The Effect of 6 versus 9 Years of Zoledronic Acid Treatment in Osteoporosis: A Randomized Second Extension to the HORIZON-Pivotal Fracture Trial (PFT).

While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n=95) and Z6P3 (n=95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was -0.54% in Z9 vs. -1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: -0.37%, 1.93%; p=0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. This article is protected by copyright. All rights reserved.

Methodological approach to the first and second lactate threshold in incremental cardiopulmonary exercise testing

Determination of an 'anaerobic threshold' plays an important role in the appreciation of an incremental cardiopulmonary exercise test and describes prominent changes of blood lactate accumulation with increasing workload. Two lactate thresholds are discerned during cardiopulmonary exercise testing and used for physical fitness estimation or training prescription. A multitude of different terms are, however, found in the literature describing the two thresholds. Furthermore, the term 'anaerobic threshold' is synonymously used for both, the 'first' and the 'second' lactate threshold, bearing a great potential of confusion. The aim of this review is therefore to order terms, present threshold concepts, and describe methods for lactate threshold determination using a three-phase model with reference to the historical and physiological background to facilitate the practical application of the term 'anaerobic threshold'.

Complete Genome Sequence of Bovine Pestivirus Strain PG-2, a Second Member of the Tentative Pestivirus Species Giraffe

We report the complete genome sequence of bovine pestivirus strain PG-2. The sequence data from this virus showed that PG-2 is closely related to the giraffe pestivirus strain H138. PG-2 and H138 belong to one pestivirus species that should be considered an approved member of the genus Pestivirus.

A comparative assessment by optical coherence tomography of the performance of the first and second generation of the everolimus-eluting bioresorbable vascular scaffolds

The first generation of the everolimus-eluting bioresorbable vascular scaffold (BVS 1.0) showed an angiographic late loss higher than the metallic everolimus-eluting stent Xience V due to scaffold shrinkage. The new generation (BVS 1.1) presents a different design and manufacturing process than the BVS 1.0. This study sought to evaluate the differences in late shrinkage, neointimal response, and bioresorption process between these two scaffold generations using optical coherence tomography (OCT).

Structural aspects of redox-mediated electron tunneling (Dedicated to the memory of professor Alexander M. Kuznetsov)

We investigated structural aspects of electron transfer (ET) in tunneling junctions (Au(1 1 1)vertical bar FcN vertical bar solution gap vertical bar Au STM tip) with four different redox-active N-thioalk(ano)ylferrocenes (FcN) embedded. The investigated molecules consist of a redox-active ferrocene (Fc) moiety connected via alkyl spacers with N = 4, 6, 8 and 11 carbon atoms to a thiol anchoring group. We found that for short FcNs (N = 4, 6,8) the redox-mediated ET response increases with the increase of the alkyl chain length, while no enhancement of the ET was observed for Fc1 1. The model of two-step ET with partial vibrational relaxation by Kuznetsov and Ulstrup was used to rationalize these results. The theoretical ET steps were assigned to two processes: (1) electron tunneling from the Fc group to the Au tip through the electrolyte layer and (2) electron transport from the Au(1 1 1) substrate to the Fc group through the organic adlayer. We argue that for the three short FcNs, the first process represents the rate-limiting step. The increase of the length of the alkyl chain leads to an approach of the Fc group to the STM tip, and consequently accelerates the first El' step. In case of the Fcl 1 junctions the rather high thickness of the organic layer leads to a decrease of the rate of the second ET step. In consequence, the contribution of the redox-mediated current enhancement to the total tunneling current appears to be insignificant. Our work demonstrates the importance of combined structural and transport approaches for the understanding of Er processes in electrochemical nanosystems. (C) 2010 Elsevier B.V. All rights reserved.

Gunshot wounds to the acetabulum

To classify the fracture patterns of gunshot wounds to the acetabulum; identify the associated injuries and complications; determine the predictors of poor outcome and deep infection; and propose a treatment algorithm based on the results.

Vascular response of the segments adjacent to the proximal and distal edges of the ABSORB everolimus-eluting bioresorbable vascular scaffold: 6-month and 1-year follow-up assessment: a virtual histology intravascular ultrasound study from the first-in-man ABSORB cohort B trial

This study sought to investigate in vivo the vascular response at the proximal and distal edges of the second-generation ABSORB everolimus-eluting bioresorbable vascular scaffold (BVS).

