Changes in bone mineral density after allogenic stem cell transplantation

ObjectiveOsteoporosis is a complication after allogenic stem cell transplantation (alloSCT). The purpose of this study was to assess changes in bone mineral density (BMD) 6 months and 3 years after alloSCT, as well as predictors of bone loss.MethodsA longitudinal, prospective, single-center study was conducted at Lille University Hospital between 2005 and 2016. Clinical, biological, radiologic (thoracic and lumbar spine) and densitometric (DXA) assessments were carried out at baseline (pre-transplant), 6 months and 3 years. Patients with myeloma were not included.ResultsTwo hundred and fifty-eight patients were included (144 men). Among them, 60.1% had leukemia and 65.8% of them, acute myeloid leukemia. At baseline, 6 months and 3 years, DXA-confirmed that osteoporosis was observed in 17%, 22.8% and 17.5% of the patients, respectively, mainly at the femoral neck. At baseline, 6 months and 3 years, 9 (8.5%), 53 (21.5%) and 38 (16.7%) patients, respectively, were receiving anti-osteoporotic treatment. From baseline to 6-month follow-up, BMD decreased significantly (p < 0.001) at the lumbar spine (?36 [95%CI; ?51 to ?20] mg/cm² of hydroxyapatite), femoral neck (?43 [95%CI; ?57 to ?29] mg/cm² of hydroxyapatite) and total hip (?53 [95%CI; ?68 to ?39] mg/cm² of hydroxyapatite). From 6-month to 3-year follow-up, a significant increase in BMD was observed at the lumbar spine only (+31 [95%CI; 20 to 42] mg/cm² of hydroxyapatite, p < 0.001). At all 3 sites, changes in BMD did not differ between patients treated or untreated by anti-osteoporotic treatment from 6-month to 3 year follow-up. Incident fractures were found in 4.1% and 5.7% of the patients at 6 months and 3 years, respectively. Between baseline and 6 months, bone loss at all 3 sites was associated with corticosteroid intake. At the total hip, 23.3% of the decrease in BMD from baseline to 6 months was due to an active hematological disease (p < 0.05), a bone marrow stem cells (p < 0.01) and a corticosteroid intake (p < 0.01).ConclusionOur study found evidence of bone fragility in alloSCT patients. Low BMD persisted at the hip 3 years after transplantation due to slower improvement at this site.     

Denosumab Densitometric Changes Assessed by Quantitative Computed Tomography at the Spine and Hip in Postmenopausal Women With Osteoporosis

FREEDOM was a phase 3 trial in 7808 women aged 60–90 yr with postmenopausal osteoporosis. Subjects received placebo or 60 mg denosumab subcutaneously every 6 mo for 3 yr in addition to daily calcium and vitamin D. Denosumab significantly decreased bone turnover; increased dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD); and significantly reduced new vertebral, nonvertebral, and hip fractures. In a subset of women (N = 209), lumbar spine, total hip, and femoral neck volumetric BMD (vBMD) were assessed by quantitative computed tomography at baseline and months 12, 24, and 36. Significant improvement from placebo and baseline was observed in aBMD and vBMD in the denosumab-treated subjects at all sites and time points measured. The vBMD difference from placebo reached 21.8%, 7.8%, and 5.9%, respectively, for the lumbar spine, total hip, and femoral neck at 36 mo (all p ≤ 0.0001). Compared with placebo and baseline, significant increases were also observed in bone mineral content (BMC) at the total hip (p < 0.0001) largely related to significant BMC improvement in the cortical compartment (p < 0.0001). These results supplement the data from DXA on the positive effect of denosumab on BMD in both the cortical and trabecular compartments.     

