Subchondral insufficiency fractures of the femoral head: associated imaging findings and predictors of clinical progression.

OBJECTIVES: To characterize the morphology and imaging findings of femoral head subchondral insufficiency fractures (SIF), and to investigate clinical outcomes in relation to imaging findings. METHODS: Fifty-one patients with hip/pelvis magnetic resonance (MR) images and typical SIF characteristics were identified and reviewed by two radiologists. Thirty-five patients had follow-up documentation allowing assessment of clinical outcome. Subgroup comparisons were performed using regression models adjusted for age and body mass index. RESULTS: SIF were frequently associated with cartilage loss (35/47, 74.5 %), effusion (33/42, 78.6 %), synovitis (29/44, 66 %), and bone marrow oedema pattern (BMEP) (average cross-sectional area 885.7 ± 730.2 mm(2)). Total hip arthroplasty (THA) was required in 16/35 patients, at an average of 6 months post-MRI. Compared to the THA cohort, the non-THA group had significantly (p < 0.05) smaller overlying cartilage defect size (10 mm vs. 29 mm), smaller band length ratio and fracture diameters, and greater incidence of parallel fracture morphology (p < 0.05). Male gender and increased age were significantly associated with progression, p < 0.05. CONCLUSIONS: SIF were associated with synovitis, cartilage loss, effusion, and BMEP. Male gender and increased age had a significant association with progression to THA, as did band length ratio, fracture diameter, cartilage defect size, and fracture deformity/morphology. KEY POINTS: • Femoral head subchondral insufficiency fractures (SIF) frequently require total hip arthroplasty (THA). • SIF frequently coexist with synovitis, cartilage loss, and bone marrow oedema pattern. • SIF cartilage defect size, band length ratio, and fracture diameter/morphology can predict progression risk.

Femoral condyle insufficiency fractures: associated clinical and morphological findings and impact on outcome.

OBJECTIVE: To determine the characteristics of femoral condyle insufficiency fracture (FCIF) lesions and their relative associations with the risk of clinical progression. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by our Institutional Review Board. Seventy-three patients (age range, 19-95) were included after excluding patients with post-traumatic fractures, bone marrow infarct, osteochondritis dissecans, or underlying tumor. Two board-certified musculoskeletal radiologists classified morphologic findings including lesion diameter, associated bone marrow edema pattern, and associated cartilage/meniscus damage. Electronic medical charts were evaluated for symptoms, risk factors, and longitudinal outcomes, including total knee arthroplasty (TKA). Imaging characteristics were correlated with clinical findings, and comparison of outcome groups was performed using a regression model adjusted for age. RESULTS: The majority of patients with FCIF were women (64.4%, 47/73), on average 10 years older than men (66.28 ± 15.86 years vs. 56.54 ± 10.39 years, p = 0.005). The most common location for FCIF was the central weight-bearing surface of the medial femoral condyle; overlying full thickness cartilage loss (75.7%, 53/70) and ipsilateral meniscal injury (94.1%, 64/68) were frequently associated. Clinical outcomes were variable, with 23.9% (11/46) requiring TKA. Cartilage WORMS score, adjacent cartilage loss, and contralateral meniscal injury, in addition to decreased knee range of motion at presentation, were significantly associated with progression to TKA (p < 0.05). CONCLUSIONS: FCIF are frequently associated with overlying cartilage loss and ipsilateral meniscal injury. The extent of cartilage loss and meniscal damage, in addition to loss of knee range of motion at the time of presentation, are significantly associated with clinical progression.

Assessment of scaphoid fracture healing.

Scaphoid fractures are among the most common hand fractures in adults. The geometry of the scaphoid as it relates to its retrograde blood supply renders it particularly prone to avascular necrosis and other fracture complications. Though there has been long-standing debate over the optimal method of diagnosing scaphoid fractures, the best and most cost-effective methods combine clinical exam with other imaging modalities such as navicular view plain films, CT, and MRI for particularly questionable presentations. Once a scaphoid fracture is diagnosed, it should be followed by an orthopaedic surgeon and treated with cast immobilization or operative management in the case of displaced fractures. Fractures should be followed to monitor healing progress in order to ensure the eventual development of bridging bone across the fracture line, usually best appreciated on CT. Proper treatment of scaphoid fractures and assessment of fracture healing can minimize the occurrence of non-unions and associated arthritic changes.

Long-term outcomes of patients undergoing endovascular infrainguinal interventions with single-vessel peroneal artery runoff.

