Endothelin-1 reduces catabolic activity of human mesenchymal stem/stromal cells during chondro- and osteo-lineage differentiation.

Human mesenchymal stem/stromal cells (hMSCs) reside in a vascularized microenvironment and experience a host of blood vessel secretions, including endothelin-1 (ET1). Previously, our group has demonstrated improved induction of osteogenesis and chondrogenesis in hMSCs through an ET1-induced increase in production of anabolic factors. The current study explores effects of ET1 on catabolic factors secreted by hMSCs during chondrogenesis and osteogenesis. Cell proliferation and extracellular matrix (ECM) deposition were also explored. Our results demonstrated that ET1 reduced mRNA transcript levels of MMP2, MMP13, ADAMTS4, and ADAMTS5 in chondrogenic hMSCs, and MMP13 and ADAMTS5 in osteogenic hMSCs. Furthermore, ET1-treated chondrogenic and osteogenic hMSCs showed more intense stains for Alcian blue and Alizarin red S, respectively, than control cells. Immunocytochemical results demonstrated that the ET1-mediated reduction of MMP13 could be reversed through blocking ET1 induction. Overall, our findings indicate that hMSCs treated with ET1 during chondrogenic or osteogenic induction attenuate catabolic activities of the cell to reduce ECM degradation, suggesting that it may be beneficial to use ET1 to enhance hMSC differentiation and protect newly synthesized ECM from degradation.

Development of a Synthetic Training Model for Canine Thoracocentesis.

Thoracocentesis, a procedure in which air or fluid is removed from the pleural space, is used to relieve respiratory distress, and as a diagnostic procedure in human and veterinary medicine. Veterinary students commonly learn and practice the procedure on canine cadavers which are in limited supply and are not amenable to long-term storage and use. Practicing thoracocentesis on a cadaveric model also provides limited feedback indicative of success and/or procedural complications. One commercial model for practicing canine thoracocentesis is available, but it costs over US$2000 and is excessively bulky. In order to improve the learning process for veterinary students, we have developed a reusable synthetic canine thorax model that accurately replicates the thoracocentesis procedure, provides immediate feedback to the students and reduces the need for canine cadavers. The low cost of our product provides an efficient alternative to cadavers for instruction in veterinary schools or hospitals.

Hodgkin lymphoma associated vanishing bile duct syndrome treated successfully with a brentuximab based regimen.

We report a combination therapy to successfully treat a patient with Hodgkin's lymphoma complicated by vanishing bile duct syndrome. Our patient was in his 20s and presented with jaundice, emesis, B symptoms and diffuse lymphadenopathy along with cholestatic liver injury prompting a liver biopsy, which revealed this diagnosis, after the exclusion of other aetiologies. Our treatment regimen incorporated brentuximab along with other more conventional agents which attempted to maximise therapeutic efficacy while minimising the consequences of hepatotoxicity on the treatment protocol. Although this patient's treatment course was complicated because of neutropenic infections, the patient achieved a complete metabolic response and is now more than 1 year off therapy.

A Quantitative and Qualitative Literature Analysis of the Orthopedic Surgeons' Experience: Reflecting on 20 Years in the Global War on Terror.