Photodissociation dynamics of tert-butylnitrite following excitation to the S(1) and S(2) states. A study by velocity-map ion-imaging and 3D-REMPI spectroscopy

Excitation of tert-butylnitrite into the first and second UV absorption bands leads to efficient dissociation into the fragment radicals NO and tert-butoxy in their electronic ground states (2)Π and (2)E, respectively. Velocity distributions and angular anisotropies for the NO fragment in several hundred rotational and vibrational quantum states were obtained by velocity-map imaging and the recently developed 3D-REMPI method. Excitation into the well resolved vibronic progression bands (k = 0, 1, 2) of the NO stretch mode in the S(1) ← S(0) transition produces NO fragments mostly in the vibrational state with v = k, with smaller fractions in v = k - 1 and v = k - 2. It is concluded that dissociation occurs on the purely repulsive PES of S(1) without barrier. All velocity distributions from photolysis via the S(1)(nπ*) state are monomodal and show high negative anisotropy (β ≈ -1). The rotational distributions peak near j = 30.5 irrespective of the vibronic state S(1)(k) excited and the vibrational state v of the NO fragment. On average 46% of the excess energy is converted to kinetic energy, 23% and 31% remain as internal energy in the NO fragment and the t-BuO radical, respectively. Photolysis via excitation into the S(2) ← S(0) transition at 227 nm yields NO fragments with about equal populations in v = 0 and v = 1. The rotational distributions have a single maximum near j = 59.5. The velocity distributions are monomodal with positive anisotropy β ≈ 0.8. The average fractions of the excess energy distributed into translation, internal energy of NO, and internal energy of t-BuO are 39%, 23%, and 38%, respectively. In all cases ∼8500 cm(-1) of energy remain in the internal degrees of freedom of the t-BuO fragment. This is mostly assigned to rotational energy. An ab initio calculation of the dynamic reaction path shows that not only the NO fragment but also the t-BuO fragment gain large angular momentum during dissociation on the purely repulsive potential energy surface of S(2).

Theoretical considerations to the verification of dynamic multileaf collimated fields with a SLIC-type portal image detector

The verification possibilities of dynamically collimated treatment beams with a scanning liquid ionization chamber electronic portal image device (SLIC-EPID) are investigated. The ion concentration in the liquid of a SLIC-EPID and therefore the read-out signal is determined by two parameters of a differential equation describing the creation and recombination of the ions. Due to the form of this equation, the portal image detector describes a nonlinear dynamic system with memory. In this work, the parameters of the differential equation were experimentally determined for the particular chamber in use and for an incident open 6 MV photon beam. The mathematical description of the ion concentration was then used to predict portal images of intensity-modulated photon beams produced by a dynamic delivery technique, the sliding window approach. Due to the nature of the differential equation, a mathematical condition for 'reliable leaf motion verification' in the sliding window technique can be formulated. It is shown that the time constants for both formation and decay of the equilibrium concentration in the chamber is in the order of seconds. In order to guarantee reliable leaf motion verification, these time constants impose a constraint on the rapidity of the image-read out for a given maximum leaf speed. For a leaf speed of 2 cm s(-1), a minimum image acquisition frequency of about 2 Hz is required. Current SLIC-EPID systems are usually too slow since they need about a second to acquire a portal image. However, if the condition is fulfilled, the memory property of the system can be used to reconstruct the leaf motion. It is shown that a simple edge detecting algorithm can be employed to determine the leaf positions. The method is also very robust against image noise.

Influence of suture tension to the tearing characteristics of the soft tissues: an in vitro experiment

OBJECTIVES: To evaluate the influence of flap tension on the tearing characteristics of mucosal tissue samples in relation to various suture and needle characteristics. MATERIAL AND METHODS: Lining and masticatory mucosal tissue samples obtained from pig jaws were prepared for in vitro testing. Tension tearing diagrams of 60 experiments were traced for 3-0, 5-0 and 7-0 sutures with applied forces up to 20 N. In the second part, the same experiments were repeated with 100 diagrams to test the influence of needle characteristics with 5-0 and 6-0 sutures using only gingival tissue samples. RESULTS: 3-0 sutures mainly lead to tissue breakage at an average of 13.4 N. In contrast, 7-0 sutures only resulted in breakage of the thread at a mean applied force of 3.7 N. With 5-0 sutures, both events occurred at random at a mean force of 14.6 N. Irrespective of the needle characteristics, the mean breaking force for gingival samples with 5-0 and 6-0 sutures was approximately 10 N. CONCLUSIONS: Tissue trauma may be reduced by choosing finer suture diameters, because thinner (6-0, 7-0) sutures lead to thread breakage rather than tissue breakage.

