Bone healing around titanium implants in two rat colitis models

OBJECTIVE Crohn's disease is a chronic inflammatory process that has recently been associated with a higher risk of early implant failure. Herein we provide information on the impact of colitis on peri-implant bone formation using preclinical models of chemically induced colitis. METHODS Colitis was induced by intrarectal instillation of 2,4,6-trinitro-benzene-sulfonic-acid (TNBS). Colitis was also induced by feeding rats dextran-sodium-sulfate (DSS) in drinking water. One week after disease induction, titanium miniscrews were inserted into the tibia. Four weeks after implantation, peri-implant bone volume per tissue volume (BV/TV) and bone-to-implant contacts (BIC) were determined by histomorphometric analysis. RESULTS Cortical histomorphometric parameters were similar in the control (n = 10), DSS (n = 10) and TNBS (n = 8) groups. Cortical BV/TV was 92.2 ± 3.7%, 92.0 ± 3.0% and 92.6 ± 2.7%. Cortical BIC was 81.3 ± 8.8%, 83.2 ± 8.4% and 84.0 ± 7.0%, respectively. No significant differences were observed when comparing the medullary BV/TV and BIC (19.5 ± 6.4%, 16.2 ± 5.6% and 15.4 ± 9.0%) and (48.8 ± 12.9%, 49.2 ± 6.2 and 41.9 ± 11.7%), respectively. Successful induction of colitis was confirmed by loss of body weight and colon morphology. CONCLUSIONS The results suggest bone regeneration around implants is not impaired in chemically induced colitis models. Considering that Crohn's disease can affect any part of the gastrointestinal tract including the mouth, our model only partially reflects the clinical situation.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, > 10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Periodontal healing after application of enamel matrix derivative in surgical supra/infrabony periodontal defects in rats with streptozotocin-induced diabetes

BACKGROUND AND OBJECTIVE Epidemiologic and clinical studies have indicated that diabetes is a risk factor for periodontal disease progression and healing. The aim of the present study was to evaluate short-term healing after enamel matrix derivative (EMD) application in combined supra/infrabony periodontal defects in diabetic rats. MATERIAL AND METHODS Thirty male Wistar rats were initially divided into two groups, one with streptozotocin-induced diabetes and another one with healthy (non-diabetic) animals. Bony defects were surgically created on the mesial root of the first maxillary molars. After root surface planing and EDTA conditioning, EMD was applied to the roots at one side of the maxillae, while those on the contralateral sides were left untreated. Animals were killed 3 wk after surgery, and block sections were prepared for histologic and histomorphometric analysis. RESULTS There was statistically significant more gingival recession in diabetic animals than in non-diabetic animals. The length of the junctional epithelium was significantly shorter in the EMD-treated sites in both diabetic and normoglycemic rats. Sulcus depth and length of supracrestal soft connective tissue showed no statistically significant differences between groups. In all animals, new bone formation was observed. Although new bone occurred more frequently in healthy animals, the extent of new bone was not significantly different between groups. In none of the teeth, a layer of new cementum was detectable. EMD had no influence on bone or cementum regeneration. Adverse reactions such as excessive inflammation due to bacterial root colonization, ankylosis and bone fractures were exclusively observed in diabetic animals, irrespective of EMD treatment. CONCLUSION Within the limits of the present study, it can be concluded that periodontal healing was impaired in streptozotocin-induced diabetic rats. EMD had no beneficial effects on new bone and cementum formation during short-term healing in this defect model and could not ameliorate the adverse effects in the systemically compromised animals.

