Patellofemoral articular cartilage damage is associated with poorer patient-reported outcomes following isolated medial patellofemoral ligament reconstruction.

PURPOSE: The purpose of this study was to investigate the impact of articular cartilage damage on outcomes following medial patellofemoral ligament (MPFL) reconstruction. METHODS: Record review identified 160 patients who underwent isolated MPFL reconstruction at a single institution between 2008 and 2016. Patient demographics, patellofemoral articular cartilage status at surgery, and patient anatomical measures from imaging were obtained via chart review. Patients were contacted and outcomes assessed through collection of Norwich Patellar Instability (NPI) score, Knee injury and Osteoarthritis Outcome Score (KOOS), and Marx activity score as well as an assessment for recurrent patellar dislocation. Outcomes of patients with grade 0-II patellofemoral cartilage damage were compared to those of patients with grade III-IV cartilage damage. RESULTS: One hundred twenty-two patients (76%) with a minimum of one year follow-up were contacted at a mean of 4.8 years post-operatively. A total of 63 patients (52%) had grade III or IV patellofemoral chondral damage at the time of surgery. The majority of the defects was on the medial patella (46 patients-72%) and the mean patellar defect size was 2.8 cm2. Among 93 patients who completed patient-reported outcome scores, the 52 with grade III or IV chondral damage reported a significantly poorer KOOS Quality of Life than the 44 patients with grade 0 to II chondral damage (p = 0.041), controlling for patient age, sex, BMI, and anatomical factors. CONCLUSION: Patients with grade III or IV articular cartilage damage of the patellofemoral joint at the time of MPFL reconstruction demonstrated poorer KOOS knee-related quality of life than patients without grade III or IV articular cartilage damage at a mean of 4.8 years following isolated MPFL reconstruction. LEVEL OF EVIDENCE: Level II.

In vitro investigation on the impact of the surface-active excipients Cremophor EL, Tween 80 and Solutol HS 15 on the metabolism of midazolam.

The impact of the surface-active formulation ingredients Cremophor EL, Tween 80 and Solutol HS 15 on the intrinsic clearance (Clint) of midazolam (MDZ) was investigated in rat hepatocytes and microsomes. In rat hepatocytes with 0.003%, 0.03% and 0.3% (w/v) Solutol HS 15 already present in the incubation medium, the Clint was significantly reduced in a dose-dependent manner by about 25%, 30% and 50%, respectively. In the presence of Cremophor EL and Tween 80 a significant reduction in Clint by about 30% and 25%, respectively, was observed at 0.03% surfactant concentration. At 0.3% of Cremophor EL and Tween 80, Clint was reduced by about 50% and 20%, respectively. A reduction in Clint was also observed in experiments with rat liver microsomes. At surfactant concentrations up to 0.03%, cytotoxicity assays (lactate dehydrogenase release, adenosine triphosphate content) as well as light microscope investigations did not reveal any cytotoxic impact of the surfactants on the hepatocyte monolayer. A potential interaction of the surfactants with biological membranes was determined using phosphatidylcholine-cholesterol liposomes loaded with self-quenching concentrations of carboxyfluorescein. No marked release of carboxyfluorescein from the liposomes (that would be an indication for a surfactant-dependent disruption of membrane integrity) was observed up to concentrations of 0.03% of the different surfactants. It is concluded that cytochrome P450 3A mediated metabolism of MDZ seems to be prevented by all surfactants at concentrations above 0.03%. In our experiments the surfactants did not show toxic effects at concentrations that resulted in a decreased Clint of MDZ. Thus, a direct inhibition of the metabolizing enzymes, a molecular interaction with the microsomes as well as an alteration of membrane properties that did not yet result in a release of LDH have to be taken into consideration as reasons for the observed changes in the metabolism of MDZ.