Bacillus Calmette-Guérin Failure in Patients with Non-Muscle-invasive Urothelial Carcinoma of the Bladder May Be Due to the Urologist's Failure to Detect Urothelial Carcinoma of the Upper Urinary Tract and Urethra

BACKGROUND: Various reasons exist for so-called bacillus Calmette-Guérin (BCG) failure in patients with non-muscle-invasive urothelial bladder carcinoma (NMIBC). OBJECTIVE: To explore whether urothelial carcinoma of the upper urinary tract (UUT) and/or prostatic urethra may be a cause for BCG failure. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 110 patients with high-risk NMIBC repeatedly treated with intravesical BCG, diagnosed with disease recurrence, and followed for a median time of 9.1 yr. INTERVENTION: Two or more intravesical BCG induction courses without maintenance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was pattern of disease recurrence (BCG failure) within the urinary tract categorised into UUT and/or urethral carcinoma (with or without intravesical recurrence), and intravesical recurrence alone. Secondary outcome was survival. Predictors of UUT and/or urethral carcinoma and the effect of pattern of disease recurrence on cancer-specific survival were assessed with multivariable Cox regression analysis adjusting for multiple clinical and tumour characteristics. RESULTS AND LIMITATIONS: Of the 110 patients, 57 (52%) had UUT and/or urethral carcinoma (with or without intravesical recurrence), and 53 (48%) had intravesical recurrence alone. In patients with UUT and/or urethral carcinoma, bladder carcinoma in situ (Tis) before the first and second BCG course was present in 42 of 57 (74%) and 47 of 57 (82%) patients, respectively. On multivariable analysis, bladder Tis before the first and/or second BCG course was the only independent predictor of UUT and/or urethral carcinoma. Of the 110 patients, 69 (63%) were alive at last follow-up visit, 18 (16%) had died due to metastatic urothelial carcinoma, and 23 (21%) had died of other causes. Pattern of disease recurrence within the urinary tract was not an independent predictor of cancer-specific survival. Main study limitations were retrospective design and limited power for survival analysis. CONCLUSIONS: In our patients with high-risk NMIBC failing after two or more courses of intravesical BCG, UUT and/or urethral carcinoma was detected in >50% of the cases during follow-up. The vast majority of these patients had bladder Tis before the first and/or second BCG course. In patients experiencing the so-called BCG failure, a diagnostic work-up of UUT and prostatic urethra should always be performed to exclude urothelial carcinoma before additional intravesical therapy or even a radical cystectomy is considered.

Anterior approaches to the acetabulum

Since the 1960s the ilioinguinal approach by Letournel with the three anatomic windows has been successfully established for the treatment of acetabular fractures involving predominantly the anterior column. The previous standard approach, the iliofemoral approach by Smith-Petersen, is still used for the therapy of anterior wall or isolated femoral head fractures. The increase in acetabular fractures in the elderly with lateral compression fractures after lateral falls, characterized by medial displacement of the quadrilateral plate and superomedial dome impaction, led to the use of the intrapelvic modified Stoppa approach with or without the first window of the ilioinguinal approach in the 1990s. To combine the advantages of the second and third windows of the ilioinguinal approach and the medial view of the modified Stoppa approach the Berne research group recently introduced the pararectus approach in acetabular surgery, which can be used as a less invasive acetabular surgical (LIAS) technique especially in the elderly.

Frameless linac-based (Novalis TX) stereotactic treatment for vestibular schwannoma that extend distally into the iac (Internal Acoustic Canal): an analysis of the dose to the cochlea

Objectives: We compare the dose parameters between 3 different radiosurgery delivery techniques which may have an impact on cochlea function. Methods: Five patients with unilateral vestibular schwannoma (VS) were selected for this study. Planning procedure was carried out using the BrainLAB® iPlan planning system v. 4.5. For each patient three different planning techniques were used: dynamic arc (DA) with 5 arcs per plan, hybrid arc (HA) with 5 arcs per plan and IMRT with 8 fields per plan. For each technique, two plans were generated with different methods: with the first method (PTV coverage) it was the goal to fully cover the PTV with at least 12 Gy (normalization: 12 Gy covered 99% of the PTV) and with the second method (cochlea sparing) it was the goal to spare the cochlea (normalization: 12 Gy covers 50% of the PTV/V4Gy of cochlea lower than 1%). Plan evaluation was done considering target volume and coverage (conformity and homogeneity) and OAR constraints (mean (Dmean) and maximum dose (Dmax) to cochlea, Dmax to brainstem and cochlea). The total number of monitor units (MU) was analyzed. Results: The median tumor volume was 0.95 cm³ (range, 0.86-3 cm³). The median PTV was 1.44 cm³ (range, 1-3.5 cm³). The median distance between the tumor and the cochlea's modiulus was 2.7 mm (range, 1.8-6.3 mm). For the PTV coverage method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.872) and in Dmean (p= 0.860). We found a significant correlation (p< 0.05) between the target volume and the cochlear Dmean for all plans with Pearson's coefficient correlation of 0.90, 0.92 and 0.94 for the DA, HA and IMRT techniques, respectively. For the cochlea sparing method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.310) and in Dmean (p= 0.275). However, in this group the V4Gy of the ipsilateral cochlea represents less than 1%. When using the HA or IMRT technique, the homogeneity and conformity in the PTV, but also the number of MUs were increased in comparison to the DA technique. Conclusion: VS tumors that extend distally into the IAC had an equivalent sparing of cochlea with DA approach compared with the HA and IMRT techniques. Disclosure: No significant relationships.