Adjunctive Use of Bone Growth Stimulation Increases Cervical Spine Fusion Rates in Patients at Risk for Pseudarthrosis.

STUDY DESIGN: A prospective multicenter clinical trial (NCT03177473) was conducted with a retrospective cohort used as a control arm. OBJECTIVE: The purpose of this study was to evaluate cervical spine fusion rates in subjects with risk factors for pseudarthrosis who received pulsed electromagnetic field (PEMF) treatment. SUMMARY OF BACKGROUND DATA: Certain risk factors predispose patients to pseudarthrosis, which is associated with prolonged pain, reduced function, and decreased quality of life. METHODS: Subjects in the PEMF group were treated with PEMF for 6 months postoperatively. The primary outcome measure was fusion status at the 12-month follow-up period. Fusion status was determined using anterior/posterior, lateral, and flexion/extension radiographs and computed tomography (without contrast). RESULTS: A total of 213 patients were evaluated (PEMF, n=160; Control, n=53). At baseline, the PEMF group had a higher percentage of subjects who used nicotine ( P =0.01), had osteoporosis ( P <0.05), multi-level disease ( P <0.0001), and were >65 years of age ( P =0.01). The PEMF group showed over two-fold higher percentage of subjects that had ≥3 risk factors (n=92/160, 57.5%) compared with the control group (n=14/53, 26.4%). At the 12-month follow-up, the PEMF group demonstrated significantly higher fusion rates compared with the control (90.0% vs. 60.4%, P <0.05). A statistically significant improvement in fusion rate was observed in PEMF subjects with multi-level surgery ( P <0.0001) and high BMI (>30 kg/m 2 ; P =0.0021) when compared with the control group. No significant safety concerns were observed. CONCLUSIONS: Adjunctive use of PEMF stimulation provides significant improvements in cervical spine fusion rates in subjects having risk factors for pseudarthrosis. When compared with control subjects that did not use PEMF stimulation, treated subjects showed improved fusion outcomes despite being older, having more risk factors for pseudarthrosis, and undergoing more complex surgeries.

The Lumbosacral Fractional Curve in Adult Degenerative Scoliosis.

Spine surgeons are often faced with a profoundly difficult challenge in surgically treating adult degenerative scoliosis. Deformity correction surgery is complicated by the difficulty in offering extensive surgical corrections to the elderly, complication-prone population it commonly affects. As spine surgeons attempt to offer minimally invasive solutions to this disease process, the need for fusion of the fractional curve at L4, L5, and S1 may be discounted. A treatment strategy to identify, address, and treat the fractional curve with either open or minimally invasive techniques can lead to improved patient outcomes and decrease revision rates in this complicated pathologic process.

Adjacent Segment Pathology After Treatment With Cervical Disc Arthroplasty or Anterior Cervical Discectomy and Fusion, Part 1: Radiographic Results at 7-Year Follow-Up.

BACKGROUND: Adjacent segment pathology (ASP) remains a concern following treatment with cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF). Radiographic ASP (RASP) is ASP identified on imaging, which may or may not include clinical symptoms. The risk factors for development of RASP and its clinical effects remain controversial. In part 1 of a 2-part publication we evaluate the incidence and predictors of RASP as well as determine whether any association exists between RASP and patient-reported outcomes (PROs). METHODS: Data were prospectively collected during a US Food and Drug Administration randomized, multicenter, investigational device exemption trial comparing CDA (Mobi-C; Zimmer Biomet, Westminster, CO) with ACDF. Multiple post hoc analyses were conducted on RASP as it related to demographics and patient outcomes. Kaplan-Meier estimates of time to Kellgren-Lawrence (K-L) grade 3/4 were calculated separately for all groups. Multivariate Cox proportional hazard models were used analyze whether RASP was associated with patient preoperative demographic characteristics and preoperative and postoperative radiographic characteristics. The association of RASP with PROs was analyzed using generalized estimating equations and matched, retrospective cohort analysis. RESULTS: The incidence of grade 3/4 RASP was lower for patients treated with CDA when initial treatment was at 1 level (27% vs 47%, P < .0001) and at 2 levels (14% vs 49%, P < .0001). Kaplan-Meier estimates indicated significantly lower probability of grade 3/4 RASP over time for patients receiving CDA (P < .001). Treatment with ACDF, treatment of 1 level, higher age, body mass index, higher preoperative physical components score, and a lower Cobb angle were associated with elevated risk of grade 3/4 RASP. CDA was shown to be more effective than ACDF (64.4%; 95% CI = 50.9, 74.2; P < .0001) at preventing RASP. CONCLUSIONS: The incidence and risk of RASP is decreased when patients are treated with CDA compared with ACDF. Although the mechanism of CDA that generates this protective effect is not understood, PROs remain unaffected through 7 years despite changes in RASP.

