Long-term response with the atypical reaction to nivolumab in microsatellite stability metastatic colorectal cancer: A case report.

Immunotherapy has become an integral part of a comprehensive treatment approach to metastatic colorectal cancer (mCRC). Nivolumab (Opdivo) is a human immunoglobulin G4 monoclonal antibody that blocks the interaction between the programmed cell death 1 (PD-1) receptor and its ligands 1/2 (PD-L1/PD-L2), leading to inhibition of T-cell proliferation, cytokine secretion, and enhanced immune response. The US Food and Drug Administration (FDA) has approved this drug for use in high microsatellite instability (MSI-high)/deficiencies in mismatch repair (dMMR) advanced CRC patients. However, its efficacy is extremely limited in microsatellite stability (MSS)/mismatch repair proficient (pMMR) patients. We report a case of a 42-year-old man diagnosed with MSS/pMMR mCRC who has achieved a durable response to nivolumab after a progression under chemotherapy with antiangiogenic treatment. We observed for the first time an atypical response after 8 months of nivolumab treatment, with the regression of previous primary pulmonary lesions and the presence of new para-aortic lymph node lesions. This report demonstrates that a subset of pretreated mCRC patients with the MSS/pMMR phenotype may benefit from nivolumab and these patients need more attention.

Analysis of Circulating Tumor and Cancer Stem Cells Provides New Opportunities in Diagnosis and Treatment of Small Cell Lung Cancer.

Current methods for diagnosis and treatment of small cell lung cancer (SCLC) have only a modest efficacy. In this pilot study, we analyzed circulating tumor cells (CTCs) and cancer stem cells (CSCs) in patients with SCLC to search for new diagnostic and prognostic markers and novel approaches to improve the treatment of the disease. In other forms of lung cancer, we showed a heterogeneity of blood CTCs and CSCs populations, as well as changes in other cell populations (ALDH+, CD87+CD276+, and EGF+Axl+) in smokers. A number of CTCs and CSCs in patients with SCLC have been shown to be resistant to chemotherapy (CT). High cytotoxic activity and resistance to apoptosis of reprogrammed CD3+CD8+ T-lymphocytes (rTcells) in relation to naive CD3+CD8+ T-lymphocytes was demonstrated in a smoking patient with SCLC (Patient G) in vitro. The target for rTcells was patient G's blood CSCs. Reprogramming of CD3+CD8+ T-lymphocytes was carried out with the MEK1/2 inhibitor and PD-1/PD-L1 pathway blocker nivolumab. The training procedure was performed with a suspension of dead CTCs and CSCs obtained from patient's G blood. The presented data show a new avenue for personalized SCLC diagnosis and targeted improvement of chemotherapy based on the use of both CTCs and CSCs.

Parameters of Tumor Microenvironment Determine Effectiveness of Anti-PD-1/PD-L1 Therapy.

Undoubtedly, one of the most promising approaches to the treatment of cancer is creation of the pathogenetically based therapeutic drugs. Researchers from all over the world are trying to answer the question on how to select a target that would be effective and, in general, they are quite successful at that. The Nobel Prize-winning discovery of mechanisms for regulating activity of the immune system cells through checkpoint molecules, as well as discovery of the ability of tumor cells to use these mechanisms to suppress immune responses was an impetus for the development of modern immunotherapy, and now such inhibitors of the immune checkpoints as PD-1/PD-L1 are included in the routine chemotherapy. Use of such drugs can prolong the patient's life, but, unfortunately, not cure the disease. This is partially due to heterogeneity of tumor cells and microenvironment, but the main reasons may be in the complex relationships between the tumor and microenvironment, which, at times, are so plastic that they can change, adjusting to newly emerging conditions. Main characteristic of the tumor microenvironment is the type of the ongoing immune-inflammatory response (IIR), and since inhibitors of the immune checkpoints act on the cells involved in IIR, it is obvious that the outcomes of cancer therapy, including outcomes of hyperprogressive disease, can be associated with this parameter. The presented review reveals the essence of interactions between the tumor and its microenvironment during therapy with PD-L1 inhibitors.