Female patients display poorer burn-specific quality of life 12 months after a burn injury

IntroductionAlthough gender differences in morbidity and mortality have been measured in patients with moderate to severe burn injury, little attention has been directed at gender effects on health-related quality of life (HRQoL) following burn injury. The current study was therefore conducted to prospectively measure changes in HRQoL for males and females in a sample of burn patients.MethodsA total of 114 adults who received treatment at a statewide burns service for a sustained burns injury participated in this study. Instruments measuring generic health status (Short Form 36 Medical Outcomes Survey version 2), burn-specific HRQoL (Burns Specific Health Scale-Brief), psychological distress (Kessler Psychological Distress Scale) and alcohol use (Alcohol Use Disorders Identification Tool) were prospectively measured at 3, 6 and 12 months post-burn.ResultsIn the 12 months post-injury, female patients showed overall poorer physical (p = 0.01) and mental health status (p < 0.001), greater psychological distress (p < 0.001), and greater difficulty with aspects of burn-specific HRQoL: body image (p < 0.001), affect (p < 0.001), interpersonal functioning (p = 0.005), heat sensitivity (p = 0.01) and treatment regime (p = 0.01). While significant interaction effects suggested that female patients had more improvement in difficulties with treatment regime (p = 0.007), female patients continued to report greater difficulty with multiple aspects of physical and psychosocial health status 12 months post-injury.ConclusionEven though demographic variables, injury characteristics and burn care interventions were similar across genders, following burn injury female patients reported greater impairments in generic and burn-specific HRQoL along with psychological morbidity, when compared to male patients. Urgent clinical and research attention utilising an evidence-based research framework, which incorporates the use of larger sample sizes, the use of validated instruments to measure appropriate outcomes, and a commitment to monitoring long-term care, can only improve burn-care.     

Efficacy of tibial nerve block,local steroid injection or both in the treatment of Plantar Heel Pain Syndrome

BackgroundPlantar Heel Pain Syndrome (PHPS) describes centralised plantar heel pain and tenderness. It can account for up to 15% of referrals to clinicians involved in the treatment of foot pain.ObjectiveTo compare tibial nerve block, local infiltration with steroid or both combined in the treatment of PHPS.MethodsPatients with PHPS were randomly assigned to three treatment groups: Group 1—steroid injection to heel; Group 2—local anaesthetic block to tibial nerve; Group 3—both procedures. Pain visual analogue scale (VAS) was measured at baseline and after 1, 6 and 26 weeks. Heel tenderness index (HTI) was measured at baseline and after 6 weeks. The patient rated their discomfort from the injection(s) using a VAS.ResultsForty-five patients (27 female) were recruited, 14 in Group 1, 12 in Group 2 and 19 in Group 3. Median age was 55, disease duration was 10 months and baseline pain VAS was 7.0 cm. All groups experienced a sustained improvement in pain VAS between baseline and weeks 1, 6 and 26 (all p < 0.0001). Group 1 reported significantly lower pain VAS that those in Group 2 (p < 0.01) or Group 3 (p < 0.05) at week 6. Group 2 found the procedure less uncomfortable than Group 1 (p < 0.01). The HTI was significantly higher in Group 2 at 6 weeks compared to Group 1 (p < 0.005) and Group 3 (p < 0.05).ConclusionsThis study suggests that the natural history of PHPS following an injection is encouraging, that a tibial nerve block reduces the discomfort of the procedure, that a steroid injection to the heel may accelerate improvement and that clinicians should consider a combination of both strategies.     

Preemptive therapy for cytomegalovirus based on real-time measurement of viral load in liver transplant recipients

BackgroundReal-time PCR has emerged as the preferred diagnostic assay for CMV. However, its utility as a preemptive therapy tool for CMV disease and related outcomes in liver transplant recipients has not been fully defined.MethodsPatients comprised 117 consecutive liver transplant recipients who underwent CMV surveillance monitoring using real-time PCR. Preemptive therapy with valganciclovir was employed upon detection of viremia. Baseline viral load was considered high based on log values (median).ResultsCMV viremia developed in 54% (63/117) of the patients, including 77% of R−/D+, 63% of R+/D+, 43% of R+/D−, and 10% of R−/D− patients. Overall, 23% (15/63) of the patients had recurrent viremia; R− serostatus (p = 0.065) but not initial viral load correlated with recurrent viremia (p = 0.80). At 12 months post-transplant, CMV disease occurred in 0.85% (1/117) of the patients (R+/D + recipient). None (0/30) of the R−/D + patients had CMV disease. Patients with CMV viremia treated preemptively did not differ significantly from those who never developed CMV viremia with regards to bacterial or fungal infections, rejection, graft loss, mortality rate, and probability of survival at 12 months (p > 0.05 for all variables). The above outcomes also did not differ for patients with high (> 1.9 logs) vs. low viral load (< 1.9 logs) (p > 0.05 for all outcomes).ConclusionsPreemptive therapy guided by real-time PCR based monitoring led to outcomes in all patients or in those with high viral loads that were comparable to outcomes in patients who never developed viremia or had low viral loads, respectively. Late-onset CMV disease at 12 months was observed in < 1% of all patients.     