Adjacent Segment Pathology After Treatment With Cervical Disc Arthroplasty or Anterior Cervical Discectomy and Fusion, Part 2: Clinical Results at 7-Year Follow-Up.

BACKGROUND: Adjacent segment pathology (ASP) following cervical disc arthroplasty (CDA) or anterior cervical discectomy and fusion (ACDF) is identified by imaging (RASP) or clinical symptoms (CASP). Clinical symptoms of CASP have been broadly defined, but subsequent adjacent-level surgeries are clear indicators of CASP. Current literature remains inconsistent in the incidence and potential predictors of CASP. Here, we will evaluate a robust data set for the incidence of CASP resulting in subsequent surgery, attempt to identify factors that might affect CASP, and analyze the association of CASP with patient-reported outcomes (PROS) and RASP. METHODS: Data were prospectively collected during a US Food and Drug Administration randomized, multicenter, investigational device exemption trial comparing CDA (Mobi-C, Zimmer Biomet, Westminster, CO) with ACDF. CASP was defined as any adjacent-level subsequent surgical intervention. Post hoc analyses were conducted on the incidence, time to CASP diagnosis, and relationship of CASP with patient demographics. Longitudinal retrospective case-control analysis was used to assess the correlation of CASP to PROs and radiographic adjacent segment pathology (RASP). RESULTS: Kaplan-Meier estimates indicated significantly lower probability of CASP over time for 1-level (P = .002) and 2-level (P = .008) CDA patients. Treatment with ACDF and younger age were associated with higher CASP risk. CDA was more effective than ACDF (70.5%; 95% CI = 45.1, 84.2; P < .0001) at preventing CASP. Case-control analysis indicated increased probability of CASP for patients with grade 3/4 RASP, but the difference was not statistically significant. When we pooled CASP patients, the median grade of RASP at the visit prior to surgery was 1, with only 6 patients presenting with grade 3/4 RASP. CONCLUSIONS: Patients treated with CDA have a lower incidence of CASP than do patients treated with ACDF, although the mechanism remains unclear. CASP and RASP remain uncorrelated in this large data set, but other predictive variables such as treatment, age, and number of levels should be further investigated.

Why Does Cysteine Enhance Metal Uptake by Phytoplankton in Seawater but Not in Freshwater?

Low-molecular-weight weak ligands such as cysteine have been shown to enhance metal uptake by marine phytoplankton in the presence of strong ligands, but the effect is not observed in freshwater. We hypothesized that these contrasting results might be caused by local cysteine degradation and a Ca effect on metal-ligand exchange kinetics in the boundary layer surrounding the algal cells; newly liberated free metal ions cannot be immediately complexed in seawater by Ca-bound strong ligands but can be rapidly complexed by free ligands at low-Ca levels. The present results consistently support this hypothesis. At constant bulk Cd2+ concentrations, buffered by strong ligands: (1) at 50 mM Ca, cysteine addition significantly enhanced Cd uptake in high-Ca preacclimated euryhaline Chlamydomonas reinhardtii (cultured with cysteine as a nitrogen source to enhance local Cd2+ liberation via cysteine degradation); (2) at 0.07 mM Ca, this enhancement was not observed in the algae; (3) at 50 mM Ca, the enhancement disappeared when C. reinhardtii were cultured with ammonium (to inhibit cysteine degradation and local Cd2+ liberation); (4) cysteine addition did not enhance Cd uptake by cysteine-cultured marine Thalassiosira weissflogii when the concentration of immediately reacting strong ligands was sufficient to complex local Cd2+ liberation.

Uptake and subcellular distribution of aluminum in a marine diatom.

