Background The availability of non-invasive means to evaluate and monitor tendon-bone healing pro... more Background The availability of non-invasive means to evaluate and monitor tendon-bone healing processes in-vivo is limited. Micro Positron-Emission-Tomography (µPET) using 18F-Fluoride is a minimally invasive imaging modality, with which osteoblast activity and bone turnover can be assessed. The aim of this study was to investigate the use of serial in-vivo µPET/CT scans to evaluate bone turnover along the graft-tunnel interface in a rat ACL (anterior cruciate ligament) reconstruction model. Methods Unilateral autograft ACL reconstruction was performed in six rats. µPET/CT-scans using 18F-Fluoride were performed 7, 14, 21, and 28 days postoperatively. Standard uptake values (SUV) were calculated for three tunnel regions (intraarticular aperture (IAA), mid-tunnel, and extraarticular aperture (EAA)) of the proximal tibia. Animals were sacrificed at 28 days and evaluated with µCT and histological analysis. Results SUVs in both bone tunnels showed an increased 18F-Fluoride uptake at 7 d...
Supplemental material, DS_10.1177_0363546519898691 for Effect of Lubricin Mimetics on the Inhibit... more Supplemental material, DS_10.1177_0363546519898691 for Effect of Lubricin Mimetics on the Inhibition of Osteoarthritis in a Rat Anterior Cruciate Ligament Transection Model by Daniel Nemirov, Yusuke Nakagawa, Zhexun Sun, Amir Lebaschi, Susumu Wada, Camila Carballo, Xiang-Hua Deng, David Putnam, Lawrence J. Bonassar and Scott A. Rodeo in The American Journal of Sports Medicine
Background: The underlying cellular and molecular mechanisms involved in the development of tendi... more Background: The underlying cellular and molecular mechanisms involved in the development of tendinopathy due to subacromial supraspinatus tendon (SST) impingement and the response to subsequent removal of impingement remain unknown. Purpose: To investigate the involvement of Indian hedgehog (IHH) signaling in the development of SST tendinopathy and the subsequent healing process after the relief of subacromial impingement in a novel mouse shoulder impingement model. Study Design: Controlled laboratory study. Methods: A total of 48 male wild-type C57BL/6 mice were used in this study. Supraspinatus tendinopathy was induced by inserting a microsurgical clip into the subacromial space bilaterally. Eleven mice were sacrificed at 4 weeks after surgery to establish impingement baseline; 24 mice underwent clip removal at 4 weeks after surgery and then were euthanized at 2 or 4 weeks after clip removal. Thirteen mice without surgical intervention were utilized as the control group. All SSTs ...
Journal of Bone and Joint Surgery-british Volume, 2016
Bone marrow concentrates are being used to augment soft tissue healing. However, only 0.01% of th... more Bone marrow concentrates are being used to augment soft tissue healing. However, only 0.01% of these cells meet the criteria of a mesenchymal stem cell (MSC), which likely accounts for the variability in reported results. Previous studies using an established rat rotator cuff repair model have demonstrated that bone marrow-derived MSCs had no effect on healing. In this study we evaluated the effect of purified human MSCs on rotator cuff healing in an athymic rat model. Hypothesis: Purified human MSCs added to the repair site will improve biomechanical strength and fibrocartilage formation of the healing tendon. Fifty-two athymic rats underwent unilateral detachment and repair of the supraspinatus tendon with either fibrin glue (control) or fibrin glue with 106 hMSCs (experimental) applied at the repair site. Flow cytometry verified the stem cell phenotype of the cells as CD73+, CD90+, CD105+, CD14-, CD34- and CD45-. Rats were sacrificed at 2 and 4 weeks, with 10 used for biomechanic...
