Retrograde ascending aortic dissection during or after thoracic aortic stent graft placement: insight from the European registry on endovascular aortic repair complications

BACKGROUND: Single-center reports have identified retrograde ascending aortic dissection (rAAD) as a potentially lethal complication of thoracic endovascular aortic repair (TEVAR). METHODS AND RESULTS: Between 1995 and 2008, 28 centers participating in the European Registry on Endovascular Aortic Repair Complications reported a total of 63 rAAD cases (incidence, 1.33%; 95% CI, 0.75 to 2.40). Eighty-one percent of patients underwent TEVAR for acute (n=26, 54%) or chronic type B dissection (n=13, 27%). Stent grafts with proximal bare springs were used in majority of patients (83%). Only 7 (15%) patients had intraoperative rAAD, with the remaining occurring during the index hospitalization (n=10, 21%) and during follow-up (n=31, 64%). Presenting symptoms included acute chest pain (n=16, 33%), syncope (n=12, 25%), and sudden death (n=9, 19%) whereas one fourth of patients were asymptomatic (n=12, 25%). Most patients underwent emergency (n=25) or elective (n=5) surgical repair. Outcome was fatal in 20 of 48 patients (42%). Causes of rAAD included the stent graft itself (60%), manipulation of guide wires/sheaths (15%), and progression of underlying aortic disease (15%). CONCLUSIONS: The incidence of rAAD was low (1.33%) in the present analysis with high mortality (42%). Patients undergoing TEVAR for type B dissection appeared to be most prone for the occurrence of rAAD. This complication occurred not only during the index hospitalization but after discharge up to 1050 days after TEVAR. Importantly, the majority of rAAD cases were associated with the use of proximal bare spring stent grafts with direct evidence of stent graft-induced injury at surgery or necropsy in half of the patients.

Classic and overlap chronic graft-versus-host disease (cGVHD) is associated with superior outcome after extracorporeal photopheresis (ECP)

The National Institutes of Health (NIH) classification of graft-versus-host disease (GVHD) is a significant improvement over prior classifications, and has prognostic implications. We hypothesized that the NIH classification of GVHD would predict the survival of patients with GVHD treated with extracorporeal photopheresis (ECP). Sixty-four patients with steroid refractory/dependent GVHD treated with ECP were studied. The 3-year overall survival (OS) was 36% (95% confidence interval [CI] 13-59). Progressive GVHD was seen in 39% of patients with any acute GVHD (aGVHD) (classic acute, recurrent acute, overlap) compared to 3% of patients with classic chronic GVHD (cGVHD) (P=.002). OS was superior for patients with classic cGVHD (median survival, not reached) compared to overlap GVHD (median survival, 395 days, 95% CI 101 to not reached) and aGVHD (delayed, recurrent or persistent) (median survival, 72 days, 95% CI 39-152). In univariate analyses, significant predictors of survival after ECP included GVHD subtype, bilirubin, platelet count, and steroid dose. In multivariate analyses overlap plus classic cGVHD was an independent prognostic feature predictive of superior survival (hazard ratio [HR] 0.34, 95% CI 0.14-0.8, p=.014). This study suggests that NIH classification can predict outcome after ECP for steroid refractory/dependent GVHD.

Risk scoring for setting priorities in a monitoring of antimicrobial resistance in meat and meat products

Meat and meat products can be contaminated with different species of bacteria resistant to various antimicrobials. The human health risk of a type of meat or meat product carry by emerging antimicrobial resistance depends on (i) the prevalence of contamination with resistant bacteria, (ii) the human health consequences of an infection with a specific bacterium resistant to a specific antimicrobial and (iii) the consumption volume of a specific product. The objective of this study was to compare the risk for consumers arising from their exposure to antibiotic resistant bacteria from meat of four different types (chicken, pork, beef and veal), distributed in four different product categories (fresh meat, frozen meat, dried raw meat products and heat-treated meat products). A semi-quantitative risk assessment model, evaluating each food chain step, was built in order to get an estimated score for the prevalence of Campylobacter spp., Enterococcus spp. and Escherichia coli in each product category. To assess human health impact, nine combinations of bacterial species and antimicrobial agents were considered based on a published risk profile. The combination of the prevalence at retail, the human health impact and the amount of meat or product consumed, provided the relative proportion of total risk attributed to each category of product, resulting in a high, medium or low human health risk. According to the results of the model, chicken (mostly fresh and frozen meat) contributed 6.7% of the overall risk in the highest category and pork (mostly fresh meat and dried raw meat products) contributed 4.0%. The contribution of beef and veal was of 0.4% and 0.1% respectively. The results were tested and discussed for single parameter changes of the model. This risk assessment was a useful tool for targeting antimicrobial resistance monitoring to those meat product categories where the expected risk for public health was greater.