Aluminum (Al) is widespread in the environment including the ocean. The effects of Al on marine organisms have attracted more and more attention in recent years. However, the mechanisms of uptake of Al by marine organisms and the subcellular distribution of Al once assimilated are unknown. Here we report the uptake and subcellular distribution of Al in a marine diatom Thalassiosira weissflogii. Short-term (< 120 min) uptake experiments showed that the Al uptake rate by the diatom was 0.033 ±â€¯0.013 fmol-1 cell-1 min-1 (internalization flux normalized to the exposure Al concentration of 2 µM = 0.034 ±â€¯0.013 nmol m-2 min-1 nM-1). Subcellular fractionation experiments showed that the internalized Al was partitioned to subcellular components in the following order: granules (69 ±â€¯5%) > debris (17 ±â€¯4%) > organelles (12 ±â€¯2%) > heat-stable peptides (HSP) (~2%) > heat-denaturable proteins (HDP) (< 1%), indicating that the majority of intracellular Al was detoxified and stored in inorganic forms. The subcellular distribution of Al in the diatom is different from that of Al in freshwater green algae, in which most of the internalized Al is partitioned to organelles. We also evaluated an artificial seawater-based EDTA rinse solution to remove Al adsorbed on the diatom cell surface. Overall, our study provides new information to understand the mechanisms of uptake of Al by marine diatoms, and the mechanisms responsible for the biological effects (both toxic and beneficial) of Al on the growth of marine phytoplankton, especially diatoms.

Heterotopic Ossification After Cervical Total Disc Replacement at 7 Years-Prevalence, Progression, Clinical Implications, and Risk Factors.

BACKGROUND: Heterotopic ossification (HO) is a known risk following cervical total disc replacement (CTDR) surgery, but the cause and effect of HO are not well understood. Reported HO rates vary, and few studies are specifically designed to report HO. The effects on outcomes, and the risk factors for the development of HO have been hypothesized and reported in small-population, retrospective analyses, using univariate statistics. METHODS: Posthoc, multiple-phase analysis of radiographic, clinical, and demographic data for CTDR as it relates to HO was performed. HO was radiographically graded for 164 one-level and 225 two-level CTDR patients using the McAfee and Mehren system. Analysis was performed to correlate HO grades to clinical outcomes and to evaluate potential risk factors for the development of HO using demographics and baseline clinical measures. RESULTS: At 7 years, 1-level clinically relevant HO grades were 17.6% grade 3 and 11.1% grade 4. Two-level clinically relevant HO grades, evaluated using the highest patient grade, were 26.6% grade 3 and 10.8% grade 4. Interaction between HO and time revealed significance for neck disability index (NDI; P = .04) and Visual Analog Scale (VAS) neck pain (P = .02). When analyzed at each time point NDI was significant at 48-84 months and VAS neck at 60 months. For predictors 2 analyses were run; odds ratios indicated follow-up visit, male sex, and preoperative VAS neck pain are related to HO development, whereas hazard ratios indicated male sex, obesity, endplate coverage, levels treated, and preoperative VAS neck pain. CONCLUSIONS: This is the largest study to report HO rates, and related outcomes and risk factors. To develop an accurate predictive model, further large-scale analyses need to be performed. Based on the results reported here, clinically relevant HO should be more accurately described as motion-restricting HO until a definitive link to outcomes has been established.

Chemical Conditions in the Boundary Layer Surrounding Phytoplankton Cells Modify Cadmium Bioavailability.

In this study we tested the hypothesis that metal uptake by unicellular algae may be affected by changes in metal speciation in the boundary layer surrounding the algal cells. The freshwater alga Chlamydomonas reinhardtii was preacclimated to different N nutrition regimes; changes in N nutrition are known to change the nature of extracellular metabolites (e.g., reactive oxygen species "ROS", and OH-) and thus boundary layer chemical conditions. Specifically, at a constant bulk free Cd2+ concentration, Cd uptake by N-starved algae in cysteine-buffered solution was significantly higher than that in NTA-buffered solution. This enhancement was likely due to an increase of the free Cd2+ concentration in the boundary layer, resulting from localized cysteine oxidation by ROS released from these algae. On the other hand, Cd uptake was markedly lower when the free Cd2+ concentration near cell surface decreased as a result of an increase in the boundary layer pH of nitrate-acclimated algae or enhanced localized metal complexation. The results imply that redox, acid-base and metal complexation processes in the boundary layer differ from those in bulk water, even under chemically stable bulk conditions, and the boundary layer effect may well be of significance to phytoplankton acquisition of other trace metals.