BACKGROUND The purpose of this study was to assess mitochondrial dysfunction in a murine model of... more BACKGROUND The purpose of this study was to assess mitochondrial dysfunction in a murine model of supraspinatus tendinopathy. METHODS Eighty-four mice (168 limbs) were included in the study. Supraspinatus tendinopathy was induced by inserting a microsurgical clip in the subacromial space of 63 mice bilaterally (126 limbs). Forty-two of these limbs were harvested at 4 weeks postoperatively, 42 underwent clip removal at 4 weeks after the initial procedure and were harvested at 2 weeks, and 42 underwent clip removal at 4 weeks and were harvested at 4 weeks. Forty-two limbs in the remaining 21 mice did not undergo surgical intervention and were utilized as the control group. Outcomes included biomechanical, histological, gene expression, superoxide dismutase (SOD) activity, and transmission electron microscopy (TEM) analyses. RESULTS Radiographs confirmed stable clip position in the subacromial space at 4 weeks. Biomechanical testing demonstrated a 60% decrease in failure force of the supraspinatus tendons at 4 weeks compared with the control group. The failure force gradually increased at 2 and 4 weeks after clip removal. Histological analysis demonstrated inflammation surrounding the tendon with higher modified Bonar scores at 4 weeks after clip placement followed by gradual improvement following clip removal. The expression of mitochondrial-related genes was decreased at 4 weeks after clip placement and then significantly increased after clip removal. SOD activity decreased significantly at 4 weeks after clip placement but increased following clip removal. TEM images demonstrated alterations in morphology and the number of mitochondria and cristae at 4 weeks after clip placement with improvement after clip removal. CONCLUSIONS Mitochondrial dysfunction appears to be associated with the development of tendinopathy. CLINICAL RELEVANCE Mitochondrial protection may offer a potential strategy for delaying the development of tendinopathy and promoting tendon healing.
press-fit humeral stem and a peripherally cemented pegged glenoid designed for central bone ingro... more press-fit humeral stem and a peripherally cemented pegged glenoid designed for central bone ingrowth. One hundred and fifty-two patients were randomized based on treatment of the central peg (NG, ABG, DBM). Functional outcome, osseous integration of the central peg, and glenoid loosening were assessed at a minimum of 1 year postoperative. Results: There were statistically significant improvements in functional outcome in all groups from baseline to postoperative, with no difference between groups. Central bone in-growth was observed in 90% of cases treated with ABG, 70% of cases treated with DBM, and 62% of cases treated with no bone graft. Conclusion: At short-term follow-up there is no difference in functional outcome or revision between different surgical techniques for treatment of the central post during placement of an allpolyethylene glenoid designed for bone in-growth. Osseous integration appears to be higher with ABG compared to leaving the central post untreated.
CDE: design of the study, acquisition of data, analysis of data, interpretation of data, drafting... more CDE: design of the study, acquisition of data, analysis of data, interpretation of data, drafting the manuscript. SW: design of the study, acquisition of data, analysis of data, interpretation of data, drafting the manuscript. CBC: acquisition of data, development of methodology. YN: acquisition of data, analysis of data. DAN: acquisition of data, analysis of data. RB: acquisition of data, analysis of data. MO: analysis of data. XHD: design of the study. SAR: design of the study, project administration, analysis of data, supervision. All authors read and approved the final manuscript.
Background: Previous studies have examined the transcriptomes and mechanical properties of whole ... more Background: Previous studies have examined the transcriptomes and mechanical properties of whole tendons in different regions of the body. However, less is known about these characteristics within a single tendon. Purpose: To develop a regional transcriptomic atlas and evaluate the region-specific mechanical properties of Achilles tendons. Study Design: Descriptive laboratory study. Methods: Achilles tendons from 2-month-old male Sprague Dawley rats were used. Tendons were isolated and divided into proximal, middle, and distal thirds for RNA sequencing (n = 5). For mechanical testing, the Achilles muscle-tendon-calcaneus unit was mounted in a custom-designed materials testing system with the unit clamped over the musculotendinous junction (MTJ) and the calcaneus secured at 90° of dorsiflexion (n = 9). Tendons were stretched to 20 N at a constant speed of 0.0167 mm/s. Cross-sectional area, strain, stress, and Young modulus were determined in each tendon region. Results: An open-acces...
Background: Previous studies have examined the transcriptomes and mechanical properties of whole ... more Background: Previous studies have examined the transcriptomes and mechanical properties of whole tendons in different regions of the body. However, less is known about these characteristics within a single tendon. Purpose: To develop a regional transcriptomic atlas and evaluate the region-specific mechanical properties of Achilles tendons. Study Design: Descriptive laboratory study. Methods: Achilles tendons from 2-month-old male Sprague Dawley rats were used. Tendons were isolated and divided into proximal, middle, and distal thirds for RNA sequencing (n = 5). For mechanical testing, the Achilles muscle-tendon-calcaneus unit was mounted in a custom-designed materials testing system with the unit clamped over the musculotendinous junction (MTJ) and the calcaneus secured at 90° of dorsiflexion (n = 9). Tendons were stretched to 20 N at a constant speed of 0.0167 mm/s. Cross-sectional area, strain, stress, and Young modulus were determined in each tendon region. Results: An open-acces...
