An Unusual Case of Left Spigelian Hernia Containing Part of a Fibroid Uterus and the Left Adnexa in a 66-Year-Old Woman.

BACKGROUND Spigelian hernia, or lateral ventral hernia, is rare and represents between 0.1-2% of all hernias of the abdominal wall. The presentation is variable, and the diagnosis may be challenging. This report is of an unusual case of Spigelian hernia that contained part of a fibroid uterus and the left adnexa. CASE REPORT A 66-year-old woman presented with an abdominal wall mass in the left lower quadrant. On physical examination, a provisional diagnosis of ventral hernia was made. Abdominal computed tomography (CT) imaging showed an unusual Spigelian hernia that contained part of a fibroid uterus and the left adnexa. Treatment using laparoscopic hysterectomy, left salpingo-oophorectomy, and hernia repair was successfully performed jointly by a general surgeon and a gynecologist. CONCLUSIONS To the best of our knowledge, the is the first reported case of Spigelian hernia that contained part of the uterus and the left adnexa.

An Intra-Operatively Diagnosed Case of Hemorrhagic Cholecystitis in a 43-year-old Patient: Case Report.

BACKGROUND Hemorrhagic cholecystitis is an uncommon occurrence in the setting of gallbladder pathology. It is a rare complication of acute cholecystitis that may have a misleading presentation and workup, making it challenging to diagnose pre-operatively. CASE REPORT We report the case of a 43-year-old female who presented for severe epigastric pain with nausea and vomiting and whose imaging was in favor of acute cholecystitis. The patient was scheduled for laparoscopic cholecystectomy, during which she was found to have hemorrhagic cholecystitis, later confirmed by pathology. CONCLUSIONS Hemorrhagic cholecystitis is an uncommon diagnosis in patients presenting with abdominal pain. The case discussed hereafter was found to have hemorrhagic cholecystitis intra-operatively. Urgent cholecystectomy is crucial in the setting of hemorrhagic cholecystitis due to its possible fatality. This case emphasizes the importance of thinking of hemorrhagic cholecystitis in a patient presenting for what appears to be a severe acute cholecystitis.

Catheter-directed thrombolysis versus suction thrombectomy in the management of acute pulmonary embolism.

BACKGROUND: Catheter-directed thrombolysis (CDT) is increasingly performed for acute pulmonary embolism (PE) because it is presumed to provide similar therapeutic benefits to systemic thrombolysis, while decreasing the dose of thrombolytic required and the associated risks. Contemporary suction thrombectomy (ST) devices have entered the market as minimal or no-lytic alternatives, but there is no evidence on their comparative effectiveness. This study aims to compare clinical outcomes of these two interventional alternatives. METHODS: Consecutive patients who underwent a ST catheter intervention for massive or submassive PE between 2011 and 2017 were identified. For each of these patients, a nearest-neighbor matching was implemented to identify at least three CDT patients who matched as closely as possible on the following six variables: PE type, age, gender, acute deep venous thrombosis, pulmonary disease, and year of procedure. The end point was clinical success defined as meeting all the following criteria: survival to hospital discharge without major bleeding (Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries moderate or severe), perioperative stroke or other major adverse procedure-related event, and decompensation for submassive or persistent shock for massive PE. RESULTS: Of 277 patients who received an intervention for acute PE, 54 CDT (63.5 ± 14.2 years of age; 18 massive PE) were matched with 18 ST (64.1 ± 14.1 years of age; 6 massive PE) patients. In the CDT group, 38 (70.4%) received ultrasound-assisted thrombolysis. The ST group had significantly more patients who had a major contraindication for lytics (1 [1.9%] for CDT vs 9 [50%] for ST; P < .001). There was no difference in major bleeding (8 [14.8%] for CDT vs 3 [16.7%] for ST; P > .999; Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries severe 1 [1.8%] for CDT vs 1 [5.6%] for ST; P > .999), stroke (3.7% for CDT vs 0 for ST; P = .408), or death (3.7% for CDT vs 16.7% for ST; P = .096). One patient in the ST group suffered tricuspid valve rupture and two patients in CDT group required surgical thrombectomy. Clinical success was not statistically different between groups (75.9% for CDT vs 61.1% for ST; P = .224). The association was similar when assessing the right/left ventricular ratio improvement (0.30 ± 0.19 for CDT vs 0.17 ± 0.16 for ST; P = .097), or the subgroup of patients with submassive PE (86.1% for CDT vs 66.7% for ST; P = .135). CONCLUSIONS: CDT seems to have similar outcomes with ST in the management of acute PE, although larger, more homogenous data are needed. In our experience, ST should be viewed as a complementary alternative for patients with contraindication for thrombolytics or severely compromised hemodynamic profile and can yield good outcomes in an otherwise highly morbid population.