Calcium supplementation does not rescue the programmed adult bone deficits associated with perinatal growth restriction

Low birth weight and poor childhood growth program a variety of adult diseases including bone disorders such as osteoporosis. We have previously reported that offspring born small, as a result of uteroplacental insufficiency, have shorter femurs, lower bone mineral content and a bone strength deficit as adults. The aim of this study was to determine the effects of calcium supplementation from adolescence on growth restricted male and female offspring which have a programmed bone deficit.Bilateral uterine vessel ligation (Restricted) or sham surgery (Control) was performed on gestational day 18 in WKY rats to induce uteroplacental insufficiency and growth restriction. At 2 months pups were allocated to one of four diet groups: diet 1—constant normal calcium diet, diet 2—variable normal calcium diet, diet 3—constant high calcium diet, diet 4—variable high calcium diet. Diet groups 1 and 3 were fed their respective diets constantly for the duration of the study. In groups 2 and 4, rats were fed one diet for 5 days, followed by a switch to a low calcium diet for the next 5 days. At 6 months Dual Energy Xray Absorptiometry (DXA) and Peripheral Quantitative Computed Tomography (pQCT) were performed on the right femur. Bone turnover markers were measured at 4 months.Male and female Restricted offspring were born 14% lighter compared to Controls (p < 0.05). At 6 months both male and female Restricted offspring remained smaller and had shorter femurs compared to Controls (p < 0.05). Restricted males and females had reduced trabecular and cortical content compared to Controls, regardless of diet (p < 0.05). Trabecular bone density was lower in Restricted females only (p < 0.05). A constant high calcium diet increased cortical BMD in Restricted male and both female groups (p < 0.05). Measures of bone geometry indicated that Restricted offspring have narrower bones with preservation of absolute cortical thickness (p < 0.05). Importantly, the stress strain index of bone bending strength was lower in male and female Restricted offspring, regardless of diet by up to 9.0% and 7.8%, respectively. DXA results were similar to pQCT results.Being born small, due to uteroplacental insufficiency, programs reduced adult femur length, dimensions and stress strain index. Supplementation with a high calcium diet from adolescence can increase adult cortical bone density in low birth weight males and females, and normal weight females. This increase in bone density was not sufficient to rescue the bone dimension and strength deficits which were programmed in utero, suggesting that the early life environment is critical for bone programming.     

The effect of aging on the hardness of foot sole skin: A preliminary study

BackgroundFoot problems are common in older people and altered biomechanical parameters under the foot sole has been proposed as a key risk factor for foot lesions. Therefore the aim of this study was to investigate the age-related differences in the hardness of foot sole skin.MethodsTwenty-six healthy volunteers without foot problems, aged from 26 to 65 years, were examined using shore meter. The hardness of the foot sole under the big toe (area 8), 1st metatarsal head (area 5), 3rd metatarsal head (area 6), 5th metatarsal head (area 7), mid foot (area 3, 4) and hind foot (area 1, 2) were measured. The correlation between age and hardness of foot sole was examined and comparisons were made between two age groups.ResultsFrom the result we observe statistical significant (p < 0.05; p < 0.01; p < 0.005) differences in hardness between age groups in hind foot, metatarsal heads (1st, 3rd & 5th) and big toe. Strong positive correlations between age and hardness of the foot sole were found at the big toe (r = 0.57; p < 0.005), 1st metatarsal head (r = 0.567; p < 0.00001), 3rd metatarsal head (r = 0.565; p < 0.00001), 5th metatarsal head (r = 0.55; p < 0.00001), and heel (r = 0.59; p < 0.0001).ConclusionThe loss of compliance in the foot sole may be one of the factors responsible for the higher incidence of foot problems in aged people. Routine foot examination and appropriate therapeutic intervention including the use of foot orthoses and optimal hardness of foot wear insole may help to prevent the serious foot injuries.     

