A propensity-matched study of patients with symptomatic lumbar spinal stenosis opting for surgery versus not.

Introduction: Although most surgeons treating patients with lumbar spinal stenosis (LSS) believe that surgical treatment is superior to conservative measures, systematics reviews have concluded that no solid evidence support this. Research question: To compare change at 1-year of walking ability, health-related quality of life, leg and back pain in patients with symptomatic LSS referred to a spine surgery clinic who opted for surgery and those who did not. Material and methods: The study included 149 operated and 149 non-operated patients seen by spine surgeons and diagnosed with LSS. The non-operated patients were propensity-matched to a cohort retrieved from the Danish national spine registry. Matching was done on demographics and baseline outcome measures. The outcomes was walking improvement measured by item 4 of the Oswestry Disability Index, EQ-5D-3L, global assessment (GA) of back/leg pain, back and leg pain on the Visual Analogue Scale and the Short Form 36 transition item 2. Results: Less than half of the non-operated reached MCID on EQ-5D-3L, VAS pain legs or VAS pain back where 2/3 of the operated did. The largest difference was VAS back pain where 27.5% of the non-operated reached an MCID of 12 points compared to 71.8% in the operated group. Discussion and conclusion: Surgical treated patients improved better than non-operated on all outcome measures. However, further research is required to compare the effectiveness of surgical decompression with non-operative care for LSS patients.

PROPOSE. Development and validation of a prediction model for shared decision making for patients with lumbar spinal stenosis.

Background: Decompression for lumbar spinal stenosis (LSS) is the most frequently performed spine surgery in Denmark. According to the Danish spine registry DaneSpine, at 1 year after surgery, about 75% of patients experiences considerable pain relief and around 66% improvement in quality of life. However, 25% do not improve very much. We have developed a predictive decision support tool, PROPOSE. It is intended to be used in the clinical conversation between healthcare providers and LSS patients as a shared decision-making aid presenting pros and cons of surgical intervention. This study presents the development and evaluation of PROPOSE in a clinical setting. Methods: For model development, 6.357 LSS patients enrolled in DaneSpine were identified. For model validation, predictor response and predicted outcome was collected via PROPOSE from 228 patients. Observed outcome at 1 year was retrieved from DaneSpine. All participants were treated at 3 Danish spine centers. The outcome measures presented are improvement in walking distance, the Oswestry Disability Index, EQ-5D-3L and leg/back pain on the Visual Analog Scale. Outcome variables were dichotomized into success (1) and failure (0). With the exception of walking distance, a success was defined as reaching minimal clinically important difference at 1-year follow-up. Models were trained using Multivariate Adaptive Regression Splines. Performance was assessed by inspecting confusion matrix, ROC curves and comparing GCV (generalized cross-validation) errors. Final performance of the models was evaluated on independent test data. Results: The walking distance model demonstrated excellent performance with an AUC of 0.88 and a Brier score of 0.14. The VAS leg pain model had the lowest discriminatory performance with an AUC of 0.67 and a Brier score of 0.22. Conclusions: PROPOSE works in a real-world clinical setting as a proof of concept and demonstrates acceptable performance. It may have the potential of aiding shared decision making.

Implementation of the S100 Calcium-Binding Protein B Biomarker in a Clinical Setting: A Retrospective Study of Benefits, Safety, and Effectiveness.

