Staged method using antibiotic beads and subsequent autografting for large traumatic tibial bone loss: 22 of 23 fractures healed after 5-20 months

Introduction The vascularity of surrounding soft tissues, which is related to muscle cover, is important for the healing of traumatic bone loss. Muscle cover on the distal tibia is limited compared to the diaphyseal and proximal tibia, and delayed healing of fractures in this area is common. We evaluated the healing of traumatic bone loss in the proximal, diaphyseal, and distal tibia.

Patients and methods 23 open tibial fractures with substantial bone loss (mean 52 (34-104) mm) were treated using a staged method with antibiotic-impregnated beads and later autologous bone grafting at second-stage surgery on average 8 weeks after the injury.

Results 22 fractures healed after mean 40 (20-79) weeks. The average healing time in the distal tibia (mean 30 weeks) was 7 weeks shorter (95% CI: 12-26 weeks) than in the proximal tibia (37 weeks), and 16 weeks shorter (95% CI: 3-29 weeks) than in the tibial shaft (47 weeks). The length of the bone and the type of soft tissue cover (free muscle or secondary suture) had no effect on healing time.

Interpretation Our study suggests that the method we used is applicable in all parts of the tibia, although the healing of bone loss is slower in the diaphyseal tibia than in the proximal and distal tibia.     

Does coronary artery bypass surgery affect metoprolol bioavailability

Background

β-blockers are commonly administered in patients with coronary artery bypass surgery (CABG). Despite this therapy, however, the incidence of postoperative atrial fibrillation (AF) is high (9–19%), and it is unknown why the β-blockers do not reduce the incidence of AF more efficiently. In this pharmacokinetics study, in which the patients acted as their own controls, we have evaluated the bioavailability of perioperative metoprolol tablets in CABG surgery patients.

Methods

Twelve male patients, aged 45–64 years, scheduled for CABG surgery were administered an initial 50 mg metoprolol tartrate tablet orally on the morning of the preoperative day and thereafter at 12-h intervals. Regular blood samples were collected up to 12 h after the first administration of the drug on the preoperative day as well on the first and third postoperative days. The plasma concentration for metoprolol was analyzed (limit of quantification = 0.001 mg/L) using liquid chromatography-tandem mass spectrometry.

Results

The bioavailability of the metoprolol was significantly less on the first postoperative day, with AUC_0–12 values ranging from 0.7 to 17.1 (median: 7.2) mg min/L, than on the preoperative day, with AUC_0–12 values of 5.1–26.7 (12.6) mg min/L; however, it returned to the preoperative values on the third postoperative day, with AUC_0–12 values of 3.5–25.2 (15.2) mg min/L. Similar changes were observed in C_max values: preoperative C_max ranged between 0.026 and 0.123 (0.060) mg/L, on the first postoperative day, the C_max ranged between 0.003 and 0.093 (0.025) mg/L, and on the third postoperative day, the C_max ranged between 0.009 and 0.136 (0.061) mg/L. There was no correlation between the pharmacokinetic parameters and patient characteristics, but both the preoperative C_max and C₆₀ correlated significantly with the postoperative C_max (Pearson correlation coefficient: 0.61–0.72). One patient with one of the lowest rates and extent of metoprolol absorption developed AF.

Conclusion

This study indicates that the bioavailability of metoprolol is markedly reduced when administered in tablet form during the early phase after CABG.

     

Philadelphia-negative clonal hematopoiesis following imatinib therapy in patients with chronic myeloid leukemia: a report of nine cases and analysis of predictive factors

There are increasing reports of Philadelphia-negative (Ph-negative) clonal hematopoiesis developing among patients with chronic myeloid leukemia (CML) treated with imatinib mesylate (IM). To establish the incidence and significance of these chromosomal abnormalities, we analyzed data on 141 consecutive patients with CML treated with IM at the British Columbia Cancer Agency and Vancouver General Hospital from 1999 to 2004. The cumulative incidence of developing a Ph-negative clone three years from the start of IM was 8.7% at a median of 13.3 months. The Ph-negative clonal abnormalities included monosomy 7 and/or trisomy 8 (seven patients), monosomy for chromosomes X and 22 (one patient), and a (12;16) translocation (one patient). Two of the patients presented with the same chromosomal abnormality in both Ph-negative and Ph-positive cells. None of the Ph-negative clonal abnormalities was associated with myelodysplasia. In a multivariate analysis, an interval from diagnosis to initiation of IM of 1 year or less was associated with an increased risk of developing a Ph-negative clone (relative risk = 20.2; P = 0.025). There was no difference, however, in event-free survival between patients who did and did not develop Ph-negative clones. Therefore, while the development of Ph-negative clonal hematopoiesis in patients with CML treated with IM is uncommon, it appears to be more frequent than that previously seen with IFN, but it does not seem to confer a worse prognosis.     