Outcomes and predictors of failure of iliac vein stenting after catheter-directed thrombolysis for acute iliofemoral thrombosis.

OBJECTIVE: Iliac vein stenting is recommended to treat venous outflow obstruction after catheter-directed thrombolysis for acute iliofemoral deep venous thrombosis (DVT). Data on the outcome of proximal and distal stent extension are limited. Proximal stent extension to the vena cava may obstruct the contralateral iliac vein, whereas distal extension below the inguinal ligament contradicts common practice for arterial stents. The aim of this retrospective study was to assess outcomes and predictors of failure of iliac vein stents and contralateral iliac vein thrombosis, taking into consideration stent positioning. METHODS: Consecutive patients who underwent thrombolysis and stenting for DVT between May 2007 and September 2017 were identified from a prospectively maintained database. The intraoperative venograms were reviewed for proximal stent placement (covering >50% contralateral iliac vein orifice) and distal placement across the inguinal ligament. End points were ipsilateral DVT recurrence, post-thrombotic syndrome (PTS; Villalta score ≥5), and contralateral DVT. Patients with chronic contralateral DVT or contralateral iliac vein stenting at baseline were excluded from the contralateral DVT outcome evaluation. Survival analysis and Cox regression models were used to determine outcomes. RESULTS: Of 142 patients lysed, 73 patients (12 bilateral DVTs; mean age, 45.8 ± 17.2 years; 46 female patients) were treated with various combinations of thrombolytic techniques and at least one self-expanding iliac stent (77 stented limbs). Thirty-day recurrence developed in nine (12.3%) patients. The 3-year primary patency and secondary patency rates were 75.2% and 82.2%, respectively. The single predictor for loss of primary patency was incomplete thrombolysis (≤50%; hazard ratio [HR], 7.41; P = .002). Overall, 3 of 12 (25%) stents extending below the inguinal ligament occluded at 1 month, 2 months, and 9 months, respectively. The overall rate of PTS (Villalta score ≥5) in the stented cohort was 14.4% at 5 years. This was predicted by incomplete lysis (<50%; HR, 7.09; P = .040), stent extension below the inguinal ligament (HR, 6.68; P = .026), and male sex (HR, 6.02; P = .041). Of the 17 stents that extended into the contralateral common iliac vein and 58 stents that did not, there were 1 (5.9%) and 5 (8.6%) contralateral DVTs (P = .588) at an average follow-up of 27.4 ± 33.7 and 22.2 ± 22.3 months (P = .552), respectively. CONCLUSIONS: Iliac stenting after thrombolysis for acute DVT guarantees high patency and low PTS rates, provided adequate thrombus resolution has been achieved before stent placement. Stent placement below the inguinal ligament does not affect the patency but may be associated with a higher PTS rate. Stenting proximal to the iliocaval confluence, although a precipitating factor, may not independently increase the likelihood of contralateral DVT.

An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP12.

Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort called WeFold, was initiated to promote collaboration within the CASP community and attract researchers from other fields to contribute new ideas to CASP. Members of the WeFold coopetition (cooperation and competition) participated in CASP as individual teams, but also shared components of their methods to create hybrid pipelines and actively contributed to this effort. We assert that the scale and diversity of integrative prediction pipelines could not have been achieved by any individual lab or even by any collaboration among a few partners. The models contributed by the participating groups and generated by the pipelines are publicly available at the WeFold website providing a wealth of data that remains to be tapped. Here, we analyze the results of the 2014 and 2016 pipelines showing improvements according to the CASP assessment as well as areas that require further adjustments and research.

Leishmania in a Patient with Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia.

BACKGROUND Leishmaniasis is a parasitic infection spread by the bite of infected sand flies that are usually present in the Middle East, Africa, and some parts of Asia and Europe. Leishmaniasis manifests in 3 different forms: Visceral (also known as Kala Azar), which is the most serious type; cutaneous, which is the most common type; and mucocutaneous. The symptoms of this infection range from a silent infection to fever, enlargement of the liver and spleen, weight loss, and pancytopenia. CASE REPORT In this case report, we discuss a 73-year-old man known to have chronic lymphocytic leukemia (CLL), presenting with unremitting fever and who to our surprise was found to have Kala Azar. CONCLUSIONS Early diagnosis and treatment are very important in treating visceral leishmaniasis. While the conventional treatment in immunocompromised patients is liposomal amphotericin B, our patient responded to corticosteroids.

Outcomes of infrageniculate retrograde versus transfemoral access for endovascular intervention for chronic lower extremity ischemia.

OBJECTIVE: Retrograde infrageniculate access is an alternative treatment strategy for patients who have failed to respond to antegrade endovascular intervention. This study compares the outcomes of infrageniculate retrograde arterial access with the conventional transfemoral access for the endovascular management of chronic lower extremity ischemia. METHODS: This was a retrospective single-center review of retrograde endovascular intervention (REI) from 2012 to 2016. Indications for intervention, comorbidities, complications, procedural success, limb outcomes, and mortality were analyzed. Technical failure was defined as the inability to complete the procedure because of failed access or unsuccessful recanalization. Infrageniculate access and transfemoral access were obtained with ultrasound or angiographic roadmap guidance. Patency rates were calculated for technically successful interventions. RESULTS: There were 47 patients (85% presenting with critical limb ischemia) who underwent sheathless REI after failed antegrade recanalization of TransAtlantic Inter-Society Consensus class D infrainguinal lesions, whereas 93 patients (83% with critical limb ischemia) underwent standard transfemoral access. There were 16 (34%) femoropopliteal, 14 (30%) tibial, and 17 (36%) multilevel interventions in the retrograde group compared with 41 (41%) femoropopliteal, 20 (20%) tibial, and 39 (39%) multilevel interventions in the transfemoral group. Access sites for the retrograde group included the dorsalis pedis (26%), midcalf peroneal (24%), anterior tibial (22%), posterior tibial (26%), and popliteal (2%) arteries. Overall technical success was achieved in 57% of the retrograde group compared with 78% of the transfemoral group. Mean follow-up was 20 months (range, 1-45 months). There were no significant differences in the primary patency rates between the two groups at 1 year and 2 years. The primary assisted patency rates were significantly better in the transfemoral group at 1 year (66% vs 46%; P = .031) and 2 years (56% vs 29%; P = .031). The secondary patency rates were higher in the transfemoral group at 1 year (93% vs 83%; P = .079) and 2 years (91% vs 76%; P = .079), although this did not reach statistical significance. The rate of reintervention was 41% for the retrograde group vs 40% for the transfemoral group. Most of the reinterventions (70% in the retrograde group and 61% in the transfemoral group) were endovascular interventions for a restenosis or occlusion. CONCLUSIONS: Infrageniculate access for REI can result in primary patency rates similar to those of antegrade interventions and does not compromise the access site. Technical failure is high in this initial experience and is mostly due to failed recanalization. Limb salvage may be achieved after technical failure with either repeated antegrade intervention or surgical bypass.

