Biomechanical comparison of semirigid junctional fixation techniques to prevent proximal junctional failure after thoracolumbar adult spinal deformity correction

BACKGROUND CONTEXTAdult spinal deformity patients treated operatively by long-segment instrumented spinal fusion are prone to develop proximal junctional kyphosis (PJK) and failure (PJF). A gradual transition in range of motion (ROM) at the proximal end of spinal instrumentation may reduce the incidence of PJK and PJF, however, previously evaluated techniques have not directly been compared.PURPOSETo determine the biomechanical characteristics of five different posterior spinal instrumentation techniques to achieve semirigid junctional fixation, or “topping-off,” between the rigid pedicle screw fixation (PSF) and the proximal uninstrumented spine.STUDY DESIGNBiomechanical cadaveric study.METHODSSeven fresh-frozen human cadaveric spine segments (T8–L3) were subjected to ex vivo pure moment loading in flexion-extension, lateral bending and axial rotation up to 5 Nm. The native condition, three-level PSF (T11–L2), PSF with supplemental transverse process hooks at T10 (TPH), and two sublaminar taping techniques (knotted and clamped) as one- (T10) or two-level (T9, T10) semirigid junctional fixation techniques were compared. The ROM and neutral zone (NZ) of the segments were normalized to the native condition. The linearity of the transition zones over three or four segments was determined through linear regression analysis.RESULTSAll techniques achieved a significantly reduced ROM at T10-T11 in flexion-extension and axial rotation relative to the PSF condition. Additionally, both two-level sublaminar taping techniques (CT2, KT2) had a significantly reduced ROM at T9-T10. One-level clamped sublaminar tape (CT1) had a significantly lower ROM and NZ compared with one-level knotted sublaminar tape (KT1) at T10-T11. Linear regression analysis showed the highest linear correlation between ROM and vertebral level for TPH and the lowest linear correlation for CT2.CONCLUSIONSAll studied semirigid junctional fixation techniques significantly reduced the ROM at the junctional levels and thus provide a more gradual transition than pedicle screws. TPH achieves the most linear transition over three vertebrae, whereas KT2 achieves that over four vertebrae. In contrast, CT2 effectively is a one-level semirigid junctional fixation technique with a shift in the upper rigid fixation level. Clamped sublaminar tape reduces the NZ greatly, whereas knotted sublaminar tape and TPH maintain a more physiologic NZ. Clinical validation is ultimately required to translate the biomechanics of various semirigid junctional fixation techniques into the clinical goal of reducing the incidence of proximal junctional kyphosis and failure.CLINICAL SIGNIFICANCEThe direct biomechanical comparison of multiple instrumentation techniques that aim to reduce the incidence of PJK after thoracolumbar spinal fusion surgery provides a basis upon which clinical studies could be designed. Furthermore, the data provided in this study can be used to further analyze the biomechanical effects of the studied techniques using finite element models to better predict their post-operative effectiveness.     

Pharmacokinetics of the antitumor antibiotic n-pentyl-sparsomycin in beagle dogs

Summary N-pentyl-sparsomycin (PSm) is a lipophilic analogue of sparsomycin (Sm), which is a well known inhibitor of protein synthesis. This compound was selected for preclinical pharmacokinetic studies because of its high in vitro and in vivo antitumor activity. In this study in which the drug was evaluated in beagle dogs under anaesthesia, the drug concentrations in plasma, urine and bile samples were determined using high performance liquid chromatography (HPLC). Plasma protein binding was approximately 54%. The mean t1/2 was 0.2 hours (12 minutes) and t1/2 was 0.75 ± 0.1 hours (45 ± 6 minutes). During continuous infusions up to 5.25 hours, the steady state was reached in 3 out of 6 experiments, suggesting that in some cases the real t1/2 was longer than measured. PSm was actively reabsorbed from the renal tubuli. This process was saturable at the higher doses. Tubular reabsorption played only a minor role in pharmacokinetics as most of the drug (67%) was eliminated by the non-renal clearance. The non-renal clearance was saturable at higher doses of PSm and was the reason for non-linearity of pharmacokinetics.     