Denosumab Significantly Increases DXA BMD at Both Trabecular and Cortical Sites: Results From the FREEDOM Study

Denosumab is an approved therapy for postmenopausal women with osteoporosis at high or increased risk for fracture. In the FREEDOM study, denosumab reduced fracture risk and increased bone mineral density (BMD). We report the spine and hip dual-energy X-ray absorptiometry (DXA) BMD responses from the overall study of 7808 women and from a substudy of 441 participants in which more extensive spine and hip assessments as well as additional skeletal sites were evaluated. Significant BMD improvements were observed as early as 1 mo at the lumbar spine, total hip, and trochanter (all p < 0.005 vs placebo and baseline). BMD increased progressively at the lumbar spine, total hip, femoral neck, trochanter, 1/3 radius, and total body from baseline to months 12, 24, and 36 (all p < 0.005 vs placebo and baseline). BMD gains above the least significant change of more than 3% at 36 months were observed in 90% of denosumab-treated subjects at the lumbar spine and 74% at the total hip, and gains more than 6% occurred in 77% and 38%, respectively. In conclusion, denosumab treatment resulted in significant, early, and continued BMD increases at both trabecular and cortical sites throughout the skeleton over 36 mo with important gains observed in most subjects.     

The recovery of post-burn hypertrophic scar in a monitored pressure therapy intervention programme and the timing of intervention

Introduction

Pressure therapy used to be considered as the mainstay non-invasive treatment of hypertrophic scar. However, the maturation process of hypertrophic scar during pressure therapy process has seldom be reported. Moreover, although early application of pressure therapy after burn injuries is reco6mmended, minimal evidence exists to support it. This study aimed to examine the maturation trajectory of post-burn hypertrophic scars in a 6-month monitored pressure therapy intervention programme and investigate the difference in the trajectory between patients receiving early intervention and patients receiving late intervention.

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study

IntroductionImmune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients.MethodsA multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months.ResultsTwenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225–525 ng/mL) in 14 (15.2%) patients and low (ATP < 225 ng/mL) in 78 (84.8%); no patients had a strong response (ATP ≥ 525 ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p = 0.043). Similar acute rejection rates were recorded in patients with mean ATP ≥ 225 vs. <225 ng/mL during the study period (7.1% vs. 9.1%, p = 0.81).ConclusionAlthough ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.     

Vitamin D levels in 577 consecutive elective foot & ankle surgery patients

BackgroundVitamin D deficiency is a global concern impacting upon large communities and certain disease populations. It can adversely affect the outcome of orthopaedic operations. We aimed to perform an audit of the Vitamin D status of patients in two centres in the United Kingdom undergoing elective foot and ankle surgery.MethodsSerum 25-hydroxyvitamin-D (vitamin D) levels were obtained prospectively in 577 consecutive elective patients undergoing elective foot and ankle surgery between October 2014 and March 2017 (29 months). Variables including age, gender, ethnicity, location, season, month and procedure type were recorded.Results577 patients were included over the study period. 62.0% were female. Mean age was 53.2 (median 54.5, range 16.7–86.6). 300 patients were treated in Northampton and 277 in Leicester. The serum 25-hydroxyvitamin-D levels for the patient group were normally distributed. The mean was 52.3 nmol/L (SD 28.0; range 7.5–175) and the median 47.5 nmol/L. 21.7% were grossly deficient, 31.9% deficient, 28.9% insufficient and 17.5% within normal range. Age, gender and procedure type did not statistically affect vitamin D levels (p = 0.5, t-test). Ethnicity, location and Winter season did affect Vitamin D levels (p < 0.05). August was the most significant month with levels significantly higher than January, February, March, April, June, November and December (p < 0.05, one-way ANOVA).ConclusionsOnly 1 in 5.7 patients had a normal Vitamin D level and 1 in 4.6 were grossly deficient. Ethnicity and patient location significantly affected Vitamin D results. Summer months were noted to demonstrate significantly the highest levels and August the highest. We did not find that age or gender affected Vitamin D levels in our cohort.     