Foreign Body Ingestion Causing Recurrent Diverticulitis.

BACKGROUND Ingested foreign bodies (IFBs) are usually asymptomatic and are excreted uneventfully. IFBs become a major concern in elderly patients due to the increase number of diverticuloses where the foreign body can lodge and cause severe complications. CASE REPORT We report a case of an elderly patient who ingested a chicken bone that caused recurrent diverticulitis. CONCLUSIONS The diagnosis of complicated IFB cases is challenging, requires physician clinical expertise, and must be considered in individuals at risk.

Princeton_TIGRESS 2.0: High refinement consistency and net gains through support vector machines and molecular dynamics in double-blind predictions during the CASP11 experiment.

Protein structure refinement is the challenging problem of operating on any protein structure prediction to improve its accuracy with respect to the native structure in a blind fashion. Although many approaches have been developed and tested during the last four CASP experiments, a majority of the methods continue to degrade models rather than improve them. Princeton_TIGRESS (Khoury et al., Proteins 2014;82:794-814) was developed previously and utilizes separate sampling and selection stages involving Monte Carlo and molecular dynamics simulations and classification using an SVM predictor. The initial implementation was shown to consistently refine protein structures 76% of the time in our own internal benchmarking on CASP 7-10 targets. In this work, we improved the sampling and selection stages and tested the method in blind predictions during CASP11. We added a decomposition of physics-based and hybrid energy functions, as well as a coordinate-free representation of the protein structure through distance-binning Cα-Cα distances to capture fine-grained movements. We performed parameter estimation to optimize the adjustable SVM parameters to maximize precision while balancing sensitivity and specificity across all cross-validated data sets, finding enrichment in our ability to select models from the populations of similar decoys generated for targets in CASPs 7-10. The MD stage was enhanced such that larger structures could be further refined. Among refinement methods that are currently implemented as web-servers, Princeton_TIGRESS 2.0 demonstrated the most consistent and most substantial net refinement in blind predictions during CASP11. The enhanced refinement protocol Princeton_TIGRESS 2.0 is freely available as a web server at http://atlas.engr.tamu.edu/refinement/. Proteins 2017; 85:1078-1098. © 2017 Wiley Periodicals, Inc.

Impact of inferior vena cava thrombus extension on thrombolysis for acute iliofemoral thrombosis.

BACKGROUND: Inferior vena cava (IVC) thrombosis may occur in patients with iliofemoral deep venous thrombosis (DVT), and its impact on thrombolysis outcomes is poorly defined. This study compared outcomes of patients undergoing thrombolysis for acute iliofemoral DVT with and without IVC involvement. METHODS: Patients who underwent thrombolysis for iliofemoral DVT between May 2007 and March 2014 were identified from a prospectively maintained database and divided into two groups: those with IVC involvement and those without. End points were technical and clinical success (≥50% lysis or freedom from 30-day DVT recurrence), long-term DVT recurrence, and post-thrombotic syndrome (PTS; Villalta score ≥5). Multivariate regression models were used to determine predictors of anatomic and clinical failures. RESULTS: There were 102 patients (127 limbs) treated with various combinations of catheter-directed or pharmacomechanical thrombolysis. In 46 patients, thrombus extended into the IVC (54.3% extended up to the renal veins; 87% had ≥50% luminal reduction; 50% occurred in association with an indwelling thrombosed IVC filter). The caval group had fewer women and more previous DVTs but otherwise was similar to the noncaval group. Pharmacomechanical thrombolysis was used more frequently in the caval thrombus group (97.8% vs 82.1%; P = .011), and iliac vein stenting was used more often in the noncaval group (41.3% vs 62.5%; P = .033). Clinical success was similar between the two groups (88.7% for caval vs 89.3% for noncaval; P = .921). All failures in the caval group occurred in patients with an indwelling thrombosed IVC filter. Primary patency at 2 years for the caval and noncaval groups was 76.7% and 78.0%, respectively (P = .787). Valve reflux and PTS at 2 years were higher in the noncaval group (50.8% and 34.3% vs 23.3% and 11.5% in the caval group; P = .013 and P = .035). On multivariate analysis, incomplete lysis was predictive of recurrence (hazard ratio [HR], 22.7; P < .001) and PTS (HR, 5.59; P = .010), whereas caval involvement (HR, 0.22; P = .005) was protective from PTS. CONCLUSIONS: IVC thrombosis does not have an impact on the technical success of thrombolysis in patients with iliofemoral DVT; the presence of a thrombosed IVC filter, though, may make failure more likely. Caval thrombosis may not affect primary patency but is associated with a lower incidence of PTS after successful lysis.

