Abstract Background Two-stage revision is the gold standard treatment of TKA infection; nevertheless various factors may influence the success rate. The aim of our study was to assess the impact of ...the number of patient comorbidities together with virulence of infectious organism on prognosis of two-stage revision procedure in chronic peri-prosthetic knee infection; moreover we tried to demonstrate correlation between the presence of positive culture during re-implantation and re-infection rate. Methods Thirty-eight cases of two-staged revision procedures for infected total knee arthroplasty were prospectively followed. The presence of high virulence microorganisms on the culture result and the number (more than three) of comorbidities were used as major risk factors. All cases were divided into three groups: Group 1 (10 patients without major risk factors), Group 2 (18 patients with only one major risk factor), Group 3 (10 patients with both of major risk factors). Results After a mean follow-up of 65 months (range 24–139 months), there was infection recurrence in nine cases: four re-infections occurred with the same organism while five patients had re-infection with a different organism. Recurrence was higher in Group 3 (33% of the cases), lower in Group 2 (12% of the cases), whereas no infection occurred in Group 1. Finally in case of positive intraoperative cultures recurrence rate was 83%, whereas when specimens were negative we had only 12.5% of re-infections. Conclusions Even if standard protocol of two-stage revision has demonstrated good results when treating low-virulence infections or patients without associated risk factors, its application to more challenging condition cannot be assumed. Level of Evidence Level IV, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence.
Congenital clubfoot is a common pediatric malformation that affects approximately 0.1% of all births. 80% of the cases appear isolated, while 20% can be secondary or associated with complex ...syndromes. To date, two genes that appear to play an important role are PTIX1 and TBX4, but their actual impact is still unclear. Our study aimed to evaluate the prevalence of pathogenic variants in PITX1 and TBX4 in Italian patients with idiopathic clubfoot. PITX1 and TBX4 genes were analyzed by sequence and SNP array in 162 patients. We detected only four nucleotide variants in TBX4, predicted to be benign or likely benign. CNV analysis did not reveal duplications or deletions involving both genes and intragenic structural variants. Our data proved that the idiopathic form of congenital clubfoot was rarely associated with mutations and CNVs on PITX1 and TBX4. Although in some patients, the disease was caused by mutations in both genes; they were responsible for only a tiny minority of cases, at least in the Italian population. It was not excluded that other genes belonging to the same TBX4-PITX1 axis were involved, even if genetic complexity at the origin of clubfoot required the involvement of other factors.
The induction and inhibition of human hepatic cytochrome P450 (CYP) isoforms by crystalline glucosamine sulfate (CGS) was investigated in vitro. Inhibition of CYP1A2, CYP2E1, CYP2C19, CYP2C9, CYP2D6, ...and CYP3A4 by CGS was assessed using recombinant human enzymes incubated with CGS (up to 3 mM expressed as free base). Induction of CYP1A2, CYP2B6, CYP2C9, CYP2C19 and CYP3A4 by CGS (0.01, 0.3 and 3 mM) was evaluated in cryopreserved human hepatocytes, by determining CYP mRNA expression using quantitative RT-PCR. CGS produced no inhibition or induction of any the CYP enzymes tested at concentrations hundred folds higher than the steady state peak plasma concentrations (approximately 10 microM) observed in man after therapeutic doses of CGS of 1500 mg once a day. Therefore, no clinically relevant metabolic interactions are expected between CGS and co-administered drugs that are substrates of the CYP enzymes investigated.
Protein binding of 14Cglucosamine (400, 1000 and 4000 ng/ml) was evaluated in human and mouse plasma and in human synovial fluid. Blood cell/plasma partitioning in human and mouse was also ...determined. There was no measurable protein binding of 14Cglucosamine. Its association with human and mouse blood cells ranged from 43-47% and from 27-29%, respectively. Therefore, the unbound (pharmacologically active) fraction of glucosamine in plasma and at the site of action (the joint) is the same. Protein binding displacement drug-drug interactions are unlikely during the clinical use of crystalline glucosamine sulfate. No corrections are needed, either for unbound fraction when comparing human and mouse pharmacokinetic data or for blood cell/plasma partitioning to assess glucosamine total blood clearance from plasma data in these two species.