Characterization of damage mechanisms associated with reference point indentation in human bone

Measurement of bone mineral density (BMD) is the clinical gold standard in cases of compromised skeletal integrity, such as with osteoporosis. While BMD is a useful measurement to index skeletal health, it is also limited since it cannot directly assess any mechanical properties. The ability to directly assess mechanical properties of bone tissue would be clinically important. Reference point indentation (RPI) is a technology that has been designed to try and achieve this goal. While RPI has been shown to detect altered bone tissue properties, the underlying physical mechanism of these measurements has not been characterized. Thus, we designed a study whereby the contribution of (1) test cycle number and (2) test load level to RPI test-induced sub-surface damage was characterized and quantified. Standardized specimens were prepared from cadaveric human tibiae (n = 6), such that 12 replicates of each testing condition could be carried out. A custom rig was fabricated to accurately position and map indentation sites. One set of tests was carried out with 1, 5, 10, 15 and 20 cycles (Max Load: 8 N, Freq: 2 Hz), and a second set of tests was carried out with Load levels of 2, 4, 6, 8 or 10 N (Cycle number: 20, Freq: 2 Hz). The RPI parameter Loading Slope (LS) was cycle dependent at 5, 10, 15 and 20 cycles (p < 0.05). First Cycle Indentation Distance (ID 1st), Total Indentation Distance (TID), Mean Energy Dissipation (ED), First Cycle Unloading Slope (US 1st), Mean Unloading Slope (US) and LS were significantly different at 6, 8 and 10 N compared to 2 N (p < 0.05). From the histomorphometric measurements, damage zone span was significantly different after 5, 10, 15 and 20 cycles compared with 1 cycle while indent profile width and indent profile depth were significantly different at 10, 15 and 20 cycles (p < 0.05). With the load varying protocol, each of these parameters differed significantly at each increased load level (4, 6, 8, 10 N) compared with the basal level of 2 N (p < 0.05). The damage area parameter in both protocols was significantly different from baseline at the three upper levels tested (i.e. 10, 15, 20 cycles and 6, 8, 10 N, in cycle and load variant protocols, respectively). Specimens were scanned by micro-computed tomography, which showed no material or microstructural differences between samples, and processed for histological analyses and damage quantification. Consistent microdamage patterns were present with evidence of damage via compaction at the indented regions. While damage in the direction of loading was established early, the damage area then increased radially with cycle number. These data help to further understand the physical manifestations of RPI parameters and will help to further facilitate its use as a clinical diagnostic tool.     

The cytokine balance during CABG surgery with and without cardiopulmonary bypass

BackgroundWe investigated the cytokine response during coronary artery bypass grafting (CABG) surgery with and without cardiopulmonary bypass (off-pump) and the effect on patient's outcome in the early postoperative period.MethodsEighteen patients were studied, 9 patients undergoing off-pump surgery (group 1) and 9 patients with CPB (group 2). Demographic and preoperative characteristics were comparable in both groups. Plasma levels of TNF-α, IL-6, IL-8, IL-10, IL-4, tumour necrosis soluble receptors-1 (TNFsr-1) and tumour necrosis soluble receptors-2 (TNFsr-2) were measured before skin incision (T0), before revascularization (T1), after revascularization (T2), 2 h (T3) and 24 (T4) hours after skin closure. Levels of myocardial enzymes were also measured in the first postoperative morning.ResultsSerum levels of TNF-α and IL-8 increased in group 2 at T3 and T4 more than at T0 (p < 0.05). IL-6 increased in both groups with higher levels in group 2 than in group 1 at T3 (773 ± 331 vs 315 ± 189 pg/ml; p < 0.05). IL-10 was higher in group 2 than in group 1 at T2 (115 ± 119 vs 13 ± 4 pg/ml; p < 0.001) and at T3 (212 ± 171 vs 31 ± 29 pg/ml; p < 0.05). At T3 levels of TNFsr-1 and TNFsr-2 were higher in group 2 than in group 1 (TNFsr-1 4858 ± 1325 vs 2089 ± 584 pg/ml; p < 0.01 and TNFsr-2 4971 ± 63 vs 3801 ± 738 pg/ml; p < 0.05). Production of IL-4 did not increase in neither group. The length of ICU stay was less in group 1 than in group 2 (52 ± 33 vs 26 ± 11 h; p < 0.05) as well as was the length of hospital stay (7.1 ± 0.4 vs 5.3 ± 0.5 days; p < 0.001).ConclusionOff-pump procedure evoked a lower cytokine response than CABG with CPB. This minimised myocardial damage and shorten the stay in the ICU and the hospital.     