Graft remodeling during growth following anterior cruciate ligament reconstruction in skeletally immature sheep

INTRODUCTION: Ruptures of the anterior cruciate ligament are being diagnosed with increasing frequency in skeletally immature individuals. It was our aim to investigate the graft remodelling process following an autologous, transphyseal reconstruction of the anterior cruciate ligament (ACL) in skeletally immature sheep. We hypothesized that the ligamentisation process in immature sheep is quicker and more complete when compared to adult sheep. MATERIALS AND METHODS: Skeletally immature sheep with an age of 4 months underwent a fully transphyseal ACL reconstruction using an autologous tendon. The animals were subsequently sacrificed at 3, 6, 12 and 24 weeks following surgery. Each group was characterised histomorphometrically, by immunostaining (VEGF, SMA), by transmission electron microscopy (TEM) and biomechanically (UFS Roboter). RESULTS: The histomorphometric analysis and presence of VEGF and SMA positive cells demonstrated a rapid return to a ligament like structure. The biomechanical analysis revealed an anteroposterior translation that was still increased even 6 months following surgery. CONCLUSION: As in adult sheep models, the remodeling of a soft tissue graft used for ACL reconstruction results in a biomechanically inferior substitute. However, the immature tissue seems to remodel faster and more complete when compared to adults.

Treatment of multiple adjacent Miller class I and II gingival recessions with a Modified Coronally Advanced Tunnel (MCAT) technique and a collagen matrix or palatal connective tissue graft: a randomized, controlled clinical trial

BACKGROUND A newly developed collagen matrix (CM) of porcine origin has been shown to represent a potential alternative to palatal connective tissue grafts (CTG) for the treatment of single Miller Class I and II gingival recessions when used in conjunction with a coronally advanced flap (CAF). However, at present it remains unknown to what extent CM may represent a valuable alternative to CTG in the treatment of Miller Class I and II multiple adjacent gingival recessions (MAGR). The aim of this study was to compare the clinical outcomes following treatment of Miller Class I and II MAGR using the modified coronally advanced tunnel technique (MCAT) in conjunction with either CM or CTG. METHODS Twenty-two patients with a total of 156 Miller Class I and II gingival recessions were included in this study. Recessions were randomly treated according to a split-mouth design by means of MCAT + CM (test) or MCAT + CTG (control). The following measurements were recorded at baseline (i.e. prior to surgery) and at 12 months: Gingival Recession Depth (GRD), Probing Pocket Depth (PD), Clinical Attachment Level (CAL), Keratinized Tissue Width (KTW), Gingival Recession Width (GRW) and Gingival Thickness (GT). GT was measured 3-mm apical to the gingival margin. Patient acceptance was recorded using a Visual Analogue Scale (VAS). The primary outcome variable was Complete Root Coverage (CRC), secondary outcomes were Mean Root Coverage (MRC), change in KTW, GT, patient acceptance and duration of surgery. RESULTS Healing was uneventful in both groups. No adverse reactions at any of the sites were observed. At 12 months, both treatments resulted in statistically significant improvements of CRC, MRC, KTW and GT compared with baseline (p < 0.05). CRC was found at 42% of test sites and at 85% of control sites respectively (p < 0.05). MRC measured 71 ± 21% mm at test sites versus 90 ± 18% mm at control sites (p < 0.05). Mean KTW measured 2.4 ± 0.7 mm at test sites versus 2.7 ± 0.8 mm at control sites (p > 0.05). At test sites, GT values changed from 0.8 ± 0.2 to 1.0 ± 0.3 mm, and at control sites from 0.8 ± 0.3 to 1.3 ± 0.4 mm (p < 0.05). Duration of surgery and patient morbidity was statistically significantly lower in the test compared with the control group respectively (p < 0.05). CONCLUSIONS The present findings indicate that the use of CM may represent an alternative to CTG by reducing surgical time and patient morbidity, but yielded lower CRC than CTG in the treatment of Miller Class I and II MAGR when used in conjunction with MCAT.

Impact of bone graft harvesting techniques on bone formation and graft resorption: a histomorphometric study in the mandibles of minipigs.

