon growth by causing the commitment of CD146+ pericytes into the tenogenic lineage, and by promoting the initial expansion of newly committed tenocytes and the production of extracellular matrix proteins.
30 citations
TL;DR: There is an adaptive immune response to tendon injury and adaptive immune cells may play a role in regulating tendon healing, according to a greater understanding of the biological processes that regulate tendon healing.
Abstract: Tendon injuries are a common clinical condition with limited treatment options. The cellular components of the innate immune system, such as neutrophils and macrophages, have been studied in tendon injuries. However, the adaptive immune system, comprising specialized lymphocytes, plays an important role in orchestrating the healing of numerous tissues, but less is known about these cells in tendon healing. To gain a greater understanding of the biological processes that regulate tendon healing, we determined how the cellular components of the adaptive and innate immune system respond to a tendon injury using two-month-old male mice. We observed that lymphatic vasculature is present in the epitenon and superficial regions of Achilles tendons, and that the lymphatics drain into the popliteal lymph node. We then created an acute Achilles tenotomy followed by repair, and collected tendons and popliteal lymph nodes 1, 2, and 4 wk after injury. Tendon injury resulted in a robust adaptive immune cell response that followed an initial innate immune cell response in tendons and lymph nodes. Monocytes, neutrophils, and macrophages initially accumulated at 1 wk after injury in tendons, while dendritic cells and CD4+ T cells peaked at 2 wk after injury. B cells and CD8+ T cells progressively increased over time. In parallel, immune cells of the popliteal lymph node demonstrated a similarly coordinated response to the injury. These results suggest that there is an adaptive immune response to tendon injury, and adaptive immune cells may play a role in regulating tendon healing.NEW & NOTEWORTHY While the innate immune system, consisting of macrophages and related hematopoietic cells, has been studied in tendon injury, less is known about the adaptive immune system. Using a mouse model of Achilles tendon tenotomy and repair, we observed an adaptive immune cell response, consisting of CD4+ and CD8+ T cells, and B cells, which occur through 4 wk after tendon injury. This response appeared to be coordinated by the draining popliteal lymph node.
22 citations
TL;DR: The results indicate that scleraxis is required for mechanically-stimulated adult tendon growth by causing the commitment of CD146+ pericytes into the tenogenic lineage, and by promoting the initial expansion of newly committed tenocytes and the production of extracellular matrix proteins.
Abstract: Scleraxis is a basic helix-loop-helix transcription factor that plays a central role in promoting tenocyte proliferation and matrix synthesis during embryonic tendon development. However, the role of scleraxis in the growth and adaptation of adult tendons is not known. We hypothesized that scleraxis is required for tendon growth in response to mechanical loading, and that scleraxis promotes the specification of progenitor cells into tenocytes. We conditionally deleted scleraxis in adult mice using a tamoxifen-inducible Cre-recombinase expressed from the Rosa26 locus (ScxΔ), and then induced tendon growth in Scx+ and ScxΔ adult mice via plantaris tendon mechanical overload. Compared to the wild type Scx+ group, ScxΔ mice demonstrated blunted tendon growth. Transcriptional and proteomic analyses revealed significant reductions in cell proliferation, protein synthesis, and extracellular matrix genes and proteins. Our results indicate that scleraxis is required for mechanically-stimulated adult tendon growth by causing the commitment of CD146+ pericytes into the tenogenic lineage, and by promoting the initial expansion of newly committed tenocytes and the production of extracellular matrix proteins.
18 citations
TL;DR: The overall findings from this study identified that although tendons across the body share a common anatomical definition based on their physical location between skeletal muscle and bone, tendon is a surprisingly genetically heterogeneous tissue.
Abstract: Key points Tendon is a hypocellular, matrix-rich tissue that has been excluded from comparative transcriptional atlases. These atlases have provided important knowledge about biological heterogeneity between tissues, and our study addresses this important gap. We performed measures on four of the most studied tendons, the Achilles, forepaw flexor, patellar and supraspinatus tendons of both mice and rats. These tendons are functionally distinct and are also among the most commonly injured, and therefore of important translational interest. Approximately one-third of the filtered transcriptome was differentially regulated between Achilles, forepaw flexor, patellar and supraspinatus tendons within either mice or rats. Nearly two-thirds of the transcripts that are expressed in anatomically similar tendons were different between mice and rats. The overall findings from this study identified that although tendons across the body share a common anatomical definition based on their physical location between skeletal muscle and bone, tendon is a surprisingly genetically heterogeneous tissue. Abstract Tendon is a functionally important connective tissue that transmits force between skeletal muscle and bone. Previous studies have evaluated the architectural designs and mechanical properties of different tendons throughout the body. However, less is known about the underlying transcriptional differences between tendons that may dictate their designs and properties. Therefore, our objective was to develop a comprehensive atlas of the transcriptome of limb tendons in adult mice and rats using systems biology techniques. We selected the Achilles, forepaw digit flexor, patellar, and supraspinatus tendons due to their divergent functions and high rates of injury and tendinopathies in patients. Using RNA sequencing data, we generated the Comparative Tendon Transcriptional Database (CTTDb) that identified substantial diversity in the transcriptomes of tendons both within and across species. Approximately 30% of filtered transcripts were differentially regulated between tendons of a given species, and nearly 60% of the filtered transcripts present in anatomically similar tendons were different between species. Many of the genes that differed between tendons and across species are important in tissue specification and limb morphogenesis, tendon cell biology and tenogenesis, growth factor signalling, and production and maintenance of the extracellular matrix. This study indicates that tendon is a surprisingly heterogenous tissue with substantial genetic variation based on anatomical location and species.
18 citations
TL;DR: In this article, the authors explore the heterogeneity of cells in mouse Achilles tendons using single-cell RNA sequencing and identify 11 distinct cell types in tendons, including 3 previously undescribed populations of fibroblasts.
Abstract: Tendon is a connective tissue that transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of tissue homeostasis and disease, but little is known about the diversity of cells that populate tendon. Our objective was to explore the heterogeneity of cells in mouse Achilles tendons using single-cell RNA sequencing. We assembled a transcriptomic atlas and identified 11 distinct cell types in tendons, including 3 previously undescribed populations of fibroblasts. Using trajectory inference analysis, we provide additional support for the notion that pericytes are progenitor cells for the fibroblasts that compose adult tendons. We also modeled cell-interactions and identified ligand-receptor pairs involved in tendon homeostasis. Our findings highlight notable heterogeneity between and within tendon cell populations, which may contribute to our understanding of tendon extracellular matrix assembly and maintenance, and inform the design of therapies to treat tendinopathies.
10 citations
TL;DR: HGH improved quadriceps strength and reduced MMP3 levels in patients undergoing ACLR, and further trials to more comprehensively evaluate the ability of HGH to improve muscle function and potentially protect against OA in patients underwent ACLR are warranted.
Abstract: Background:Anterior cruciate ligament (ACL) tears are common knee injuries. Despite undergoing extensive rehabilitation after ACL reconstruction (ACLR), many patients have persistent quadriceps mus...
TL;DR: In this article, the Murphy Roths Large (MRL) strain of mice was compared with the commonly used C57Bl/6 (B6) strain, and the MRL mice would have less muscle fiber atrophy and fat accumulation, and be protected against the loss in force production that occurs after cuff tear.