图形设计中的写意造型

中国画的写意造型 ,展示的是似与不似之间、寓意于象、以象尽意“心物统一”的意象。在图形设计中采用写意造型方法 ,能使设计意念的表达更显符号化与象征性 ,同时也丰富观者感受层面与审美经验。     

Photorefractive keratectomy with the erbium: YAG laser

BACKGROUND: Ablation experiments and preclinical studies have shown increased thermal damage and surface roughness after photorefractive keratectomy (PRK) with the erbium: YAG laser. MATERIALS AND METHODS: In this study, the thermal damage was investigated on enucleated pig corneas for various laser pulse durations (80 ns to 1 ms) and radiant exposures (0.2-5 J/cm2). The "scanning-spot" method and the fundamental mode photo-ablation were used for spherical corrections. SEM pictures and surface roughness measurements enabled comparison with the morphology after ArF-excimer laser treatment. The surface roughness is one order of magnitude higher compared to the ArF-excimer laser ablation. The surface of the tissue after ablation looks melted. RESULTS: The thermal damage reduces with increased intensity, and at high intensities the thermal damage results in a constant thickness of > 5 microns. CONCLUSIONS: Laser-induced melting processes might be the main reason for the high thermal damage and the increased surface roughness after erbium: YAG laser treatment. This leads to the conclusion that the erbium: YAG laser is not a real alternative to the ArF-excimer laser in PRK.     

Quality control of estrogen receptor assays in the Netherlands

Summary Lyophilized receptor-positive tissue powders and cytosols, prepared from calf uterus and human breast tumor tissue, are used to assess the validity of routine dextran-coated charcoal estrogen receptor assays. Since 1978 lyophilized reference preparations have been analyzed twice yearly by 18 laboratories in the Netherlands. During 8 consecutive trials 20 different lyophilized samples were studied. The inter-laboratory variability of estrogen receptor results decreased with time. Most laboratories found receptor values around the median value of all groups together, though some participants consistently reported estrogen receptor values that were higher or lower than the median. The variability of estrogen receptor results between labs seemed to be associated with cytosol dilution, determination of non-specific binding, concentration and volume of dextrancoated charcoal, and the use of single dose assays or Scatchard analysis. The agreement on the presence or absence of estrogen receptors was more than 98% for lyophilized reference samples with high receptor content. For samples with low receptor content 85% agreement was observed, while 12% of the assays performed on receptor-negative material were reported to be estrogen receptor-positive. The use of the same protein determination (Coomassie Brilliant Blue) and human serum albumin standard has decreased the interlaboratory variation coefficient of the protein results to 7.5%. Address for reprnts: A. Koenders, Dept. of Experimental and Chemical Endocrinology, St. Radboud Hospital, Geert Grooteplein Z 8, 6500 HB Nijmegen, the Netherlands List of participating laboratories and institutions: Hospital de Lichtenberg, Amersfoort; Antoni van Leeuwenhoek Hospital, Amsterdam; Foundation Medical Laboratories, Breda; Foundation of Cooperative Hospitals Delft (SSDZ), Delft; Catharina Hospital, Eindhoven; Hospital de Stadsmaten and Ziekenzorg, Enschede; Academic Hospital, Groningen; The Wever Hospital, Heerlen; Laboratory of Public Health, Leeuwarden; Department of Pathological Chemistry, Academic Hospital, Leiden; Department of Experimental and Chemical Endocrinology, Sint Radboud Hospital, Nijmegen; Scientific Development Group Organon International B.V., Oss; Department of Biochemistry II, Erasmus University Rotterdam, Rotterdam; Rotterdam Radio-Therapeutic Institute/ Dr Daniel den Hoed Clinic, Rotterdam; Institute of Oncology Dr Bernard Verbeeten, Tilburg; Department of Endocrinology, Academic Hospital, Utrecht; Laboratory for Nuclear Medicine Voorburg, Vught; Sophia Hospital, Zwolle.     

Transient evoked otoacoustic emissions pattern as a prognostic indicator for hearing preservation in acoustic neuroma surgery.

