Associations of musculoskeletal dysfunction, time to brake, and patient reported outcomes following lower extremity trauma.

INTRODUCTION: Inability to drive a motor vehicle due to lower extremity injury is a major inconvenience. Timing of safe return to driving has not been much studied. Objective measurements such as time to brake (TTB) have been proposed; however, utility and concordance of functional outcome measurements have not been previously evaluated. The purpose of this project is to measure these parameters and to assess for associations with ability to safely return to driving, improving the ability of clinicians to assess for measurements of driving readiness without specifically measuring TTB. METHODS: A prospective, cohort study of 232 patients with complex lower extremity injuries to the pelvis, acetabulum, hip, femur, knee, tibia, ankle, and foot was performed. Time to brake (TTB) was measured once weightbearing was allowed. Function was assessed by the Musculoskeletal Function Assessment (MFA) questionnaire, and pain, mobility, and physical functions, via patient reported outcome measurement information system (PROMIS) surveys. RESULTS: Patients with longer TTB had significantly elevated MFA scores indicating increased musculoskeletal dysfunction post-injury. As the MFA score increased by 1 point, TTB increased by 0.013 s (p<0.001). PROMIS metrics were also significantly associated with patients experiencing more pain and worse mobility as TTB increased. DISCUSSION: Many patients continue to exhibit musculoskeletal dysfunction several months post-treatment for complex lower extremity injuries. Patients with better PROMIS metrics and MFA scores, and shorter TTB are more appropriate to return to driving. Surgeons may be better informed about safe driving ability by considering these measurements. LEVEL OF EVIDENCE: II.

The Lymphatic Endothelial Cell Secretome Inhibits Osteoblast Differentiation and Bone Formation.

Complex lymphatic anomalies (CLAs) are a set of rare diseases with unique osteopathic profiles. Recent efforts have identified how lymphatic-specific somatic activating mutations can induce abnormal lymphatic formations that are capable of invading bone and inducing bone resorption. The abnormal bone resorption in CLA patients has been linked to overactive osteoclasts in areas with lymphatic invasions. Despite these findings, the mechanism associated with progressive bone loss in CLAs remains to be elucidated. In order to determine the role of osteoblasts in CLAs, we sought to assess osteoblast differentiation and bone formation when exposed to the lymphatic endothelial cell secretome. When treated with lymphatic endothelial cell conditioned medium (L-CM), osteoblasts exhibited a significant decrease in proliferation, differentiation, and function. Additionally, L-CM treatment also inhibited bone formation through a neonatal calvaria explant culture. These findings are the first to reveal how osteoblasts may be actively suppressed during bone lymphatic invasion in CLAs.

Psoas Abscess Precipitated by an Uncommon Pathogen: Pasteurella multocida.

A psoas abscess is a rare infection; it is an accumulation of purulent material within the psoas muscle. Common pathogens include Staphylococcus aureus, streptococci, Escherichia coli, and other enteric Gram-negative bacilli and anaerobes. These abscesses are thought to occur by either hematogenous spread, contiguous spread from adjacent organs, trauma, or local inoculation. Pasteurella multocida is a pathogen that usually infects a patient via a bite or scratch from dogs or cats and causes cellulitis at the site of the injury. Pasteurella multocida may also cause infection by the colonization of human respiratory and gastrointestinal (GI) tracts with spontaneous bacteremia seeding remote organs by the bacterial translocation process. Pasteurella multocida is highly susceptible to penicillins, cephalosporins, and other antibiotics. However, psoas abscesses usually require a drainage procedure as well as an extended course of antibiotics. We present a patient presenting with a psoas abscess due to P. multocida, an uncommon presentation of infection by this bacterium.

Multiorgan Failure in Hemophagocytic Lymphohistiocytosis Secondary to Acute Monocytic Leukemia and Myocarditis in a Pediatric Patient.

Acute monocytic leukemia (AML), a subtype of acute myeloid leukemia, is a rare leukemia found in children. It occurs more frequently in adults over the age of 60. Myocarditis represents inflammation of the muscular layer of the heart, the myocardium causing weakening of the muscles that can lead to hemodynamic instability from a reduced ejection fraction. Myocarditis in the pediatric population is most commonly secondary to a viral or infectious etiology. Hemophagocytic lymphohistiocytosis (HLH) is a rare condition of immune dysregulation characterized by severe organ damage induced by an increased inflammatory response and uncontrolled T-cell and macrophage activation. In this case report, we examine a rare presentation of leukemic myocarditis in the presence of HLH, which displays an uncommon cause of an inflammatory state with several complicated concomitant diagnoses. Our patient developed severe multiorgan dysfunction involving liver and kidney failure that required prolonged critical care support, and the patient expired due to his multiorgan failure. We highlight the unusual clinical presentation of myocarditis in the setting of HLH and AML in this complicated pediatric patient and aim to improve outcomes of patients presenting similarly in the future.