Randomised Controlled Trial Comparing Sapheno-Femoral Ligation and Stripping of the Great Saphenous Vein with Endovenous Laser Ablation (980 nm) Using Local Tumescent Anaesthesia: One Year Results

ObjectivesComparison of sapheno-femoral ligation and stripping (SFL/S) versus endovenous laser ablation (EVLA, 980-nm) in the treatment of great saphenous vein (GSV) insufficiency, using local tumescent anaesthesia.DesignRandomised, single centre trial.Materials and methodsPatients with GSV incompetence and varicose veins were randomised to either SFL/S or EVLA. At days 1, 2, 3, 7, 10, and 14 post-treatment, patients completed questionnaires on pain and quality of life. Recurrent varicose veins were evaluated by Duplex ultrasound (DUS) performed at 1 and 6 weeks, and 6 and 12 months.Results130 legs in 121 patients were treated by SFL/S (n = 68) or EVLA (n = 62). Significantly more post-treatment pain was noted after EVLA at days 7, 10 and 14 (p < 0.01; p < 0.01; p = 0.01), more hindrance in mobility at days 7 (p < 0.01) and 10 (p = 0.01), and in self care (p = 0.03) and daily activities (p = 0.01) at day 7 compared to SFL/S. DUS at 1-year follow-up showed 9% recurrences (5/56) after EVLA and 10% (5/49) after SFL/S.ConclusionBoth SFL/S and EVLA, using local tumescent anaesthesia, were well tolerated, with no difference in short-term recurrence rate. In the second week after EVLA, patients experienced significantly more pain resulting in restricted mobility, self care and daily activity compared to SFL/S.     

Single high-dose oral vitamin D3 (stoss) therapy — A solution to vitamin D deficiency in children with cystic fibrosis?

ObjectivesTo determine the safety and efficacy of stoss therapy on vitamin D levels over a 12 month period in children with cystic fibrosis and vitamin D deficiency (< 75 nmol/L).Study designRetrospective chart review of 142 paediatric CF patients from 2007 till 2011.ResultsThirty eight children received stoss therapy and 37 children with vitamin D deficiency were not treated and served as a control group. The stoss treated group had a significant and sustained increase in 25-hydroxyvitamin D levels measured at 1, 3, 6 and 12 months post treatment compared to controls (94.82 ± 41.0 nmol/L, p = 0.001; 81.54 ± 24.6 nmol/L, p = 0.001; 92.18 ± 36.5 nmol/L, p = 0.008 and 64.6 ± 20.0 nmol/L, p = 0.006 respectively). At 12 months post intervention, the mean difference in vitamin D levels from baseline between the stoss treated group and controls was significant at 15 nmol/L compared to 5 nmol/L (p = 0.038).ConclusionStoss therapy effectively achieves and maintains levels of 25-hydroxyvitamin D greater than 75 nmol/L over 12 months.     

Knee loading protects against osteonecrosis of the femoral head by enhancing vessel remodeling and bone healing