Short-term outcomes of lateral lumbar interbody fusion without decompression for the treatment of symptomatic degenerative spondylolisthesis at L4-5.

OBJECTIVE Recently, authors have called into question the utility and complication index of the lateral lumbar interbody fusion procedure at the L4-5 level. Furthermore, the need for direct decompression has also been debated. Here, the authors report the clinical and radiographic outcomes of transpsoas lumbar interbody fusion, relying only on indirect decompression to treat patients with neurogenic claudication secondary to Grade 1 and 2 spondylolisthesis at the L4-5 level. METHODS The authors conducted a retrospective evaluation of 18 consecutive patients with Grade 1 or 2 spondylolisthesis from a prospectively maintained database. All patients underwent a transpsoas approach, followed by posterior percutaneous instrumentation without decompression. The Oswestry Disability Index (ODI) and SF-12 were administered during the clinical evaluations. Radiographic evaluation was also performed. The mean follow-up was 6.2 months. RESULTS Fifteen patients with Grade 1 and 3 patients with Grade 2 spondylolisthesis were identified and underwent fusion at a total of 20 levels. The mean operative time was 165 minutes for the combined anterior and posterior phases of the operation. The estimated blood loss was 113 ml. The most common cage width in the anteroposterior dimension was 22 mm (78%). Anterior thigh dysesthesia was identified on detailed sensory evaluation in 6 of 18 patients (33%); all patients experienced resolution within 6 months postoperatively. No patient had lasting sensory loss or motor deficit. The average ODI score improved 26 points by the 6-month follow-up. At the 6-month follow-up, the SF-12 mean Physical and Mental Component Summary scores improved by 11.9% and 9.6%, respectively. No patient required additional decompression postoperatively. CONCLUSIONS This study offers clinical results to establish lateral lumbar interbody fusion as an effective technique for the treatment of Grade 1 or 2 degenerative spondylolisthesis at L4-5. The use of this surgical approach provides a minimally invasive solution that offers excellent arthrodesis rates as well as favorable clinical and radiological outcomes, with low rates of postoperative complications. However, adhering to the techniques of transpsoas lateral surgery, such as minimal table break, an initial look-and-see approach to the psoas, clear identification of the plexus, minimal cranial caudal expansion of the retractor, mobilization of any traversing sensory nerves, and total psoas dilation times less than 20 minutes, ensures the lowest possible complication profile for both visceral and neural injuries even in the narrow safe zones when accessing the L4-5 disc space in patients with degenerative spondylolisthesis.

Binding of trace elements (Ag, Cd, Co, Cu, Ni, and Tl) to cytosolic biomolecules in livers of juvenile yellow perch (Perca flavescens) collected from lakes representing metal contamination gradients.

Biomolecules involved in handling cytosolic metals in the liver of the yellow perch (Perca flavescens) were characterized in juvenile fish collected from 4 lakes constituting metal contamination gradients. Using size-exclusion liquid chromatography coupled to an inductively coupled mass spectrometer, we determined metal distributions among ligands of different molecular weights in the cytosol, before and after a heat denaturation step designed to isolate metallothionein-like peptides and proteins. Silver, Cd, and Cu found in the heat-stable protein supernatants were indeed largely present as metallothionein-like peptide complexes; but Co, Ni, and Tl, also present in the heat-stable protein supernatants, did not coelute with metallothionein-like peptides and proteins. This difference in metal partitioning is consistent with the known preference of "soft" metals such as Ag, Cd, and Cu(I) for thiolated ligands and the contrasting tendency of Co and Ni to bind to ligands with oxygen and nitrogen as donor atoms. Metal handling in the whole cytosol also reflected these differences in metal-binding behavior. For Cd and Cu, the importance of the molecular weight pool that includes metallothionein-like peptides and proteins increased relative to the other pools as the total cytosolic metal concentration ([M]cytosol ) increased, consistent with a concentration-dependent detoxification response. In contrast, for Ni and Tl the increase in [M]cytosol was accompanied by a marked increase in the high-molecular weight (670-33 kDa) pool, suggesting that hepatic Ni and Tl are not effectively detoxified. Overall, the results suggest that metal detoxification is less effective for Ni, Tl, and Co than for Ag, Cd, and Cu. Environ Toxicol Chem 2018;37:576-586. © 2017 SETAC.