The Role of Natriuretic Peptides in the Regulation of Cardiac Tolerance to Ischemia/Reperfusion and Postinfarction Heart Remodeling.

In the past 10 years, mortality from acute myocardial infarction has not decreased despite the widespread introduction of percutaneous coronary intervention. The reason for this situation is the absence in clinical practice of drugs capable of preventing reperfusion injury of the heart with high efficiency. In this regard, noteworthy natriuretic peptides (NPs) which have the infarct-limiting effect, prevent reperfusion cardiac injury, prevent adverse post-infarction remodeling of the heart. Atrial natriuretic peptide does not have the infarct-reducing effect in rats with alloxan-induced diabetes mellitus. NPs have the anti-apoptotic and anti-inflammatory effects. There is indirect evidence that NPs inhibit pyroptosis and autophagy. Published data indicate that NPs inhibit reactive oxygen species production in cardiomyocytes, aorta, heart, kidney and the endothelial cells. NPs can suppress aldosterone, angiotensin II, endothelin-1 synthesize and secretion. NPs inhibit the effects aldosterone, angiotensin II on the post-receptor level through intracellular signaling events. NPs activate guanylyl cyclase, protein kinase G and protein kinase A, and reduce phosphodiesterase 3 activity. NO-synthase and soluble guanylyl cyclase are involved in the cardioprotective effect of NPs. The cardioprotective effect of natriuretic peptides is mediated via activation of kinases (AMPK, PKC, PI3 K, ERK1/2, p70s6 k, Akt) and inhibition of glycogen synthase kinase 3ß. The cardioprotective effect of NPs is mediated via sarcolemmal KATP channel and mitochondrial KATP channel opening. The cardioprotective effect of brain natriuretic peptide is mediated via MPT pore closing. The anti-fibrotic effect of NPs may be mediated through inhibition TGF-ß1 expression. Natriuretic peptides can inhibit NF-κB activity and activate GATA. Hemeoxygenase-1 and peroxisome proliferator-activated receptor γ may be involved in the infarct-reducing effect of NPs. NPs exhibit the infarct-limiting effect in patients with acute myocardial infarction. NPs prevent post-infarction remodeling of the heart. To finally resolve the question of the feasibility of using NPs in AMI, a multicenter, randomized, blind, placebo-controlled study is needed to assess the effect of NPs on the mortality of patients after AMI.

A micro-architecturally biomimetic collagen template for mesenchymal condensation based cartilage regeneration.

The unique arcade-like orientation of collagen fibers enables cartilage to bear mechanical loads. In this study continuous-length aligned collagen threads were woven to emulate the interdigitated arcade structure of the cartilage. The weaving pattern provided a macropore network within which micromass cell pellets were seeded to take advantage of mesenchymal condensation driven chondrogenesis. Compression tests showed that the baseline scaffold had a modulus of 0.83±0.39MPa at a porosity of 80%. The modulus of pellet seeded scaffolds increased by 60% to 1.33±0.37MPa after 28days of culture, converging to the modulus of the native cartilage. The scaffolds displayed duress under displacement controlled low-cycle fatigue at 15% strain amplitude such that load reduction stabilized at 8% after 4500 cycles of loading. The woven structure demonstrated a substantial elastic recoil where 40% mechanical strain was close to completely recovered following unloading. A robust chondrogenesis was observed as evidenced by positive staining for GAGs and type II collagen and aggrecan. Dimethyl methylene blue and sircol assays showed GAGs and collagen productions to increase from 3.36±1.24 and 31.46±3.22 at day 3 to 56.61±12.12 and 136.70±12.29µg/µg of DNA at day 28 of culture. This woven collagen scaffold holds a significant potential for cartilage regeneration with shorter in vitro culture periods due to functionally sufficient mechanical robustness at the baseline. In conclusion, the mimicry of cartilage's arcade architecture resulted in substantial improvement of mechanical function while enabling one of the first pellet delivery platforms enabled by a macroporous network. STATEMENT OF SIGNIFICANCE: Mesenchymal condensation is critical for driving chondrogenesis, making high density cell seeding a standard in cartilage tissue engineering. Efforts to date have utilized scaffold free delivery of MSCs in pellet form. This study developed a macroporous scaffold that is fabricated by weaving highly aligned collagen threads. The scaffold can deliver high density cell condensates while providing mechanical stiffness comparable to that of cartilage. The scaffold also mimicked the arcade-like orientation of collagen fibers in cartilage. A highly robust chondrogenesis was observed in this mesenchymal cell pellet delivery system. Baseline mechanical robustness of this scaffold system will enable delivery of cell pellets as early as three days.