Five-year results evaluating the effects of platelet-rich plasma on the healing of intrabony defects treated with enamel matrix derivative and natural bone mineral

BACKGROUND Regenerative periodontal surgery using the combination of enamel matrix derivative (EMD) and natural bone mineral (NBM) with and without addition of platelet-rich plasma (PRP) has been shown to result in substantial clinical improvements, but the long-term effects of this combination are unknown. METHODS The goal of this study was to evaluate the long-term (5-year) outcomes after regenerative surgery of deep intrabony defects with either EMD + NBM + PRP or EMD + NBM. Twenty-four patients were included. In each patient, one intrabony defect was randomly treated with either EMD + NBM + PRP or EMD + NBM. Clinical parameters were evaluated at baseline and 1 and 5 years after treatment. The primary outcome variable was clinical attachment level (CAL). RESULTS The sites treated with EMD + NBM + PRP demonstrated a mean CAL change from 10.5 ± 1.6 to 6.0 ± 1.7 mm (P <0.001) at 1 year and 6.2 ± 1.5 mm (P <0.001) at 5 years. EMD + NBM-treated defects showed a mean CAL change from 10.6 ± 1.7 to 6.1 ± 1.5 mm (P <0.001) at 1 year and 6.3 ± 1.4 mm (P <0.001) at 5 years. At 1 year, a CAL gain of ≥4 mm was measured in 83% (10 of 12) of the defects treated with EMD + NBM + PRP and in 100% (all 12) of the defects treated with EMD + NBM. Compared to baseline, in both groups at 5 years, a CAL gain of ≥4 mm was measured in 75% (nine of 12 in each group) of the defects. Four sites in the EMD + PRP + NBM group lost 1 mm of the CAL gained at 1 year. In the EMD + NBM group, one defect lost 2 mm and four other defects lost 1 mm of the CAL gained at 1 year. No statistically significant differences in any of the investigated parameters were observed between the two groups. CONCLUSIONS Within their limits, the present results indicate that: 1) the clinical outcomes obtained with both treatments can be maintained up to a period of 5 years; and 2) the use of PRP does not appear to improve the results obtained with EMD + NBM.

Traditional and novel methods for occlusal caries detection: performance on primary teeth

This study aimed to assess the performance of International Caries Detection and Assessment System (ICDAS), radiographic examination, and fluorescence-based methods for detecting occlusal caries in primary teeth. One occlusal site on each of 79 primary molars was assessed twice by two examiners using ICDAS, bitewing radiography (BW), DIAGNOdent 2095 (LF), DIAGNOdent 2190 (LFpen), and VistaProof fluorescence camera (FC). The teeth were histologically prepared and assessed for caries extent. Optimal cutoff limits were calculated for LF, LFpen, and FC. At the D (1) threshold (enamel and dentin lesions), ICDAS and FC presented higher sensitivity values (0.75 and 0.73, respectively), while BW showed higher specificity (1.00). At the D (2) threshold (inner enamel and dentin lesions), ICDAS presented higher sensitivity (0.83) and statistically significantly lower specificity (0.70). At the D(3) threshold (dentin lesions), LFpen and FC showed higher sensitivity (1.00 and 0.91, respectively), while higher specificity was presented by FC (0.95), ICDAS (0.94), BW (0.94), and LF (0.92). The area under the receiver operating characteristic (ROC) curve (Az) varied from 0.780 (BW) to 0.941 (LF). Spearman correlation coefficients with histology were 0.72 (ICDAS), 0.64 (BW), 0.71 (LF), 0.65 (LFpen), and 0.74 (FC). Inter- and intraexaminer intraclass correlation values varied from 0.772 to 0.963 and unweighted kappa values ranged from 0.462 to 0.750. In conclusion, ICDAS and FC exhibited better accuracy in detecting enamel and dentin caries lesions, whereas ICDAS, LF, LFpen, and FC were more appropriate for detecting dentin lesions on occlusal surfaces in primary teeth, with no statistically significant difference among them. All methods presented good to excellent reproducibility.