Laparoscopic gastric band removal complicated by splenosis.

In any patient, the occurrence of postsplenectomy splenosis can complicate the planning of further surgeries. In our case, the gastric sleeve procedure was aborted, as it would have put the patient's life in danger. Therefore, only the gastric band was removed, eliminating future erosion.

Trauma in CT: The Role of Severe Injury on Satisfaction of Search Revised.

PURPOSE: The satisfaction-of-search (SOS) effect occurs when an abnormality on an image is missed because another is found. The aim of this experiment was to test whether severe distracting fractures control the magnitude of SOS on other fractures when both appear in a single CT image. METHODS: The institutional review board approved this study. The experimental (SOS) condition included 35 cervical spine CT cases, all of which contained severe cervical spine injuries. For each of these cases, a similar case was found that had no injuries. Image modification software was developed to add simulated fractures to each pair of cases, with and without a major injury. Sixteen different minor fractures were added to 16 of the 35 pairs of images. The 35 cases without native injuries constituted a control (non-SOS) condition mixed in a random order. Twenty radiologists read 35 mixed cases in each of two sessions. False-positive evaluations were collected only for cases without simulated fractures. RESULTS: An SOS effect on the detection of simulated fractures was not observed. There was a nonsignificant (P = .07) finding of poorer detection in the presence of cases with severe injuries. However, the magnitude of the effect was no greater than has been observed for less severe distracting injuries. CONCLUSIONS: The outcome agrees with the results of two previous experiments that failed to yield an SOS effect associated with detecting severe injuries, suggesting that the severity of a distracting injury does not determine whether a second injury is discovered.

conSSert: Consensus SVM Model for Accurate Prediction of Ordered Secondary Structure.

Accurate prediction of protein secondary structure remains a crucial step in most approaches to the protein-folding problem, yet the prediction of ordered secondary structure, specifically beta-strands, remains a challenge. We developed a consensus secondary structure prediction method, conSSert, which is based on support vector machines (SVM) and provides exceptional accuracy for the prediction of beta-strands with QE accuracy of over 0.82 and a Q2-EH of 0.86. conSSert uses as input probabilities for the three types of secondary structure (helix, strand, and coil) that are predicted by four top performing methods: PSSpred, PSIPRED, SPINE-X, and RAPTOR. conSSert was trained/tested using 4261 protein chains from PDBSelect25, and 8632 chains from PISCES. Further validation was performed using targets from CASP9, CASP10, and CASP11. Our data suggest that poor performance in strand prediction is likely a result of training bias and not solely due to the nonlocal nature of beta-sheet contacts. conSSert is freely available for noncommercial use as a webservice: http://ares.tamu.edu/conSSert/.

Fibro-osseous lesion of the cranium in an adolescent patient.

