Pre-operative arthritis severity as a predictor for total knee arthroplasty patients’ satisfaction

Purpose

Studies have shown that up to 25 % of TKA patients are dissatisfied with the implanted knee, even if registry data shows ten-year revision rates below 5 %. It has been the question of our study, if it would be possible to identify those patients at risk for dissatisfaction pre-operatively.

Methods

The data of 1,121 consecutive TKA patients with a follow-up between one and six years have been analysed retrospectively. Demographic, radiologic and perioperative variables have been recorded and all patients were asked by questionnaire for satisfaction with the implanted knee. Logistic regression models have been used to identify significant risk factors.

Results

The data of 996 patients (89 %) were complete, 849 (85.2 %) reported satisfaction and 147 (14.8 %) dissatisfaction. Patients’ satisfaction was independent of the time after operation (p = 0.285). The only factor which influenced patients’ satisfaction was the osteoarthritic severity. In comparison to severe arthritis Kellgren Lawrence IV°, the risk for dissatisfaction was 2.556-fold elevated for arthritis grade III° (p < 0.001) and 2.956-fold higher for grade II° (p = 0.001).

Conclusions

Patients suffering from mild or moderate osteoarthritis are at risk for dissatisfaction after TKA. The TKA indication in those patients should therefore be critically proven. Furthermore, to adjust patients’ expectations, the elevated dissatisfaction risk in case of mild or moderate osteoarthritis should be included into patients’ pre-operative information.     

BMD improvements after operation for primary hyperparathyroidism

Purpose

This study aims to quantify bone mineral density (BMD) changes following surgery in patients with primary hyperparathyroidism (PHPT) and to assess their relationship with clinical and biochemical variables.

Methods

A historic cohort of 236 PHPT patients with DXA scans pre- and 1-year postoperatively, clinical data, and biochemical data was analyzed.

Results

The mean age was 60 years (range 19–86) and 81 % of the patients were women. A significant postoperative 2.6 % (95 % CI, 2.1; 3.1) increase in lumbar spine BMD was seen. The increase in BMD was positively associated with preoperative plasma PTH (p?=?0.002), Ca²⁺ (p?<?0.001), and alkaline phosphatase (p?=?0.014). Hip BMD increased 1.5 % (1.1; 1.9). The increase in BMD was positively associated with preoperative plasma PTH (p?=?0.005) and Ca²⁺ (p?<?0.001) and inversely associated with plasma creatinine (p?=?0.004) and age (p?=?0.018). Total forearm BMD did not change significantly (?0.2 % (?0.5; 0.1)). An increase in forearm BMD was seen in 38 % of all patients, and the changes were positively associated with plasma PTH (p?<?0.001) and Ca²⁺ (p?=?0.009). In all 91 patients with mild PHPT (plasma Ca²⁺?<?1.45 mmol/l), there was a significant postoperative increase in spine BMD (1.9 % (1.2; 2.7)) and in hip BMD (1.0 % (0.4; 1.6)), but not in the forearm BMD (?0.3 % (?0.7; 0.2)). The postoperative BMD gain was higher in the hip and forearm in patients operated for adenomas compared with patients treated for hyperplasia.

Conclusions

We found significant postoperative BMD improvements both at the hip and the spine. BMD improvements were also significant in mild cases. At all scan sites, there were positive associations between preoperative plasma PTH levels and postoperative BMD increases. The measured BMD changes may mainly be due to a decrease in PTH-induced bone turnover with refilling of the remodeling space.     

Pilot Study Comparing Systemic and Tissue Pharmacokinetics of Irinotecan and Metabolites after Hepatic Drug-Eluting Chemoembolization

Differences in drug metabolism associated with UGT1A1 polymorphism could result in individualized local response to hepatic chemoembolization with irinotecan-eluting beads (DEBIRI) or predictable toxicities. Five patients with inoperable hepatic metastases from colorectal or anal malignancies treated with DEBIRI were assessed for UGT1A1 mutations. No difference in area under the curve (AUC) for SN38 in normal liver and tumor tissue samples was noted with variant or wild-type UBT1A1 (P = .16 and P = .05, respectively). Plasma SN-38 AUC was significantly lower in wild-type compared to variant patients (P < .0001). UGT1A1 genotype may not be predictive of hematologic toxicity after DEBIRI.     

A surgical protocol for bicondylar four-quadrant tibial plateau fractures

Purpose

Bicondylar tibial plateau fractures involving four articular quadrants are severe and complex injuries, and they remain a challenging problem in orthopaedic trauma. The aim of this study was to introduce a new treatment protocol with dual-incision and multi-plate fixation in the floating supine patient position as well as to report the preliminary clinical results.