Background: Since healing of anterior cruciate ligament (ACL) grafts occurs by formation of a fib... more Background: Since healing of anterior cruciate ligament (ACL) grafts occurs by formation of a fibrovascular scar-tissue interface rather than by reformation of the native fibrocartilage transition zone, the purpose of our study was to examine expression of various signaling molecules and transcription factors that are known to be involved in embryologic insertionsite development following ACL reconstruction. We also aimed to characterize a murine model of ACL reconstruction to allow future study of the molecular mechanisms of healing. Methods: Seventy-nine mice underwent reconstruction of the ACL with autograft. Healing was assessed using histology in 12 mice and quantitative real-time polymerase chain reaction (qRT-PCR) gene-expression analysis in 3 mice at 1 week postoperatively (Group-1 mice) and by biomechanical analysis in 7, histological analysis in 7, immunohistochemical analysis in 5, microcomputed tomography analysis in 5, and qRT-PCR analyses in 8 at 2 weeks (Group-2 mice) and 4 weeks (Group-3 mice) postoperatively. Fifteen additional mice did not undergo surgery and were used for biomechanical (7 mice), qRT-PCR (3 mice), and immunohistochemical (5 mice) analyses to obtain baseline data for the native ACL. Results: Histological analysis demonstrated healing by formation of fibrovascular tissue at the tendon-bone interface. Immunohistochemical analysis showed a positive expression of proteins in the Indian hedgehog, Wnt, and parathyroid hormone-related protein (PTHrP) pathways. There was minimal Sox-9 expression. Gene-expression analysis showed an initial increase in markers of tissue repair and turnover, followed by a subsequent decline. Mean failure force and stiffness of the native ACL were 5.60 N and 3.44 N/mm, respectively. Mean failure force and stiffness were 1.29 N and 2.28 N/ mm, respectively, in Group 2 and were 1.79 N and 2.59 N/mm, respectively, in Group 3, with 12 of 14 failures in these study groups occurring by tunnel pull-out. Conclusions: The spatial and temporal pattern of expression of signaling molecules that direct embryologic insertionsite formation was not adequate to restore the structure and composition of the native insertion site. Clinical Relevance: Development of a murine model to study ACL reconstruction will allow the use of transgenic animals to investigate the cellular, molecular, and biomechanical aspects of tendon-to-bone healing following ACL reconstruction, ultimately suggesting methods to improve healing in patients. F unction of an anterior cruciate ligament (ACL) graft is dependent on secure healing in a bone tunnel 1,2. Prior work has demonstrated that healing at the tendon-bone interface in ACL reconstruction occurs by formation of a fibrovascular scar-tissue interface that does not recapitulate the microscopic architecture of the native enthesis 2-6. Bone resorption along the tunnel (tunnel widening) may also compromise attachment strength, contributing to recurrent knee laxity 7,8. Accordingly, research has focused on understanding the biologic healing mechanism in an attempt to optimize healing 2-6 .
Discussion. The Alvarado scale permits the classification of patients with suspected appendicitis... more Discussion. The Alvarado scale permits the classification of patients with suspected appendicitis in groups: a low-risk group (0-4 points) with a probability of appendicitis of 7.7%; an intermediate risk-risk group (5-7 points) with probability of appendicitis of 57.6%; and a high risk group (8-10 points) with a probability of appendicitis of 90.6%. Application of the scale diminished costs by 10% and reduced the rate on negative appendectomies by 8%. Its use is reproducible and offers the advantage a more rational use of resources and diminution in the number of unnecessary operations.
Introducción. Una parte fundamental del entrenamiento de un residente de cirugía es lograr un vol... more Introducción. Una parte fundamental del entrenamiento de un residente de cirugía es lograr un volumen operatorio suficiente para alcanzar una competencia adecuada en su vida laboral independiente. Tanto el volumen como la autonomía, son desafíos para los programas de residencia en cirugía general de Colombia. Métodos. Se realizó un estudio multinstitucional, con la participación de 5 programas de especialización en cirugía general, de diferentes regiones del país. Se utilizó la bitácora electrónica Logbook para el registro de procedimientos durante un periodo de 12 meses. Se hizo un análisis de la base de datos recolectada. Resultados. Un total de 111 médicos residentes participaron en el estudio. Se registraron 29.622 procedimientos quirúrgicos, que correspondieron a 23.206 pacientes. El 51,7 % de los procedimientos fueron cirugías electivas, el 46,9 % cirugías de urgencia y el 1 % de emergencia. El 22,6 % de los procedimientos se realizó a través de un abordaje mínimamente invasiv...