Osteonecrosis of the femoral head is a serious orthopedic problem. Moderate loads with knee loading promote bone formation, but their effects on osteonecrosis have not been investigated. Using a rat model, we examined a hypothesis that knee loading enhances vessel remodeling and bone healing through the modulation of the fate of bone marrow-derived cells. In this study, osteonecrosis was induced by transecting the ligamentum teres followed by a tight ligature around the femoral neck. For knee loading, 5 N loads were laterally applied to the knee at 15 Hz for 5 min/day for 5 weeks. Changes in bone mineral density (BMD) and bone mineral content (BMC) of the femur were measured by pDEXA, and ink infusion was performed to evaluate vessel remodeling. Femoral heads were harvested for histomorphometry, and bone marrow-derived cells were isolated to examine osteoclast development and osteoblast differentiation. The results showed that osteonecrosis significantly induced bone loss, and knee loading stimulated both vessel remodeling and bone healing. The osteonecrosis group exhibited the lowest trabecular BV/TV (p < 0.001) in the femoral head, and lowest femoral BMD and BMC (both p < 0.01). However, knee loading increased trabecular BV/TV (p < 0.05) as well as BMD (p < 0.05) and BMC (p < 0.01). Osteonecrosis decreased the vessel volume (p < 0.001), vessel number (p < 0.001) and VEGF expression (p < 0.01), and knee loading increased them (p < 0.001, p < 0.001 and p < 0.01). Osteonecrosis activated osteoclast development, and knee loading reduced its formation, migration, adhesion and the level of “pit” formation (p < 0.001, p < 0.01, p < 0.001 and p < 0.001). Furthermore, knee loading significantly increased osteoblast differentiation and CFU-F (both p < 0.001). A significantly positive correlation was observed between vessel remodeling and bone healing (both p < 0.01). These results indicate that knee loading could be effective in repair osteonecrosis of the femoral head in a rat model. This effect might be attributed to promoting vessel remodeling, suppressing osteoclast development, and increasing osteoblast and fibroblast differentiation. In summary, the current study suggests that knee loading might potentially be employed as a non-invasive therapy for osteonecrosis of the femoral head.     

Effects of badminton and ice hockey on bone mass in young males: A 12-year follow-up

The purpose of the present study was to investigate the influence of different types of weight bearing physical activity on bone mineral density (BMD, g/cm²) and evaluate any residual benefits after the active sports career. Beginning at 17 years of age, BMD was measured 5 times, during 12 years, in 19 badminton players, 48 ice hockey players, and 25 controls. During the active career, badminton players gained significantly more BMD compared to ice hockey players at all sites: in their femoral neck (mean difference (Δ) 0.06 g/cm², p = 0.04), humerus (Δ 0.06 g/cm², p = 0.01), lumbar spine (Δ 0.08 g/cm², p = 0.01), and their legs (Δ 0.05 g/cm², p = 0.003), after adjusting for age at baseline, changes in weight, height, and active years. BMD gains in badminton players were higher also compared to in controls at all sites (Δ 0.06–0.17 g/cm², p < 0.01 for all). Eleven badminton players and 37 ice hockey players stopped their active career a mean of 6 years before the final follow-up. Both these groups lost significantly more BMD at the femoral neck and lumbar spine compared to the control group (Δ 0.05–0.12 g/cm², p < 0.05 for all). At the final follow-up, badminton players had significantly higher BMD of the femoral neck, humerus, lumbar spine, and legs (Δ  0.08–0.20 g/cm², p < 0.01 for all) than both ice hockey players and controls. In summary, the present study may suggest that badminton is a more osteogenic sport compared to ice hockey. The BMD benefits from previous training were partially sustained with reduced activity.     

Decrement of serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis (RA) patients achieving remission after 6 months of etanercept treatment: Comparison with CRP,IgM-RF,MMP-3 and anti-CCP Ab

ObjectiveThe aim of this study was to evaluate whether serum COMP can estimate the therapeutic response of RA after 6 months of treatment with etanercept.MethodsForty-five RA patients receiving 25 mg of etanercept twice a week for 6 months were registered in this prospective observational study. Clinical response to the therapy was evaluated by DAS 28. Laboratory variables– COMP, CRP, ESR, IgM-RF, MMP-3, and anti-CCP Ab –were assessed at baseline and after 6 months of treatment. We assessed the correlations between serum COMP and other variables and whether serum COMP is associated with DAS28 remission.ResultsSerum COMP correlated with DAS28-ESR (p < 0.05, r = 0.40) at baseline. At 6 months of etanercept treatment, 10 patients entered remission (DAS28-ESR < 2.6) whereas the other 35 patients did not (DAS28-ESR > 2.6). The decrement of serum COMP at 6 months was significant in the remission group (N = 10) but not in the non-remission group (N = 35). On the other hand, CRP, ESR and MMP-3 decreased at 6 months regardless of remission status. IgM-RF titer as well as anti-CCP Ab titer did not differ at 6 months.ConclusionsSerum COMP at baseline reflects clinical disease activity of RA. Serum COMP is a valuable serologic marker to identify the subset of RA patients achieving remission during treatment with etanercept.     

