Direct comparison of non-osteoarthritic and osteoarthritic synovial fluid-induced intracellular chondrocyte signaling and phenotype changes.

OBJECTIVE: Since the joint microenvironment and tissue homeostasis are highly dependent on synovial fluid, we aimed to compare the essential chondrocyte signaling signatures of non-osteoarthritic vs end-stage osteoarthritic knee synovial fluid. Moreover, we determined the phenotypic consequence of the distinct signaling patterns on articular chondrocytes. METHODS: Protein profiling of synovial fluid was performed using antibody arrays. Chondrocyte signaling and phenotypic changes induced by non-osteoarthritic and osteoarthritic synovial fluid were analyzed using a phospho-kinase array, luciferase-based transcription factor activity assays, and RT-qPCR. The origin of osteoarthritic synovial fluid signaling was evaluated by comparing the signaling responses of conditioned media from cartilage, synovium, infrapatellar fat pad and meniscus. Osteoarthritic synovial fluid induced pathway-phenotype relationships were evaluated using pharmacological inhibitors. RESULTS: Compared to non-osteoarthritic synovial fluid, osteoarthritic synovial fluid was enriched in cytokines, chemokines and growth factors that provoked differential MAPK, AKT, NFκB and cell cycle signaling in chondrocytes. Functional pathway analysis confirmed increased activity of these signaling events upon osteoarthritic synovial fluid stimulation. Tissue secretomes of osteoarthritic cartilage, synovium, infrapatellar fat pad and meniscus activated several inflammatory signaling routes. Furthermore, the distinct pathway signatures of osteoarthritic synovial fluid led to accelerated chondrocyte dedifferentiation via MAPK/ERK signaling, increased chondrocyte fibrosis through MAPK/JNK and PI3K/AKT activation, an elevated inflammatory response mediated by cPKC/NFκB, production of extracellular matrix-degrading enzymes by MAPK/p38 and PI3K/AKT routes, and enabling of chondrocyte proliferation. CONCLUSION: This study provides the first mechanistic comparison between non-osteoarthritic and osteoarthritic synovial fluid, highlighting MAPKs, cPKC/NFκB and PI3K/AKT as crucial OA-associated intracellular signaling routes.

Comparison of fixed and mobile-bearing total knee arthroplasty in terms of patellofemoral pain and function: a prospective, randomised, controlled trial.

BACKGROUND: Despite growing evidence in the literature, there is still a lack of consensus regarding the use of the mobile-bearing (MB) design total knee arthroplasty (TKA). METHODS: In a prospective, comparative, randomised, single centre trial, 106 patients with end-stage osteoarthritis of the knee were randomised to either an MB or fixed-bearing (FB) group to receive posterior stabilised (PS)-TKA using a standard medial parapatellar approach and patellar resurfacing with follow-up (FU) for 5 years. The primary outcome was anterior knee pain (AKP) during the chair rise test and the stair climb test 5 years after surgery. The secondary outcome was the ability to rise from a chair and to climb stairs, range of motion (ROM), Knee Society Score (KSS), RAND-36 scores and radiological analysis of the patellar tilt. RESULTS: No statistically significant difference was found between the two groups at 5 years FU in terms of median AKP during the chair rise test and the stair climb test (p = 0.5 and p = 0.8, respectively). There was no significant difference in any of the other secondary outcome parameters between the groups at 5 years FU. CONCLUSION: A mobile-bearing TKA does not decrease AKP compared to fixed bearings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02892838 . LEVEL OF EVIDENCE: II.

Mosaicplasty for the treatment of articular defects of the knee and ankle.

Efficacious treatment of full-thickness cartilage defects of the weightbearing surfaces is a multi-faceted challenge for the orthopaedic surgeon. Autologous osteochondral transplantation represents one solution: to bring about a hyaline or hyalinelike repair of the defected area. The current authors discuss the experimental background and their 8 years of clinical experience with the autologous osteochondral mosaicplasty. Several series of animal studies and subsequent clinical practice have confirmed the survival of the transplanted hyaline cartilage. Hyaline cartilage and fibrocartilage fill the donor sites located on the nonweightbearing surfaces and surfaces that bear less weight. Clinical scores, imaging techniques, control arthroscopies, histologic examination of biopsy samples, and cartilage stiffness measurements were used to evaluate the clinical outcomes and quality of the transplanted cartilage. According to these investigations, femoral condylar implantations have shown good to excellent results in 92%, tibial resurfacing in 88%, patellar and/or trochlear mosaicplasties in 81%, and talar procedures in 94% of patients. The Bandi score showed long-term donor site disturbances in 3% of patients. Fifty-eight of the 68 control arthroscopies had good gliding surfaces, histologically-proven survival of the transplanted hyaline cartilage, and fibrocartilage covering of the donor sites. In the entire series, there were four deep infections and 34 painful hemarthroses after surgery. A multicentric, comparative, prospective evaluation of 413 arthroscopic resurfacing procedures (mosaicplasty, Pridie drilling, abrasion arthroplasty, and microfracture cases in homogenized subgroups) showed that mosaicplasty gave a more favorable clinical outcome in the long-term followup, than the other three techniques. Intermediate-term evaluation of the femoral condylar implantations (3-6-years followup) and talar mosaicplasties (3-7-years followup) confirmed the durability of the early results. From these encouraging results from an increasingly large series and similar results from other centers, it seems that autologous osteochondral mosaicplasty may be a viable alternative treatment of localized full-thickness cartilage damage of the weightbearing surfaces of the knee and other weightbearing synovial joints.