Pesiqta Rabbati is a unique homiletic midrash that follows the liturgical calendar in its present... more Pesiqta Rabbati is a unique homiletic midrash that follows the liturgical calendar in its presentation of homilies for festivals and special Sabbaths. This article attempts to utilize Pesiqta Rabbati in order to present a global theory of the literary production of rabbinic/homiletic literature. In respect to Pesiqta Rabbati it explores such areas as dating, textual witnesses, integrative apocalyptic meta-narrative, describing and mapping the structure of the text, internal and external constraints that impacted upon the text, text linguistic analysis, form-analysis: problems in the texts and linguistic gap-filling, transmission of text, strict formalization of a homiletic unit, deconstructing and reconstructing homiletic midrashim based upon form-analytic units of the homily, Neusner’s documentary hypothesis, surface structures of the homiletic unit, and textual variants. The suggested methodology may assist scholars in their production of editions of midrashic works by eliminating superfluous material and in their decoding and defining of ancient texts
Ultra-short Echo Time Magnetic Resonance Imaging of Rabbit Flexor Tendons in An Anterior Cruciate... more Ultra-short Echo Time Magnetic Resonance Imaging of Rabbit Flexor Tendons in An Anterior Cruciate Ligament Reconstruction Model Sarah L Pownder, Parina Shah, Michael Schaer, Richard Ma, Xiang-Hua Deng, Matthew F Koff, Scott A Rodeo, and Hollis G Potter MRI, Hospital for Special Surgery, New York, NY, United States, Laboratory for Soft Tissue Research, Hospital for Special Surgery, NY, United States, Missouri Orthopaedic Institute, University of Missouri, Columbia, MO, United States, Sports Medicine and Shoulder Service, Hospital for Special Surgery, NY, United States
The purpose of this study is to determine the effect of the magnitude of static mechanical tensio... more The purpose of this study is to determine the effect of the magnitude of static mechanical tension on the anterior cruciate ligament (ACL) graft at the time of surgery on healing within the graft tunnels. Ninety male rats underwent unilateral ACL resection followed by reconstruction with a soft tissue tendon autograft. The ACL graft mechanical environment was modulated by different ACL graft pretension levels at the time of surgery (no pretension: 0N; moderate tension: 5N; over tension: 10N). External fixators were used to eliminate graft and joint motion during cage activity. Graft–tunnel healing was assessed at 3- and 6-week postoperatively, and articular joint surfaces were assessed at 9 weeks. Our results demonstrate that the ACL graft–tunnel healing was sensitive to different static graft pretension levels as demonstrated by different load-to-failure and stiffness properties among the different pretension levels. Pretensioning the graft to 5N (7–8% of the rat ACL ultimate load ...
Background: Emerging data suggest that human cells derived from extraembryonic tissues may have f... more Background: Emerging data suggest that human cells derived from extraembryonic tissues may have favorable musculoskeletal repair properties. The purpose of this study was to determine whether the injection of human placenta-derived mesenchymal-like stromal cells, termed placental expanded cells (PLX-PAD), would improve tendon healing in a preclinical model of tendinopathy. Methods: Sixty male Sprague-Dawley rats underwent bilateral patellar tendon injection with either saline solution (control) or PLX-PAD cells (2 • 10 6 cells/100 mL) 6 days after collagenase injection to induce tendon degeneration. Animals were killed at specific time points for biomechanical, histological, and gene expression analyses of the healing patellar tendons. Results: Biomechanical testing 2 weeks after the collagenase injury demonstrated better biomechanical properties in the tendons treated with PLX-PAD cells. The load to failure of the PLX-PAD-treated tendons was higher than that of the saline-solution-treated controls at 2 weeks (77.01 ± 10.51 versus 58.87 ± 11.97 N, p = 0.01). There was no significant difference between the 2 groups at 4 weeks. There were no differences in stiffness at either time point. Semiquantitative histological analysis demonstrated no significant differences in collagen organization or cellularity between the PLX-PAD and saline-solution-treated tendons. Gene expression analysis demonstrated higher levels of interleukin-1b (IL-1b) and IL-6 early in the healing process in the PLX-PAD-treated tendons. Conclusions: Human placenta-derived cell therapy induced an early inflammatory response and a transient beneficial effect on tendon failure load in a model of collagenase-induced tendon degeneration. Clinical Relevance: Human extraembryonic tissues, such as the placenta, are an emerging source of cells for musculoskeletal repair and may hold promise as a point-of-care cell therapy for tendon injuries. Disclosure: Funding used for study supplies in this investigation was provided by Pluristem Therapeutics Inc., Haifa, Israel. The investigation and analyses were performed independent of the funding source. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked "yes" to indicate that the author had other relationships or activities that could be perceived to influence, or have the potential to influence, what was written in this work (Pluristem donation of study supplies) (http://links.lww.com/ JBJS/F336).
