Characteristics of patients requiring early total knee replacement after surgically treated lateral tibial plateau fractures-A comparative cohort study.

PURPOSE: The primary aim of the present study was to compare basic characteristics of patients requiring early treatment with TKR and patients not requiring TKR within 3 years following a lateral tibial plateau fracture. METHODS: Comparative cohort study. From December 2013 to November 2016, 56 patients were included. Five patients required a TKR within the first 3 years. We compared the basic characteristics (age, gender, BMI, comorbidity, osteoporosis, fracture classification, soft tissue injuries and trauma mechanism) between patients. RESULTS: Comparing baseline characteristics of the two groups of patients shows a higher rate of females (56.4% vs 80%), a higher BMI (25.9 vs 29.9), a higher rate of patients with diabetes (8% vs 20%), a higher rate of the fracture type AO 41-B1 (8% vs 80%) and a higher rate of soft tissue injuries (46% vs 100%). Age, smoking status and preoperative maximum joint depression were comparable between the two groups. CONCLUSIONS: Female gender, severe comorbidity, obesity, osteopenia, fracture type AO 41-B and soft tissue injuries were associated to early total knee replacements following surgically treated lateral tibial plateau fractures.

Long-Term Prognosis of Plantar Fasciitis: A 5- to 15-Year Follow-up Study of 174 Patients With Ultrasound Examination.

BACKGROUND: Plantar fasciitis (PF) affects 7% to 10% of the population. The long-term prognosis is unknown. PURPOSE: Our study had 4 aims: (1) to assess the long-term prognosis of PF, (2) to evaluate whether baseline characteristics (sex, body mass index, age, smoking status, physical work, exercise-induced symptoms, bilateral heel pain, fascia thickness, and presence of a heel spur) could predict long-term outcomes, (3) to assess the long-term ultrasound (US) development in the fascia, and (4) to assess whether US-guided corticosteroid injections induce atrophy of the heel fat pad. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: From 2001 to 2011 (baseline), 269 patients were diagnosed with PF based on symptoms and US. At follow-up (2016), all patients were invited to an interview regarding their medical history and for clinical and US re-examinations. Kaplan-Meier survival estimates were used to estimate the long-term prognosis, and a multiple Cox regression analysis was used for the prediction model. RESULTS: In all, 174 patients (91 women, 83 men) participated in the study. All were interviewed, and 137 underwent a US examination. The mean follow-up was 9.7 years from the onset of symptoms and 8.9 years from baseline. At follow-up, 54% of patients were asymptomatic (mean duration of symptoms, 725 days), and 46% still had symptoms. The risk of having PF was 80.5% after 1 year, 50.0% after 5 years, 45.6% after 10 years, and 44.0% after 15 years from the onset of symptoms. The risk was significantly greater for women (P < .01) and patients with bilateral pain (P < .01). Fascia thickness decreased significantly in both the asymptomatic and symptomatic groups (P < .01) from 6.9 mm and 6.7 mm, respectively, to 4.3 mm in both groups. Fascia thickness (P = .49) and presence of a heel spur (P = .88) at baseline had no impact on prognosis. At follow-up, fascia thickness and echogenicity had normalized in only 24% of the asymptomatic group. The mean fat pad thickness was 9.0 mm in patients who had received a US-guided corticosteroid injection and 9.4 mm in those who had not been given an injection (P = .66). CONCLUSION: The risk of having PF in this study was 45.6% at a mean 10 years after the onset of symptoms. The asymptomatic patients had PF for a mean 725 days. The prognosis was significantly worse for women and patients with bilateral pain. Fascia thickness decreased over time regardless of symptoms and had no impact on prognosis, and neither did the presence of a heel spur. Only 24% of asymptomatic patients had a normal fascia on US at long-term follow-up. A US-guided corticosteroid injection did not cause atrophy of the heel fat pad. Our observational study did not allow us to determine the efficacy of different treatment strategies.

Some transformations of tacrolimus, an immunosuppressive drug.

Transformations of the macrocyclic lactone tacrolimus (1), an important immunosuppressive drug produced by Streptomyces species, are described. These transformation products are primarily of interest as reference substances for drug impurity analyses. Upon action of acid (p-toluenesulfonic acid in toluene), tacrolimus is dehydrated by loss of water from the ß-hydroxyketone moiety with partial inversion of configuration at C-8, resulting in formation of 5-deoxy-Δ(5,6)-tacrolimus and 5-deoxy-Δ(5,6)-8-epitacrolimus. The structure of the latter was determined by single-crystal X-ray crystallography. The same products are formed upon action of free radicals (iodine in boiling toluene), along with formation of 8-epitacrolimus. The latter is converted by p-toluenesulfonic acid to 5-deoxy-Δ(5,6)-8-epitacrolimus. Treatment of tacrolimus with weak base (1,5-diazabicyclo[4.3.0]nonene) gives, in addition to 8-epitacrolimus, the open-chain acid corresponding to 5-deoxy-Δ(5,6)-tacrolimus, a rare non-cyclic derivative of tacrolimus. Strong base (t-butoxide) causes pronounced degradation of the molecule. Thermolysis of tacrolimus leads to ring expansion by an apparent [3,3]-sigmatropic rearrangement of the allylic ester moiety with subsequent loss of water from the ß-hydroxyketone moiety. ¹H and ¹³C NMR spectra of the obtained compounds, complicated by the presence of amide bond rotamers and ketal moiety tautomers, were assigned by extensive use of 2D NMR techniques.

Synthesis and characterization of an epimer of tacrolimus, an immunosuppressive drug.

8-Epitacrolimus (2), a new l-pipecolic acid macrolide lactone, was obtained by base-catalyzed epimerization of tacrolimus (FK-506, 1), an important immunosuppressive drug, and its structure determined by a single-crystal X-ray diffraction method. The compound was fully characterized by spectroscopic techniques. The epimer is of importance due to its potential biological effects as well as because of its possible formation during formulation, handling, and use of tacrolimus products.

High speed development work by preparation of an "in-hand" library of NMR-quantified degradation products.

Standard materials of impurities are needed in pharmaceutical development such as for validating impurity analytical methods. Most often the impurities possess structures, which are difficult and very time consuming to synthesize. In the present work, we demonstrate that a library of degradation products of ragaglitazar--a novel tricyclic-gamma-alkyloxyphenylpropionic acid with hypolipidemic and antidiabetic activity--observed in stability indicating samples of a solid dosage formulation by LC-MS can be produced in a one pot oxidation reaction. The library entities were isolated in small quantities (microg-mg) by preparative HPLC and structurally characterized by NMR spectroscopy and mass spectrometry. The concentrations of the library entities were determined in solution by NMR using an internal standard method. The library was successfully used in the validation work of a newly developed purity method for the drug product providing useful response factors and relative retention times (RRTs) of the degradation products.