Hepatic oxidative stress and metal subcellular partitioning are affected by selenium exposure in wild yellow perch (Perca flavescens).

Yellow perch (Perca flavescens) collected from 11 lakes in the Canadian mining regions of Sudbury (Ontario) and Rouyn-Noranda (Quebec) display wide ranges in the concentrations of cadmium (Cd), nickel (Ni), selenium (Se), and thallium (Tl) in their livers. To determine if these trace elements, as well as copper (Cu) and zinc (Zn), are causing oxidative stress in these fish, we measured three biochemical indicators (glutathione (GSH), glutathione disulfide (GSSG) and thiobarbituric acid-reactive substances (TBARS)) in their livers. We observed that 44% of the yellow perch that we collected were at risk of cellular oxidative stress and lipid peroxidation. Considering all fish from all lakes, higher liver Se concentrations were coincident with both lower proportions of GSSG compared to GSH and lower concentrations of TBARS, suggesting that the essential trace-element Se acts as an antioxidant. Furthermore, fish suffering oxidative stress had higher proportions of Cd, Cu and Zn in potentially sensitive subcellular fractions (organelles and heat-denatured proteins) than did fish not suffering from stress. This result suggests that reactive oxygen species may oxidize metal-binding proteins and thereby reduce the capacity of fish to safely bind trace metals. High Cd concentrations in metal-sensitive subcellular fractions likely further exacerbate the negative effects of lower Se exposure.

Identification of complications that have a significant effect on length of stay after spine surgery and predictive value of 90-day readmission rate.

OBJECT: Complications after spine surgery have an impact on overall outcome and health care expenditures. The increased cost of complications is due in part to associated prolonged hospital stays. The authors propose that certain complications have a greater impact on length of stay (LOS) than others and that those complications should be the focus of future targeted prevention efforts. They conducted a retrospective analysis of a prospectively maintained database to identify complications with the greatest impact on LOS as well as the predictive value of these complications with respect to 90-day readmission rates. METHODS: Data on 249 patients undergoing spine surgery at Thomas Jefferson University from May to December 2008 were collected by a study auditor. Any complications occurring within 30 days of surgery were recorded as was overall LOS for each patient. Stepwise regression analysis was performed to determine whether specific complications had a statistically significant effect on LOS. For correlation, all readmissions within 90 days were recorded and organized by complication for comparison with those complications affecting LOS. RESULTS: The mean LOS for patients without postoperative complications was 6.9 days. Patients who developed pulmonary complications had an associated increase in LOS of 11.1 days (p < 0.005). The development of a urinary tract infection (UTI) was associated with an increase in LOS of 3.4 days (p = 0.002). A new neurological deficit was associated with an increase in LOS of 8.2 days (p = 0.004). Complications requiring return to the operating room (OR) showed a trend toward an increase in LOS of 4.7 days (p = 0.09), as did deep wound infections (3.3 days, p = 0.08). The most common reason for readmission was for wound drainage (n = 21; surgical drainage was required in 10 [4.01%] of these 21 cases). The most common diagnoses for readmission, in decreasing order of incidence, were categorized as hardware malpositioning (n = 4), fever (n = 4), pulmonary (n = 2), UTI (n = 2), and neurological deficit (n = 1). Complications affecting LOS were not found to be predictive of readmission (p = 0.029). CONCLUSIONS: Postoperative complications in patients who have undergone spine surgery are not uncommon and are associated with prolonged hospital stays. In the current cohort, the occurrence of pulmonary complications, UTI, and new neurological deficit had the greatest effect on overall LOS. Further study is required to determine the causative factors affecting readmission. These specific complications may be high-yield targets for cost reduction and/or prevention efforts.

Transcriptional and biochemical markers in transplanted Perca flavescens to characterize cadmium- and copper-induced oxidative stress in the field.