Background The availability of non-invasive means to evaluate and monitor tendon-bone healing pro... more Background The availability of non-invasive means to evaluate and monitor tendon-bone healing processes in-vivo is limited. Micro Positron-Emission-Tomography (µPET) using 18F-Fluoride is a minimally invasive imaging modality, with which osteoblast activity and bone turnover can be assessed. The aim of this study was to investigate the use of serial in-vivo µPET/CT scans to evaluate bone turnover along the graft-tunnel interface in a rat ACL (anterior cruciate ligament) reconstruction model. Methods Unilateral autograft ACL reconstruction was performed in six rats. µPET/CT-scans using 18F-Fluoride were performed 7, 14, 21, and 28 days postoperatively. Standard uptake values (SUV) were calculated for three tunnel regions (intraarticular aperture (IAA), mid-tunnel, and extraarticular aperture (EAA)) of the proximal tibia. Animals were sacrificed at 28 days and evaluated with µCT and histological analysis. Results SUVs in both bone tunnels showed an increased 18F-Fluoride uptake at 7 d...
Supplemental material, DS_10.1177_0363546519898691 for Effect of Lubricin Mimetics on the Inhibit... more Supplemental material, DS_10.1177_0363546519898691 for Effect of Lubricin Mimetics on the Inhibition of Osteoarthritis in a Rat Anterior Cruciate Ligament Transection Model by Daniel Nemirov, Yusuke Nakagawa, Zhexun Sun, Amir Lebaschi, Susumu Wada, Camila Carballo, Xiang-Hua Deng, David Putnam, Lawrence J. Bonassar and Scott A. Rodeo in The American Journal of Sports Medicine
Background: The underlying cellular and molecular mechanisms involved in the development of tendi... more Background: The underlying cellular and molecular mechanisms involved in the development of tendinopathy due to subacromial supraspinatus tendon (SST) impingement and the response to subsequent removal of impingement remain unknown. Purpose: To investigate the involvement of Indian hedgehog (IHH) signaling in the development of SST tendinopathy and the subsequent healing process after the relief of subacromial impingement in a novel mouse shoulder impingement model. Study Design: Controlled laboratory study. Methods: A total of 48 male wild-type C57BL/6 mice were used in this study. Supraspinatus tendinopathy was induced by inserting a microsurgical clip into the subacromial space bilaterally. Eleven mice were sacrificed at 4 weeks after surgery to establish impingement baseline; 24 mice underwent clip removal at 4 weeks after surgery and then were euthanized at 2 or 4 weeks after clip removal. Thirteen mice without surgical intervention were utilized as the control group. All SSTs ...
Journal of Bone and Joint Surgery-british Volume, 2016
Bone marrow concentrates are being used to augment soft tissue healing. However, only 0.01% of th... more Bone marrow concentrates are being used to augment soft tissue healing. However, only 0.01% of these cells meet the criteria of a mesenchymal stem cell (MSC), which likely accounts for the variability in reported results. Previous studies using an established rat rotator cuff repair model have demonstrated that bone marrow-derived MSCs had no effect on healing. In this study we evaluated the effect of purified human MSCs on rotator cuff healing in an athymic rat model. Hypothesis: Purified human MSCs added to the repair site will improve biomechanical strength and fibrocartilage formation of the healing tendon. Fifty-two athymic rats underwent unilateral detachment and repair of the supraspinatus tendon with either fibrin glue (control) or fibrin glue with 106 hMSCs (experimental) applied at the repair site. Flow cytometry verified the stem cell phenotype of the cells as CD73+, CD90+, CD105+, CD14-, CD34- and CD45-. Rats were sacrificed at 2 and 4 weeks, with 10 used for biomechanic...
