Smaller intercondylar notch size and smaller ACL volume increase posterior cruciate ligament rupture risk.

PURPOSE: Little is known about risk factors for sustaining a posterior cruciate ligament (PCL) rupture. Identifying risk factors is the first step in preventing a PCL rupture from occurring. The morphology of the knee in patients who ruptured their PCL may differ from that of control patients. The hypothesis was that the intercondylar notch dimensions, 3-D volumes of the intercondylar notch and, the 3-D volumes of both the ACL and the PCL were correlated to the presence of a PCL rupture. METHODS: The magnetic resonance imaging (MRI) scans of 30 patients with a proven PCL rupture were compared to 30 matched control patients with proven intact ACL and PCL. Control patients were selected from patients with knee trauma during sports but without cruciate ligament injury. Patients have been matched for age, height, weight, BMI, and sex. The volumes of the intercondylar notch and both the ACL and PCL were measured on 3D reconstructions. Second, the bicondylar width, the notch width, and the notch width index were measured of all subjects. The relationship between our measurements and the presence of a PCL rupture was analysed. RESULTS: The results show a significant difference in the volumes of the intercondylar notch and the ACL between patients with a ruptured PCL and control patients. Patients with a PCL rupture have smaller intercondylar notch volumes and smaller ACL volumes. There were no significant differences in the bicondylar width, notch width, and notch width index. In the control patients, a significant correlation between the volume of the PCL and the volume of the ACL was found (0.673, p < 0.001). CONCLUSION: Patients with a PCL rupture have smaller intercondylar volumes and smaller ACL volumes when compared to control patients. Second, patients with smaller ACL volumes have smaller PCL volumes. This study shows, for the first time, that there are significant size and volume differences in the shape of the knee between patients with a PCL rupture and control patients. LEVEL OF EVIDENCE: IV.

The hypoxia-sensor carbonic anhydrase IX affects macrophage metabolism, but is not a suitable biomarker for human cardiovascular disease.

Hypoxia is prevalent in atherosclerotic plaques, promoting plaque aggravation and subsequent cardiovascular disease (CVD). Transmembrane protein carbonic anhydrase IX (CAIX) is hypoxia-induced and can be shed into the circulation as soluble CAIX (sCAIX). As plaque macrophages are hypoxic, we hypothesized a role for CAIX in macrophage function, and as biomarker of hypoxic plaque burden and CVD. As tumor patients with probable CVD are treated with CAIX inhibitors, this study will shed light on their safety profile. CAIX co-localized with macrophages (CD68) and hypoxia (pimonidazole), and correlated with lipid core size and pro-inflammatory iNOS+ macrophages in unstable human carotid artery plaques. Although elevated pH and reduced lactate levels in culture medium of CAIX knock-out (CAIXko) macrophages confirmed its role as pH-regulator, only spare respiratory capacity of CAIXko macrophages was reduced. Proliferation, apoptosis, lipid uptake and expression of pro- and anti-inflammatory genes were not altered. Plasma sCAIX levels and plaque-resident CAIX were below the detection threshold in 50 and 90% of asymptomatic and symptomatic cases, respectively, while detectable levels did not associate with primary or secondary events, or intraplaque hemorrhage. Initial findings show that CAIX deficiency interferes with macrophage metabolism. Despite a correlation with inflammatory macrophages, plaque-resident and sCAIX expression levels are too low to serve as biomarkers of future CVD.

Posterior cruciate ligament injury is influenced by intercondylar shape and size of tibial eminence.

AIMS: Little is known about the risk factors that predispose to a rupture of the posterior cruciate ligament (PCL). Identifying risk factors is the first step in trying to prevent a rupture of the PCL from occurring. The morphology of the knee in patients who rupture their PCL may differ from that of control patients. The purpose of this study was to identify any variations in bone morphology that are related to a PCL. PATIENTS AND METHODS: We compared the anteroposterior (AP), lateral, and Rosenberg view radiographs of 94 patients with a ruptured PCL to a control group of 168 patients matched by age, sex, and body mass index (BMI), but with an intact PCL after a knee injury. Statistical shape modelling software was used to assess the shape of the knee and determine any difference in anatomical landmarks. RESULTS: We found shape variants on the AP and Rosenberg view radiographs to be significantly different between patients who tore their PCL and those with an intact PCL after a knee injury. Overall, patients who ruptured their PCL have smaller intercondylar notches and smaller tibial eminences than control patients. CONCLUSION: This study shows that differences in the shape of the knee are associated with the presence of a PCL rupture after injury. A smaller and more sharply angled intercondylar notch and a more flattened tibial eminence are related to PCL rupture. This suggests that the morphology of the knee is a risk factor for sustaining a PCL rupture. Cite this article: Bone Joint J 2019;101-B:1058-1062.

Effect of interleukin (IL)-8 on benzo[a]pyrene metabolism and DNA damage in human lung epithelial cells.

It has been well established that inflammation and concurrent mutagenic exposures drive the carcinogenic process in a synergistic way. To elucidate the role of the inflammatory cytokine IL-8 in this process, we studied its effect on the activation and deactivation of the chemical mutagen benzo[a]pyrene B[a]P in the immortalized pulmonary BEAS-2B cell line. After 24h incubation with B[a]P in the presence or absence of IL-8, the B[a]P induced cytochrome P450 1A1 and 1B1 (CYP1A1 and CYP1B1) gene expression and CYP1A1 enzyme activity was significantly higher in the presence of the cytokine. Consistent with these findings, we observed higher concentration of the metabolite B[a]P-7,8-diol under concurrent IL-8 treatment conditions. Interestingly, we also found higher concentrations of unmetabolized B[a]P. To explain this, we examined the downstream effects of IL-8 on NADPH oxidases (NOXes). IL-8 lowered the intracellular NADPH level, but this effect could not explain the changes in B[a]P metabolism. IL-8 also significantly depleted intracellular glutathione (GSH), which also resulted in enhanced levels of unmetabolized B[a]P, but increased concentrations of the metabolite B[a]P-7,8-diol. No differences in B[a]P-DNA adducts level were found between B[a]P and B[a]P combined with IL-8, and this might be due to a 3-fold increase in nucleotide excision repair (NER) after IL-8 treatment. These findings suggest that IL-8 increased the formation of B[a]P-7,8-diol despite an overall delayed B[a]P metabolism via depletion of GSH, but DNA damage levels were unaffected due to an increase in NER capacity.

Knee shape might predict clinical outcome after an anterior cruciate ligament rupture.

We have investigated whether shape of the knee can predict the clinical outcome of patients after an anterior cruciate ligament rupture. We used statistical shape modelling to measure the shape of the knee joint of 182 prospectively followed patients on lateral and Rosenberg view radiographs of the knee after a rupture of the anterior cruciate ligament. Subsequently, we associated knee shape with the International Knee Documentation Committee subjective score at two years follow-up. The mean age of patients was 31 years (21 to 51), the majority were male (n = 121) and treated operatively (n = 135). We found two modes (shape variations) that were significantly associated with the subjective score at two years: one for the operatively treated group (p = 0.002) and one for the non-operatively treated group (p = 0.003). Operatively treated patients who had higher subjective scores had a smaller intercondylar notch and a smaller width of the intercondylar eminence. Non-operatively treated patients who scored higher on the subjective score had a more pyramidal intercondylar notch as opposed to one that was more dome-shaped. We conclude that the shape of the femoral notch and the intercondylar eminence is predictive of clinical outcome two years after a rupture of the anterior cruciate ligament.