Implant Size Availability Affects Reproduction of Distal Femoral Anatomy.

A total knee arthroplasty system offers more distal femoral implant anterior-posterior (AP) sizes than its predecessor. The purpose of this study is to investigate the impact of increased size availability on an implant system's ability to reproduce the AP dimension of the native distal femur. We measured 200 cadaveric femora with the AP-sizing guides of Zimmer (Warsaw, IN) NexGen (8 sizes) and Zimmer Persona (12 sizes) total knee arthroplasty systems. We defined "size deviation" as the difference in the AP dimension between the anatomic size of the native femur and the closest implant size. We defined satisfactory reproduction of distal femoral dimensions as < 1 mm difference between the implant and native femur size. The NexGen system was associated with a mean 0.46 mm greater implant size deviation than Persona (p < 0.001). When using a 1 mm size deviation as a cutoff for satisfactory replication of the native distal femoral anatomy, 85/200 specimens (42.5%) were a poor fit by NexGen, but a satisfactory fit by Persona. Only 1/200 specimens (0.5%) was a poor fit by Persona, but a satisfactory fit by NexGen (p < 0.001). The novel knee system with 12 versus 8 sizes reproduces the AP dimension of the native distal femur more closely than its predecessor. Further study is needed to determine the clinical impact of these differences.

Important Differences Exist in Posterior Condylar Offsets in an Osteological Collection of 1,058 Femurs.

Posterior condylar offset (PCO) has important implications in total knee arthroplasty (TKA) function and design. In an osteological study of 1,058 femurs, we measured PCO using two separate techniques with a 3D digitizer. Measurements were standardized for the size of the femur. The medial PCO was greater than lateral PCO (32.6mm vs. 31.2mm, P<0.0001). In 53% of individuals, the medial PCO differed between sides by more than 2mm. Age did not affect standardized medial or lateral PCO. Compared with African-Americans, Caucasians had a larger standardized medial (1.3mm vs. 1.2mm, P=0.006) and lateral (1.1mm vs. 1.0mm, P=0.004) PCOs. The standardized medial (1.2mm vs. 1.3mm, P=0.073), and lateral (1.1mm vs. 1.1mm, P=0.098), PCO did not differ between men and women, respectively.

Machine oil inhibits the osseointegration of orthopaedic implants by impairing osteoblast attachment and spreading.

The most important factor contributing to short-term and long-term success of cementless total joint arthroplasties is osseointegration. Osseointegration leads to a direct structural and functional connection between living bone and the surface of an implant. Surface contaminants may remain on orthopaedic implants after sterilization procedures and impair osseointegration. For example, specific lots of hip replacement Sulzer Inter-OP(TM) acetabular shells that were associated with impaired osseointegration and early failure rates were found to be contaminated with both bacterial debris and machine oil residues. However, the effect of machine oil on implant integration is unknown. Therefore, the goal of this study was to determine if machine oil inhibits the osseointegration of orthopaedic implants. To test this hypothesis in vivo we used our murine model of osseointegration where titanium alloy implants are implanted into a unicortical pilot hole in the mid-diaphysis of the femur. We found that machine oil inhibited bone-to-implant contact and biomechanical pullout measures. Machine oil on titanium alloy discs inhibited early stages of MC3T3-E1 osteogenesis in vitro such as attachment and spreading. Inhibition of osteoblast attachment and spreading occurred in both areas with and without detectable oil. Osteoblast growth was in turn inhibited on discs with machine oil due to both a decrease in proliferation and an increase in cell death. Later stages of osteogenic differentiation and mineralization on titanium alloy discs were also inhibited. Thus, machine oil can inhibit osseointegration through cell autonomous effects on osteoblast cells. These results support routine testing by manufacturers of machine oil residues on orthopaedic implants.