OBJECTIVE: To determine whether pre-operative transient otoacoustic emission (TEOAE) patterns are predictive of successful hearing preservation in acoustic neuroma surgery. STUDY DESIGN: Retrospective observational study. SETTING: Tertiary referral medical center. PATIENTS: A convenience sample was identified in whom pre-operative TEOAE data were available in patients undergoing acoustic neuroma surgery from 1993-2004. Ninety-three patients were identified who met this inclusion criterion. INTERVENTIONS: Subjects underwent attempted hearing preservation surgery via middle cranial fossa or retrosigmoid approaches. Routine audiometry, ABR, and TEOAE. MAIN OUTCOME MEASURES: Pre- and post-operative pure tone and speech results were categorized into hearing classes A, B, C, and D as described in the American Academy of Otolaryngology guidelines (1995). Hearing preservation was defined by maintenance of the pre-operative hearing class or downgrade to within one hearing class post-op. Pre-operative TEOAE results were divided into five frequency bands and described as positive in each band if there was a response above the noise floor with >50% reproducibility. RESULTS: Hearing was preserved in 51 patients (55%). Of these, 11 (22%) had positive TEOAE response in all five frequency bands measured (1, 1.5, 2, 3, 4 kHz), whereas 40 (78%) had TEOAE responses ranging from 0 to 4 frequency bands. 42 patients failed to preserve their hearing. Of these, only three (7%) had positive TEOAE in all five frequency bands, and 39 (93%) had TEOAE responses ranging from 0 to 4 frequency bands (p<0.05). Other variables of prognostic significance to hearing preservation in our series included smaller tumor size, tumor location within the IAC, better pre-operative hearing, and shorter latencies on ABR. Logistic regression was then used to compare the prognostic value of TEOAE against these variables. In our series, ABR latencies and 5 frequency band response on TEOAE showed the highest significant correlation to hearing preservation (p<0.05). CONCLUSION: A robust pre-operative TEOAE frequency band pattern may be used as a favorable prognostic indicator for potential hearing preservation in acoustic neuroma surgery. The prognostic value may be enhanced when combined with other prognostic factors such as tumor size, tumor location, pre-operative ABR and audiometric results.     

The impact of geographic unit of analysis on socioeconomic inequalities in cancer survival and distant summary stage – a population‐based study

Objective: When using area‐level disadvantage measures, size of geographic unit can have major effects on recorded socioeconomic cancer disparities. This study examined the extent of changes in recorded socioeconomic inequalities in cancer survival and distant stage when the measure of socioeconomic disadvantage was based on smaller Census Collection Districts (CDs) instead of Statistical Local Areas (SLAs). Methods: Population‐based New South Wales Cancer Registry data were used to identify cases diagnosed with primary invasive cancer in 2000–2008 (n=264,236). Logistic regression and competing risk regression modelling were performed to examine socioeconomic differences in odds of distant stage and hazard of cancer death for all sites combined and separately for breast, prostate, colorectal and lung cancers. Results: For all sites collectively, associations between socioeconomic disadvantage and cancer survival and distant stage were stronger when the CD‐based socioeconomic disadvantage measure was used compared with the SLA‐based measure. The CD‐based measure showed a more consistent socioeconomic gradient with a linear upward trend of risk of cancer death/distant stage with increasing socioeconomic disadvantage. Site‐specific analyses provided similar findings for the risk of death but less consistent results for the likelihood of distant stage. Conclusions: The use of socioeconomic disadvantage measure based on the smallest available spatial unit should be encouraged in the future. Implications for public health: Disadvantage measures based on small spatial units can more accurately identify socioeconomic cancer disparities to inform priority settings in service planning.     

Suppression of Anti-Inflammatory Mediators in Metabolic Disease May Be Driven by Overwhelming Pro-Inflammatory Drivers

