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Background: Multiligament knee injuries (MLKIs) can also involve the medial patellofemoral ligament (MPFL), but there is a paucity of information regarding prevalence and relevance of MPFL involvement in this setting. Purpose: (1) To identify the prevalence of MPFL injury in MLKIs, (2) to determine whether an MPFL tear results in symptomatic patellar instability, and (3) to report clinical and functional outcomes of patients with and without MPFL tears after MLKI surgical reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: The records of all patients who underwent surgical reconstruction of MLKI (defined as a grade 3 injury of ≥2 ligaments) at a single institution from 2007 to 2010 were reviewed. Age, sex, knee dislocation classification (according to Schenck), and MRI findings were documented. All preoperative MRI scans were reviewed by an experienced musculoskeletal radiologist to determine the presence or absence of MPFL involvement. If an MPFL tear was present, its anatomic location and severity as well as the presence of patellar or lateral femoral condyle bone bruises were documented. Inclusion criteria included (1) MLKI treated at a single institution, (2) presence of MPFL tear on preoperative MRI, and (3) minimum 2-year clinical follow-up. Patellar instability symptoms were assessed with the Kujala Knee Questionnaire. Functional outcomes were measured using the International Knee Documentation Committee (IKDC) score. IKDC scores were compared between patients who sustained MLKIs with and without MPFL tears. There were 21 patients in each group. Results: Over the 4-year study period, 30 of 51 patients (59%) treated surgically for a MLKI had MRI evidence of an MPFL tear. Nine were lost to follow-up, leaving 21 patients for review. There were 13 complete (62%), 5 high-grade partial (24%), and 3 partial (14%) MPFL tears. Sixteen of 21 tears (76%) occurred at the proximal third, with the remainder exhibiting diffuse signal abnormality consistent with tearing throughout the length of the MPFL. The superficial medial collateral ligament was involved in all patients. In no case was the MPFL repaired or reconstructed. At mean follow-up of 3.6 years (range, 2.0-5.7 years), only 1 of 21 patients (5%) complained of patellofemoral instability symptoms whereas 20 of 21 patients (95%) did not experience patellar subluxation or dislocation. No significant difference was found when IKDC scores were compared between patients with and without an MPFL tear (mean ± SD, 65.5 ± 22.9 vs 79.4 ± 16.1; P = .07). Conclusion: MPFL tears occur frequently in patients with MLKI but rarely cause instability. In the majority of cases, MPFL tears do not need to be addressed at the time of surgery.

The aim of this study was to quantify connective tissue fibre orientation and alignment in young, old and glaucomatous human optic nerve heads (ONH) to understand ONH microstructure and predisposition to glaucomatous optic neuropathy. Transverse (seven healthy, three glaucomatous) and longitudinal (14 healthy) human ONH cryosections were imaged by both second harmonic generation microscopy and small angle light scattering (SALS) in order to quantify preferred fibre orientation (PFO) and degree of fibre alignment (DOFA). DOFA was highest within the peripapillary sclera (ppsclera), with relatively low values in the lamina cribrosa (LC). Elderly ppsclera DOFA was higher than that in young ppsclera ( p < 0.00007), and generally higher than in glaucoma ppsclera. In all LCs, a majority of fibres had preferential orientation horizontally across the nasal–temporal axis. In all glaucomatous LCs, PFO was significantly different from controls in a minimum of seven out of 12 LC regions ( p < 0.05). Additionally, higher fibre alignment was observed in the glaucomatous inferior–temporal LC ( p < 0.017). The differences between young and elderly ONH fibre alignment within regions suggest that age-related microstructural changes occur within the structure. The additional differences in fibre alignment observed within the glaucomatous LC may reflect an inherent susceptibility to glaucomatous optic neuropathy, or may be a consequence of ONH remodelling and/or collapse.

BACKGROUNDNVP‐AUY922 (AUY; Luminespib) with or without bortezomib showed preclinical activity against multiple myeloma (MM) cells. This phase 1/1B study assessed NVP‐AUY922 alone and with bortezomib in patients with relapsed or refractory MM.METHODSDose escalation was guided by an adaptive Bayesian logistic regression model. In phase 1, patients who progressed after 2 to 4 prior therapies received NVP‐AUY922 intravenously once weekly. In phase 1B, patients who progressed after 2 or fewer prior therapies received NVP‐AUY922 plus bortezomib. The primary objective was to determine the maximum tolerated dose (MTD) of NVP‐AUY922.RESULTSTwenty‐four patients received NVP‐AUY922 monotherapy at doses of 8 to 70 mg/m2. One dose‐limiting toxicity (DLT) was observed (grade 3 blurred vision at 70 mg/m2); no MTD was reached. The recommended phase 2 dose was 70 mg/m2. The most frequent drug‐related adverse events (AEs) were diarrhea, nausea, and ocular toxicities. Grade 3/4 AEs were uncommon (<10%). Eight patients discontinued treatment because of AEs; 5 had ocular toxicities (≥45 mg/m2). The best response was stable disease in 66.7% of the patients. There were no partial or complete responses. Five patients received NVP‐AUY922 (which was started at 50 mg/m2) plus bortezomib (1.3 mg/m2). Three of these patients experienced DLT. No further dose escalation was performed; the MTD for NVP‐AUY922 plus bortezomib was not established.CONCLUSIONSThis study showed disease stabilization with NVP‐AUY922 in patients with relapsed or refractory MM. The MTD for NVP‐AUY922 was not reached, but reversible ocular toxicity has been reported at high dose levels. Bortezomib at the standard recommended dose plus NVP‐AUY922 was not tolerated. Cancer 2015;121:2185–2192. © 2015 American Cancer Society.