Frequency of EGFR mutations in non-small cell lung cancer patients: screening data from West Siberia.

BACKGROUND: Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice has shown great promise to provide personalized therapy of the non-small cell lung cancer (NSCLC) in the developed world. However, the genetic testing of EGFR mutations has not yet become routine clinical practice in territories remote from the central regions of Russia. Therefore, we aimed to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients residing in West Siberia. MATERIALS AND METHODS: We examined EGFR mutations in exons 19 and 21 in 147 NSCLC patients (excluding squamous cell lung carcinomas) by real time polymerase chain reaction. RESULTS: EGFR mutations were detected in 28 of the 147 (19%) patients. There were 19 (13%) cases with mutations in exon 19 and 9 cases (6%) in exon 21. Mutations were more frequently observed in women (42%, p=0.000) than in men (1%). A significantly higher incidence of EGFR mutations was observed in bronchioloalveolar carcinomas (28%, p=0.019) and in adenocarcinomas (21%, p=0.024) than in large cell carcinomas, mixed adenocarcinomas, and NOS (4%). The EGFR mutation rate was much higher in never-smokers than in smokers: 38% vs. 3% (p=0.000). The frequency of EGFR mutations in the Kemerovo and Tomsk regions was 19%. CONCLUSIONS: The incorporation of molecular analysis of the EGFR gene into routine clinical practice will allow clinicians to provide personalised therapy, resulting in a significant increase in survival rates and improvement in life quality of advanced NSCLC patients.

Predictors of range of motion in patients undergoing manipulation after TKA.

BACKGROUND: Knee stiffness or limited range of motion (ROM) after total knee arthroplasty (TKA) may compromise patient function. Patients with stiffness are usually managed with manipulation under anesthesia (MUA) to improve ROM. However, the final ROM obtained is multifactorial and may depend on factors such as comorbidities, implant type, or the timing of MUA. QUESTIONS/PURPOSES: We asked whether diabetes mellitus, implant type, and the interval between TKA and MUA influenced post-MUA ROM. METHODS: From a group of 2462 patients with 3224 TKAs performed between 1999 and 2007 we retrospectively reviewed 96 patients with 119 TKAs (4.3%) who underwent MUA. We determined the presence of diabetes mellitus, implant type, and the interval between TKA and MUA. RESULTS: The average increase in ROM after MUA was 34°. Patients with diabetes mellitus experienced lower final ROM after MUA (87.5° versus 100.3°) as did patients with cruciate-retaining (CR) prostheses versus posterior-stabilized (92.3° versus 101.6°). The interval between TKA and MUA inversely correlated with final ROM with a decrease after 75 days. CONCLUSIONS: Most patients experience improvements in ROM after MUA. Patients with diabetes mellitus or CR prostheses are at risk for lower final ROM after MUA. Manipulation within 75 days of TKA is associated with better ROM.

Adherent lipopolysaccharide inhibits the osseointegration of orthopedic implants by impairing osteoblast differentiation.