Recent years have seen the emergence of the S100 calcium-binding protein B (S100B) biomarker used in the initial management of minor traumatic brain injury (TBI) patients. S100B has been found to reduce cerebral computed tomography (CT-C) scans and was recently implemented in the Scandinavian Neurotrauma Committee (SNC) guidelines. In a clinical setup, we retrospectively investigated the use of the S100B biomarker in relation to the SNC guidelines in the respective year before and after implementation. Accordingly, minor TBI patients with the International Classification of Diseases, Tenth Revision diagnostic code of S06.0 commotio cerebri were included in 2018 (n = 786) and 2019 (n = 709) for comparison of emergency department time (EDT) and CT-Cs. In 2019, we included all patients with an S100B sample (n = 547; 348/199 male:female; median age, 52 years). We found an S100B sensitivity of 92% and negative predictive value (NPV) of 99% (cutoff, 0.10 µg/L) regardless of SNC guideline compliance. With strict SNC guideline management, sensitivity and NPV increased to 100%, even at a 0.20-µg/L cutoff that increased the specificity from 49% to 76%. After S100B implementation, we found the median EDT to significantly increase from 196 min (interquartile range [IQR] = 127-289) in 2018 to 216 min (IQR = 134.0-309.5) in 2019 (p = 0.0148), which may have resulted from poor guideline compliance (53.9%). Contrarily, the proportion of CT-C scanned patients decreased from 70% to 56.3% equal to a relative 27.5% decrease of scanned patients (p < 0.0001). Conclusively, our study supported the safe and efficient clinical use of the S100B biomarker, albeit with a minor EDT increase. S100B combination with the SNC guidelines improved clinical potential.

[Ureaplasma parvum arthritis affecting knee, hip, and sacroiliac joint].

In this case report a rare case of Ureaplasma parvum arthritis affecting the left knee, hip, and the sacroiliac joint in a 57-year-old woman is investigated. The patient was initially treated with intravenous piperacillin/tazobactam and later on meropenem with no clinical effect. After surgery of the hip and knee, tissue biopsies and synovial fluids were all culture negative. Eventually, Ureaplasma parvum was detected by 16S analysis, and the antibiotic regimen was changed to intravenous moxifloxacin. The patient improved and after four weeks the therapy was changed to lifelong oral therapy with moxifloxacin.

Effects of freshwater release on oyster reef density, reproduction, and disease in a highly modified estuary.

Few estuaries remain unaffected by water management and altered freshwater deliveries. The Caloosahatchee River Estuary is a perfect case study for assessing the impact of altered hydrology on natural oyster reef (Crassostrea virginica) populations. The watershed has been highly modified and greatly enlarged by an artificial connection to Lake Okeechobee. Accordingly, to generate data to support water management recommendations, this study monitored various oyster biometrics over 15 years along the primary salinity gradient. Oyster reef densities were significantly affected by both prolonged high volume freshwater releases creating hyposaline conditions at upstream sites and by a lack of freshwater input creating hypersaline conditions at downstream sites. Low freshwater input led to an increase in disease caused by Perkinsus marinus and predation. Moderate (< 2000 cfs) and properly timed (winter/spring) freshets benefited oysters with increased gametogenesis, good larval mixing, and a reprieve from disease. If high volume freshets occurred in the late summer, extensive mortality occurred at the upstream site due to low salinity. These findings suggest freshwater releases in the late summer, when reproductive stress is at its peak and pelagic larvae are most vulnerable, should be limited to < 2000 cfs, but that longer freshets (1-3 weeks) in the winter and early spring (e.g., December-April) benefit oysters by reducing salinity and lessening disease intensity. Similar strategies can be employed in other managed systems, and patterns regarding the timing of high volume flows are applicable to all estuaries where the management of healthy oyster reefs is a priority.

Inter- and intrarater reliability of measuring lengthening of magnetically controlled growing rods on digital radiographs.

PURPOSE: The aim of this study was to determine inter- and intraobserver reliability of delta rod extension, and total rod length measured on digital x-rays in patients with early onset scoliosis (EOS) treated with magnetically controlled growing rods (MCGR). For the last decade, patients with EOS have been treated with MCGR. Replacement of MCGR relies heavily on the measurement done at every lengthening session. Only a few studies have looked at inter- and intraobserver reliability of rod lengthening, and none have used the delta extension before. METHODS: 202 radiographs presented in random order were rated and measured twice with at least a 14-day interval and differing order of the radiographs. The measuring was done at both rods. All x-rays came from 15 patients diagnosed with EOS and treated with MCGR from 2009 until 2019. The total extension length and the delta extension (the difference in total extension length between two lengthening in succession) were measured, and the intraclass correlation coefficient (ICC) calculated for both measurements RESULTS: Intrarater ICC scores varied from moderate to good, but non-significantly. Interrater reliability increased significantly from moderate (ICC 0.72 [0.68; 0.76] and 0.73 [0.69; 0.77] to excellent (ICC 0.91 [0.88; 0.93] and 0.97 [0.96: 0.98]), when examining delta extension every sixth instead of every second month. CONCLUSION: Measuring rod lengthening on x-rays can be done every 6 months, with an ample reliability. The ICC's for the delta extension with 2-3 months interval were only moderately precise, compared to the near perfect ICC's for the total extension length.