BACKGROUND The purpose of this study was to assess mitochondrial dysfunction in a murine model of... more BACKGROUND The purpose of this study was to assess mitochondrial dysfunction in a murine model of supraspinatus tendinopathy. METHODS Eighty-four mice (168 limbs) were included in the study. Supraspinatus tendinopathy was induced by inserting a microsurgical clip in the subacromial space of 63 mice bilaterally (126 limbs). Forty-two of these limbs were harvested at 4 weeks postoperatively, 42 underwent clip removal at 4 weeks after the initial procedure and were harvested at 2 weeks, and 42 underwent clip removal at 4 weeks and were harvested at 4 weeks. Forty-two limbs in the remaining 21 mice did not undergo surgical intervention and were utilized as the control group. Outcomes included biomechanical, histological, gene expression, superoxide dismutase (SOD) activity, and transmission electron microscopy (TEM) analyses. RESULTS Radiographs confirmed stable clip position in the subacromial space at 4 weeks. Biomechanical testing demonstrated a 60% decrease in failure force of the supraspinatus tendons at 4 weeks compared with the control group. The failure force gradually increased at 2 and 4 weeks after clip removal. Histological analysis demonstrated inflammation surrounding the tendon with higher modified Bonar scores at 4 weeks after clip placement followed by gradual improvement following clip removal. The expression of mitochondrial-related genes was decreased at 4 weeks after clip placement and then significantly increased after clip removal. SOD activity decreased significantly at 4 weeks after clip placement but increased following clip removal. TEM images demonstrated alterations in morphology and the number of mitochondria and cristae at 4 weeks after clip placement with improvement after clip removal. CONCLUSIONS Mitochondrial dysfunction appears to be associated with the development of tendinopathy. CLINICAL RELEVANCE Mitochondrial protection may offer a potential strategy for delaying the development of tendinopathy and promoting tendon healing.
press-fit humeral stem and a peripherally cemented pegged glenoid designed for central bone ingro... more press-fit humeral stem and a peripherally cemented pegged glenoid designed for central bone ingrowth. One hundred and fifty-two patients were randomized based on treatment of the central peg (NG, ABG, DBM). Functional outcome, osseous integration of the central peg, and glenoid loosening were assessed at a minimum of 1 year postoperative. Results: There were statistically significant improvements in functional outcome in all groups from baseline to postoperative, with no difference between groups. Central bone in-growth was observed in 90% of cases treated with ABG, 70% of cases treated with DBM, and 62% of cases treated with no bone graft. Conclusion: At short-term follow-up there is no difference in functional outcome or revision between different surgical techniques for treatment of the central post during placement of an allpolyethylene glenoid designed for bone in-growth. Osseous integration appears to be higher with ABG compared to leaving the central post untreated.
CDE: design of the study, acquisition of data, analysis of data, interpretation of data, drafting... more CDE: design of the study, acquisition of data, analysis of data, interpretation of data, drafting the manuscript. SW: design of the study, acquisition of data, analysis of data, interpretation of data, drafting the manuscript. CBC: acquisition of data, development of methodology. YN: acquisition of data, analysis of data. DAN: acquisition of data, analysis of data. RB: acquisition of data, analysis of data. MO: analysis of data. XHD: design of the study. SAR: design of the study, project administration, analysis of data, supervision. All authors read and approved the final manuscript.
Background: Previous studies have examined the transcriptomes and mechanical properties of whole ... more Background: Previous studies have examined the transcriptomes and mechanical properties of whole tendons in different regions of the body. However, less is known about these characteristics within a single tendon. Purpose: To develop a regional transcriptomic atlas and evaluate the region-specific mechanical properties of Achilles tendons. Study Design: Descriptive laboratory study. Methods: Achilles tendons from 2-month-old male Sprague Dawley rats were used. Tendons were isolated and divided into proximal, middle, and distal thirds for RNA sequencing (n = 5). For mechanical testing, the Achilles muscle-tendon-calcaneus unit was mounted in a custom-designed materials testing system with the unit clamped over the musculotendinous junction (MTJ) and the calcaneus secured at 90° of dorsiflexion (n = 9). Tendons were stretched to 20 N at a constant speed of 0.0167 mm/s. Cross-sectional area, strain, stress, and Young modulus were determined in each tendon region. Results: An open-acces...
Background: Previous studies have examined the transcriptomes and mechanical properties of whole ... more Background: Previous studies have examined the transcriptomes and mechanical properties of whole tendons in different regions of the body. However, less is known about these characteristics within a single tendon. Purpose: To develop a regional transcriptomic atlas and evaluate the region-specific mechanical properties of Achilles tendons. Study Design: Descriptive laboratory study. Methods: Achilles tendons from 2-month-old male Sprague Dawley rats were used. Tendons were isolated and divided into proximal, middle, and distal thirds for RNA sequencing (n = 5). For mechanical testing, the Achilles muscle-tendon-calcaneus unit was mounted in a custom-designed materials testing system with the unit clamped over the musculotendinous junction (MTJ) and the calcaneus secured at 90° of dorsiflexion (n = 9). Tendons were stretched to 20 N at a constant speed of 0.0167 mm/s. Cross-sectional area, strain, stress, and Young modulus were determined in each tendon region. Results: An open-acces...