BACKGROUND: Harvesting techniques can affect cellular parameters of autogenous bone grafts in vitro. Whether these differences translate to in vivo bone formation, however, remains unknown. OBJECTIVE: The purpose of this study was to assess the impact of different harvesting techniques on bone formation and graft resorption in vivo. MATERIAL AND METHODS: Four harvesting techniques were used: (i) corticocancellous blocks particulated by a bone mill; (ii) bone scraper; (iii) piezosurgery; and (iv) bone slurry collected from a filter device upon drilling. The grafts were placed into bone defects in the mandibles of 12 minipigs. The animals were sacrificed after 1, 2, 4 and 8 weeks of healing. Histology and histomorphometrical analyses were performed to assess bone formation and graft resorption. An explorative statistical analysis was performed. RESULTS: The amount of new bone increased, while the amount of residual bone decreased over time with all harvesting techniques. At all given time points, no significant advantage of any harvesting technique on bone formation was observed. The harvesting technique, however, affected bone formation and the amount of residual graft within the overall healing period. Friedman test revealed an impact of the harvesting technique on residual bone graft after 2 and 4 weeks. At the later time point, post hoc testing showed more newly formed bone in association with bone graft processed by bone mill than harvested by bone scraper and piezosurgery. CONCLUSIONS: Transplantation of autogenous bone particles harvested with four techniques in the present model resulted in moderate differences in terms of bone formation and graft resorption.

Effects of exogenous surfactant on the non-heart-beating donor lung graft in experimental lung transplantation - a stereological study.

The use of non-heart-beating donor (NHBD) lungs may help to overcome the shortage of lung grafts in clinical lung transplantation, but warm ischaemia and ischaemia/reperfusion injury (I/R injury) resulting in primary graft dysfunction represent a considerable threat. Thus, better strategies for optimized preservation of lung grafts are urgently needed. Surfactant dysfunction has been shown to contribute to I/R injury, and surfactant replacement therapy is effective in enhancing lung function and structural integrity in related rat models. In the present study we hypothesize that surfactant replacement therapy reduces oedema formation in a pig model of NHBD lung transplantation. Oedema formation was quantified with (SF) and without (non-SF) surfactant replacement therapy in interstitial and alveolar compartments by means of design-based stereology in NHBD lungs 7 h after cardiac arrest, reperfusion and transplantation. A sham-operated group served as control. In both NHBD groups, nearly all animals died within the first hours after transplantation due to right heart failure. Both SF and non-SF developed an interstitial oedema of similar degree, as shown by an increase in septal wall volume and arithmetic mean thickness as well as an increase in the volume of peribron-chovascular connective tissue. Regarding intra-alveolar oedema, no statistically significant difference could be found between SF and non-SF. In conclusion, surfactant replacement therapy cannot prevent poor outcome after prolonged warm ischaemia of 7 h in this model. While the beneficial effects of surfactant replacement therapy have been observed in several experimental and clinical studies related to heart-beating donor lungs and cold ischaemia, it is unlikely that surfactant replacement therapy will overcome the shortage of organs in the context of prolonged warm ischaemia, for example, 7 h. Moreover, our data demonstrate that right heart function and dysfunctions of the pulmonary vascular bed are limiting factors that need to be addressed in NHBD.

Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: insights from the PLATelet inhibition and patient outcomes (PLATO) trial

BACKGROUND Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG. METHODS Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P(interaction) = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P(interaction) = .46) prior CABG. CONCLUSIONS Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.

Cytomegalovirus Serology and Replication Remain Associated With Solid Organ Graft Rejection and Graft Loss in the Era of Prophylactic Treatment

BACKGROUND Cytomegalovirus (CMV) replication has been associated with more risk for solid organ graft rejection. We wondered whether this association still holds when patients at risk receive prophylactic treatment for CMV. METHODS We correlated CMV infection, biopsy-proven graft rejection, and graft loss in 1,414 patients receiving heart (n=97), kidney (n=917), liver (n=237), or lung (n=163) allografts reported to the Swiss Transplant Cohort Study. RESULTS Recipients of all organs were at an increased risk for biopsy-proven graft rejection within 4 weeks after detection of CMV replication (hazard ratio [HR] after heart transplantation, 2.60; 95% confidence interval [CI], 1.34-4.94, P<0.001; HR after kidney transplantation, 1.58; 95% CI, 1.16-2.16, P=0.02; HR after liver transplantation, 2.21; 95% CI, 1.53-3.17, P<0.001; HR after lung transplantation, 5.83; 95% CI, 3.12-10.9, P<0.001. Relative hazards were comparable in patients with asymptomatic or symptomatic CMV infection. The CMV donor or recipient serological constellation also predicted the incidence of graft rejection after liver and lung transplantation, with significantly higher rates of rejection in transplants in which donor or recipient were CMV seropositive (non-D-/R-), compared with D- transplant or R- transplant (HR, 3.05; P=0.002 for liver and HR, 2.42; P=0.01 for lung transplants). Finally, graft loss occurred more frequently in non-D- or non-R- compared with D- transplant or R- transplant in all organs analyzed. Valganciclovir prophylactic treatment seemed to delay, but not prevent, graft loss in non-D- or non-R- transplants. CONCLUSION Cytomegalovirus replication and donor or recipient seroconstellation remains associated with graft rejection and graft loss in the era of prophylactic CMV treatment.