Despite recent progress achieved in elucidating the mechanisms underlying local adaptation to pollution, little is known about the evolutionary change that may be occurring at the molecular level. The goal of this study was to examine patterns of gene transcription and biochemical responses induced by metal accumulation in clean yellow perch (Perca flavescens) and metal depuration in contaminated fish in a mining and smelting region of Canada. Fish were collected from a reference lake (lake Opasatica) and a Cd, Cu and Zn contaminated lake (lake Dufault) located in the Rouyn-Noranda region (Qc, Canada) and caged for one or four weeks in their own lake or transplanted in the other lake. Free-ranging fish from the same lakes were also collected. Kidney Cd and Cu concentrations in clean fish caged in the contaminated lake increased with the time of exposure, but metal depuration did not occur in contaminated fish caged in the clean lake. After 4 weeks, the major retinoid metabolites analysed, the percentage of free dehydroretinol (dROH) and the retinol dehydrogenase-2 (rdh-2) transcription level in liver decreased in clean fish transplanted into the metal-contaminated lake, suggesting that metal exposure negatively impacted retinoid metabolism. However, we observed an increase in almost all of the retinoid parameters analysed in fish from the metal-impacted lake caged in the same lake, which we interpret as an adaptation response to higher ambient metal concentration. In support of this hypothesis, liver transcription levels of microsomal glutathione-S-transferase-3 (mgst-3) and glucose-6-phosphate dehydrogenase (g6pdh) were enhanced in clean fish transplanted into the metal-contaminated lake and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, involved in antioxidant response. However, although in the same fish the transcription level of Cu/Zn superoxide dismutase (Cu/Zn sod) was also increased, this did not lead to a change in the activity of the SOD enzyme, suggesting that this upregulation was aimed at maintaining SOD-related antioxidant capacities. In contrast, the transcription level of the cat gene, which did not change in contaminated fish, did not compensate for the decrease of CAT activity. After 4 weeks of exposure, some plastic responses of the clean fish were observed when they were transplanted in the metal-contaminated lake. However, probably as a consequence of the prior 80 years of exposure to metals, the contaminated population showed a limited plastic response in the expression of the majority of the candidate genes tested, when they were transplanted in the reference lake. The overall findings of this field investigation highlight how yellow perch molecularly and biochemically responded to a sudden or relatively long-term exposure (4 weeks) to a cocktail of metals.

Cadmium accumulation and toxicity in the unicellular alga Pseudokirchneriella subcapitata: Influence of metal-binding exudates and exposure time.

Predicting metal availability and toxicity for chronic (several hours or days) metal exposure scenarios, even for unicellular algae, is a major challenge to existing toxicity models. This is because several factors affecting metal uptake and toxicity, such as the release of metal-binding exudates, changes in the kinetics of metal uptake and toxicity over time, and algal physiological acclimation to internalized metals, are still poorly understood. The present study assessed the influence of these factors on Cd uptake and toxicity in laboratory batch cultures of the freshwater alga Pseudokirchneriella subcapitata. To do so, changes in the free Cd(2+) concentrations caused by the release of metal-binding algal exudates were monitored, (109)Cd accumulation in algal cells was measured, and Cd-induced inhibition of algal growth as a function of exposure time (from 12 h to 96 h) was followed. Results indicate that metal-binding exudates may decrease the proportion of the free Cd(2+) ion in solution up to 2-fold, a decrease that affects Cd uptake and toxicity. Pseudokirchneriella subcapitata has the capacity to decrease net Cd uptake rate on short time scales (<24 h), but this reduction in the Cd uptake rate disappeared after 24 h, and Cd toxicity occurred at relatively high Cd concentrations in solution. These data illustrate some of the pitfalls of standard algal toxicity assays, which were designed for acute exposures, and suggest how robust chronic bioassays might be developed.

International classification of disease clinical modification 9 modeling of a patient comorbidity score predicts incidence of perioperative complications in a nationwide inpatient sample assessment of complications in spine surgery.