Osseointegration is the process by which an orthopedic implant makes direct bone-to-implant contact and is crucial for the long-term function of the implant. Surface contaminants, such as bacterial debris and manufacturing residues, may remain on orthopedic implants after sterilization and impair osseointegration. For example, specific lots of implants that were associated with impaired osseointegration and high failure rates were discovered to have contaminants including bacterial debris. Therefore, the goals of this study were to determine if bacterial debris exists on sterile orthopedic implants and if adherent bacterial debris inhibits the osseointegration of orthopedic implants. We found that debris containing lipopolysaccharide (LPS) from Gram-negative bacteria exists on both sterile craniofacial implants and wrist implants. Levels of bacterial debris vary not only between different lots of implants but within an individual lot. Using our murine model of osseointegration, we found that ultrapure LPS adherent to the implants inhibited bone-to-implant contact and biomechanical pullout measures. Analysis of osseointegration in knock-out mice demonstrated that adherent LPS inhibited osseointegration by signaling through its primary receptor, Toll-like receptor 4, and not by signaling through Toll-like receptor 2. Ultrapure LPS adherent to titanium alloy discs had no detectable effect on early stages of MC3T3-E1 osteogenesis in vitro such as attachment, spreading or growth. However, later stages of osteogenic differentiation and mineralization were inhibited by adherent LPS. Thus, LPS may inhibit osseointegration in part through cell autonomous effects on osteoblasts. These results highlight bacterial debris as a type of surface contaminant that can impair the osseointegration of orthopedic implants.

The shape of the proximal femur influences acetabular wear patterns over time.

BACKGROUND: Femoroacetabular impingement has been proposed as a cause of early osteoarthritis, but it is not known how this develops over time or whether the shape of the proximal femur influences this risk. QUESTIONS/PURPOSES: (1) Which areas of the acetabulum are worn more frequently by individuals with a cam deformity of the proximal femur? (2) Do observed acetabular wear patterns differ based on the etiology of the cam deformity? (3) Do wear patterns of individuals with a cam deformity differ based on an individual's age? METHODS: We examined 645 corresponding femora and acetabuli from the Hamann-Todd Osteological Collection and determined the offset and alpha angle using photographs; 370 specimens met inclusion criteria and were examined for signs of wear and the locations of wear were recorded. Specimens were separated into eight subgroups based on age either younger than 40 years or older than 60 years, alpha angle greater or less than 55°, and degree of anterior head-neck offset. We compared the prevalence of wear between groups in each location. RESULTS: Individuals with abnormal geometry of the proximal femur demonstrated different wear patterns from individuals with normal geometry. There were few differences in wear patterns identified based on the etiology of the femoral deformity. Abnormal femoral geometry was associated with more frequent wear primarily at the anterosuperior acetabulum for individuals younger than 40 years of age and globally for individuals older than 60 years of age. CONCLUSION: Femoral geometry appears to influence the pattern of acetabular wear occurring over time.

Micrometer scale guidance of mesenchymal stem cells to form structurally oriented cartilage extracellular matrix.

Tissue engineering is a possible method for long-term repair of cartilage lesions, but current tissue-engineered cartilage constructs have inferior mechanical properties compared to native cartilage. This problem may be due to the lack of an oriented structure in the constructs at the microscale that is present in the native tissue. In this study, we utilize contact guidance to develop constructs with microscale architecture for improved chondrogenesis and function. Stable channels of varying microscale dimensions were formed in collagen-based and polydimethylsiloxane membranes via a combination of microfabrication and soft-lithography. Human mesenchymal stem cells (MSCs) were selectively seeded in these channels. The chondrogenic potential of MSCs seeded in these channels was investigated by culturing them for 3 weeks under differentiating conditions, and then evaluating the subsequent synthesized tissue for mechanical function and by type II collagen immunohistochemistry. We demonstrate selective seeding of viable MSCs within the channels. MSC aligned and produced mature collagen fibrils along the length of the channel in smaller linear channels of widths 25-100 µm compared to larger linear channels of widths 500-1000 µm. Further, substrates with microchannels that led to cell alignment also led to superior mechanical properties compared to constructs with randomly seeded cells or selectively seeded cells in larger channels. The ultimate stress and modulus of elasticity of constructs with cells seeded in smaller channels increased by as much as fourfolds. We conclude that microscale guidance is useful to produce oriented cartilage structures with improved mechanical properties. These findings can be used to fabricate large clinically useful MSC-cartilage constructs with superior mechanical properties.

An initial experience with hip resurfacing versus cementless total hip arthroplasty.