Daily serum creatinine monitoring promotes earlier detection of acute kidney injury in children and adolescents with cystic fibrosis

BackgroundThe epidemiology of aminoglycoside-associated acute kidney injury (AG-AKI) has not been well described in pediatric patients with cystic fibrosis (CF). We aimed to assess the impact of daily serum creatinine (SCr) measurement on detection of AG-AKI at our institution.MethodsWe examined a cohort of hospitalized patients with CF who received an intravenous (IV) aminoglycoside for ≥ 3 days. We compared the rate, timing, and medical management surrounding detection of AG-AKI during 2 periods: January 2010–May 2011 (Era 1, SCr measured at the discretion of the medical team, N = 124) and June 2011–June 2012 (Era 2, SCr measured daily, N = 103). Our primary outcome was detection of AG-AKI defined as ≥ 50% increase in SCr from baseline (lowest value in prior 6 months), or ≥ 0.3 mg/dL rise within 48 h, occurring after day 2.ResultsThe use of once daily tobramycin (p = 0.02) and IV fluids (p < 0.001) was higher during Era 2, while AG courses were shorter (p = 0.04), and fewer concomitant nephrotoxins (p = 0.04) were given; higher daily tobramycin doses (p < 0.001) were administered. Although the rate of AG-AKI was not significantly different (12% during Era 1 vs. 20% during Era 2, p = 0.09), the number of AG-AKI days detected increased (5.5 vs. 2.9 per 100 AG days, p = 0.003), and detection occurred earlier (median 6 vs. 9 days, log rank test p = 0.02) during the daily SCr period.ConclusionsDaily SCr measurement promoted earlier and increased detection of AG-AKI in patients with CF at our institution. We suggest systematic evaluation for AKI during aminoglycoside administration in patients with CF.     

Multiple Small-Dose Injections Can Reduce the Passage of Sclerosant Foam into Deep Veins During Foam Sclerotherapy for Varicose Veins

ObjectiveTo compare the proportion of foam sclerosant that enters deep veins between multiple injections of <0.5 ml foam per injection and a few injections of >0.5 ml foam per injection.Design & methodsOne hundred and seven patients with superficial venous incompetence were randomised to receive either multiple injections of <0.5 ml 1% polidocanol (POL) -foam (multiple injections) or a few injections of >0.5 ml 1% POL-foam per injection (few injections) for the treatment of varicose tributaries. All patients then received ultrasound-guided foam sclerotherapy for refluxing great saphenous vein (GSV) using 3% POL-foam. Only a single session was allowed per patient in order to standardise treatment. Qualitative ultrasonographic inspection of the foam was carried out during a 5-min period before compression was applied. Post-sclerotherapy surveillance was done at day 3, 2 weeks, 1 month, 3 months, and 6 months.ResultsFifty-six limbs in 53 patients were treated with multiple injections and the remaining 56 limbs in 54 patients were treated with a few injections. There were no significant differences in age or male:female ratio between the groups. The mean volume of 1% POL-foam was 2.2 S.D. 0.6 ml (range: 0.7–4.0 ml) in the multiple injections group and 2.5 S.D. 0.6 ml (range: 1.0–4.0 ml) in the few injections group (p = 0.003). The mean volume of 3% POL was 1.5 ml (range: 0.7–3.0 ml) and 1.4 ml (range: 0.7–3.0 ml), respectively (p = 0.137). Ultrasonographic inspection immediately after sclerotherapy demonstrated that foam was distributed significantly more commonly in the deep veins of patients treated with a few injections (p = 0.0003). Two (4%) of the patients treated with a few injections developed migraine during the procedure, but recovered quickly with no further complications. There was no significant difference in the success rate between the groups at 6 months (p = 0.257).ConclusionsThese findings suggest that multiple small-dose injections can reduce the amount of foam sclerosant and the risk of foam sclerosant entering the deep veins in patients with superficial venous insufficiency.