Submerged Vegetation Responses to Climate Variation and Altered Hydrology in a Subtropical Estuary: Interpreting 33 Years of Change.

Links between hydrologic modifications, flow and salinity regimes, and submerged aquatic vegetation (SAV) species composition and abundance were assessed with an empirical analysis of 33 years of monitoring data collected at nine sites in Florida's Caloosahatchee River Estuary (CRE). Freshwater inflows to the estuary (30-day means) were often outside the previously recommended envelope of 12.74 to 79.29 m3 s-1. Discharges from Lake Okeechobee through a synthetic hydrologic link were responsible for 43% of the above-envelope flows, but reduced the incidence of below-envelope flows by 30%. A salinity model and salinity stress indices developed for each SAV species indicated that the observed flows generated variable salinity conditions likely to harm both seagrasses and freshwater SAV in the estuary. Regression modeling of SAV abundance generally confirmed the flow and salinity responses expected for each species: Halodule wrightii and Thalassia testudinum in the lower estuary were both harmed by high-flow, low-salinity conditions, while Vallisneria americana in the upper estuary was decimated by low-flow, high-salinity conditions. There was a species-specific effect of the seasonal timing of high flows-T. testudinum was more negatively correlated with high flows in the dry season; H. wrightii in the wet season. The regression analyses also highlighted strong, year-to-year autocorrelations in SAV abundance, indicating reduced resilience after severe losses, particularly for V. americana. Large residual variation in some regression models suggested that factors other than salinity (e.g., optical water quality or grazing impacts) may also influence the system dynamics and should be incorporated in continuing research. This analysis suggests that use of artificial water management infrastructure to reduce extreme high and low flows to the Caloosahatchee and other estuaries could help maintain SAV health in light of intensifying climate variability and degraded watershed flow regulation capacity.

Decadal and seasonal trends of nutrient concentration and export from highly managed coastal catchments.

Understanding anthropogenic and hydro-climatic influences on nutrient concentrations and export from highly managed catchments often necessitates trend detection using long-term monitoring data. This study analyzed the temporal trend (1979-2014) of total nitrogen (TN) and total phosphorus (TP) concentrations and export from four adjacent coastal basins in south Florida where land and water resources are highly managed through an intricate canal network. The method of integrated seasonal-trend decomposition using LOESS (LOcally weighted regrESSion) was employed for trend detection. The results indicated that long-term trends in TN and TP concentrations (increasing/decreasing) varied with basins and nutrient species, reflecting the influence of basin specific land and water management practices. These long-term trends were intervened by short-term highs driven by high rainfall and discharges and lows associated with regional droughts. Seasonal variations in TP were more apparent than for TN. Nutrient export exhibited a chemostatic behavior for TN from all the basins, largely due to the biogenic nature of organic N associated with the ubiquity of organic materials in the managed canal network. Varying degrees of chemodynamic export was present for TP, reflecting complex biogeochemical responses to the legacy of long-term fertilization, low soil P holding capacity, and intensive stormwater management. The anthropogenic and hydro-climatic influences on nutrient concentration and export behavior had great implications in nutrient loading abatement strategies for aquatic ecosystem restoration of the downstream receiving waterbody.

Determining the effects of freshwater inflow on benthic macrofauna in the Caloosahatchee Estuary, Florida.