OBJECTIVES: Recent reports have shown promising early results after endovascular revascularization (percutaneous transluminal angioplasty [PTA]/stent) of patients with peroneal artery-only runoff (PAOR), although the long-term durability is unclear. This study evaluated long-term primary patency and limb salvage of PTA/stent in patients with single-vessel runoff and critical limb ischemia to determine if the peroneal artery yields inferior results. METHODS: From January 2002 to December 2007, 1075 infrainguinal PTA/stent procedures were performed in 920 patients. The study cohort comprised 201 limbs in 187 patients with single-vessel runoff and critical limb ischemia. End points included primary patency, assisted patency, limb salvage, and survival. Long-term outcomes were determined by Kaplan-Meier life-table and multivariate Cox regression analyses. RESULTS: There were 104 PAOR and 97 limbs with single-vessel posterior or anterior tibial artery runoff (non-PAOR). Median follow-up was 25 months (range, 0-75 months). PAOR patients tended to be older (77.36 ± 0.92 vs 72.65 ± 1.18 years, P = .002) and were more likely to be taking clopidogrel at presentation (88% vs 76%; P = .04). There were no statistically significant differences in 5-year primary patency (26% ± 6.8% vs 30% ± 7.6%; P = .79), assisted patency (75% ± 8.8% vs 81% ± 7.0%; P = .77), limb salvage (74% ± 8.0% vs 75% ± 7.1%; P = .47), and survival (38% ± 7.7% vs 47% ± 6.6%; P = .99) between the PAOR and the non-PAOR groups, respectively. On Cox regression multivariate analysis, total occlusions predicted decreased assisted patency (hazard ratio, 2.99; 95% confidence interval, 1.21-7.41; P = .02), whereas younger age predicted poor limb salvage (hazard ratio, 0.97; 95% confidence interval, 0.94-0.99; P = .04). PAOR was not an independent predictor of any outcome on multivariate analysis. CONCLUSIONS: Patients with PAOR have similar long-term outcomes to patients with non-PAOR. Thus, infrainguinal endovascular revascularization can be considered a first-line therapy for patients with PAOR and critical limb ischemia.

Endovascular management of patients with critical limb ischemia.

BACKGROUND: Although percutaneous intervention (PTA) is considered first-line therapy for peripheral vascular disease in many scenarios, its role in critical limb ischemia (CLI), wherein anatomic disease is more extensive, remains unclear. In the present study, late (5-year) clinical and patency data for PTA in CLI are defined. METHODS: From January 2002 to December 2007, 409 patients underwent infrainguinal PTA ± stent for CLI (Rutherford IV-VI) of 447 limbs. Primary patency, assisted patency, limb salvage, and survival were assessed using Kaplan-Meier. Predictors of patency, limb salvage, and death were determined using multivariate models. RESULTS: Demographics included age (70 ± 12 years old), diabetes (65.8%), and dialysis dependence (13%). The superficial femoral artery was treated in 58% of the patients, 16% were limited to the crural vessels, 38% had multilevel treatment, and stents were placed in 26%. Eighty percent of patients received postprocedure clopidogrel. Mean follow-up was 28 months (0-83). Five-year primary and assisted patency were 31% ± 0.04 and 75% ± 0.04, respectively. Limb salvage at 5 years was 74% ± 0.038. Sixty-three patients had major amputations. Survival at 5 years was 39% ± 0.03. Multivariate analysis identified dialysis dependence (P = .0005; 2.7 [1.6-4.8]), ≤1 vessel runoff (P = .02; 1.5 [1.1-2.0]), and warfarin use (P = .001; 1.7 [1.25-2.3]) as negative predictors of primary patency, but none of these were negative predictors of assisted patency. Dialysis dependence (P = .006; 2.5 [1.3-4.8]), female gender (P = .02; 2.0 [1.1-3.7]), and ≤1 vessel run-off (P = .04; 1.8 [1.0-3.2]) predicted limb loss. Dialysis dependence (P = .0003; 2.3 [1.5-3.5]), diabetes (P = .04; 1.5 [0.5-2.1]), and poor run-off (P = .04; 1.6 [1.2-2.1]) were predictors of mortality. CONCLUSION: Although primary patency is low, excellent limb salvage rates can be achieved in patients with CLI through close follow-up and secondary interventions. These data, and the 12% annual death rate, validate PTA as first-line therapy in patients with CLI.