Methods

From January 2006 to December 2011, 16 consecutive patients with closed bicondylar four-quadrant tibial plateau fractures (Schatzker type VI, OTA/AO 41C2/3) were treated with posteromedial inverted L-shaped and anterolateral incisions. With the posteromedial approach, three quadrants (posteromedial, anteromedial and posterolateral) can be exposed, reduced and fixed with multiple small antiglide plates and short screws in an enclosure pattern. With the anterolateral approach, after articular elevation and bone substitute grafting, a strong locking plate with long screws to the medial cortex is used to raft-buttress the reduced lateral plateau fracture, hold the entire reconstructed tibial condyles together, and contact the condyles with the tibial shaft. All patients were encouraged to exercise knee motion at an early stage. The outcome was evaluated clinically and radiologically after a minimum two-year follow-up.

Results

The average operation time was 98?±?26 minutes (range 70–128) and the average duration of hospitalization was 29?±?8.6 days (range 20–41). Three cases used five plates, nine cases used four plates, and four cases used three plates. All patients were followed for a mean of 28.7?±?6.1 months (range 26–38). Fifteen incisions healed initially, while one patient developed a medial wound dehiscence and was successfully managed by debridement. All patients achieved radiological fracture union after an average of 20.2 weeks. At the two-year follow up, the average knee range of motion (ROM) was 98°?±?13.7 (range 88–125°), with a Hospital for Special Surgery (HSS) knee score of 87.7?±?10.3 (range 75–95), and SMFA score of 21.3?±?8.6 (range 12–33).

Conclusion

For bicondylar four-quadrant tibial plateau fractures, the treatment protocol of multiple medial-posterior small plates combined with a lateral strong locking plate through dual incisions can provide stable fracture fixation to allow for early stage rehabilitation. Good clinical outcomes can be anticipated.     

Mechanistic Understanding of Brain Drug Disposition to Optimize the Selection of Potential Neurotherapeutics in Drug Discovery

Purpose

The current project was undertaken with the aim to propose and test an in-depth integrative analysis of neuropharmacokinetic (neuroPK) properties of new chemical entities (NCEs), thereby optimizing the routine of evaluation and selection of novel neurotherapeutics.

Methods

Forty compounds covering a wide range of physicochemical properties and various CNS targets were investigated. The combinatory mapping approach was used for the assessment of the extent of blood-brain and cellular barriers transport via estimation of unbound-compound brain (K_p,uu,brain) and cell (K_p,uu,cell) partitioning coefficients. Intra-brain distribution was evaluated using the brain slice method. Intra- and sub-cellular distribution was estimated via calculation of unbound-drug cytosolic and lysosomal partitioning coefficients.

Results

Assessment of K_p,uu,brain revealed extensive variability in the brain penetration properties across compounds, with a prevalence of compounds actively effluxed at the blood-brain barrier. K_p,uu,cell was valuable for identification of compounds with a tendency to accumulate intracellularly. Prediction of cytosolic and lysosomal partitioning provided insight into the subcellular accumulation. Integration of the neuroPK parameters with pharmacodynamic readouts demonstrated the value of the proposed approach in the evaluation of target engagement and NCE selection.

Conclusions

With the rather easily-performed combinatory mapping approach, it was possible to provide quantitative information supporting the decision making in the drug discovery setting.     

In situ investigation of the kinetics and microstructure during photopolymerization by positron annihilation technique and NIR-photorheology

The microstructural free volume evolution during a photopolymerization process was studied on a commercial photopolymer (SPOT LV) in situ by positron annihilation lifetime spectroscopy (PALS) and concomitant NIR-photorheology. Analysis of the positron lifetime spectra revealed a high sensitivity of the PALS technique to the different phases of photopolymerization associated with different reaction rates as well as to the evolution of microstructural free-volume shrinkage, which was described at the molecular level by the Kohlrausch–Williams–Watts equation. The in situ PALS study of microstructural changes in photopolymerization was related to the vitrification (gel point) accompanied by shrinkage stress registered via NIR-photorheology. The simultaneous NIR measurements yield information on the monomer conversion of SPOT LV, which can be correlated to the occurrence of the gel point and the evolution of the microstructural free volume. This combined study allows us to see deeper into the crosslinking process and its influence on the resulting material characteristics.

Positron annihilation lifetime spectroscopy is a sensitive tool for the in situ study of the microstructural evolution during photopolymerization.