INTRODUCTION: After over 20 years of war in the Middle East, orthopedic injuries have been among the most prevalent combat-related injuries, accounting for 14% of all surgical procedures at Role 2/3 (R2/R3) facilities according to the DoD Trauma Registry. To further delineate the role of the deployed orthopedic surgeon on the modern battlefield, a retrospective review was performed highlighting both quantitative and qualitative analysis factors associated with orthopedic surgical care during the war in the Middle East. METHODS: A retrospective review was conducted of orthopedic surgeons in the Middle East from 2001 to 2021. A comprehensive literature search was conducted using the PubMed and Embase databases using a two-reviewer strategy. Articles were compiled and reviewed using Covidence. Inclusion criteria included journal articles focusing on orthopedic injuries sustained during the Global War on Terror (GWoT) in an adult U.S. Military population. In the event of a conflict, a third author would determine the relevance of the article. For the remaining articles, a full-text review was conducted to extract relevant predetermined quantitative data, and the Delphi consensus method was then utilized to highlight relevant qualitative themes. RESULTS: The initial search yielded 1,226 potentially relevant articles. In all, 40 studies ultimately met the eligibility criteria. With the consultation of previously deployed orthopedic surgeons at the Walter Reed National Military Medical Center, a retrospective thematic analysis of the 40 studies revealed five themes encompassing the orthopedic surgeons experience throughout GWoT. These themes include unique mechanisms of orthopedic injury compared to previous war injuries due to novel weaponry, differences in interventions depending on R2 versus R3 locations, differences in injuries from those seen in civilian settings, the maintained emphasis on humanitarian aspect of an orthopedic surgeon's mission, and lastly relation of pre-deployment training to perceived deployed success of the orthopedic surgeons. From this extensive review, we found that explosive mechanisms of injury were greatly increased when compared to previous conflicts and were the etiology for the majority of orthopedic injuries sustained. With the increase of complex explosive injuries in the setting of improved body armor and overall survival, R2/3 facilities showed an increased demand for orthopedic intervention including debridement, amputations, and external fixation. Combat injuries sustained during the GWoT differ in the complications, management, and complexity when compared to civilian trauma. "Humanitarian" cases made up a significant number of operative cases for the deployed orthopedic surgeon. Lastly, heterogeneous training opportunities were available prior to deployment (fellowship, combat extremity surgical courses, and dedicated pre-deployment training), and the most commonly identified useful training was learning additional soft-tissue coverage techniques. CONCLUSION: These major themes indicate an emphasis on pre-deployment training and the strategic positioning of orthopedic surgeons to reflect the changing landscape of musculoskeletal trauma care. Moving forward, these authors recommend analyzing the comfort and perceived capability of orthopedic surgeons in these unique military environments to best prepare for a changing operational format and the possibility of future peer-peer conflicts that will likely lead to a lack of medical evacuation and prolonged field care.

All-Suture Suspensory Button Has Similar Biomechanical Performance to Metal Suspensory Button for Onlay Subpectoral Biceps Tenodesis.

Purpose: To evaluate the maximal load at failure, cyclic displacement, and stiffness of onlay subpectoral biceps tenodesis (BT) with an intramedullary unicortical metal button (MB) versus a unicortical all-suture button (ASB). Methods: Eighteen matched paired human cadaveric proximal humeri were randomly allocated for subpectoral BT with either ASB or MB using a high-strength suture. Specimens were tested on a servohydraulic mechanical testing apparatus under cyclic load for 1,000 cycles and then loaded to failure. The clamp was then adjusted to isolate the suture-anchor point interface and loaded to failure. Maximal load to failure, displacement, and stiffness were compared. Results: There was no significant difference between groups in stiffness, displacement, or yield load. The maximal load to failure for the MB was greater than the ASB (347.6 ± 74.1N vs 266.5 ± 69.3N, P = .047). Eight specimens in each group failed by suture pull-through on the tendon. When the suture-anchor point interface was isolated, there was no significant difference in maximal load at failure (MB 586.5 ± 215.8N vs ASB 579.6 ± 255.9N, P = .957). Conclusions: This study demonstrates that the MB and ASB have similar biomechanical performance when used in subpectoral BT. Although the MB showed statistically significant greater maximal load to failure, there was no difference between the MB and ASB when the suture-tendon interface was eliminated. Suture pull-through was the most common mode of failure for both implants, underscoring the importance of the suture-tendon interface. Clinical Relevance: Fixation techniques for the treatment of long head of the biceps brachii tenodesis continue to evolve. The use of an all-suture suspensory button has advantages, but it is important to understand if this implant is a biomechanically suitable alternative to a metal suspensory button.