BACKGROUND: Hip resurfacing is an alternative to total hip arthroplasty. QUESTIONS/PURPOSE: We aimed to compare an experienced hip surgeon's initial clinical results of hip resurfacing with a new cementless total hip arthroplasty (THA). METHODS: The first 55 consecutive hip resurfacing arthroplasties were compared to 100 consecutive cementless THAs using a cylindrical tapered femoral stem. The learning curve between the two procedures was compared utilizing the incidence of reoperation, complications, Harris Hip Scores (HHS), and implant survivorship. RESULTS: The reoperation rate was significantly higher (p = 0.019) for hip resurfacing (14.5%) versus THA (4%). The overall complication rate between the two groups was not significantly different (p = 0.398). Preoperative HHS were similar between the two groups (p = 0.2). The final mean HHS was similar in both the resurfacing and THA groups (96 vs. 98.3, respectively, p < 0.65). Kaplan-Meier survival analysis with an endpoint of reoperation suggests complications occurred earlier in the resurfacing group versus the THA group (log-rank test, p = 0.007). CONCLUSIONS: In comparison to our initial experience with a cementless THA stem, operative complications occur earlier and more often after hip resurfacing during the learning period. The clinical outcomes in both groups however are similar at 5 year follow-up.

Retrieval analysis of Harris-Galante I and II acetabular liners in situ for more than 10 years.

BACKGROUND AND PURPOSE: There have been few reports documenting the wear and oxidation performance of the polyethylene bearing surface of HGPI and HGPII THA devices. We evaluated retrieved HGPI and HGPII acetabular liners that had been in situ for more than 10 years and determined whether there was a relationship between clinical and radiographic factors, surface damage, wear, and oxidation. MATERIALS AND METHODS: 129 HGPI and II acetabular liners with implantation times of > 10 years were retrieved at 4 institutions between 1997 and 2010. The liners were made from a single resin and were gamma radiation-sterilized in air. Surface damage, linear wear, and oxidation index (OI) were assessed. Differences in clinical and radiographic factors, surface damage, linear wear, and OI for the 2 designs were statistically evaluated separately and together. RESULTS: Articular surface damage and backside damage was similar in the 2 designs. The linear penetration rate was 0.14 (SD 0.07) mm/year for the HGPI liners and 0.12 (SD 0.08) mm/year for the HGPII liners. For both cohorts, the rim had a higher OI than the articular surface. 74% of the liners had subsurface cracking and 24% had a complete fracture through the acetabular rim. INTERPRETATION: Despite modification of the HGP locking mechanism in the HGPII design, dissociation of the liner from the acetabular shell can still occur if fracture of the rim of the liner develops due to oxidative degradation.

Surface contaminants inhibit osseointegration in a novel murine model.

Surface contaminants, such as bacterial debris and manufacturing residues, may remain on orthopedic implants after sterilization procedures and affect osseointegration. The goals of this study were to develop a murine model of osseointegration in order to determine whether removing surface contaminants enhances osseointegration. To develop the murine model, titanium alloy implants were implanted into a unicortical pilot hole in the mid-diaphysis of the femur and osseointegration was measured over a five week time course. Histology, backscatter scanning electron microscopy and X-ray energy dispersive spectroscopy showed areas of bone in intimate physical contact with the implant, confirming osseointegration. Histomorphometric quantification of bone-to-implant contact and peri-implant bone and biomechanical pullout quantification of ultimate force, stiffness and work to failure increased significantly over time, also demonstrating successful osseointegration. We also found that a rigorous cleaning procedure significantly enhances bone-to-implant contact and biomechanical pullout measures by two-fold compared with implants that were autoclaved, as recommended by the manufacturer. The most likely interpretation of these results is that surface contaminants inhibit osseointegration. The results of this study justify the need for the development of better detection and removal techniques for contaminants on orthopedic implants and other medical devices.

Nondestructive evaluation of hydrogel mechanical properties using ultrasound.