Imaging of abdominal hernias.

Abdominal hernias are a common clinical problem. The main types of abdominal hernias are external or abdominal wall hernias, which involve protrusion of abdominal contents through a defect in the abdominal wall; internal hernias, which involve protrusion of viscera through the peritoneum or mesentery and into a compartment in the abdominal cavity; and diaphragmatic hernias, which involve protrusion of abdominal contents into the chest. Clinical diagnosis of abdominal hernias can be difficult. However, plain radiography, radiography performed after administration of barium, and computed tomography allow evaluation of suspected abdominal hernias and detection of those that are clinically occult. The anatomic location of the hernia, the contents, and complications such as incarceration, bowel obstruction, volvulus, and strangulation can be demonstrated with radiologic examination. Occasionally, complications such as neoplasms or inflammatory conditions can be identified in the hernial contents. With abdominal imaging modalities, a variety of abdominal hernias can be confidently diagnosed.

Metastatic disease involving the gastrointestinal tract.

Secondary involvement of the gastrointestinal tract by malignancies is encountered frequently. It usually reflects a poor prognosis because it is often multicentric and associated with metastases in other organs. Any therapy is usually palliative. Because of this, conventional barium studies or CT is sufficient for diagnosis and can obviate further studies.

Radiologic evaluation of constipation and anorectal disorders.

This article has outlined the orderly radiographic approach to evaluating the patient who presents with constipation or other anorectal complaints. Defecography alone provides only a visual record of events taking place during defecation, and it seems likely that further understanding of the pathophysiology will require manometric, electromyographic, and proctographic data in those patients. Defecography is potentially more available than these other techniques because every hospital has a fluoroscopy suite. Studies that relate the proctographic findings with other physiologic studies are underway and necessary. More studies relating pre- and postoperative defecography with clinical results are needed.

Clinical significance of pneumatosis of the bowel wall.

The presence of gas within the bowel wall is an uncommon condition that is typically first diagnosed by the radiologist. Although it is often seen on abdominal radiographs, computed tomography is more sensitive in demonstrating pneumatosis and its complications. There is a spectrum of disease states that produce this abnormality, ranging from the innocuous to the fatal. Its radiographic appearance is variable, particularly the location, extent, severity, and presence of pneumoperitoneum or portal venous gas. None of these imaging characteristics can be considered pathognomonic for the underlying cause of the pneumatosis. The radiologist must be aware of the different conditions associated with this entity, as well as their variable appearances.

Angioimmunoblastic lymphadenopathy of the colon with malignant transformation.

Angioimmunoblastic lymphadenopathy (AILD) is a rare disorder characterized by lymphadenopathy, constitutional symptoms, skin rashes, and a variety of hematologic disorders. Its occurrence in the colon is rare. Late in the disease, immunosuppression occurs, and there is an increased risk of malignant transformation. We present a case of AILD of the colon with eventual transformation into malignant lymphoma.

Gastrointestinal carcinomas in renal transplant recipients.

The development of malignancies in renal transplant recipients is well documented. Typically, these are cutaneous tumors or lymphomas. During the past 5 years, we have encountered six patients with documented carcinomas of the gastrointestinal tract, which developed after these patients received renal transplants. These carcinomas developed at an average of 10 years (range 2-16 years) after renal transplantation. There were three carcinomas of the colon, and one each of the esophagus, stomach, and anal canal. In many instances, the patients had examinations prior to transplantation which were normal. Several surveys of transplant recipients indicate there is an increased incidence of gastrointestinal tract malignancies after transplantation. These studies also recommend that screening of the gastrointestinal tract in long-term transplant recipients be performed. Since these patients are often imaged in the radiology department, radiologists must be aware of this possible complication.

Nonspecific radiographic abnormalities in collagenous colitis.