The reliability of paraspinal muscles composition measurements using routine spine MRI and their association with back function

This study examines the reliability of quantitative and qualitative muscle composition measurements of paraspinal muscle cross-sectional areas (CSAs) from routine lumbar spine magnetic resonance images and their association with maximal isokinetic lifting performance. The extent of paraspinal muscle composition reflects back function is currently not known. Measurements were repeated 4–8 weeks apart and different measurements of related constructs were compared. Participants were a population-based sample of 169 males, 35–67 years old, without considering the presence or absence of a history of low back pain or related problems in the selection of subjects. The quantitative and qualitative muscle composition measurements for axial magnetic resonance (MR) images of paraspinal muscles at the L3–L4 lumbar spine level, isokinetic lifting force and work, and body fat percentage were the main outcome measures. Results showed that the reproducibility of different paraspinal muscle composition measurements at the L3–L4 level was excellent for CSAs (ICC=0.95–0.99) and quantitative muscle composition measurements using cerebrospinal fluid adjusted signal intensity (ICC=0.96–0.99), and moderate for qualitative muscle composition ratings (Kappa=0.54–0.76). The correlations of the quantitative and qualitative muscle composition measurements with isokinetic lifting force and work were generally low (r=0.02–0.41), and favoured the qualitative assessments. In conclusion, quantitative and qualitative muscle composition measurements of paraspinal muscles are highly reproducible tissue measures, have low associations with body fat and isokinetic lifting performance, and show that paraspinal muscle morphology using routine spine magnetic resonance imaging (MRI) is poorly related to back function.     

Long-term outcome of intensive chemotherapy for adults with de novo acute myeloid leukaemia (AML): the nationwide AML-92 study by the Finnish Leukaemia Group

OBJECTIVE: To investigate the long-term outcome of idarubicin- and cytarabine-based intensive chemotherapy in adult acute myeloid leukaemia (AML). PATIENTS AND METHODS: A total of 327 consecutive patients with de novo AML (promyelocytic leukaemia excluded) aged 16-65 yr were recruited into the study between September 1992 and December 2001. The latest follow-up data were collected in October 2006. After remission achievement with the first (conventional cytarabine) or second (high-dose cytarabine) chemotherapy cycle, three intensive consolidation courses each containing high- or intermediate-dose cytarabine were given. RESULTS: A total of 268 patients (82%) achieved complete remission (CR). CR rate was 82% and 84% for patients <60 and > or =60 yr of age, respectively. CR rates in patients with favourable (93%) and intermediate/normal karyotypes (87%) were significantly (P < 0.01) higher than CR rate in patients with adverse karyotype (61%). Median relapse-free survival (RFS) for the patients not transplanted in the first CR (n = 195) was 1.7 yr (95% CI: 0.81-2.60). At 4 yr, a plateau of 70% in RFS was reached for patients with favourable karyotypes. The 5-yr survival was 71%, 47% and 37% for the non-transplanted patients (n = 202) with favourable, intermediate/normal and intermediate/abnormal karyotypes, respectively, while only 8% of the patients having adverse karyotype were alive at 5 yr (P < 0.01). Of the patients with favourable, intermediate/normal or intermediate/abnormal karyotypes, respectively, 58%, 41% and 31% were expected to be alive at 10 yr. CONCLUSIONS: Idarubicin- and cytarabine-based intensive chemotherapy regimen is very effective in de novo AML for adult patients up to 65 yr of age. New treatment strategies are needed, however, to improve the outcome of the patients with intermediate and adverse karyotypes.     

Enrolment of 22,000 adolescent women to cancer registry follow-up for long-term human papillomavirus vaccine efficacy: guarding against guessing

Human papillomaviruses (HPVs, most notably types 16 and 18) cause cervical carcinoma, the second most common cancer among women. Vaccination of adolescents against HPV16/18 might prevent large proportion of cervical and other anogenital cancers. However, because of ethical reasons this cannot be proven by clinical studies. To determine the long-term vaccine efficacy (VE) of HPV16/18 virus-like-particle (VLP) vaccine against cervical carcinoma in situ (CIS+) and invasive cervical carcinoma, the following three population-based cohorts of adolescent women have been enrolled: (1) women vaccinated with the HPV vaccine; (2) women vaccinated with hepatitis A control vaccine; and (3) unvaccinated control women. These cohorts will be passively followed for cumulative incidence of CIS+ endpoints by population-based cancer registry. Overall 24,046 16- to 17-year-old adolescent women from 18 cities in Finland were invited between May 2004 and June 2005 to participate in a phase III trial with bivalent HPV16/18 VLP vaccine. A total of 58,996 18- to 19-year-old women were invited in May 2005 to participate as unvaccinated controls. Women who reported their willingness to participate in an HPV vaccination trial had they been 1-2 years younger were eligible. Cumulative incidence (CI) of CIS+ in our cohorts over 15 years is approximately 0.45%. VE of 70% against CIS+ with 80% power requires 3357-3189 HPV16/18 vaccine recipients, 3357-3189 other vaccine recipients, and 6714-9567 unvaccinated controls. We have now enrolled 2404 HPV16/18 vaccine recipients, 2404 hepatitis A-vaccine recipients, and 5130 unvaccinated controls. This enrolment in addition to our earlier enrolment in another phase III trial guarantees enough power so that by 2020 we can ultimately provide data on the efficacy of HPV16/18 vaccination against CIS+.     

The use of feathers of birds of prey as indicators of metal pollution

Published results concerning metal levels in feathers of birds of prey were listed and evaluated. Mercury concentrations have been studied most and the background values normally vary between 0.1 and 5 mg/kg dry weight the highest concentrations being in birds from aquatic food chains. Pollution causes elevated levels of mercury in feathers. The concentrations of cadmium, copper, lead and zinc show reasonable variation between species, areas and time periods. Feathers of birds of prey have proved to be good indicators of the status of environmental heavy metal pollution. Special attention should be paid to clean sampling and preparation of samples. Interpretation of the results requires knowledge on food habit, molting and migration patterns of the species. Several species representing different food chains should be included in comprehensive monitoring surveys. Chick feathers reflect most reliably local conditions.