Background: Since healing of anterior cruciate ligament (ACL) grafts occurs by formation of a fib... more Background: Since healing of anterior cruciate ligament (ACL) grafts occurs by formation of a fibrovascular scar-tissue interface rather than by reformation of the native fibrocartilage transition zone, the purpose of our study was to examine expression of various signaling molecules and transcription factors that are known to be involved in embryologic insertionsite development following ACL reconstruction. We also aimed to characterize a murine model of ACL reconstruction to allow future study of the molecular mechanisms of healing. Methods: Seventy-nine mice underwent reconstruction of the ACL with autograft. Healing was assessed using histology in 12 mice and quantitative real-time polymerase chain reaction (qRT-PCR) gene-expression analysis in 3 mice at 1 week postoperatively (Group-1 mice) and by biomechanical analysis in 7, histological analysis in 7, immunohistochemical analysis in 5, microcomputed tomography analysis in 5, and qRT-PCR analyses in 8 at 2 weeks (Group-2 mice) and 4 weeks (Group-3 mice) postoperatively. Fifteen additional mice did not undergo surgery and were used for biomechanical (7 mice), qRT-PCR (3 mice), and immunohistochemical (5 mice) analyses to obtain baseline data for the native ACL. Results: Histological analysis demonstrated healing by formation of fibrovascular tissue at the tendon-bone interface. Immunohistochemical analysis showed a positive expression of proteins in the Indian hedgehog, Wnt, and parathyroid hormone-related protein (PTHrP) pathways. There was minimal Sox-9 expression. Gene-expression analysis showed an initial increase in markers of tissue repair and turnover, followed by a subsequent decline. Mean failure force and stiffness of the native ACL were 5.60 N and 3.44 N/mm, respectively. Mean failure force and stiffness were 1.29 N and 2.28 N/ mm, respectively, in Group 2 and were 1.79 N and 2.59 N/mm, respectively, in Group 3, with 12 of 14 failures in these study groups occurring by tunnel pull-out. Conclusions: The spatial and temporal pattern of expression of signaling molecules that direct embryologic insertionsite formation was not adequate to restore the structure and composition of the native insertion site. Clinical Relevance: Development of a murine model to study ACL reconstruction will allow the use of transgenic animals to investigate the cellular, molecular, and biomechanical aspects of tendon-to-bone healing following ACL reconstruction, ultimately suggesting methods to improve healing in patients. F unction of an anterior cruciate ligament (ACL) graft is dependent on secure healing in a bone tunnel 1,2. Prior work has demonstrated that healing at the tendon-bone interface in ACL reconstruction occurs by formation of a fibrovascular scar-tissue interface that does not recapitulate the microscopic architecture of the native enthesis 2-6. Bone resorption along the tunnel (tunnel widening) may also compromise attachment strength, contributing to recurrent knee laxity 7,8. Accordingly, research has focused on understanding the biologic healing mechanism in an attempt to optimize healing 2-6 .
Discussion. The Alvarado scale permits the classification of patients with suspected appendicitis... more Discussion. The Alvarado scale permits the classification of patients with suspected appendicitis in groups: a low-risk group (0-4 points) with a probability of appendicitis of 7.7%; an intermediate risk-risk group (5-7 points) with probability of appendicitis of 57.6%; and a high risk group (8-10 points) with a probability of appendicitis of 90.6%. Application of the scale diminished costs by 10% and reduced the rate on negative appendectomies by 8%. Its use is reproducible and offers the advantage a more rational use of resources and diminution in the number of unnecessary operations.
Introducción. Una parte fundamental del entrenamiento de un residente de cirugía es lograr un vol... more Introducción. Una parte fundamental del entrenamiento de un residente de cirugía es lograr un volumen operatorio suficiente para alcanzar una competencia adecuada en su vida laboral independiente. Tanto el volumen como la autonomía, son desafíos para los programas de residencia en cirugía general de Colombia. Métodos. Se realizó un estudio multinstitucional, con la participación de 5 programas de especialización en cirugía general, de diferentes regiones del país. Se utilizó la bitácora electrónica Logbook para el registro de procedimientos durante un periodo de 12 meses. Se hizo un análisis de la base de datos recolectada. Resultados. Un total de 111 médicos residentes participaron en el estudio. Se registraron 29.622 procedimientos quirúrgicos, que correspondieron a 23.206 pacientes. El 51,7 % de los procedimientos fueron cirugías electivas, el 46,9 % cirugías de urgencia y el 1 % de emergencia. El 22,6 % de los procedimientos se realizó a través de un abordaje mínimamente invasiv...