Long-term outcomes of diabetic patients undergoing endovascular infrainguinal interventions.

OBJECTIVE: Diabetes mellitus (DM) has traditionally predicted poor outcomes after lower extremity revascularization for peripheral vascular disease (PVD). This study assessed the influence of DM on long-term outcomes of percutaneous transluminal angioplasty, with or without stenting (PTA/stent), in patients with PVD. METHODS: From January 2002 to December 2007, 920 patients underwent 1075 PTA/stent procedures. Patients were stratified into DM and non-DM cohorts. Study end points included primary patency (PP), assisted patency (AP), limb salvage, and survival and were evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: There were 533 DM and 542 non-DM limbs. Median follow-up was 34 months. Overall, the 5-year actuarial PP was 42% +/- 2.4%, AP was 81% +/- 2.0%, limb salvage was 89% +/- 1.6%, and survival was 60% +/- 2.4%. On univariate analysis, DM vs non-DM was associated with inferior 5-year PP (37% +/- 3.4% vs 46% +/- 3.3%; P = .009), limb salvage (84% +/- 2.6% vs 93% +/- 1.8%, P < .0001), and survival (52% +/- 3.5% vs 68% +/- 3.1%, P = .0001). AP did not differ between DM and non-DM patients (P = .18). In the entire cohort, DM (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.01-1.54; P = .04), single-vessel peroneal runoff (HR, 1.54; 95% CI, 1.16-2.08; P = .003), and dialysis (HR, 1.59; 95% CI, 1.10-2.33; P = .02) were associated with decreased PP on multivariate analysis. The only variables on multivariate analysis to predict limb loss and death were critical limb ischemia (HR, 9.09; 95% CI, 4.17-20.00; P < . 0001; HR, 2.99; 95% CI, 2.01-4.44; P < .0001, respectively) and dialysis (HR, 2.94; 95% CI, 1.39-5.00; P = .003; HR, 4.24; 95% CI 2.80-6.45; P < .0001, respectively). CONCLUSIONS: DM is an independent predictor of decreased long-term primary patency after PTA/stent. Although acceptable assisted patency rates can be achieved with close surveillance and reintervention, long-term limb salvage remains inferior in diabetic patients compared with non-diabetic patients due to a more severe clinical presentation and poor runoff.

Involvement of the second extracellular loop and transmembrane residues of CCR5 in inhibitor binding and HIV-1 fusion: insights into the mechanism of allosteric inhibition.

C-C chemokine receptor 5 (CCR5), a member of G-protein-coupled receptors, serves as a coreceptor for human immunodeficiency virus type 1 (HIV-1). In the present study, we examined the interactions between CCR5 and novel CCR5 inhibitors containing the spirodiketopiperazine scaffolds AK530 and AK317, both of which were lodged in the hydrophobic cavity located between the upper transmembrane domain and the second extracellular loop (ECL2) of CCR5. Although substantial differences existed between the two inhibitors--AK530 had 10-fold-greater CCR5-binding affinity (K(d)=1.4 nM) than AK317 (16.7 nM)-their antiviral potencies were virtually identical (IC(50)=2.1 nM and 1.5 nM, respectively). Molecular dynamics simulations for unbound CCR5 showed hydrogen bond interactions among transmembrane residues Y108, E283, and Y251, which were crucial for HIV-1-gp120/sCD4 complex binding and HIV-1 fusion. Indeed, AK530 and AK317, when bound to CCR5, disrupted these interhelix hydrogen bond interactions, a salient molecular mechanism enabling allosteric inhibition. Mutagenesis and structural analysis showed that ECL2 consists of a part of the hydrophobic cavity for both inhibitors, although AK317 is more tightly engaged with ECL2 than AK530, explaining their similar anti-HIV-1 potencies despite the difference in K(d) values. We also found that amino acid residues in the beta-hairpin structural motif of ECL2 are critical for HIV-1-elicited fusion and binding of the spirodiketopiperazine-based inhibitors to CCR5. The direct ECL2-engaging property of the inhibitors likely produces an ECL2 conformation, which HIV-1 gp120 cannot bind to, but also prohibits HIV-1 from utilizing the "inhibitor-bound" CCR5 for cellular entry--a mechanism of HIV-1's resistance to CCR5 inhibitors. The data should not only help delineate the dynamics of CCR5 following inhibitor binding but also aid in designing CCR5 inhibitors that are more potent against HIV-1 and prevent or delay the emergence of resistant HIV-1 variants.