Recurrent Klebsiella pneumoniae Bacteremia Due to Endotipsitis.

Transjugular intrahepatic portosystemic shunt (TIPS) procedures are commonly performed in patients with cirrhosis to decrease the pressure in the portal system. An unusual complication of this procedure is endotipsitis, an infection of the shunt/stent with resultant sustained bacteremia caused by vegetation within the TIPS. The most commonly associated pathogens include staphylococci, enterococci, streptococci, and enteric Gram-negative bacilli. We present a patient who developed endotipsitis due to Klebsiella pneumoniae and presented with refractory K. pneumoniae bacteremia. Our patient had a progressively worsening clinical picture and after recognition of endotipsitis was transferred to another facility for liver transplantation and removal of the TIPS. Rapid diagnosis of endotipsitis in the setting of refractory bacteremia is essential to patient survival.

A Rare Presentation of Hydralazine-Induced Lupus in the Setting of Pericarditis With Concomitant Angioedema.

Drug-induced lupus (DIL) usually presents after starting a medication known to induce DIL. However unusual presentations are rare, as such, our patient presented with initial signs and symptoms of pericarditis. Once treated as such, he progressively declined to symptoms of angioedema and worsening cardiopulmonary status. On first admission, the patient presented with chest pain that was worsened by laying down and improved by sitting up. CT Angiography (CTA) showed mild pericardial effusion, and EKG showed diffuse ST elevation, both suggestive of pericarditis, for which the patient was discharged on colchicine. The patient was readmitted one day later with swelling of the neck and tongue. The patient was re-evaluated, tested for autoantibodies, and found a positive antinuclear antibody (ANA) suggesting a diagnosis of lupus, most likely due to hydralazine. We report a rare presentation of drug-induced lupus initially presenting with pericarditis which evolved into worsening angioedema which has not been reported in the literature thus far. Pericarditis and angioedema may be the initial presentation for a patient with drug-induced lupus. Antinuclear and anti-histone antibodies are highly sensitive and specific respectfully for drug-induced lupus. Early diagnosis and time-appropriate discontinuation of the offending agent for patients can be life-saving.

Non-ketotic Hyperglycemia Hemichorea-Hemiballismus Syndrome: A Case Report.

Non-ketotic hyperglycemia is an uncommon cause of hemichorea-hemiballismus syndrome that has been associated with high levels of glucose that are not well controlled. Lesions typically occur in the globus pallidus and putamen, which can be identified via computed tomography (CT) or magnetic resonance imaging (MRI). These lesions generally correspond with ballistic and choreiform movements on the contralateral side of the observed imaging findings. Additionally, amelioration of hyperglycemia is the first-line treatment and usually reduces and resolves these hyperkinetic movement symptoms. This case report demonstrates a case of non-ketotic hyperglycemia hemichorea-hemiballismus syndrome in an individual with a history of poorly controlled type 2 diabetes mellitus and a highly elevated hemoglobin A1C (HbA1C), who subsequently improved with insulin therapy.

Asbestos Exposure and Development of Pulmonary Pleomorphic Carcinoma in a Non-smoker: A Rare Non-small Cell Lung Cancer.

Pulmonary pleomorphic carcinoma (PPC) is a subtype of non-small cell lung cancer that is extremely rare and carries a poor prognosis due to its inadequate response to treatment. Patients that present with PPC often exhibit similar symptoms of other malignancies of the lung, making it hard for clinicians to distinguish between each type. However, cytology and gene mutation testing are two approaches that can aid physicians in an accurate and definitive diagnosis. We present a case of an 88-year-old male patient with a diagnosis of pulmonary pleomorphic carcinoma after experiencing recurrent sanguineous pleural effusions. The patient had no smoking history but did have a history of asbestos exposure and pulmonary fibrosis. The patient underwent thoracotomy with pleurodesis and analysis of the surgical pleural biopsy specimen stained positive for markers indicative of PPC. The pathology report was also consistent with the associated cell morphology. Lung cancer is the leading cause of mortality due to cancer in the United States, and exposure to certain substances contributes to the development of these poorly treatable lung malignancies. Smoking and asbestos exposure are well known to act synergistically with each other as risk factors in developing these lung malignancies. In addition to clinical suspicion, screening for these risk factors with laboratory values and imaging is important to diagnose these rare cases of lung malignancies.