BACKGROUND: Fibrous dysplasia, ossifying fibroma, and desmoplastic fibroma are rare benign calvarial lesions, which can have local aggressive behavior. These tumors can present with similar clinical and radiologic characteristics making diagnosis difficult at times. CASE DESCRIPTION: A 16-year-old male presents after noting an indentation of his skull. Comparison with current and previous imaging revealed progressive erosion of the skull underlying the indentation. CONCLUSION: Fibrous dysplasia, ossifying fibroma, and desmoplastic fibroma are rare fibro-osseous tumors with similar characteristics radiographically. Accurate diagnosis of these tumors can be difficult even with the combination of clinical presentation, imaging, and pathology. The treatment of choice is resection and cranial reconstruction, if necessary, with close follow-up as recurrence can occur.

New compstatin peptides containing N-terminal extensions and non-natural amino acids exhibit potent complement inhibition and improved solubility characteristics.

Compstatin peptides are complement inhibitors that bind and inhibit cleavage of complement C3. Peptide binding is enhanced by hydrophobic interactions; however, poor solubility promotes aggregation in aqueous environments. We have designed new compstatin peptides derived from the W4A9 sequence (Ac-ICVWQDWGAHRCT-NH2, cyclized between C2 and C12), based on structural, computational, and experimental studies. Furthermore, we developed and utilized a computational framework for the design of peptides containing non-natural amino acids. These new compstatin peptides contain polar N-terminal extensions and non-natural amino acid substitutions at positions 4 and 9. Peptides with α-modified non-natural alanine analogs at position 9, as well as peptides containing only N-terminal polar extensions, exhibited similar activity compared to W4A9, as quantified via ELISA, hemolytic, and cell-based assays, and showed improved solubility, as measured by UV absorbance and reverse-phase HPLC experiments. Because of their potency and solubility, these peptides are promising candidates for therapeutic development in numerous complement-mediated diseases.

De novo design and experimental characterization of ultrashort self-associating peptides.

Self-association is a common phenomenon in biology and one that can have positive and negative impacts, from the construction of the architectural cytoskeleton of cells to the formation of fibrils in amyloid diseases. Understanding the nature and mechanisms of self-association is important for modulating these systems and in creating biologically-inspired materials. Here, we present a two-stage de novo peptide design framework that can generate novel self-associating peptide systems. The first stage uses a simulated multimeric template structure as input into the optimization-based Sequence Selection to generate low potential energy sequences. The second stage is a computational validation procedure that calculates Fold Specificity and/or Approximate Association Affinity (K*association) based on metrics that we have devised for multimeric systems. This framework was applied to the design of self-associating tripeptides using the known self-associating tripeptide, Ac-IVD, as a structural template. Six computationally predicted tripeptides (Ac-LVE, Ac-YYD, Ac-LLE, Ac-YLD, Ac-MYD, Ac-VIE) were chosen for experimental validation in order to illustrate the self-association outcomes predicted by the three metrics. Self-association and electron microscopy studies revealed that Ac-LLE formed bead-like microstructures, Ac-LVE and Ac-YYD formed fibrillar aggregates, Ac-VIE and Ac-MYD formed hydrogels, and Ac-YLD crystallized under ambient conditions. An X-ray crystallographic study was carried out on a single crystal of Ac-YLD, which revealed that each molecule adopts a ß-strand conformation that stack together to form parallel ß-sheets. As an additional validation of the approach, the hydrogel-forming sequences of Ac-MYD and Ac-VIE were shuffled. The shuffled sequences were computationally predicted to have lower K*association values and were experimentally verified to not form hydrogels. This illustrates the robustness of the framework in predicting self-associating tripeptides. We expect that this enhanced multimeric de novo peptide design framework will find future application in creating novel self-associating peptides based on unnatural amino acids, and inhibitor peptides of detrimental self-aggregating biological proteins.

Forcefield_NCAA: ab initio charge parameters to aid in the discovery and design of therapeutic proteins and peptides with unnatural amino acids and their application to complement inhibitors of the compstatin family.