Traditional and emerging roles for the SLC9 Na(+)/H (+) exchangers

The SLC9 gene family encodes Na(+)/H(+) exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi, and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [22, 46, 128]. The SLC9 gene family (solute carrier classification of transporters: www.bioparadigms.org ) is divided into three subgroups [46]. The SLC9A subgroup encompasses plasmalemmal isoforms NHE1-5 (SLC9A1-5) and the predominantly intracellular isoforms NHE6-9 (SLC9A6-9). The SLC9B subgroup consists of two recently cloned isoforms, NHA1 and NHA2 (SLC9B1 and SLC9B2, respectively). The SLC9C subgroup consist of a sperm specific plasmalemmal NHE (SLC9C1) and a putative NHE, SLC9C2, for which there is currently no functional data [46]. NHEs participate in the regulation of cytosolic and organellar pH as well as cell volume. In the intestine and kidney, NHEs are critical for transepithelial movement of Na(+) and HCO3 (-) and thus for whole body volume and acid-base homeostasis [46]. Mutations in the NHE6 or NHE9 genes cause neurological disease in humans and are currently the only NHEs directly linked to human disease. However, it is becoming increasingly apparent that members of this gene family contribute to the pathophysiology of multiple human diseases.

The cement prosthesis-like spacer: an intermediate halt on the road to healing.

BACKGROUND Periprosthetic infections remain a devastating problem in the field of joint arthroplasty. In the following study, the results of a two-stage treatment protocol for chronic periprosthetic infections using an intraoperatively molded cement prosthesis-like spacer (CPLS) are presented. METHODS Seventy-five patients with chronically infected knee prosthesis received a two-stage revision procedure with the newly developed CPLS between June 2006 and June 2011. Based on the microorganism involved, patients were grouped into either easy to treat (ETT) or difficult to treat (DTT) and treated accordingly. Range of motion (ROM) and the knee society score (KSS) were utilized for functional assessment. RESULTS Mean duration of the CPLS implant in the DTT group was 3.6 months (range 3-5 months) and in the ETT group 1.3 months (range 0.7-2.5 months). Reinfection rates of the final prosthesis were 9.6% in the ETT and 8.3% in the DTT group with no significant difference between both groups regarding ROM or KSS (P = 0.87, 0.64, resp.). CONCLUSION The results show that ETT patients do not necessitate the same treatment protocol as DTT patients to achieve the same goal, emphasizing the need to differentiate between therapeutic regimes. We also highlight the feasibility of CLPS in two-stage protocols.

Increased vascularization during early healing after biologic augmentation in repair of chronic rotator cuff tears using autologous leukocyte- and platelet-rich fibrin (L-PRF): a prospective randomized controlled pilot trial

HYPOTHESIS We hypothesized that arthroscopic rotator cuff repairs using leukocyte- and platelet-rich fibrin (L-PRF) in a standardized, modified protocol is technically feasible and results in a higher vascularization response and watertight healing rate during early healing. METHODS Twenty patients with chronic rotator cuff tears were randomly assigned to 2 treatment groups. In the test group (N = 10), L-PRF was added in between the tendon and the bone during arthroscopic rotator cuff repair. The second group served as control (N = 10). They received the same arthroscopic treatment without the use of L-PRF. We used a double-row tension band technique. Clinical examinations including subjective shoulder value, visual analog scale, Constant, and Simple Shoulder Test scores and measurement of the vascularization with power Doppler ultrasonography were made at 6 and 12 weeks. RESULTS There have been no postoperative complications. At 6 and 12 weeks, there was no significant difference in the clinical scores between the test and the control groups. The mean vascularization index of the surgical tendon-to-bone insertions was always significantly higher in the L-PRF group than in the contralateral healthy shoulders at 6 and 12 weeks (P = .0001). Whereas the L-PRF group showed a higher vascularization compared with the control group at 6 weeks (P = .001), there was no difference after 12 weeks of follow-up (P = .889). Watertight healing was obtained in 89% of the repaired cuffs. DISCUSSION/CONCLUSIONS Arthroscopic rotator cuff repair with the application of L-PRF is technically feasible and yields higher early vascularization. Increased vascularization may potentially predispose to an increased and earlier cellular response and an increased healing rate.