OF BACKGROUND DATA: A patient comorbidity score (RCS) was developed from a prospective study of complications occurring in spine surgery patients. OBJECTIVE: To validate the RCS, we present an International Classification of Disease Clinical Modification (ICD-CM)-9 model of the score and correlate the score with complication incidence in a group of patients from the Nationwide Inpatient Sample database. We compare the predictive value of the score with the Charlson index. STUDY DESIGN: We conducted a retrospective assessment of Nationwide Inpatient Sample patients undergoing cervical or thoracolumbar spine surgery for degenerative pathology from 2002 to 2009. METHODS: We generated an ICD-9-CM coding-based model of our prospectively derived RCS, categorizing diagnostic codes to represent relevant comorbidities. Multivariate models were constructed to eliminate the least significant variables. ICD-9-CM coding was also used to calculate a Charlson comorbidity score for each patient. The accuracy of the RCS was compared with the Charlson index through the use of a receiver-operating curve. RESULTS: A total of 352,535 patients undergoing 369,454 spine procedures for degenerative disease were gathered. Hypertension and hyperlipidemia were the most common comorbidities. Cervical procedures resulted in 8286 complications (4.50%), whereas thoracolumbar procedures produced 25,118 complications (13.55%). Increasing RCS correlated linearly with increasing complication incidence (odds ratio [OR] 1.11; 95% confidence interval [CI], 1.10-1.13; P<0.0001). Logistic regression revealed that neurological deficit, cardiac conditions, and drug or alcohol use had greatest association with complication occurrence. The Charlson index also correlated with complication occurrence in both cervical (OR 1.25; 95% CI, 1.23-1.27) and thoracolumbar (OR 1.11; 95% CI, 1.10-1.12) patient groups. Receiver-operating curve analysis allowed a comparison of accuracy of the indices by comparing predictive values. The RCS performed as well as the Charlson index in predicting complication occurrence in both cervical and thoracic spine patients. CONCLUSIONS: ICD-9-based modeling validated that RCS correlates with complication occurrence. The RCS performed as well as the Charlson index in predicting risk of complication in spine patients.

Uptake and subcellular distributions of cadmium and selenium in transplanted aquatic insect larvae.

We transplanted larvae of the phantom midge Chaoborus punctipennis from a lake having lower concentrations of Cd and Se (Lake Dasserat) to a more contaminated lake (Lake Dufault) located near a metal smelter in Rouyn-Noranda, Quebec. Transplanted individuals were held in mesh mesocosms for up to 16 days where they were fed with indigenous contaminated zooplankton. Larval Cd and Se burdens increased over time, and came to equal those measured in indigenous C. punctipennis from contaminated Lake Dufault. Larval Se burdens increased steadily, whereas those of Cd showed an initial lag phase that we explain by a change in the efficiency with which this insect assimilated Cd from its prey. We measured Cd and Se in subcellular fractions and found that larvae sequestered the majority (60%) of the incoming Cd in a detoxified fraction containing metal-binding proteins, whereas a minority of this nonessential metal was in sensitive fractions (20%). In contrast, a much higher proportion of the essential element Se (40%) was apportioned to metabolically active sensitive fractions. Larvae took up equimolar quantities of these elements over the course of the experiment. Likewise, Cd and Se concentrations in wild larvae were equimolar, which suggests that they are exposed to equimolar bioavailable concentrations of these elements in our study lakes.

Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch.

In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to waterborne Ni. There was a general lack of consistency between muscle transcription level and enzyme activities analyzed. The overall findings from this investigation highlight the usefulness of transcriptional and biochemical endpoints in the identification of oxidative stress and vitamin A metabolism impairment biomarkers and the potential use of multi-level biological approaches when assessing environmental risk in fish.

ASA grade and Charlson Comorbidity Index of spinal surgery patients: correlation with complications and societal costs.