The modified coronally advanced tunnel combined with an enamel matrix derivative and subepithelial connective tissue graft for the treatment of isolated mandibular Miller Class I and II gingival recessions: a report of 16 cases.

OBJECTIVES To clinically evaluate the healing of mandibular Miller Class I and II isolated gingival recessions treated with the modified coronally advanced tunnel (MCAT) in conjunction with an enamel matrix derivative (EMD) and subepithelial connective tissue graft (SCTG). METHOD AND MATERIALS Sixteen healthy patients (13 women and 3 men) exhibiting one isolated mandibular Miller Class I and II gingival recessions of a depth of ≥ 3 mm, were consecutively treated with the MCAT in conjunction with EMD and SCTG. Treatment outcomes were assessed at baseline and at 12 months postoperatively. The primary outcome variable was complete root coverage (CRC) (eg, 100% root coverage). RESULTS Postoperative pain and discomfort were low and no complications such as postoperative bleeding, allergic reactions, abscesses, or loss of SCTG were observed. At 12 months, statistically significant (P < .0001) root coverage was obtained in all 16 defects. CRC was measured in 12 out of the 16 cases (75%) while in the remaining 4 defects root coverage amounted to 90% (in two cases) and 80% (in two cases), respectively. Mean root coverage was 96.25%. Mean keratinized tissue width increased from 1.98 ± 0.8 mm at baseline to 2.5 ± 0.9 mm (P < .0001) at 12 months, while mean probing depth did not show any statistically significant changes (ie, 1.9 ± 0.3 mm at baseline vs 1.8 ± 0.2 mm at 12 months). CONCLUSION Within their limits, the present results indicate that the described treatment approach may lead to predictable root coverage of isolated mandibular Miller Class I and II gingival recessions.

Proteomic analysis of porcine bone-conditioned medium.

PURPOSE Autografts are considered to support bone regeneration. Paracrine factors released from cortical bone might contribute to the overall process of graft consolidation. The aim of this study was to characterize the paracrine factors by means of proteomic analysis. MATERIALS AND METHODS Bone-conditioned medium (BCM) was prepared from fresh bone chips of porcine mandibles and subjected to proteomic analysis. Proteins were categorized and clustered using the bioinformatic tools UNIPROT and PANTHER, respectively. RESULTS Proteomic analysis showed that BCM contains more than 150 proteins, of which 43 were categorized into "secreted" and "extracellular matrix." Growth factors that are not only detectable in BCM, but potentially also target cellular processes involved in bone regeneration, eg, pleiotrophin, galectin-1, transforming growth factor beta (TGF-β)-induced gene (TGFBI), lactotransferrin, insulin-like growth factor (IGF)-binding protein 5, latency-associated peptide forming a complex with TGF-β1, and TGF-β2, were discovered. CONCLUSION The present results demonstrate that cortical bone chips release a large spectrum of proteins with the possibility of modulating cellular aspects of bone regeneration. The data provide the basis for future studies to understand how these paracrine factors may contribute to the complex process of graft consolidation.

In vitro characterization of a synthetic calcium phosphate bone graft on periodontal ligament cell and osteoblast behavior and its combination with an enamel matrix derivative.