Florida legislation requires determining and implementing an appropriate range and frequency of freshwater inflows that will sustain a fully functional estuary. Changes in inflow dynamics to the Caloosahatchee Estuary, Florida have altered salinity regimes that, in turn, have altered the ecological integrity of the estuary. The purpose of this current project is to determine how changes in freshwater inflows affect water quality, and in turn, benthic macrofauna, spatially within the Caloosahatchee Estuary and between multiyear wet and dry periods. Thirty-four benthic species were identified as being indicator species for salinity zones, and the estuary was divided into 4 zones based on differences in community structure within the estuary. Community structure had the highest correlations with water quality parameters that were common indicators of freshwater conditions resulting from inflows. A significant relationship between salinity and diversity occurs both spatially and temporally because of increased numbers of marine species as salinities increase. A salinity-based model was used to estimate inflow during wet and dry periods for each of the macrofauna community zones. The approach used here (identifying bioindicators and community zones with corresponding inflow ranges) is generic and will be useful for developing targets for managing inflow in estuaries worldwide. Integr Environ Assess Manag 2016;12:529-539. © 2015 SETAC.

Simulation of potential oyster density with variable freshwater inflow (1965-2000) to the Caloosahatchee River Estuary, southwest Florida, USA.

Oyster beds are disappearing worldwide through a combination of over-harvesting, diseases, and salinity alterations in the coastal zone. Sensitivity of oysters to variable discharge and salinity is particularly acute in small sub-tropical estuaries subject to regulated freshwater releases. South Florida has sub-tropical estuaries where watershed flood control sometimes results in excessive freshwater inflow to estuaries during the wet season (May-Oct) and reduced discharge and increased salinities in the dry season (Nov-Apr). The potential to reserve freshwater accumulated during the wet season could offer the capacity to regulate freshwater at different temporal scales, thus optimizing salinity conditions for estuarine biota. The goal of this study was to use simulation modeling to explore the effects of freshwater inflows and salinity on adult oyster survival in the Caloosahatchee River Estuary (CRE) in southwest Florida. Water managers derived three different freshwater inflow scenarios for the CRE based on historical and modified watershed attributes for the time period of 1965-2000. Three different salinity time series were generated from the inflow scenarios at each of three sites in the lower CRE and used to conduct nine different oyster simulations. Overall, the predicted densities of adult oysters in the upstream site were 3-4 times greater in seasons that experienced reduced freshwater inflow (e.g., increased salinity) with oyster density in the lower estuary much less influenced by the inflows. Potential storage of freshwater reduced the frequency of extreme flows in the wet season and helped to maintain minimum inflow in the dry season near the estuarine mouth. Analyses of inflows indicated that discharges ranging from 0 to 1,500 cfs could promote favorable salinities of 10-25 in the lower CRE depending on wet versus dry season climatic conditions. This range of inflows is similar to that derived in other studies of the CRE and emphasizes the value of simulation models to help prescribe freshwater releases which benefit estuarine biota.

Chemical blocking of zinc ions in CNS increases neuronal damage following traumatic brain injury (TBI) in mice.

BACKGROUND: Traumatic brain injury (TBI) is one of the leading causes of disability and death among young people. Although much is already known about secondary brain damage the full range of brain tissue responses to TBI remains to be elucidated. A population of neurons located in cerebral areas associated with higher cognitive functions harbours a vesicular zinc pool co-localized with glutamate. This zinc enriched pool of synaptic vesicles has been hypothesized to take part in the injurious signalling cascade that follows pathological conditions such as seizures, ischemia and traumatic brain injury. Pathological release of excess zinc ions from pre-synaptic vesicles has been suggested to mediate cell damage/death to postsynaptic neurons. METHODOLOGY/PRINCIPAL FINDINGS: In order to substantiate the influence of vesicular zinc ions on TBI, we designed a study in which damage and zinc movements were analysed in several different ways. Twenty-four hours after TBI ZnT3-KO mice (mice without vesicular zinc) were compared to littermate Wild Type (WT) mice (mice with vesicular zinc) with regard to histopathology. Furthermore, in order to evaluate a possible neuro-protective dimension of chemical blocking of vesicular zinc, we treated lesioned mice with either DEDTC or selenite. Our study revealed that chemical blocking of vesicular zinc ions, either by chelation with DEDTC or accumulation in zinc-selenium nanocrystals, worsened the effects on the aftermath of TBI in the WT mice by increasing the number of necrotic and apoptotic cells within the first 24 hours after TBI, when compared to those of chemically untreated WT mice. CONCLUSION/SIGNIFICANCE: ZnT3-KO mice revealed more damage after TBI compared to WT controls. Following treatment with DEDTC or selenium an increase in the number of both dead and apoptotic cells were seen in the controls within the first 24 hours after TBI while the degree of damage in the ZnT3-KO mice remained largely unchanged. Further analyses revealed that the damage development in the two mouse strains was almost identical after either zinc chelation or zinc complexion therapy.

Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury.

Traumatic brain injury results in loss of neurons caused as much by the resulting neuroinflammation as by the injury. Gold salts are known to be immunosuppressive, but their use are limited by nephrotoxicity. However, as we have proven that implants of pure metallic gold release gold ions which do not spread in the body, but are taken up by cells near the implant, we hypothesize that metallic gold could reduce local neuroinflammation in a safe way. Bio-liberation, or dissolucytosis, of gold ions from metallic gold surfaces requires the presence of disolycytes i.e. macrophages and the process is limited by their number and activity. We injected 20-45 mum gold particles into the neocortex of mice before generating a cryo-injury. Comparing gold-treated and untreated cryolesions, the release of gold reduced microgliosis and neuronal apoptosis accompanied by a transient astrogliosis and an increased neural stem cell response. We conclude that bio-liberated gold ions possess pronounced anti-inflammatory and neuron-protective capacities in the brain and suggest that metallic gold has clinical potentials. Intra-cerebral application of metallic gold as a pharmaceutical source of gold ions represents a completely new medical concept that bypasses the blood-brain-barrier and allows direct drug delivery to inflamed brain tissue.

Kupffer cells are central in the removal of nanoparticles from the organism.

BACKGROUND: The study aims at revealing the fate of nanoparticles administered intravenously and intraperitoneally to adult female mice, some of which were pregnant. Gold nanoparticles were chosen as a model because these particles have been found to be chemically inert and at the same time are easily traced by autometallography (AMG) at both ultrastructural and light microscopic levels. RESULTS: Gold nanoparticles were injected intravenously (IV) or intraperitoneally (IP) and traced after 1, 4 or 24 hours. For IV injections 2 and 40 nm particles were used; for IP injections 40 nm particles only. The injected nanoparticles were found in macrophages only, and at moderate exposure primarily in the Kupffer cells in the liver. IV injections resulted in a rapid accumulation/clustering of nanoparticles in these liver macrophages, while the uptake in spleen macrophages was moderate. IP injections were followed by a delayed uptake in the liver and included a moderate uptake in macrophages located in mesenteric lymph nodes, spleen and small intestine. Ultrastructurally, the AMG silver enhanced nanocrystals were found in lysosome-like organelles of the Kupffer cells and other macrophages wherever located.Accumulations of gold nanoparticles were not found in any other organs analysed, i.e. kidneys, brain, lungs, adrenals, ovaries, placenta, and fetal liver, and the control animals were all void of AMG staining. CONCLUSION: Our results suggest that: (1) inert gold nanoparticles do not penetrate cell membranes by non-endocytotic mechanisms, but are rather taken up by endocytosis; (2) gold nanoparticles, independent of size, are taken up primarily by Kupffer cells in the liver and secondarily by macrophages in other places; (3) gold nanoparticles do not seem to penetrate the placenta barrier; (4) the blood-brain barrier seems to protect the central nervous system from gold nanoparticles; (5) 2 nanometer gold particles seem to be removed not only by endocytosis by macrophages, and we hypothesize that part of these tiny nanoparticles are released into the urine as a result of simple filtration in the renal glomeruli.