BACKGROUND CONTEXT: The Charlson Comorbidity Index (CCI) and the American Society of Anesthesiologists (ASA) Physical Status Classification System (ASA grade) are useful for predicting morbidity and mortality for a variety of disease processes. PURPOSE: To evaluate CCI and ASA grade as predictors of complications after spinal surgery and examine the correlation between these comorbidity indices and the cost of care. STUDY DESIGN/SETTING: Prospective observational study. PATIENT SAMPLE: All patients undergoing any spine surgery at a single academic tertiary center over a 6-month period. OUTCOME MEASURES: Direct health-care costs estimated from diagnosis related group and Current Procedural Terminology (CPT) codes. METHODS: Demographic data, including all patient comorbidities, procedural data, and all complications, occurring within 30 days of the index procedure were prospectively recorded. Charlson Comorbidity Index was calculated from International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and ASA grades determined from the operative record. Diagnosis related group and CPT codes were captured for each patient. Direct costs were estimated from a societal perspective using Medicare rates of reimbursement. A multivariable analysis was performed to assess the association of the CCI and ASA grade to the rate of complication and direct health-care costs. RESULTS: Two hundred twenty-six cases were analyzed. The average CCI score for the patient cohort was 0.92, and the average ASA grade was 2.65. The CCI and ASA grade were significantly correlated, with Spearman ρ of 0.458 (p<.001). Both CCI and ASA grade were associated with increasing body mass index (p<.01) and increasing patient age (p<.0001). Increasing CCI was associated with an increasing likelihood of occurrence of any complication (p=.0093) and of minor complications (p=.0032). Increasing ASA grade was significantly associated with an increasing likelihood of occurrence of a major complication (p=.0035). Increasing ASA grade showed a significant association with increasing direct costs (p=.0062). CONCLUSIONS: American Society of Anesthesiologists and CCI scores are useful comorbidity indices for the spine patient population, although neither was completely predictive of complication occurrence. A spine-specific comorbidity index, based on ICD-9-CM coding that could be easily captured from patient records, and which is predictive of patient likelihood of complications and mortality, would be beneficial in patient counseling and choice of operative intervention.

Predicting cadmium accumulation and toxicity in a green alga in the presence of varying essential element concentrations using a biotic ligand model.

This study refines the Biotic Ligand Model (BLM) approach by integrating the modulating effects of various essential elements on cadmium (Cd) uptake kinetics in the freshwater alga Chlamydomonas reinhardtii. The algae were first acclimated to a low (LM) or high trace metal (HM) medium as well as to low or high free Cd(2+) and Co(2+) concentrations. The short-term Cd transport capacity and affinity were then quantified in exposure media in which essential trace metals and calcium concentrations were manipulated. The results show that after acclimation to the LM medium, exposure to high free Ca(2+) decreases the capacity of the Cd transport system. Also, acclimation to high (10(-9) M free Co(2+)) or low (10(-11) M free Co(2+)) did not significantly affect Cd uptake rates. When all essential trace metals were simultaneously increased in the acclimation (and exposure) medium, the capacity of the transport system decreased by ∼ 60%, a decrease close to that due to high [Zn(2+)] alone, suggesting that Zn is the main trace metal modulator of the Cd transporter capacity. Changes in Cd toxicity (growth inhibition) in the presence of different essential trace metal concentrations were strongly related to the steady-state concentration of intracellular cadmium, regardless of the cell's nutritional state. Our BLM incorporating the physiological effects of Ca(2+) and other trace metals predicts steady-state Cd accumulation in the presence of varying concentrations of essential elements at 7 nM free Cd(2+), but predictions over a wide range of free [Cd(2+)] proved to be more difficult.

How does exposure to nickel and cadmium affect the transcriptome of yellow perch (Perca flavescens)--results from a 1000 candidate-gene microarray.

The molecular mechanisms underlying nickel (Ni) and cadmium (Cd) toxicity and their specific effects on fish are poorly understood. Documenting gene transcription profiles offers a powerful approach toward identifying the molecular mechanisms affected by these metals and to discover biomarkers of their toxicity. However, confounding environmental factors can complicate the interpretation of the results and the detection of biomarkers for fish captured in their natural environment. In the present study, a 1000 candidate-gene microarray, developed from a previous RNA-seq study on a subset of individual fish from contrasting level of metal contamination, was used to investigate the transcriptional response to metal (Ni and Cd) and non metal (temperature, oxygen, and diet) stressors in yellow perch (Perca flavescens). Specifically, we aimed at (1) identifying transcriptional signatures specific to Ni and Cd exposure, (2) investigating the mechanisms of their toxicity, and (3) developing a predictive tool to identify the sublethal effects of Ni and Cd contaminants in fish sampled from natural environments. A total of 475 genes displayed significantly different transcription levels when temperature varied while 287 and 176 genes were differentially transcribed at different concentrations of Ni and Cd, respectively. These metals were found to mainly affect the transcription level of genes involved in iron metabolism, transcriptional and translational processes, vitamin metabolism, blood coagulation, and calcium transport. In addition, a linear discriminant analysis (LDA) made using gene transcription levels yielded 94% correctly reassigned samples regarding their level of metal contamination, which indicates the potential of the microarray to detect perch response to Cd or Ni effects.