A novel technique, dynamic intraligamentary stabilization creates optimal conditions for primary ACL healing: A preliminary biomechanical study

BACKGROUND Anterior cruciate ligament (ACL) rupture is a common lesion. Current treatment emphasizes arthroscopic ACL reconstruction via a graft, although this approach is associated with potential drawbacks. A new method of dynamic intraligamentary stabilization (DIS) was subjected to biomechanical analysis to determine whether it provides the necessary knee stability for optimal ACL healing. METHODS Six human knees from cadavers were harvested. The patellar tendon, joint capsule and all muscular attachments to the tibia and femur were removed, leaving the collateral and the cruciate ligaments intact. The knees were stabilized and the ACL kinematics analyzed. Anterior-posterior (AP) stability measurements evaluated the knees in the following conditions: (i) intact ACL, (ii) ACL rupture, (iii) ACL rupture with primary stabilization, (iv) primary stabilization after 50 motion cycles, (v) ACL rupture with DIS, and (vi) DIS after 50 motion cycles. RESULTS After primary suture stabilization, average AP laxity was 3.2mm, which increased to an average of 11.26mm after 50 movement cycles. With primary ACL stabilization using DIS, however, average laxity values were consistently lower than those of the intact ligament, increasing from an initial AP laxity of 3.00mm to just 3.2mm after 50 movement cycles. CONCLUSIONS Dynamic intraligamentary stabilization established and maintained close contact between the two ends of the ruptured ACL, thus ensuring optimal conditions for potential healing after primary reconstruction. The present ex vivo findings show that the DIS technique is able to restore AP stability of the knee.

Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Differential healing response attributed to culprit lesions of patients with acute coronary syndromes and stable coronary artery after implantation of drug-eluting stents: An optical coherence tomography study

BACKGROUND Pathology studies have shown delayed arterial healing in culprit lesions of patients with acute coronary syndrome (ACS) compared with stable coronary artery disease (CAD) after placement of drug-eluting stents (DES). It is unknown whether similar differences exist in-vivo during long-term follow-up. Using optical coherence tomography (OCT), we assessed differences in arterial healing between patients with ACS and stable CAD five years after DES implantation. METHODS AND RESULTS A total of 88 patients comprised of 53 ACS lesions with 7864 struts and 35 stable lesions with 5298 struts were suitable for final OCT analysis five years after DES implantation. The analytical approach was based on a hierarchical Bayesian random-effects model. OCT endpoints were strut coverage, malapposition, protrusion, evaginations and cluster formation. Uncovered (1.7% vs. 0.7%, adjusted p=0.041) or protruding struts (0.50% vs. 0.13%, adjusted p=0.038) were more frequent among ACS compared with stable CAD lesions. A similar trend was observed for malapposed struts (1.33% vs. 0.45%, adj. p=0.072). Clusters of uncovered or malapposed/protruding struts were present in 34.0% of ACS and 14.1% of stable patients (adj. p=0.041). Coronary evaginations were more frequent in patients with ST-elevation myocardial infarction compared with stable CAD patients (0.16 vs. 0.13 per cross section, p=0.027). CONCLUSION Uncovered, malapposed, and protruding stent struts as well as clusters of delayed healing may be more frequent in culprit lesions of ACS compared with stable CAD patients late after DES implantation. Our observational findings suggest a differential healing response attributable to lesion characteristics of patients with ACS compared with stable CAD in-vivo.

Assessing traditional knowledge on forest uses to understand forest ecosystem dynamics

Forest ecosystems worldwide are heavily influenced by human activities. Information on these human activities are key for understanding ecosystem dynamics, especially as some of these human activities have long-term consequences, i.e. legacy effects. We assessed the diversity of forest uses across the Swiss Alps and the respective traditional forest-related knowledge (TFRK) by conducting 56 oral history interviews in five regions. As TFRK tends to be underrepresented in written records, oral history proves to be a very valuable approach. We classified the information gathered in 61 specific forest use practices, characterized by activity, product and use, in order to gain a comprehensive picture of the regional variability but also cross-regional ubiquity of certain forest uses. Based on these results we are able to name the ecologically most relevant forest uses which were most likely, or potentially occurring in Central European forests. We suggest a simple, systematic historical assessment of these relevant forest uses to be applied in all studies on forest ecosystems. This procedure will enable scientists to better evaluate to what degree human activities had an impact on forest ecosystem dynamics in their study area.