We describe the development and testing of ab initio derived, AMBER ff03 compatible charge parameters for a large library of 147 noncanonical amino acids including ß- and N-methylated amino acids for use in applications such as protein structure prediction and de novo protein design. The charge parameter derivation was performed using the RESP fitting approach. Studies were performed assessing the suitability of the derived charge parameters in discriminating the activity/inactivity between 63 analogs of the complement inhibitor Compstatin on the basis of previously published experimental IC50 data and a screening procedure involving short simulations and binding free energy calculations. We found that both the approximate binding affinity (K*) and the binding free energy calculated through MM-GBSA are capable of discriminating between active and inactive Compstatin analogs, with MM-GBSA performing significantly better. Key interactions between the most potent Compstatin analog that contains a noncanonical amino acid are presented and compared to the most potent analog containing only natural amino acids and native Compstatin. We make the derived parameters and an associated web interface that is capable of performing modifications on proteins using Forcefield_NCAA and outputting AMBER-ready topology and parameter files freely available for academic use at http://selene.princeton.edu/FFNCAA . The forcefield allows one to incorporate these customized amino acids into design applications with control over size, van der Waals, and electrostatic interactions.

WeFold: a coopetition for protein structure prediction.

The protein structure prediction problem continues to elude scientists. Despite the introduction of many methods, only modest gains were made over the last decade for certain classes of prediction targets. To address this challenge, a social-media based worldwide collaborative effort, named WeFold, was undertaken by 13 labs. During the collaboration, the laboratories were simultaneously competing with each other. Here, we present the first attempt at "coopetition" in scientific research applied to the protein structure prediction and refinement problems. The coopetition was possible by allowing the participating labs to contribute different components of their protein structure prediction pipelines and create new hybrid pipelines that they tested during CASP10. This manuscript describes both successes and areas needing improvement as identified throughout the first WeFold experiment and discusses the efforts that are underway to advance this initiative. A footprint of all contributions and structures are publicly accessible at http://www.wefold.org.

Synovitis in knee osteoarthritis assessed by contrast-enhanced magnetic resonance imaging (MRI) is associated with radiographic tibiofemoral osteoarthritis and MRI-detected widespread cartilage damage: the MOST study.

OBJECTIVE: To examine the cross-sectional association of whole-knee synovitis assessed by contrast-enhanced magnetic resonance imaging (CEMRI) with radiographic tibiofemoral osteoarthritis (OA), non-CEMRI-assessed cartilage damage, and meniscal status. METHODS: Multicenter Osteoarthritis Study (MOST) is a cohort study of people with or at high risk of knee OA. Subjects are a subset of MOST who volunteered for both CEMRI and non-CEMRI. Using CEMRI, synovitis was assessed at 11 sites and graded 0-2 at each site. Presence of "whole-knee synovitis" was defined as the synovitis score of ≥ 1 at any site from each knee. Cartilage and meniscal damage was evaluated using non-CEMRI based on the Whole Organ MRI Score. Logistic regression was used to assess associations of synovitis with radiographic OA (Kellgren-Lawrence grade ≥ 2), widespread cartilage damage, and meniscal damage, adjusting for age, sex, and body mass index (BMI). Additional analyses were performed excluding subjects who had chondrocalcinosis on radiography and those taking antiinflammatory medications. RESULTS: Four hundred four subjects were included (mean age 58.8 ± 7.0 yrs, BMI 29.6 ± 4.9 kg/m(2), 45.5% women). On CEMRI, the maximum synovitis score across 11 sites in each knee was 0 in 106 knees (26.2%), 1 in 135 (33.4%), and 2 in 163 (40.4%). Synovitis was associated with radiographic OA [adjusted OR (aOR) 3.25, 95% CI 1.98-5.35] and widespread cartilage damage (aOR 1.91, 95% CI 1.24-2.92). Severe meniscal damage showed a borderline significant association with synovitis (aOR 1.74, 95% CI 0.99-3.04). Additional analyses as described did not notably change the results. CONCLUSION: CEMRI-detected synovitis is strongly associated with tibiofemoral radiographic OA and MRI-detected widespread cartilage damage.