Prolonged Time to Brake Following Lower Extremity Injuries.

INTRODUCTION: No guidelines exist for recommending return to driving. This study will examine time to brake (TTB) after lower extremity injuries versus in uninjured people. The potential effect of various types of lower extremity injuries on TTB will be measured. METHODS: Patients with injuries to the pelvis, hip, femur, knee, tibia, ankle, and foot underwent testing using a driving simulator to assess TTB. Comparison was with a control group of uninjured people. RESULTS: Two-hundred thirty-two patients with lower extremity injuries participated. The majority were in the tibia and ankle regions (47%). Mean TTB for control subjects was 0.74 seconds, compared with 0.83 for injured patients, noting a 0.09-second difference (P = 0.017). Left-sided injuries averaged TTB of 0.80 seconds, right-sided injuries averaged TTB of 0.86 seconds, and bilateral injuries averaged TTB of 0.83 seconds, all prolonged versus control subjects. The longest TTB was exhibited after ankle and foot injuries (0.89 seconds) while the shortest was after tibial shaft fractures (0.76 seconds). DISCUSSION: Any lower extremity injury caused a prolonged TTB compared with control patients. Left, right, and bilateral injuries all had longer TTB. Ankle and foot injuries experienced the longest TTB. Additional investigation is warranted to develop safe guidelines for return to driving.

A Pre-clinical Standard Operating Procedure for Evaluating Orthobiologics in an In Vivo Rat Spinal Fusion Model.

The rat animal model is a cost effective and reliable model used in spinal pre-clinical research. Complications from various surgical procedures in humans often arise that were based on these pre-clinical animal models. Therefore safe and efficacious pre-clinical animal models are needed to establish continuity into clinical trials. A Standard Operating Procedure (SOP) is a validated method that allows researchers to safely and carefully replicate previously successful surgical techniques. Thus, the aim of this study is to describe in detail the procedures involved in a common rat bilateral posterolateral intertransverse spinal fusion SOP used to test the efficacy and safety different orthobiologics using a collagen-soaked sponge as an orthobiologic carrier. Only two orthobiologics are currently FDA approved for spinal fusion surgery which include recombinant bone morphogenetic protein 2 (rhBMP-2), and I-FACTOR. While there are many additional orthobiologics currently being tested, one way to show their safety profile and gain FDA approval, is to use well established pre-clinical animal models. A preoperative, intraoperative, and postoperative surgical setup including specific anesthesia and euthanasia protocols are outlined. Furthermore, we describe different postoperative methods used to validate the spinal fusion SOP, which include µCT analysis, histopathology, biomechanical testing, and blood analysis. This SOP can help increase validity, transparency, efficacy, and reproducibly in future rat spinal fusion surgery procedures.

Osteopathy in Complex Lymphatic Anomalies.

Complex Lymphatic Anomalies (CLA) are lymphatic malformations with idiopathic bone and soft tissue involvement. The extent of the abnormal lymphatic presentation and boney invasion varies between subtypes of CLA. The etiology of these diseases has proven to be extremely elusive due to their rarity and irregular progression. In this review, we compiled literature on each of the four primary CLA subtypes and discuss their clinical presentation, lymphatic invasion, osseous profile, and regulatory pathways associated with abnormal bone loss caused by the lymphatic invasion. We highlight key proliferation and differentiation pathways shared between lymphatics and bone and how these systems may interact with each other to stimulate lymphangiogenesis and cause bone loss.

Epigenetic Regulation of Chondrocytes and Subchondral Bone in Osteoarthritis.

The aim of this review is to provide an updated review of the epigenetic factors involved in the onset and development of osteoarthritis (OA). OA is a prevalent degenerative joint disease characterized by chronic inflammation, ectopic bone formation within the joint, and physical and proteolytic cartilage degradation which result in chronic pain and loss of mobility. At present, no disease-modifying therapeutics exist for the prevention or treatment of the disease. Research has identified several OA risk factors including mechanical stressors, physical activity, obesity, traumatic joint injury, genetic predisposition, and age. Recently, there has been increased interest in identifying epigenetic factors involved in the pathogenesis of OA. In this review, we detail several of these epigenetic modifications with known functions in the onset and progression of the disease. We also review current therapeutics targeting aberrant epigenetic regulation as potential options for preventive or therapeutic treatment.