The feasibility of using ultrasound technology as a noninvasive, nondestructive method for evaluating the mechanical properties of engineered weight-bearing tissues was evaluated. A fixture was designed to accurately and reproducibly position the ultrasound transducer normal to the test sample surface. Agarose hydrogels were used as phantoms for cartilage to explore the feasibility of establishing correlations between ultrasound measurements and commonly used mechanical tissue assessments. The hydrogels were fabricated in 1-10% concentrations with a 2-10 mm thickness. For each concentration and thickness, six samples were created, for a total of 216 gel samples. Speed of sound was determined from the time difference between peak reflections and the known height of each sample. Modulus was computed from the speed of sound using elastic and poroelastic models. All ultrasonic measurements were made using a 15 MHz ultrasound transducer. The elastic modulus was also determined for each sample from a mechanical unconfined compression test. Analytical comparison and statistical analysis of ultrasound and mechanical testing data was carried out. A correlation between estimates of compressive modulus from ultrasonic and mechanical measurements was found, but the correlation depended on the model used to estimate the modulus from ultrasonic measurements. A stronger correlation with mechanical measurements was found using the poroelastic rather than the elastic model. Results from this preliminary testing will be used to guide further studies of native and engineered cartilage.

Post damage in contemporary posterior-stabilized tibial inserts: influence of implant design and clinical relevance.

The mechanisms of damage at the polyethylene post in 3 contemporary tibial insert designs were evaluated and compared with a historical standard (Insall-Burstein II; Zimmer, Warsaw, Ind). One hundred five gamma sterilized posterior-stabilized tibial inserts were revised after an average of 4.7 years (0.05-13.6 years). Retrievals were classified according to their designs: Insall-Burstein II (n = 28); PFC (Johnson & Johnson, Raynham, Mass; n = 30); NexGen (Zimmer; n = 32); and Scorpio (Stryker Orthopaedics, Mahwah, NJ; n = 15). Reasons for revision and patient details were available. Surface damage scoring and photogrammetry were performed on all the retrieved tibial inserts. Oxidation analysis was carried out for traceable historical, gamma air-sterilized and conventional, gamma inert-sterilized tibial inserts (n = 61) with the use of infrared spectroscopy. The posts for all 3 contemporary designs exhibited damage similar to the historical controls. Articular, post, and backside damage scores significantly increased with implantation time. Post damage was insensitive to design and patient factors but was exacerbated by oxidation. An association between damage at the post and articular surface was also confirmed. Logistic models suggested an interaction between post damage, backside surface damage, and implant loosening.

Incidence of postthrombotic syndrome in patients undergoing primary total hip arthroplasty for osteoarthritis.

BACKGROUND: Postthrombotic syndrome (PTS) is a chronic condition in the lower extremity that develops after deep vein thrombosis (DVT). The incidence of PTS after total hip arthroplasty (THA) is not well established. QUESTIONS/PURPOSES: We (1) determined the incidence of PTS after DVT in patients undergoing primary THA for osteoarthritis; and (2) determined whether the incidence of PTS was greater in patients with DVT than without. METHODS: We retrospectively reviewed records of all 1037 patients who underwent primary THA for osteoarthritis during a 4-year period. All patients underwent postoperative screening ultrasound. We identified 21 (2%) patients with a DVT by ultrasound of whom 14 had a minimum 1-year followup (mean, 3.4 years; range, 1.0-6.0 years). PTS was diagnosed if any two of the six clinical signs were documented. RESULTS: Three of 14 patients with DVT had at least two signs consistent with PTS; two of these had a DVT proximal to the soleal arch. Three of 91 randomly matched patients undergoing THA without DVT had at least two signs of PTS. The incidence of developing PTS after THA appeared higher in patients with DVT than in patients without DVT. CONCLUSIONS: While we observed a difference between the incidence of PTS after THA in patients with and without DVT, that incidence was based on only three of 1037 patients with DVT after THA. PTS does not appear to be a major complication after DVT in patients undergoing THA. LEVEL OF EVIDENCE: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.