Pesiqta Rabbati is a unique homiletic midrash that follows the liturgical calendar in its present... more Pesiqta Rabbati is a unique homiletic midrash that follows the liturgical calendar in its presentation of homilies for festivals and special Sabbaths. This article attempts to utilize Pesiqta Rabbati in order to present a global theory of the literary production of rabbinic/homiletic literature. In respect to Pesiqta Rabbati it explores such areas as dating, textual witnesses, integrative apocalyptic meta-narrative, describing and mapping the structure of the text, internal and external constraints that impacted upon the text, text linguistic analysis, form-analysis: problems in the texts and linguistic gap-filling, transmission of text, strict formalization of a homiletic unit, deconstructing and reconstructing homiletic midrashim based upon form-analytic units of the homily, Neusner’s documentary hypothesis, surface structures of the homiletic unit, and textual variants. The suggested methodology may assist scholars in their production of editions of midrashic works by eliminating superfluous material and in their decoding and defining of ancient texts
Ultra-short Echo Time Magnetic Resonance Imaging of Rabbit Flexor Tendons in An Anterior Cruciate... more Ultra-short Echo Time Magnetic Resonance Imaging of Rabbit Flexor Tendons in An Anterior Cruciate Ligament Reconstruction Model Sarah L Pownder, Parina Shah, Michael Schaer, Richard Ma, Xiang-Hua Deng, Matthew F Koff, Scott A Rodeo, and Hollis G Potter MRI, Hospital for Special Surgery, New York, NY, United States, Laboratory for Soft Tissue Research, Hospital for Special Surgery, NY, United States, Missouri Orthopaedic Institute, University of Missouri, Columbia, MO, United States, Sports Medicine and Shoulder Service, Hospital for Special Surgery, NY, United States
The purpose of this study is to determine the effect of the magnitude of static mechanical tensio... more The purpose of this study is to determine the effect of the magnitude of static mechanical tension on the anterior cruciate ligament (ACL) graft at the time of surgery on healing within the graft tunnels. Ninety male rats underwent unilateral ACL resection followed by reconstruction with a soft tissue tendon autograft. The ACL graft mechanical environment was modulated by different ACL graft pretension levels at the time of surgery (no pretension: 0N; moderate tension: 5N; over tension: 10N). External fixators were used to eliminate graft and joint motion during cage activity. Graft–tunnel healing was assessed at 3- and 6-week postoperatively, and articular joint surfaces were assessed at 9 weeks. Our results demonstrate that the ACL graft–tunnel healing was sensitive to different static graft pretension levels as demonstrated by different load-to-failure and stiffness properties among the different pretension levels. Pretensioning the graft to 5N (7–8% of the rat ACL ultimate load ...
Background: Emerging data suggest that human cells derived from extraembryonic tissues may have f... more Background: Emerging data suggest that human cells derived from extraembryonic tissues may have favorable musculoskeletal repair properties. The purpose of this study was to determine whether the injection of human placenta-derived mesenchymal-like stromal cells, termed placental expanded cells (PLX-PAD), would improve tendon healing in a preclinical model of tendinopathy. Methods: Sixty male Sprague-Dawley rats underwent bilateral patellar tendon injection with either saline solution (control) or PLX-PAD cells (2 • 10 6 cells/100 mL) 6 days after collagenase injection to induce tendon degeneration. Animals were killed at specific time points for biomechanical, histological, and gene expression analyses of the healing patellar tendons. Results: Biomechanical testing 2 weeks after the collagenase injury demonstrated better biomechanical properties in the tendons treated with PLX-PAD cells. The load to failure of the PLX-PAD-treated tendons was higher than that of the saline-solution-treated controls at 2 weeks (77.01 ± 10.51 versus 58.87 ± 11.97 N, p = 0.01). There was no significant difference between the 2 groups at 4 weeks. There were no differences in stiffness at either time point. Semiquantitative histological analysis demonstrated no significant differences in collagen organization or cellularity between the PLX-PAD and saline-solution-treated tendons. Gene expression analysis demonstrated higher levels of interleukin-1b (IL-1b) and IL-6 early in the healing process in the PLX-PAD-treated tendons. Conclusions: Human placenta-derived cell therapy induced an early inflammatory response and a transient beneficial effect on tendon failure load in a model of collagenase-induced tendon degeneration. Clinical Relevance: Human extraembryonic tissues, such as the placenta, are an emerging source of cells for musculoskeletal repair and may hold promise as a point-of-care cell therapy for tendon injuries. Disclosure: Funding used for study supplies in this investigation was provided by Pluristem Therapeutics Inc., Haifa, Israel. The investigation and analyses were performed independent of the funding source. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked "yes" to indicate that the author had other relationships or activities that could be perceived to influence, or have the potential to influence, what was written in this work (Pluristem donation of study supplies) (http://links.lww.com/ JBJS/F336).
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