OBJECTIVES Recent studies suggest that a combination of enamel matrix derivative (EMD) with grafting material may improve periodontal wound healing/regeneration. Newly developed calcium phosphate (CaP) ceramics have been demonstrated a viable synthetic replacement option for bone grafting filler materials. AIMS This study aims to test the ability for EMD to adsorb to the surface of CaP particles and to determine the effect of EMD on downstream cellular pathways such as adhesion, proliferation, and differentiation of primary human osteoblasts and periodontal ligament (PDL) cells. MATERIALS AND METHODS EMD was adsorbed onto CaP particles and analyzed for protein adsorption patterns via scanning electron microscopy and high-resolution immunocytochemistry with an anti-EMD antibody. Cell attachment and cell proliferation were quantified using CellTiter 96 One Solution Cell Assay (MTS). Cell differentiation was analyzed using real-time PCR for genes encoding Runx2, alkaline phosphatase, osteocalcin, and collagen1α1, and mineralization was assessed using alizarin red staining. RESULTS Analysis of cell attachment revealed significantly higher number of cells attached to EMD-adsorbed CaP particles when compared to control and blood-adsorbed samples. EMD also significantly increased cell proliferation at 3 and 5 days post-seeding. Moreover, there were significantly higher mRNA levels of osteoblast differentiation markers including collagen1α1, alkaline phosphatase, and osteocalcin in osteoblasts and PDL cells cultured on EMD-adsorbed CaP particles at various time points. CONCLUSION The present study suggests that the addition of EMD to CaP grafting particles may influence periodontal regeneration by stimulating PDL cell and osteoblast attachment, proliferation, and differentiation. Future in vivo and clinical studies are required to confirm these findings. CLINICAL RELEVANCE The combination of EMD and CaP may represent an option for regenerative periodontal therapy in advanced intrabony defects.

Implants placed in fresh extraction sockets in the maxilla: clinical and radiographic outcomes from a 3-year follow-up examination

AIM The aim of this prospective, randomized, controlled multicenter study was to determine the 3-year efficacy and stability of the soft and hard tissues at implants with a different geometry that were placed in fresh extraction sockets. MATERIAL AND METHODS Implants with two different configurations, cylindrical (Group A) or conical/cylindrical (Group B) were installed, and healing abutments were attached. Sixteen weeks after implant placement, subjects returned for a re-entry procedure. Prosthetic restorations were delivered 22 weeks after implant placement. Each subject was placed in a 3-year follow-up program, including examinations at yearly visits including various soft tissue and bone level parameters. RESULTS The percentage of sites that were considered inflamed during the follow-up period was stable and varied between 8.8% and 10.2%. The radiographic examinations documented improved bone levels at the final examination and the mean improvement from baseline (placement of permanent restoration; PR) amounted to 0.17 ± 0.67 mm. More than 70% (54 of 76) of the implants monitored in this study suffered no bone loss during the maintenance period. Moreover, there was an obvious "gain" of interproximal soft tissue volume and at the 3-year examination around 25% of all embrasure gaps were completely filled with "papillae". CONCLUSIONS Both conical/cylindrical and cylindrical implants placed in fresh extraction sockets allowed proper soft and hard tissue healing to occur. At both types of implants, mucosal inflammation was infrequent, marginal bone levels were maintained, and soft tissue volume increased gradually after the placement of the permanent restoration.

ACL reconstruction with physiological graft tension by intraoperative adjustment of the anteroposterior translation to the uninjured contralateral knee.

PURPOSE Fixation of anterior cruciate ligament (ACL) substitutes with non-physiological anteroposterior translation (APT) worsens outcome. The aim was to present a technique for physiological APT adjustment of the transplant in ACL reconstruction and its outcome at midterm. METHODS In a consecutive series of 28 patients (age 32 ± 11 years, 24 male), chronic ACL deficiency was treated by bone-patella-tendon-bone reconstruction. Transplant APT was adjusted to that of the contralateral uninjured ACL, measured 3, 6, and 12 months postoperatively using the Rolimeter. At a median follow-up of 5.3 years (3-8 years), 82% of the patients were re-evaluated with APT measurement and using IKDC-, Tegner-, Lysholm-Scores, conventional radiographs and MRI. RESULTS No differences in APT (mean ± SD) between uninjured and reconstructed knees were observed after adjustment (6 ± 1 versus 6 ± 1 mm, n.s.). Three months postoperatively, a statistically significant increase in APT (7 ± 1 mm) and a further increase at midterm (9 ± 2 mm) were observed. Patients scored "normal" or "nearly normal", respectively, in 79% (IKDC) and 4 (3-9) points (Tegner; median, range) or 89 ± 9 points (Lysholm; mean ± SD). Radiological evaluation showed no, minimal or moderate joint degeneration in 5, 20 and 75% of patients, respectively. MRI confirmed intact ACL transplants in all patients. CONCLUSION ACL reconstruction using the presented technique was considered successful, as patients did not suffer from subjective instability, radiographic analysis did not provide evidence for graft rupture at midterm. However, APT increase and occurrence of degenerative changes in reconstructed knees at the midterm might not be prevented even by restoration of a physiological APT in ACL reconstruction. The Rolimeter can be used for quick and easy intraoperative indirect control of the applied tension to the ACL transplant by measuring the APT to obtain physiological tensioning resulting in a satisfying outcome at midterm. LEVEL OF EVIDENCE IV.