Collagenous colitis (CC) is characterized clinically by a chronic, watery diarrhea. Pathologically, there is a chronic lymphocytic infiltrate with abnormal thickening of the subepithelial collagen layer. This disease occurs predominantly in females, and is more frequent in the elderly. Previous clinical studies suggest that radiographic examination of the colon is of no value in this condition. We reviewed five cases of CC all of whom had colon examination within 2 weeks of the biopsy. Two of our patients showed evidence of mucosal granularity and irregularity of the rectosigmoid on double-contrast barium enema (DCBE). One patient had nodularity of the rectal wall on single-contrast colon examination. Two patients had no inflammatory changes evident on colon examination. These radiographic changes are nonspecific and may be seen in other forms of colitis, particularly ulcerative colitis and nonspecific proctitis.

Increased frequency of reactions to contrast materials during gastrointestinal studies.

Although there have been several reports of adverse reactions to contrast material during barium gastrointestinal (GI) studies, these are considered highly unusual. During a 27-month period at the author's institution, seven reactions to contrast material occurred during 6,918 colon examinations, and four reactions to contrast material occurred during 11,534 upper GI procedures. This frequency is greater than what has been reported previously. Most reactions were fairly mild, with urticaria and pruritus, although two patients, both with a history of asthma, had severe reactions that required emergency treatment. One patient had similar adverse reactions during both upper and lower GI examinations. Since only two patients received glucagon, this is not believed to be a factor. It is likely that patients react to some additive in the barium suspension. The radiologist must be aware of these complications and be ready to begin appropriate treatment.

Evolution of the technologist specialist in gastrointestinal radiology.

Over the past few years, a program was initiated at the author's institution to train radiologic technologists to perform the fluoroscopic aspect of gastrointestinal examinations. The program was undertaken in an attempt to improve patient flow through the division, as well as in response to the decreasing number of residents being accepted into the radiology program. The results with respect to diagnostic quality of examination, improved patient flow, and patient and resident acceptance have been satisfactory.

Digital radiography of the gastrointestinal tract.

The gastrointestinal tract lends itself quite well to digital imaging. Since fluoroscopy is already employed, the images can easily be obtained in digital format and several manufacturers have now developed systems for commercial use. Because of the type of pathology as well as the inherent subject contrast, it would appear the resolution requirements for digital imaging of the gastrointestinal tract are less than in other organ systems. The necessary resolution level is already technically available and feasible without significant cost. Digital imaging also holds promise of at least a modest reduction in radiation dose to the patient, as well as a reduction in costs, although these factors are operator dependent. However, digital imaging provides a latitude in performing the examination that is not available with screen-film systems. Finally, there is promise that by acquiring gastrointestinal images in digital format, manipulation of the images may help increase diagnostic accuracy by improving both technical and perceptive components of diagnosis. Not only will simple image manipulation be helpful but there is even potential for computer-assisted evaluation of gastrointestinal images.

Acute diverticulitis in patients under 40 years of age: radiologic diagnosis.

During a 4-year period, eight patients 40 years old or younger had surgically proved diverticulitis at our institution. None of these patients had connective-tissue diseases or were on medication (i.e., steroids) that would predispose them to diverticulosis. The presenting clinical symptoms in this group of patients were often misleading, and in only one of the eight cases was the correct clinical diagnosis made at the time of admission. Of the three diagnostic studies that were performed (barium enema, sonography, and CT), barium enema was the most accurate, yielding evidence for diverticulitis in six of seven cases. The degree and extent of diverticulosis in these patients was minimal compared with that in the older patients. CT showed abdominal abscesses in two patients; in one, a mistaken diagnosis of Crohn disease was made; in the other, diverticulitis was correctly identified. In the three patients in whom sonography was performed, the findings were negative for diverticulitis. Our experience suggests that the diagnosis of acute diverticulitis should be considered in patients with abdominal pain who are less than 40 years old.

Digital gastrointestinal imaging: the effect of pixel size on detection of subtle mucosal abnormalities.

Five radiographs of double-contrast colon examinations demonstrating subtle mucosal changes of inflammatory bowel disease and five radiographs of healthy colonic mucosa were selected and digitized to four levels of resolution. Pixel sizes of 0.1 mm, 0.2 mm, 0.4 mm, and 0.8 mm were used. Ten radiologists interpreted the images, which were displayed on laser-printed film. Analysis of variance with repeated measures was performed and receiver operator characteristic curves were determined. The results demonstrate that the sensitivity in detecting subtle mucosal abnormalities improved as the resolution improved, with the best sensitivity at the highest resolution; more experienced readers detected details well even at the poorer levels of resolution; the resolution necessary for successfully evaluating the colonic mucosa was lower than expected; and given low noise levels, the matrix size used in conventional television fluoroscopy would be adequate for mucosal evaluation.