Obesity is a multifactorial disease and is associated with an increased risk of developing metabolic syndrome and co-morbidities. Dysregulated expansion of the adipose tissue during obesity induces local tissue hypoxia, altered secretory profile of adipokines, cytokines and chemokines, altered profile of local tissue inflammatory cells leading to the development of low-grade chronic inflammation. Low grade chronic inflammation is considered to be the underlying mechanism that increases the risk of developing obesity associated comorbidities. The glucocorticoid induced protein annexin A1 and its N-terminal peptides are anti-inflammatory mediators involved in resolving inflammation. The aim of the current study was to investigate the role of annexin A1 in obesity and associated inflammation. To achieve this aim, the current study analysed data from two feasibility studies in clinical populations: (1) bariatric surgery patients (Pre- and 3 months post-surgery) and (2) Lipodystrophy patients. Plasma annexin A1 levels were increased at 3-months post-surgery compared to pre-surgery (1.2 ± 0.1 ng/mL, n = 19 vs. 1.6 ± 0.1 ng/mL, n = 9, p = 0.009) and positively correlated with adiponectin (p = 0.009, r = 0.468, n = 25). Plasma annexin A1 levels were decreased in patients with lipodystrophy compared to BMI matched controls (0.2 ± 0.1 ng/mL, n = 9 vs. 0.97 ± 0.1 ng/mL, n = 30, p = 0.008), whereas CRP levels were significantly elevated (3.3 ± 1.0 µg/mL, n = 9 vs. 1.4 ± 0.3 µg/mL, n = 31, p = 0.0074). The roles of annexin A1 were explored using an in vitro cell based model (SGBS cells) mimicking the inflammatory status that is observed in obesity. Acute treatment with the annexin A1 N-terminal peptide, AC2-26 differentially regulated gene expression (including PPARA (2.8 ± 0.7-fold, p = 0.0303, n = 3), ADIPOQ (2.0 ± 0.3-fold, p = 0.0073, n = 3), LEP (0.6 ± 0.2-fold, p = 0.0400, n = 3), NAMPT (0.4 ± 0.1-fold, p = 0.0039, n = 3) and RETN (0.1 ± 0.03-fold, p < 0.0001, n = 3) in mature obesogenic adipocytes indicating that annexin A1 may play a protective role in obesity and inflammation. However, this effect may be overshadowed by the continued increase in systemic inflammation associated with rapid tissue expansion in obesity.     

BDNF Is Needed for Postnatal Maturation of Basal Forebrain and Neostriatum Cholinergic Neurons In Vivo

Neurotrophins regulate survival, neurite outgrowth, and phenotypic maturation of developing neurons. Brain-derived neurotrophic factor (BDNF) can promote the survival of developing cholinergic forebrain neurons in vitro and reduce their degeneration following injury in adult rats. We investigated the role of endogenous BDNF during postnatal development of these cholinergic neurons by analyzing homozygous BDNF-deficient (−/−) mice and their littermates (+/+, +/−). At P6, the number of choline acetyltransferase- (ChAT) positive neurons in the medial septum was 23% lower in BDNF−/− mice, although their brain and body weight was normal. At P15, control (+/+) littermates had 45% more and 45% larger ChAT-positive neurons and a much denser cholinergic hippocampal innervation than at P6, indicative of maturation of the septohippocampal system. In BDNF−/− mice, the number, size, and ChAT-immunostaining intensity of the cholinergic neurons remained the same between P6 and P15 (few mice survive longer). BDNF−/− mice had about three times more TUNEL-labeled (a marker of apoptosis) cells in the medial septum at P6, consistent with (but not proof of) the possibility that the cholinergic neurons were dying. The cholinergic hippocampal innervation in BDNF−/− mice expanded to a lesser extent than in controls and had reduced levels of acetylcholinesterase staining at P15. The developmental deficits were largely similar in the neostriatum of BDNF−/− mice. These findings suggest that BDNF is critical for postnatal development and maturation of cholinergic forebrain neurons.     

Smart Bone Graft Composite for Cancer Therapy Using Magnetic Hyperthermia

Magnetic hyperthermia (MHT) is a therapy that uses the heat generated by a magnetic material for cancer treatment. Magnetite nanoparticles are the most used materials in MHT. However, magnetite has a high Curie temperature (Tc~580 °C), and its use may generate local superheating. To overcome this problem, strontium-doped lanthanum manganite could replace magnetite because it shows a Tc near the ideal range (42–45 °C). In this study, we developed a smart composite formed by an F18 bioactive glass matrix with different amounts of Lanthanum-Strontium Manganite (LSM) powder (5, 10, 20, and 30 wt.% LSM). The effect of LSM addition was analyzed in terms of sinterability, magnetic properties, heating ability under a magnetic field, and in vitro bioactivity. The saturation magnetization (M_s) and remanent magnetization (M_r) increased by the LSM content, the confinement of LSM particles within the bioactive glass matrix also caused an increase in Tc. Calorimetry evaluation revealed a temperature increase from 5 °C (composition LSM5) to 15 °C (LSM30). The specific absorption rates were also calculated. Bioactivity measurements demonstrated HCA formation on the surface of all the composites in up to 15 days. The best material reached 40 °C, demonstrating the proof of concept sought in this research. Therefore, these composites have great potential for bone cancer therapy and should be further explored.